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Deepa et al., Int J Med Res Health Sci. 2014;3(1):1-4

International Journal of Medical Research

&

Health Sciences

www.ijmrhs.com Volume 3 Issue 1(Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 2

ndSep 2013 Revised: 8

thOct 2013 Accepted: 3

rdNov 2013

Research article

A STUDY OF LUMBARISATION OF FIRST SACRAL VERTEBRA AMONG THE SOUTH INDIANS

* Deepa TK1, Martin K John

2

1,2Assistant Professor, Department of Anatomy, MES medical college, Perinthalmanna, Kerala

*Corresponding author e-mail: [email protected]

ABSTRACT

Background: In the lumbosacral region, anatomical variations occur with changes in the number of sacral vertebra

by deletion of first sacral vertebra or by the union of fifth lumbar or first coccyx with sacrum. The fifth lumbar

vertebra may be fused with the sacrum in the case of sacralisation, or the first sacral vertebra may be fused with fifth

lumbar vertebra in the case of lumbarisation. This may cause serious problems during spinal surgery if we may fail

to recognise the lumbosacral transitional vertebra. Materials and methods: We studied 117 dry human sacra of

South Indian population of known sex. Out of 117 sacra, 70 male and 47 female. The sacra with four vertebral

segments were selected and studied its morphology. Its features were carefully examined and noted. Result: A

typical sacrum consisting of five segments was observed in 103 (88.03%) specimen, while presence of

lumbarisation was noted in 2 (1.70%) cases and sacralisation was noted in 12 (10.25%) cases. Sacrum with 3 pairs

of sacral foramina is 1.70%. Among the 2 specimen, we got 1 male and 1 female respectively Conclusion: Presentstudy shows that the lumbarisation of first sacral vertebra leads to the formation of three pairs of sacral foramina,

which is 1.70% in South Indian population. This awareness of lumbosacral transitional vertebra (LSTV) will help to

understand its importance during surgical procedures and also in reporting the radiographs such as X-rays, CT and

MRI.

Keywords: Anatomic variations, congenital anomaly, lumbarisation, sacral foramina

INTRODUCTION

The sacrum lies below the fifth lumbar vertebra and is

formed by the fusion of five sacral vertebras. It is

wedged between the two hip bones and takes part in

forming the pelvis. It is triangular in shape. Its upper

end or base which articulates with the fifth lumbar

vertebra: a lower end or apex which articulate with the

coccyx. It has four pairs of sacral foramina that

communicate with sacral canal.

At the cranial end of sacrum, when the fifth lumbar

vertebra fuses with first sacral vertebra, known as the

sacralisation of lumbar vertebra and when the first

sacral vertebra fuses with the fifth lumbar vertebra,

known as lumbarisation of first sacral vertebra.1

Normally, the sacrum is formed by the fusion of five

rudimentary vertebrae. But anatomical variations of

the sacrum have been reported like sacralisation of

fifth lumbar vertebra and lumbarisation of first sacral

vertebra. Sacralisation of fifth lumbar vertebra is the

most common, whereas the lumbarisation of first

sacral vertebra is less common.2

In the present study, the sacrum had four sacral

vertebrae instead of five sacral vertebrae as in normal

sacrum. There were three sacral foramina along the

dorsal and pelvic sacral surface. This is due to non

fusion of 1st

and 2nd

segments of the sacrum ie, the

lumbarisation of the first sacral vertebra. S5 vertebra

was normal and S2 vertebra was well developed as

like S1. S1being completely separated from it, which

may be due to developmental defect.

DOI: 10.5958/j.2319-5886.3.1.001



2


Bertolotti observed for the first time that,

lumbarisation and sacralisation which comes under

lumbosacral transitional vertebra are congenital

anomalies of lumbosacral region.3

Defect in the

segmentation of the lumbosacral spine during

development is the main cause for this condition.3,4

Genetic factors and ossification defects are also the

potential cause of variation for the lumbosacral

transitional vertebra. In both case the morphology is

the same. So it is difficult to differentiate between the

two defects.5,6

In this study, we focused on the prevalence of sacrum

with 3 pairs of sacral foramina among the South Indian

population, that in turns help to find out the variations

in patients during radiological investigations

complaining low back pain. Knowledge of this

variation is important to diagnose lower back pain;

disc prolapsed and is helpful in procedures like lumbar

puncture and spinal anaesthesia.

MATERIALS AND METHODS

The present study includes 117 human sacra of known

sex, were studied. All the sacra were of adult, but

precise age was not known. Any change in the number

of sacral vertebrae were selected and studied. The

sacrum with four segments and three sacral foramina

was noted.

The specimen with lumbarisation were examined and

recorded. Two fold subdivision of lumbarisation was

used. (1) Unilateral complete lumbarisation (11)

bilateral complete lumbarisation of first sacral

vertebra.

In this study, 2 sacrum with four sacral vertebrae and 3

pairs of sacral foramina showing bilateral complete

lumbarisation of 1st

sacral vertebra was selected.

Incidence of sacrum with 3 pairs of sacral foramina is

1.70%. Among the 2 specimen, one is male and theother one is female respectively.

RESULTS

In the current study of 117 dry human sacra, 70

(60.5%) were male and 47 (39.5%) were female sacra.

14 cases (12.3%) of lumbosacral transitional vertebra

and 103 (87.7%) normal vertebra are found.

Among the 14 cases of lumbosacral transitional

vertebras, we got 2sacra with four sacral vertebrae

and three pairs of sacral foramina showing bilateralcomplete lumbarisation of 1

stsacral vertebra. One is

male and the other one is female. Incidence of sacrum

with 3 pairs of sacral foramina is 1.70%.

Table 1: Frequency distribution of lumbarisation of

1st

sacral vertebra & sacralisation of 5th

lumbar

vertebra

Male Female TotalTotal number of sacra 70 47 117

Normal 61 42 103

Lumbarisation 1 1 2

Sacralisation 8 4 12

Fig 1. Dorsal surface of sacrum

(DSF-1: First pair of dorsal sacral foramina, DSF-2:

Second pair of dorsal sacral foramina, DSF-3:Third

pair of dorsal sacral foramina)

We came across the sacrum with only bilateral

complete lumbarisation and not any unilateral

complete lumbarisation in any specimen. Parameters

in sacrum with bilateral complete lumbarisation were

smaller than normal dimension.

Fig 2: Pelvic surface of sacrum.

(PSF1-first pair of pelvic sacral foramina, PSF2-

second pair of pelvic sacral foramina, PSF3- third pair

of pelvic sacral foramina)

DSF-1

DSF-2

DSF-3

PSF-1

PSF-2

PSF-3



3


DISCUSSION

Variations in vertebrae are affected by gender,

developmental factors and race. An increased number

of vertebrae occur more often in males and a reduced

number occurs more frequently in females.

Normally sacrum is formed by the fusion of five sacral

vertebrae and it contains four pairs of sacral foramina.

In the current study, we got sacrum with three pairs of

sacral foramina showing bilateral complete

lumbarisation of first sacral vertebra. In our study, the

prevalence of sacrum with three pairs of sacral

foramina is 1.70%.

In the lumbosacral region, anatomical variations occur

frequently, making the sacrum the most variable

portion of spine. The variation may be attributed to the

dependency of the final sacral morphology to the loadrelated fusion of the bone structure.

7Failure to

complete the ascending fusion may create a sixth

lumbar vertebra, leaving a four piece or lumbarised

sacrum.

The occurrence of lumbosacral transitional vertebrae is

linked to its embryological development and

osteological defects. Vertebras are derived from the

sclerotomes of the somites. Each sclerotome divides

into three parts: cranial, middle and caudal.

Embryologically, the vertebra receives contributionfrom caudal half of one sclerotome and from the

cranial half of succeeding sclerotome. Thus

lumbosacral transitional vertebras are caused by the

border shifts. Sacralisation of fifth lumbar vertebra is

due to cranial shift and the lumbarisation of first sacral

segment is due to caudal shift.8

The vast majority of people are affected by this spinal

abnormality are born with it ie, it is congenital. Less

common reasons could be traumatic injury, extreme

arthritic changes and purposeful spinal fusion surgery.

Mutations in the HOX 10 and HOX 11 paralogous

genes results in the normal pattering of lumbar and

sacral vertebra as well as the changes in the axial

pattern, such as lumbosacral transition vertebrae.6,9,10

A sacrum with three pairs of sacral foramina has

clinical and medicolegal implications. In order to

avoid surgery at an incorrect level, it is important to

identify the lumbarisation of first sacral vertebra and

the sacralisation of fifth lumbar vertebra. The

condition of lumbarisation of 1st

sacral vertebra

deserves attention of clinical anatomist, radiologists,

morphologists and forensic experts. Hence we are

presenting such a variation which emphasize on its

clinical relevance.11-13

Variation in segmental structure of vertebral column

results in lumbarisation that demands more attention

during anaesthetic and surgical intervention11

.

Knowledge of this variation is important to diagnose

lower back pain, sciatica; disc prolapse and is helpful

in procedures like spinal anesthesia and lumbar

puncture.14

CONCLUSION

The present study shows lumbarisation of first sacral

vertebra with three pairs of sacral foramina instead of

four pairs of sacral foramina.

Sacrum is clinically important for caudal epidural

block. So incorrect numbering can theorectically lead

to problems with the administration of intradural or

epidural anaesthetics.14

Surgical treatment of sacral

lesions requires understanding of the underlying

anatomy, a task made easier by understanding the

developmental aspects and morphological changes that

occur with growth.

The knowledge of this kind of anomaly is important

while reporting the CT, MRI films and Xrays for

correct clinical and radiological assessment. Thus

clinically the lumbarisation of 1st

sacral vertebra is of

paramount importance to surgeons, clinical anatomists,

forensic experts and morphologists.

REFERENCES

1. Bajami Singh. Sacrum with five pairs of sacral

foramina. IJAV 2011;4:139-40

2. Frymoyer JW, Hadler NM, Kostuik JP, Weinsttein

JN, Whitecloud TS. The adult spine: Principles

and practice. New York: Raven press.

1991;2:2099

3. Delport EG, Cucuzzella TR, Marley J, Pruitt C,

Delport AG. Lumbosacral transitional vertebrae;

incidence in a consecutive patient series. Pain

physician.2006;9(1); 53-56

4. Kim NH, Suk KS. The role of transitional

vertebrae in spondylolysis and spondylolytic

spondylolisthesis Bull, hosp. Jt.Dis.1997;56(3):

161-66

5. Tini PG, Wieser C, Zinn WM. The transitional

vertebrae of lumbosacral spine: its radiological

classification, incidence, prevalence and clinicalsignificance. Rheumatology & rehabilitation.

1977;16(3) 180-85.



4


6. Wellik DM, Capecchi MR. Hox 10 and Hox 11

genes are required to globally pattern the

mammalian skeleton. Science 2003; 301: 363-67.

7. Joseph S Cheng MD, John K Song MD. Anatomy

of the Sacrum. Neurosurg Focus 2003; 15(2):

8. Sharma VA, Sharma DK, Shukla CK, Osteogenic

study of lumbosacral transitional vertebra in

central india region J.Anat Soc India.2011; 60(2)

212-17

9. Sadler TW. Langman’s medical embryology.

Lippincott Williams & Wilkins, Philadelphia

2010: 11th

edition :142

10. Carapuco M, Novoa A, Bobola N, Mallo M. Hox

genes specify vertebral types in the presomatic

mesoderm. Genes Dev 2003; 19; 2116-21

11. Bron LJ, Van Royan BJ and Wuisman P. The

Clinical significance of lumbosacral transitional

anomalies. Acta orthopaedica Belgica 2007;73(6)

687-95

12. Dharati MK, Shailesh kumar K , Chintan Lakhani,

Srushti S Ruparelia, Shilpa patel, Padma Varlekar.

A study of sacrum with three pairs of sacral

foramina in Western India. IJMSPH 2012;1:127-

31.

13. Frazer JE. Anatomy of the human skeleton., edited

by Breathnach ASJ and A. Churchill Livingstone

London .1958; 5th ed: 33-38

14. Panjakash Samreen, Londhe shashikala and Kori

Rohini. Lumbarisation of first sacral vertebra – a

case report. IJBAMS 2012;2;154-57.



5

Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11


&

Health Sciences




rdNov 2013

Research article

THE USE OF PERITONEAL DIALYSIS IN THE MANAGEMENT OF PATIENTS WITH RENAL

FAILURE AT INSTITUTE OF KIDNEY DISEASES, PESHAWAR

*Akhtar Sultan Z1, Saleem Nasir

2, Hajira Bibi

3

1Professor and Head, Department of Nephrology, Institute of Kidney Diseases, Hayatabad Medical Complex,

Peshawar2Training Medical Officer, Medical B Unit, Hayatabad Medical Complex, Peshawar.

3Clinical Nutritionist, Institute of Kidney Diseases, Hayatabad Medical Complex, Peshawar.

*Corresponding author email: [email protected]

ABSTRACT

Peritoneal dialysis (PD) using an ordinary stylet cannula was studied in 253 patients (67% male and 33% female

with age ranging from 3-67 years) suffering from renal failure. The study was conducted between January 2007

and December 2012. The procedure was well tolerated by the patients. The desired aims of dialysis including

improvement in chemistry were achieved in all surviving (94.5%) cases. Mortality during PD was 5.5% and was

related to the underlying causes of renal failure. Peritonitis seen in 30% cases was the commonest complication.

Other complications in order of frequency were, hypokalemia (8%), severe hyperglycemia in diabetic patients(6%), and sever hypovolemia (5%), pericatheter leak (5%) and catheter blockage (2%). Perforation of the bowel, a

serious complication occurring during insertion of the PD cannula was not seen in any of the cases. It is

concluded from the study that PD is a simple and cost effective alternative to hemodialysis and have special

advantages in the current set-up of the institute. The objective of our work was to study the results and

complications of peritoneal dialysis in light of its efficacy as an alternative form of renal replacement therapy

(RRT) to hemodialysis.

Keywords: Peritoneal dialysis, peritonitis, hyperglycemia, hypovolemia

INTRODUCTION

Renal replacement therapy (RRT) in the form of

dialysis (hemodialysis/ peritoneal dialysis) or

transplantation remains the sole treatment for patients

who sustain renal failure. The gold standard for renal

failure (End stage renal disease-ESRD) is

transplantation but unfortunately it is restricted by

financial limitations in developing countries like

Pakistan.1

Similarly the hemodialysis (HD) facilities

are scarce due to the lack of necessary funds. At

present there are only 175 dialysis centers throughout

the country2 and few of them are available in remoteareas. The dialysis treatment is in-fact expensive and

at the same time lifesaving but due to meager

facilities and poverty, the PD is a cheaper option in

CKD patients with good residual renal function.

Renal failure is becoming a public health problem

with increasing incidence and prevalence, high cost

and unfortunately poor outcome.3The total burden of

ESRD continues to rise including patients with many

advanced comorbidities.4The growing burden of this

special population requires the use of alternative renal

replacement therapy. Peritoneal dialysis (PD) is an

alternative renal supportive therapy (RST) to HD

which if use wisely can share some of the load. Theutilization of peritoneal dialysis is low despite of

equal patient survival on HD and PD, and fluctuates

DOI: 10.5958/j.2319-5886.3.1.002



6


only at around 15% of the ESRD population.5,6

Both

PD and HD have their specific advantages and

disadvantages and different factors influence the

choice of RRT. PD is generally preferred to HD in

very small children and those with severe

cardiovascular instability.7,8

The better preservation of residual renal function,

lower risk of infections with hepatitis B and C, better

outcome after transplantation, preservation of

vascular access and lower cost are arguments to

promote PD as a good initial treatment. Hospital

based PD may be the only option for elderly with

significant morbidities making them unable to

undergo HD. Despite a valuable and effective option

with acceptable survival rates the use of PD is still

low for special group of ESRD.6,9

There have been very few publications on the clinical

experience of PD in our country; this study was

therefore conducted with the aim to describe our

experience and results of PD at our institute.

MATERIAL AND METHODS

Sample size and study location: This study was

conducted at the department of Nephrology, Institute

of Kidney Diseases, HMC, Peshawar between Jan

2007 and December 2012 after taking approval from

the ethics committee of our institution. A total of 253patients who presented with end stage renal disease

(ESRD) / Acute Renal Failure (ARF) were recruited

from January 2007 to December 2012 (6 years).

Study subjects

Inclusion criteria: Subjects from all age groups,

including paediatric population (less than 8 years

old), patients with poor cardiovascular status (blood

pressure less than 100 systolic, evidence of previous

myocardial infarction or cerebrovascular accident)

and those with hepatitis B surface antigen were givenPD instead of HD. Patents from far flung areas were

given palliative PD if it was felt that their prospects

of long term dialysis or transplant were extremely

poor. Lack of HD slot or unavailability of

consumables in the HD unit as well as refusal for HD

by the patients or their relative were another reason

for choosing PD. Verbal and written informed

consent was obtained from the participants of the

study.

Exclusion criteria: Patients, who werehemodynamically stable, had prospects for long term

maintenance hemodialysis and had prospects for renal

transplantation. Those patients who had access and

affordability for dialysis were excluded from the PD

group. Age group more than 10 years with

hemodynamic stability was also not included in the

PD group.

Peritoneal Dialysis Procedure: Following urinary

catheterization, PD cannula insertion was performed

as a bedside procedure in the ward using aseptic

techniques and local anesthesia. In order to avoid

perforation of the bowl and facilitate optimum

positioning of the PD catheter, intraperitoneal

infusion of about two liter dialysate using an ordinary

intravenous cannula was usually carried out prior to

insertion of the PD cannula. The cannula was secured

and the entry point was closed by applying a purse-

string suture. Hourly exchanges with 500 ml to 2000

ml standard PD solution (Braun or Otsuka) were

carried out. Two hundred units of heparin were added

to each liter of dialysate. Proper record of exchange

with emphasis on accurate fluid balance was kept.

Clinical and Biochemical assessment: Patients were

assessed clinically and pre- and post-dialysis

chemistry was measured to look at the efficacy of the

dialysis.

Statistical analysis: All the results were expressed as

percentages and frequencies by using Microsoft Excel

(version 2010).

RESULTS

Gender based distribution of patients with renal

failure

The data in table 1 show gender based distribution of

patients with renal failure. It is clear from the table

that among 253 patients 170 were male and 83 were

female. The mean age of patients was 23 years ranged

between 3 to 67 years.

Table 1: Gender based distribution of patientswith renal failure

Gender Number Percentage

Male 170 67

Female 83 33

Causes of chronic renal failure (CRF)

The data in table 2 shows the various causes of

chronic renal failure. Out of 253 cases 152 (60%)

were suffering from chronic renal failure. Most of

these patients had small echogenic kidneys (n=93)suggesting the underlying causes of

glomerulonephritis in the majority followed by



8


Complications during peritoneal dialysis

Various complications during peritoneal dialysis were

also experienced (Table 7). The most common

complication was peritonitis which occurred in 76

(30%) cases, which responded to antibiotic therapy

and removal of the PD cannula. Traumatic

complications from insertion of the PD cannula were

infrequent and were mainly minor intra-peritoneal

bleed (n=15). None of the patient had perforation of

the bowl. Other catheter related complications

included pericatheter leak (n=13). Scrotal edema

(n=10), pain on running fluid (n=8) and blockage of

catheter (n=5), the later responding to repositioning

of the catheter. Metabolic complications encountered

were hypokalemia in 20 cases, severe hyperglycemia

in 15 diabetic patients and severe hypovolemia

requiring intravenous fluids in 13 cases.

Table.7 Complications during peritoneal dialysis

Complications Number %

PD peritonitis 76 30.04

Blood stained effluent 15 5.93

Pericatheter leak 13 5.14

Scrotal edema 10 3.95

Pain on running fluid 8 3.16

Blockage of catheter

(catheter repositioned)

5 1.98

Hypokalemia 20 7.91

Hyperglycemia

(in diabetes)

15 5.93

Hypovolemia 13 5.14

Signs and symptoms of peritonitis

Signs and symptoms of peritonitis in order of

frequency were abdominal pain (98%), fever (77%),

rigors (33%), diarrhea (17%), nausea and vomiting

(13%) and constipation (10%).

Table 8: Signs and symptoms of peritonitis (n=76)

Symptoms and signs Number %

Abdominal pain 75 98

Fever 59 77

Rigors 25 33

Diarrhea 13 17

Nausea and vomiting 10 13

Constipation 8 10

Abdominal tenderness 64 84

Leukocytosis 56 74Cloudy fluid 76 100

Most patients with peritonitis had pyrexia (77%),

abdominal tenderness (84%) and leukocytosis (74%).

All (100%) patients suffering from peritonitis had

cloudy fluid on return. Multiple other studies have

also observed that more than 90% of the patients have

cloudy fluid (100% of ours) and many have

abdominal pain (98% of our patients).27,28

Frequency of organisms isolated from patients

peritonitis

Table 9 shows the incidence of different organisms

responsible for peritonitis. Gram positive organisms

were responsible for 44 cases of peritonitis and were

either due to Staph aureus (28 cases) or Staph

epidermis (16 cases). Peritonitis caused by Gram

negative organisms was seen in 32 cases. These

comprised Pseudomonas (19 cases), Enterobacter (10cases) and E.coli (3 cases). Culture from 13 cases of

peritonitis did not reveal any growth. Findings from

other studies also revealed that gram-positive

organisms are more responsible for causing most

episodes of peritonitis (64.6%) than gram-negative

organisms (20.5%).29

Table 9: Frequency of organisms isolated from

patients peritonitis (n=76)

Organisms Number %

Staphylococcus aureus 28 36.84

Pseudomonas 19 25.00

Staphylococcus Epidemidis 16 21.05

Enterobacter 10 13.16

E.coli 3 3.95

DISUCUSSION

The effectiveness of PD was evaluated in 253

subjects at the institute of Kidney Diseases,

Peshawar. Kidney failure was more prevalent among

male than in female. This was in agreement with the

finding of Neugarten et al., (2000) that man

experiences a more rapid decline in renal function

and worse outcome than in female. The underlying

mechanisms for this gender disparity are potentially

related to differences between the sexes in glomerular

structure, glomerular hemodynamics, diet, variations

in the production and activity of local cytokines and

hormones, and/or the direct effect of sex hormones on

kidney cells.10,11

Further it is stated that men with

chronic kidney disease (CKD) are 50% more likely to

progress to renal failure.12



9


The causes of CRF findings suggested that a broader

spectrum of CKD risk factors including both

infectious and environmental factors as well as

genetics predisposes to earlier onset and more rapid

progression of CKD. Therefore a basic understanding

of the vulnerabilities will help the treatment and

prevention of CKD in this population.13

On the other

hand there is variably among the causes of ARF and

differ from country to country and vary from center

to center in a country. However, there has been an

overall increase in the incidence of ARF with the

changing etiology of ARF in the recent years. The

incidence of obstetrical, surgical and diarrhea related

ARF have decreased significantly, whereas those of

ARF associated with malaria, sepsis, nephrotoxic

drugs and liver diseases have increased.14

The reason for using PD in our unit has gradually

increased not only in ARF but also in CRF. 60% of

our patients who had received PD had CRF. The

usual form of PD given to CRF patients is CAPD

using tencknoff catheter.15,16

Unfortunately, both the

tenckoff catheter and the CAPD solution are imported

items making the treatment costly and practically

unaffordable for most of our patients. Hence we carry

out IPD using stylet cannula and ordinary PD

solution.

In addition to financial restraints there are other

reasons for our increasing use of PD. The majority of

patients with CRF are usually illiterate with poor

insight and hence generally non-compliant. Suffering

from “denial syndrome” they often consult Hakims

and visit shrines with the hope that their illness will

be cured. Some of the patients belong to the far flung

areas and are unable to attend frequently for

maintenance HD. Commencing such patients on HD

without ensuring HD its maintenance is of little

benefit and may, in fact hazardous. For example, HDoften causes loss of residual renal function and

aggravates oliguria.17

Oliguria has been implicated as

a poor prognostic factor in ARF and often lead to life

threatening pulmonary edema in CRF.18,19

A few days

of palliative PD rather than commencing on HD, in

our experience stabilizes such patients and provides

time for counseling and further planning such as

establishing a permanent vascular access.

Our patients with CRF often face delays in getting a

successful arterio-venous fistula. Dialysis in themeantime is often provided via a temporary vascular

catheter usually inserted into the subclavian vein,

which often gets infected. This can lead to life-

threatening septicemia.20

It also causes stenosis or

occlusion of the vein and may lead to failure of

arteio-venous fistula on that side subsequently.21,22

By

giving PD initially, we can prevent these

complications.

Provided certain precautions are taken, insertion of

the style peritoneal cannula is usually a safe

procedure. Perforation of the bowl is, however, a

known complication which usually responds to

conservative treatment.25,26

None of patients had

either perforation of the bowel or severe hemorrhage.

This was mainly due to our policy of introducing 2 to

3 liters of fluid into the peritoneal cavity before

cannulation which minimizes the trauma. Minor

bleeding occurred in five patients.

Peritonitis curing in 76 patients was the commonest

complication and was mainly due to lack of proper

aseptic condition on part of patient’s relative. Dialysis

was concluded when either the required aims were

achieved or when peritonitis occurred. With removal

of catheter and antibiotic therapy, peritonitis usually

quickly settled. Pericatheter leak occurred in only five

patients and responded to reduction in volume

exchanges. Due to tremendous ultra-filtration,

significant hypovolemia requiring the replacement

fluid occurred in thirteen patients. Hypokalemia

occurring in twenty of our cases was treated by the

addition of potassium in the dialysate.

Most our patients accepted PD well. The immediate

aims of dialysis such as amelioration of uremic

symptoms, correction of acidosis and improvement in

azotemia were achieved in all patients. Fluid overload

was also successfully treated with PD. Fluid removal

facilitated the use of nutritional fluid. Some of the

patients initially treated with PD due to lack of space

in HD unit were later shifted to HD when spacebecame available and further dialysis required.

CONCLUSION

From our experience, we conclude that PD is an

excellent form of dialysis for the treatment of ARF,

especially in children and elderly with

cardiovascular-instability. In addition, it can be used

as an initial treatment in those cases of CRF where

the prospects of regular follow-up for long-term

dialysis are extremely poor or when there islikelihood of delay in getting a permanent vascular

access established.



10


ACKNOWLEDGMENT

The authors sincerely thank the record keepers of our

institution for maintaining and helping in retrieval of

the relevant record.

RECOMMENDATION

There is a need for further studies including a larger

sample size and long term follow up.

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7. Donalson MDC, Spargeon P, Haycock GB,

Chantler C. Peritoneal dialysis in infants. Br

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8. Pur G, Korzets A, Hochhauzer E, Eschar Y,

Blum M, Avirum A. Cardiac arrhythmia during

continuous ambulatory peritoneal dialysis.

Nephron.1987; 45(3): 192-95.

9. Fourtounas C, Hardalias A, Dousdampanis P,

Savidaki E and Vlachojannis JG. Intermittent

peritoneal dialysis (IPD): an old but still effective

modality for severely disabled ESRD patients.

Nephrol. Dial. Transplant. 2009;24 (10): 3215-

18.

10. Silbiger SR, Neugarten J. The role of gender in

the progression of renal disease. Adv. Ren.

Replace Ther. 2003;10(1):3-14.

11. Neugarten J, Acharya A, Silbiger SR. Effect of

gender on the progression of nondiabetic renal

disease: a meta-analysis. J. Am. Soc. Nephrol.

2000;11:319 – 29.

12. National Chronic Kidney Disease Fact Sheet

2010. http://www.cdc.gov/diabetes/pubs/

factsheets/ kidney.htm

13. Martins D, Agodoa L, and Norris K.Chronic

Kidney Disease in Disadvantaged Populations.

Int. J Nephrol.2012; http://dx.doi.org/10.1155/

2012/469265

14. Prakash J, Singh TB, Ghosh B, Malhotra V,

Rathore SS, Vohra R, etal. Changing

epidemiology of community-acquired acute

kidney injury in developing countries: analysis of

2405 cases in 26 years from eastern India. Clin

Kidney J. 2013;6(2): 150-55.

15. Nolph KD, Cutler SJ, Steinberg SM and Novak

JW. Continuous ambulatory peritoneal dialysis in

the United States: a three year study. Kidney Int.

1985;28:198-205.

16. Gokal R. Continuous ambulatory peritoneal

dialysis- Ten years on. Q J Med. 1987;63(242):

465-72.

17. Ahmed M Alkhunaizi and Ribert. Management of

Acute Renal Failure: New Prospectives. W

Schrier. Am J Kidney Dis. 1996;28(3); 315-28.

18. Bullock ML, Umen AJ, Finkelstein M and Kean

WF. The assessment of risk factots in 426

patients with ARF. Am J Kidney Dis. 1985;5 (2):

97-103

19. Anderson RJ, Linas SL, Bens AS, Henrich WL,

Miller TR, Gabow PA etal., Nonoliguric acute

renal failure. N Engl J med.1977;296 (20): 1134-

38.

20. Derrick LR, Vance GF, Daniel JS, Ralph GC,

Peter JC. Bacterial endocarditis in hemodialysispatients. Am J Kidney Dis. 1997;30 (4):521-24.

21. Shaheen FA, Sheikh IA, Badawi L, Al-Aqeil N,

Reyati JM. Complication of subclavian vein

cannulation in hemodialysis patietns. Saudi

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22. Schillinger F, Schillinger D, Montagnac R, Miller

T. Postcatheterization vein stenosis on

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12Gandhi et al., Int J Med Res Health Sci. 2014;3(1):12-15


&

Health Scienceswww.ijmrhs.com Volume3 Issue1(Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 6th Sep 2013 Revised: 9th Oct 2013 Accepted: 4th Nov 2013

Research article

A STUDY ON CHANGES IN SERUM GGT AND MAGNESIUM LEVEL IN ALCOHOLIC LIVER

DISEASE

*Gandhi Paulin A1, Sendhav Sandip S

2, Sanghani Hiren I

2, Patel Arpita P

3

1Tutor, Departments of Biochemistry, G.C.S. Medical College, Ahmedabad, Gujarat, India

2Senior Resident, Departments of Biochemistry, B. J. Medical College & Civil Hospital, Ahmedabad, Gujarat

3Junior Lecturer, Departments of Biochemistry, N.H.L. Medical College, Ahmedabad, Gujarat, India


ABSRACT

Aims: A study on changes in Serum GGT and Magnesium level in Alcoholic Liver Disease. Material and

Methods: Serum GGT and Serum Mg++

were estimated with the help of commercially available kit in patients of

Alcoholic Liver Disease (n=50) and Normal Individuals (n=50) on fully automated biochemistry analyzer Erba

XL-640. Results: Serum GGT level was found significantly higher (P< 0.01) in Alcoholic patients as compared to

healthy non-alcoholics. Moreover Serum Mg++

was found significantly lower (P< 0.01) in Alcoholic Liver

Disease as compare to normal Individuals. In addition to that there is significant inverse correlation (r= - 0.553)

between serum GGT and Mg++

in study group. Conclusions: None of the individual tests of conventional liver

function tests are of much importance in diagnosis of liver disease; however when many of the liver function tests

are abnormal at the same time, liver disease is the most probable diagnosis. Data of the present study clearly

conclude that serum GGT activity along with serum Mg++

status can be useful marker for alcoholic liver disease.

Keywords: Gamma Glutamyl Transferase, Magnesium, Alcoholic Liver Disease

INTRODUCTION

Excessive alcohol consumption and consequent

medical disorders are considerable problems in our

countries which causes a wide variety of medical and

social problems1. It is estimated that only 20-50 % of

patients with alcoholism are actually identified in

health care and thus more reliable and accurate

methods are urgently needed. There is no exact

clinical finding or symptom clinical setting that

can detect alcohol abuse in its early phase. So

there are some biochemical substances in the body

that can indicate the presence or progress of a

condition or any genetic predisposition toward it, are

called “Biomarkers”2

which may detect excessive

drinking and evaluate the extent of the resultant tissue

damage.

Gamma-glutamyl transferase (GGT) is a membrane-

bound glycoprotein enzyme which catalyzes the

transfer of the gamma-glutamyl moiety of glutathione

to various peptide acceptors. Chronic ethanol

consumption induces a rise in serum GGT, and it has

therefore been widely used as an index of excessive

ethanol intake3-4

. Its sensitivity varied from 15 to

85% in previous studies8-10

. Recent work by

comparing alcoholic group with normal control group

which emphasis on important factor serum GGT

activities which can increase in case of alcoholics5-6

.

Magnesium (Mg++)

a ubiquitous element, involve in

membrane stabilization, ion transport, and Ca++

channel activity, cofactor for more than 300 enzymes7, may get depleted by several mechanisms associated

with alcoholism like magnesium deficiency,

including urinary Mg++ wastage, malnutrition,

gastrointestinal losses, phosphate deficiency,

acidosis/alkalosis, vitamin D deficiency etc.

DOI: 10.5958/j.2319-5886.3.1.003




This work was aimed at investigating the diagnostic

value of serum GGT level and Serum Mg++

level and

correlation of serum GGT and Mg in the evaluation

of chronic alcoholic liver disease.


In the present cross-sectional study, 50 cases of

Alcoholic liver disease and 50 normal individuals

were selected from OPD and various clinical wards of

B.J. Medical College and Civil Hospital, Ahmadabad,

Gujarat during the period of April 2010 to December

2012. The study was approved by the BJ Medical

college, Ahmadabad and inform consent form was

obtained form the all participants. All patients were

primarily evaluated by clinical examination and then

confirmed by investigations for liver involvement due

to alcoholism. In study group (n=50), we have

included male patients between age of 20 – 60 years,

BMI ≤ 30 kg/m2, alcohol consumption for at least last

5 years with clinical evidence of alcoholic liver

dysfunction. In control group (n=50), we have

included normal healthy individuals having same age

and sex. Exclusion criteria: Age < 20 or >60 years,

Athletes, Clinical Evidence of current illness, Clinical

evidence of any chronic infection, Smoking had not

been allowed 1 hour prior to sampling, Protein energy

malnutrition, Post operative patient, Patient taking

anticonvulsant therapy (Benzodiazepines,

Phenobarbitone), BMI > 30 kg/m2, Serum Bilirubin

level > 20 mg/dL.

Venous blood was collected in clot activator serum

vacutte from all the participants. Serum was separated

and analyzed for GGT, Mg on fully Auto Analyzer –

Erba XL-640 at Biochemistry Section. Serum GGT

was analyzed by carboxy substrate8

method and

serum Mg was analyzed by calmagite method9

with

commercially available ready to use reagent kits.

Numerical variables are reported in terms of mean

and standard deviation. Comparison between two

groups is made with the Mann-Whitney test10

.

Correlations were calculated with pearson product

moment correlation coefficient by using graphpad

prism version 3.03 statistical software.

RESULTS

Table 1: Comparison of Serum GGT and Magnesium in Alcoholic Liver Disease and Normal Individual

ParameterBiological

Reference Interval

Group-1(ALDPatients)

n=50

Group-2(Control

Group)

n=50

Significance

Mean ± SD Mean ± SD P value

GGT 10-50 U/L 101.04 ± 52.2 42.02 ± 12.82 P<0.01*

Magnesium 1.6 – 3.0 mg/dL 1.50 ± 0.49 2.03 ± 0.36 P<0.01*

*P< 0.01: highly significant difference between two groups

In this study we measured Serum activity of Gamma

Glutamyl Transferase and Magnesium in both groups.

There is highly significant difference observed in

between study group and control group. Correlation

between serum GGT and Magnesium level in

alcoholic liver disease and normal individual during

observation significant inverse correlation (r= - 0.533,

P<0.01) was found in alcoholic patients whereas it

was not significant in normal individual (r= 0.031,

P>0.05).

Fig 1; Correlation of serum GGT with magnesium in

Study group

0

0.5

1

1.5

2

2.5

3

3.5

0 100 200 300

M a g n e s i u m ( m g / d L )

GGT (U/L)

Graph 1: Study Group




Fig 2: Correlation of serum GGT with magnesium in

control group

DISCUSSION

Liver serves many important biological functions to

sustain life, so early diagnosis of liver involvement is

of utmost priority to prevent life threatening

complications. Over past decade a large number of

new laboratory markers have emerged for alcohol

abuse. One of these is Gamma Glutamyl Transferase.

In order to assess its usefulness, I have studied Serum

GGT level and Serum Magnesium in 50 patients of

alcoholic liver disease and 50 normal individual. I

have tried to match control with the disease

population as far as possible.

Glutamyl transpeptidase (γGT) is an enzyme

produced in the bile duct. It is induced by alcohol and

its serum activity may be increased in heavy drinkers

even in the absence of liver damage or inflammation.

In this study the serum γGT levels were markedly

increased in alcoholic patients (P<0.01). The GGT

activity in serum increases after induction of the

enzyme, and the possibility of parenchymal damageshould always be considered. The elevation of γGT

alone with no other liver function test abnormalities

often results from induction by alcohol11

. The

results of present study are correlate well with earlier

studies by B. Usharani et al 201212

, Turecky L et al.

20067, Subir kumar Das et al 2005

13etc.

Chronic alcohol abuse also causes primary

malnutrition by insufficient dietary magnesium

intake. Moreover, as the cause of secondary

malnutrition chronic ethanol intake leads tofunctional and structural disorders in the

gastrointestinal tract that result from its direct action

on the gastrointestinal tract and damage to the liver

and pancreas. In also affects the magnesium transport

mechanisms in the plasma membrane, either directly

(alcohol-related modification of the phospholipid

environment or acetaldehyde-protein interaction) or

indirectly (via the decrease in cellular ATP

content).One of the major reasons for ethanol-

induced hypomagnesaemia in alcohol abusers is

increased urinary magnesium excretion due to

damage to the renal proximal tubules and the Henle

loop directly induced by ethanol15-17

. These study is

also supported by data of previous studies Elisaf M.

et al 199518

and Virginija Stasiukynienė et al 200219

.

It is concluded from the present study that the

estimation of serum GGT can be useful and more

cost-effective in diagnosing alcoholic liver diseases

as it significantly rises in alcoholic liver disease.

Moreover, serum Mg can also be used as a marker of

chronic alcoholic liver disease along with serum GGT

as they have significant correlation in alcoholic liver

disease.

CONCLUSION

It is concluded from the present study that the

estimation of serum GGT can be useful and more

cost-effective in diagnosing alcoholic liverdiseases as it significantly rises in alcoholic liver

disease. Moreover, serum Mg can also be used as

a marker of chronic alcoholic liver disease along

with serum GGT as they have significant

correlation in alcoholic liver disease.

REFERENCES

1. Room R, Babor T, Rehm, J. Alcohol and public

health. Lancet 2005; 365: 519 – 30.2. Peterson K. Biomarkers for alcohol use and

abuse: A summary. Alcohol Res Health 2004-

2005; 28(1):30-37.

3. Zein M, Discombe G. Serum gamma-glutamyl

transpeptidase as a diagnostic aid. The Lancet

1970; 296: 748 – 50.

4. Gogoi JB, Tyagi PK, Amit Singh. Study of serum

gamma glutamyl transferase as a diagnostic

marker in alcoholic hepatitis. IOSR Journal of

Pharmacy (IOSRPHR) 2012; 2; 69-71.5. Peters TJ, Cook CC. Obesity as a cause of

‘falsepositive’ alcohol misuse laboratory

0

0.5

1

1.5

2

2.5

3

3.5

0 20 40 60 80 100

M a g n e s i u m ( m

g / d L )

GGT ( U/L)

Graph 2: Control Group




investigations. Addiction Biology 2002; 7:443 –

46.

6. Katri Puukka. Gamma-glutamyl Transferase As a

Marker of Alcohol Abuse: Effects of Moderate

Drinking, Obesity & Increasing Age on

Reference Intervals, University of Tampere,

Medical School Seinajoki Central Hospital,

Department of Laboratory Medicine and Medical

Research Unit, Finland, 2007: pp 15.

7. Turecky L, Kupcova V, Szantova M. Serum

magnesium levels in patients with alcoholic and

non-alcoholic fatty liver. Bratisl Lek Listy. 2006;

107(3):58-61.

8. Bergmeyer H-U, Horder M, Rej R. IFCC

methods for the measurement of catalytic

concentrations of enzymes, J. Clin. Chem.Clin Biochem. 1986; 24: 497-510.

9. Gindler E. Colorimetric Determination With

Bound "Calmagite" of. Magnesium in Human

Blood Serum. Clin. Chem.1971; 17: 662.

10. Rosie Shier. Statistics:2.3 The Mann-Whitney U

Test. Mathematics learning support center

2004:1-5.

11. Keeffe EB, Sunderland MC, Gabourel JD. Serum

gamma-glutamyl transpeptidase activity in

patients receiving chronic phenytoin therapy.DigDis Sci. 1986; 31(10): 1056-61.

12. Usharani B, Vennila R, Nalini N. Biochemical

changes in Alcoholics: A case control study.

International Journal of Research in

Pharmaceutical and Biomedical Sciences 2012; 3:

201-05.

13. Subir Kumar Das, Prasunpriya Nayak,

Vasudevan DM. Biochemical markers for alcohol

consumption. IJCB 2005, 20(1): 35-42

14. Kocur J. Concentration of bioelements in alcohol

dependent patients. Biul.Magnezol. 1997; 2: 239.

15. Elisaf M, Merkooropoulos M. Pathogenetic

mechanisms of hypomagnesaemia in alcoholic

patients. J. Trace Elem. Med. Biol. 1996; 9: 210.

16. Vormann J. Magnesium: nutrition and

metabolism. Mol. Aspects Med.2003; 24: 27.

17. Elisaf M, Merkouropoulos M, Tsianos EV.

Pathogenetic mechanisms of hypomagnesemia

in alcoholic patients. J Trace Elem Med Biol

1995; 9: 210-14.

18. Virginija Stasiukynienė. Blood plasma

potassium, sodium and magnesium levels in

chronic alcoholic patients during alcohol

withdrawal. Medicina 2002; 38:892-95.



16

Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22


&

Health Sciences


thSep 2013 Revised: 15


thNov 2013

Research article

EFFECT OF GONADAL HORMONES ON HYPOPHAGIC PROPERTY OF OPIOID ANTAGONIST

NALOXONE

Gargate Ashwini R1, Kulkarni Dushant V

2

1Associate Professor,

2M. Sc (Med Physiology) Student, Department of Physiology, Krishna Institute of Medical

Sciences Deemed University, Karad, Maharashtra, India.


ABSTRACT

Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food

intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in

regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid

antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these

Gonadal hormones interact with Opioid receptors to modulate food intake. Objective: The aim of the study was to

find out how Gonadal hormones affect hypophagic property of Naloxone. Methods: Basal food intake of 40

healthy adult females and 20 healthy adult male rats was recorded. Then they were injected intraperitoneally with

Naloxone after fasting for 24 hrs. In female rats food intake was measured during different phases of the estrous

cycle. All the rats were then subjected to gonadectomy. The food intake was measured after gonadectomy. The

effect of Naloxone was also measured in deprivation paradigm after gonadectomy. Results: Female rats showed

decreased food intake during proestrous and estrous phases. In female rats there was no hypophagia after Naloxone

injection during these phases. Male rats showed hypophagia on Naloxone injection. Male rats showed increased

food intake after gonadectomy. In female rats the increase in food intake was not significant when gonadectomy

was done during metestrous and diestrous. However, Naloxone could induce hypophagia in all female rats after

gonadectomy. Conclusion: Estrogen decreases food intake, it decreases sensitivity of female rats to hypophasic

effects of Naloxone. Testosterone decreases food intake. Testosterone does not interfere with hypophagic effect of

Naloxone.

Keywords: Food intake, Gonadal hormones, Naloxone, Hypophagia.

INTRODUCTION

Appetite, energy balance and body weight gain are

modulated by diverse neurochemical and

neuroendocrine signals from different organs in the

body and diverse regions in the brain. Alterations in

the regulation of food intake and energy expenditure

underlie the development, progression and recurrence

of obesity.1,2

This has been the cause of obesityrelated complications like diabetes and hypertension

etc.

This energy balance and fuel utilization are

significantly affected by gonadal hormones, estrogen

in females and testosterone in males. Estrous cycle

related effects on food intake have been linked to the

effects of estrogen on central nervous system and

peripheral tissues.3,4,5

Rodents typically cycle over 4-5

days and phases of estrous cycle are commonlyclassified by histological changes in vaginal cytology

which is roughly divided into estrous, metestrous,

DOI: 10.5958/j.2319-5886.3.1.004



17


diestrous and proestrous.6

Food intake is generally

increased during diestrous and decreased during

estrous.7

So we confirmed these findings in our

laboratory by conducting the present study.

Previous studies suggest that estradiol acts on mu-

opioid receptors to modulate the antinociception in

rats.8

So estradiol may also modulate food intake by its

action on mu-opioid receptors. Therefore it may affect

the anorectic property of Opioid antagonist naloxone

during different phases of estrous cycle in female rats.

There are studies which show that in male rats

testosterone reduces food intake. Other studies also

show that opioid antagonist naloxone facilitates sexual

behaviour9

and there is no satisfactory explanation to

this. However, possible explanation could be the

interaction between testosterone and Naloxone which

can affect food intake as well.

So the present study was undertaken to evaluate if

Gonadal hormones alter food intake by acting on

opioid receptors in the central nervous system in

addition to their action on other parts of the CNS.


The present study was approved Institutional Animal

Ethics Committee of KIMS, Karad. 40 healthy adult

female and 40 healthy adult male Wistar rats were

used for the study. The average age was 3-4months

old. Animals were weighed, marked and housed in

separate polyvinyl cages in animal room having

controlled room temp (25±20c). They were maintained

on 12 hrs dark and 12 hrs light cycle with standard

laboratory diet and water ad lib.

First 8 days baseline food intake in all animals were

recorded. In female rats food intake was recorded

during different phases of estrous cycle.

In deprivation paradigm, the animals were kept fasting

for 24 hrs. Then saline 2ml was injected

intraperitoneally at 9 am on the day of test. 30 mins

after injection the food was weighed and introduced

into the cage. Then the food intake was measured at an

interval of ½ hr, 1hr, 2hrs and 24hrs. These values

were considered as control. Same animals were used

as control on 1st

24 hrs deprivation with saline

injection and on 2nd

24 hrs deprivation they were

injected with naloxone

The animals were kept fasting for 24 hrs again on the

next day. Then 2.5 mg/kg naloxone was injectedintraperitoneally at 9 am on the day of test. 30 mins

after injection the food was weighed and introduced

into the cage. Then the food intake was measured at an

interval of ½ hr, 1hr, 2hrs and 24hrs.

Every time the intake was measured by weighing food

prior to and after each condition and adjusting for

spillage that was collected in paper towel under wire

mesh.

Food intake in deprivation paradigm after saline and

after naloxone injection in male and female rats was

recorded. In addition to this the female rats’ food

intake was recorded during different phases of estrous

cycle after naloxone injection in deprivation paradigm.

Vaginal cytology for stage of estrous cycle: Daily

vaginal smears were obtained at 8.30am to assess the

stage of estrous cycle. Smears were examined under

light microscope. Stage of the cycle was assigned

using the following criteria as previously described6

1) Proestrous when predominantly nucleated epithelial

cells in the absence of leukocytes were present.

2) Estrous when sheets of nonnucleated squamus

cornified cells in absence of leucocytes were present.

3) Metestrous (D1) when there was an equal

distribution of leucocytes and cornified and nucleated

epithelial cells.

4) Diestrous (D2) when a mixture of epithelial cells

and leucocytes with predominance of leucocytes was

present.

Then both male and female rats were gonadectomised.

Procedure for ovariectomy: The female rats were

weighed and then injected with atropine sulphate in a

dose of 0.25mg subcutaneously to minimise the

respiratory discomfort. Intraperitoneal Sodium

pentobarbitone in the dose of 35mg/kg body weight

was injected for anaesthesia, whereas Ether inhalation

was used to maintain a steady level of anaesthesia

while doing gonadectomy.

Anaesthetised rat was placed on a rat operating table

with ventral surface facing towards operator. Animalwas secured properly to the operation table.

Midline incision was taken on lower abdomen

extending for 2cms lengthwise. A snip was made

through the fascia of abdominal rectus muscle. The

points of forceps were forced through the snip and

hole was extended opening the forceps. The ovary was

found embedded in the fat lying just below the dorsal

muscle mass. It was identified by fimbrial end. The

ovary was drawn through the incision, uterus clamped

in a haemostat and a ligature placed around the uterus just below fallopian tube and was tied tightly. The

ovary was removed. Similarly other ovary was also

removed. The muscle incision was closed with catgut



18


and skin incision with thread. Powder Nebasulf was

sprinkled over the sutures and Benzathin Penicillin, 3

lakh units was injected intramuscularly to prevent

infection. Animal was allowed to recover from

anaesthesia and then was transferred to respective

cage.

A period of 10 days was allowed for recovery from

operative injury following which vaginal smears were

examined for 1 week. Continuous diestrous was taken

as an indication for successful gonadectomy.

Procedure for Orchidectomy: The male rats were

weighed and then injected with atropine sulphate in

dose of 0.25mg subcutaneously to minimise the

respiratory discomfort. Then they were anaesthetised

as in female rats. Anaesthetised rat was kept on the rat

operating table. Part to be operated was shaved

properly. Under aseptic precautions ventral midline

incision was made through the skin of the scrotum.

The slight pressure was given on abdomen as rats are

able to retract testes in abdominal cavity. They were

freely movable within the scrotum. One testis was

drawn through a skin incision. A slit was made

through tunica and the testis was freed. The spermatic

cord which was attached to the testis was doubly

ligated and cord was cut between the ties. Other testis

was removed similarly. Skin incision was closed with

thread sutures. Powder Nebasulph was sprinkled on

sutured skin and rat was injected with 3 lakh units of

Benzathin Penicillin intramuscularly to prevent

infection. 10 days were allowed for recovery from

operative injury.

After measuring 8 days basal food intake, all

gonadectomised rats were injected with 2.5mg/kg

intraperitoneally naloxone after keeping them fasting

for 24 hrs. The food intake was measured as was done

before gonadectomy. Food intake was measured in

grams.

Statistical analysis: For data analysis all the values

were expressed in terms of mean ± standard error of

mean. Differences between means were compared by

applying paired‘t’ test. The effect was considered

statistically significant if the probability of chance was

less than 0.05 (p<0.005).

RESULT

Table 1: Food intake in female rats during different phases of estrous cycle

Phase of estrous cycle Food intake (in gms.) at different time of the day

1hr 1.5hr 2.5hr 24hr

Proestrous 0.6 ±0.44* 1.1±0.30* 2.0 ± 0.71* 7.1 ± 0.24*

Estrous 1.35± 0.43 1.86±0.53 3.3±0.71 9.5 ±0.98

Metestrous 2.87±0.55* 4.16±0.98* 6.29 ±0.92* 13.16 ±0.71*

Diestrous 2.5 ± 0.15* 3.9 ±0.24* 5.3±0.23* 13.82± 0.39

*P< 0.05, data presented as Mean ± SEM

Table 2: Effect of different phases of estrous cycle on Naloxone induced hypophagia in deprivation paradigm

in female rats.

Phase of estrous cycle Food intake (in gms.)

Proestrous 1hr 1.5hr 2.5hr 24hr.

After saline injection 1.7 ±0.11 2.75 ± 0 4.2 ± 0.37 10.25 ±0.33After Naloxone injection 1.2 ± 0.32 2.5 ± 0.16 3.9 ±0.24 19.0 ±0.39

Estrous

After saline injection 1.33 + 0.40 1.98 ± 0.46 3.45 ±0.42 8.23 ± 0.77

After Naloxone injection 0.93 ±0.09 1.75 ±0.27 3.00 ±0.42 10.11 ± 0.29

Metestrous

After saline injection 3.9 ±0.55 5.0 ±0.93 7.1 ±0.92 15.2±0.71

After Naloxone injection 1.2± 0.31* 1.98 ± 0.23* 3.56± 0.53* 14.7 ± 0.29

Diestrous

After saline injection 3.1 ± 0.22 4.5 ±0.62 6.8 ±1.1 14.3±0.35

After Naloxone injection 1.5 ± 0.44* 2.25 ± 0.33* 4.25 ±0.53* 15.2 ± 0.75


Table 2 shows the effect of food deprivation on food

intake in different phases of estrous cycle. After 24 hrs

fasting in female rats during estrous phases there was

no significant increase in food intake.



19


However, in metestrous, diestrous and proestrous

phases the food intake was significantly increased after

24 hrs fasting.

This table also shows effect of naloxone on food

intake in different phases of estrous cycle. It was seen

that Naloxone induced significant hypophagia in rats

after 24hrs fasting in metestrous and diestrous. In

proestrous and estrous phases naloxone could not

induce hypophagia in deprivation paradigm.

Table 3: Effect of gonadectomy on food intake and naloxone induced hypophagia in female rats in

deprivation paradigm.

Phase of estrous cycle Food intake (in gms)

Proestrous 1hr 1.5hr 2.5hr 24hr.

saline injection before gonadectomy 1.7 ± 0.11 2.75 ± 0 4.2 ± 0.37 10.25 ± 0.33

saline injection after gonadectomy 4.8± 1.1* 5.89 ±0.76* 6.7 ± 0.83* 14.6 ± 0.45*

Naloxone injection after gonadectomy 2.9 ±0.32* 4.2 ±0.16* 5.3± 0.24* 13.9± 0.39

Estrous

saline injection before gonadectomy 1.33 ± 0.40 1.98± 0.46 3.45± 0.42 8.23 ±0.77

saline injection after gonadectomy 3.16 ± 0.42* 3.6 ±0.53* 5.06± 0.71* 13.66±0.98*Naloxone injection after gonadectomy 1.58 ± 0.29* 2.5± 0.15* 3.75± 0.53* 12.95 ±1.46

Metestrous

saline injection before gonadectomy 3.9 ± 0.55 5.0 ± 0.93 6.1 ± 0.92 15.2 ± 0.71

saline injection after gonadectomy 4.4 ±0.55 5.2 ±0.44 6.7 ± 0.13 15.6 ± 0.89

Naloxone injection after gonadectomy 2.12± 0.31* 3.75 ± 0.23* 4.25± 0.53* 15.7 ± 0.29

Diestrous

saline injection before gonadectomy 3.1± 0.22 4.5 ± 0.62 6.8 ±1.1 14.3 ± 0.35

saline injection after gonadectomy 4.9 ±0.33* 5.5 ± 0.9* 7.7 ± 0.24* 15.4 ± 0.56*

Naloxone injection after gonadectomy 2.15 ± 0.65* 3.96 ± 1.07* 5.43± 0.47* 15.9 ± 0.98


Table 4: Food intake after orchidectomy and naloxone injection

Before Gonadectomy Food intake (in gms.)

1hr 1.5hrs 2.5hrs 24hrs

Basal food intake 2.2 ± 0.27 3.2 ± 0.46 4.6 ± 0.80 15.1± 0.82

After 24 hrs fasting

After Saline injection 3.0 ± 0.36* 4.3 ± 0.55* 5.7 ± 0.82* 15.6 ±0.82

After Naloxone injection 0.6 ± 0.24* 1.7 ± 0.28* 3.0 ± 0.59* 11.8 ± 1.1

After Gonadectomy

Basal food intake 4.2 ± 0.48* 5.5 ± 0.45* 6.5 ± 0.60* 17.0 ± 0.71*

After 24hrs fasting 1hr 1.5hrs 2.5hrs 24hrs

After Saline injection 4.9 ± 0.57* 6.2 ± 0.42* 7.2 ± 0.76* 17.2 ±1.88

After Naloxone injection 1.0 ± 0.19* 1.6 ± 0.42* 3.0 ± 0.59* 11.2 ±1.37


Table 3 shows the effect of ovariectomy on food

intake and hypophagia induced by Naloxone in female

rats. It is seen that the food intake was significantly

increased after ovariectomy in all female rats.

However, the increase was not significant when

ovariectomy was done during metestrous phase.

This increase was more pronounced in the female rats

in which ovariectomy was done in estrous and

proestrous phases. Naloxone induced significant

hypophagia in all rats after ovariectomy in initial

period after 24hrs food deprivation.

Table 4 shows food intake in male rats. Food intake issignificantly increased after orchidectomy. In



20


deprivation paradigm naloxone induced hypophagia in

initial period of the day before and after orchidectomy.

DISCUSSION

The present study was designed to examine whether

the gonadal hormones affect the hypophagic propertiesof naloxone upon food deprivation induced

hyperphagia. It appears that naloxone induces

hypophagia in food deprived male and female rats as

compared to controls (saline). These concur with the

earlier studies.10

It is known that after puberty male rats weigh and eat

more than do female rats of same age. This sex

difference is more pronounced with age. We also

studied the role of sex hormones in regulation of food

intake. We found that during the estrous phase thefood intake of female rats was less and least in

proestrous phase. The food intake was increased

during diestrous but it was highest during metestrous.

These findings are consistent with other workers.11-13

This could be because of wide variations in estrogen

levels during the phases of estrous cycle. The sequence

of phases in the cycle is proestrous, estrous,

metestrous and diestrous. The estrogen levels start

rising in diestrous reaching its peak in proestrous and

start declining during estrous decreasing to lowest

level during metestrous.14,15 Estrogen is known to

affect food intake thorough central and peripheral

mechanisms. Several lines of evidence indicate that the

effects of estradiol on food intake are mediated by its

actions on estrogen receptors within the brain. In the

early 1970's, Wade and Zucker were the first to report

that direct stimulation of the ventromedial

hypothalamus (VMH) by estradiol influenced feeding

behavior in female rats. They found that central

implants of undiluted estradiol benzoate (EB) in the

VMH decreased food intake in ovariectomized rats. 16

In this study we found that after gonadectomy in

female rats there was a significant increase in food

intake. This increase was more pronounced in female

rats where gonadectomy was done during proestrous

and estrous. Perhaps this explains the effect of

withdrawal of high estrogen after gonadectomy.

In our study we found that Naloxone which is an

opioid receptor antagonist blocking mu- receptors,

induces hypophagia in food deprived male and female

rats (p<0.05) as compared to controls (saline). Itappears that naloxone induces hypophagia in food

deprived male and female rats as compared to controls

(saline injection). These concur with the earlier

studies.17,18

One of the main functions proposed for

opioid peptides in the CNS is involvement in

mediation of hunger component in the control of food

intake. Changes in the beta endorphin content of

pituitary or hypothalamus have been demonstrated

under condition designed to reflect changes in the state

of hunger or satiety in rats. In normal rats fasted for 2-

3 days beta endorphin content of the whole

hypothalamus is decreased.19

Several investigators

have also reported that administration of beta

endorphins in CNS increased food intake.20

Intake of

palatable food containing sugar or high fat is

selectively increased by mu-opioid agonist when

injected into ventromedial striatum including nucleus

accumbens.10

Other studies also show that agonists of

mu, delta, kappa and ORL Opioid receptors increase

food intake while Opioid receptor blockade decreases

food intake.21

In female rats we studied the effect of estrous cycle

phases on the hypophagic effect of Naloxone. It was

observed that during proestrous and estrous phases the

Naloxone failed to induce hypophagia in these rats.

Our findings are consistent with earlier studies.22

It is

seen from the previous studies that gonadal steroids

modulate opioid peptides and receptors in the central

nervous system.23- 25 Ovariectomy in rats results in an

increased sensitivity to suppressive effects of

Naloxone on food intake compared with estradiol-

treated ovariectomised rats.26-29

The probable

explanation for this may be that estrogen acts on mu-

opioid receptors in the brain to modulate the functions

of Opioid peptides.8

When Naloxone is injected it fails

to block the Opioid receptors which are already

blocked competitively by estrogen. So Naloxone fails

to induce hypophagia in the presence of high estrogen.

In this study we found that after gonadectomy in allthe female rats naloxone induced significant

hypophagia when estrogen was no more there for

competitive blockade of the receptors.

In male rats also Naloxone induced hypophagia in

deprivation paradigm. After gonadectomy the basal

food intake of male rats was increased. After

gonadectomy in these male rats food intake was

significantly increased. In all these rats Naloxone

induced significant hypophagia before and after

gonadectomy. These findings suggest that testosteronein males interferes with the mechanisms on energy

intake however unlike estrogen it does not interact



21


with opioid receptors to alter the hypophagic effect of

Naloxone. Our findings concur with the other studies.

Gonadectomised male rats treated with testosterone

propionate showed decrease in food intake.21

CONCLUSION

Amongst the Gonadal hormones estrogen in females

and testosterone in males modulates food intake.

However, estrogen interferes with the hypophagic

effects of naloxone perhaps by competitive blockade

while there is no such alteration caused by

testosterone. How do these Gonadal hormones and

Opioid receptors interact to modulate food intake

needs to be further investigated.

ACKNOWLEDGEMENT

The authors are thankful to the vice chancellor and

principle KIMS deemed university, Karad for

providing us all the laboratory facilities for doing this

work. We are also thankful to our laboratory

technicians for assisting us during operative

procedures.

Conflict of interest-None declared.

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1. Levin BE, Dunn-Meynell AA, Banks WA.

Obesity-prone rats have normal blood-brain barrier

transport but defective central leptin signalling

before obesity onset. Am J Physiol Regul Integr

Comp Physiol. 2004; 286: 143 – 50.

2. MacLean PS, Higgins JA, Johnson GC. Metabolic

adjustments with the development, treatment, and

recurrence of obesity in obesity-prone rats. Am J

Physiol Regul Integr Comp Physiol. 2004;

287:288 – 97.3. Asarian L, Geary N. Modulation of appetite by

gonadal steroid hormones. Philos Trans R Soc

Lond B Biol Sci. 2006; 361: 1251 – 63.

4. Henry BA, Clarke IJ. Adipose tissue hormones

and the regulation of food intake. J

Neuroendocrinol. 2008; 20: 842 – 49.

5. Peter C. Butera. Estradiol and the control of food

intake. Physiol. Behav. 2010; 9:99-175.

6. Schedin P, Mitrenga T, Kaeck M. Estrous cycle

regulation of mammary epithelial cell

proliferation, differentiation, and death in the

Sprague-Dawley rat: a model for investigating the

role of estrous cycling in mammary

carcinogenesis. J Mammary Gland Biol Neoplasia.

2000; 5: 211 – 25.

7. Eckel LA, Houpt TA, Geary N. Spontaneous meal

patterns in female rats with and without access to

running wheels. Physiol Behav. 2000; 70: 397 –

405.

8. Erin C. Stoffel, Ulibarri CM, Folk JE. Gonadal

hormone modulation of mu, kappa and delta

Opioid nociception in male and female rats. J pain.

2005;6: 261-74.

9. Cassidy Vuong, Stan H. M. Van Uum, Laura E.

O'Dell. The Effects of Opioids and Opioid analogs

on Animal and Human Endocrine Systems.

Endocr Rev. 2010; 31: 98 – 132.

10. Jones JG, Ritcher J A. The site of action of

naloxone in suppressing food and water intake in

rats. Life science 1981; 18:2055-64.

11. Blaustein JD, Wade GN. Ovarian influences on

meal patterns of female rats. Physiol

Behav.1976;17: 201 – 08.

12. Butcher RL, Collins WE, Fugo NW. Plasma

concentrations of LH, FSH, prolactin,

progesterone and estradiol-17β throughout the 4-

day estrous cycle of the rat. Endocrinology 1974;

94:1074 – 78.

13. Ter Haar MB. Circadian and estrual rhythms in

food intake in the rat. Horm Behav 1972;3: 213 –

20.

14. Ariel Garcia, Iman Allawzi, Kayla McGuire. The

effects of progesterone and estrogen on

vasoconstriction in rats. Biological Sciences

Purdue University, W. Lafayette, IN,47907 1985:

poster 11-16

15. Marcondes FK, Bianchi FJ, Tanno AP.

Determination of the estrous cycle phases of rats:

some helpful considerations. Brazilian Journal of

Biology. 2002; 62: 609-614

16. Wade GN, Zucker I. Modulation of food intake

and locomotor activity in female rats by

diencephalic hormone implants. J Comp Physiol

Psychol 1970; 72: 328 – 38.

17. Meli R, Pacilio M, Raso GM. Estrogen and

raloxifene modulate leptin and its receptors in

hypothalamus and adipose tissue from

ovariectomized rats. Endocrinology. 2004; 145:

3115 – 21.



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18. Gambert SR, Garthwaite JL, Pontzer CH, Hagen

TC Fasting is associated with decrease in

hypothalamic beta endorphin. Science 1981;

213: 1282-83

19. Temple DL, Leibiwitz SF. PVN implants: Effects

on feeding pattern and micronutrient selection.Brain. Res. Bull. 1989; 23: 553-60.

20. Glass M J, Billinton CJ, Levin AS. Opioid and

food intake: distribution of neural pathways.

Neuropeptides 1999; 33: 360-68

21. DuPont A, Barden N, Cusan C. P-endorphin and

met-enkephalin: Their distribution, modulation by

estrogens and haloperidol, and role

inneuroendocrine control. Fed Proc. 1980; 39:

2544.

22. Hahn EF, Fishman J. Changes in rat brain opiate

receptor content upon castration and testosterone

replacement. Biochem Biophys Res Commun.

1979; 90: 819-23.

23. Hong JS, Yoshikawa K, Lamartiniere CA. Sex

related difference in the rat pituitary [Met”]-

enkephalin level-altered by gonadectomy. Brain

Res. 1982; 251: 382-83.

24. Lee SA, Panerai E, Bellabara D, Friesen HG.

Effect of endocrine modifications and

pharmacological treatments on brain and pituitary

concentrations of P-endorphin. Endocrinology.

1980; 107: 245-48.

25. Morley JE, Levine AS, M Grace, The effect of

ova~ectomy, estradiol and progesterone on opioid

modulation of feeding. Physiol Behav. 1984;33:

237-41.

26. Harishankar N, Giridharan N. Restoration of libido

in male rats by administration of high dose

testosterone propionate. Advanced Studies in

Biology. 2012; 4: 557-71.

27. Witte MM, Resuehr D, Chandler AR. Female miceand rats exhibit species-specific metabolic and

behavioral responses to ovariectomy. Gen Comp

Endocrinol. 2010; 166: 520 – 28.

28. Rogers NH, Perfield JW, Strissel KJ. Reduced

energy expenditure and increased inflammation

are early events in the development of

ovariectomy-induced obesity. Endocrinology.

2009; 150:2161 – 68.

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controlling food intake and body weight.

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23

Hassan et al., Int J Med Res Health Sci.2014;3(1):23-27


&

Health Sciences

www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 23

rdSep 2013 Revised: 17


thNov 2013

Research article

HEMOGLOBIN A1C INDUCED DOWN-REGULATION OF CD36 OF PLASMODIUM FALCIPARUM

PARASITIZED RED CELL

Hassan Hijazi1, Atif Alagib

2, *Hisham Waggiallah

3

1AL-Ghad International Colleges for Applied Health Science, Qassim, Saudia Arabia

2Tropical Medicine Research Institute, National Centre for research, Ministry of Science and Technology, P. O.

1304, Sudan.3Department of Medical Laboratory, Faculty of Medical Applied Science, Taibah University. P.O Box 3001,

Almadinah Almonawarah, Saudia Arabia.


ABSTRACT

Objective: High values of glycosylated hemoglobin have been found to correlate with decreased deformability of

erythrocyte. CD36 (Cluster of Differentiation 36) is an integral membrane protein found on the surface of many cell

types of class B scavenger receptor family. Plasmodium falciparum and diabetes mellitus is associated many

complications. Aim of this study to investigate the down-regulation of HbA1c to CD36 on P. falciparum parasitized

red blood cells Diabetes mellitus patients. Methods: This is cross section study conducted among diabetic patients

attending in Jabir Abo Eleiz diabetic center in Khartoum state. Venous blood samples were collected in heparin

containers for Plasmodium falciparum culture, and random blood sugar. For HbA1c in 0.04 mg EDTA

anticoagulant, 2-5 ml of blood was collected. Sample size was 45 samples and was collected from known diabetic

patients with HbA1c more than 8%. All data were analyzed by using Statistical Package for Social Science (SPSS).

Results: show the mean difference between CD36 negative control and CD36 positive control was found to be

statistically significant increasing of CD36 presence at P. value =0.001 (P ≤0.001). The mean difference between

CD36 positive control and diabetic patients with HbA1C more 8% was found to be statistically significant reduction

of CD36 expression at p=0.001. Conclusion: Hyperglycemia (HbA1c) leads to decrease of CD36 expression and

interfere with innate and active immunity. In this study HbA1c participates in increasing of P. falciparum malaria

complications.

Keywords: HbA1c, CD36, Plasmodium falciparum, Diabetes mellitus.

INTRODUCTION

Glycation of proteins is a frequent occurrence, but in

the case of hemoglobin, a non-enzymatic reaction

occurs between glucose and the N-end of the beta

chain. Abnormal glycation, which can adversely affect

hemoglobin and membrane proteins in erythrocytes,

has been shown to correlate with reduced membrane

fluidity1 separately, high values of glycosylated

hemoglobin have been found to correlate with

decreased deformability of erythrocyte.2

CD36 is a multi-functional molecule. It has

independent binding sites for different classes of

ligands Such as modified phospholipids,

thrombospondins, and free fatty acids. This enables

CD36 responsible for several different cellular

processes depending on the nature of the ligand and

the type and location of the cell on which it is

expressed. On phagocytes CD36 functions as a

scavenger receptor helping in recognition and

DOI: 10.5958/j.2319-5886.3.1.005



24


internalization of apoptotic cells3, falciparum malaria

infected erythrocytes.4,5

CD36 also functions as an adhesion molecule, it has

been identified CD36 as the receptor that helps in

cytoadherence of Plasmodium Falciparum parasitized

erythrocytes6, It has been reported that CD36 on

platelet mediates clumping of P. falciparum infected

erythrocytes is strongly associated with severe

malaria.7

In contrast, CD36 on monocytes or

macrophages can help phagocytosis of falciparum

Infected erythrocytes. Thus the location of CD36

receptor can regulate the severity of malarial disease.

Several studies have suggested an important role of

CD36 in phagocytic clearance of apoptotic and

Senescent cells.8

Malaria culture is the method to grow

malaria parasite outside the body i.e. in an in vitro

environment. P. falciparum is currently the only

human malaria parasite that has been successfully

cultured continuously in vitro. Although attempts for

propagation of the parasites outside of humans or

animal models.9

METHODOLOGY

Ethical approval: Ethical clearance obtained from the

Ethical Committee Board of the Tropical Medicine

Research Institute. The consent was taken from

patients and taken the permission from medical

management of Jaber Abu Ezz Diabetes Center and

selected individual after being informed with all

objectives of the study and its health impact in the

future.

This is cross section study was conducted in Khartoum

state among diabetic patients attending in Jabir Abo

Eleiz diabetic Centre. In an aseptic conditions ml

venous blood samples were collected in heparin

containers for culture, Ox LDL, and Random Blood

Sugar (RBS). For HbA1c in 0.04 mg EDTA

anticoagulant, 2-5 ml of blood was collected. Thesamples were mixed well and tested within 6 hour.

Samples were classified into three groups:

Group I: 15 samples were collected from apparently

health People free from any disease as negative

control.

Group II: 15 samples were cultured with Plasmodium

falciparum as CD36 positive control. Culture

technique as following: Erythrocytes were washed 3

times in Roswell Park Memorial Institute medium

(RPMI) 1640 to remove citrate phosphate dextrose

(CPD), serum, and leukocytes if present. Dilute to 5%

hematocrit with cMCM in small flasks of 25cm2 (0.2

mL of packed cells to 4 mL of malaria culture media

(MCM) or in 75-cm2 flasks (1.0 mL to 20 mL).

Parasites were added to an appropriate parasitemia.

Flask was put in a candle jar and loosens the screw

cap. Produce low oxygen by burnt out candle and

place the jar at 37 °C. MCM was replace every day

(not necessary the day after sub cultivation).

Subculture was cultured 2 times / week.

Group III: 15 samples from known diabetic patients

(HbA1c more than 8%) and were tested for CD36.

CD36 was measured by Flow cytometer uses the

principles of light scattering, light excitation, and

emission of fluorochrome molecules to generate

specific multi-parameter data from particles and cells

in the size range of 0.5um to 40um diameter. Cells are

hydro-dynamically focused in a sheath of phosphate

buffer saline (PBS) before intercepting an optimally

focused light source; Lasers are most often used as a

light source in flow cytometer properties of single

particles (e.g. cells, nuclei, chromosomes) during their

passage within a narrow, precisely defined liquid

stream.

The hemolysate, where the labile fraction is eliminated

hemoglobin’s are retained by a cationic exchange

resin. Hemoglobin A1C (HbA1c) is specifically eluted

after washing away the hemoglobin A1a+b fraction1

(HbA1a+b), and is quantified by direct photometric

reading at 415 nm.

Quality control: All reagents and test equipment

were controlled according to the instructions in theprocedures manual, manufacturing control and control

sample were used in each test.

Data analysis: Data were analyzed by using Statistical

Package for Social Science (SPSS) version 21 and

Microsoft Excel 2013. Results were obtained by using

student T .test.

RESULTS

Table 1: Shows the mean difference of CD36 amount in negative control and positive control:

Group N Mean ± SD DF T P Value

CD36 negative control 15 0.3600 ± 0.12923 28 10.513 0.001**CD36 positive control 15 26.1000 ± 9.48194

P *≤ 0.05, P **≤ 0.01



25


Table 2: Shows the mean difference of CD36 amount in negative control and diabetic patients with HbA1C ≥ 8%

Group N Mean ± SD DF T P Value

CD36 negative control 15 0.3600 ± 0.12923 28 12.943 0.001**

CD36 in diabetic patient with HbA1C ≥ 8% 15 5.9460 ± 1.66648

Table 3: Shows the mean difference of CD36 amount in positive control and diabetic patient with HbA1C ≥ 8%Group N Mean ± SD DF T Sign

CD36 positive control 15 26.1000 ± 9.48194 28 8.108 0.001**

CD36 in diabetic patient with HbA1C ≥ 8% 15 5.9460 ± 1.66648

Table 4: Shows mean difference of RBCs percentage containing (CD36); between CD36 negative control and

positive control:

Group N Mean ± SD DF T-value P-value

CD36 negative control 15 1.7600 ± 0.64454 28 3.29 0.003**

CD36 positive control 15 11.1800 ± 11.05740

Table 5: Shows mean difference of RBCs percentage containing (CD36) between CD36 positive control and

diabetic patients with HbA1 C ≥ 8%

Group N Mean ± SD DF T-value P-value

CD36 positive control 15 11.1800 ± 11.05740 28 2.64 0.013*

CD36 in diabetics patients with HbA1 C≥8% 15 3.6067 ± 1.11257

Forty five (45) individuals participated in the present study.

In table: 1 the mean difference between CD36

negative control and CD36 positive control was found

to be statistically significant at P. value =0.001 (P≤0.001).

The mean difference between CD36 negative control

and CD36 in diabetic patients with HbA1C ≥ 8% was

highly significant at P. value = 0.001 as shows in

table 2.

The mean difference between CD36 positive control

and diabetic patient with HbA1C more 8% was found

to be statistically significant at p=0.001 as shows in

table 3.

The mean difference percentage of RBCs containing(CD36) between CD36 negative control and CD36

positive control was found to be statistically

significant at p = 0.003 as shown in table 4.

The mean difference of percentage of RBCs

containing (CD36) between CD36 Positive control and

CD36 in diabetics patients with HbA1 C>8% was found

to be statistically significant at p = 0.013 as shown in

table 5.

DISCUSSION

HbA1c occurs when hemoglobin joins with glucose in

the blood. Hemoglobin molecules make up the red

blood cells in the blood stream. When glucose sticks to

these molecules it forms a glycosylated hemoglobin

molecule, also known as A1c and HbA1c. The moreglucose found in the blood the more glycated

hemoglobin (HbA1c) will be present.10

CD36 is a broadly expressed membrane glycoprotein

that acts as a facilitator of fatty acid uptake, a receptor

for low density lipoprotein, and malaria infected

erythrocytes. Despite an impressive increase in

knowledge of CD36 functions, in depth understanding

of the mechanistic aspects of this protein remains

elusive. This study focuses on the impact of

hemoglobin A1c on CD36 of Plasmodium falciparuminfection in diabetic patients.

In present study when data of red blood cells infected

with P. falciparum (P.F) was compared with normal

healthy RBCs there was significant (P < 0.001)

expression of CD36 in the red blood cell in addition,

comparison between the same groups also found

significant (P < 0.003) increasing of RBCs percentage

containing CD36 that means plasmodium falciparum

could increases the expression of CD36 on the surface

of the parasitized red cells. This agreed with Ho, M.and White, N.J. 1999,11

who were proposed CD36 a

major receptor for P. falciparum-infected red blood



26


cells (IRBCs). Moreover, comparison of the group

that contains parasitized red blood cell (P. falciparum)

with high concentration of glycosylated hemoglobin

(HbA1c) more than 8% with normal healthy RBCs

(negative control) there was significant (P < 0.001)

expression of CD36, and the CD36 expression was

expressed in the presence of HbA1c in small amount

which indicates the P.F plays a role in IRBCs cell

membrane leads to CD36 expression, this is has no

conflict with previous study that represented .These

abnormal circulatory properties of erythrocytes

involve parasite-induced alterations in their

biomechanical and adhesive properties and are

important for survival and pathogenicity of P

falciparum.12

Cytoadhesion is mediated by the

antigenically variant P. falciparum erythrocyte

membrane protein-1 (PfEMP1), which can bind to host

receptors including CD36 and chondroitin sulfate A

˶CSA˵

13PfEMP1 is concentrated on electron-dense

elevations of the membrane referred to as knobs.14,15

providing a platform for adherence under physiologic

flow conditions.16

Increased erythrocyte rigidity and

adhesiveness result in dramatically augmented

hemodynamic resistance observed in microvasculature

perfused with P falciparum – infected erythrocytes.17

However, the group that contains CD36 with high

concentration of glycosylated hemoglobin (HbA1c)

more than 8% has been compared with the group

which contains CD36 in patient with P. falciparum

malaria only (positive control) there was significant

reduction of CD36 expression (P < 0.001), also this

study agreed with Van Nieuwenhoven et al, 199818

was proposed that hyperglycemia might play an

important role in the regulation of CD36 expression

.The result in this study shows the significant effect of

HbA1c on CD36 expression reduction. Thus, these

results was agreed with the previous study shown thathyperglycemia is also associated with increased levels

of reactive oxygen species in diabetic red blood cell

and rise in the levels of the reactive carbonyl

compounds that worsen their compromised functions,

leading to diminished lifespan, accelerated non-

enzymatic modification of proteins, and loss of protein

function.19,20

A result of increased protein

glycosylation could participate in the mechanism,

whereby diabetic erythrocytes may acquire membrane

abnormalities.

21

Spectrin is a very important protein of erythrocyte membrane and a target for glycosylation

and further oxidation, which might be responsible for

increased number of poorly deformable erythrocytes

found among diabetic erythrocytes.22

Abnormal

glycation, which can adversely affect hemoglobin and

membrane proteins in erythrocytes, has been shown to

correlate with reduced membrane fluidity1

separately,

high values of glycosylated hemoglobin have been

found to correlate with decreased deformability of

erythrocyte.2

The reduction of CD36 expression may

have remarkable in the development of severity P.

falciparum malaria in diabetic patients.

CONCLUSION

We conclude that Plasmodium falciparum might

increase the density and amount of CD36 in

parasitized red blood cells. Hyperglycemia (HbA1c)

leads to down-regulate of CD36 expression and

interfere with innate and active immunity. In this studyHbA1c participates in increasing of P. falciparum

malaria complications.

ACKNOWLEDGEMENT

My sincere thanks extended to Hussain Higazi, and

Sayed Alshamy for their strong helping and support. I

am really indebted to the laboratories staff of Jaber

Abu Ezz Diabetic center for their help and assistance.

Conflict of Interest Statement: The authors of this

paper have no conflicts of interest, including specificfinancial interests, relationships, and/ or affiliations

relevant to the subject matter or materials included.

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8. Podrez, E. A., Febbraio, M., Sheibani, N., Schmitt,

D., Silverstein, R. L., Hajjar, D. P., Cohen, P. A.,

Frazier, W. A., Hoff, H. F., and Hazen, S. L.

Macrophage scavenger receptor CD36 is the major

receptor for LDL modified by Monocyte-

generated reactive nitrogen species. J Clin Invest.

2000; 105:1095-108.

9. Trager W, Jensen JB. "Continuous culture of

Plasmodium falciparum: its impact on malaria

research". Int J Parasitol. 1997; 27 (9): 989 – 1006.

10. Pani LN, Korenda L, Meigs JB, Driver C,

Chamany S, Fox CS etal., Relationship Between

A1C and Glucose Levels in the General Dutch

Population Diabetes Care. 2008; 10:1991-6.

11. Ho M. and White NJ. Molecular mechanisms of

cytoadherence in malaria. Am. J. Physiol. 1999;

276: C1231 – C42.

12. Cooke BM, Mohandas N, Coppel RL. Malaria and

the red blood cell membrane. Semin Hematol.

2004; 41:173-188.

13. Baruch DI, Rogerson SJ, Cooke BM. asexualblood stages of malaria antigens: cytoadherence.

Chem Immunol. 2002; 80:144-162.

14. Su XZ, Heatwole VM, Wertheimer SP. The large

diverse gene family var encodes proteins involved

in cytoadherence and antigenic variation of

Plasmodium falciparum-infected erythrocytes.

Cell. 1995; 82:89-100.

15. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian

J, Miyata M. Decreased atherosclerosis in mice

deficient in both macrophage colony-stimulatingfactor (op) and apolipoprotein E. Proc. Natl.

Acad. Sci. U.S.A. 1995; 92: 8264-68.

16. Crabb BS, Cooke BM, Reeder JC, Waller JC,

Caruana SR., Davern KM, et al., Targeted gene

disruption shows that knobs enable malaria-

infected red cells to cytoadhere under

physiological shear strees. Cell. 1997; 89:287-96.

17. Raventos SC, Kaul DK, Macaluso F, Nagel RL.

Membrane knobs are required for the

microcirculatory obstruction induced by

Plasmodium falciparum- infected erythrocytes.

Proc Natl Acad Sci U S A. 1985; 82:3829-3833.

18. Van Nieuwenhoven FA, Luiken JJ, De Jong YF,

Grimaldi PA, Van der Vusse GJ, Glatz JF Stable

transfection of fatty acid translocase (CD36) in a

rat heart muscle cell line (H9c2). J Lipid Res.

1998; 39:2039 – 47.

19. Constantin A, Constantinescu E, Dumitrescu M,

Calin A, & Popov D. Effects of ageing on

carbonyl stress and antioxidant defense in RBCs

of obese Type 2 diabetic patients. Journal of

Cellular and Molecular Medicine. 2005; 9: 683 –

91

20. Schwartz RS, Madsen JW, Rybicki AC, Nagel RL.

Oxidation of spectrin and deformability defects in

diabetic erythrocytes. Diabetes. 1991; 40(6):701-

08.

21. Lux SE. Spectrin-actin membrane skeleton of

normal and abnormal red blood cells. Seminars in

Hematology. 1979; 16(1):21-51.

22. McMillan DE, Brooks SM. Erythrocyte spectrin

glucosylation in diabetes. Diabetes. 1982;

31(3):64-69.



28

Abilasha et al., Int J Med Res Health Sci. 2014;3(1):28-31


&

Health Sciences


rdSep 2013 Revised: 19


thNov 2013

Research article

DERMATOGLYPHICS: A PREDICTOR TOOL TO ANALYZE THE OCCURRENCE OF BREAST

CANCER

Abilasha S1, *Harisudha R

2, Janaki CS

3

1Tutor, Department of Anatomy, KSR Institute of Dental Science & Research, Tiruchengode, Namakkal, Tamil

Nadu, India2

Tutor, Department of Anatomy, Melmaruvathur Adhiparasakthi Institute of Medical Science and Research,Melmaruvathur, Kanchipuram, Tamil Nadu, India3

Assistant Professor Department of Anatomy , Meenakshi Medical College and Research Institute, Enathur,

Kanchipuram, Tamil Nadu, India


ABSTRACT

Background: Dermatoglyphics is the branch of science that deals with the study of ridge patterns on finger tips,

palm, sole and toes and when once formed, they remain unchanged throughout the except after severe injuries.

These patterns can serve as a non-invasive, cost-effective tool which can be used for the prediction of cancer. This

can also serve as a baseline guide to identify women with breast cancer. Objective: To study the digital

dermatoglyphic patterns among women with breast cancer in comparison with normal individuals. Materials and

methods: 50 female patients with breast cancer of age group between 30-70 years were compared with 50 control

group of individuals with no history of cancer. The breast cancer patients and the control group were of the same

age and sex. Digital dermatoglyphic patterns were taken among these individuals with the aid of a dermatoglyphic

kit. Procedure involved was modified purvis smith method. Results: digital dermatoglyphic patterns were analyzed

between the patients and control group of individuals which showed statistical difference. Conclusion: we conclude

that there is a genetic influence on the dermatoglyphic patterns. With the aid of this, the occurrence of breast cancer

can be predicted and this dermatoglyphics can serve as a non-invasive, anatomical marker and a predictor tool to

determine the individuals with breast cancer.

Keywords: Breast cancer, Dermatoglyphics, Ridge patterns, Genetic marker

INTRODUCTION

Dermatoglyphics is a branch of science that deals with

the study of ridge patterns on finger tips, palm, sole

and toes. Dermatoglyphics traits are epidermal ridges

formed under genetic control early in development but

may be affected by environmental factors during the

first trimester of pregnancy. They however do not

change significantly thereafter, thus maintaining

stability not greatly affected by age. These epidermal

ridges are closely related to volar pads and these ridge

patterns form at the site of these pads. Harold and

Cummins1coined the term dermatoglyphics in 1926,

which they first used in a paper, the American journal

of physical anthropology. A detailed description on

ridge patterns was described in 17th

century2.

Widespread medical interest towards epidermal ridges

developed only in the last few decades when it became

an apparent factor that many patients with

chromosomal aberrations had unusual ridge patterns.

DOI: 10.5958/j.2319-5886.3.1.006



29


Inspection of these ridges therefore seems to provide a

simple and cost effective means of information to

determine whether the patients could have any

underlying changes in genotype.3


The material for this present study consisted of

fingerprints of patients selected from those attending

outpatient and inpatient clinics in the department of

Meenakshi Hospital, Kanchipuram and Jeevodhaya

Cancer Hospital – Retteri, Chennai.

Sample size:

The study consisted of 100 subjects categorized into

two groups including 50 patients with breast cancer

and 50 control groups of individuals.

Inclusion criteria: 1. 50 histopathologically

conformed female breast cancer patients age between

30-65 years.

2. Age matched 50 female control group individuals

with no history of cancer or any other genetic

disorders.

3. Treated, untreated and operated patients were used

for this study.

Exclusion criteria: 1. Individuals who had

deformities in their hands like burns or injury were

excluded.

2. Genetic disorders other than breast cancer were also

excluded. 3. Females under 30 years of age.

MATERIAL & METHODS

Data collection: After obtaining permission from the

Institutional Ethics Committee also inform consent

form was taken from the patient. Total 100 patients

(50 histopathologically conformed breast cancer and

50 normal age match control) were informed about the

procedure in detail and data comprising of age, sex

and address were taken.

Method : In our study with the help of the modified

Purvis smith method4

we have studied the fingerprint

patterns of controls and breast cancer individuals by

the arrangements of loop-ulnar loop, radial loop,

whorl- plain whorl, central pocket loop whorl, arches-

plain arch, tented arch, radial twinned loop, ulnar

twinned loop, accidental loop. The prints were

analyzed with the help of the finger print analyst.

RESULTS

In left hand thumb, ulnar loop, twinned loop ulnar and

twinned radial loop was maximum in control group of

individuals and whorl was maximum in breast cancer

patients which showed statistical significance.(p>0.05)

Fig 1: Comparison of dermatoglyphics pattern

between control and breast cancer (left hand)

(A=Arch, UL= Ulnar Loop,RL= Radial Loop, W=Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral

Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp=

Central Pocket Loop, Al= Accidental Loop.)

In left hand ring finger, arch and ulnar loop were

maximum in control group of individuals and whorls

were maximum in breast cancer patients when

compared to normal group.

In left hand little finger ulnar loop was maximum in

control group and arch, whorl was maximum in breast

cancer patients which showed statistical significance.

Fig 2: Comparison of dermatoglyphics pattern

between control and breast cancer (right hand)

(A=Arch, UL= Ulnar Loop,RL= Radial Loop, W=

Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral

Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp=

Central Pocket Loop, Al= Accidental Loop.)

In right hand ring finger arch and whorl were

maximum in breast cancer patients and arch wasmaximum in control group of individuals which

showed statistical significance. (p>0.05)



30


DISCUSSION

Chintamani5, Bierman

6, RJ Meier

7, has identified a

pattern of 6 or more digital whorls has been used to

identify women with breast cancer and whorls were

commonly observed in right ring finger and right little

finger in breast cancer patients. Hence, thedetermination of dermatoglyphic pattern of the finger

and palm is genetic, so it could serve as a suitable

parameter for differentiating individuals. Our study

also goes in accordance with the previous study that

we identified a pattern of whorls in 6 out of 10 digits

in 62% of the breast cancer patients whereas in a

control group of individuals it was the ulnar loop

pattern present in 6 out of digits. So this was a major

difference observed in our study, and in our study too

whorls were commonly seen in right ring finger andlittle finger among the breast cancer patients. Oladipo

8

has observed a significant association with ulnar loop

in 8 out of 10 digits in Nigerians and he has also

concluded that these dermatoglyphic findings will

serve as a baseline in the identification of women who

are at increased risk of developing breast cancer and

perhaps aid early treatment of the disease. He has also

observed that ulnar loop had highest mean percentage

frequency of the digital dermatoglyphic pattern

followed by whorl, arch and radial loop i.e., ulnar loopand whorl was higher in right hand and radial loop and

arch in left hand of breast cancer -patients. In our

study, we identified a significant association with

whorls and we have also observed that ulnar loop had

highest mean percentage frequency followed by whorl,

arch and radial loop. According to Natekar PE9, out of

1000 fingerprints, cancer patients had 33% whorls,

66.6% loops, 0.4% arches whereas the control group

had 63.8% whorls, 35.5% loops and 0.7% arches.

There was the presence of more than 6 loops in breast

cancer patients. In our study, out of 2000 fingerprints,

breast cancer patients had 47% loops, 44% whorls, 4%

arches, 2% ulnar twinned loop, 0.8% radial twinned

loop whereas the control group had 56% loops, 25%

whorls, 8% arches, 7% ulnar twinned loop, 3% radial

twinned loop. We have also observed there was the

presence of 0.4% tented arch and 0.4% accidental loop

among the breast cancer patients which was absent in a

control group of individuals. There was presence of

whorls in 6 out of 10 digits in 62% of the breast cancer

patients. Sakineh Abbasi 10, with an ever increasing

population it is important that methods be developed

to identify individuals who are either at risk or already

having illness in the most cost – efficient manner

without sacrificing quality of care. The use of

dermatoglyphics is a unique approach and cost

effective for identification in such individuals. In his

study of dermatoglyphic patterns, he has observed the

significant difference in right hand middle finger, ring

finger, left hand index finger, middle finger, ring

finger, little finger where there was an increase in loop

in all these digits and also observed whorls in 6 out of

10 digits in 48.7% of the breast cancer cases. In our

study, we have observed the significant difference in

the left hand thumb, ring finger, little finger, right

hand ring finger. We have also observed that the

whorls in <6 out of 10 digits in 62% of the breast

cancer patients.

CONCLUSION

The present study concludes that as there is a genetic

influence on the digital ridge patterns, these do not

change throughout the life. Hence with the aid of this

digital and dermatoglyphic pattern we can predict the

occurrence of breast cancer and this dermatoglyphics

can serve as a non-invasive, anatomical marker and a

predictor tool to determine the individuals with breast

cancer. We also conclude that with the help of this

ability to predict the earliest changes associated with

breast cancer it may allow to the introduction of more

effective preventive strategies.

ACKNOWLEDGEMENT

I would like to thank Dr. Deenadayalan for his

immense support to this work.

REFERENCES

1. Cummins HH. Epidermal Ridge Configurations in

Developmental Defects, with Particular

References to the Ontogenetic Factors Which

Condition Ridge Direction. American Journal of

Anatomy.1926;38(1), 89-151.

2. Huang CM, Mi MP. Digital dermal patterns in

breast cancer. Proc Natl Sci Counc Repub China

B. 1987;11(2): 133-6

3. Book JA. A fingerprint method for genetical

studies. Hereditas 1948;34:368

4. Purvis-Smith SG. Finger and palm printing

technique for the children. Med J Austria 1969;

2:189.

5. Chintamani, Rohan khandelwal, Aliza mittal,

Saijanani, Amita tuteja, Anju bansal etal.,



31


Qualitative and quantitative dermatoglyphic traits

in patients with breast cancer. New Delhi, India.

BMC Cancer 2007, 7:44

6. Bierman HR, Faith MR, Stewart ME. Digital

dermatoglyphics in mammary cancer. Cancer

Invest., 1988; 6(1): 15-27.

7. Schaumann BA, Meier RJ. Trends in

dermatoglyphic research. International Journal of

Anthropology1989;4(4):247- 54

8. Oladipo GS, Paul CW, Bob-Manuel IF,

Fawehinmi HB, Edibamode EI. Study of digital

and palmar dermatoglyphic patterns of Nigerian

women with malignant mammary neoplasm. J.

Appl. Biosci.2009; 15: 829-34.

9. Natekar PE, Desouza S, Motghare DD, Pandey

AK. Digital dermal patterns in Carcinoma Breast.

J. Anthropologist. 2006; 8: 251 –

254.

10. Sakineh Abbasi, Nahid Einollahi, Nasrin Dashti,

Vaez-zadeh F. Study of dermatoglyphic patterns of

hands in women with breast cancer. Pak J Med

Sci.2006,22(1): 18-22



32

Celine etal., Int J Med Res Health Sci. 2014;3(1): 32-36


&

Health Scienceswww.ijmrhs.com Volume 3 Issue 1(Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886

Received: 1st

Oct 2013 Revised: 30th

Oct 2013 Accepted: 13th

Nov 2013

Research article

A PROFILE OF CARDIOVASCULAR DISEASES IN A TEACHING HOSPITAL IN KERALA

*Celine TM1, Jimmy Antony

2

1Assistant Professor of Statistics,

2Assistant Professor of Health Education, Department of Community Medicine,

MOSC Medical College, Kolenchery, Kerala, India


ABSTRACT

Background and objective: cardiovascular diseases are increased in each year in India. Cardiovascular diseases

more are occurred in the economically productive age group. This will affect their family and also the nation. Aim

of the study is to find out the different types of heart diseases and the case fatality rate of cardiovascular disease

from 1st

April 2005 to 31st

March 2010 in a teaching hospital. Materials and Methods: The retrospective study

conducted on hospitalized patients admitted with cardiovascular diseases from 1st

April 2005 to 31st

March 2010.

Medical records department follows the guide lines of International Classification of Diseases (ICD)-10 coding for

entering the data, from that data were collected. Results: Of 10427 cases, 6324 (60.65%) were males and

4103(39.35%) females. Cardiovascular disease was more among males than females. It was more occurred in ≥60

years. Most of them were occurred due to cerebrovascular disease (33.7%). Ischemic heart disease was more among

males than females. Total number of deaths due to cardiovascular disease was 797. Of them 525(65.87%) were

males and 272(34.13%) females. Case fatality due to cardiovascular diseases was 7.64%. Case fatality among males

(8.3%) were more than females (6.63%) (P=0.00). Conclusion: This study mentioned that most of the cases and

deaths were occurred in 60 and above years. Second leading age group is 25-59 years. Accident in economically

productive people was high. It will affect their family and also the nation. Hence it can be reduced by conducting

health awareness programme.

Key words: Case fatality, cardiovascular diseases, ischemic heart disease.

INTRODUCTION

Heart and blood vessel disease is called cardiovascular

disease (CVD) or heart disease. It is the number one

killer of women in worldwide, accounting for one-

third of all deaths. Atherosclerosis is a term which

describes any hardening of large arteries; it happened

due to plaque. It causes the arteries narrow and this

leads to the flow of blood through the arteries is

difficult. Blood clots in anywhere in the narrow

arteries then blood cannot flow it will lead to heartattack or stroke. An ischemic stroke occurred due to

obstruction within the blood vessel supplying blood to

brain. When the blood supply of that part of the brain

is cutoff; it will cause the brain cell die. It will affect

the smooth functioning of the body. A hemorrhagic

stroke mostly happened due to the unrestrained

hypertension; it leads to explosion of blood vessel in

the brain. Heart failure, it occurs when the heart cannot

supply sufficient blood for the functioning of the body.

If it is not treated in time it becomes most terrible.

A cross sectional study reported that the prevalence of

coronary heart disease (CHD) in rural and urban areasof India was 3-4% and 8-10% respectively.

1The main

objective of the study is to find out the different types

of heart diseases and the case fatality rate of

DOI: 10.5958/j.2319-5886.3.1.007



33


cardiovascular disease during the period from 1st

April

2005 to 31st

March 2010 in a teaching hospital.

METHOD

Study design: The study was a retrospective studyconducted on patients admitted with cardiovascular

diseases in M.O.S.C Medical College, Kolenchery,

Ernakulam, Kerala, India from 1st April 2005 to 31st

March 2010.

Selection of Description of patients:

The study population consists of all patients admitted

in the hospital due to cardiovascular diseases during

the period from 1st

April 2005 to 31st

March 2010. The

data were collected with the permission of Institutional

Ethical Committee from the Medical Records

department, follows the guide lines of International

Classification of Diseases (ICD)-10 coding.2

Statistics: Z test is applied for the comparison

between proportions. Z test is used for comparing the

sex wise difference between proportions of age, type

of diseases. Critical ratio (Z) = sex wise difference

between proportions age / standard error of difference

between sex wise proportions. Formula for calculating

Standard error of difference between sex wise

proportions is √(p1q1 / n1) + (p2q2 / n2). P value is taken

from the unit normal distribution table with the

corresponding value of Z (critical ratio), its cut off

value is 0.05. If it is less than or equal to 0.05 then

there is significant difference between proportions

otherwise there is no significant difference between

proportions. Analyzing the data by using Microsoft

excel.

RESULT

Table 1: Demographic distribution

Age

(Yr)

Male (%) Female

(%)

Total (%) P Value

0-4 143(2.3) 97 (2.4) 240(2.3) 0.74

5-24 352 (5.6) 242(5.9) 594(5.7) 0.52

25-49 1096 (17.3) 534(13) 1630(15.6) 0.00

50-59 1309 (20.7) 610 (14.9) 1919(18.4) 0.00

60 &

above

3424(54.1) 2620(63.9) 6044(58.0) 0.00

Total 6324 4103 10427

Out of 10427 cardiovascular cases 6324 (60.65%)

were males and 4103(39.35%) were females.

Cardiovascular disease was more in the age group of

60 and above years. In this age group, it was more in

females than males. But it was more among males than

females in the age group of 25-59, Shown in Table

No.1.

Table 2: Sex wise cardiovascular diseases of

patients admitted with cardiovascular diseases

Of the cardiovascular cases, most of them due to

cerebrovascular disease and it occurred in both sex

was same. Chronic rheumatic heart disease,

hypertension and other forms of heart disease were

more among females than males. But ischemic heart

disease was more among males than females, shown in

Table No.2.

Of the ischemic heart disease, most of them were due

to Chronic ischemic heart disease 1859(63.4%), 273

(9.3%) were due to Acute Myocardial infarction,

410(14.0%) were due to subsequent myocardial

infarction and 390(13.3%) were due to other reasons.

Of the cerebrovascular diseases, most of them were

due to cerebral infarction1394(39.72%), 924(26.32%)

were due to stroke, not specified as hemorrhage or

infarction, 414(11.79%)were due to intracerebral

hemorrhage, 193(5.5%) were due to subarachnoid

hemorrhage and 585(16.67%) were due other reasons.

Diagnosis M F TotalP

Value

Acute Rheumatic

fever(I00)

18 14 321

0.3% 0.3% 0.3%

Chronic rheumatic

heart diseases(I05-I09)

65 99 1640.00

1.0% 2.4% 1.6%

Hypertension(I10-I15)1072 936 2008

0.0017.0% 22.8% 19.3%

Ischemic heart

disease(I20-I25)

2070 862 29320.00

32.7% 21.0% 28.1%

Pulmonary heart

disease and diseases

of pulmonary

circulation(I26-I28)

63 40 103

11.0% 1.0% 1.0%

Other forms of heart

disease(I30-I52)

840 691 15310.00

13.3% 16.8% 14.7%

Cerebrovascular

diseases (I60-I69)

2093 1417 35100.14

33.1% 34.5% 33.7%

Diseases of arteries,

arterioles and

capilliaries(I70-I79)

103 44 147

0.631.6% 1.1% 1.4%

Total6324 4103 10427

100.0% 100.0% 100%



34


Fig 1: Sex wise Trend of Cardiovascular cases

reported in a Teaching Hospital from 1st

April 2005

to 31st

March 2010

Highest number of cases reported during the year 1st

April 2009 to 31st

March 2010. Cardiovascular disease

was more among males than females in each year,shown in Figure 1.

Of the 10427 cases, 797 deaths were reported during

the period from 1st

April 2005 to 31st

March 2010.Case

fatality due to cardiovascular diseases was 7.64%. Of

797 deaths, 525(65.87%) were males and 272(34.13%)

were females. Case fatality among male was 8.30%

and among females 6.63%. Case fatality among males

was more than females. (P=0.00)

Table 3: Age wise case fatality of patients admittedwith cardiovascular diseases from 1

stApril 2005 to

31st

March 2010

AgeNo. of

deathsTotal

casesP value

0-4 14 (5.8) 240 0.52

5-24 23(3.9) 594 0.4

25-49 78(4.8) 1630 Reference group

50-59 133(6.9) 1919 0.00

60 & above 549(9.1) 6044 0.00

Total 797(7.6) 10427

Within the column 2, represent the number of deaths

and case fatality of each age group. Case fatality was

more in the age group of 50 and above years compared

to the age group 25-49 years. Case fatality was more in

the age group of 60 and above years compared to the

age group 50-59 years (P=0.00), shown in Table No. 3.

Deaths due to cardiovascular diseases were more

during 1st

April 2007 to 31st

March 2008. Male deaths

were more than females in each year, shown in Fig 2.

Fig 2: Sex wise trend of deaths due to

cardiovascular diseases from 1st April 2005 to 31st

March 2010

DISCUSSION

In the developing countries most of the people havestimulated from their agrarian diets with physical

activities to fast food with inactive habits. These types

of changes lead to increase the possibility of

developing cardiovascular diseases among people. It is

a burden of disease over several decades in the

developed countries. It is the leading cause of death in

India.2

Several studies in India mentioned that prevalence of

coronary heart disease in urban and rural areas was

between 7-13 % and 2-7 % respectively.

3,4

Dinesh CSharma reported that the proportion of deaths due to

heart disease is more in south India ,it was 25% and

least in central region, it was 12 %.5

A study reported

that 25% of total mortality was due to cardiovascular

diseases.6

Another study reported that cardiovascular

disease in South India showed 10-15% increase

occurred among young women.7

A study mentioned

that 50% of all deaths occurred in Kerala was due to

cardiovascular diseases.(8)

In the present study

cardiovascular diseases was more among males

(60.65%) than females (39.35%). It was more occurred

in the age group of 60 and above years. It was more

among females than males in the age group of 60 and

above years. But it was more among males than

females in the age group of 25-59.

Hypertension was an important factor in the beginning

of both cerebrovascular and ischemic heart disease.

Thus 22 per cent of the cases of ischemic heart disease

and 31.7 per cent of cases of myocardial infarction

were hypertensive; 42.0 per cent of the cases of

cerebral thrombosis were also hypertensive. The

overall ratio of ischemic heart disease to

cerebrovascular disease was 1.4:1; this ratio was same



35


for both sexes. A study mentioned that 8.72 million

individuals go through hypertension and 3.48 million

individuals go through diabetics in Kerala..8

Hypertension was the most powerful cause of vascular

diseases among females than males. In the present

study 19.3.3% hypertensive cases were reported.

Hypertension was more among females than males.

A study reported that the prevalence of Coronary

Artery Diseases in the urban and rural areas of India

was 12% and 7.5% respectively.1

Raghavan’s study 9

mentioned that out of 4,335 autopsies, 13.1 per cent

was due to cardiovascular diseases. Of the

cardiovascular disease, 9.8% was due coronary artery

disease. According to Wig’s study, the incidence of

coronary artery disease was more in Amritsar and

Calcutta.10, 11 Padmavati’s study report mentioned that

0.2 % of the medical admissions above 40 years of age

was due to coronary artery diseases.12

In the present

study mentioned that 1.4% of cardiovascular diseases

were due to diseases of arteries, arterioles and

capilliaries.

According to Schroeder13

the incidence of

cerebrovascular and ischemic heart disease is different

in different parts of the world. The prevalence of

coronary artery disease in India is found to be less than

other countries. Cerebrovascular disease was moreoccurred than ischemic heart disease in males. Among

females cerebrovascular disease was occurred twice as

that of ischemic heart disease. Chambers’s studypointed out that in India the consumption of less

amount vitamin B-6 and folate content food and the

increase fatty food consumption without physical

exercise may increase the risk of ischemic heart

disease.14

A study mentioned that mortality due

ischemic heart disease among Indians living abroad

was 40% more than that of Europeans.15

According toDhar’s study, 0.3% of all admission and 0.7% of all

medical admission was due to ischemic heart disease.

Myocardial infarction was 6.5 times more in males

than females.16

In the present study ischemic heart

disease was 28.1% of all cases. Ischemic heart disease

was more among males than females. In the present

study, of the ischemic heart disease, most of them

were occurred due to Chronic ischemic heart disease

1859(63.4%), 273 (9.3%) were due to Acute

Myocardial infarction, 410(14.0%) were due tosubsequent myocardial infarction and 390(13.3%)

were due to other reasons.

Result of Dhar’s study mentioned that 0.44% of all

admission and 1.1% of medical admission was due to

cerebrovascular diseases. The incidence of

crebrovascular disease is 0.44 per cent and 1.1 per cent

of total and medical admissions, respectively.16

Muir’s study17reported that incidence of

cerebrovascular diseases was high in Indians and less

among Chinese in Singapore. Another study also

found the same result.18

In the present study 33.7% of

cardiovascular diseases was due to cerebrovascular

disease. Of the cardiovascular cases most of the

patients were admitted with Cerebrovascular disease.

Proportion of Cerebrovascular disease in both sexes

was same. In the present study, of the cerebrovascular

cases, most of them were due to cerebral infarction

1394 (39.72%), 924(26.32%) were due to stroke, not

specified as hemorrhage or infarction, 414(11.79%)

were due to intracerebral hemorrhage, 193(5.5%) were

due to subarachnoid hemorrhage and 585(16.67%)

were due other reasons.

Report of a study mentioned that about 25% of

mortality occurred in the age group of 25- 69 years

was due to heart diseases. Mortality occurred due to

heart disease in the urban and rural areas was 32.8%

and 22.9% respectively5

In the present study case

fatality was more in the age group of 60 and aboveyears (9.1%) compared to the age group 50-59

years(6.9%).Case fatality occurred in the age group of

25-59 years was 5.9%.

Padmavati’s study mentioned that 7.7% of total

medical causes of death and 3% of total deaths was

due to heart disease.12

A study report mentioned that in

the western countries 50% of total deaths were due to

heart disease.19,20

Another study mentioned that 19%

of total deaths was due to heart disease and also

mentioned that it is a leading cause of in both sexes.5

In the present study case fatality due to cardiovascular

diseases was 7.64%. Case fatality among males (8.3%)

was more than females (6.63%).

CONCLUSION

Cardiovascular disease was more among males than

females. It was a no.1 killer disease. It will affect the

smooth running of the affected people’s family.

“Prevention is better than cure”. For reducing this with

the help of implementing simple but effectiveprevention strategies, strengthening the health system

and conduct quality improvement programmes. And

also identify the reason for the onset of cardiovascular



36


disease in the younger age group and conduct

awareness programmes.

REFERENCES

1. Cardiological Society of India, Kerala Chapter.ACS Registry. http://www.csikerala.org/

acsregistry.php

2. Dorairaj Prabhakaran and Salim Yusuf, Guest

Editors. Cardiovascular disease in India: Lessons

learnt & challenges ahead. Indian Journal of

Medical Research 2010;132(5): 529 – 530.

3. Xavier D, Pais P, Devereaux PJ, Xie C,

Prabhakaran D, Reddy KS et al. Treatment and

outcomes of acute coronary syndromes in India

(CREATE): a prospective analysis of registry data.Lancet 2008; 371 : 1435-42

4. Prabhakaran D, Yusuf S, Mehta S, Pogue J,

Avezum A, Budai A, et al. Two-year outcomes in

patients admitted with non-ST elevation acute

coronary syndrome: results of the OASIS registry

1 and 2. Indian Heart J 2005; 57 : 217-25

5. Dinesh C. Sharma India's no.1 killer: Heart

disease. India Today. 2010;April12

6. Mukherjee AK. India’s health: today andtomorrow. J Indian Med Assoc1995;93: 312 – 15.

7. The Times of India. Heart diseases rising among

women. Hyderabad.2013; June 29.

8. Shyam PV. In Kerala, 110 die of heart disease

daily Times of India. 2011;Sep 24

9. Raghavan, P. Etiological incidence of heart

disease in Bombay. Analysis of 4335 autopsies. J.

Indian M. A. 1941;10: 365,

10. Wig KL, Malhotra RP, Pathania NS. A study of

clinical data of 500 cases of congestive heart

failure. Indian Heart J.1953;5: 45

11. Gupta JC. A plea for concerted attack on

atherosclerosis. Indian Heart J. 1957;9: 59

12. Padmavati S. The cardiac patient in

underdeveloped countries. Am. Heart J. 1959;8:

418

13. Schroeder HA. Degenerative cardiovascular

disease in the Orient. I. Atherosclerosis. Chron.

Dis. 1958;8: 287

14. Chambers JC, Obeid OA, Refsum H. Plasma

homocysteine concentrations and risk of coronary

heart disease in UK Indian Asians and Europeanmen. Lancet 2000; 355: 523 – 27

15. Balarajan R. Ethnicity and variations in mortality

from coronary heart disease. Health

Trends1996;28:45 – 51

16. Dhar P. Thesis for M.D. (Medicine). Unpublished.

17. Muir CS. Coronary heart disease in seven racial

groups in Singapore. Brit. Heart J.1960; 22:45

18. Danraj TJ, Acker MS, Danraj W, Ong WH, Yan

TV. Ethnic group differences in coronary heart

disease in Singapore. An analysis of necropsy

records. Am. Heart J. 1959;58: 518

19. Wood PH. Diseases of the Heart and Circulation.

Ed. 2. London, Eyre and Stottiswoode.1956.

20. White PD. Heart Disease. New York, The

Macmillan Company, 1951,4th

ed.



37

Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42


&

Health Sciences


ndOct 2013 Revised: 20

thNov 2013 Accepted: 23

rdNov 2013

Research article

USE OF PROTON PUMP INHIBITORS IN GENERAL PRACTICE: IS IT RATIONALE?

*Nousheen1, Tadvi NA

2, Shareef SM

3

1II

ndyear MBBS student, Kamineni Institute of Medical Sciences, Narketpally, Andhra Pradesh, India

2Department of Pharmacology, College of Medicine, Majmaah University, Kingdom of Saudia Arabia

3Assistant Professor, Department of Pharmacology, Kamineni Institute of Medical Sciences, Narketpally

*Corresponding author email:[email protected]

ABSTRACT

Background: The incidence of improper use of PPIs varies from 40-70% in various studies. Initiation and the

continuous use of these drugs without correct indications will result in significant cost to the patient. The present

study was planned with the aim of finding out the rational use of PPIs in the in patients of a rural tertiary care

hospital. Objectives: To assess indications of use of PPIs along with their dose, frequency, rationality of treatment,

safety and efficacy. Methods: Prospective observational drug-utilization study of PPIs was conducted for two

months in the inpatients of General Medicine and General Surgery wards. The sample size of study was (n=100).

The case sheets of the patients were reviewed for PPIs prescription and relevant data was taken. A five point Likert

scale with validated Reflux Disease Diagnostic Questionnaire (RDQ) having 12 items was used for evaluating

symptoms score for assessing efficacy of PPIs. Results: A total of 46.72% inpatients were on proton pump

inhibitors, in surgery(47.52% ) and medicine wards (46.01%). The indications for PPIs therapy were acute gastritis

(4%) , Gastro Esophageal reflux disease (5%) , Duodenal ulcer(1%) , co-administration with Non Steroidal Anti-

Inflammatory Drugs(32%). PPIs were prescribed irrationally in 58 % of patients without any valid indication. The

incidence of polypharmacy was high, average number of drugs per prescription was 4.93. Antimicrobials were the

most common drugs used in (71%). CONCLUSION: Proton pump inhibitors should be used more judiciously and

awareness should be created among the clinicians in the hospital so that appropriate prescription of PPIs will

improve the patient care at low cost.

Keyword: Proton pump inhibitors, General practice, Rationale

INTRODUCTION

Proton pump inhibitors (PPIs) are a group of drugs that

cause pronounced and long-lasting reduction of gastric

acid production. They are most potent gastric acid

suppressing drugs currently in clinical use.1

PPIs

irreversibly inhibit the gastric H+-K

+ATPase pump

also known as proton pump and reduce both basal and

stimulated gastric output. Currently the PPIs available

in India are omeprazole, esomeprazole, pantoprazole,rabeprazole and lansoprazole. PPIs are used

therapeutically in active ulcers, Zollinger-Ellison

syndrome, Gastro oesophageal Reflux

Disease(GERD), GI bleeding, dyspepsia from

NSAID’s and along with antibiotics for helicobacter

pylori.2

PPIs are also given prophylactically along

with NSAID’s or Steroids in patients with history of

peptic ulcer / previous GI bleed / elderly patients.3

Proton pump inhibitors have been demonstrated to be

safe and well tolerated drugs but short term adverse

effects like headache, dizziness, diarrhoea, fatigue,

rashes and abdominal pain have been reported in 5%

of the patients taking proton pump inhibitors.4,5

Chronic therapy of PPIs carries an increased risk of

bacterial enteritis due to decreased gastric acidity

DOI: 10.5958/j.2319-5886.3.1.008



38


allowing colonization of ingested pathogens and also

infection with clostridium difficile .6,7

long term use of

PPIs have also been associated with increased risk of

hip fractures, and community acquired pneumonia.8,9

In setting with low rate of such infections benefit of

PPI therapy outweighs the risk developing it.10

Polypharmacy can also make the elderly patients

more likely to confuse their use of medication

schedule.11

Such risks are worth taking for life saving

drugs that are clearly indicated, but prescribing PPIs

that may not be clinically necessary can put patients at

risk of complications.

Inspite of the above mentioned concerns with PPIs,

they have become one of the most commonly

prescribed medicines worldwide. Some reports suggest

that upto 60% of patients suffering from dyspepsia are

on drugs like PPIs without proper indication. 12,13 .

PPIs take longer time to provide symptom relief than

H2 blockers or antacids. For sporadic dyspepsia, and

immediate symptoms relief agents other than PPIs will

provide greater patient satisfaction and better clinical

outcomes.14

The prescriptions for the PPIs have increased

consistently over the past years. Many drug utilization

studies have reported widespread use of PPIs and that

are outside the current prescribing guidelines.15,16

The

incidence of improper use of PPIs varies from 40-70%

in various studies.17-19

Initiation and the continuous use of these drugs

without correct indications will result in significant

cost to the patient. The significance of rational use of

drugs can be described by WHO definition which

states that rational use of drugs require that, patients

receive medications appropriate to their clinical needs

in doses that meet their own individual requirement for

an adequate period of time at lowest cost to them and

their community.17

Hence in this present scenario, where the use of PPIs is

overwhelming, the present study is planned to know

the rational use of PPIs in the in patients of General

Surgery and General Medicine wards of a rural tertiary

care hospital.

Objectives

• To assess the indications of PPIs usage

• To find out percentage of irrational prescriptions

with PPIs (Improper prescriptions without justified

indication)• To assess the frequency of usage of PPIs along with

their dosage.

• To assess the safety, efficacy and cost effectiveness

of PPIs.

METHODOLOGY

The study was conducted in the inpatient wards of

General medicine and General surgery in KamineniInstitute of Medical Sciences (KIMS), Hospital in

collaboration with the Department of pharmacology

after taking permission from Institutional Ethics

Committee. It was a prospective observational study

conducted during the period of June 2013 to August

2013. Patients of either sex, admitted into the inpatient

wards of General Medicine and General Surgery in

KIMS hospital, Narketpally, between the age group of

20-70 yrs were included in the study. Informed

consent was taken from all the patients. Patients notwilling to give consent were excluded from the study.

The sample size for the study was (n=100).

The demographic data and the detailed history of

patient regarding past, present, family, personal and

drug history was taken. The other details like the

present diagnosis, reason for the present admission,

any investigations done to confirm the diagnosis, like

endoscopy etc were also noted. The number of drugs,

dosage form, frequency and duration of medications

the patient is kept on were also taken. Patient were

inquired regarding improvement in the symptoms or

any adverse drug reactions during the present stay. A

five point Likert scale with validated Reflux Disease

Diagnostic Questionnaire (RDQ)20

having 12 items

was used for evaluating symptoms score for assessing

efficacy of PPIs. This questionnaire was filled by

personal interview of the patient on inclusion in the

study and on discharge of the patient from hospital.

The questionnaire had maximum scoring of 40 and

minimum of 12 depending on severity of symptoms

like epigastric pain, bloating, vomiting, nausea, heart

burn, belching, anorexia etc.21

Inquiry regarding the

adverse or untoward events occurring during the

therapy with PPIs was also made from patients

included in the study. The cost analysis of the PPIs

was done by taking into consideration the available

PPIs in the hospital and used in the study. Rationality

of the prescription was assessed according to criteria

mentioned in previous studies.16,18,22-27

RESULTS

Total 214 case sheets were reviewed, 101 from surgery

department and 113 from medicine department over a



39


period of two months. Out of these 214 cases 100

(46.72%) were on proton pump inhibitors. 47.52%

inpatients of surgery wards and 46.01% of inpatients

in medicine wards were on proton pump inhibitor

therapy as shown in Table 1.

Table1: Department wise distribution of patients on

Proton pump inhibitors

Department

No. of

patients

on PPIs

No. of case

sheets

reviewed

patients

on PPIs

(%)

Surgery 48 101 47.52

Medicine 52 113 46.01

Total 100 214 46.72

Z=0.442, Hence no significant difference in the

prescription of PPIs between the Departments (test fordifference between two proportions). Out of 100

patients on proton pump inhibitors majority of them

41% were middle aged between 41-60 years age

group, and 61% were males and 39 % females shown

in Table 2 and Table 3.

Table 2: Age wise distribution of patients on proton

pump inhibitors

Age % of Patients

20-40 44

41-60 4160 and above 15

Table 3: Gender Distribution of patients on proton

pump inhibitors

Gender % of patients

Male 61

Female 39

Z= 4.5081, Hence significant difference in the

prescription of PPIs between males and females

Table 4: Indications for prescribing PPIs

S.No Indication % of patients

1. Acute Gastritis 4

2. Duodenal ulcer 1

3. With NSAIDS 32

4. GERD 05

5. Others 58

4% of patients with acute gastritis , 5 % of patients for

Gastro Esophageal Reflux Disease (GERD) , 1%

Duodenal ulcer , 32 % of patients along with Non

Steroidal Anti-Inflammatory Drug and 58 % of

patients were prescribed PPIs for other reasons and

were neither on NSAIDS nor were having any

symptom related to GERD or acid peptic disease as

shown in Table 4. Oral therapy with PPIs was

prescribed in 70 % of patients and intravenous PPIs in

30% of patients. The intravenous PPI used in all these

patients was Pantoprazole 40 mg given once daily

early in the morning.

Majority of the patients were prescribed PPIs once

daily 97% only in 3% of the patients Twice daily

therapy was administered. As shown in Table 5and

Table 6.

Table 5: Route of administration of PPI

Route % of patients

Oral 70

Intravenous 30

Table 6: frequency of administration of PPIs

Frequency % of patients

Once daily 97

Twice daily 03

Concomitant drugs

The incidence of polypharmacy was high all the

patients in the study were prescribed multiple drugs.

Average number of drugs per prescription was 4.93.

Antimicrobials were the most common drugs used in

(71%) patients followed by non steroidal anti-

inflammatory drugs and multivitamin preparations in

32% patients as shown in Table 7.

Table 7: Concomitant drugs used along with Proton

pump inhibitors

S.No Drugs used patients %

1. Antimicrobials 71

2. NSAIDs 32

3. Multivitamin preparations 32

4. Calcium and vitamin D 07

5. Antihypertensives 09

6. Vitamin C 10

7. Antidiabetics 03

8. Antiemetics 13

9. Antiplatelets 03

10. Purgatives /laxatives 02

11. Corticosteroids 01

12. Diuretics 03

13. Antiepileptics 01

14. Antacids 03

15. Antimalarial 04

16. Oral Iron therapy 05

17. Hypolipidemics 03

18. Tramadol 22



40


Majority of the patients 88% were having a low Likert

score of < 20, prior to start of therapy only 12 % of the

patients were having significant symptoms (Likert

score above 21) related to Acid peptic disease or

GERD as shown in Table 9.

Table 8: Categorization based on likert scale

Likert

scale

score

% of patients at

onset of therapy

% of patients at

discharge

12 47 73

13-20 41 22

21-30 07 05

Above 30 05 00

Table 9: Likert Score of patients at start of therapywith PPIs and at discharge (Mean ±SD)

Likert score

(Mean ±SD)

At start of therapy 15.15 ± 5.28

At discharge 12.98 ± 1.90

Z Value= 3.86, Hence significant difference in the

Likert score demonstrating efficacy of PPIs.

Pantoprazole was most commonly prescribed PPI in

82% of patients followed by omeprazole in 11% and

esomepraole in 7 % as shown in Table 10.

Table 10: Proton pump inhibitors used in the study

PPI % of patients

Pantoprazole 82

Omeprazole 11

Esomeprazole 07

Table 11: Cost analysis of Proton pump inhibitors

used in the study

DrugFormu

lationDose

Freq

uency

Cost per

day

Pantoprazole Oral 40 mg OD 6.5 Rs

Pantoprazole IV 40 mg OD 60 RS

Omeprazole Oral 20 mg OD 3 RS

Esomeprazole Oral 20 mg OD 3 RS

OD= Once daily, Rs=Rupees

Omeprazole and esomeprazole were cheaper in

comparison to pantoprazole

Table 12: Common adverse effects during therapy

with PPIs

S.No Adverse effect% of

patients

1. At least one adverse effect 14

2. Headache 53. Rash 3

4. Abdominal pain 3

5. Nausea 2

6. Constipation 2

7. Diarrhoea 1

8. Rhinitis 1

DISCUSSION

The prescriptions of proton pump inhibitors are

increasing rapidly in India as well as worldwide andPPIs have become one of the most commonly

prescribed drugs. The present study shows that total of

46.72 % of hospitalized patients were on proton pump

inhibitors during the study period. This is in

accordance with the previous study by Ramirez E et

al28

, who reported that the use of PPIs range from

28.65 % to 82.65% and Sandozi T17

who reported use

in 45 % of hospitalized patients. There was no

significant difference in the prescription of proton

pump inhibitor between the surgery and medicinedepartments (Z=0.442). The use of PPIs was

significantly more in males in comparison to females

Z= 4.5081. This is in accordance with the previous

study by Mayet AY16

. Only 42 % of the patients were

prescribed PPIs according to the criteria of rationality.

58 % of the prescriptions of PPI were unjustifiable.

This is in accordance to the study by Sandozi T17

(55

%) but more than the study by Mayet AY16

(43%).

Study by Brandhagen DJ et al29

has reported 77.5% of

unjustified prescriptions. Naunton M et al15

(39.6%).

The frequency of administration of PPIs was once

daily in 97% of cases, the doses of PPIs are

recommended as once daily but can be given twice

daily also for rapid action as steady state is achieved

rapidly. The most common concomitant medications

used with PPIs were Antimicrobials, this is a serious

issue as 58% of the prescriptions of PPI were

unjustified and it is well known fact that patients on

proton pump inhibitors are also susceptible to

colonization of pathogens which can lead to bacterial

gastroenteritis and also their is higher risk of

development of infection by Clostridium difficle

(antibiotic associated diarrhoea). 32% of cases PPIs



41


were given along with NSAIDS. This is in accordance

with the studies by Kumar A et al30

and Raghavendra B

et al31

who have found high incidence of co-

prescription of PPIs with NSAIDs. The use of NSAIDs

is an important predisposing factor for peptic ulcer

disease in the community thus one of the important

indications of PPIs is co-administration with NSAIDS

to reduce the risk of gastrointestinal bleeding and

peptic ulcers. In our study we used questionnaire based

five point Likert assessment scale to evaluate the

presence of GERD symptoms, dyspepsia and to assess

the symptom severity and response to treatment.20

Though a number of symptom scales and Quality of

life instruments have been used in clinical trials , not

all have been fully validated. We used the Reflux

Disease Diagnostic Questionnaire (RDQ) as it is

specific for GERD and dyspepsia. The validity,

reliability and responsiveness of this test have been

well demonstrated. In our study 47 % of patients had

RDQ score of 12 indicating that majority of the

patients had no symptoms of GERD as this was the

minimum possible score and only 12% patients had

significant symptoms as demonstrated by RDQ score

of more than 20. There was significant improvement in

the RDQ score of the patients demonstrating the

efficacy of PPIs (Z= 3.86). We cannot comment much

on the efficacy as our study was non interventional and

the duration of therapy with PPIs varied in the

patients. The study design was not appropriate to

evaluate our objective of efficacy with PPIs.

Randomized prospective clinical trials are better in this

regards. The most common proton pump inhibitor

used was Pantoprazole in 82% of patients, followed by

Omeprazole(11%) and Esomeprazole (7%). Atleast

one adverse effect was seen in 14 % of the patients.

Most common adverse effect was headache seen in 5

% of the patients. No serious or life threateningadverse effect was observed in patients receiving

proton pump inhibitors. Cost analysis revealed that

pantoprazole was twice more costly than omeprazole

and esomeprazole formulations available in the

hospital pharmacy.

CONCLUSION

Fifty eight percent of the patients in our study received

Proton pump inhibitors improperly for unjustified

indications. Increased awareness should be createdamong the clinicians in the hospital so that appropriate

prescription of PPIs will improve the patient care at

low cost. Although we found PPIs to be efficacious in

our study, the study design was not suitable for

evaluating efficacy. More drug utilization and

pharmacoeconomic studies should be conducted in

future to compare the rationality of use of proton pump

inhibitors and other anti secretory drugs like H2

blockers to know the exact scenario and plan the

remedial measures.

ACKNOWLEDGEMENT

We thank Indian Council of Medical Research (ICMR)

for funding this project through Short Term

Studentship Programme. We also thank the

Management and Principal, Kamineni Institute of

Medical Sciences, Narketpally for cooperation during

the conduct of study.

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proton pump inhibitors. Drug Safety. 2006;29(9):

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2. Hetzel D. Acid pump inhibitors. The treatment of

gastroesophageal reflux. Australian Family

Physician.1998;27(6):487-91.

3. Hawkins C, Hank GW. The gastroduodenaltoxicity of nonsteroidal anti-inflammatory drugs:A

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4. Katelaris PH. Proton pump inhibitors. Medical

Journal of Australia.1998; 169(4):208-11.

5. Reilly JP. Safety profile of the proton-pump

inhibitors. American Journal of Health-System

Pharmacy.1999;56(23 Suppl 4):S11-7.

6. Lewis SJ, Franco S, Young G, O Keefe SJ.

Altered bowel function and duodenal bacterial

overgrowth in patients treated with omeprazole.

Alimentary Pharmacology and Therapeutics.

1996;10(4):557-61.

7. Waldum HL, Brenna E, Kleveland PM, Sandvik

AK, Syversen U. Review article: the use of gastric

acid-inhibitory drugs, physiological and

pathophysiological considerations. Alimentary

Pharmacology and Therapeutics.1993;7(6):589-96.

8. Yang YX, Lewis JD, Epstein S, Metz DC. Long-

term proton pump inhibitor therapy and risk of hip

fracture. JAMA. 2006;296(24):2947 – 53.

9. Eurich DT, Sadowski CA, Simpson SH, Marrie

TJ, Majumdar SR. Recurrent community-acquired



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pneumonia in patients starting acid-suppressing

drugs. Am J Med. 2010;123(1):47-53.

10. Dalton BR, Lye-Maccannell T, Henderson EA,

Maccannell DR. Proton pump inhibitors increase

significantly the risk of Clostridium difficile

infection in a low-endemicity, non-outbreak

hospital setting. Alimentary Pharmacology and

Therapeutics.2009; 29(6): 626 – 34

11. Colley CA. Polypharmacy: The cure becomes the

disease. Journal of General Internal

Medicine.1993;8(5):278-83.

12. Sachs G. Proton pump inhibitors and acid-related

diseases. Pharmacotherapy. 1997;17(1):22-37.

13. Bashford JN, Norwood J, Chapman SR. Why

patients are prescribed proton pump inhibitors?

Retrospective analysis of link between morbidity

and prescribing in the General Practice Research

Database.BMJ 1998;317(7156):452-6.

14. Zacny J, Zamakhshary M, Sketris I, Veldhuyzen

van Zanten S. Systematic review: the efficacy of

intermittent and on-demand therapy with

histamine H2-receptor antagonists or proton pump

inhibitors for gastro-oesophageal reflux disease

patients. Alimentary Pharmacology and

Therapeutics. 2005;21(11): 1299 – 312.

15. Naunton M, Peterson GM, Bleasel MD. Overuse

of proton pump inhibitors. J Clin Pharm Ther

2000;25(5):333-40.

16. Mayet AY. Improper use of antisecretory drugs in

tertiary care teaching hospital: An observational

study. The Saudi Journal of Gastroenterology.

2007;13(3):124-8.

17. Sandozi T. A Comparative Study of Cost

Analysis of H2 Antagonists and Proton Pump

Inhibitors in a Tertiary Care Hospital. Research

Journal of Pharmaceutical, Biological and

Chemical Sciences .2013;4(1):888-97.18. Mat Saad AZ, Collins N, Lobo MM, O Connor

HJ. Proton pump inhibitors: a survey of

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19. Walker NM, McDonald J. An evaluation of the

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2001;23(3):116-7.

20. Shaw MJ, Talley NJ, Beebe TJ,Rockwood T,

Carlsson R,Adlis S, et al. Initial validation of a

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96(1):52 – 7.

21. Forgacs I, Loganayagam . Overprescribing proton

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43

Anil et al., Int J Med Res Health Sci. 2014;3(1):43-46


&

Health Sciences


thOct 2013 Revised: 6


thNov 2013

Research article

A STUDY ON SEXUAL DIMORPHISM OF THE HUMERUS IN TAMILNADU REGION

*Anil Kumar Reddy Y1, Sheela Grace Jeevamani

1, Indira Vijay Ingole

2, Raghavendra

1

1Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India2Department of Anatomy, Dr. PDMMC, Amravati, Maharashtra, India


ABSTRACT

Sex determination from bones is of vital importance in anthropological studies and medico-legal cases. The present

study focused on measurements of the Humerus and to evaluate the differences in sex present in the morphology

through statistical analysis. Method: In our study, 120 dry adult humeri (56 right side & 64 left side) were studied

of known sex. Damaged bones were excluded from the study. Each Humerus was measured for 11 parameters;

measurements were taken by using a sliding caliper as described in the textbook of anthropology and previous

studies. The osteometric data of the Humerus of present study is statistically analyzed and compared with other

similar studies. Results: Statistical tests were applied to the metrical data obtained to assess whether the differences

between the means of each parameter are statistically significant or not. Length of Humerus, the weight of the

Humerus, Mid-shaft circumference, Transverse and Vertical diameter of superior articular surface, Bi-epicondylar

width of the Humerus have been found to be more discriminatory parameters for the identification of sex from

Humerus.

Keywords: Sex determination, Humerus, Anthropology, Tamil Nadu

INTRODUCTION

Sex determination from bones is of vital importance in

anthropological studies and medico-legal cases. The

role of the skeleton is invaluable in estimating

attributes such as age, sex, race, stature and presenceof disease. If the whole skeleton is available, there

should be no difficulty in arriving at an accurate

diagnosis of sex, but when only a part of the skeleton

is available, it poses increasing difficulty in

assessment. Origin: L humerus, umerus, the shoulder,

upper arm < IE *om(e)sos, the shoulder > Sans áṃsa-,

Gr ōmos

The humerus is the longest and largest bone of the

upper extremity; it is divisible into a body and two

extremities.1

Many workers have studied the

morphometric data for the humerus in both sexes and

statistical assessment of the value of this metrical

study for sex determination of humerus. Present study

focused on measurements of the humerus and to

evaluate the differences in sex present in the

morphology through statistical analysis. This study

gives information regarding the role of humanhumerus in the determination of sex and to compare

the present data with that of other workers. Many

workers have studied the morphometric data for the

humerus in both sexes and statistical assessment of the

value of this metrical study for sexing humerus.

Almost all bones of the human skeleton show some

degree of sexual dimorphism. The accuracy of sex

determination depends on the type and condition of the

bone, age of the subject, the degree of fragmentation

of the bones and biological variability. Obvious sex

differences do not become apparent until after puberty,

though specialized measurements on the pelvis can

indicate sex even in fetal material. It is recognized that

DOI: 10.5958/j.2319-5886.3.1.009



44


long bone cross-sectional area is greater in males as

compared to females which reflects more rapid

periosteal bone growth in boys.2


120 dried adult humeri (56right side & 64 left side)were collected from the Anatomy Department of

Karpagam Faculty of Medical Sciences & Research,

Coimbatore. Damaged bones were excluded from the

study. Measurements were taken by using a caliper as

described in textbook of anthropology3

and previous

studies.

Metrical data of each humerus was collected using 11

Anthropometric parameters as described below.

1. Vertical diameter of the superior articular surface

2. Transverse diameter of superior articular surface3. Circumference of the superior articular surface of

humerus

4. Maximum width of the upper end or transverse

diameter of the upper end

5. Circumference of the surgical neck

6. Mid-shaft circumference

7. Least shaft circumference

8. Transverse diameter of the lower articular surface

9. Transverse diameter of the lower end or

Biepicondylar width

10. Maximum length of the humerus

11. Weight of the humerus

Fig 1: Measuring the maximum width of the upper end

RESULT

120 dried adult humerus (56right side & 64 left sides)

were studied in present study. Each humerus was

measured for 11 parameters were already described as

above. The measurements were tabulated and

statistically analyzed. For each parameter we

calculated Mean, Median, Mode, Standard deviation,

T value and P Value.

Table 1: Measurements of Right Humerus (n=56)

Mean Range Standard

Deviation

T

value

Degree of

Freedom

P

value

Vertical diameter of the superior articular

surface (cms)

M* 4.2 3.3-4.5 0.382.37 54 <0.02

F* 3.8 3.2-4.1 0.55

Transverse diameter of superior articular

surface (cms)

M 3.96 3.5-4.1 0.262.2 54 <0.02

F 3.7 3.2-4.3 0.38

Circumference of the superior articular

surface of humerus (cms)

M 12.8 11.5-14.3 0.882.9 54 <0.001

F 12.1 10.8-14.5 1.10

Maximum width of the upper end or

transverse diameter of the upper end cms)

M 4.63 4.2-5.2 0.282.2 54 <0.02

F 4.4 3.9-5.2 0.36

Circumference of the surgical neck (cms) M 8.6 6.7-10 1.11

2.7 54 <0.001F 7.2 5.6-9.4 1.13Mid-shaft circumference (cms) M 6 5.1-5.2 0.67

2.49 54 <0.01F 5.5 5.2-6.6 0.56

Least shaft circumference (cms) M 5.6 5.2-6.4 0.581.24 54 >0.1

F 5.4 5-6.4 0.52

Transverse diameter of the lower articular

surface (cms)

M 5.1 3.5-6.2 0.991.6 54 >0.1

F 4.6 4.5-5.9 0.74

Transverse diameter of the lower end or

Biepicondylar width (cms)

M 5.2 4.2-6.4 0.892.5 54 <0.01

F 4.5 3.3-6 1.2

Maximum length of the humerus (cms) M 31 26-32.7 6.642.2 54 <0.02

F 26 28.5-33.6 9.68

Weight of the humerus (cms) M 99.3 60-126 24.9 2.1 54 <0.05F 84.8 60-120 19.2

P<0.05 considered as Significance; M-Male; F- Female



45


Table 2: Measurements of Left Humerus (n=64)

Mean Range Standard

Deviation

T

value

Degree of

Freedom

P

value

Vertical diameter of the superior

articular surface (cms)

M* 3.87 3.2-4.4 0.382.79 62 <0.01

F* 3.9 3.4-4 0.45

Transverse diameter of superior


M 3.91 3.6-4.2 0.242.4 62 <0.01

F 3.7 3.1-4.4 0.36

Circumference of the superior articular

surface of humerus (cms)

M 12.2 10.8-13.5 0.832.73 62 <0.01

F 11.5 10.2-13.4 1.14

Maximum width of the upper end or

transverse diameter of the upper end

(cms)

M 4.4 3.9-4.8 0.29

1.8 62 <0.05F4.22 3.7-5.2 0.41

Circumference of the surgical neck

(cms)

M 6.85 6.6-9.3 1.472.06 62 <0.05

F 6.25 5.8-9.7 1.05

Mid-shaft circumference (cms) M 5.8 5.2-6.8 0.47

3.7 62 <0.001F 5.69 5.2-6.4 0.53

Least shaft circumference (cms) M 5.54 5-6.6 0.481.6 62 >0.1

F 5.22 3.5-5.9 0.82

Transverse diameter of the lower


M 4.52 4.3-6.1 0.920.5 62 >0.3

F 4.39 4.2-6.1 0.88

Transverse diameter of the lower end or

Biepicondylar width (cms)

M 4.9 3.8-6.4 0.972.5 62 <0.01

F 4.35 3.4-6.2 0.86

Maximum length of the humerus (cms) M 30.2 26.3-32.4 1.992.5 62 <0.01

F 29 27.8-32.5 1.77

Weight of the humerus (cms) M 97.2 70-140 22.842.3 62 <0.02F 81.2 60-120 28.97

P<0.05 considered as Significance; *M- Male; F-Female

DISCUSSION

In the present study, there has been found a difference

in the Vertical diameter, Transverse diameter and

Circumference of the superior articular surface of right

and left sides in the male and female humerus.

These findings of our study are in conformity with the

studies of Girish Patil (2011)4

study on south Indians

and Derya Atamturk, M. Akif Akcal, Nucket mas

(2010)5, but it is lower than the studies of Iscan MY et

al (1998).6

The Maximum width of the upper end

shown high differences between right and left sides in

male and female humerus. Similar findings are

reported by Derya Atamturk (2010).5

Significant range of differences observed in the

measurements of Mid-shaft circumference and least

shaft circumference. These findings of our study are in

conformity with the studies of Singh S (1972)7,

Kshirasagar et al (2001)8, Salles AD et al (2009)9,Derya Atamturk, (2010)

5and Iscan M.Y et al (1998)

6,

and Girish patil (2011)4, a study on south Indians.


in the Bi-epicondylar width of right (table-17) and left

sides (table-18) in male and female humerus and it is

statistically highly significant. Results of our study are

tallying with the results of studies by Singh S (1972)7,

Singh et al (1974), Derya Atamturk, (2010)5, Girish

patil (2011)4 study on south Indians, but not tallying

with the findings of Iscan MY et al (1998).6

In the present study, the Maximum length of humerus

is highly significant parameter there is a considerable

amount value difference is found between males and

females. Our findings are in conformity with the

findings reported by Singh S (1972)7, Derya

Atamturk, (2010)5

and Iscan M.Y et al (1998)6, and

Girish patil (2011)4

study on south Indians, show

statistically significant sex differences between mean

of Maximum length of right and left in males andfemales.



46



in the Weight of the humerus of right and left sides in

male and female humerus. Reports of similar study

(same parameter) are not available for comparison.

CONCLUSION

To know the significant findings for identification of

sex of humerus 120 (56right side & 64 left side) adult,

fully ossified, dried humeri were studied. The

measurements obtained from the humerus were

compared to the values reported by previous workers.

From the results it is cleared that based on no single

parameter, sex of humeri cannot be decided. All the

parameters have to be considered together for this

purpose.

Length of the humerus, Weight of the humerus, Mid-shaft circumference, Transverse and Vertical diameter

of the superior articular surface, Bi-epicondylar width

of humerus have been found to be more

discriminating parameters for the identification of sex

from humerus. However, the sex overlap is observed

in all the parameters and indices. This may be due to

genetic, nutritional and socio-economical difference in

the individuals or may be due to hypo masculinity in

female humerus and hyper masculinity in male

humerus.

REFERENCES

1. Arnold F. Handbook of Functional Anatomy.

Ester babnd Freiburg Im Breisgau. 1844. 1st

Edition, p. 243.

2. Williams and Warwick Editors. Grays Anatomy

Churchill Livingstone (1995), 38th

Edition, p.626.

3. Krogman WM. The human skeleton in Forensic

Medicine charise and Thomax springeld Illinosin,

U.S.A. 1st

Edition. 1962)

4. Girish patil, Sanjeev Kolagi, Umesh Ramadurg.

Sexual dimorphism in the Humerus: South

Indians. Journal of clinical and Diagnostic

Research. 2011;5(3): 538-41.

5. Derya Atamturk, M. Akif Akcal, Izzet Duyar and

Nuket Mas. Sex estimation from the radiographic

measurements of the humerus. Eurasian J.

Anthropol. 2010;1(2): 99-108.

6. Iscan MY. Forensic Anthropology around the

world. For. Scl. Inter. 1998;74: 1-3.

7. Singh S, Singh SP. Identification of sex from the

humerus. Indian Journal of Medicine and

Research. 1972, 60:1061-66.

8. Salles AD. Reconstruction of humeral length from

measurements of its proximal and distal

fragments. Braz. J. Morphol. Sci. 2009;26 (2): 55-

61

9. Kshirasagar SV, Chavan SK, Makhani CS,

Kamkhedkar SG. Sexual Dimorphism of

Humerus: A Study in Marathwada Region. Indian

journal of Forensic Medicine and Pathology. 2001,

2(4): 10-45

10. A Tagaya, inter to pelation variation of sex

disseresnces, an analesis of the extremity long

bone measurements of Japonese, J.Anshroses, soe,

Nippon 1987; 95: 45 – 76

11. Robinson MS, Bldmos MA. The Skull and

humerus in the determination of sex: reliability of

discriminant function equations. Forensic Sci Int.

2009, 186(1-3): 86e1-5

12. Beck TJ, Ruff CB, Shaffer RA, Betsinger K,

Trone DW, Brodine SK (2000) Stress fracture in

military recruits: gender differences in muscle and

bone susceptibility factors. 2000, 27(3):437-44



47

Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52


&

Health Sciences




thNov 2013

Research article

PROGNOSTIC INDICATORS AND PATTERNS OF RENAL RECOVERY IN PATIENTS REQUIRING

HEMODIALYSIS FOR ACUTE KIDNEY INJURY

*Vaddadi Suresh

1, Usha Bhargavi E

2, N.S.R.C Guptha

3, Vinod L

4, Vijay Kumar P

5, Ravinder P

6.

1Associate professor,

3Assistant professor,

4Post Graduate,

5Professor; Dept of Medicine, GSL General Hospital,

Rajahmundry, Andhra Pradesh, India.2Assistant professor, Dept of Pathology, GSL General Hospital, Rajahmundry, Andhra Pradesh, India

6Consultant Nephrologist, Apollo hospitals, Kakinada, Andhra Pradesh, India


ABSTRACT

Background: The outcome of patients with acute kidney injury (AKI) is highly variable. Patients who receive

renal replacement therapy (RRT) for similar diseases may recover differently. The factors that operate in each

patient may alter the prognosis and outcome. Aims: Our study aims at identification of prognostic factors

influencing recovery in patients who required hemodialysis for AKI. Material and Methods: Patients admitted in

different ICUs with AKI who underwent hemodialysis in a tertiary care hospital over a three year period were

included in the study. Time from day one of disease to first dialysis, hematological and biochemical parameters

were noted. Patients were grouped based on the time taken for recovery of renal function following hemodialysis

into group A (<2 weeks) and group B (>2 weeks). Studied parameters have been statistically analyzed to find any

significant association with recovery time. Results: Out of 63 patients, 9 progressed to chronic kidney disease.

In the remaining 54, Group A comprised 31 and group B 23. Out of all the factors studied, serum creatinine

(7.0±1.3 vs 8.4±3.8; P=0.018), S. bicarbonate (21.7±2.8 vs 19.7±3.8; P=0.03), pH at admission (7.25±0.13 vs

7.1±0.19; P=0.048); number of hemodialysis sessions (3.5 ±1.5 vs 5±2.4; P=0.016) and time lag from day one of

disease to first hemodialysis (8.6 ± 3.6 vs 11.5±5.9; P=0.007) showed significant association with recovery time.

Conclusion: Recovery following AKI is influenced by factors liked delayed presentation, late initiation of

hemodialysis, low pH and low bicarbonate which can predict delayed renal recovery following hemodialysis.

Keywords: Acute Kidney Injury, Hemodialysis, Seurm creatinine.

INTRODUCTION

Acute kidney injury (AKI) is defined as a sudden loss

of kidney function that results in the retention of urea

and other nitrogenous waste products along with

dysregulation of extracellular volume, electrolytes

and acid base balance.1

It constitutes up to 20% of

critically ill patients and is easily identified by a rise

in the serum creatinine.2

The quantitative definition of AKI has long been a

debate due to gross variations in various methods

employed in measuring the glomerular filtration rate

(GFR). In view of the need for a simple and uniform

definition, RIFLE criteria was proposed and was later

modified and presented as AKIN criteria.3,4

This,

along with the recent change in the name of ARF to

AKI will represent the entire spectrum of kidney

disease and help in early detection of cases. These

criteria rely on the baseline serum creatinine and the

relative rise is used in the categorization into risk or

injury or failure group. Even though serum creatinine

is not an ideal marker of renal failure, it is

DOI: 10.5958/j.2319-5886.3.1.010



48


inexpensive and is readily available making it an

invaluable investigation. Novel biomarkers of AKI

like cystatin-C, Neutrophil gelatinase-associated

lipocalin (NGAL), Kidney injury molecule 1(KIM 1)

and many others are available, but their clinical utility

is still under validation.5

The etiologies of AKI vary, most common being

sepsis as reported from many studies globally.

Infectious causes dominate the charts all over the

world and severe malaria is an important addition to

the list of AKI in India. It is known that patients with

persistently high serum creatinine are at increased

risk of developing chronic kidney disease due to

tubular damage and interstitial scarring. The rates of

renal recovery in different studies varied from 36-

99%, but these studies defined recovery by dialysis

independence.6-8

Renal replacement therapy is life saving, especially in

AKI and the decision to initiate, type and timing of

RRT is the choice of the treating physician as per

certain indications like anuria, uremic symptoms,

refractory hyperkalemia, volume overload and

metabolic acidosis. It is prudent to initiate “timely”

rather than “early” hemodialysis as too early dialysis

is as bad as delayed dialysis as it can result in

increase in mortality.9

Intermittent hemodialysis is

the most common method of RRT employed in India

with varied outcomes. Renal transplantation is rarely

if at all, needed for AKI patients. Following RRT, the

decision to wean to conservative management is done

based on the recovery of clinical, biochemical and

metabolic parameters. These patients who are weaned

from RRT generally recover; some early, some late

and some may progress to ESRD, the factors

operating are unclear.10

In India, non availability of

RRT in many centers, financial constraints and

patient unawareness regarding disease are majorbarriers for measuring the burden of renal disease in

the community. The factors that determine the

prognosis in these patients are believed to be multiple

and our study aims at their identification.

MATERIAL & METHOD

This study was done in a tertiary hospital over a three

year period from 2010 March to February 2013.

Informed consent was taken from all the patients and

Ethical clearance was obtained from InstitutionalEthics Committee of the hospital.

Inclusion criteria: 1) Patients both male and female

aged between 20 to 70 years. 2) Patients admitted for

various diseases in different intensive care units

(ICU) including medical, surgical, cardiac, obstetric,

Cardiothoracic and burns unit who developed AKI or

admitted with AKI. 3) Patients who required

hemodialysis in our hospital for severe renal disease.

A total number of 63 patients formed the study

population.

Exclusion criteria: Patients with renal disease who

did not receive hemodialysis, Patients with previous

history of renal disease, obstructive uropathy or acute

on chronic kidney disease and patients who already

received hemodialysis outside before admission were

excluded from the study.

Their age, sex, place of living and occupation were

noted. Physical examination was done and history

regarding possible risk factors was taken. All patients

have undergone hematological tests including Hb%,

total and differential counts, and platelet counts.

Their Serum creatinine, urea, random blood sugar,

electrolytes and arterial blood gas analysis at

admission were noted. Along with the treatment for

primary condition, all patients underwent

hemodialysis for different indications like uremic

encephalopathy, Anuria/oliguria, refractory

hyperkalemia, metabolic acidosis, volume overload

etc. Standard bicarbonate hemodialysis protocol was

given to all the patients which included two hours of

dialysis at initiation and then increased to four hours

during subsequent sessions. The number of sessions

of dialysis required for the recovery of each patient

was noted. The decision to wean from dialysis was

made after the correction of primary metabolic

abnormality or achievement of significant clinical

improvement or adequate urine output. These patients

were followed up thereafter starting from day oneafter weaning from dialysis. Serial measurements of

S. Creatinine and urea were done after the 1st week,

2nd

week, 3rd

week and after 3 months. Falling

patterns of Serum creatinine in patients who

successfully completed the follow up was noted.

Patients were classified based on the time taken for

normalization of Serum creatinine (recovery) into two

groups: Those who recovered within 2 weeks were

placed in group A (N=31 ) and those who recovered

after 2 weeks were kept under Group-B (N=23 ).Various parameters mentioned above were studied

between the two groups to identify any significant



49


differences which are likely to influence the

prognosis and outcome.

RESULTS

Out of 64 patients admitted for hemodialysis,

41(65%) were males and 22 (35%) were females.Most of the patients were agricultural laborers (65%).

Out of 63 patients who completed three months of

follow up, 9 (14.3%) met the definition of CKD at

third month and hence these patients were not

considered to have recovered. The remaining 54

Patients who recovered following hemodialysis, were

grouped into group-A (n=31) and group-B. (n=23).

The most common age group involved was between

41-50 years.

Table 1: Patients age groups

Various hematological and biochemical parameters, risk factors, number of dialysis sessions were compared

between the two groups to find any association with recovery time, as shown in Table-2

Table 2: showing comparison of various parameters between the two groups.

Group-A (n=31) Group-B (n=23)

P valueMean ± SD Mean ±SD

Age in years 48.4 ± 12.9 45.5±10.6 0.38

Hb% 9.6±2.5 9.5±2.2 0.87

TLC (cells/mm3) 12890±5602 13626±5974 0.64

RBS (mg/dl) 146±68.6 156.7±123.7 0.68

S.Creatinine (mg/dl) 6.4±1.1 8.6±3.7 0.01*

B.Urea (mg/dl) 183.3±58.9 210.8±76.1 0.14

Serum.Na+

(mEq/L) 142±7.94 137±9.8 0.06

Serum.K+

(mEq/L) 4.98±1.12 5.39±1.34 0.22

PH

7.25±0.13 7.16±0.19 0.048*

S.Bicarbonate (meq/L) 21.7±2.86 19.7±3.86 0.03*

HDS 3.54±1.52 5.04±2.40 0.01*

T.D (days) 8.6±3.6 11.5±5.9 0.04*

Recovery duration(weeks) 1.83±0.37 3.57±1.2 -----

HDS- number of hemodialysis sessions required, T.D- time delay between first symptom tohemodialysis. *Significance.

Table 3: showing Gender, Habits and Other risk factors between two groups

RISK FACTOR Group-A (n=31) Group-B (n=23) P value

Sex Male 18 16 0.28

Female 13 7 0.27

Diabetes 5 10 0.028*

Hypertenson 8 3 0.21

Smoking 11 9 0.5

Alcoholism 4 3 0.56

NSAID abuse 7 2 0.16. Group A – Patients who recovered within two weeks; Group B – Patients who recovered after

two weeks; (* represents statically significant )

Age in years Group A (%) Group B (%)

20 or below 20 1 0

21-30 2 2

31-40 6 5

41-50 9 10

51-60 8 4

Above 60 5 2

Total 31 ( 57 %) 23 ( 43 %)



50


Table 4: showing different causes of AKI

Etiology of AKI N=54 (%)

Severe Malaria 17 (27.2%)

Sepsis 9 (14.3%)

Post Gastroenteritis 7 (11.1%)

Leptospirosis 6 (9.6%)Acute glomerulonephritis 5 (8%).

Unknown 7(11%)

Post cardiac or abdominal surgery 5 (8%)

Acute pyelonephritis 2 (3.2%)

Dengue Hemorrhagic fever 1 (1.61%)

Road traffic accident with Rhabdomyolysis 1 (1.61%)

Snakebite 1 (1.61%)

Contrast Nephropathy 1 (1.61%)

Acute Pancreatitis 1 (1.61%)

Total 54 (100%)

Fig 1: Shows fall of serum creatinine from day-1 after last session of hemodialysis

(Note: The curves belonging to both the groups are steep during the first week)

Statistics: All the statistical work was performed by

using SPSS trail version 16 and Microsoft Excel

2007. Descriptive statistics were presented in the

form of Mean ± Standard Deviation and Percentages.

The independent samples T test is used to compare

means and a p value < 0.05 is taken as statically

significant.

DISCUSSION

Hemodialysis forms an important therapeutic option

for severe AKI, but treatment of the primary

condition is as important. In our study, all the patients

fell into failure stage of RIFLE due to very high

serum creatinine at presentation and stage 3 of AKIN

criteria as all of them underwent hemodialysis. Malesare commonly affected as they mostly work outside,

getting exposed to infections, toxins and sustain

dehydration.11

Patients over 40 years of age

comprised 75% of the cases. This could be explained

by gradually falling renal reserve with age. Our study

highlighted the importance of recognizing severe

malaria as important cause of AKI in India as it was

the most common cause. Overall, infections

comprised 75% of all causes of AKI. Nine patients

(14.3%) met the definition of CKD after three months

but their disease progression was not followed

thereafter. Maximum recovery following weaning

from hemodialysis was noticed in the immediate first

week. There was a gradual fall of serum creatinine

during subsequent three months.

Comparison between patients with early (group-A)

and late recovery (group-B) was done after the follow

up period of three months. Age and hematological

parameters showed no difference between the two

0

1

2

3

4

5

1 WEEK 2 WEEK 3WEEK 3MTH

S . C

r e a t i n i n e i n m g / d L

Followup creatinine between two groups

gr A

gr B



51


groups. Mean random blood sugar, blood urea, serum

potassium are higher in group-B but showed no

statical significance. Mean serum creatinine (6.4±1.1

vs 8.6±3.7; p <0.05), S. Bicarbonate (21.7±2.8 vs

19.7±3.8; p <0.05) and pH at admission ( 7.25±0.13

vs 7.1±0.19; p < 0.05), total number of hemodialysis

sessions (3.5±1.5 vs 5±2.4; p <0.05 ), time delay

between disease and treatment ( 8.6±3.6 vs 11.5±5.9;

p <0.05), has shown statically significant association

with the recovery time. Patients with high serum

creatinine at admission (implying higher renal

functional loss) took much longer to recover. Studies

have shown that higher stages of AKI can result in

prolonged hospital stay due to delayed renal

recovery.12

patients with severe metabolic acidosis

characterized by low bicarbonate and low pH took

much longer time to recover. Metabolic acidosis

results due to multiple factors apart from inability of

the kidney to excrete metabolic acids. Hepatic

involvement, which is commonly seen in Malaria,

Leptospirosis, Dengue infections, Sepsis and as a

component of multi organ dysfunction syndrome

(MODS) along with starvation in these patients can

contribute to significant metabolic acidosis.

AKI patients who required more number of

hemodialysis sessions had delayed recovery. This is

because patients who had severe disease required

more number of sessions and the recovery after

weaning is also delayed owing to the severity. A very

important outcome of this study is that delay in the

initiation of hemodialysis in indicated patients

resulted in delayed recovery following weaning. This

is evidenced by the significantly higher time gap (

days ) between first symptoms and first hemodialysis

in group B patients ( A vs B = 8.6 ± 3.6 vs 11.5 ± 5.9;

p=0.04). The exact timing of dialysis, duration and

withdrawal of dialysis sessions is Physician’sdiscretion, and is subjected to variations.

13Adding to

delayed hospitalization, conservative approach is

implemented by some, even when there is clear

indication for RRT, which can actually worsen the

metabolic complications and there by mitigating the

chances of recovery even after subsequent RRT. The

term “door to dialysis time” is suggested by some

authors to emphasize the importance of timely

hemodialysis.14

In our study, patients with diabetes had delayedrecovery. This could be because of underlying

preexisting diabetic nephropathy in these patients.

Contrast nephropathy is one condition where

unequivocal evidence exists regarding renal damage

and poor recovery following RRT in diabetes.15

whether or not, this can be extrapolated to other

causes of AKI is not known. In our study, factors like

gender, hypertension, smoking, alcoholism and even

NSAID intake have not shown any association with

recovery time. This is in contrast to earlier studies

documenting NSAID use as a potential cause of renal

damage as well as delayed renal recovery.16

However,

we did not collect the data regarding the type,

quantity and duration of use of NSAIDS in any

patient included in the groups due to unreliability of

patient history.

The limitations of our study include small sample

size, lack of application of Glomerular filtration rate,

lack of long term follow up in recovered patients as

some of them could have landed in worsening of

renal function following apparent recovery, thus

missing the true burden of AKI progressing into

CKD.

CONCLUSION

AKI can have varied etiologies, and infections form

the bulk of these cases. Along with the correction of

primary cause, timely RRT can have significant

impact on the recovery of patients. Patients

presenting late, patients with high serum creatinine,

low Ph and low serum bicarbonate at admission,

patients who required more number of hemodialysis

sessions and known diabetics irrespective of diabetes

control, are prone for delayed recovery following

weaning from hemodialysis.

ACKNOWLEDGEMENTS

We are thankful G.K Anand Kumar, dialysis

technician and Ganapathi Swamy, statistician fortheir immense help in this project.

REFERENCES

1. Fauci AS, Braunwald E, Kaspar DL, Hauser SL,

Longo DL, Jameson JL. Acute renal failure.

Harrison’s Principles of Internal Medicine.17th

Ed.,McGraw‑Hill; 2008:1752‑61

2. Lameire N, Van Biesen W, Vanholder R. The

changing epidemiology of Acute renal failure.

Nat Clin Pract Nephrol 2006;2:364-77.



52


3. Bellomo R, Ronco C, Kellum JA Mehta RL,

Palevsky P. Acute renal failure -

definition,outcome measures, animal models,

fluid therapy and information technology needs:

the Second International Consensus Conference

of the Acute Dialysis Quality Initiative (ADQI)

Group. Crit Care 2004; 8:204 – 12.

4. Mehta RL, Kellum JA, Shah SV, Molitoris

BA, Ronco C, Warnock DG, et al. Acute kidney

injury network: report of an initiative to improve

outcomes in acute kidney injury. Crit Care

2007;11: R31.

5. Waring WS, Stephen AF. Earlier recognition of

nephrotoxicity using novel biomarkers of acute

kidney injury. Clinical Toxicology.2011;49: 720 –

28.

6. Ishani A, Xue JL, Himmelfarb J, Eggers PW.

Acute kidney injury increases risk of ESRD

among elderly. J Am Soc Nephrol.2009; 20: 223 –

228.

7. Coca SG, Yusuf B, Shlipak MG, Garg AX,

Parikh CR. Long-term risk of mortality and other

adverse outcomes after acute kidney injury: a

systematic review and meta-analysis. Am J

Kidney Dis.2009; 53: 961 – 73.

8. Wald R, Quinn RR, Luo J, Li P, Scales

DC, Mamdani MM, et al. Chronic dialysis and

death among survivors of acute kidney injury

requiring dialysis. JAMA .2009;302:1179 – 1185

9. Shiao CC, Ko WJ, Wu VC, Huang TM, Lai CF,

Lin YF, et al. U-curve association between timing

of renal replacement therapy initiation and in-

hospital mortality in postoperative acute kidney

injury. PLoS One 2012;7:e42952

10. Steven GC, Swathi Singanamala. Chronic Kidney

Disease after Acute Kidney Injury: A Systematic

Review and Meta-analysis.kidneyIntestinal.2012; 81(5): 442-48.

11. Kute VB, Shah PR. Outcome and prognostic

factors of malaria-associated acute kidney injury

requiring hemodialysis: A single center

experience. Indian J nephrol. 2012; 22(1): 33-38.

12. Mehta P, Sinha A,Sami Hari P, Kalaivani

M, Gulati A. Incidence of acute kidney injury in

hospitalized children. Indian Pediatr.2012;49:

537 – 42

13. Gibney N, Hoste E, Burdmann EA, Bunchman T,Kher V, Viswanathan R et.al Timing of Initiation

and Discontinuation of Renal Replacement

Therapy in AKI: Unanswered Key Questions.

Clin J Am Soc Nephrol. 2008;3(3):876-80

14. Andrade L, Cleto S, Seguro AC. Door-to-dialysis

time and daily hemodialysis in patients with

leptospirosis: Impact on mortality. Clin J Am Soc

Nephrol. 2007; 2: 739 – 44

15. Weisberg, Lawrence S., Peter B. Kurnik, and

Brenda RC Kurnik. Risk of radiocontrast

nephropathy in patients with and without diabetes

mellitus. Kidney international. 1994;45(1): 259-

65.

16. Abraham PA, Keane WF. Glomerular and

interstitial disease induced by nonsteroidal anti-

inflammatory drugs. American Journal of

Nephrology. 1984;4(1): 1-6



53Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58


&

Health Scienceswww.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 27th Oct 2013 Revised: 18th Nov 2013 Accepted: 28th Nov 2013

Research article

PSYCHOSOCIAL DETERMINANTS OF CONTRACEPTIVE USE AMONG WOMEN OF

REPRODUCTIVE AGE IN A RURAL AREA OF MAHARASHTRA

*Minhas S1, Sekhon H

2

1Reader, Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India.

2Psychiatrist & Chief Medical Officer, Composite Hospital, Central Reserve Police Force, Bantalab, Jammu, Jammu

& Kashmir, India.


ABSTRACT

The World Health Organisation reports that an estimated 94 per cent of the population of the world lives in

countries with policies that favour family planning. Despite this, five of every six couples of reproductive age do not

use adequate measures of fertility regulation. Gender inequalities in patriarchal societies ensure that men play a

critical role in the decisions on family matters. The present study was undertaken to study the nature of acceptance

of contraceptive practices and the psychosocial determinants. Methods: This was a community based cross

sectional descriptive study. The anticipated prevalence of contraceptive practices among the 206 women in the age

group of 15-49 years was 50%. Considering a margin of error of 10%, with finite correction and 10% of non-

response and 95% CI, the sample size was calculated. 90 married women in the reproductive age group of 15-49

years residing at the village were studied after drawing the sample with simple random sampling method. Results:

There were 55 (61.11%) women who practised contraception. In case of 03 (3.33%) couples, husbands used

condoms, while in case of remaining 52 (57.78%), wife had undergone tubectomy. Conclusion: From the present

study, it was concluded that the most common method of contraception practiced in the study population was

tubectomy and a range of psychosocial factors played an important role in decision making.

Keywords: Women, Rural, Contraception, Psychosocial, Tubectomy.

INTRODUCTION

An expert Committee of the World HealthOrganisation (WHO) has defined family planning as

“a way of thinking and living that is adopted

voluntarily, upon the basis of knowledge, attitudes and

responsible decisions by individuals and couples to

attain certain objectives”.1

Even though the technology

was available, only nine per cent of women in the

developing countries had access to contraceptive

services in 1965. The use increased to 50 per cent by

1990. Nonetheless, wide geographical variations still

persisted.

2

The world conference of the InternationalWomen’s Year 1975 declared “the right of the women

to decide freely and responsibly on the number and

spacing of their children and to have access to

information and means to enable them to exercise thatright”. The United Nations International Women’s

Decade (1976-1985) helped to increase awareness

about many issues concerning women’s health

including excessive pregnancies, inappropriate timing

and spacing of pregnancies and poor educational

levels2. During the International Conference on

Population Development programme of action, it was

recognized that demographic goal-driven family

planning programmes, may by their very nature violate

basic human rights (ICPD 1994).

3

The WHO reportsthat an estimated 94 per cent of population of the

world lives in countries with policies that favour

family planning. Despite these policies five of every

DOI: 10.5958/j.2319-5886.3.1.011




six couples of reproductive age do not use adequate

measures of fertility regulation.4

Currently, over 97

percent of sterilisations are tubectomies.5

It has been

deduced by research that family planning is the first

and most important step for rural development.6

Family planning means better health for the mothers

and their children and more opportunities for the

family as a whole.7

A majority of women in most

developing countries are aware of the health risks

posed by frequent pregnancies, and thus the

importance of birth spacing, but this awareness has not

satisfactorily translated into action.2A study conducted

on eligible rural women revealed that most of them

were concerned about child survival and also that they

viewed children as an important source of their

support in old age. The size of family was usually

decided by in-laws and partner support played a

predominant role in the decision. Pressure from the in-

laws to have more number of children was found to be

significantly higher in families where the women were

less educated or illiterate.8

Despite the decline in total

fertility rate worldwide, there are still millions of

women with unmet contraceptive needs in developing

countries. There are more married women with an

unmet contraceptive need (about 31 million) in India

than any other country.9

The National Family Health

Survey III (NFHS III), carried out in 29 states during

2005-06, shows that nearly 45 per cent of women in

India were married off before they turned 18. It also

shows that over 71 per cent of women who got

married under 18 years had received no education.

Early marriage impacts a woman's health and

education. It shows that women who are getting

married early are giving birth also at an early age.

While 52.5 per cent of the under 18 marriages were in

rural areas, it was 28.1 per cent in urban areas.10

But

the Total Fertility Rate (TFR) has shown a declineover the years. In the state of Maharashtra itself, the

TFR has shown a decline, from 2.9 (NFHS-I), to 2.5

(NFHS -II) and 2.1 (NFHS -III).11

Many studies have

been conducted till now on this issue but still there are

gaps in the information on the sporadic nature of

acceptance of contraceptive practices, especially in

this rural area of the state.12

In view of the same, this

study was undertaken in a rural area of Maharashtra,

India.

Aim: This study aimed at conducting anepidemiological survey among the married women in

the age group of 15-49 years, residing a rural area of

Maharashtra, India to find out the current

contraceptive practices.

Objectives: 1. To determine the current contraceptive

practices among married women in a village in Pune

district of Mahrashtra. 2. To suggest promotional

strategies for better utilisation of family planning

services


It was a community based cross sectional descriptive

study. The reference population was women who were

married and in the reproductive age group (aged 15-49

years) residing in the rural areas of Maharashtra. The

exclusion criteria were all women who were divorced,

separated, widowed, infertile, who had attained

menopause, who had undergone hysterectomy and

women who had migrated to the village but were not

permanently residing there. The actual study

population included all married women in the

reproductive age group of 15 – 49 years residing in the

village. Simple random sampling was done. The

anticipated prevalence of contraceptive practices

among the 206 married women, considering a margin

of error of 10%, with finite correction and 10% of non-

response and 95% CI, the sample size was calculated

to be 90. For selection of subjects, a serial list of all

the married women in the reproductive age group of

15 – 49 years was made. Using random number table

generated random numbers and the women

corresponding to these numbers from this population

were included in the sample. House to house visits

were carried out and the eligible women were

interviewed using a pre-tested standardized

questionnaire. Verbal consent of the respondents was

taken before the questionnaire was administered. A

pilot study was undertaken on 20 subjects (who were

later excluded from the actual study) which helped tofurther standardize the questionnaire and make certain

amendments in it. A brief introduction about the study

was given by the principal worker to the subjects. The

services of a medico-social worker were sought for

interpretation and better communication with the

subjects. Confidentiality of the identity of the

respondent and the information provided was assured.

RESULTS

Out of the sample of 90, there were 55 (61.11%) whopracticed contraception (table-1).




Table 1: Distribution of Respondents Based on

Contraception Usage

Contraceptive users (%) Non-users

(%)

Total

Tubectomy Condom

52 (57.78) 03 (3.33) 35 (38.89) 90

In case of three (3.33%) couples, the husbands usedcondoms, while in the case of remaining 52 (57.78%),

the wives had undergone tubectomy. No other mode of

contraception was found in the subjects who were

studied as a sample. For analysis purposes, the three

(3.33%) couples using condoms were excluded.

Subsequent analysis was done against tubectomy users

and non-users of any contraceptive method. On

studying the distribution of tubectomy status by age of

respondent (table-2), a significant association was

found between defined age groups and tubectomystatus (p<0.01).

Table 2: Distribution of Tubectomy Status by Age

of Respondent

Age

(Years)

Tubectomy (%)

Total (%)User Non-User

<25 06 (11.54) 19 (54.29) 25 (28.73)

25-34 24 (46.15) 12 (34.29) 36 (41.38)

≥35 22 (42.31) 04 (11.43) 26 (29.89)

Total 52 (100.00) 35 (100.00) 87 (100.00)Chi square Statistic: 20.689 df = 2 p<0.01

Mean (SD): Users: 33.23 (6.94) Non-users: 25.31

(6.03), ‘t’ statistic=5.49, df=85, p<0.01

There was a significant difference in age of husbands

between users and non-users (p<0.01) (table – 3).


of Husband

Age

(Years)

Tubectomy (%)


<30 04 (07.69) 19 (54.29) 23 (26.44)

30-40 31 (59.62) 14 (40.00) 45 (51.72)

>40 17 (32.69) 02 (05.71) 19 (21.84)

Total 52 (100.00) 35 (100.00) 87 (100.00)

Chi square Statistic: 25.706 df = 2 p<0.01

Mean (SD): Users: 37.83 (6.75) Non-users: 29.23

(6.64), ‘t’ statistic=5.86, df=85, p<0.01

Two-third of users i.e. 39 (75.00%) users got married

before the age of 18 years and only 13 (25.00%) users

did so at or after attaining the age of 18 years (table 4).


of Respondent at Marriage

Age

(Years)

Tubectomy (%)


<18 39 (75.00) 14 (40.00) 53 (60.92)

≥18 13 (25.00) 21 (60.00) 34 (39.08)Total 52 (100.00) 35 (100.00) 87 (100.00)

Chi square Statistic (Yates corrected): 9.344, p value:

<0.01

Median age at marriage: Users:16, Non-users: 18

It was found that significantly higher percentage of

users had age at marriage less than 18 years as

compared to non-users (p<0.01). There were more

users with three or more children than non-users

(table-5).

Table 5: Distribution of Tubectomy Status by TotalNumber of Children

Number of

Children

Tubectomy(%)

Total (%)User Non-user

1-2 18 (34.62) 24 (88.89) 42 (53.16)

≥3 34 (65.38) 03 (11.11) 37 (46.84)

Total 52 (100.00) 27 (100.00) 79 (100.00)

Note: Eight couples who do not have any children

were excluded.

Chi square Statistic (Yates corrected): 18.90, p

value<0.01The highest level of education was found to be

graduation while the lowest was illiterate in the case of

husbands, while it was high school and illiterate in the

case of the respondents (table -6,7).

Table 6: Distribution of Tubectomy Status by

Educational Qualification of Husband

Educational

Qualification

Tubectomy (%)


<Middle 14 (26.92) 12 (34.29) 26 (29.89)

≥Middle 38 (73.08) 23 (65.71) 61 (70.11)

Total 52 100.00) 35 (100.00) 87 (100.0)

Chi square Statistic (Yates corrected): 0.246, p value =

0.6

Table 7: Distribution of Tubectomy Status by

Educational Qualification of Respondent

Educational

Qualification

Tubectomy (%)


<Middle 22 (42.31) 17 (48.57) 39 (44.83)

≥Middle 30 (57.69) 18 (51.43) 48 (55.17)Total 52 35 87




Chi square Statistic (Yates corrected): 0.126, p value =

0.7

Level of education of the husband did not have a

significant association with tubectomy (p>0.05). It was

also observed that greater is the income, the more is

the acceptance for tubectomy (table – 8).

Table 8: Distribution of Tubectomy Status by Total

Monthly Income

Income Tubectomy (%)


<2000 01 (01.92) 07 (20.00) 08 (09.19)

2000-2999 10 (19.23) 13 (37.14) 23 (26.44)

3000-3999 25 (48.08) 09 (25.71) 34 (27.59)

≥4000 16 (30.77) 06 (17.14) 22 (25.29)

Total 52 (100.00) 35 (100.00) 87 (100.0)

Chi square Statistic (Yates corrected): 10.30, pvalue <0.01

Logistic Regression

A model for Logistic Regression Analysis was

prepared, taking those predictor variables which had

shown a significance of p≤0.1 in the univariate

analysis. The multivariate analysis was done to assess

the effect or association or impact of age of

respondents, age of husband, age of respondent at

marriage, age of respondent at birth of first child, total

number of children, occupation of respondents,

combined income of respondents and husband, on

tubectomy status. Women with no child were excluded

from this analysis, since they will not have information

regarding age at birth of the first child and a number of

children will be zero. In this analysis, only the

combined income was found to have a significant

association with tubectomy status, with p value less

than the conventional i.e. p<0.05, Odds Ratio = 15.29

with 95% Confidence Interval: 2.44 – 95.69. It was

observed that the odds of acceptance of tubectomyamong those couples who had a combined income of

≥3000 rupees per month were 15.29 times more than

the couples who had a combined monthly income less

than this figure.

DISCUSSION

In the present study, the figures for contraceptive

prevalence as well as female sterilization, both are

above the corresponding national figures. The current

level of contraceptive use i.e. contraceptive prevalencerate defined as percentage of currently married women

aged 15-49 years who are currently using a method or

whose husbands are using a contraceptive method, is

one of the principal determinants of fertility. It is also

an indicator of the success of family planning

programmes.11

As per NFHS III, contraceptive

prevalence rate for currently married women in India

is 56 percent (four percent more than NFHS II).

Female sterilization with a prevalence of 37 percent,

accounts for 66 percent of all contraceptive use (NFHS

II: 34.2 percent; NFHS I: 27.3 percent). In the state of

Maharashtra, the prevalence of female sterilization is

44.2 percent.11

Sterilisation has been a widely used

method of contraception in India.

It has been found that unmet need decreases with age,

from 27 percent for women aged 15-19 years, to two

percent for women aged 45-49 years. The unmet need

for family planning among currently married women is

13 percent, down from 16 percent in NFHS II.11 In the

present study, it was revealed that the age of users was

significantly higher than non-users, which is similar to

findings of previous studies.13-15

A significant

association was also found between tubectomy and the

age of the respondent at marriage (p<0.01). The

median age at marriage is 16 years and 18 years

among users and non-users respectively. One in six

women begins childbearing in the age group 15-19

years. The age at which women start bearing children

is an important demographic determinant of fertility.11

Similar results were observed in the present study i.e.,

46 (58.22%) of the respondents had given birth to their

first child before they turned 20 years of age. Delayed

childbearing may reduce maternal and infant health

risks but in addition, also provide increased

opportunities for women to acquire education, skills

and great aspiration for herself and her family.15

The

permanent method of contraception has been found to

be accepted by 70.7% of the women with three or

more children and only 29.3% accepted this methodwith one or two living children.

16In the present study,

a significant association was observed between

tubectomy and the total number of children (p<0.01).

The mean number of children for currently married

women was found to be 2.96 and 1.37 in case of users

and non-users respectively. There were six

respondents who had only female children and all of

them were non-users. It appears that the family is

considered complete only if male children are there,

whether they are in addition to the female children ornot; only then is tubectomy resorted to. It shows that

the gender of the children is a determining factor for




undergoing tubectomy. The extent to which the status

of women is related to awareness, knowledge, and

practice of family planning in India shows a definite

statistical relationship between women's status and

women's ability to control fertility. It was found that a

higher percentage of couples who have two or more

surviving children, particularly if they are boys,

practiced family planning.17, 18

Education as such has not been found to have any

significant association with tubectomy although better

is the educational qualification, more likely is the

decision to resort to it.16,17,19-21

In NFHS III, overall,

just over half i.e. 55 percent of women were found to

be literate while 78 percent males were found to be so.

In case of rural areas, 49.7 percent of women and 23.0

percent of men were found to be illiterate. In fact,

besides income, the greatest difference in fertility was

found to be due to education. The use of female

sterilization is higher for females with less education.11

In a study conducted in a developed country, it was

hypothesised that the current contraceptive use among

the sexually active, fertile women was related to their

attitude towards the different types of contraceptive

methods available, social influences, the perceptions

of ability to use a method correctly and also

consistently, and communication with their respective

partner. In the present study too, education has been

observed to play an important role in partner support

and the decision making process.22

Wealth has been found to have a positive effect on

women’s contraceptive use. In NFHS III,

contraceptive use was found to be 42 percent among

the lowest quintile, while it increased to 68 percent in

the highest quintile. It was observed in the present

study that in the case of those couples who had both

members earning, acceptance of tubectomy was more.

Income has been found to influence the acceptance of family planning methods and an increasing trend of

acceptance has been observed with the increase in

income.16

From the present study it is evident that sterilization is

fairly well accepted, however more knowledge is

needed on reversible methods. Since the findings of

the current study are comparable to other similar

studies and the NFHS III data, it highlights that the

results of the current study can be used as a

background to conduct more such studies so as to addon to the information that already exists. It would help

to generate community specific data in order to benefit

for research, development and planning purposes.

CONCLUSION

This study brings out that knowledge about

contraceptive is nearly universal and that educationenhances the ability of individuals to achieve desired

demographic goals.11

It reiterates the fact that

education plays a major role in creating better

awareness amongst people. The choice of

contraceptive appears to be determined a lot more by a

general like or dislike towards medical methods, rather

than weighing merits of the individual available

methods.22

Effective contraceptive practices have the

potential, not only to improve the lives of the women,

men and children involved, but also to benefit couples,

families and communities.23

RECOMMENDATIONS

Based on this study, it is recommended that what is

required is the need to strengthen social marketing

programmes for non-clinical family planning products

and services in such areas. Greater effort needs to be

made to involve men in the process of family planning

and male sterilization requires to be given impetus.

Awareness about methods other than female

sterilization must be improved by village level

campaigns. To help encourage adoption of family

planning and reduce fertility, the government should

emphasize education for women, enforce the legal

minimum age at marriage, promote employment

opportunities for women, improve women's role in

decision making, and encourage inter-spousal

communication in family affairs.

Conflicts of interest; None identified.

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59

Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64


&

Health Sciences



rdDec 2013 Accepted: 12

thDec 2013

Research article

CLINICO-PATHOLOGICAL PROFILE IN THE INFANTS AND CHILDREN IN DENGUE 2012

EPIDEMIC, KOLKATA

*Saha K Ashis1, Ghosh Shibendu

2.

1Assistant Professor, General Medicine, K P C Medical College & Hospital, Jadavpur, Kolkata, West Bengal

2Professor, General Medicine, Ramkrisna Mission Seba Pratisthan, Kolkata, West Bengal, India


ABSTRACT

Background: Dengue fever (DF) is responsible for cyclical and frequent epidemic in different parts of India in its

varieties of presentations. In 1992 large number of children died of Dengue hemorrhagic fever (DHF). Aims and

objective: In this study, we evaluated the demography and clinico-pathological profile in dengue affected infants

and children in 2012 Kolkata epidemic. Materials and methods: Total 233 patients (between 1-18 years, with

either Non structural protein 1 antigen or dengue Immunoglobulin positive) admitted in our hospital. After taking

proper history and physical examination, blood were sent for different hematological and biochemical examinations

on the day of admission and after 24-48 hours of admission. We differentiated the dengue patients into DF and DHF

based on platelet count. Results: Male female ratio and DF to DHF ratio were 1: 0.86 and 1: 3.5 respectively. Mean

age of DF and DHF were 10.31±5.41 years and 12.6±4.51 years respectively. Mean duration of fever in DF and

DHF cases were 5.33±1.13 and 6.08±1.79 days respectively. Headache, backache, nausea/vomiting, rash, anorexia,

loose motions were statistically significant in DF. In spite of significant positive tourniquet test in DHF patients

(76.92%), only 13 patients showed evidence of bleeding. Hematocrit (Hct) values between 30-40 and below 30

were significant in DHF and DF patients respectively. Leucopenia and increased liver enzymes (SGOT and SGPT)

were commonly observed in both DF and DHF patients. Hepatomegaly was observed in 13.72% of DF patients,

whereas, isolated hepatomegaly, ascites, combined hepatomegaly with ascites and evidence of pleural effusion were

observed in 4.94%, 1.64%, 3.29% and 7.14% of DHF patients respectively. Conclusion: In seropositive DHF

patients, fever, headache, backache, loose motions were the predominant symptoms associated with hepatomegaly,

elevated liver enzymes and evidence of plasma leakage.

Keywords: Clinico-pathology, Dengue epidemic, Infants, Children, Kolkata

INTRODUCTION

Over several decades, Dengue, an Arbo virus

infection, is responsible for cyclical and more frequent

epidemic in rural as well as urban areas of India,

showing a wide variety of presentations from

subclinical or mild self limiting disease to severe form

of disease, like, dengue hemorrhagic fever (DHF) anddengue shock syndrome (DSS).

1DHF first crept into

Kolkata in 1963-65, this was followed by the recurrent

occurrence of outbreaks.2

In the 1992 epidemic, large

number of affected children died of DHF/DSS.

Dengue may be manifested by its typical clinical

features, but its presentation may be variable making

the doctor puzzled. Our present study was to evaluatethe demography and clinic-pathological profile of

DOI: 10.5958/j.2319-5886.3.1.012



60


dengue fever in infants and children during the 2012

dengue epidemic in Kolkata.

PATIENTS & METHODOLOGY

Inclusion criteria: In 2012 epidemic, total 233 infants

and children between the ages of 1 to 18 years, were

admitted in our hospital on and from the month of 1st

August to 31st

October with either Non structural

protein 1 antigen (NS1, antigen) positive or dengue

Immunoglobulin M (IgM) positive.

Exclusion criteria: Patient suffering from any

infection, viral hepatitis during this period.

Ethical clearance: This study was started after getting

approval from Ethical Committee and informed

consent form obtained from the patients’ parties.

Methodology: Thorough history-taking and physical

examination was performed in all these patients. Justafter admission, 5 ml. of blood was collected

aseptically from each patient. 1 ml of clotted blood

was used for non structural protein 1 (NS1) antigen

and immunoglobulin M (IgM) antibody by Mac

ELISA manufactured by Panibo Diagnostics,

remaining 4ml of Blood sample was used for

examination of hematological and biochemical profile

immediately.

Between the interval of 24 and 48 hours after

admission, 4 ml of blood sample was collected. 2 mlof blood was kept in EDTA vial and was sent for

platelet count both by manual methods (light

microscopy and Neubauer chamber) and Coulter

counter method and hematocrit. Rest 2 ml of clotted

blood was used for biochemical tests (SGPT, SGOT).

Daily platelet count was advised for those patients

having platelet count less than 100000/cc.

Imaging studies like, Ultrasonography and chest x-ray

were performed to detect Ascites and pleural effusion

respectively. We differentiated the dengue patientsinto Dengue fever (DF) and DHF based on platelet

count. (Since there was no DSS detected among in this

group). These patients were treated with intravenous

fluid, Paracetamol according to WHO protocol.3

No

patient was treated with NSAID. When vital statistics

of these patients came to normal; they were discharged

from hospital.

Statistics: Then, we compared the demographic data,

symptoms, laboratory investigations between DF and

DHF by Open stat and Statcalc statistical Calculators.

P value of <0.05 was considered as statistical

significance.

RESULTS

In our study, all our patients were either NS1 (79%) or

IgM (21%) positive. Male female ratio was 1: 0.86,

whereas ratio of DF to DHF ratio was 1: 3.5. Male to

female ratio in DF was 1: 1 and in DHF, 1:1.16. Mean

age of DF and DHF were 10.31±5.41 years and

12.6±4.51 years respectively [table 1]. All the patients

were admitted with fever. Mean duration of fever in

DF and DHF cases were 5.33±1.13 and 6.08±1.79

days respectively. Common symptoms were

Headache (62.74%, 30.76%), backache (58.82%,

30.76%), nausea/vomiting (62.74%, 47.25%), rash

(29.41%, 15.93%), anorexia (60.78%, 13.73%), loose

motion (35.29%, 18.68%) in both DF and DHF

respectively. In spite of significant positive tourniquet

test in DHF patients (76.92%), severe bleeding was

seen in only 13 patients. [Table 2]. Most of the

patients were anemic. Hematocrit (Hct) between 30-40

was significant in DHF patients, whereas, Hct was

observed below 30 in significant number of DF

patients. Leucopenia and raised liver enzymes (SGOT

and SGPT) were commonly observed in both DF and

DHF patients without any statistical difference. But,

the International normalized ratio (INR) was only

elevated more than 1.5 in DHF patients [Table 3].

Sonographically, Isolated hepatomagaly observed in

13.72% and 4.94% DF and DHF patients respectively,

whereas, ascites and ascites associated withhepatomagaly were observed in 1.64% and 3.29% of

DHF patients respectively. Again, chest x-ray showed

evidence of pleural effusion in DHF patients only

[Table 4].

Table 1: Demographic distribution

Features DF (51) DHF (182) P value

Mean age yrs 10.31 ±5.41 12.6 ±4.51 0.04*

Male sex 26 98 0.35

Female sex 25 84 0.35*significant



61


Table 2: Common symptoms

Symptoms DF (51) DHF (182) % Amongst total (233) P value

Fever (days) 5.33±1.13 6.08±1.79 - 0.0001**

Headache 32 (62.74 %) 56(30.76%) 88 (37.76%) 0.00001***

Backache 30 (58.82%) 56 (30.76%) 86(36.90%) 0.0001**

Nausea/vomiting 32 (62.74%) 86 (47.25%) 136(58.36%) 0.02*Rash 15 (29.41%) 29 (15.93%) 44 (18.88%) 0.01*

Anorexia 31 (60.78%) 52 (13.73%) 83(35.62%) 0.00001***

Loose motion 18 (35.29%) 34 (18.68%) 52 (22.31%) 0.005**

Retro orbital pain 4 (7.8%) 6 (3.29%) 10 (4.29%) 0.07

Types of bleeding

Positive tourniquet test 0 140 (76.92%) 140 (60.08%)

Epistaxis 0 3 (1.64%) 3(1.28%)

Skin 0 4 (2.19%) 4(1.71%)

Gum 0 3 (1.64%) 3(1.28%)

Hematemesis/melena 0 3 (1.64%) 3 (1.28%)*-- Significant, **-- Very significant, *** -- Extremely significant

Table 3: Hematological, biochemical distribution:

Parameter DF (51) DHF (182) % amongst total (233) P value

Hematocrit (L/L)

≥40 (37) 2 (3.92%) 4 (2.19%) 6 (2.57%) 2.46

(30-40) 20 (39.21%) 120 (65.93%) 140 (60.08%) 0.0003**

(<30) 29 (56.86%) 58 (31.86%) 37.33 0.0006**

Hemoglobin (gm/dl) 10.5±1.4 10.3±1.1 -

Total leukocyte count

<1000-3000/cc 20 (39.21%) 60 (32.96%) 80 (34.33%) 0.20>3000-4000/cc 19 ( 37.25%) 80 (43.95%) 99(42.48%) 0.19

>4000/cc 12 (23.52%) 42 (23.07 %) 54(23.17%) 0.47

Platelet count

≤20000/cc (8) 0 8 ( 4.39%) 8(3.43%) -

>20000 – 40000/cc 0 28 (15.38%) 28(12.01%) -

SGOT >3 times normal 15 (29.41%) 66 (36.26%) 81(34.76%) 0.18

SGPT >100 – 200 IU/L 10 (19.60%) 31 (17.03%) 41(17.59%) 0.33

SGPT >200 – 350 IU/L 5 (9.80%) 18 (9.89%) 23 (9.87%) 0.49

SGPT >350 IU/L 2 (3.92%) 14 (7.69%) 16 (6.86%) 0.17

INR >1.5 (21) 0 21 (11.53%) 21 (9.01%) -

** Very significant, SGOT: Serum aspartate aminotransferase, SGPT: Serum alanine aminotransferase; INR:

International normalized ratio

Table 4: Radiological distribution:

Items DF (51) DHF (182) % Amongst total patients (233)

USG

Ascites 0 3 (1.64%) 1.28

Hepatomegaly 7 (13.72%) 9 (4.94%) 6.86

Ascites & Hepatomegaly 0 6 (3.29%) 2.57

Hepatosplenomegaly 0 0 0

Chest x-ray 0 13 (7.14%) 5.57



62


DISCUSSION

Age group affected by dengue fever as shown by

Narayanan et al4

was 7 to 8 years of age, which was

similar to the study done by Kabra SK et al5

and Banik

GB et al.6

Though dengue fever is a well-known

disease of child-age group, but since 1980’s there is

slight inclination towards higher age group in case of

DHF, as shown in various studies in Latin America

and South-East Asia. Similarly, in our study, the mean

age was 10.31 and 12.6 years in DF and DHF

respectively. Though according to previous belief,

DHF/DSS is due to either previous infection or passive

transfer of antibody from the mother7, but in our study,

DHF occurred at higher age group – so it may be due

to antibodies, acquired by the patients at earlier ages.

According to some author, it may be due to virulentvirus rather than pre-infection antibody status.

8

Few available hospital studies demoed male-female

distribution in dengue fever. Kabra SK et al5

showed

girl preponderance as also seen in the study done by

Mittal H et al.9Three independent studies in India and

Singapore showed that males were twice more

common than females.10 , 11

Hospital based study in

Delhi showed male to female ratio 2.5:1.12

Similarly,

in our study, there was slight edging of boys over girls.

In study done by Mittal et al showed that fever(100%), headache (63%), abdominal pain (71%) and

petechiae (35.5%) were more common.9

Fever,

vomiting were most frequent symptoms as shown by

Narayanan M et al.4

Similar pictures were observed in

our study, but in addition, headache, anorexia was also

frequently found.

In our study, 76.92% DHF patients showed positive

tourniquet test, which was much higher than that was

observed in the study of Kabra et al.5

It may be due to

thrombocytopenia and capillary fragility, either orboth. Low proportion of positivity in tourniquet test in

Indian population may be due to darker skin color or

dengue strain difference in Indian subcontinent.13, 14

.

The tourniquet test will never correlate with overt

bleeding manifestation as shown by Wali et al.15

It

may be due to difference in pathogenesis, like,

vascular permeability and/or capillary fragility.

Since in our study, only 13 patients showed evidence

of bleeding, amongst them, evidence of epistaxis, gum

bleeding and hematemesis were observed in 1.64% of

DHF patients, which was very low as compared to

other studies5. According to WHO’s protocol for

management of DHF, 1-2 hourly documentation of

Hematocrit (Hct) value is very essential for monitoring

intravenous fluid therapy. But, if pretreatment Hct

value is not known, it is very difficult to demonstrate

the percentage of hemoconcentration in DHF.

Hemoconcentration is very important factor that

correlates platelet count with bleeding manifestations.

This was shown in different studies.16, 17

. In our study,

Hct >40 was observed in 3.92% of DF and 2.19% of

DHF patients, whereas, Hct >30-40 was observed in

65.93% of DHF patients. So according to our study, it

may not be a good indicator of monitoring fluid

therapy in infants and children in presence of moderate

anemia which was near 10 gm% in our study

population.

In our study, leucopenia (<5000/cc) was observed in

76.81% of patients, whereas, Ratageri et al18

showed

21% of patients suffered from leucopenia and

Benerjee19

et al demonstrated no evidence of

leucopenia in their studies. So, leucopenia may be an

indicator of virulent dengue strain in our epidemic.

Our study showed 182 (78.11%) children suffered

from thrombocytopenia, amongst them, 36 (19.77%)

had platelet count <40000/cc. Similarly, 82% and

96%rombocytopenic patients were described in the

studies of Ratageri et al18 and Banerjee et al19

respectively. This thrombocytopenia may be due to

decreased production in bone marrow, temporary bone

marrow suppression20

, virus-antibody complex

mediated immune destruction21

of platelet or increased

consumption of platelet induced by secondary

infection associated with release of high level of

platelet activating factors or increased adhesiveness of

platelet to the vascular endothelial cells.22

In DHF, there may be evidence of plasma leakage as

evidenced by ascites and pleural effusion. In our study,13 (7.14%) patients showed evidence of pleural

effusion in the chest x-ray, 3 (1.64%) patients suffered

from isolated ascites and 6 patients (3.29%) suffered

from ascites associated with hepatomegaly. On the

contrary, 70% and 54% of children demonstrated

pleural effusion and ascites respectively in the study of

Ratageri et al.18

According to some observations,

massive T-cell activation producing cytokines

(interferon γ, interleukin 2 and TNF α) and infected

cell lysis by CD 4+ and CD8+ dengue specificlymphocytes are mainly responsible for plasma



63


leakage. Interaction between infected cells and

immune cells induces release of cytokines directly by

macrophages and monocytes.

One important laboratory finding is elevation of liver

enzymes, which was reported in various studies.23-.25

.

Similarly, in our study, the rise in SGPT >100 U/L

was observed in 34.32% of patients.

Evidence of vomiting, hepatomegaly and elevated

liver enzymes may be a clue to the diagnosis of

dengue in the background of the epidemic.

CONCLUSION

Dengue fever is more prevalent in Kolkata. Mean age

of DF and DHF patients were 10.31 and 12.6 years

respectively. Male to female ratio was 1.13:1. In

seropositive DHF patients, fever, headache, backache,

loose motions were the predominant symptoms

associated with hepatomegaly, elevated liver enzymes

and evidence of plasma leakage. Leucopenia may be

due to a virulent strain of dengue virus.

Key-massage: Evidence of fever, vomiting, backache

with or without bleeding associated with

hepatomegaly, elevated liver enzymes and

thrombocytopenia may be a clue to the diagnosis of

dengue hemorrhagic fever. Due to the high prevalenceof anemia, rise in Hematocrit is not at all helpful to the

diagnosis of DHF.

Funding: Nil.

Competing interests: Nil.

REFERENCES

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whqlibdoc.who.int/publications/1997/9241545003

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4. Narayanan M, Arvind MA, Thilothammal N,

Prema R, Sargunum CS, Rex, Ramamurty N.

Dengue fever Epidemic in Chennai- A study of

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5. Kabra SK, Jain Y, Pandey RM, Madhulika,

Singhal T, Tripathi P, Broor S, Seth P, Seth V.

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Delhi epidemic. Trans R Soc Trop Med Hyg.

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6. Banik GB, Pal TK, Mandal A, Chakrabarty MS,

Chakrabarti SK. Dengue hemorrhagic fever in

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7. Halstead SB. Antibody, macrophage, dengue

virus infection, shock and hemorrhage. A

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8. Sumaro W, Jahja E, Gubler DJ, Suharyono W,

Sorensen K. Clinical observations on virologically

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Clinicohematological profile and platelet trends in

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Indian J Pediatr 2012; 79:467-71

10. Agarwal R, Kapoor S, Nagar R, Mishra A, Tandon

R, Mathur A et al. A clinical study of the patients

with dengue hemorrhagic fever during the

epidemic of 1996 at Lucknow, India. Southeast

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11. Goh KT, Ng SK, Chan YC, Lim SJ, Chua EC:

Epidemiological aspects of an outbreak of dengue

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Southeast Asian J Trop Med Public Health 1987;

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12. Wali JP, Biswas A, Handa R, Aggarwal P, Wig N,

Dwivedi SN. Dengue hemorrhagic fever in adults:a prospective study of 110 cases. Trop Doct 1999;

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13. Srivastava VK, Suri S, Bhasin A, Srivastava A,

Bharadwaj M. An epidemic of dengue

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Delhi: a clinical study. Ann Trop Pediatr

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KN, Gupta P, Gupta P et al. Hematological

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hemorrhagic fever- a reappraisal. Indian Pediatr

2001; 38:477-81

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Handa R. Validity of tourniquet test in dengue

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1999;47:203-04

16. Bethell DB, Gamble J, Loc PP, Dung NM, Chau

TTH, Loan HT et al. Non-invasive measurement

of microvasvascular leakage in patients with

dengue hemorrhagic fever. Clin Infect Dis 2001;

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17. Tripathi BK, Gupta B, Sinha RS, Prasad S,

Sharma DK. Experience in adult population in

dengue outbreak in Delhi. J Assoc Physicians

India 1998; 46:273-76

18. Ratageri H, Shepur TA, Wari PK, Chavan SC.

Clinical profile and outcome of Dengue fever

cases. Ind J of Pediatrics 2005; 72:705-06

19. Banerjee M, Chatterjee T, Chowdhury GS,

Srinivas V, Kataria VK. Dengue: A

Clinicohematological profile. MJAFI 2008; 64:

333-36

20. Halstead SB. Dengue. Lancet. 2007; 370:1644-52

21. Wang S, He R, Patarapotikul J, Innis BL,

Anderson R. Antibody-enhanced binding of

dengue-2 virus to human platelets. Virology 1995;

213:254-57

22. Yang KD, Wang CL, Shaio MF. Production of

cytokines and platelet activating factor in

secondary dengue virus infection. J Infect Dis

1995; 172:604

23. Kalayanarooj S, Vaughn DW, Nimmannitya S,

Green S, Sutayakom S, Kunentrasai N et al. Early

clinical and laboratory indicators of acute dengue

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24. Pushpa V, Venkatadesikalu M, Mohan S, Cherian

T, John TJ, Ponnuraj EM. An epidemic of denguehemorrhagic fever/dengue shock syndrome in

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Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70


&

Health Sciences


stOct 2013 Revised: 14


thNov 2013

Research article

EVALUATION OF MODIFIED HODGE TEST AS AN INDICATOR OF KLEBSIELLA PNEUMONIAE

CARBAPENEMASE (KPC) PRODUCTION BY USING bla KPC GENE PCR

*Priyadarshini Shanmugam, Nirupa Soundararajan, Jeya Meenakshisundaram

Department of Microbiology, Chettinad Hospital and Research Institute, Tamilnadu, India


ABSTRACT

Introduction: Carbapenems belong to the Beta Lactam group of antimicrobial agents. They are often used as “last -

line agents” or “antibiotics of last resort” in critically ill patients. Carbapenem resistance in Enterobacteriaceae may

be due to various reasons but Klebsiella pneumoniae Carbapenemase (KPC) enzyme production is the commonest.

Phenotypic as well as genotypic methods can be used to detect Carbapenemases. Among the phenotypic tests,

Modified Hodge Test (MHT) is relatively easy to perform. Aims and Objectives: This study aimed to determine

the prevalence of carbapenem resistance among Enterobacteriaceae isolates and calculate the sensitivity of MHT as

an indicator of KPC production. Materials and Methods: All Enterobacteriaceae isolates from clinical samples

were included in this study and were screened for Carbapenem resistance. 45 randomly chosen Carbapenem

Resistant Enterobacteriaceae isolates were subjected to MHT and blaKPC gene detection by PCR. Results: 2035

Enterobacteriaceae isolates were tested and 5.2% were found to be resistant to Imipenem, 22.9 % were resistant to

Meropenem and 4.42 % were resistant to both Imipenem and Meropenem. The sensitivity of MHT was calculated to

be 90% and specificity was calculated to be 60%

Keywords: Carbapenemase, Modified Hodge Test, Enterobacteriaceae, bla KPC gene

INTRODUCTION

Bacteria belonging to the Enterobacteriaceae family

are normally present as harmless human gut flora.

These bacteria are the leading cause of a wide range of

opportunistic infections.1

Carbapenems belongs to the

Beta Lactam group of antimicrobial agents, which kill

bacteria by inhibiting the bacterial cell wall synthesis.2

They possess the broadest spectrum of activity and

greatest potency against Gram-positive and Gram-

negative bacteria.3

As a result, they are often used as

“last-line agents” or “antibiotics of last resort” when

patients with infections become gravely ill or are

suspected of harboring resistant bacteria.3

Carbapenem

resistance among Enterobacteriaceae members is of great concern as these bacteria are easily transmissible

among patients, leading to hospital acquired infections

(HAI), but can also spread into the community,

resulting in community acquired cases.1

Carbapenem resistance in Enterobacteriaceae may be

due to various reasons that include hyper production of

the Amp C beta lactamase, loss of porins, production

of metallo beta lactamases (MBL) and production of K

pneumonia carbapenemases.1

Carbapenemases increasingly have been reported

worldwide in Enterobacteriaceae in the past 10

years.4, 5

A large variety of carbapenemases has been

identified in Enterobacteriaceae belonging to 3 classes

of β-lactamases: the Ambler class A, B, and D β-

lactamases.3

In addition, rare chromosome encodedcephalosporinases (Ambler class C) produced by

Enterobacteriaceae may possess slight extended

DOI: 10.5958/j.2319-5886.3.1.013



66


activity toward carbapenems.4

Their identification is of

primary importance since carbapenemase producers

are resistant not only to most Beta-lactams but also to

other main classes of antibiotics.5

Carbapenemases can be detected by phenotypic as

well as genotypic methods.6

Modified Hodge Test

(MHT) is a phenotypic method which is relatively

simple and easy to perform in a laboratory.6

This

cloverleaf technique, or Modified Hodge test, has been

extensively used as a phenotypic technique for

detecting carbapenemase activity.5

Limitations of the MHT in terms of clinical

performance are its lack of specificity and the delay in

obtaining the results upto 24 or 48 hours after isolation

of a bacterial colony.5

The molecular detection of

blaKPC is the gold standard for diagnosis, but the

majority of laboratories in our country does not have

the resources necessary to perform this test.7

The aim of this study was to determine the prevalence

of Carbapenem resistance among Enterobacteriaceae

and detect the bla KPC gene prevalence among

randomly chosen Carbapenem resistant

Enterobacteriaceae clinical isolates in our 750 bed

hospital. The study also aimed to evaluate the

performance of the Modified Hodge test and calculate

the sensitivity of MHT as an indicator of Klebsiella

Pneumoniae Carbapenemase (KPC) production.


The isolates in this study were collected in a period of

one year from July 2012 to June 2013. The study was

conducted at Chettinad Hospital and Research

Institute, Chennai. The institutional ethical committee

approval was obtained prior to commencement of this

study. All Enterobacteriaceae isolates from clinical

samples like pus, wound swab, sputum, endotracheal

aspirate, blood and urine were included in this study.

The samples were collected after obtaining informed

consent from the patients. For evaluation of Modified

Hodge Test by PCR, 45 isolates which were resistant

to both or either Imipenem or Meropenem were

randomly selected. MHT and bla KPC PCR were

performed on these 45 isolates

These isolates were screened for Carbapenem

resistance in addition to the routine antibiotic

susceptibility testing, which was performed by the

Kirby Bauer method, as per the CLSI guidelines 2012.8

Antimicrobial discs used were Ampicillin (10μg),

Gentamicin (10μg), Amikacin (30μg), Cefazolin (30

μg), Cefuroxime (30μg) Ceftazidime (30μg),

Cefotaxime (30μg), Ceftriaxone (30μg), Cefepime

(30μg), Ciprofloxacin (5μg), Cotrimoxazole

(23.75/1.25μg), Piperacillin/ tazobactam (100/10μg),

Imipenem (10μg), Meropenem (10 µg), Polymyxin B

(300 units) and Colistin (10µg).

Modified Hodge Test

Phenotypic detection of Carbapenemase production

was done by using the Modified Hodge test. This test

was performed as per the CLSI guidelines 2012.8

A

0.5 Mac Farland’s suspension of ATCC Escherichia

coli 25922 was diluted 1:10 in sterile saline. This was

inoculated on a Mueller Hinton agar plate, as for the

routine disc diffusion testing. The plate was dried for 5

minutes and a disc of Imipenem 10 μg was placed in

the centre of the agar plate. 3-5 colonies of the testorganism were picked and inoculated in a straight line,

from the edge of the disc, up to a distance of at least

20mm. The plates were incubated at 370C overnight

and they were examined next day. They were checked

for an enhanced growth around the test organism, at

the intersection of the streak and for a zone of inhibi-

tion. The presence of an enhanced growth indicated

Carbapenemase production, and the absence of an

enhanced growth meant that the test isolate did not

produce carbapenemase.8

bla KPC gene detection

The isolates which gave positive results for the

modified Hodge test were submitted to molecular

detection of the bla KPC gene by PCR. The PCR Kits

were procured from Helini Biomolecules, Chennai.

Isolates with negative test results were also randomly

chosen for PCR. The Polymerase Chain Reaction was

set up in a PCR vial, after adding the master mix, the

forward and reverse primers and the extracted DNA

from the isolates. The primers used for PCRamplification and the reaction conditions were

Forward Primer: 5’-GCT CAG GCG CAA CTG TAA

G-3’ Reverse Primer: 5’-AGC ACA GCG GCA GCA

AGA AAG-3’. The PCR vial was placed in PCR

machine (Corpect Research 96 wells, Australia) and it

was subjected to initial denaturation at 94ºC for 3 min,

followed by 30 cycles of denaturation at 94ºC for 1

minute, annealing at 60ºC for 1minute and extension at

72ºC for 1minute. A final extension procedure was

carried out at 72º C for 5 min. Next the PCR products

were subjected to electrophoresis on 2% agarose gel

stained with ethidium bromide and visualized with UV



67


light The antibiogram for the Carbapenem Resistant

Enterobacteriaceae was analyzed

RESULTS

2035 non repetitive isolates of Enterobacteriaceae

were obtained from clinical samples such as pus, urine,

blood, sputum and endotracheal aspirates, over aperiod of 1 year. Of these, 1178 (57.88%) were

Escherichia coli, 444 (21.81) were Klebsiella species,

178 (8.7%) Proteus species, 154 (7.56%) Citrobacter

species and 81 (3.9%) were Enterobacter isolates

(Figure1). Figure 2 shows the number of carbapenem

resistant isolates among the individual genera. The

antibiogram of the Enterobacteriaceae isolates is

tabulated in Table 1 and the antibiotic resistance

pattern of the CRE are tabulated in Table 2.

Of the total of 2035 isolates, 106 (5.2%) were resistant

to Imipenem and 468 (22.9 %) were resistant to

Meropenem and 90 (4.42 %) were resistant to both

Imipenem and Meropenem.

Fig 1: Total number of Enterobacteriaceae isolates Fig 2: Carbapenem Resistance pattern of the Isolates

Table 1: Antibiotic Resistance pattern of the Enterobacteriaceae (% of Resistance)ANTIBIOTIC Ecoli Klebsiella Proteus Citrobacter Enterobacter

Amikacin 9.67 % 16.64 % 31.46 % 16.88 % 11.11 %

Ampicillin 85.7 % 100 % 71.51% 88.42 % 69.14 %

Cefazolin 71.3% 66.67 % 82.58 % 72.73 % 82.72 %

Cefuroxime 64.9 % 59.46 % 66.83 % 58.44 % 65.43 %

Cefotaxime 61.1 % 53.38 % 49.43 % 51.3 % 46.91 %

Cefepime 53.2 % 42.79 % 39.32 % 37.66 % 38.27 %

Ciprofloxacin 63.1 % 47.07 % 58.99 % 40.26 % 41.98 %

Cotirmox 55.2 % 50.9 % 68.02 % 46.75 % 45.68 %Colistin 0 % 0 % 100 % 2.6 % 0 %

Genta 36.76 % 34.0 %1 46.07 % 34.42 % 32.1 %

Imipenem 3.23 % 9.68 % 6.82 % 5.84 % 4.94 %

Meropenem 21.3 % 20.95 % 50.15 % 16.23 % 13.58 %

Nitrofurantoin 11.7 % 31.15 % 87.87 % 33.78 % 43.48 %

Norfloxacin 59.54 % 31.15 % 49.2 % 36.49 % 30.43 %

Piperacillin Tazobactam 19.9 % 21.78 % 15.47 % 21.52 % 13.58 %

Polymyxin B 0 % 0 % 100 % 0 % 1.23 %

Tobramycin 39.47 % 16.17 % 48.14 % 29.49 % 34.78 %



68


Table 2: Antibiotic resistance pattern of the 45 Multi Drug Resistant Enterobacteriaceae

Percentage of Resistance Klebsiella(n =22) Ecoli (n =20) Citrobacter (n =2 Proteus (n = 1)

Amikacin 59 % 33% 100 % 100 %

Ampicillin 100 % 100 % 100 % 100 %

Cefazolin 100 % 100 % 100 % 100 %

Cefuroxime 100 % 100 % 100 % 100 %

Cefotaxime 100 % 100 % 100 % 100 %Cefipime 96% 100 % 100 % 100 %

Ciprofloxacin 91 % 91% 100 % 100 %

Cotrimoxazole 100 % 100 % 100 % 100 %

Colistin 0 % 5% 0 % 100 %

Gentamicin 73 % 67% 100 % 100 %

Imipenem 77 % 67% 100 % 100 %

Meropenem 96 % 95% 50 % 100 %

Nitrofurantoin (urine) 100% 20% 100 % 100 %

Piperacillin Tazobactam 100 % 100 % 100 % 100 %

Polymyxin B 0 % 0% 0 % 100 %

Tobramycin 94 % 73% 100 % 100 %

For evaluation of Modified Hodge Test by bla KPC

detection using PCR, 45 isolates which were resistant

to both or either Imipenem or Meropenem had been

selected. Of these, 22 were Klebsiella pneumoniae, 20

were Escherichia coli, 2 were Citrobacter species and

1 was Proteus mirabilis). Of the 45 isolates, 43 (95.5

%) were resistant to Meropenem, 34 (75.5%) were

resistant to Imipenem and 29 (64.4%) were resistant to

both Imipenem and Meropenem. Modified Hodge Test

was positive in 37 (82.2%) out of 45 isolates and bla

KPC gene was detected in 30 (66.7 %) isolates (Table

3). Of the 30 blaKPC gene positive isolates, MHT was

positive in 27 and negative in 3 isolates. Of the 15

blaKPC gene negative isolates, MHT was positive in 10

(66.6%) and negative in 5 (33.3%) isolates.

Considering PCR for bla KPC gene as the gold standard

for the detection of Klebsiella pneumoniae

Carbapenemase, the sensitivity and specificity of MHT

was calculated using the formula: Sensitivity = a/a+b

and Specificity = d/ c+d. [Where ‘a’ is True Positive(27), 'b' is False Negative (3), 'c' is False Positive (10)

and’d’ is True Negative (15) ]. In the present study, the

sensitivity of MHT was calculated to be 90 % and the

specificity was 60%. The positive predictive value was

72.97% and the Negative predictive value was

83.33%. Figure 3 shows isolates with positive MHT,

displaying the characteristic clover leaf like

indentation and Figure 4 shows the visualization of the

PCR products by gel electrophoresis.

Fig 3: Positive Modified Hodge Test

Fig4: bla KPC gene PCR : Gel Electrophoresis

showing positive and negative isolates

Table 3: Results of MHT and blaKPC gene PCR

Total

Isolates

MHT

(+ve)

Bla KPC

gene(+ve)

MHT &

bla KPC

gene (+ve)

Klebsiella 22 19 13 11

E coli 20 16 15 14

Citrobacter 2 1 1 1Proteus 1 1 1 1

Total 45 37 30 27



69


DISCUSSION

In our study, 5.2% of the isolates were resistant to

Imipenem, 22.9 % were resistant to Meropenem and

4.42 % were resistant to both Imipenem and

Meropenem. The highest percentage of resistance to

Carbapenems was seen in Klebsiella species, 9.68% toImipenem and 20.9% to Meropenem, followed by

Escherichia coli, Proteus, Citrobacter and Enterobacter

(Table 1). A study by Ramana et al1

showed that,

among the different Enterobacteriaceae members

tested, Klebsiella spp. showed the highest percentage

of carbapenem resistance at 30%, whereas Proteus

spp. and Citrobacter spp revealed comparatively low

carbapenem resistance of 17% and 12%, respectively.

The prevalence of carbapenem resistance in our study

was less than that of Ramana et al. Another study byParveen et al

9showed that 45 (43.6%) of K.

pneumoniae from clinical specimens, were resistant to

meropenem by the disk diffusion test. Among isolates

reported to the National Healthcare Safety Network in

2006 – 2007 carbapenem resistance was reported in up

to 4.0% of Escherichia coli and 10.8% of K.

pneumoniae isolates that were associated with certain

device-related infections.10

In the present study, the sensitivity of Modified Hodge

test was calculated to be 90%. A similar study byAnderson et al

11which had also evaluated the

modified Hodge test for detection of KPC-mediated

resistance inferred that the test demonstrated 100%

sensitivity and specificity for detection of KPC

activity. Diana Doyle et al12

in her study showed that

MHT had a sensitivity of 98% for detecting KPC

producers and 93% for OXA-48-like enzyme

producers but was less than optimal for detecting

MBLs. The sensitivity of MHT as inferred by our

study was less than that of the sensitivity of the other 2

studies. This could necessitate changes in the MHT to

make it more sensitive. A study was carried out by

Pasteren et al13

using an optimized MHT known as

Pseudomonas aeruginosa MHT (PAE MHT) which

demonstrated 100% sensitivity and 98% specificity for

detection of KPC activity without any indeterminate

result. Another study in Greece, showed that Modified

Hodge test detected 98% KPC producers, keeping

PCR as the gold standard[6]

In contrast, another study

by D. Girlich et al5

showed that the overall sensitivity

and specificity of the MHT was low (77.4% and

38.9%, respectively). In our study too, the specificity

of MHT was low- only 60%. Hatipoglu et al14

also

state that the MHT has a low specificity. This could be

because Modified Hodge Test detects other

carbapenemase enzymes in addition to KPC.

Of the 3 MHT negative isolates, one was positive for

bla KPC gene. Adriane BC et al15

have also reported

such isolates carrying silent genes. 8 (17.7%) isolates

were resistant to carbapenems, but were MHT

negative. They may have developed a different

resistance mechanism other than carbapenemase

production.

Prevalence of bla KPC gene was found to be 66.67%

among the carbapenem resistant isolates. blaKPC gene

was not detected in 10 MHT positive isolates. This

could indicate the presence of a carbapenemase other

than KP Carbapenemase. Resistance to both imipenem

and meropenem is a strong indicator of carbapenemase

production rather resistance to either one of the

carbapenems, as this may imply a different resistance

mechanism

CONCLUSION

Modified Hodge Test is a sensitive test for Klebsiella

pneumoniae Carbapenemase production. It is

recommended that all isolates showing intermediate

sensitivity or resistance pattern to carbapenems be

screened for the production of carbapenemases by

Modified Hodge test, which will provide a cost-

effective and rapid approach for the detection of

carbapenemases in Enterobacteriaceae.

REFERENCES

1. Ramana KV, Rao R, Sharada V, Kareem MA,

Reddy LR, Ratna Mani MS. Modified Hodge test:

A useful and the low cost phenotypic method for

detection of carbapenemase producers in

Enterobacteriaceae members. Journal of Natural

Science, Biology and Medicine. 2013;4(2):346-48

2. Nagaraj S, Chandran SP, Shamanna P, Macaden

R. Carbapenem resistance among Escherichia

coli and Klebsiella pneumoniae in a tertiary care

hospital in south India, Indian Journal of Medical

Microbiology. 2012; 30(1): 93-95.

3. Krisztina MP, Wallace, Endimiani A, Magdalena

AT, Robert A B. Minireview Carbapenems: Past,

Present, and Future. Antimicrobial Agents and

Chemotherapy. 2011; 55(11): 4943 – 60.

4. Nordmann P, Naas T, and Poirel L. Global Spread

of Carbapenemase producing Enterobacteriaceae.

Emerging Infectious Diseases. 2011;17(10):1791



70


5. Girlich D, Poirel L, and Nordmann P. Value of the

Modified Hodge Test for Detection of Emerging

Carbapenemases in Enterobacteriaceae. Journal of

Clinical Microbiology p. 2012; 50(2): 477 – 79.

6. Amjad A, Mirza IA, Abbasi SA, Farwa U, Malik

N, Zia F. Modified Hodge test: A simple and

effective test for detection of carbapenemase

production. Iranian Journal of Microbiology.

2011;3(4): 189-93

7. Cury AP, Andreazzi D, Maffucci M, Hehl H C,

Rossi F . The modified Hodge test is a useful tool

for ruling out Klebsiella pneumoniae

Carbapenemase. CLINICS 2012; 67(12):1427-31

8. The Clinical and Laboratory Standards Institute.

Performance Standards for Antimicrobial

Susceptibility testing, twenty second informational

supplement, M100-S22, Clinical and Laboratory

Standards Institute, 2012.

9. Parveen RM, Harish BN, Parija SC. Emerging

Carbapenem Resistance Among Nosocomial

Isolates of Klebsiella pneumoniae in South India.

International Journal of Pharma And Bio Sciences.

2010;1(2):

10. Gupta N, Brandi M. Limbago M, Patel JB and

Kallen AJ60 d Carbapenem-Resistant

Enterobacteriaceae: Epidemiology and Prevention.

CID 2011:53; 60-67

11. Anderson KF, Lonsway DR, Rasheed JK, Biddle

J, Jensen B, McDougal LK, et al Evaluation of

Methods to Identify the Klebsiella pneumoniae

Carbapenemase in Enterobacteriaceae. Journal of

Clinical Microbiology, 2007; 45(8): 2723 – 25.

12. Diana Doyle D, Peirano G, Lascols C, Lloyd T,

Church DL. and Pitouta JDD. Laboratory

Detection of Enterobacteriaceae That Produce

Carbapenemases. Journal of Clinical

Microbiology.2012 ;50 (12 ): 3877 – 8013. Pasteran F, Veliz O, Rapoport M, Guerriero L, and

Corso A. Sensitive and Specific Modified Hodge

Test for KPC and Metallo-Beta- Lactamase

Detection in Pseudomonas aeruginosa by Use of a

Novel Indicator Strain, Klebsiella pneumoniae

ATCC 700603. Journal of Clinical Microbiology.

2011;49 (12): 4301 – 03.

14. Hatipoglu M, Balta S, Cakar M, Demirkol S, Kurt

O, Dinc M .Modified Hodge test as screening test

for spreading Carbapenemase resistance hasbecome more important. 2013 CLINICS, 1175.

15. Adriane BC, Rita de Cassia de Andrade Melo,

Maria AVM, Ana CSL . Multidrug resistant gene,

including bla KPC and bla CTX-M-2 among

Klebsiella pneumoniae isolated in Recife, Brazil.

Rev.da Sociedade Brasileira de Medicina Tropical.

2012; 45 (5): 572-78.



71

Nikhat et al., Int J Med Res Health Sci. 2014;3(1): 71-75


&

Health Sciences


thNov 2013 Revised: 24


thDec 2013

Research article

STUDY OF NEURAL PLASTICITY IN BRAILLE READING VISUALLY CHALLENGED

INDIVIDUALS

*Nikhat Yasmeen1, Mohammed Muslaiuddin Khalid

2, Abdul Raoof Omer siddique

1, Madhuri Taranikanti

1,

Sanghamitra Panda1, D.Usha Rani

3

1Department of Physiology, Shadan Institute of Medical Sciences, Hyderabad, Andhrapradesh, India

2

Department of Emergency Medicine, Care Hospital, Hyderabad, Andhra Pradesh, India3Department of Physiology, Apollo Institute of Medical Sciences & Research, Hyderabad,Andhra Pradesh, India

*Corresponding author mail: [email protected]

ABSTRACT

Background: Neural plasticity includes a wide range of adaptive changes due to loss or absence of a particular

sense. Cortical mapping or reorganization is evolutionary conserved mechanism which involves either an

unmasking of previously silent connections and/or sprouting of new neural elements. Aims & Objectives -To

compare the Somatosensory evoked potentials (SSEPs) wave form in normal and visually challenged individuals.

Materials & Methods: 20 visually challenged males in the age group of 21 -31 yrs were included in the study along

with 20 age & sex matched individuals. Subjects were screened for general physical health to rule out any medical

disorder, tactile sensibility i.e., sensation of light touch, pressure, tactile localization & discrimination to rule out

any delay in the peripheral conduction disorder. Somatosensory evoked potentials were recorded on Nicolet Viking

select neuro diagnostic system version 10.0.The placement of electrodes & recording of potentials were done based

on methodology in chiappa. Data was subjected to various statistical analyses using SPSS version 17.0 software.

N20 & P25 latencies were shorter and amplitudes were larger in visually challenged individuals compared to age &

sex matched individuals. Conclusions: In visually challenged individuals, decrease in latencies indicate greatly

improved of information in the nervous system & increase in amplitudes indicate the extent and synchronization of

neural network involved in processing of vision.

Keywords: Neural plasticity, Somatosensory evoked potentials, Cortical mapping, Visually challenged

INTRODUCTION

In humans as well as in many animals, cortical area

has enormous capacity for reorganization i.e plastic

changes.1

The present study was undertaken to study

the cross modal interactions of sensory modalities in

visually challenged individuals for the exploration of

neural plasticity using somatosensory evoked

potentials. In our central nervous system perception is

modulated due to the redundant informational inputsfrom more than one sensory organ. In blind individuals

Occipital cortex that is deprived of its normal inputs is

invaded by inputs from other modalities supporting the

concept of cross-modal plasticity.2-5

Specific electrophysiological recordings & functional

imaging studies of visually challenged individuals

have depicted that touch modality is not only

sharpened in these individuals but also plays a major

role in their perception.Various animal models have

been used to study the changes occur both at thecellular & synaptic level i.e activity based competition

between the differential sensory inputs.6

DOI: 10.5958/j.2319-5886.3.1.014



72


The molecular mechanism underlying neural plasticity

is probably due to unmasking of connections or the up-

regulation of synaptic efficacy.7

As we all know that

the thalamus is considered as the gateway for the

sensory information reaching the cortex, the

reorganization can occur at this level or at the level of

polymodal association areas.8

Specific somatosensory & auditory evoked potentials

have demonstrated that cross-modal plasticity

develops in visually challenged individuals due to their

dependence on tactile & auditory information.9- 12

In

blind Braille readers there was structural & functional

cortical reorganization along with relevant changes in

the behavior & perceptual capacities as demonstrated

by imaging studies.

METHODS

20 visually challenged individuals were recruited from

Govt. hostel for blind boys, Dilsukhnagar area,

Hyderabad & study was conducted at the

Electrophysiology lab, Upgraded Department of

Physiology, Osmania Medical College, Koti, Hyd.,

during Dec.2009 to Dec.2011. 20 Age & Sex matched

controls were also included in the study. Subjects with

history of nervous system disorders, usage of

antidepressants, narcotic drugs, CNS stimulants werenot included in the study. Subjects with late onset of

blindness due to other medical reasons were excluded

from the study. Subjects were screened for general

physical health to rule out any medical disorder, tactile

sensibility i.e sensation of light touch, pressure, tactile

localization & discrimination to rule out any delay in

the peripheral conduction disorder. Prior to study,

ethical guidelines were followed; consent was taken,

after the subjects were told about the aims &

objectives of the study.Procedure : This study was conducted on patients

using 3-channel with normal averaging technique.13

The procedure was explained to the patient and

consent taken.Patient was asked to sit comfortably on

a chair and instructed to gently close his/her eyes

while relaxing all the head and neck muscles during

the recording. Patient is asked to count the number of

stimuli so as to get proper recordings. Electrodes of

the 3 channels were placed on the patient at

appropriate sites after it’s proper abrasion. Placement

of electrodes & recording of potentials were done in

accordance with the methodology in Chiappa.13

Surface EEG electrodes are used. Frontol electrode

[Fz] is used as the reference in most montages.

Active recording electrodes are placed as follows:

1. 1st

channel: Over the contralateral C3’/C4’ scalp

region (2cm posterior to C3 or C4)

2. 2nd channel: Over the C5/C2 cervical spinous

process (referred to as C5S or C2S and located

relative to the prominent C7 spinous process with

the neck flexed.

3. 3rd

channel: At Erb’s point (2-3 cm above clavicle

in the angle between it and posterior border of the

clavicular head of the Sternocleidomastoid muscle

ipsilaterally.

4. Inactive recording electrodes of the 3 channels

were placed on Fz position on the scalp.

5. Ground electrode: is placed between thestimulating and the recording electrodes relatively

close to the former. We have used a band around

the forearm.

6. Stimulation electrode: using surface disk

electrodes placed between the tendons of palmaris

longus and flexor carpi radialis, i.e., at the

supinated wrist, median nerve was stimulated.

Stimuli of 0.2-0.3 msec duration are given at 4-7

Hz. The intensity of the current was adjusted till a

visible twitch was produced.Data-sheet was made using Microsoft word & excel

sheets.Statistical analysis was done using PASW

18.0 (SPSS Inc.Chicago,USA)

RESULTS

This Comparative study consisted of 20 congenitally

blind males (Group A) and 20 normal sighted

individuals(Group B)

The mean pattern of latency of SEP-N20 after wrist

stimulation was found to be significant I.e P value =0.000 (<0.0001) for right side & P-value = 0.001

(<0.005) for left wrist.The mean pattern of latency of

SEP-P25 after wrist stimulation was found to be

significant i.e. P value =0.000(<0.0001) &

p=0.022(<0.05).The mean pattern of latencies of N9&

N13, inter- peak latencies of SEP’s did not show

significant difference (P > 0.05) between the two

groups.(TABLE – I)



73


Table 1: Statistical analysis of mean pattern of latencies on wrist stimulation

MEAN PATTERN OF LATENCIES WRIST GROUP A GROUP B P-VALUE

N9 RIGHT 9.25±0.62 9.48±0.68 0.274

LEFT 9.17±0.69 8.89±0.64 0.270

N13 RIGHT 12.54±0.39 12.68±0.78 0.463LEFT 12.54±0.43 12.49±0.53 0.725

N20 RIGHT 17.5±0.58 18.49±0.7 0.000

LEFT 17.8±0.53 18.54±0.79 0.001

P25 RIGHT 20.63±0.53 21.69±1.08 0.000

LEFT 21.03±1.08 21.81±1.0 0.022

N9-N13 RIGHT 3.41±0.62 3.47±1.06 0.83

LEFT 3.58±0.84 3.22±0.77 0.168

N9-N20 RIGHT 8.07±0.22 8.20±0.19 0.105

LEFT 8.69±0.81 8.88±0.72 0.438

N13-N20 RIGHT 5.31±0.52 5.33±0.39 0.894LEFT 5.19±0.25 5.28±0.34 0.406

Table 2: Statistical analysis of mean pattern of Amplitude on wrist stimulation

MEAN PATTERN OF

AMPLITUDE

WRIST GROUP A GROUP B P-VALUE

N9 RIGHT 2.12±2.44 1.9±1.73 0.778

LEFT 1.90±1.57 1.67±1.77 0.667

N13 RIGHT 0.87±0.55 0.91±0.66 0.834

LEFT 0.79±0.73 0.41±0.68 0.092

N20 RIGHT 4.82±1.36 2.74±0.95 0.000

LEFT 4.2±2.5 2.76±0.83 0.004

P25 RIGHT 1.24±0.68 0.77±0.52 0.021

LEFT 1.28±0.56 1.14±0.62 0.452

The mean pattern of amplitude of SEP-N20 after wrist

stimulation was found to be significant i.e

P- value = 0.000 (<0.0001) for right side & P-value =

0.004 (<0.005) for left wrist. The mean pattern of

amplitude of SEP-P25 after wrist stimulation was

found to be significant i.e. P value =0.021(<0.05) for

right side .The mean pattern of amplitudes of N9&

N13 SEP’s did not show significant difference (P >

0.05) between the two groups.(TABLE-II)

DISCUSSION

This study compares the latencies and amplitudes of

SEP’s in normal and congenitally blind individuals

thereby giving an insight into the sharpening of other

sensory modalities in the absence of vision.

The present study throws light on the efficiency and

rapidity of neural processing of information in

congenitally blind subjects.

Following SEP parameters were recorded - N20, P25,

N13, N9 latencies and amplitude; N9-N13, N9-N20,

N13-N20 inter-peak latencies and N20-P25 amplitude

in blind and was compared with that of age-matched

normal controls using the independent sample‘t’ test.

The congenitally blind individuals use more than one

finger for Braille reading;index middle & ring finger.

Hence the median nerve was stimulated in the wrist to

get a cumulative record of the reading fingers.

Somatosensory evoked potentials like other evoked

potentials are path-specific electrical signals are

produced in the areas of signal processing which

correspond to the synaptic junctions of various

neurons and they give good temporal resolution in

milliseconds domain.N20 & P25 Latencies were

decreased and N20 & p25 amplitudes increased in the

congenitally blind when compared to same group in

the congenitally blind individuals,there were highly



74


significant differences in N20 & P25 Latencies &

amplitudes stimulation on right side than the left side.

According to previous studies done by Alvaro et al &

Dayanand G et al;there was increase in amplitude of

N20 Potential & the increase was more on the

right/dominant side14

In another comparative study SEPs were recorded in

10 blind & 15 control subjects & data revealed that

there were significant increase in N20 & P22 SEP’S

on right-sided stimulation suggesting activity

dependant alteration in spatio-temporal components of

signal processing15

In a PET study to decipher the cross-modal plasticity

in the visually challenged individuals by electro-tactile

stimulation of tongue,results have shown that the

occipital area is part of a neural network for

discriminating touch sensations along with posterior

parietal cortex as there was increase in regional blod

flow(rRBF) in the occipital cortex & that the increase

was related to the performance of particular task 16

In another functional magnetic resonance imaging

study 12 congenitally and early-onset blind

subjects were studied with fMRI reading & results

reveal that there was activation of the primary sensory

area along with polymodal association areas17

Studies in congenitally blind Braille readers have

shown that there was reorganization of tactile &

auditory tracts to the central retinal targets both at the

sub-cortical & cortical levels.18-20

Another brain -imaging study demonstrated that there

is difference in pattern of activation of visual cortex in

late and congenitally blind subjects. Early blind

subjects when compared to late blind have better

tactile & auditory sensibility as demonstrated by event

related potentials recorded over the posterior cortical

areas.21-22

CONCLUSIONS

In congenitally blind individuals, decrease in N20 &

P25 latencies indicate greatly improved processing of

information in the nervous system; increase in N20 &

P25 amplitudes indicate the extent and

synchronization of neural network involved in

processing of information for a wider Neural network

could be due to changes in the local connectivity as

several local mechanisms have been proposed,

including sprouting, unmasking of silent synapses

and/or changes in the modulatory effects of lateral

connections.

In accordance with the principles of lateral inhibition;

the tactile & auditory modalities also exert the

modulatory effects on perception of visual modality

both at the sub-cortical & cortical level.

Thus it can be formulated that in the spatio-temporal

framework the demarcation between uni-modal &

polymodal association areas can undergo re-

organization i.e plastic changes both at gross & at

molecular level.

ACKNOWLEDGEMENT

I would like to express my heartfelt gratitude to Prof.&

Hod Dr. B.Ram Reddy & all those who have helped

me in completing my work

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ed.371-473

14. Dayanand G, Roopkala MS, Srinivas R, Ranjeev

Sharma. A Comparative study of median nevre

somatosensory evoked potentials in the totally

blind and normal subjects. Indian journal of

physiology and pharmacology.2008 ; 52(2 ) 183-

188

15. Alvaro Pascual-Leone, Fernando Torres. Plasticity

of the sensorimotor cortex representation of the

reading finger in Braille readers

Brain.1992;116:39-52

16. Ptito M, Moesgaard S, Gjedde A and Kupers R.

Cross modal plasticity revealed by electro tactile

stimulation in the congenitally blind. Brain.

12824.

17. Norihiro Sadato, Tomohisa Okada, Manabu

Honda, Yoshiharu Yonekura. Critical Period for

Cross-Modal Plasticity in Blind Humans: A

Functional MRI

18. Ron Kupers, Arnaud Fumal, Alain Maertens, De

Noordhout, Albert Gjedde, Jean Schoenen, etal.,

Maurice Ptito; Transcranial magnetic stimulationof the visual cortex induces somatotopically

organized qualia in blind subjects. Proc Natl Acad

Sci USA;2006;103(35):1325

19. rost DO. Boire, D, Gingras, G, Ptito M. Surgically

created neural pathways mediate visual pattern

discrimination. Proc. Natl. Acad. Sci. USA;2000;

97, 11068 – 73

20. Sur M. Garraghty PE. Roe AW. Experimentally

induced projections into auditory thalamus and

cortex. Science. 1988; 242, 1437 – 41

21. Neimeyer W, Starlinger I. Do the blind hear

better? Investigations on auditory processing in

congenital or early acquired blindness. II. Central

functions. Audiology;1981; 20;510-15

22. Roder B, Teder-Salejarvi W, Sterr A, Rosier

F,Hillyard SA, Neville HJ. Improved auditory

spatial tuning in blind humans. Nature. 1999;

400(6740): 162 – 166



76

Sukhdas et al., Int J Med Res Health Sci. 2014;3(1):76-79


&

Health Sciences



thDec 2013 Accepted: 15

thDec 2013

Research article

NUTRITIONAL STATUS OF TRIBAL CHILDREN IN ANDHRA PRADESH

*Gangam Sukhdas1, Sairam Challa

1, Prakash Bhatia

2, A.R. Rao

3, Koteswara Rao.P

4


2Principal and Professor,

3Assistant Professor, Department of Community Medicine, Apollo

Institute of Medical Sciences and Research, Hyderabad, India4Health Officer, Urban Health Center (AIMSR), Shaikpet Nala, Hyderabad, India.

* Corresponding author email:[email protected]

ABSTRACT

Context: Tribes constitute separate socio-cultural groups, having distinct customs, traditions, marriage, kinship, and

property inheritance systems. They live largely in agricultural and pre-agricultural level of technology. Their

dependency on nature and impoverished economy bear effect on the nutritional status different compared to the

general population. Aims: To study the prevalence of malnutrition in the under-five years age group tribal children

in the three regions of Andhra Pradesh and compare the same with national statistics. Methods and Material: A

cross sectional survey was carried out to assess the nutritional status of under-five age group children in three

Integrated Tribal Development Agency (ITDA) blocks of Andhra Pradesh. Results & Conclusions: Based on theWHO Child Growth Standards, the prevalence of malnutrition was lower in the AP tribal blocks than the national

averages among tribal populations, but higher than the overall national and state averages.

Keywords: Nutrition, Scheduled Tribes, Wasting, Stunting, Underweight.

INTRODUCTION

The Tribal Population in India is 8.6 percent according

to 2011 census.1

Tribes constituted separate socio-

cultural groups having distinct customs, traditions,

marriage, kinship, property inheritance system and

living largely in agricultural and pre-agricultural level

of technology. Their dependency on nature and

impoverished economy may affect the nutritional

status as compared to their counterparts in the general

population. Young children in India suffer from some

of the highest levels of stunting, underweight, and

wasting observed in any country in the world, and 7

out of every 10 young children are anaemic.2

The

percentage of children under age five years who are

underweight is almost 20 times as high in India as

would be expected in a healthy, well-nourishedpopulation and is almost twice as high as the average

percentage of underweight children in sub-Saharan

African countries. Near about fifty percent of the

children under the age of five years in India are

moderately or severely malnourished. The prevalence

of under nutrition is more in vulnerable groups like

Tribal population. While Andhra Pradesh harbors

nearly 9 percent of the Indian Tribal population, there

are limited studies on the nutritional status of Tribal

Children in Andhra Pradesh. Hence a study was

contemplated to assess the nutritional status of Tribal

children in Andhra Pradesh.

Objectives

1. To study the prevalence of malnutrition in the

Under-Five years age group tribal children in the

three regions of Andhra Pradesh.

2. To compare the nutritional status of tribal childrenin Andhra Pradesh with that of national statistics.

DOI: 10.5958/j.2319-5886.3.1.015



77


METHODS AND MATERIAL

Study Design: A large community based, cross

sectional study was conducted in 2007 to assess

various health indicators in tribal blocks of Andhra

Pradesh. The current article is an extract from this

study. The study was planned to cover three Integrated

Tribal Development Agency (ITDA) blocks one each

in Rayalseema, Telangana and Coastal area to cover

all the three regions of the state of Andhra Pradesh.

Three ITDA blocks were selected including, Srisailam

ITDA project (21 villages; Rayalaseema region),

Bhadrachalam ITDA project (25 villages; Telangana

region), and Rampachodavaram ITDA (19 villages;

Coastal region).

In each of the selected ITDA blocks 1000 households

were covered thereby a total of 3000 households werecovered with 5% as attrition rate to accommodate the

locked houses and also migrated population. The

target was to cover over 10,000 populations. The

villages were listed out in cumulative order as was

provided by the tribal welfare department and among

them villages were randomly selected to cover the

1000 households.

Clearance from Institutional Ethics Committee was

obtained. All children less than five completed years

of age were included in the study with the informedconsent of the mother. A pretested questionnaire was

used to interview the mothers and record the Child’s

anthropometric data. The questionnaire included

variables of demography, gestational history, birth

history, immunization status, feeding history and

clinical findings apart from Height/Length, Weight

and Mid Arm circumference. Standard procedures

were followed to measure Weight and Height/Length

of the child. WHO Child Growth Standards3,4

were

used for assessment of nutritional status of the

children.

A stunted child4

has a height-for-age z-score that is at

least 2 standard deviations (SD) below the median for

the WHO Child Growth Standards. Chronic

malnutrition is an indicator of linear growth

retardation that results from failure to receive adequate

nutrition over a long period and may be exacerbated

by recurrent and chronic illness. A wasted child4has a

weight-for-height z-score that is at least 2 SD below

the median for the WHO Child Growth Standards.

Wasting represents a recent failure to receive adequate

nutrition and may be affected by recent episodes of

diarrhea and other acute illnesses. An underweight

child4

has a weight-for-age z-score that is at least 2 SD

below the median for the WHO Child Growth

Standards. This condition can result from either

chronic or acute malnutrition, or both.

RESULTS AND DISCUSSION

A total of 1,013 Tribal children under five years of age

were surveyed. Of these 544 were boys and 469 girls.

Among the 1,013 tribal children who were assessed for

malnutrition, 489 (48.27 %) were stunted, 239 (23.59

%) wasted and 490 (48.37%) underweight as per

WHO Growth Standards.

4

The Prevalence of stuntingwas 49.50 percent in Bhadrachalam, 51.21 percent in

Srisailam and 48.66 percent in Rampachodavaram.

The prevalence of wasting was 23.08 percent in

Bhadrachalam, 24.06 percent in Srisailam and 23.37

percent in Rampachodavaram. The prevalence of

underweight was 48.16 percent in Bhadrachalam,

49.23 percent in Srisailam and 47.13 percent in

Rampachodavaram (Table 1).

The prevalence of stunting (height-for-age) in the

tribal children of Andhra Pradesh (48.27 percent) as

assessed by the current study is similar to that of the

national average of 48 percent. But it is much lower

than the national average of stunting among the

scheduled tribes of 54 percent as found in National

Family Health Survey (NFHS -3).2

Whereas it is

higher than the overall prevalence in Andhra Pradesh

of 43 percent as found in NFHS-35

(Fig 1).

The prevalence of wasting (weight-for-height) is 23.59

percent in the current study which is more than overall

percent of India (20 percent) or Andhra Pradesh (12

percent). But lesser percent are wasted as compared to

a national average of wasting among the scheduled

tribes of 28 percent as found in NFHS-3.

The prevalence of underweight (weight-for-age) in the

current study was 48.37 percent which is higher than

the overall average of the country (43 percent) and AP

state (33 percent). But it is lower than the prevalence

of underweight among the tribal children of India (55

percent).



78


Table 1 : Prevalence of Under Nutrition Among Under Five Age Group Children in Three ITDA Blocks Of

Andhra Pradesh

48.2743

48

54

23.59

12

20

28

48.37

33

43

55

0

10

20

30

40

50

60

AP ITDA AP INDIA INDIA TRIBAL

Stunted Wasted Underweight

(All values in percentages)

Fig1: Status of Under-Five Child Nutrition: Current Study & NFHS-3

CONCLUSION

Malnutrition continues to be a persistent public health

problem in India and more so among the Scheduled

Tribes of the country. While the indicators of

malnutrition among the under five tribal children in

the current study done in Andhra Pradesh are better

than the country figures, they are much higher than the

national averages of tribal populations. With a wide

cultural diversity among tribes, like in AP, efforts to

identify food taboos and fads and addressing the same

through ICDS support may help in the long run to

bridge the gaps.

POPULATION Sample Stunted Wasted Underweight

N % N % N %

AP (TRIBAL)Boys 544 260 47.79 129 23.71 263 48.35

Girls 469 229 48.83 110 23.45 227 48.40

Pooled 1013 489 48.27 239 23.59 490 48.37

Bhadrachalam

Boys 163 80 49.08 38 23.31 78 47.85

Girls 136 68 50.00 31 22.79 66 48.53

Pooled 299 148 49.50 69 23.08 144 48.16

Srisailam

Boys 252 130 51.59 61 24.21 124 49.21

Girls 201 102 50.75 48 23.88 99 49.25

Pooled 453 232 51.21 109 24.06 223 49.23

Rampachodavaram

Boys 129 62 48.06 30 23.26 61 47.29

Girls 132 65 49.24 31 23.48 62 46.97

Pooled 261 127 48.66 61 23.37 123 47.13



79


ACKNOWLEDGMENTS

We are thankful to the Director, Tribal Cultural

Research and Training Institute, Tribal welfare

Department, Hyderabad, and also thankful to Project

Officers of ITDA Bhadrachalam, Srisailam and

Rampachodavaram for their support while conductingthe study.

REFERENCES

1. Primary Census Abstract for Total population,

Scheduled Castes and Scheduled Tribes, 2011

Office of the Registrar General & Census

Commissioner,India.http://www.censusindia.gov.i

n/2011-Documents/SCST%20Presentation%2028-

10-2013.ppt

2. Fred Arnold, Sulabha Parasuraman, P.Arokiasamy, and Monica Kothari. Nutrition in

India. National Family Health Survey (NFHS-3),

India, 2005-06. Mumbai: International Institute for

Population Sciences; Calverton, Maryland, USA:

ICF Macro. 2009

3. WHO Multicentre Growth Reference Study

Group. WHO Child Growth Standards based on

length/height, weight and age. Acta Paediatr Suppl

2006;450:76 -85.

4. World Health Organization. Training Course onChild Growth Assessment. Geneva, WHO, 2008.

5. International Institute for Population Sciences

(IIPS) and Macro International. 2008. National

Family Health Survey (NFHS-3), India, 2005-06:

Andhra Pradesh. Mumbai: IIPS.



80

Senthil Kumar. S et al., Int J Med Res Health Sci. 2014;3(1):80-83


&

Health Sciences




thDec 2013

Research article

INCIDENCE AND LOCATION OF ZYGOMATICOFACIAL FORAMEN IN ADULT HUMAN SKULLS

Senthil Kumar. S*, Kesavi D

Department of Anatomy; Sri Ramachandra Medical College and Research Institute, Chennai – 600 116


ABSTRACT

This study was to investigate the morphology, topographic anatomy and variations of Zygomaticofacial foramen

(ZFF). Frequency variations and Location/distance of ZFF from surrounding standard landmarks were evaluated in

100 adult human dry skulls. The frequency of ZFF was varied from being single to as many as four foramina and

absence of ZFF, which was classified into Type I – V for single, double, triple, four foramina and absence of ZFF

respectively. The frequency (%) of these types was Type I: 46 & 51, Type II: 31 & 26, Type III: 4 & 6, Type IV: 1

& 1 and Type V: 18 & 16 respectively on right & left sides of the skulls. The mean distance of Zygomaticofacial

foramen from Zygomaticomaxillary suture, nearest part of Orbital margin, Frontozygomatic suture,

Zygomaticotemporal suture and Zygomatic angle was 13.8 & 12.2mm, 6.8 & 6.9mm, 24.8 & 26.7mm, 20.8 &

21.5mm and 12.4 & 13.5mm respectively on right & left sides of skulls. Knowledge on these variables will be

helpful for surgeons for various surgical procedures like Orbitozygomatic craniotomy, for nerve block and Malar

reduction surgeries.

Keywords: Zygomaticofacial foramen, Orbital margin, Zygomaticbone, Zygomaticofacial nerve

INTRODUCTION

Zygomaticofacial foramen (ZFF) usually situated on

the Zygoma nearer to infraorbital margin.1

Zygomaticofacial nerves and vessels emerge out

through this foremen.1, 2

It is more predominant on

right side in male and left side in female population.

3

The location and frequency of ZFF vary significantly

among individuals and races due to the difference of

anthropometry of human from region to region.

Current understanding on ZFF is very limited in the

Indian population. ZFF with its structures serves as an

important landmark for locating inferior orbital fissure

during Orbitozygomatic craniotomy,4

for nerve block,

Malar reduction surgeries5, in management of

infraorbital tumors, Plastic and Reconstructive

surgeries. Hence this study has been aimed to evaluate

the location and frequency variations of ZFF in adult

human dry skulls.


Study has been conducted in the Department of

Anatomy, Sri Ramachandra Medical College and

Research Institute, Chennai. A total of 100 adult dry

skulls were collected from the dissection hall and

observed for frequency variations of ZFF. Distance of

Zygomaticofacial foramen from Zyomaticomaxillary

suture, nearest part of Orbital margin,

Frontozygomatic suture, Zygomaticotemporal suture

and Zygomatic angle (fig: 1) has been measured with

digital vernier caliper on both sides (Right and Left) of

the skull and compared.

Specimens with very small decalcified pits were

excluded.

DOI: 10.5958/j.2319-5886.3.1.016



81


Fig 1: Showing the distance from ZFF (encircled) to

Zygomaticomaxillary suture (a), nearest part of Orbital

margin (b), Zygomaticofrontal suture (c), Zygomatic

angle (d), Zygomaticotemporal suture (e)

Observations:

A total of 100 dry skulls were examined.

The frequency of ZFF were varied from being absent

to as many as four foramina. Based on it all the skulls

were classified in to following types.

Type I: Single Foramen (fig: 2)

Type II: Double Foramina (fig: 3)

Type III: Triple Foramina (fig: 4)

Type IV: Four Foramina (fig: 5)

Type V: Absence of ZFF (fig: 6)

Fig 2: Type I: Single Foramen

Fig 3: Type II: Double Foramina

Fig 4: Type III: Triple Foramina

Fig 5: Type IV: Four Foramina

Fig 6: Type V: Absence of ZFF

Table 1: Frequencies of different types of

Zygomaticofacial foramina

SIDE Type I

(%)

Type II

(%)

Type III

(%)

Type IV

(%)

Type V

(%)

RIGHT 46 31 4 2 18

LEFT 51 26 6 1 16

The mean distance of ZFF from Zyomaticomaxillary

suture, nearest part of Orbital margin,

Frontozygomatic suture, Zygomaticotemporal suture

and Zygomatic angle was 13.8 & 12.2mm, 6.8 &

6.9mm, 24.8 & 26.7mm, 20.8 & 21.5mm and 12.4 &13.5mm respectively on right & left sides of skulls.



82


DISCUSSION

In the present study absence of ZFF (Type V) has been

found in 18 & 16% of right & left sides of skulls. Aksu

F et al6

stated absence of ZFF at 15.6% of cases which

includes both right and left side skulls. Whereas

Marios Loukas et al7 quoted absence of ZFF at 1%among 200 specimens. Cajeron DM et

8al found ZFF

in 38 and 13% of right and left of the skulls which is

lower than our study (right: 82 and left: 84%).

In line with most of the studies frequency of ZFF was

ranging from absent to as many as four but Aksu F et

al6

found five foramina in 1.3% of skulls (5 of

160sides, i.e. 80 skulls). Based on the frequency of

ZFF we classified them into Type I – V as mentioned

earlier.

Type I to IV were occurred in 46 & 51%, 31 & 26%, 4& 6% and 1 & 1% of right & left sides of the 100

skulls. In the similar study with 100 sample conducted

by Ongeti et al9

only three types i.e. from Type I, II

and III of our study were reported in 42 & 45%, 35 &

31% and 23 & 17% of right and left side of skulls

respectively. Among these types only Type I and II are

similar to present study and Type III was with higher

frequency than the present findings.

Likewise, the current study is showing the wide

variations from the existing studies in the frequency of ZFF (table 2).

The mean distance of ZFF from Zygomaticomaxillary

suture was 13.8mm (right) and 12.2mm (left) among

100 skulls whereas it was 18.8mm in the study by

Aksu F et al6.

The mean distance of ZFF from nearest part of Orbital

margin was 6.8 & 6.9 mm (right & left) respectively in

our study which is higher than Aksu F et al6

(5.94mm)

and Hwang SH et al5

(7.61mm).

ZFF situated in 24.8mm (right) & 26.7mm (left)

distance from Frontozygomatic suture which is almost

similar to the Martins C et al (25mm)4

and Aksu F et

al6

(26.2mm).

Likewise the mean distance of ZFF from

Zygomaticotemporal suture was 20.8mm (right) &

21.5mm (left) and Zygomatic angle was 12.4mm

(right) & 13.5mm (left) in the present study.

The etiology behind the absence of ZFF and the path

by which the neurovascular bundle emerges out in

such cases has not reported in the existing literature

and the same could not be evaluated in the present

study because of the fact that present study has been

conducted in the dry skulls, which holds the limitation

of the study. Since the cone-beam computed

tomography (CBCT) has an excellent accuracy in

evaluating the ZFF10, further studies can be conducted

using CBCT to evaluate the fate of neurovascular

bundle in absence of ZFF along with the medical

history of subjects.

The present study is not similar to the most of the

existing studies. The comparisons made in the

discussion were with non Indian studies as there was

very less/nil number of studies we encountered in

literature search. The variant anthropometric

measurements were probably due to difference of skull

anthropometry in different regions of the World.

Similar studies are suggested to be conducted in the

India in order to standardize the foresaid findings

which will be helpful for different surgical procedures

like Orbitozygomatic craniotomy, for nerve block,

Malar reduction surgeries and in management of

infraorbital tumors.

Table 2: Comparison of Present study findings with different existing studies

TYPE

AUTHOR

Present study Ongeti et al9

Aksu

etal6

Cajeron DM et

al8

Marios

Loukas et al7

Hwang SH

et al5

Right

(%)

Left

(%)

Right

(%)

Left

(%) (%)

Righ

t (%)

Left

(%) (%)

(%)

TYPE I 46 51 42 52 44 46 12 40 50.9

TYPE II 31 26 35 31 45 20 75 15 30

TYPE III 4 6 23 17 6.3 13 13 5 9

TYPE IV 1 1 -- -- 4.4 0.5 0.5 1 0.9

TYPE V Absent 1.3 Absent



83


CONCLUSION

Frequency of ZFF and its distance from surrounding

standard landmarks were varying from existing studies

and knowledge on them is helpful for surgeons for

various surgical procedures.

ACKNOWLEDGEMENT

I would like to thank Sri Ramachandra University for

giving the opportunity.

REFERENCES

1. Susan Standring. Face and Scalp In Gray’s

Anatomy – An Anatomical Basis of Clinical

Practice. 5th

ed. Elsevier. China. 467-497.

2. Dutta AK. The Skull In Essentials of HumanAnatomy Current Books

International.Kolkata.2012: 2(5th

ed);3-65.

3. Kaur J, Choudhry R, Raheja S, Dhissa NC. Non

metric traits of the skull and their role in

anthropological studies. J. Morphol. Sci,

2012;29(4):189-94

4. Martins C, Li X, Rhoton Al Jr. role of the

Zygomaticofacial foramen in the orbitozygomatic

craniotomy: Anatomic report. Neurosurgery 2003

Jul; 53(1): 168 -735. Hwang SH, Jin S, Hwang K. Location of the

Zygomaticofacial foramen related to malar

reduction. J Craniofac Surg 2007; 18(4):872 – 74

6. Aksu F, Ceri NG, Arman C, Zeybek FG, Tetik S.

Location and Incidence of the zygomaticofacial

foramen: An anatomic study. Clin Anat. 2009;

22(5):559 – 62

7. Marios Loukas, Deyzi Gueorguieva Owens, Shane

Tubbs, Georgi. Zygomaticofacial,

Zygomaticoorbital and Zygomaticotemporal

foramina: anatomical study. Anatomical Science

International 2008; 83(2):77 - 82

8. Cajeron DM, Osses AO, Faig-leite H.

Zygomaticofacialforamen’s anatomical stusy and

its importance in the ondontology.2007. available

from: http://ojs.fosjc.unesp.br/index.php/cob/

article/download/329/259

9. K. Ongeti, J. Hassanali, J. Ogeng’o, H. Saidi.

Biometric features of facial foramina in adult

Kenyan skulls. Eur J Anat 2008; 12(1):89-95

10. Del Neri NB, Araujo-Pires AC, Andreo JC,

Rubira-Bullen IR, Ferreira Junior O.

Zygomaticofacial foramen location accuracy and

reliability in cone-beam computed tomography.

Acta Odontol Scand. 2013; Posted online on 1 Jul

2013. (doi:10.3109/00016357.2013.814804)



84Rajpal et al., Int J Med Res Health Sci. 2014;3(1):84- 87


&

Health Scienceswww.ijmrhs.com Volume 3 Issue 1 (Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 15th Nov 2013 Revised: 11th Dec 2013 Accepted: 18th Dec 2013

Research article

ROLE OF MRI IN EVALUATION OF PAINFUL KNEE

*Rajpal Yadav1, Sushil G Kachewar

2

1Chief Resident,

2Professor, Department of Radio-diagnosis, Rural Medical College, PIMS (DU), Loni,

Maharashtra, India


ABSTRACT

Introduction: Requests for knee Magnetic Resonance Imaging (MRI) are most often made when the patient

presents with a painful knee. This pain might be due to trauma or infection or inflammation. Complete clinical

examination is not possible in such situations as the patients cannot co-operate due to severe pain. There comes the

role of noninvasive multiplanar imaging. Hence this study was undertaken to evaluate how MRI can evaluate

painful knee. Methods: 50 consecutive patients who were referred for MRI evaluation of painful knee were

included in this study. Specific findings that explained the cause of pain were compiled. Results: In this present

study of 50 patients, and 17 were females (34%) and 33 were males (66%).The mean age was 36.70± 13.14 years.

Traumatic causes outnumbered non traumatic etiologies of painful knee. Injury to the anterior cruciate ligament

(ACL) was the commonest soft tissue abnormality encountered. Partial tears were more common than completetears. Tibial attachment was commonly affected than femoral attachment. Injured posterior horn of the medial

meniscus and medial collateral ligament, were the commonest associated findings. Conclusion: MRI evaluation in

patients with painful knee is of vital importance, as MRI can demonstrate the exact nature and extent of bony as

well as soft tissue abnormality. Multiplanar imaging capacity and noninvasive nature of MRI enable a satisfactory

diagnosis in such patients in whom a complete clinical examination is almost impossible due to pain.

Keywords: Painful Knee; MRI; Ligaments, Imaging.

INTRODUCTION

Painful knees can bring tears to our eyes. It may either

be of traumatic origin or non traumatic origin like

infection or inflammation. Examination by a surgeon

or orthopedician is usually not conclusive to pinpoint

the exact lesion causing pain.1, 2

Hence optimum

treatment is hampered. Therefore non invasive

imaging which can demonstrate the underlying

pathology without any significant discomfort to the

patient is needed.3

This study was therefore undertaken

to analyze the utility of magnetic resonance imaging

(MRI) in pinpointing the cause of painful knee. The

aim was to find common imaging findings in oursetup.


Inclusion criteria: Patients of either sex from

>20years, having acute or chronic painful knee were

included in this study, history of painful knee was

noted but as such patients cannot be accurately

evaluated clinically due to their pain. Exclusion

criteria: Patients who could not co-cooperate for MRI

examination, patients have undergone prior surgical

procedures and who had metallic implants or metallic

clips in situ were also excluded as these are

contraindications for MRI evaluation. Methodology:Philips Achieva 1.5Tesla High Gradient MRI Scanner

was used for evaluating 50 consecutive patients having

DOI: 10.5958/j.2319-5886.3.1.017




painful knee as the presenting complaint. The present

study was approved by the Institutional Ethical and

Research Cell and informed consent from all the

patients was obtained for this study.

RESULTS

Analysis of demographic characteristics shows that in

this present study of 50 patients, 17 were females

(34%) and 33 were males (66%). This is because

males are generally more active than females and

travel a lot. Hence their knees are exposed to more

wear and tear. Also they are at more risk of injury.

The following table shows the distribution of patients

as per different age groups. The mean age of patients

in this study was 36.70± 13.14. The maximum

numbers of patients were seen in 40-50 years age

group.

Table 1: Distribution of patients according to age

AGE (Years) No. of Patients %

<20 08 16%

20-30 10 20%

30-40 10 20%

40-50 14 28%

50-60 07 14%

>60 01 02%

TOTAL 50 100%MEAN ± SD 36.70±13.14

MRI could satisfactorily identify the exact nature of

injury in all cases. Anterior cruciate ligament (ACL)

was the most commonly injured ligament. Right sided

injuries were more common than the left side. Partial

thickness tears were more common. Tibial attachment

was more involved than the femoral attachment.

Table 2: Distribution of MRI findings of ACL

involvement

FindingsNumber of

Patients%

Side

Left 18 36%

Right 32 64%

ACL tear

Compete 17 34%

Partial 27 54%

Location of ACL tear

Midsubstance 14 28%Femoral attachment 8 16%

Tibial attachment 27 54%

Involvement of medial as well as lateral meniscus was

also seen satisfactorily on MRI. The distribution of

findings of meniscal involvement is summarized in

Table 3. Overall medial meniscus was more

commonly involved rather than the lateral meniscus.

Posterior horn was more involved in either of the casesthan the anterior horn.

Table 3: Distribution of findings of meniscal

involvement on MRI

Findings

Medial

Meniscus

Lateral

Meniscus

No. of patients (%) No. of patients (%)

Anterior Horn 7(14%) 8(16%)

Posterior Horn 35(70%) 21(42%)

Involvement of posterior cruciate ligament (PCL) was

also satisfactorily demonstrated by MRI. The

distribution of findings of PCL involvement is

summarized in Table 4.

Table 4: Distribution of findings of meniscal

involvement on MRI

Findings No. of patients (%)

Complete Tear 04 08%

Partial Tear 02 04%

BUCKLING 21 42%

DISCUSSION

A plethora of pathologies can present as painful knee.

Imaging is useful to identify and confirm the clinically

suspected pathologies and also to assessing its extent

and gravity.3-6

Clinical examination in such cases usually suggests

internal derangement. So correct diagnosis is needed

to perform or to avoid invasive procedures like

Arthroscopy.

A host of imaging modalities is available forevaluation of the knee joint. Plain radiographs

demonstrate bone pathologies clearly. Soft tissue and

cystic lesions may be missed. Only a focal bulge on

overlying soft tissues may be noticed. Computerized

tomography (CT scan) may show the lesions, but the

exact tissue characterization may be limited. In

experienced hands, musculoskeletal ultrasound can

very well depict the soft tissue pathology. The biggest

advantage of MRI is that it shows the entire lesion in

multiple planes so that correct diagnosis andmanagement strategy can be planned. The MRI




appearance of various soft tissue lesions has been

studied and mentioned in literature.4-16

On MRI ACL and PCL are seen as hypo intense bands

on T1W, T2W as well as STIR (Short Tau Inversion

Recovery) images. Any injury to them manifests as a

hyperintense appearance on T2W and STIR images.

This injury may result in partial or full thickness tear

of these structures.

Fig 1: STIR sagittal images showing pathologies of

ACL and PCL

Similarly, the meniscus of knee too is seen as a hypo

intense structure on T1W, T2W as well as STIR

images. Any injury to them manifests as a

hyperintense appearance on T2W and STIR images.

This injury may result in partial or full thickness tearof these structures.

MRI is used to obtain the sections of these regions of

interest in different planes. Standard planes are the

axial, coronal and sagittal planes. Sometimes oblique

images too may be required. The representative MRI

appearance of soft tissue injury presenting as painful

knee is shown in following image.

It has been found that the disruption of a knee

ligament is commonest pathology in patients having

post traumatic knee pain. It is important to develop a

mechanistic approach to associate the imaging

findings with their anatomic relevance.17

Substantial pain and disability caused in Osteoarthritis

of the knee shows a poor correlation with plain

radiographs. Pain receptors have been found in joint

capsule, ligaments, synovium as well as in the

subchondral bone. It has now been understood that no

definitive treatment modality can relieve the pain and

knee surgery does not necessarily guarantee

improvement. Hence a proper clinical assessment of

knee and appropriate MRI examination can permit

proper treatment.18

Not only adults, but children and adolescents too,

commonly present with knee pain. Again the

commonet performed a pediatric cross-sectional

imaging study is the MRI of the knee. Differences

between adult and pediatric knee imaging exist and in

younger age group one has to remember normal

developmental variants, injury and disease patterns

unique to children and adolescents.19

MRI has revolutionized diagnostic imaging of the knee

as this innovative technology allows superior soft

tissue details with multiplanar imaging capability that

provide accurate evaluation of the intra and extra

articular structure of the knee which are demonstrated

with other imaging modalities.MRI is accurate, non

invasive technique for evaluating the structures of the

knee, marrow space, synovium and periarticular soft

tissue concerning the knee.20, 21 It has great capacity in

diagnosing meniscal tear and classifying them into

grade and type which would avoid unnecessary

arthroscopic examination. It is a very good modality to

diagnose a complete tear of the ACL.

New discoveries in the field of computer science and

telecommunications have reduced the cost of MRI

knee studies. This too has increased the acceptance of

MRI imaging by the orthopedic community with quote

results almost same and satisfactory as a non invasive

replacement for arthrography and non therapeutic

Arthroscopy.22

CONCLUSION

Plethora of causes can cause painful knee. It is a

common symptom in all age groups. Correct treatment

necessitates accurate noninvasive diagnosis. Imaging

of the knee joint by MRI can satisfactorily provide the

correct diagnosis. This has led to the increase use as

well as the increased acceptance of MRI in the

imaging evaluation of painful knee.

REFERENCES

1. Terry GC, Tagert BE, Young MJ. Reliability of

the clinical assessment in predicting the cause of

internal derangement of the knee. Arthroscopy.

1995;11(5):568-76

2. Yoon YS, Rah JH, Park HJ: A prospective study

of the accuracy of clinical examination evaluated

by arthroscopy of the knee. Int Orthop.

1997;21(4):223-27




3. McCarthy CL, McNally EG. The MRI appearance

of cystic lesions around the knee. Skeletal Radiol.

2004;33:187 – 209

4. Trieshmann HW Jr, Mosure JC: The impact of

magnetic resonance imaging of the knee on

surgical decision making. Arthroscopy.

1996;12(5):550-55

5. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP.

Painful suprapatellar swelling: Diagnosis and

discussion. Skeletal Radiol. 2008;37:937 – 38

6. Christian SR, Anderson MB, Workman R,

Conway WF, Pope TL. Imaging of anterior knee

pain. Clin Sports Med. 2006; 25(4):681-702

7. Janzen DL, Peterfy CG, Forbes JR, Tirman PF,

Genant HK. Cystic lesions around the knee joint:

MR imaging findings. AJR Am J Roentgenol.

1994;163:155 – 61.

8. Hirji Z, Hanjun JS, Choudur HN. Imaging of

Bursae. J Clin Imaging Sci. 2011;1:22.

9. Burk DL, Dalinka MK, Kanal E. Meniscal and

ganglion cysts of the knee: MR evaluation AJR

Am J Roentgenol 1988; 150:331-336

10. Pouders C, De Maeseneer M, Van Roy P,

Gielen J, Goossens A, Shahabpour M. Prevalence

and MRI-anatomic correlation of bone cysts in

osteoarthritic knees. Am J Roentgenol. 2008;

190:17 – 21.

11. Recht MP, Applegate G, Kaplan P. The MR

appearance of cruciate ganglion cysts: A report of

16 cases. Skeletal Radiol. 1994;23:597-600

12. Fielding JR, Franklin PD, Kustan J . Popliteal

cysts: a reassessment using magnetic resonance

imaging. Skeletal Radiol. 1991;20:433-35

13. Miller TT, Staron RB, Koenigsberg T. MR

imaging of Baker’s cyst: association with internal

derangement, effusion and degenerative

arthropathy. Radiology. 1996;201:247-5014. Fritschy D, Fasel J, Imbert JC, Bianchi S, Verdonk

R, Wirth CJ. The popliteal cyst. Knee Surg Sports

Traumatol Arthrosc. 2006; 14:623 – 28

15. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP.

Painful suprapatellar swelling: Diagnosis and

discussion. Skeletal Radiol. 2008; 37:937 – 38

16. Recht MP, Applegate G, Kaplan P. The MR

appearance of cruciate ganglion cysts: A report of

16 cases. Skeletal Radiol. 1994; 23:597-600

17. Miller LS, Yu JS. Radiographic indicators of acuteligament injuries of the knee: a mechanistic

approach. Emerg Radiol. 2010;17(6):435-44

18. Haviv B, Bronak S, Thein R. The complexity of

pain around the knee in patients with

osteoarthritis. Isr Med Assoc J. 2013;15(4):178-81

19. Orth RC. The pediatric knee. Pediatr Radiol.

2013;43:90-98

20. Kachewar SG, Kulkarni DS. Distant perijoint

calcifications: sequel of non traumatic brain

injury-a review and case report. Journal of Clinical

and Diagnostic Research. 2013;7:2606-2609.

21. Kachewar SG, Singh H. Perigenicular Heterotopic

Ossification: A rare sequelae of non traumatic

brain injury. Nepal Journal of Neurosciences.

2010;1:21-23

22. Nikken JJ, Oei EHG, Ginai AZ. Acute peripheral

joint injury: cost and effectiveness of low-field-

strength MR imaging results of randomized

controlled trail. Radiology. 2005;236: 958 – 67



88Bala Sharmin et al., Int J Med Res Health Sci. 2014;3(1):88-91


&

Health Scienceswww.ijmrhs.com Volume 3 Issue 1 (Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 27th Nov 2013 Revised: 15th Dec 2013 Accepted: 21st Dec 2013

Research article

A RETROSPECTIVE STUDY OF PRESCRIPTION PATTERN OF ANTIMICROBIALS IN AN URBAN

HEALTH CENTRE RUN BY A MEDICAL COLLEGE

*Bala Sharmin S, Chincholkar Aparna S, Wagh Ranjit J, Mutalik Madhav M.

Department of Pharmacology, MIMER Medical College, Talegaon Dabhade, India

* Corresponding author email: [email protected]

ABSTRACT

Background: Antimicrobials are widely prescribed agents in clinical practice. Overuse of antimicrobials has led to

emergence of drug resistance. Aims: The present study was aimed at knowing the choice of antimicrobial

prescribing and to understand the rationality of antimicrobial usage. Materials and Methods: A retrospective

prescription audit was done of all 655 prescriptions issued between 01/01/2012 and 31/12/2012 at the outpatient

department of Urban Health Centre attached to a medical college. Demographic information, diagnosis, and

medication details (dose, duration, frequency) were recorded and analyzed, and data was expressed as percentages.

Results: Of the total number of prescriptions, 46% prescriptions were containing at least one or more than one

antimicrobial agent. Average number of antimicrobials prescribed per prescription was 1.35. Cotrimoxazole was the

most common antimicrobial agent prescribed. Of the total 307 items of prescribed antimicrobials, 57% wereprescribed by proprietary name and 43% by nonproprietary name. Out of the antimicrobial items prescribed, 44%

were available at the pharmacy of the Urban Health Centre. Fifty eight percent of antimicrobials prescribed were

from WHO Essential Drug List. Conclusion: Among the various antimicrobials prescribed at the Urban Health

Centre, cotrimoxazole was found to be the most commonly prescribed antimicrobial agent in the year 2012. More

than half of the antimicrobials were prescribed by proprietary name. Less than half of the antimicrobials prescribed

were available at the Urban Health Centre. Majority of the antimicrobials prescribed were from the WHO Essential

Drug List.

Keywords: Prescription pattern, Antimicrobials, retrospective study, Cotrimoxazole

INTRODUCTION

Antimicrobial agents are widely prescribed in health

care set-ups for treatment of common ailments like

coryza, cough, fever or pain in abdomen.1

Irrational

and unnecessary use of antimicrobials remains

common in developing countries.1,2

The overuse or

inadvertent use of antimicrobials is known to lead to

the emergence of drug resistance.3,4

Drug resistance is

one of the major obstacles in medical management of

diseases.1

Many physicians augment the drug therapy

with a high dose of antimicrobials and prescribevarious antimicrobial combinations. A study showed

that polypharmacy is now-a-days a common practice.5

Also, many medications are available as ‘over the

counter’ drugs. Many antimicrobials thus may be

taken without knowing the appropriate dosage and

frequency. Many times the antimicrobials are

discontinued before completing the antimicrobial

course of the specified days. This results in inadequate

treatment, and also increases the possibility of

emergence of drug resistance. Considering all these

issues, the present study was undertaken. Theobjectives of the present study were: 1) To know the

DOI: 10.5958/j.2319-5886.3.1.018




prevalence of conditions associated with infections

and to know what antimicrobial agents were

prescribed, 2) To determine whether the drug

prescribing was rationally in accordance with WHO

guidelines for prescribing drugs, 3) To identify

common errors in prescriptions, and propose

interventions for improvement.


This was a retrospective prescription audit. The study

was approved by the Institutional Ethics Committee.

All the prescriptions issued in the outpatient

department of the Urban Health Centre of Bhausaheb

Sardesai Rural Hospital attached to MIMER Medical

College, Talegaon-Dabhade (located in Pune district of

Maharashtra) were studied. The prescriptions issued

from 01/01/2012 to 31/12/2012 were included in the

study, and the total number of prescriptions were 655.

It was not necessary to exclude any prescriptions on

account of incompleteness or illegibility. Demographic

information of the patients, diagnosis of the illnesses,

the medication details (dose, duration, frequency,

formulation, and whether prescribed from WHO

Essential Drug List6

or not), and the follow-up details

of the patients were recorded. All prescriptions were

critically evaluated using guidelines of WHO as

described in ‘How to investigate drug use in health

facilities’.10

The common antimicrobial agents

prescribed, the different types of antimicrobials

prescribed, the number of antimicrobials prescribed

per prescription, and the availability of antimicrobial

agents at the Urban Health Centre were recorded.

Further, whether the physicians prescribed the

medications with proprietary or nonproprietary names

was also noted.

Indicators used for prescription pattern study:

A. Prescribing Indicators: 1, 8

1. Average number of drugs per encounter was

calculated by dividing the total number of drugs

prescribed by the total number of prescriptions.

2. Average number of antimicrobials per prescription

was calculated by dividing total number of

antimicrobials prescribed by the total number of

prescriptions.

3. Percentage of drugs prescribed from WHO Essential

Drug List was determined by dividing the number of

products prescribed from the WHO Essential DrugList by the total number of drugs prescribed,

multiplied by 100.

B) Facility indicators:1, 8

a) Availability of copy of Essential Drug List by

stating “Yes” or “No”.

b) Availability of drugs was calculated by dividing the

number of specified products actually in stock by the

total number of drugs on the checklist of essential

drugs multiplied by 100.

Selection of Cases: All the prescriptions issued at the

Urban Health Centre from 01/01/2012 to 31/12/2012

were included in the study.

Statistical Analysis: It is a descriptive study and

purposive sampling was done. Data was analyzed and

expressed as a percentage.

RESULTS

Of the total 655 prescriptions, 46% prescriptions werecontaining at least one or more antimicrobial agents.

Average number of antimicrobials prescribed per

prescription was 1.35. Of the total 226 patients taking

antimicrobials, 82 were males and 142 were females.

There were 84 children. Upper respiratory tract

infection was the most common diagnosis in all adults

and children followed by diarrhea (Figure 1) (Table 1).

There were 26 different antimicrobials prescribed, of

which 4 were prescribed most commonly.

Cotrimoxazole was the most common drug prescribed

to both adults and children (36.2%) followed by

metronidazole, norfloxacin, and amoxicillin (Figure

2). A single antimicrobial was prescribed in 81% of all

prescriptions, whereas 17% prescriptions contained

two antimicrobial agents. The prescriptions containing

cephalosporins were 2%. Percentage of antimicrobial

items prescribed by brand name (proprietary name)

was 57% and those prescribed by non-proprietary

name was 43%. The doses of the antimicrobial

medications were prescribed according to standard

regimens. Of the 226 patients, 63 came for follow-up

and 22 of them received antimicrobials on follow-up.

Antimicrobial agent was changed in 15% patients on

follow-up. Out of all the antimicrobial items

prescribed, 44% were available at the pharmacy of the

Urban Health Centre. Most common antimicrobial

prescribed from outside the Urban Health Centre was

doxycycline. The WHO Essential Drug List was

available at the Urban Health Centre. Fifty eight

percent of antimicrobials prescribed were from WHO

Essential Drug List. Of the antimicrobials prescribedfrom WHO Essential Drug checklist, 46% were

available at the pharmacy of the Urban Health Centre.




Fluoroquinolones (norfloxacin, ciprofloxacin) were

administered to 5 children, of which three had the

diagnosis of diarrhea, and two were diagnosed with

fever and chills.

Table 1: Some common disease conditions and

corresponding antimicrobial prescribed

Most common diagnosis Most common

antimicrobials

prescribed

Upper respiratory tract

infection (URTI)

Cotrimoxazole

Loose Motion Metronidazole

Urinary Tract Infection

(UTI)

Norfloxacin

Injury Cotrimoxazole

Folliculitis Cotrimoxazole

48.20%

14.60%9.60%

4.20%

23.40%

URTI Loose motion UTI Injury Others

Fig 1: Diagnosis observed in percentage:

URTI- Upper respiratory tract infection, UTI- Urinary

tract infection

36.20%

15.70%11.20%

4.70%

32.20%

0.00%

10.00%

20.00%

30.00%

40.00%

Fig 2: Antimicrobials prescribed

DISCUSSION

There is a widespread use of antimicrobials all over

the world. In a study from rural clinics in WesternChina, almost half of the prescriptions contained

antimicrobial agents.9

This figure was 54.8% in

Lagos, Nigeria, 67% in Hai Phong Province, Vietnam,

27.1% in a primary healthcare centre in Lebanon,

15.3% in United States, and 32% in Spain.9

In a study

from India, 69% prescriptions contained one or more

antimicrobial agents.4

In the present study, 46%

prescriptions contained one or more antimicrobial

agents. The difference is statistically significant.

(Z=8.08, p<0.001). Upper respiratory tract infection

was the most common diagnosis, and cotrimoxazole

was the most commonly prescribed antimicrobial

agent (36%) followed by metronidazole, norfloxacin,

and amoxicillin. Two other studies also found

cotrimoxazole as the most commonly prescribed

antimicrobial agent (36% prescriptions).4, 7

The results

are comparable with our study. In a study conducted in

Kyrgyz Republic, penicillin G was the most common

antimicrobial agent prescribed3. Now-a-days the

cephalosporins are one of the most commonly

prescribed antimicrobials in various countries. A study

in South India reported cefixime to be the most

commonly prescribed antimicrobial agent2. In the

present study there were 26 different antimicrobials

prescribed of which 4 were prescribed most

commonly; however, the cephalosporins were

infrequently prescribed. In a study conducted in China,

there were 49 antimicrobials prescribed in total, 17 of

them were prescribed frequently.9 In the present

study, prescriptions with one antibiotic comprised 81%

of all prescriptions, those with two antimicrobials

represented 17%. In the study conducted in China,

prescriptions with one antibiotic comprised 40.6% of

all prescriptions, and those with two antibiotics

represented 7.08%9. The frequency and proportion of

prescribed antimicrobials in the present study are

higher compared with the other studies.9

The average

number of medicines per encounter (2.8%) is higher

than the range of 1.3 – 2.2 found in similar studies inother countries conducted at the district or regional

levels, either in hospitals or health centers.1

Though a

significant number of antimicrobials were prescribed

by the non-proprietary name, the physicians prescribed

majority of the antimicrobials by brand (proprietary)

name. It was found in the prescriptions that the doses

of the antimicrobial medications were appropriate in

context with the medical conditions and the patient

factors. Almost one third of the patients taking

antimicrobials returned for follow up. Less than half of the antimicrobials prescribed were available at the

Urban Health Centre. Majority of the antimicrobials




were prescribed from the WHO Essential Drug List

(58%). When this figure was compared with those

from other studies, it was found that the percentage of

antimicrobials prescribed from WHO Essential Drug

List was higher in other studies, e.g. being 79% in a

study done in Lesotho and with the WHO study

showing that the adherence to the Essential Medicine

List in Tanzania was 88% (Ofori-Adjei, 1992) and in

Nepal 86%.1

It was suggested that improvements in

the prescribing pattern can be made by prescribing the

drugs to a larger extent by their non-proprietary name.

More antimicrobial agents should be prescribed from

the WHO Essential Drug List. We suggest that more

drugs which are prescribed and included in the WHO

Essential Drug List should be available in the Urban

Health Centre pharmacy. In the present study, it was

noticed that fluoroquinolones were administered to 5

patients less than 18 years of age. Fluoroquinolones

may damage growing cartilage and cause arthropathy.

Therefore these drugs are not routinely recommended

for patients less than 18 years of age.11

CONCLUSION

Prescription audit of prescriptions over a period of 1

year at the Urban Health Centre of a rural hospital

showed that antimicrobials were widely prescribed.

Cotrimoxazole was the most common antimicrobial

prescribed. There were antimicrobial items found to be

prescribed by the proprietary name in significant

number of prescriptions. Suggestions and

recommendations from this particular audit would be

useful to improve the prescribing trends for the benefit

of the recipients.

ACKNOWLEDGEMENTS

I sincerely thank the Urban Health Centre staff and the

Department of Preventive and Social Medicine for

extending help in providing all the necessary

information of the patients visiting the Urban Health

Centre.

REFERENCES

1. Antibiotics prescribing pattern at 6 hospitals in

Lesotho. Retrieved from apps.who.int/

medicinedocs/documents/s21028en/s21028en.pdf.

(Accessed on November 15, 2013).

2. Khade A, Shakeel M, Bashir M, George S,

Annaldesh S, Bansod K. Prescription pattern of

antimicrobial agents in a teaching hospital of

South India. Int J Basic Clin Pharmacol 2013;

2(5): 567-70.

3. Baktygul K, Marat B, Ashirali Z, Rashid H,

Sakamoto J. An assessment of antibiotics

prescribed at the secondary health care level in the

Kyrgyz Republic. Nagoya J. Med. Sci. 2011;73:

157-68.

4. Indira K, Chandy S, L Jeyaseelan, Kumar R and

Suresh S. Antimicrobial prescription patterns for

common acute infections in some rural and urban

health facilities of India. Indian J Med Res

2008;128:165-71.

5. Kumari R, Idris M, Bhushan V, Khanna A,

Agrawal M, Singh. S.K. Assessment of

prescription pattern at the public health facilities

of Lucknow district. Indian J Pharmacol.

2008;40(6):243-7.

6. WHO Essential Drug List. Retrieved from:

www.who.int/medicines/publications/essentialmed

icines. (Accessed on February 24, 2013)

7. Furones J A. Drug utilization Study related to

Antibiotics in Primary Health Care; INABIS98.

Retrieved from: www.mcmaster.ca/inabis98/

occupational/furones0821/index.html. (Accessed

on November 15, 2013).

8. Introduction to Drug Utilization and Research/

WHO International Working Group forDrug

Statistics Methodology, Drug Utilization Research

and Clinical Pharmacological Services. Retrieved

from: http://apps.who.int/medicinedocs

/en/d/Js4882e/8.4.html#Js4882e.8.4. (Accessed on

February 25, 2013).

9. Dong L, Yan H, Wang D. Antibiotic prescribing

patterns in village health clinics across 10

provinces of Western China. J Antimicrob

Chemother. 2008;62(2):410-15.

10. WHO. How to investigate drug use in healthfacilities: selected drug use indicators, Geneva,

World Health Organisation, 1993, WHO/DAP/93

1993;1:1-87. (Accessed on February 24, 2013)

11. Deck DH, Pharm D, Lisa G, Winston, MD.

Sulfonamides, trimethoprim, and quinolones. In:

Katzung BG, Masters S, Trevor A. Basics and

clinical pharmacology. Tata McGraw-

Hill;2012;12th edition:836



92

Prakash et al., Int J Med Res Health Sci. 2014;3(1):92-97


&

Health Sciences




rdDec 2013

Research article

PREVALENCE AND FUNGAL PROFILE OF PULMONARY ASPERGILLOSIS IN

IMMUNOCOMPROMISED AND IMMUNOCOMPETENT PATIENTS OF A TERTIARY CARE

HOSPITAL

Prakash Ved1, *Mishra Prem P

2, Verma Shashi K

3, Sinha Shivani

4, Sharma Mahendra

5


2Assistant Professor,

4MD student Department of Microbiology, RMCH, Bareilly, UP, India

3

Professor, Department of Physiology, RMCH, Bareilly, UP, India5Statistician cum lecturer, Dept of community Medicine; RMCH, Bareilly, UP, India


ABSTRACT

Background: Aspergillus is a fungus which may present an array of pulmonary manifestations, depending on the

patient's immunological and physiological state. Although the incidence of pulmonary aspergillosis occurs primarily

in immunocompromised patients but the incidence is also rising in immunocompetent individuals, especially in

developing countries. Aim: The objective of the study was to determine the prevalence and predisposing factors of

pulmonary aspergillosis along with species identification. Materials and Methods: One hundred and three patients

admitted to the Department of Chest and Tuberculosis and in the Department of Medicine from Jan 2012 to Jan2013 were included in this study. The patients were epitomized on the basis of clinical signs and symptoms,

physical examination, chest radiography, CT scans, histopathological examination, bronchoscopy and fungal

examination including potassium hydroxide mount, fungal culture of sputum and bronchoalveolar lavage. Species

identification was done by colony characteristics, slide culture and Lactophenol Cotton blue mount. Results: Out of

the 103 patients, (63 males and 40 females) Aspergillus species has been isolated from 17 (16.5%) males and 07

(6.79%) females. Various predisposing factors of pulmonary aspergillosis have been identified in which pulmonary

tuberculosis, chronic smoking and environmental exposure to asbestos, cement its tops the list. Many of the patients

had multiple predisposing factors. Aspergillus species were isolated in 24 (23.3%) cases. Aspergillus fumigatus was

the predominant species isolated in 13 (54.16%) cases followed by Aspergillus flavus in 07 (29.16%) cases,

Aspergillus niger in 03 (12.5 %) and Aspergillus terrus in 1 (4.16%) cases. Conclusion: It is concluded that theprevalence of pulmonary Aspergillosis is quite high in immunocompromised individuals and low in

immunocompetent individuals. An adequate and efficient evaluation of the etiological agents has a crucial role in

the management of such patients.

Keywords: Aspergillus, Tuberculosis, Sputum, Immunocompromised.

INTRODUCTION

In recent years fungal infections are one of the

important cause of pulmonary infections.1

Aspergillus

primarily affects the lungs, causing a variety of

manifestations, including allergic bronchopulmonary

aspergillosis (ABPA), aspergilloma, and invasive

aspergillosis. Invasive pulmonary aspergillosis is an

increasingly common fungal infection with high

morbidity and mortality in immunocompromised

patients. The incidence and clinical impact of these

infections is on the rise in the developed countries,

DOI: 10.5958/j.2319-5886.3.1.019



93


which is possibly related to increased number of

immunocompromised patients, owing to improved

survival from AIDS, malignancies and more intensive

cytotoxic therapy, organ transplantation and better

treatment and prophylaxis for other fungal infections.2

Immunocompromised individuals are susceptible to

pulmonary aspergillosis, but invasive aspergillosis is

extremely uncommon in individual’s with intact

immunity. Immunocompetent persons seldom develop

this infection and do so only in the presence of other

pulmonary and systemic abnormalities such as fibrotic

lung disease,3

suppurative infection4

or treatment with

corticosteroids.5

Pulmonary aspergillosis shows a

variable inimitable pattern of lung disease that

primarily depend on the patient's immune status.

Preexisting lung diseases acts as a significant

predisposing cause for pulmonary aspergillosis.6,7

Pulmonary aspergillosis is generally presented as a

wide range of pulmonary manifestations, from

aspergilloma with a comparatively benign course, to

invasive pulmonary aspergillosis, which can be

terminal. Pulmonary aspergillosis is one of the main

causes of pulmonary infections and creates a

complicated diagnostic challenge due to lack of

pathognomonic clinical features. The diagnosis of

aspergillosis is frequently missed as the diagnostic

tests for their detection is not done in routine

diagnostic laboratories and/or is not suspected by the

physician.

Therefore, the present study aims to a) detect the

prevalence of pulmonary aspergillosis in

immunocompromised and immunocompetent

individuals. b) To study the various predisposing

factors. c) Isolation and differentiation of

Aspergillus species from clinical specimens of patients

suffering from pulmonary infections.

METHODS

This study was conducted on 103 patients with

different chronic pulmonary infections admitted in the

wards of Department of Chest and Tuberculosis, and

Department of Medicine between the period of

January 2012 to January 2013. The cases are the

patients with various chronic pulmonary infections of

more than one year on whom bronchoscopy, radio

imaging was done. This work has been approved by

the Institutional Ethical Committee.Data were collected regarding age, sex, detailed

medical history (immunosuppressive conditions like

pulmonary tuberculosis, Diabetes mellitus, AIDS etc,

chronic smoking and environmental exposure to

asbestos, cement etc smoking), physical examination

(vital signs, cyanosis, pallor, clubbing etc), chest

radiography, Computed Tomography (C.T) scan,

bronchoscopy etc. A complete blood picture and

histopathological examination were done. We have

considered the infections/diseases as a prime risk

factor in patients with multiple risk factors.

The sputum and bronchoalveolar lavage was

homogenized and direct microscopy was performed by

using 10% KOH mount. It was inoculated on one set

of Sabouraud's Dextrose Agar (SDA) [HIMEDIA,

MUMBAI] plain and SDA with Chloramphenicol

(0.05 mg/mL) [HIMEDIA, MUMBAI] and also on

Czapek Dox agar [HIMEDIA, MUMBAI]. The

inoculated SDA were incubated at 25˚C and at 37˚C.

The colony morphology of obverse as well as reverse

was studied.8

Tease Mount Preparation (TMP) of the

mould isolated was prepared in Lacto Phenol Cotton

Blue (LPCB) for identification detailed morphology

including hyphae, phialides, vesicles and spores. The

confirmation of fungal species was done by slide

culture.9

Statistical analysis: The data were analyzed by using

SPSS version 17. The descriptive analysis and chi

square test were applied. The results obtained were

presented by using appropriate tables and charts.

RESULTS

A total of 103 patients {63 (61.16%) males and 40

(38.83 %)} of various age groups with indications of

chronic pulmonary infections were admitted in the

wards of the Hospital during the study period as shown

in Table 1 and Table 2. The chi square test is

appropriate at 5% level which shows no significance

among culture positive males and females whilesignificant in age group > 40 years (Elderly).

Aspergillus species have been isolated from 17

(16.5%) males and 07 (6.79%) females. The elderly

patients (>40 years) had a higher incidence of

pulmonary aspergillosis in males as well as females.

There are 17 culture positive cases among

immunocompromised and 07 cases among

immunocompetent cases. Based on the data of the

clinical history, the various risk factors like pulmonary

tuberculosis, diabetes mellitus, HIV infection, chronicsmoking, recurrent respiratory tract infections,

Bronchial Asthma, Pleural effusion, environmental



Prakash et al.,

exposure to asbestos, cement and o

documented in Figure 1.

Aspergillus fumigatus was the pre

isolated from 13 (54.17%) cases

Table 1: Distribution of culture po

SEX Culture Positive Patie

MALE 17

FEMALE 07

TOTAL 24

Table 2: Age group of culture posi

Age Group Culture Positi

0-20 YRS 01

21-40 YRS 08

>40 YRS 15TOTAL 24

Table 3: The incidence of Aspergil

SPECIES No. of Po

Aspergillus fumigatus 13

Aspergillus flavus 07

Aspergillus niger 03

Aspergillus terrus 01

Fig 1: The various risk factors in t

Note: various patients had multiple r

0

5

10

15

20

25

30

35

40

45

33

15

69

3 3

Int J Med Res Health

ther chemicals are

dominant species

significant by chi

square test, followed b

isolated in 7 (29.17%

Aspergillus Niger and

terrus as depicted in Ta

sitive and culture negative patients on the bas

nts Culture Negative

Patients

Total

46 63

33 40

79 103

ive and culture negative patients.

ve Culture Negative Total

23 24

24 32

32 4779 103

us species isolated among patients of chronic l

sitive Cultures Percentage

54.17%

29.17%

12.5%

4.7 %

he patients that may be associated with pulmo

isk factors.

2421

4

42

22

31

0 1 14

2 1 to

no

94

Sci. 2014;3(1):92-97

Aspergillus flavus which was

) cases, 3 (12.5%) cases of

1 (4.7 %) case of Aspergillus

le 3 and figure 2.

s of sex.

P value

=1.231

P= 0.2671

P value

=6.92

P= 0.0314*

*Significant

ung disease.

P value

= 6.92

P= 0.0314*

*Significant

nary aspergillosis

tal no of patients

of positive culture



Prakash et al.,

Fig 2: Percentage of Aspergillus

positive patients.

DISCUSSION

Aspergillus species are common sa

and their vegetative spores are ever

only immunocompromised patients

who suffer from other chronic lu

susceptible. Recently, reports of in

aspergillosis in immunocompete

increased in the clinical

Immunocompetent patients

asymptomatic and only incidentally

have aspergillosis.

12-14

Though, tpulmonary aspergillosis in patients

system have been documented.11

reports about invasive pulmonar

COPD patients and ap

immunocompromized patients15-22

ha

In our study, the prevalence of pulm

was 23.3%. The prevalence

Henderson et al23

who reported an i

Pepy et al24

reporting 8% and Cam

8.2 % respectively.25

This might b

exposure of the patients to the predis

environmental conditions favouring

fungus.

Among the risk factors pulmo

chronic smoking, bronchial Asth

carcinoma was seen. Multiple risk

found in patients admitted. Risk

COPD, systemic corticosteroid

haematological malignancy, chron

liver failure, diabetes mellitus, ne

infection, etc have been described i29

The incidence of aspergillosis wa

Asperg

us

fumiga

s

54%

Aspergill

us flavus

29%

Aspergill

us niger

13%

Aspergill

us terrus

4%

Int J Med Res Health

pecies in culture

probic in the soil,

resent. Generally,

or the individuals

ng conditions are

vasive pulmonary

t patients have

literature.10,11

are generally

they are found to

e rare cases of ith intact immune

In recent time,

aspergillosis in

parently non-

ve been reported.

onary aspergillosis

as higher than

incidence of 11%,

pbell and Clayton

due to the more

posing factors and

the growth of the

ary tuberculosis,

a, bronchogenic

factors were also

factors such as

therapy, non-

ic renal disease,

ar-drowning, HIV

earlier studies.26-

more common in

males as compared to

compared to children

exposure to risk factor

incidence of

immunocompromised

immunocompetent indi

have described

patients with normal i

invasive infections ca

most commonly Asper

chest wall30

, brain, midd

Methods of prompt

aspergillosis are based

culture, serological m

examination which is a

both clinicians and p

undertake. The culture

samples. Aspergillus fu

species isolated in 13 (

with the findings of Bor

The other species isol

Aspergillus niger and A

3 (12.5%), and 1 (4.7 %

CONCLUSION

Finding of Aspergillusamples in the patie

discarded as colonizati

immunocompetent[27]

. It

study that the prevalen

in immunocompromise

patients is rising in our

chronic lung infection

antibiotic therapy shoul

by Aspergillus. Any i

positive sputum cultu

compel the physician to

ACKNOWLEDGME

We would like to expr

teachers who made us

project which also hel

from experience. Seco

thank Miss Vandana Th

helped us to carry out o

Thanks again to all who

Disclaimer: None

ill

tu

95

Sci. 2014;3(1):92-97

females, more in adults as

hich may be due to increased

s. Our study showed a higher

Aspergillosis among

individuals and low in

iduals. More recently, reports

munity and invasive or semi-

used by Aspergillus species,

illus fumigatus, involving the

le ear31

, and lung10,14

.

diagnosis of pulmonary

on isolation of Aspergillus in

ethods and histopathological

n invasive method, for which

atients may be reluctant to

was positive in 24 (23.3%)

migatus was the predominant

4.17%) cases which is in line

dane et al and Shahid et al.32, 33

ated were Aspergillus flavus,

pergillus terrus in 7 (29.17%),

) cases respectively.

species in respiratory tract ts should not be routinely

ion, even if the patients are

is concluded from the present

e of pulmonary Aspergillosis

as well as immunocompetent

country; hence, any patient of

not responding to regular

d be investigated for infection

ndication of aspergillosis, by

re, serological tests, should

initiate anti-fungal treatment.

T

ess our special thanks to our

capable to do this wonderful

ed us to gain the knowledge

ndly, we would also like to

akur and other technicians who

r work smoothly.

helped us.



96


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JC. Renal and respiratory failure in Scottish

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MR. Necrotizing fasciitis. Importance of

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19. Lewis M, Kallenbach J, Ruff P, Zaltzman M,

Abramowitz J, Zwi S. Invasive pulmonary

aspergillosis complicating influenza A pneumonia

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patient. Chest. 1985;87:691 – 93

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J, Ducel G, Thorens JB etal., Unusual cause of

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Respir Crit Care Med. 1996;154:541 – 44

21. Bulpa PA, Dive AM, Garrino MG, Delos MA,

Gonzalez MR, Evrard PA, Glupczynski Y, Installe

EJ. Chronic obstructive pulmonary disease

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Med. 2001;27:59 – 67

22. Karam GH, Griffin FM. Invasive pulmonary

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63

23. Henderson AH, English MP, Veeht RJ. Pulmonary

Aspergillosis: A survey of its occurrence in the

patients with chronic lung diseases and a

discussion of the significance of diagnostic tests.Thorax. 1968;23:513-21



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24. Pepys J, Riddel RW, Citron KM, Clayton YM,

Short EL. Clinical and immunological significance

of Aspergillus fumigatus in sputum. Am Rev Resp

Dis. 1959;80:167-180.

25. Campbell MJ, Clayton YM. Bronchopulmonary

aspergillosis. Am Rev Resp Dis. 1964; 89: 186

26. Vandewoude KH, Blot SI, Depuydt P, et al.

Clinical relevance of Aspergillus isolation from

respiratory tract samples in critically ill patients.

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27. Dimopoulos G, Piagnerelli M, Berre J.

Disseminated aspergillosis in intensive care unit

patients: an autopsy study. J Chemother

2003;15:71 – 75

28. Vandewoude KH, Blot SI, Benoit D, et al.

Invasive aspergillosis in critically ill patients:

attributable mortality and excesses in length of

ICU stay and ventilator dependence. J Hosp Infect

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29. Meersseman W, Vandecasteele SJ, Wilmer A.

Invasive aspergillosis in critically ill patients

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30. Fisher MS. Case report 750: aspergillosis of the

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31. Kim DG, Hong SC, Kim HJ. Cerebral

aspergillosis in immunologically competent

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98

Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103


&

Health Sciences

www.ijmrhs.com Volume 3 Issue1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 7

thDec 2013 Revised: 19


stDec 2013

Research article

SOCIODEMOGRAPHIC PROFILE OF SPEECH AND LANGUAGE DELAY UP TO SIX YEARS OF

AGE IN INDIAN CHILDREN

*Abraham Binu1, Raj Sunil

1, Stephenson Baburaj

2, Mohandas MK

2


2Professor, Department of Pediatrics, Dr SMCSI Medical College, Trivandrum, Kerala


ABSTRACT

Background: Speech and language is the most important skill for the child’s development and scholastic

performance. Awareness of the delay is important in the programs for early identification. Purpose: to assess the

prevalence of speech and language delay in children from age group 0 to six years of age. Methodology: The

speech and language development of children coming in the well baby clinic and daily pediatric clinic of age group

from birth to 6 years were evaluated using Language Evaluation Scale Trivandrum (LEST). The prevalence of

speech and language delay in each age group was calculated and also analyzed in the sociodemograhic profile.

Results: A total of 102 children were studied in which 13.7% had language delay. 18% had questionable language

delay and 15.7% had suspect language delay. Though among language delay mixed type was more, children had

more difficulty in doing expressive items. Language delay was also found to be more prevalent in males, single

child, first born child and children of working mothers. Parental age, education or socioeconomic status was not

found to be related to language delay. Conclusion: The 13.7% prevalence of language delay in the children

indicates the need of early identification and for it a simple screening tool like LEST is a must during the routine

evaluation of young children in pediatric clinics. Health care givers and parents should ensure that babies grow up

in a language rich, nurturing and stimulating environment right from birth onwards.

Key words: LEST, Language delay, Speech delay, First born child

INTRODUCTION

Speech and language is the most useful and mostwidely used form of communication. Communication

is integral to overall developmental progress in young

children mainly in cognitive, social – emotional and

adaptive development. Speech helps the children to

get attention from others, to satisfy their needs, to

influence the behavior of others, to develop social

relations and as they grow, it plays an important role in

their academic achievements.1

Language typically develops in a very predictable

fashion, and assessment of language developmentshould be a central part of every well-child visit.

Pediatricians are in an excellent position to identifychildren's speech and language problems early and to

make appropriate referrals for further evaluation and

treatment services.

The children who have communication problems may

develop behavior problems and difficulty to read and

write later in life.2

Children’s capacity to communicate

and the vocabulary power when they enter preschool

are important for good scholastic performance.

Children with language problems in preschool are at

risk of poor educational achievement in school age andare at increased risk to develop emotional and

DOI: 10.5958/j.2319-5886.3.1.020



99


behavioral disorders.3

Early intervention may prevent

or decrease the severity of language delays in school

age and increase later academic success in school. To

underline this fact, there is increasing number of

evidences coming up that intervention given or started

during infancy or preschool age has a greater positive

effect than services provided at school age.4

The language development of a child may be a good

marker of developmental delay. Delay in acquiring

language development is often an early indicator of

pervasive developmental problems and future learning

disability. This indicates the need for assessment of all

babies less than 2 years.

This study is planned to evaluate the prevalence of

language and speech delay in children from birth to 6

years of life as preschool years are the most ideal time

for the early identification of communication delay

which will help to start the early intervention. It will

also be useful to evaluate the prevalence of expressive

and receptive type of delay among the children which

help to focus our attention to that part.

This study also tries to evaluate the communication

delay in the context of maternal and paternal education

and occupational status. There is a scarcity of studies

involving all these factors. So this study is aimed to

involve all these factors which will help to know the

multiple factors influencing the language and speech

development.

Aims and Objectives: The aim of the present study

was to assess the speech and developmental outcomes

in children from age group 0 to six years. The

objectives were to find the prevalence of speech and

language delay in children from age birth to six years

of age and to find the sociodemographic characteristics

associated with it.


The Study was conducted by Department of Pediatrics

after getting ethical clearance from the institutional

ethical committee of Dr SMCSI Medical College,

Trivandrum, Kerala, also taken informed consent from

parents.

Study design: A descriptive study of cross sectional

design.

Study population: The children attending well baby

clinic and daily pediatric clinic of a tertiary care

centre, Dr SMCSI Medical College, Karakonam of agegroup birth to six years. Considering the prevalence of

developmental delay as 6.6%(p) as per the study done

by Nair MKC et al5, margin of error at 5%(m),

confidence level as 95%(t=1.96), the minimum

sample size is estimated to be 102 using the formula

t2xp(1-p)/m

2

Selection of cases: The inclusion criteria consist of

children in the age group 0-6 years coming in the

outpatient and well baby clinic of Pediatric

Department for routine checkups, minor illnesses and

also for vaccination. Those children with severe

sickness and those with developmental delay in other

domains like gross motor, fine motor and social were

excluded.

Tools for the study

The study is done by using a performa consisting of

the socio demographic parameters like age, sex, family

order, living with parents or not and sibling details.

Details of paternal age, education and occupation are

assessed. The socioeconomic class is assessed using

Modified Kuppuswami Scale.6

Maternal details of age;

education and occupational status as house wife or

working mother were also assessed. The speech and

language assessment is done using Language

Evaluation Scale Trivandrum (LEST) which was

developed by Child Development Centre,

Trivandrum7. Other tests are Receptive Expressive

Emergent Language Scale (REELS) and Early

Language Milestone Scale (ELM Scale 2).7

But LEST

is a culturally appropriate locally relevant simple

language development screening tool which can be

used both to professionals, those who are working in

the field of child development and even with the

mothers to pick up speech delay in the early years of

life. The assessment of language delay was done by

assessing if the child is able to do all items on the left

side of their corresponding age in the LEST Chart. The

interpretation is done in four ways as in Table1

Table1: Interpretation of language delay using

LEST7

Normal – All items

done

Suspect – Two

items not done

Questionable – One item

not done.

Delay – Three or

more items not done

The distribution of children in different age groups are

calculated in 0-1 year, 1-2 year, 2-3 year, 3-4 year, 4-5

year and 5-6 years and the speech and languagedevelopmental pattern was assessed in these age



100


groups. The prevalence speech and language delay

was calculated as normal, questionable, suspect and

delay which were the outcome variables. Each item is

compared in the sociodemographic schedule with

different age groups. The type of delay was also

assessed as expressive, receptive or mixed type. The

delays were compared with different age groups.

Statistical analysis: Mean, standard deviation and

Student t tests were used for analysis of continuous

variables and Chi Square test was used for categorical

variables. A p value below or equal to 0.05 was

considered to be statistically significant for a 95%

Confidence Interval. The Statistical software SPSS

16.0 was used for the analysis of the data and

Microsoft Excel was used to generate tables.

RESULTS

The study was conducted in children attending the

well baby and pediatric clinics of Department of

Pediatrics, Dr SMCSI Medical College Trivandrum,

Kerala. A total of 102 children were assessed for the

study in which 49(48%) were females and 53(52%)

were males and the difference was not statistically

significant (P value 0.73). Depending on the age of

children they were divided into 6 groups 0-1 year, 1-2

year, 2-3 year, 3-4 year, 4-5 year and 5-6 years.

Among the 102 children studied, the total percentage

of children with language delay was 13.7%. 15.7%

children were in the suspect and 18 % were in the

questionable group. The prevalence of language delay

in each age group is given in table 2

Among the total 14 of 102 children who had language

delay, 10.8% children were having a mixed type of

delay, 1% was having receptive and 2% were having

an expressive type of delay. Regarding the type of

items children could not do during assessment, 20%

had difficulty in doing both items.

Comparing expressive and receptive type of language

items individually, 16% could not do expressive items

only compared to 9.1% who could not do receptive

items only. This shows that children had more

difficulty in doing expressive items.

The percentage of males having delay were found to

be more compared with that of females (15.1% males

with 12.2% females) and the difference was not found

to be statistically significant (p value 0.67). The sub

analysis of children with language delay according to

delay, questionable and suspect group is given in table

3.

Table 2: Language delay in each age group

Age Group (yr) Normal (%) Questionable (%) Suspect (%) Delay (%) Total

0-1 14(70.0) 4(20.0) 1(50) 1(5) 20

1-2 11(52.4) 6(28.6) 3(14.3) 1(4.8) 21

2-3 7(46.7) 1(6.7) 3(20) 4(26.7) 15

3-4 6(40) 3(20) 3(20) 3(20) 15

4-5 7(43.8) 2(12.5) 4(25) 3(18.8) 16

5-6 9(60) 2(13.3) 2(13.3) 2(13.3) 15

Total 54(52.9) 18(17.6) 16(15.7) 14(13.7) 102

Table 3: Gender related variation in language delaySex Normal (%) Questionable (%) Suspect (%) Delay (%) Total

Female 30(61.2) 6(12.2) 7(14.3) 6(12.2) 49

Male 24(45.3) 12(22.6) 9(17) 8(15.1) 53

Total 54(52.9) 18(17.6) 16(15.7) 14(13.7) 102

The majority of the children were of the first order

which was 67 (61.8%). Of the rest, 37 children

(36.3%) were 2nd

order. Language Delay was found to

be more prevalent among the first born child in this

present study. 17.5% delay was seen in the first child

compared to 8.1% seen in the second born child.

Language delay was found also to be more prevalent

in the single child in the family. 17.3% of 52 single

children were having delay compared to 10% of 50

children who were not single kids in the family and it

was significant (p value -0.033)

In the present study no association could be made with

the parental age and language delay. Among the 14

children with language delay, fathers of half children



101


had passed 10th

class and other half were degree

holders. Similarly of those 14 children, 5 mothers had

passed 10th

class and 9 mothers were degree holders.

This shows that all the parents of children with

language delay were educated.

It has been found that among the children of house

wife mothers’, 4 children (11.2%) had language delay.

But among the children of working mothers’, 10

children (30.8%) had language delay.

Among the 14 children who had language delay, 11

children were living with parents. For 2 children their

fathers were not in the state and for one child, both

parents were not in the state. No association could be

made about the language delay in children not living

with both their parents as the number of children in

those groups was very less.

The socioeconomic class grading was also done

among the children studied using Modified

Kuppuswami Grade and the socioeconomic class of

the children with language delay was analyzed and

shown in table 4.

Table 4: Socioeconomic class and language delay

Social

Class

No Delay

(%)

Delay

Present (%)

Total

Class 1 1(100) - 1

Class 2 19(86.4) 3(13.6) 22Class 3 50(86.2) 8(13.8) 58

Class 4 17(85) 3(15) 20

Class 5 1(100) 1

Majority of children belonged to 2, 3 and 4

socioeconomic grades. No significant association was

seen with lower or higher socioeconomic class and

language delay.

DISCUSSION

A cross sectional study in 102 children was conductedusing Language Evaluation Scale Trivandrum (LEST

0-6) from the age group birth to 6 years of age to find

out the prevalence of language and speech delay.

The total percentage of children with language delay

was 13.7. In the study done by Nair MKC et al5, 6.6 %

of language delay was observed for the age group 0-12

months using LEST against 4% prevalence for the

same using Receptive Expressive Emergent Language

Scale (REELS). In the present study it was 5% below

1 yr age was comparable.

For the age group 13 to 24 months, the study done by

Nair MKC et al5, prevalence of speech and language

delay among at risk babies was 29.7% using LEST as

against 6.6% by using REELS and 5.7% using both

tests. In the present study it was found to be 4.8%. The

difference may be due to the factor that in the present

study the babies coming to the well baby clinic were

observed and at risk babies were not included in the

study.

In a study done by James et al in 1980 the speech and

language delay in the age group 0 to 2 years was

around 5%8. In the present study, it was 4.87% which

was comparable.

For the age group 2-3 years, the speech and/or

language delay was 6.9% in the study done by Burdon

et al, it was 6.9%9. The language delay was 2.6 % in

the study done by Silva et al in 1983.10

But in the

present study it was 26.7% which was significantly

higher that the other studies.

For the age group 3-4 years, in the study done by

James et al the speech or / and language delay was

5%.6

In our study it was 20% which was higher.

For the age group 5-6 years, in the study by Beitchman

et al, the speech and/or language delay was 11.78%.11

In another study by Stevenson et al it was 6.8%.12

In

the present study the speech delay was 13.3% which

can be compared to the study done by Beithchman et

al.

In a study done by Nair MKC et al5

in children of age

13 to 24months, 24% had a language delay in the

receptive area using LEST as against 5.1% using

REELS. Similarly 42% had a language delay in

expressive area by using LEST as against 7.4% using

REELS. In the study done by James et al the mixed

language delay was 2.14%8, expressive delay was

4.27% and receptive delay was 3.95%. In the present

study the mixed language delay was found to be more.

Among the items not done by children in our study,

16% could not do expressive items and 9.1% could

not do receptive items. This showed that children havemore difficulty in doing the expressive items. In the

study done by Nair MKC et al5

in children of age 13 to

24months, 24% had delay in the receptive language

and 42% had delay in expressive language by using

Language Evaluation Scale Trivandrum (LEST).

In the study done by Tomblin13

et al 87% of children

with articulation disorders were boys and in the study

done by Choudhary et al 70% of the children were

males.14

In the present study though the number of

males with language delay was more (57%), thedifference was not significant.

In the study done by Broookerhouser et al15

children

born late in family birth order was a significant factor



102


for language delay. In another study by Nelson et al

single child in the family was also found to be a

factor.16

In the present study also first born children

had a more language delay. Similarly a single child in

the family was also found to be a significant factor.

In the study done by Nelson et al, older parents and

younger mother age was found to be a significant

factor16

. From the present study no such association

could be made with parental age. The study done by

Campell et al showed an association between lower

maternal education and language delay.17

The

systematic evidence review done by Nelson et al also

showed similar picture..

Another study done by Tallal

et al also showed an association between lower

paternal education level and language delay.18

This

study does not support that fact and all the parents of

the children were educated.

Children of house wife mothers had significantly less

language delay than children of working mothers.

Similarly those living with both the parents had less

delay but the difference were not significant. In the

study done by Tallal et al18

lower socioeconomic class

was a risk factor for language delay. In our study there

was no significant association between socioeconomic

status and language delay.

CONCLUSION

The study showed that language delay was more

prevalent in below 2 years of age, in first born child

and single child in the family. This reveals the

importance of early screening and the importance of

the stimulation they get from the whole family. The

language development does not depend on the age,

educational or socioeconomic status of the parents but

the quality time the care givers spend with the child.

The prevalence of 13.7% speech and language delay in

the normal children enlightens the need for earlyscreening programs. Because communication is central

to personal development, social interaction and

learning ability of child, delay in the language and

speech development should be identified as early as

possible. Health workers should make sure that the

babies are growing in a language rich environment and

parents should be educated about it as well.

ACKNOWLEDGEMENT

The authors are very thankful to the Department andManagement of Dr SMCSI Medical College for their

generous support and encouragement during the period

of study. The authors also acknowledge Mr Sanu

Johnson for computer work and Mrs Deepa S Mony

for her contribution in data collection.

REFERENCES

1. Elizabeth B Hurlock. Child Development. 6thEdition, Tata McGraw Hill Publishers: 1942;135-

49

2. Backer l, Cantwell D. A prospective psychiatric

follow up of children with speech/language

disorder. Journal of the American Academy of

child and Adoslescent psychiatry.1987; 26 :546-53

3. Prizant B. Communication disorders and

emotional /behavioural disorders in children.

Journal of Speech and Hearing

Disorders.1990;55:179-924. Barnett W, Escobar C. Economic costs and

benefits of early intervention, Hand book of early

childhood Intervention,3rd

Edn, In SJ Meisels & J

P Shoukoff:1990; 560-82

5. Kavitha SR, Nair MKC. Validation of LEST (1-2

years) against REELS Language Evaluation Scale

Trivandrum (1-2 Research Form 2006) Against

Receptive Expressive Emergent Language Scale.

Teens .2006; 1(2):29-31

6. Sushama Bai S. History taking. Clinical

Evaluation of New borns, Infants and Children 2nd

Edition. Jaypee Brothers Medical Publishers.

2009; Chapter 3:13

7. MKC Nair ,GS Harikumaran Nair, AO Mini, S

Indulekha,S Letha and PS Russel.Development

and Validation of Language Evaluation Scale

Trivandrum for Children Aged 0-3 years - lest (0-

3). Indian Pediatr. 2013;50:463-67

8. James Law, James Boyle. Francis Harris.

Prevelance and natural history of primary and

language delay: findings from a systematic review

of literature. Int J Lang Comm Dis. 2000;35(2):

169-72

9. Burden V, Stott CM, Forge J, Goodyer I. The

Cambridge Language and Speech Project

(CLASP): I. Detection of language difficulties at

36 to 39 months. Dev Med Child Neurol.

1996;38:613 – 31

10. Silva PA, Williams SM, McGee R. A longitudinal

study of children with developmental language

delay at age three: later intelligence, reading andbehaviour problems. Developmental Medicine and

Child Neurology. 1987;29:630 – 40



103


11. Beitchman JH, Nair R, Clegg M. Prevalence of

psychiatric disorders in children with speech and

language disorders. J Am Acad Child Adolesc

Psychiatry 1986; 25: 528-35

12. Stevenson J. Developmental changes in the

mechanisms linking language disabilities and

behaviour disorders. In JH Beitchman, Cohen NJ,

Konstantareas MM, Tannock R. Language,

Learning and Behavior Disorders: Developmental,

Biological and Clinical Perspectives Cambridge

University Press;1996;5th

edition:234-45

13. Tomblin JB, Smith E, Zhang X. Epidemiology of

specific language impairment: prenatal and peri-

natal risk factors. Journal of Communication

Disorders.1997;30:325 – 44

14. Choudhury N, Benasich AA. A family aggregation

study: the influence of family history and other

risk factors on language development. J Speech

Lang Hear Res. 2003;46:261 – 72

15. Brookhouser PE, Hixson PK, Matkin ND. Early

childhood language delay: the otolaryngologist’s

perspective. Laryngoscope. 1979;89:1898 – 13

16. Nelson HD, Peggy Nygrien, Miranda Walker, Rita

Panoscha. Screening for speech and language

delay in preschool children: systematic evidence

review for the US Preventive Services Task Force.

Pediatrics. 2006;117(2):301-02

17. Campbell TF, Dollaghan CA, Rockette HE. Risk

factors for speech delay of unknown origin in 3-

year-old children. Child Dev. 2003;74:346 – 57

18. Tallal P, Ross R, Curtiss S. Familial aggregation

in specific language impairment. J Speech Hear

Disord. 1989;54:167 – 73



104

Vittal et al., Int J Med Res Health Sci. 2014;3(1):104-109


&

Health Sciences




stDec 2013

Research article

URIC ACID AND HYPERTENSION: DOES URIC ACID LICK THE JOINTS AND BITES THE HEART?

* Vittal BG1, Bhaskara K

2, Naveenkumar GH

3

1Associate Professor of Biochemistry,

2Associate Professor of Orthopaedics,

3Assistant Professor of Community

Medicine, Bidar Institute of Medical Sciences, Bidar, Karnataka, India


ABSTRACT

Background: Uric acid a metabolic end product of purine degradation is implicated in gout as aetiology. Its

increased levels have also been associated with hypertension, cardiovascular morbidity and mortality. Few studies

have been conducted, especially in India to elucidate association of uric acid with prehypertension.

Aims: This study intends to assess the association of serum uric acid levels with blood pressure in normotensive,

prehypertensive and hypertensive population. It also intends to check whether there is an incremental rise of serum

uric acid with increasing blood pressure. Material and methods: Two hundred outpatients who met inclusion and

exclusion criteria and consented formed study population. Blood pressure of each participant was measured

followed by venipuncture to collect venous blood for measurement of serum uric acid. Participants were categorised

into 4 groups as Normal, Prehypertension, Hypertension – Stage 1, Hypertension Stage -2 as per Joint National

Committee 7 classification. Data was analysed to know levels of serum uric acid among the four categories and to

verify association of uric acid with blood pressure. Results and Conclusions: Stepwise increase in serum uric acid

levels was observed along with increasing blood pressure. Strong positive linear correlation was observed between

serum uric acid levels and mean blood pressure (Pearson’s correlation coefficient r = 0.74; p< 0.0001 ). Uric acid

was associated (r = 0.442) with blood pressure in prehypertension population. Serum uric acid levels are associated

with prehypertension and hypertension and are independent and strong predictors of cardiovascular mortality.

Keywords: Blood pressure, Prehypertension, Uric acid.

INTRODUCTION

Uric acid is an end product of purine degradation in

humans and is primarily excreted through urine.

Serum uric acid levels are regulated by dietary purine

intake, endogenous metabolism of purines, and its

urinary excretion rate. In the process of evolution 15

million years ago, two mutations rendered uricase

gene non-functional in humans and great apes.

Consequently uric acid is not converted to readily

water soluble and easily excreted product allantoin,

thus resulting in higher serum uric acid levels inhumans and great apes.1

As early as in 1848 AD, Sir Alfred Garrod

demonstrated that Gout, an inflammatory disease of

joints was associated with Hyperuricemia i.e,

increased levels of serum uric acid (>7mg/dl in males

and >6mg/dl in females).2

Gout is a disease of joints

characterised by the deposition of monosodium urate

crystals in joint space causing inflammation and

painful joints.

A few years later, in 1874 AD, Frederick Mohamed

postulated for the first time that “People with high blood pressure belong to gouty families” suggesting

DOI: 10.5958/j.2319-5886.3.1.021



105


the possible association of Hyperuricemia with high

blood pressure.3

Association of elevated serum uric acid with

hypertension was further reported by many

researchers. At the end of the 19th century many

studies demonstrated that uric acid was also associated

with cardiovascular morbidity. However, lack of

possible mechanism by which hypertension and uric

acid are associated led to conclusion that uric acid is

not a true risk factor for cardiovascular disease.4-9

Amidst contradicting reports, Mohamed’s hypothesis

that uric acid has a causative role in hypertension

remains controversial even after over 130 years.

Recent animal studies and clinical observations

indicate the possible direct causal role of uric acid in

pathogenesis of hypertension by various

mechanisms.10 Of late, increasing evidence is being

gathered suggestive of association and causal role of

uric acid in hypertension and cardiovascular

morbidity.11

Hitherto studies conducted have not assessed the

association of serum uric acid levels blood pressure in

prehypertensives and its incremental rise with

increasing blood pressure. So in this study we intend

to assess the association of serum uric acid levels with

blood pressure in normotensive, prehypertensive and

hypertensive participants. We also intend to check

whether there is an incremental rise of serum uric acid

with increasing blood pressure.


Our study was conducted at Regional Diagnostic

Laboratory of District Hospital, Bidar, a teaching

hospital affiliated to the Bidar Institute of Medical

Sciences, Karnataka, India. Study spanned over a

period of 3 months from August to October 2013.

Institutional Ethical committee approval was takenbefore commencement of study and our procedures

were in accordance with the Helsinki Declaration of

1975, as revised in 2000.12

The subjects for this prospective study were

outpatients who visited regional diagnostic laboratory

for routine investigations. Two hundred participants

(103 men and 97 women) of age group 20 to 60 years

formed the study population.

Subjects who fulfilled below mentioned inclusion and

exclusion criteria were informed and explained aboutthe study and after their informed written consent were

included in the study.

Inclusion and exclusion criteria: Paediatric and

psychiatric patients, pregnant women, diagnosed cases

of essential secondary hypertension, medications like

uricosuric drugs and antihypertensive drugs were

excluded in the study.

Study participants were made to sit comfortably on a

chair for five minutes. Systolic and diastolic blood

pressures were measured twice by auscultatory method

with a mercury sphygmomanometer (cuff size, 12.5 x

40 cm) on the right arm. The first and fifth phases of

Korotkoff’s sounds were taken as the criteria for SBP

and DBP respectively. The mean of two consecutive

readings was recorded and used for analysis.13

Mean

of systolic and diastolic blood pressure was calculated

(SBP+DBP/2) and noted as mean blood pressure.

As per Joint National Committee (JNC)7

classification

of blood pressure, Participants were categorised as

normal if systolic blood pressure (SBP) was <120mm

of Hg and Diastolic blood pressure (DBP) was <80mm

of Hg; prehypertensive if SBP/DBP is 120-139/or 80-

89 mm of Hg; Stage 1 Hypertensive if SBP/DBP is

140-159/or 90-99mm of Hg and were categorised as

Stage 2 hypertensives if SBP/DBP is ≥160/or ≥100

mm of Hg.14

Under aseptic precautions, venipuncture was

performed on median cubital vein and 2ml of blood

was collected into a sterile evacuated plastic tube with

red stopper with no additives. Blood samples were

allowed to clot at room temperature for 30 minutes.

Samples were centrifuged at 1500g for 15 minutes for

serum separation.15

Serum uric acid levels were measured by modified

Trinder’s method16, 17

using ERBA XL 300 fully

automated analyser. To ensure quality, daily internal

quality control samples were run and day to day

coefficient of variance (CV) was <5%. The laboratory

also had an external quality assurance programme inplace.

Statistical Analysis: Statistical analysis of participant

data was performed using “IBM SPSS Statistics 20”

software. The data was analysed to measure age-sex

distribution of participants, to categorise participants

as normal, prehypertension, Stage-1 hypertension and

stage-2 hypertension along with their mean blood

pressures and mean serum uric acid levels. Pearson’s

correlation coefficient was calculated to elucidate the

statistically significant association between serum uricacid levels and blood pressure.

18



106


RESULTS

Characteristics of study population: The demographic

characteristics of the study population are summarised

in table 1. Study population comprised of 200

participants of whom 103 were men and 97 were

women..

Table: 1. Age sex distribution of study population

with mean blood pressure

Age

(years)

Number

of Males

Number

of females

Blood pressure*

(mm of Hg)

20 - 30 35 44 98.08 ± 9.09

31 - 40 14 14 101.96 ± 13.13

41 - 50 17 15 107.21 ± 14.27

51 - 60 37 24 112.23 ± 12.69

* mean ± standard deviation

Mean age of the study population was 40.06±13.8

years and mean age of males and females was 41.98 ±

13.48 years and 38.03 ± 13.91 years respectively. The

mean blood pressure of study population showed an

increasing trend with age

The prevalence of undiagnosed hypertension in

population was 22% (n = 44) and of undiagnosed

prehypertension was 42% (n = 84), put together

comprising nearly 65% of study population. A

stepwise increase in serum uric acid levels was

observed when study population was categorised into

four groups namely, Normal, Prehypertension,

Hypertension stage-1, Hypertension stage-2 based on

the JNC 7 classification of blood pressure. Similar

increasing trend in mean serum uric acid level was

observed along with mean blood pressure of the study

population. (Table-2)

Table: 2. Serum uric acid and blood pressure in normotensives, prehypertensives and hypertensives

JNC 7 BP classification14

(SBP/DBP mm of Hg)Males Females

Serum Uric acid*

(mg/dl)

Blood Pressure* (mm

of Hg)

Normal

(<120/ and <80)30 42 5.09 ± 0.65 92.95 ± 4.7

Prehypertension

(120-139/ or 80-89)47 37 5.70 ± 0.73 104.08 ± 5.21

Hypertension Stage-1

(140-159/ or 90-99)

18 14 6.81 ± 0.77 119 ± 6.94

Hypertension Stage-2

(≥160/ or ≥ 100)8 4 7.59 ± 0.57 136.41 ±6.86

* mean ± standard deviation

Statistically highly significant (p<0.0001) difference in

mean serum uric acid was observed between normal

and prehypertension categories; and also between

prehypertension and hypertension stage-1 JNC 7

categories. Similar but less profound, statistically

significant difference (<0.01) was noted between

Stage-1 and Stage-2 hypertension categories.A strong positive linear correlation was observed

between serum uric acid levels and mean blood

pressure (Pearson’s correlation coefficient r = 0.74).

Correlation is highly significant at the 0.05 level (2-

tailed) and the P-value is < 0.0001. (Figure 1). Similar

correlation was also noted between serum uric acid

and systolic blood pressure (r = 0.746) and diastolic

blood pressure (r = 0.609). Uric acid was associated

strongly (r = 0.442) with blood pressure in the

prehypertension population while a weak correlation (r= 0.113) was observed in normal population.

Fig 1: Scatter diagram showing correlation of

serum uric acid levels with mean blood pressure.

DISCUSSION

Our prospective study consisting of 200 participants

showed an association of serum uric acid with bloodpressure in apparently healthy individuals,

undiagnosed prehypertensive subjects and



107


hypertensive individuals. This is the first study

conducted in India to elucidate the association of

serum uric acid levels with blood pressure in

prehypertensive population.

Study population comprised of adult individuals from

20 years to 60 years. Mean age of the study population

was 40.06±13.8 years comparable to other similar

studies that had a mean age of 42.3±0.2 years19 and

41.6 years.20

Although known hypertensive patients were excluded

from the study, 22% (n = 44) of participants were

hypertensivses and 42% (n = 84) were

prehypertensives. Similar prevalence of

prehypertension (39%) among adults in India21

and

Unitesd states of America22

was reported by separate

researchers. It is noteworthy that, a large percentage of

the population who are at risk of developing

hypertension (42%) and undiagnosed hypertensives

(22%) who may develop cardiovascular morbidity go

unnoticed.

Serum uric acid levels were positively (r = 0.740) and

significantly (p < 0.0001) associated with blood

pressure in our study. A similar positive and

statistically significant correlation was observed by

other researchers.19, 20, 22, 23

A stepwise incremental rise of serum uric acid was

observed with increasing blood pressure when

participants were categorised as per JNC7

classification as normal, prehypertension, hypertension

stage-1, and hypertension stage-2. A similar

incremental increase of uric acid was observed in a

cross sectional study conducted in Japan. However this

study categorised the participants based on Japanese

society guidelines JSH-2009 rather than JNC 7

classification.19

A similar association (r = 0.15; p < 0.001) was

demonstrated by a study on large prospective malecohort. They also demonstrated that serum uric acid

was independently related to mortality from

congestive heart failure and stroke.20

Positive association (r = 0.32) of serum uric acid with

prehypertension independent of smoking BMI and

other confounding factors was observed in a study.22

A study demonstrated significant (p < 0.0001)

correlation between uric acid and prehypertension in

adults but the study also noted, unlike our study, that

the association was not statistically significant in olderindividuals over 65 years of age.

23

In a nine year follow-up study, association of serum

uric acid with incident hypertension was observed and

stronger association was noted among blacks.24

PIUMA study, with a cohort of 1720 patients with

follow-up of 12 years noted that, subjects with higher

uric acid levels were at higher risk of developing

cardiovascular events (relative risk 1.73; 95%

confidence interval) than the subjects with lower uric

acid levels.25

A study on 125 children (age group 6-18 years) with

primary hypertension demonstrated the association of

serum uric acid with systolic blood pressure (r = 0.80)

and diastolic blood pressure (r = 0.66).26

Another

study in paediatric age group also observed the

association of serum uric acid levels with ambulatory

diastolic blood pressure (r = 0.29; p = 0.0033).27

Serum uric acid has long been associated with

hypertension, the primary aetiology of cardiovascular

morbidity. Several large cohort studies have

demonstrated that serum uric acid was predictive of

mortality due to ischaemic heart diseases in women.28

Few studies demonstrated the independent and

significant association of uric acid with risk of

cardiovascular mortality29

and myocardial infarction.30

It was observed in a study that serum uric acid level

was a strong and independent predictor of

cardiovascular mortality in middle aged men. 31

Increased serum uric acid levels have been associated

with elevated blood pressure and cardiovascular

morbidity and mortality. But the causal role of uric

acid in hypertension and pathogenesis of

cardiovascular events has not been clear.5- 9

Recent studies have elucidated the plausible

mechanisms that explain how elevated uric acid causes

hypertension. Studies on animal models have shown

that increased uric acid levels cause renal

microvascular and tubular interstitial injury. Uric acidalso increases juxtaglomerular renin production and

decreases nitric oxide synthase expression in macula

densa; collectively contributing to blood pressure

elevation.10

CONCLUSION

Serum uric acid levels are associated with

hypertension and are independent and strong

predictors of cardiovascular mortality, myocardialinfarction and coronary artery diseases in both sexes of

different ethnic groups. So it may not an exaggeration



108


to state that “Uric acid licks the joints and bites the

heart”

Limitations of the study: The study population was

drawn from outpatients of a hospital that may not form

a representative sample of the general population.

Confounders like serum creatinine, serum uric acid,serum albumin, history of alcohol intake, and dietary

protein and sodium consumption that alter serum uric

acid and /or blood pressure were not taken into

consideration.

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2. Garrod A. Observations on the blood and urine of

gout, rheumatism and Bright’s disease. Medical

Chirurgical Transactions 1848; 31:83

3. Mohamed F. On chronic Bright’s disease, and its

essential symptoms. Lancet 1879; 1:399 – 401.

4. Heinig M, Johnson RJ. Role of uric acid in

hypertension, renal disease, and metabolic

syndrome. Cleve Clin J Med. 2006; 73 (12): 1059-

64

5. Kanbay M, Solak Y, Dogan E, Lanaspa MA,

Covic A. Uric acid in hypertension and renal

disease: the chicken or the egg? Blood Purif.

2010;30(4):288-95

6. Mazzali M, Kanbay M, Segal MS, Shafiu M, Jalal

D, Feig DI, Johnson RJ. Uric acid and

hypertension: cause or effect? Curr Rheumatol

Rep. 2010;12 (2): 108-17

7. Johnson RJ, Kang DH, Feig D, Kivlighn S,

Kanellis J, Watanabe S, etal., Is there a

pathogenetic role for uric acid in hypertension andcardiovascular and renal disease? Hypertension.

2003; 41 (6): 1183-90.

8. Feig DI, Mazzali M, Kang DH, Nakagawa T, Price

K, Kannelis J, Johnson RJ. Serum uric acid: a risk

factor and a target for treatment? J Am Soc

Nephrol. 2006; 17 (4 Suppl 2): S69-73.

9. Feig DI. The role of uric acid in the pathogenesis

of hypertension in the young. J Clin Hypertens

(Greenwich). 2012 Jun; 14 (6): 346-52.

10. Hwu CM, Lin KH. Uric acid and the developmentof hypertension. Med Sci Monit. 2010; 16 (10):

RA224-30.

11. Johnson RJ, Feig DI, Herrera-Acosta J, Kang DH.

Resurrection of uric acid as a causal risk factor in

essential hypertension. Hypertension. 2005; 45

(1): 18-20.

12. WMA Declaration of Helsinki - Ethical Principles

for Medical Research Involving Human Subjects

accessed from

http://www.wma.net/en/30publications/10policies/

b3/ on 20.12.2013.

13. Pickering TG, Hall JE, Appel LJ, Falkner BE,

Graves J, Hill MN etal., Recommendations for

blood pressure measurement in humans and

experimental animals: part 1: blood pressure

measurement in humans: a statement for

professionals from the Subcommittee of

Professional and Public Education of the

American Heart Association Council on High

Blood Pressure Research. Circulation. 2005;111

(5): 697-716.

14. The Seventh Report of the Joint National

Committee on Prevention, Detection, Evaluation,

and Treatment of High Blood Pressure (JNC 7)

(Internet) (updated 4 December 2013) available

from

http://www.nhlbi.nih.gov/guidelines/hypertension/

jnc7full.pdf

15. CLSI. Collection, Transport, and Processing of

Blood Specimens for Testing Plasma-Based

Coagulation Assays and Molecular Hemostasis

Assays: Approved Guideline. 5th Ed. CLSI

document H21-A5. Wayne, PA: Clinical and

Laboratory Standards Institute; 2008.

16. Trinder P. Determination of blood glucose using

4-amino Phenazone as oxygen acceptor. J Clin

Pathol. 1969 March; 22 (2): 246.

17. Trivedi RC, Rebar L, Berta E, Stong L. New

enzymatic method for serum uric acid at 500 nm.Clin Chem. 1978; 24 (11): 1908-11.

18. Cohen J, Cohen P, West SG, Aiken LS. Applied

Multiple Regression/Correlation Analysis for the

Behavioural Sciences.2003;3rd

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Lawrence Earlbaum Associates.

19. Kansui Y, Ohtsubo T, Goto K, Sakata S, Ichishima

K, Fukuhara M, Ohta Y, Matsumura K.

Association of serum uric acid with blood pressure

in Japanese men. Cross-sectional study in work-

site group. Circ J. 2011;75(12):2827-3220. Strasak A, Ruttmann E, Brant L, Kelleher C,

Klenk J, Concin H, Diem G, Pfeiffer K, Ulmer H;



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VHM&PP Study Group. Serum uric acid and risk

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term study of 83,683 Austrian men. Clin Chem.

2008; 54 (2): 273-84.

21. Gupta R, Deedwania PC, Achari V, Bhansali A,

Gupta BK, Gupta A, Mahanta TG, Asirvatham AJ,

Gupta S, Maheshwari A, Saboo B, Jali MV, Singh

J, Guptha S, Sharma KK. Normotension,

prehypertension, and hypertension in urban

middle-class subjects in India: prevalence,

awareness, treatment, and control. Am J

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adults. J Hypertens. 2007; 25 (8): 1583-9.

23. Liang J, Xue Y, Zou C, Zhang T, Song H, Qi L.

Serum uric acid and prehypertension among

Chinese adults. J Hypertens. 2009; 27 (9): 1761-5.

24. Mellen PB, Bleyer AJ, Erlinger TP, Evans GW,

Nieto FJ, Wagenknecht LE etal., Serum uric acid

predicts incident hypertension in a biethnic cohort:

the atherosclerosis risk in communities study.

Hypertension. 2006 Dec; 48 (6): 1037-42.

25. Verdecchia P, Schillaci G, Reboldi G, Santeusanio

F, Porcellati C, Brunetti P. Relation between

serum uric acid and risk of cardiovascular disease

in essential hypertension. The PIUMA study.

Hypertension. 2000; 36 (6): 1072-78

26. Feig DI, Johnson RJ. Hyperuricemia in childhood

primary hypertension. Hypertension. 2003; 42 (3):

247-52.

27. Jones DP, Richey PA, Alpert BS, Li R. Serum uric

acid and ambulatory blood pressure in children

with primary hypertension. Pediatr Res. 2008; 64

(5): 556-61.

28. Freedman DS, Williamson DF, Gunter EW, Byers

T. Relation of serum uric acid to mortality andischaemic heart disease. The NHANES I

Epidemiologic Follow-up Study. Am J Epidemiol

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29. Fang J, Alderman MH. Serum uric acid and

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30. Bos MJ, Koudstall PJ, Hofman A, Witteman JCM,

Breteler MM. Uric acid is a risk factor for

myocardial infarction and stroke: the RotterdamStudy. Stroke 2006;37:1503 – 7

31. Niskanen LK, Laaksonen DE, Nyyssonen K,

Alfthan G, Lakka HM, Lakka TA, Salonen JT.

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Kapure et al., Int J Med Res Health Sci. 2014;3(1):110-114


&

Health Sciences


ndDec 2013 Revised: 18


ndDec 2013

Research article

STUDY OF PRESCRIBING PATTERN OF ANTIMICROBIAL AGENTS IN AN IPD OF A TERTIARY

CARE HOSPITAL IN AHMEDNAGAR

*Kapure NL, Nayak BB, Raul AR, Vijaykumar AN, Vijayprasad S, Vakade KP, Jadhav AR

Department of Pharmacology, PDVVPF’S Medical College, Ahmednagar, Maharashtra


ABSTRACT

Objectives: To evaluate the pattern of use of Antimicrobial drugs in IPD patients admitted for various illnesses.

Materials and Methods: It is a retrospective and observational study, conducted during the period of January, 2011

to December, 2011. Prescription record of 252 patients admitted in IPD of Medicine & Surgery departments of the

PDVVPFs Medical College & Hospital, Ahmednagar were studied. These data were obtained from Medical Record

Departmeent (MRD) of the hospital. The study was conducted after obtaining permission from the Institutional

Ethics Committee (IEC) of the college. Data were analyzed for- average number of antimicrobials prescribed per

prescription, the relationship between patient age and sex, percentage usage of various antimicrobial groups and

percentage use of individual antimicrobials. Results: It was observed that 75 % of patients were prescribed 1-2

antimicrobial agent and 25 % were prescribed 3 or more than 3 antimicrobials. Cephalosporins were the most

preferred antimicrobials followed by quinolones and aminoglycosides. Fluconazole was found to be most

commonly prescribed antifungal whereas Artesunate and Metronidazole were most preferred antimalarial and

antiamoebic drugs. Conclusion: It can be concluded from the present study that physicians preferred to prescribe 2

or more than 2 antibacterial agents in a prescription. To treat various infections Cephalosporins and quinolones were

observed to be most prescribed antibacterials. Fluconazole, Artesunate & Metronidazole were found to be

commonly prescribed antifungal, antimalarial and antiamoebic agents. Uses of Macrolides, Tetracyclines &

Vancomycin were very low. However, aminoglycosides were commonly prescribed to young males and

Cepahalosporins to young female patients.

Keywords: Drug utilization, Antimicrobial agent, Prescription

INTRODUCTION

As per data by All India Origin Chemists and

Distributors-Advance Working, Action & Correction

Sy s t e m ( AIOCD-AWACS) ma r k e t research firm,

antibiotics therapy rank as the 1st

in all the super

groups in pharmaceutical market with 14.8% growth

in the month of February 2012. It occupies around 19

% in over 60,000 cr market. However they are the

least studied drugs in terms of drug utilization studies.

1

The principal aim of drug utilization research is to

facilitate appropriate use of drugs in patient

populations, minimize the adverse event and drug

interactions leading to better patient outcome. Drug

utilization studies are powerful exploratory tools to

ascertain the role of drugs in the society. They create a

sound sociomedical and health economic basis for

making health care decisions.2

Drug utilization is

defined as marketing, distribution, prescription and the

use of drugs in society, with special emphasis on theresultant medical, social and economic consequences.

3

Often, drugs are not used, keeping in mind their safety

DOI: 10.5958/j.2319-5886.3.1.022



111


and efficacy.4

Rational drug prescribing is the use of

the least number of drugs to obtain the best possible

effect in the shortest period and at a reasonable

cost .5

Irrational prescribing and disparity between the

prescription and the consumption of medicines may

offset the benefits which are demonstrated by

randomized controlled trials on drug efficacy.6-9

The present study was planned to examine the

patterns of drug prescription of Antimicrobials in the

IPD of the internal medicine and surgery in the

PDVVPF’s Medical Co ll eg e Hospital, Ahmednagar

a tertiary care hospital.


Study Design: A retrospective, observational study.

Study Duration: 1 year from 01/01/2011 to

31/12/2011

Study Population: Medical Record (MR) data were

obtained from MRD department; consisting of

prescription records of 252 patients that admitted

in the internal medicine and surgery in the PDVVPF’s

Medical College Hospital, Ahmednagar a tertiary

care hospital in Ahmednagar district.

Procedure: The study was conducted after the

permission from the Institutional Ethics Committee.

Total 327 patients’ data were screened and analyzed

as per the inclusion and exclusion criteria and 252

patients were selected for this study. Patient related

information like age, gender, diagnosis, month of

admission, drug related information like number of

drugs prescribed were collected on a customized

data collection sheet.

Inclusion criteria: All patients who were admitted in

the IPD of the Medicine and Surgery departments and

were prescribed on the antibiotics for various

infections.

Exclusion criteria: Incomplete data.Parameters studied:Following parameters were taken

in the study

1.Average number of antimicrobials prescribed per

prescription.

2.Percentage usage of various antimicrobials

3.Percentage usage of drugs in each antimicrobial

group

4.Frequency of systemic infection at different

months

5.Relationship between patient de mo gr ap hi cs andprescription pattern

Statistical analysis: The data were subjected to

descriptive analysis using Microsoft Excel. Utilization

of different classes of drugs as well as individual drugs

was analyzed and presented as a percentage.

RESULT

The total number of prescriptions analyzed was

252 .The numbers of drugs per prescription varied

from one to more than four (Table-1)

Table 1: Number of antimicrobials per

prescriptions in number and percentage

Number of antimicrobials per

prescriptions

No of pts ( % )

One 112(44.44)

Two 80 (31.74)

Three 36(14.28)

Four or more than four 24( 9.52)

Total no of prescriptions studied 252

Table 2: Percentage usage of drugs in each

antimicrobial group

Drug class Drug (%) of

prescriptions

Cephalosporins Cefuroxime 33.3

Cefotaxime 25.3

Ceftriaxone 6.32

Cefoperazone 1.58

Cefixime 1.58

Cefepime 1.58Quinolones Ciprofloxacin 14.28

Ofloxacin 12.69

Levofloxacin 7.92

Norfloxacin 4.75

Aminoglycosides Amikacin 20.62

Gentamicin 4.75

Streptomycin 3.17

Penicillins Amoxicillin 11.1

Penicillin - V 4.75

Ampicillin 3.17Antifungals Fluconazole 4

Itraconazole 2.7

Ketoconazole 1.3

Antimalarials Artesunate 2

Chloroquine 1.7

Primaquine 0.8

Antiamoebics Metronidazole 13.6

Tinidazole 6.4

Ornidazole 4

Others Macrolides 3.17Tetracyclines 3.17

Vancomycin 1.58



112


Table 3: Frequency of systemic infection in

different months

System

Involved

Highest

frequency

Lowest

frequency

GIT Sep (70%) Feb (15%)

CVS May (85%) Jan (10%)

CNS Feb (50%) July (5%)RS Oct (70%) Jan (10%)

OTHER Aug (60%) March (10%)

Fig 1: Prescribing frequency of antimicrobial group of

drugs

4 40 0 0 0 0 0

1612

20

48

2 3

76

14

28

36

16

04

2

48

12

2016 16

4 3 2

0

10

20

30

40

50

60

70

80

0- 15 16- 30 31- 60 >60

Fig 2: Age-wise prescribing frequency of antimicrobials

in males

0 0 0 0 0 0 0 0

8 86

1 0

43 3

2

8

4

2

6

2 2

4

1

20

8

4

12

6

34

1

0

5

10

15

20

25 0-15

16-30

31-60

>60

Fig 3: Age-wise prescribing frequency of antimicrobial

in females

It was observed that 1, 2, 3 & 4 or >4 Antimicrobials

were prescribed to 44.44%, 31.74%, 14.28% & 9.52%

respectively (Table-1). Among the Antimicrobials

Cephalosporins was found to be prescribed to the

largest number (71.42%) of patients, followed by

Quinolone (39.68%), Aminoglycoside (28.57%),

Antiamoebic (24%), Penicillins (19.04%), Antifungal

(8%), Antimalarial (4.5%) & others were 8% (Fig-1).

Among the cephalosporin’s use of cefuroxime was

highest (33.33%), followed by cefotaxime (25.39%),

ceftriaxone (6.32%), Cefoperazone, Cefixime,

Cefepime each were 1.58% respectively. Among the

fluoroquinolones it was found Ciprofloxacin was

mostly preferred (14.28%), followed Ofloxacin

(12.69%), Levofloxacin (7.9%), Norfloxacin (4.79%).

Amikacin among the Aminoglycosides was the most

chosen drug (20.62%) followed by Gentamicin

(4.75%), streptomycin (3.75%). Among Penicillins

Amoxicillin was used to the extent of 11.1%, followed

by Benzyl Penicillin 4.75% and Ampicillin 3.17%.

Among the oral antifungal drugs Flucanazole was

observed to be the most favoured to the extent of 4 %

followed by Itraconazole 2.7% and Ketoconazole

1.3% . Artesunate was prescribed to 2 %. Chloroquine

1.7 % & Primaquine 0.8% as antimalarials. Among

Antiamoebic drugs Metronidazole was used to the

extent of 13.6% , followed by Tinidazole 6.4% &

Ornidazole 4 % . Macrolides, Tetracyclines,

Vancomycin were used in 3.1%, 3.1% & 1.5%

respectively (Table-2) . Patients admitted due to CVS

disease were observed highest among all the diseases

(85%) in the month of May & lowest in the month of

January (10%). Infections of the nervous system

caused to the extent of 15 % in the February & 5 % in

the July. Other infection were found 60% in August

and the lowest occurrence was in March (10%) (Table-

3). In young male patients Aminoglycisides &Antimalarials were found to be highest & lowest

prescribed drugs respectively whereas Cephalosporins

& Quinolone were highly preferred for younger as

well as older female patients .Younger age male

patients were mostly admitted for the CVS &

endocrine disorders. However in younger & adult

female patients were commonly associated with CVS

& GI disorders. (Fig 2 & 3)

DISCUSSION

The clinical setting in the medical ward wa rr an ts

the use of drugs from various drug classes. Rational

prescription of drugs is essential for better patient

010

20

30

40

50

60

70

80

P E R C E N T A G E



113


care. The first step in any intervention programme to

improve drug utilization is to assess the extent of

existing problem in prescribing. The objective of our

study was to evaluate the drug utilization patterns

among patients admitted to the IPD of a tertiary care

hospital.

The demographic results of patients admitted to the

IPD over a period of 12 months revealed a male

preponderance with a mean age of around 50 years,

similar to a study carried out in Nepal in 2005.10

In

contrast, Smythe et al (1993) showed an equal number

of male and female patients admitted to the hospital

with a mean age of 65 years.11

Previous Indian studies

also documented male predominance which suggests

that more males are admitted in an Indian setting for

infections.

12

The probable reasons for this findingcould be the male to female ratio is higher in the state

of Maharashtra and overall in the India. In the Indian

scenario it is noticed that female populations are

reluctant to utilize health care facilities even if

they are critically ill and especially from lower

socioeconomic strata.

A wide spectrum of clinical diagnoses was observed

including sepsis, renal failure, acute respiratory

distress syndrome, multi organ dysfunction, head

injury, cvs related disorder and diabetes complication.

Debilitating condition of the patients due to underlying

disease, invasive diagnostic and therapeutic

procedures and prolonged utilization of life support

equipment predisposes these patients to infections

It was noticed that most of the antimicrobial agents

were prescribed by brand name (60%) which requires

revision of current prescribing practice. Extensive

polypharmacy (> 90 %) that is more than five drugs

were prescribed in all the patients. Polypharmacy is

defined as concomitant use of five or more drugs and

it could enhance drug interactions and drug related

problems.13

It is difficult to treat patients in the IPD

with multiple co‐morbidities with less number of

drugs as they require drugs for treatment of specific

conditions as well as for prophylaxis, but it is also

essential to keep a balance between the number of

drugs and effective pharmacotherapy.

High antimicrobial prescribing frequency was

observed in our study inconsistent with earlier studies

from Nepal14

which documented 30%. More than one

antimicrobial agent was prescribed among (69%) of

the prescriptions. This could be expected since

Diabetes, multi organ dysfunction, IHD, respiratory

tract infections was prevalent among the patients of

the present study necessitating therapeutic as well as

prophylactic utilization of antimicrobials.

Antimicrobial protocol and guidelines; formulary

based antimicrobial restrictions can be used to

improve rational usage of antimicrobials. A

multidisciplinary approach can be adopted in the ICU

and IPD set up involving intensive care specialist;

infectious disease control s pe c i a l i s t , pharmacists

and microbiologists can work together for more

rational antimicrobial pharmacotherapy.

CONCLUSION

It can be concluded from the present study that

physicians preferred to prescribe 2 or more than 2

antibacterial agents in a prescription. To treat various

infections Cephalosporins and quinolones were

observed to be most prescribed antibacterials.

Fluconazole, Artesunate & Metronidazole were found

to be commonly prescribed antifungal, antimalarial

and antiamoebic agents. Use of Macrolides,

Tetracyclines & Vancomycin was very low. However,

aminoglycosides were commonly prescribed to young

males and Cepahalosporins to young female patients.

In conclusion, a wide spectrum of clinical diagnosis

and a variety of drugs were utilized for various drug

classes. Overall, the scope for improving rational use

of antimicrobial agents exists. Antibiotic resistance is

increasing at an alarming rate leading to increasing

morbidity, mortality and treatment cost. A key factor

in the development of an antibiotic resistance is

inappropriate use of antibiotics. The medical

fraternity needs to understand that antibiotics are

precious and finite resources, and unless conscious

efforts are made to contain the problem of drug

resistance, multidrug resistant organism untreatable

by ever known antibiotic may emerge reversing themedical progress by ranking and returning as back to

pre-antibiotic. Pharmacoeconomic studies in the

hospital can encourage cost effective antimicrobial

drug therapy. This will help in rationalizing

prescribing practices based on the feedback from these

studies and practices between institutions, regions and

countries can be compared.

REFERENCES

1. Mukherjee R. Antidiabetic drugs post highest

growth in Feb. Times o f I nd ia . Mumbai

edition. 5th

April 2012: 36.



114


2. Bakssas I, Lunde PKM. National drug policies;

the need for drug utilization studies. Trends

Pharmacolo Sci 1986; 7: 331.

3. WHO, The selection of essential drugs. WHO

technical report 1977; 615: 36.

4. Lunde PKM, Levy M. Drug utilization –

geographical d ifferences and clinical implications.

Introductory remarks. In: Duchene-Marullaz, P,

ED. Advances in pharmacology and

therapeutics. Oxford, Pergamon Press 1978;6:79-

82.

5. Gross F. Drug utilization therapy and practice.

The present situation in the Federal Republic of

Germany. Eur J Clin Pharmacol 1981; 19:387-94.

6. Cochrane AL. Effectiveness and efficiency –

Random reflections on health services. London, the

Nuffield Provincial Hospitals Trust,1982.

7. Stolley PD, Lasagna L. Prescribing patterns of

physicians. Journal of chronic diseases 1969;

22:395-405.

8. Westerholm B. Therapeutic auditing at the national

and international levels. Br J Clin Pharmacol,

1986;22:55S-9S.

9. Pullar T, Kumar S, Tindall H, Freely M. Time to

stop counting the tablets? Clin Pharmacol Ther

1989;46:163-8

10. Srishyla MV, Krishnamurthy M, Nagarani MA.

Prescription audit in an Indian hospital setting

using the DDD (Defined Daily Dose) concept.

Indian J Pharmacol 1994; 26:23‐8.

11. Smythe MA, Melendy S, Jahns B. An exploratory

analysis of medication utilization in a medical

intensive care unit. Crit Care MED 1993; 21 (9):

319‐23.

12. Biswal S, Mishra P, Malhotra S. Drug utilization

pattern in the intensive care unit of a tertiary care

hospital. J Clin Pharmacol 2006; 46:945‐51.

13. Viktil KK, Blix HS, Moger TA. Polypharmacy as

commonly defined is an indicator value in the

assessment of drug‐related problems. Br J Clin

Pharmacol 2007; 63(2):187‐95.

14. Shankar PR, Partha P, Dubey AK. Intensive care

unit drug utilization in a teaching hospital in

Nepal. Kathmandu Univ Med J 2005;

3(10):130‐7.



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Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119


&

Health Sciences




thDec 2013

Research article

MORPHOMETRIC STUDY OF THE SACRAL HIATUS IN NIGERIAN DRY HUMAN SACRAL BONES

*Ukoha Ukoha U1, Okafor Joseph I

2, Anyabolu Arthur E

1, Ndukwe Godwin U

3, Eteudo Albert N

4,

Okwudiba Nchedo J2

1Department of Anatomy, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria.

2Department of Anatomy, Anambra State University, Uli, Nigeria.

3Department of Anatomy, Ebonyi State University, Abakaliki, Nigeria.4Department of Anatomy, College of Medicine and Health Sciences, Abia State University, Uturu, Nigeria.


ABSTRACT

Background: The sacrum is a large triangular bone formed by the fusion of the five sacral vertebrae and forms the

caudal region of the vertebral column. Aims: This was aimed at studying the morphometry of the sacral hiatus

noting its anatomical variations that is useful in caudal epidural anaesthesia. Materials and Methods: Eighty three

intact adult sacra of unknown sex were measured with vernier callipers and the various shapes of the sacral hiatus

were also noted. Results: The findings revealed that inverted U (48.2%) was the most predominant shape; followedby inverted V (34.9%), dumbbell (4.8%), bifid (4.8%) and irregular (4.8%). The mean anteroposterior diameter at

the apex was 5.52 ± 1.89mm. The mean length of the sacral hiatus was 20.05 ± 9.22mm and the transverse width at

base of hiatus was 12.35 ± 3.12mm. There was complete spina bifida in 1.2% and absence of sacral hiatus in

another 1.2%. Conclusion: The knowledge of anatomical variations of sacral hiatus is important in the

administration of caudal epidural anaesthesia in the studied population and may help to reduce its failure rate.

Keywords: Sacral hiatus, caudal epidural block (CEB), sacral vertebra.

INTRODUCTION

The sacrum is a large triangular bone formed by the

fusion of five sacral vertebrae and it also forms the

caudal region of the vertebral column. It forms the

posterosuperior wall of the pelvic cavity, wedged

between the innominate bones.1

Due to its great size,

the sacrum is usually the last bone of a buried body to

rot. The ancients may thus have believed the sacrum to

be the focal point, around which the body could be

reassembled in the after-life.1

The opening at the

caudal end of the sacral canal is the sacral hiatus

formed due to failure of fusion of laminae of the fifth

(occasionally 4th) sacral vertebrae.The sacral hiatus is an inverted V-shaped space

located at the distal part of the sacrum. This space is

formed by incomplete midline fusion of the posterior

elements of the distal portion of the fifth or sometimes,

the fourth sacral vertebra. The sacral hiatus is covered

posteriorly by the posterior aspect of the

sacrococcygeal membrane and is an important

landmark in caudal epidural block.2

Sacral approach to epidural space is used for giving

analgesics and anaesthesia for a variety of operations.

Caudal epidural block (CEB) has been widely used for

the treatment of lumbar spinal disorders, management

of chronic back pain, in obstetrics,3

and orthopaedic

practice.4

The technique of CEB depends uponaccurate localization of sacral hiatus through which

access to sacral epidural space is gained. Some authors

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116


have reported that one of the anatomic reasons of

caudal epidural anaesthesia failure is the absence of

sacral hiatus. One of the important key factors for

successful caudal epidural anaesthesia may be clear

understanding of the normal anatomy of sacral hiatus

and surrounding structures.4

Sacral hiatus exhibits variations in morphology which

differ among populations and the reliability and

success of epidural anaesthesia depend upon these

anatomical variations. These variations have not been

well documented in the Nigerian population, hence

this study is meant to address this.


The study was conducted on 83 intact adult dry human

sacra obtained from various Anatomy museums in the

South-East and South-South zones of Nigeria. Bones

of undetermined age and gender were used. They were

preserved in dry conditions free from moisture, dust,

insects or moths. Direct measurements were taken

with vernier callipers (God Marc Tools, Japan;

accurate to 0.02mm).

The parameters studied were the following:

i. Shapes of the sacral hiatus.

ii. Level of apex with respect to the sacral

vertebrae.

iii. Level of base with respect to the sacral

vertebrae.

iv. The length of the sacral hiatus measured from

the apex to the midpoint of the base.

v. The anteroposterior diameter – at the apex.

vi. The transverse width at the base measured

between the inner aspects of the inferior limits

of sacral cornua.

Only sacra with complete sacral hiatus were used for

the study and damaged, mutilated and deformed sacra

were excluded.

Data Analysis: Data were expressed as mean and

standard deviation for continuous variables, and

percentage for categorical variables. Comparative

analysis was done using Analysis of variance

(ANOVA). The statistical software used was SPSS

Version 16.0.

RESULTS

Table 1: Frequency distribution of the shape of sacral hiatus

Shape of Sacral Hiatus Frequency Percentage

Absent 1 1.2Bifid 4 4.8

Complete spina bifida 1 1.2

Dumbbell 4 4.8

Inverted U 40 48.2

Inverted V 29 34.9

Irregular 4 4.8

Total 83 100

Table 2: Frequency distribution of the level of apex with respect to the sacral vertebrae.

Level of apex with respect to the sacral vertebrae Frequency Percentage

None 2 2.4S2 2 2.4

S3 17 20.5

S4 58 69.9

S5 4 4.8

Total 83 100

Table 3: Frequency distribution of the level of base with respect to the sacral vertebrae

Level of base with respect to the sacral vertebrae Frequency Percentage

None 2 2.4

Coccyx 6 7.2

S4 2 2.4

S5 73 88



117


Total 83 100

Table 4: The length, transverse width and anteroposterior diameter of the sacral hiatus

Variables Mean±SD Median Range

Length (mm) 20.05 ± 9.22 20.50 6.10 – 57.0

Transverse Width (mm) 12.35 ± 3.12 13.00 5.0 – 20.50

Anteroposterior Diameter (mm) 5.52 ± 1.89 5.10 0.40 – 11.10

Table 5: Mean and standard deviation of the length, transverse width and anteroposterior diameter according to the

shape of sacral hiatus

Shape of Sacral Hiatus Length (mm) Transverse

Width (mm)

Anteroposterior

Diameter (mm)

Bifid 11.03 ± 2.48 11.03 ± 2.48 4.60 ± 1.73

Dumbbell 13.50 ± 1.08 13.50 ± 1.08 4.78 ± 0.52

Inverted U 22.17 ± 8.42 12.45 ± 2.80 5.26 ± 1.83

Inverted V 20.91 ± 9.88 12.81 ± 3.52 6.07 ± 2.06

Irregular 8.20 ± 2.51 8.20 ± 2.51 5.80 ± 1.70Data are expressed as means and standard deviations.

Table 6: Mean and standard deviation of the length, transverse width and anteroposterior diameter of sacral hiatus

according to the level of apex with respect to the sacral vertebrae

Level of apex with respect to

sacral vertebrae

Length (mm) Transverse

Width (mm)

Anteroposterior

Diameter (mm)

S2 49.55 ± 10.54 14.05 ± 1.34 8.60 ± 3.54

S3 26.59 ± 8.27 12.35 ± 2.55 5.43 ± 1.85

S4 17.81 ± 6.52 11.99 ± 3.05 5.42 ± 1.82

S5 10.0 ± 1.15 16.78 ± 4.25 5.78 ± 1.71

Data are expressed as means and standard deviations.

Table 7: Mean and standard deviation of the length, transverse width and anteroposterior diameter of the sacral hiatus

according to the level of base with respect to the sacral vertebrae

Level of base with respect to

sacral vertebrae

Length (mm) Transverse

Width (mm)

Anteroposterior

Diameter (mm)

S4 28.0 ± 4.24 15.0 ± 2.83 6.50 ± 2.12

S5 19.48 ± 9.24 12.18 ± 3.14 5.44 ± 1.90

Coccyx 24.35 ± 8.64 13.57 ± 2.80 6.18 ± 1.82

Data are expressed as means and standard deviations.

DISCUSSION

The detailed morphometric study of sacral hiatus is of

great relevance, since this route is frequently utilized

for caudal epidural anaesthesia in perineal surgery, and

caudal analgesia for painless delivery. Edward and

Hingson in 1942 for the first time took advantage of

this natural gap in the lower end of the sacral canal for

continuous caudal analgesia during labour.3

Since

then, the sacral hiatus has been an important landmark

in caudal epidural block. However, failures have often

been encountered in caudal epidural block owing to

anatomical variations in the sacral hiatus. In 1999,

Tsui et al reported that the failure rate was about 25%.5

Shape

Table 1 showed the frequencies of the various shapes

of sacral hiatus in the study population. The inverted U

shape (48.2%) was most dominant, followed by the

inverted V shape (34.90%), both of which were

considered normal. The results were similar to studies

by Seema et al6

and Shewale et al.7

In a study by

Vijisha and Baskaran,8

the inverted U and inverted V

had equal frequencies of 35% each. The abnormal

shapes constituted 15.6% and 1.2% were absent.

Comparison with studies by other authors (



118


Table 8) showed similarities in the normal shapes, but

the present study had lower frequencies in the

abnormal shapes. Only the population under study

presented with a bifid sacral hiatus.

Level of Apex

The level of apex of sacral hiatus in relation to sacral

vertebrae in the study population is shown in Table 2.

It was quite variable and extended between the middle

of S2 and mid-S5. The S4 vertebra (69.9%) was the

most dominant level. In 2.4%, the wall was open. The

results of the present study in comparison (Table 9)

agreed with studies by Ramamurthi and Anil9

and

Seema et al6

as well as standard Anatomy textbooks.1

Level of Base

In the study population, Table 3 showed the various

levels of base with respect to the sacral vertebrae. The

most dominant level was the S5 (88%) vertebra. In

2.4% of the sacra, the sacral hiatus was completely

obliterated and the lower end of the canal was closed

due to bony undergrowth. Comparison with other

studies supported the fact that the level of base was at

the S5 vertebra in most of the population (Table 10).

Length, transverse width and anteroposterior diameter

at apex

The results are shown in Table 4. The mean length and

mean transverse width were 20.05mm and 12.35mm

respectively. The anteroposterior diameter at apex of

sacral hiatus is important as it should be sufficiently

large to admit a needle, and varying diameters could

cause subcutaneous deposition of anaesthetic drug. In

the present study, mean anteroposterior diameter was

5.52mm.

Table 5 showed the mean length, transverse width and

anteroposterior diameter of the sacral hiatus according

to its shape. Analysis of variance (ANOVA) indicated

significant variations in length (F = 4.32; P = 0.003)

among the different shapes. On the other hand, no

significant differences were observed in transverse

width (F = 2.41; P = 0.057) and in the anteroposterior

diameters (F = 1.22; P = 0.309) of the various shapes.

The mean length, transverse width and anteroposterior

diameter of sacral hiatus according to the level of apex

is seen in Table 6. Analysis of variance (ANOVA)

showed significant variations in length (F = 22.37; P =

0.000) and transverse width (F = 3.42; P = 0.021)

among the different levels. No significant difference

(F = 1.93; P = 0.132) was observed in the

anteroposterior diameter of the various levels.

In

Table 7, the mean length, transverse width and

anteroposterior diameter of the sacral hiatus according

to the level of base is determined. Analysis of variance

(ANOVA) indicated no significant variations in length

(F = 1.56; P = 0.217), transverse width (F = 1.29; P =

0.280) and the anteroposterior diameter (F = 0.70; P =

0.498) among the different levels.

Table 8: Incidence of various shapes of sacral hiatus in dry human sacral bones by various authors

Shape Seema et al (2013) Shewale et al (2013) Anil et al (2013) Current Study (2013)

Inverted U 42.95% 40.69% 31% 48.20%

Inverted V 27.52% 32.35% 25.80% 34.90%

Irregular 16.11% 9.31% 20.60% 4.8%

Dumbbell 13.42% 5.89% 5% 4.8%

Bifid - - - 4.8%Complete

spina bifida

- 0.98% - 1.2%

Elongated - 9.31% 17.20% -

Absent - 0.98% - 1.2%Table 9: Incidence of level of apex of sacral hiatus in dry human sacral bones recorded by various authors

Level Anil et al (2013) Seema et al (2013) Shewale et al (2013) Current Study (2013)

S2 7.76% 4.03% 4% 2.40%

S3 41.38% 35.57% 15% 20.50%

S4 50.86% 56.37% 66.50% 69.90%

S5 - 4.03% 14.50% 4.80%

Table 10: Incidence of level of base of sacral hiatus in dry human sacral bones reported by various authorsLevel Anil et al (2013) Seema et al (2013) Shewale et al (2013) Current Study (2013)

S4 18.97% 13.42% 2% 2.4%



119


S5 72.41% 70.47% 82% 88%

Coccyx 8.62% 16.11% 16% 7.2%

CONCLUSION

Information obtained from studies on anatomical

variations of the sacral hiatus is important in caudal

epidural block (CEB). In the present study, 83 dryhuman sacra were studied and the irregular, bifid and

dumbbell shapes were 4.8% each. The sacral hiatus

was completely absent in 1.2% and 1.2% had spina

bifida, bringing the total rate of sacral hiatus

abnormalities to 16.9%. The rate should be kept in

mind when administering caudal epidural anaesthesia

in the Nigerian population.

REFERENCES

1. Williams PL (ed). Gray’s Anatomy, 38th edition,Churchill Livingstone, 2000; 592-31, 673-74.

2. http://www.MedicineNet.com. The Sacrum The

Holy Bone, 2003. Accessed 15th June, 2013.

3. Senoglu N, Senoglu M, Oksuz H, Gumusalan Y,

Yuksel KZ, Zencirci B et al. Landmarks of the

hiatus for caudal epidural block: An anatomical

study. British Journal of Anaesthesia. 2005; 95

(5):692- 695.

4. Edwards WB, Hingson RA. Continuous caudal

anesthesia in obstetrics. American Journal of surgery. 1942; 57:459-464.

5. Sekiguchi M, Yabuki S, Satoh K, Kikuchi S. An

Anatomic study of the sacral Hiatus: A Basis for

successful caudal epidural Block. Clinical Journal

of Pain. 2004; 20(1): 51-54.

6. Tsui BC, Tarkkila P, Gupta S, Kearney R.

Confirmation of caudal needle placement using

nerve stimulation. Anaesth Analg 1999; 91:374-8.

7. Seema, Singh M, Mahajan A. An anatomical study

of variations of sacral hiatus in sacra of North

Indian origin and its clinical significance. Int. J.

Morphol., 2013; 31(1):110-114.

8. Shewale SN, Laeeque M, Kulkarni PR, Diwan

CV. Morphological and Morphometrical Study of

Sacral Hiatus. International Journal of Recent

Trends in Science And Technology. 2013;

6(1):48-52.

9. Vijisha P, Baskaran S. Morphometrical analysis of

sacral hiatus and its clinical significance. The

Health Agenda, 2013; 1(1): 10-14.

10. Ramamurthi KS, Anil KR. Anatomical study of

sacral hiatus for successful caudal epidural block.

Int J Med Res Health Sci, 2013; 2(3):496-500



120

Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127


&

Health Sciences




thDec 2013

Research article

COMPARISON OF HEMATOLOGICAL PARAMETERS BETWEEN PLASMODIUM FALCIPARUM,

PLASMODIUM VIVAX AND CONTROL GROUP

*Ashis Kumar Saha1, Somnath Maitra2, Subhas Chandra Hazra3

1Assistant Professor, 2Senior Resident, 3Professor and Head, Department of General Medicine, K P C Medical

College & Hospital, Kolkata, India


ABSTRACT

Aims: Malaria, a morbid disease of Tropical countries, may harmful if it cannot be diagnosed at its early phase, by

observing the changes in hematological parameters. Our aim was to compare the hematological parameters between

Plasmodium falciparum and vivax in relation to control healthy group in West Bengal. Methods and materials: In

total 238 slide or dual antigen positive patients (120= Plasmodium vivax, 118=plasmodium falciparum) clinical

hematological, renal parameters were compared. Results: In Plasmodium vivax and falciparum, male to female

ratio was 3:1 and 1.3:1 respectively. Significant elevation in erythrocyte sedimentation rate (ESR),differential

lymphocyte count, creatinine and significant lowering of platelet count, fasting blood sugar (FBS) were observed in

plasmodium vivax group, whereas, significant elevation of hemoglobin, differential monocyte count, meancorpuscular hemoglobin concentration were seen in plasmodium falciparum group. Haemoglobin and FBS were

significantly lower, whereas, ESR, creatinine, differential monocyte count were high in vivax group, total white

blood cell and platelet count, hematocrit were low in both Plasmodium infection and mean corpuscular hemoglobin,

differential lymphocyte count were significantly low in falciparum group as compared to control group.

Conclusion: Combination of low hemoglobin, fasting blood sugar and significantly raised ESR is highly significant

in predicting severity of Plasmodium infection in patients of malaria endemic areas, which was evidenced in our

present study. P. falciparum and vivax suffered from lymphopenia and thrombocytopenia respectively.

Keywords: Hematological parameters, Plasmodium falciparum, Plasmodium vivax, West Bengal

INTRODUCTION

Malaria, a morbid disease of Tropical countries, like,

India, Pakistan, Bangladesh, is now of global

importance; because, it is responsible for 1.5 to 2

million of deaths yearly in the world1, and three fourth

of cases were suffered in India amongst 2.48 million

of malarial cases of South-East Asia.2 In Tropical

countries, where malaria is endemic, it is very

essential to differentiate malaria from other viral or

bacterial infections by symptoms and signs3 to prevent

future fatal complications, like, cerebral, renal, and

gastrointestinal. Hence in these areas, unnecessary

antimalarial treatment to treat the possible cases before

diagnosis is one of the causes of drug resistance. 4 In

India, Plasmodium falciparum (p. falciparum) and

Plasmodium vivax (p. vivax) are responsible for

malaria. This disease is transmitted by the bite of the

anopheles mosquito. Incubation period in malaria is

ten to fifteen days. After entry, the sporozoites in the

circulation in the human body, attach to the

hepatocytes through the receptors for thrombospondin

and properdin.5

In the hepatocytes, sporozoites aretransformed to schizonts. Each schizont produces a

large number of merozoites in the hepatocyte. Most of

DOI: 10.5958/j.2319-5886.3.1.024



121


the merozoites are released into circulation. In the

circulation, each merozoite is entered in the red blood

cell (RBC) and produces 24 to 32 merozoites during

the asexual stage of the life cycle. As p. falciparum

enters the RBC, following thing things may occur.

Firstly, increased secretion of inflammatory cytokines

(tumor necrosis factor α, interleukin 1, 10 and

interferon γ), secondly, due to over expression of cell

adhesion molecule, endothelial cell become activated,

thirdly, coagulation cascade activation as a result of

platelet activation and endothelial damage, fourthly,

sequestration of parasitized RBC due to over

expression of cell adhesion molecule, iNOS.6-10 As a

result, there are changes in the morphology and

number in different cell lines. Now-a-days, in case of

p. vivax malaria, biochemical and hematological

parameters occur. Hematological changes include

hemoglobin, packed cell volume (Hct), total white

blood cell count (WBC), platelet count, blood glucose,

Creatinine. These changes may vary with the

nutritional status, demographic factors, individual and

environmental immunity.11 Our aim was to compare

the hematological and renal parameters between p.

falciparum and p. vivax affected patients in relation to

healthy group in West Bengal.


Inclusion criteria: Total 238 patients [120

plasmodium vivax (males 90 and females 30) and 118

plasmodium falciparum ( males 68 and females 50)]

between the ages of 2 to 80 years who were admitted

in our hospital from 2011 to 2013 years with

symptoms and signs suggestive of malaria, like, fever

with chill and rigor, headache, nausea with or without

vomiting, arthralgia, diarrhea, weakness, drowsiness,

confusion, stupor, anemia, jaundice, signs of

dehydration, hepatomegaly, and slpenomegaly, whoseblood were positive for malaria parasite in thick or thin

blood film stained by Giemsa stain and/or dual antigen

positive for plasmodium vivax or plasmodium

falciparum. They were subdivided into 2 groups

according their antigen positive type (Group A:

Plasmodium vivax (N=120), Group B: Plasmodium

falciparum (N=118)

Exclusion criteria: We excluded the patients

suffering from different infection producing sepsis,

dengue infection, viral hepatitis, Leptospirosis duringthis period.

Ethical clearance: This three years study was

conducted only after getting permission from the

ethics committee of our hospital and informed consent

obtained from our patients’ parties.

Detailed clinical history was taken from the patient,

followed by, thorough clinical examination. Then

blood was used for thick and thin blood film, stained

with Gimsa stain, for detection of malaria parasite

under microscope and for detection of malarial antigen

of both p. falciparum and p. vivax. If at least, one

asexual form of parasite was detected in 100

microscopic fields of thick blood film examined under

microscope using oil - immersion lens

(100xmagnification) – it is considered as positive.

After confirmation of the diagnosis, 5 ml. of blood was

collected from each patient aseptically in a vial

containing ethylene diamine tetra acetic acid (EDTA)

and was promptly analyzed for routine hematological

parameters, which included, the following, like, total

WBC count, hemoglobin (Hb) estimation, hematocrit

(Hct), Mean Corpuscular Hemoglobin (MCV), Mean

Corpuscular Hemoglobin (MCH), mean corpuscular

hemoglobin (MCHC), erythrocyte sedimentation rate

(ESR), platelet count.

Another 2 ml. of blood was collected in a vial and

serum was separated and estimated Creatinine, blood

sugar. Hemoglobin was estimated by the acid hematinmethod, PCV by Wintrobe’s method, blood sugar by

enzymatic method, Creatinine by the alkaline picrate

method. These are all conventional methods.

Similarly, blood from 100 patients in the healthy group

(Group C: n=100), which consist of patient’s party, lab

technicians having no history of disease in the recent

past or present were done of same parameters. Data

were collected and analyzed statistically.

Statistical analysis : The data were expressed in terms

of means±SD (standard deviation). Then, all the meanswere compared between p. vivax and p. falciparum

group and control group separately at 95% confidence

interval using student ‘t’test and, ‘p’ value were

extracted. ‘p’ value of less than 0.05 was considered as

statistically significant. In statistics, a confidence

interval (CI) is a type of interval estimate of

a population parameter and is used to indicate the

reliability of an estimate. It is an observed interval. In

applied practice, confidence intervals are typically

stated at the 95% confidence level.



122


RESULTS

Table:1 Comparison between p. vivax and p. falciparum affected patients as compared to control group

ParametersP. vivax(Group A )

P. falciparum(Group B )

ControlGroup C(100)

95% CI$ P value$ 95% CI@Pvalue@

95% CI P value

Age (years) 42.82±88.4 27.2±14.2

32.49±4.15 -0.61 —

31.85 0.059

-7.11 –

27.77

0.24 -8.18

-2.39

0.00**

Temperatures(oF)

101.72±0.20 100.9±0.19 98.1±0.31 0.75 –

0.84 0.00** 3.55–3.68 0.00** 2.73–2.86 0.00**

Hemoglobin(gm%)

11.785±2.1 12.32±1.52 12.51±0.45 -1.008–

-0.07 0.02*

-1.14-- -0.30 0.00** -0.50 –0.12

0.22

ESR mm/1st hour 75.18±6.42 68.78±7.79 15.75±5.56 4.57 –

8.22 0.000***

43.01—77.20

0.00** 51.87—55.54

0.00**

MCV (fl) 82.74±8.41 83.14±7.85 84.62±8.56 -2.47 –

1.67 0.704

-4.14–0.38 0.10 -3.67 –0.71

0.18

MCH (pg) 27.72±8.21 28.94±6.45 32.64±4.52 -3.10 –

0.66 0.204

-6.73 -- -3.10

0.00** -5.21–-2.18

0.00**

MCHC (g/dl) 34.18±1.62 35.47±1.48 35.10±1.98 -1.58–

-0.79 0.000***

-1.14–0.70 0.64 -0.09 –0.83

0.11

Hematocrit 34.88±4.346 33.179±3.136

41.45±5.2 0.73—

2.669 0.000***

-7.84 -- -

5.29

0.00** -9.39–

-7.14

0.00**

Total WBC count/cc

6653.16±1999.0 6008.92±1393.5 8096.21±35.4 203.50—

1084.98 0.00**

-1837.23-1048.86

0.00** -2362.13 ---1812.44

0.00**

Differential count

lymphocyte count(%)

42.14±12.42 36.39±15.45 44.13±15.87 2.17 –

9.32 0.00**

-5.75–1.77 0.29 - 11.93–- 3.54

0.000***

Monocyte count(%)

10.10±2.17 13.59±6.80 8.68±4.95 -4.77–

-2.205 0.00**

-0.57–1.77 0.01* 2.29–5.52 0.00**

Neutrophil count(%)

42.67±21.02 46.39±18.18 43.77±21.31 -8.74 –

1.302 0.145

- 6.14 –5.14 0.86-2.65–7.89

0.32

Eosinophil count(%)

3.01±4.19 4.12±4.79 2.92±7.1 -2.25 –

0.04 0.58

- 1.43 –1.61 0.90 -0.39– 2.79 0.14

Basophil count

(%) 1.45±2.12 1.72±1.64

0.57±0.12 -0.75 –

0.21 0.27

-0.01–1.07 0.055 0.82–1.47 0.00**

Platelet countLack/ cc

1.61.±0.61 1.81.±0.91 2.51.±0.81 -293.95—

39410.8 0.053

-1.851241---70602.88

0.00** -93244 -- -46753.37

0.00**

Creatinine mg/dl 0.94±0.57 0.71±0.45 0.71±0.25 0.098—

0.361 0.00**

0.109—0.35 0.00** 0.09-0.09 1.0

Fasting bloodsugar mg/dl

93.8±18.67 100.35±10.89 98.25±11.92 -10.46—

-2.63 0.00**

-8.70—-0.19 0.04* -0.94 –5.14

0.17

$= Comparison with P.Vivax vs P. Falciparum, @= Comparison with P. Vivax vs Control, ^= Comparison with P. Falciparum

vs Control, *Significant, **Very significant, ***extremely significant

A. Characteristics of the studied population – In case

of p. vivax, affected male (n=90) to female (n=30)

ration was 3:1, whereas, in case of falciparum

(male=68, female=50), it was 1.36:1. Temperature

in both p. vivax and p. falciparum groups were

significantly raised as compared to control group.

B. Comparison of hematological parameters between

p. vivax (120) and p. falciparum (n=118) group –

P. vivax showed a significant elevation in ESR

(75.18±6.42 vs. 68.78±7.79 mm / 1st hour,

p=0.00), differential lymphocyte count

[(42.14±12.42) % vs. (36.39±15.45) %, p=0. 00],

creatinine (0.94±0.57 vs. 0.71±0.45 mg/dl, p=0.

00) and significant lowering of platelet count

(161792.45±61165.62 vs.

181350.87±91122.45/cc, p=0. 05) Fasting blood

sugar level (93.8±18.67 vs. 100.35±10.89 mg/dl,

p=0. 00) as compared to p. falciparum group.

Whereas, p. falciparum group showed a significant

elevation in hemoglobin (12.32±1.52 vs.

11.78±2.1 gm/dl, p=0.02), differential monocyte

count [(13.59±6.80) % vs. (10.10±2.17) %], and

MCHC (35.47±1.48 vs. 34.18±1.62 g/dl, p=0.00),

and significant lowering of WBC count

(6653.16±1999.01 vs. 6008.92±1393.56 /cc,

p=0.00), as compared to p. vivax group.

C. Comparison of hematological parameters between

p. vivax group (n=120) and control group (n=100)

– In p. vivax group, hemoglobin (11.78±2.1 vs.

12.51±0.45 gm/dl, p=00), MCH (27.72±8.21 vs.



123


32.64± 4.52 pg, p=0.00), Hct (34.88±4.34 vs.

41.45±5.2, p=0.00), total WBC count

(6653.16±1999.01 vs. 8096.21±35.41 /cc, p=0.00),

total platelet count (161792.45±1165.62 vs.

251350.10±81315.62 / cc, p=0.00), fasting blood

sugar level (93.8±18.67 vs. 98.25±11.92 gm/dl,

p=0.04) were significantly low as compared to

healthy control group. Whereas, in former group

showed significantly raised ESR (75.18±6.42 vs.

15.75±5.56 mm / 1st hour, p=0.00), differential

monocyte count [(10.10±2.17) % vs. (8.68±4.95)

%, p=0.01] and serum creatinine (0.94±0.57 vs.

0.71±0.25 mg/dl, p=0.00) as compared to later

group.

D. Comparison of hematological parameters between

p. falciparum group (n=118) and control group

(n=100) -- MCH (28.94±6.45 vs. 32.64±4.52 pg),

Hct (33.17±3.13 vs. 41.45±5.2, p=0.00), total

WBC count (6008.92±1393.56 vs.

8096.21±1035.41), differential lymphocyte count

[(36.39±15.45) % vs. (44.13±15.87) %, p=0.00]

total platelet count (181350.87±91122.45 vs.

251350.10±81315.62 /cc, p=0.00) were reduced

significantly in p. falciparum group, whereas, ESR

(68.78±7.79 vs. 15.75±5.56 mm /1st hour),

differential monocyte count[(13.59±6.80) % vs.

(8.68±4.95) %, p=0.00], basophil count[(1.72±1.64) % vs. (0.57±0.12) %, p=0.00] were

raised significantly as compared to control group.

DISCUSSION

After the development of the microscope by Antonie

Van Leeuwenhoek in the 15th century, diagnosis of

many parasitic diseases including malaria was

possible. Moreover, in the last three decades, many

more investigation methods have come into action,

thus refine and modify our diagnosis. Due to huge costfor development Newer tests based on serology

(Falkon assay screening test ELISA (FAST-ELISA,

Rapid antigen detection systems (RDTs), real-time

polymerase chain reaction, loop-mediated isothermal

amplification (Lamp and Luminex), mass

spectrometry12 to diagnose accurately the malaria

infection at its earliest phase, direct microscopy and

sociological methods and hematological parameters

for supporting diagnosis are still the gold standard for

the diagnosis of malaria infection.

In our present study, male to female ratio were 3:1,

1.36:1 in p. vivax and p. falciparum respectively. But,

when we considered the total number of affected

patients, the ratio was 1.97:1, whereas, in the study

done by Muwonge H et al. The ratio was 2.5:1.13 In a

study done by Hussain M M et al14. The ratios were

1.73:1 and 2:1 at p. vivax and p. falciparum

respectively. Our study showed the extreme male

preponderance over female in case of p. vivax

infection than p. falciparum infection.

Mean age of incidence of malaria in our study in p.

vivax, p. falciparum and control group were

42.88±88.4 years, 27.2±14.2 years and 32.49±4.15

years respectively, which showed an age incidence in

p. falciparum was close to the control group. But in a

study done by Hussain M M et al14 age incidence were

29.25±1.9 years, 27.98±2.4 years and 29.48±2.6 years

in p. vivax, P. falciparum and control group

respectively, which showed an age incidence in the

case of p. falciparum group was nearer to the our value

(, 27.2±14.2 years), whereas, in the case of p. vivax

group, age incidence was much higher in our study

than the study of Hussain M M et al14 (42.88±88.4

years vs. 29.25±1.9 years).

P. vivax, p. falciparum and control groups in our study

showed mean axillary temperature of 101.7±0.01o F,

100.9±0.1o F and 98.1±0.31o F respectively, whichwas higher as compared to the study done by Hussain

M M et al (99.65±0.1o F, 98.91±0.3o F and 97.68±0.1o

F in p. vivax, p. falciparum and the control group

respectively). 14

In malaria, anemia is multifactorial in origin — like,

hemolysis of parasitized and non-parasitized RBC,

depressed or ineffective erythropoiesis15, nutritional

deficiency, especially in case of females, blood due to

hook worm infestation (which is most common in

West Bengal), decreased erythrocyte production.16

Present study demoed significantly low hemoglobin in

p. vivax group (11.785±2.1 gm/dl) as compared to the

p. falciparum group (12.32±1.52 gm/dl, p=0.02) and

control group (12.51±0.45 gm/dl, p=0.00). This

observation is not consistent with previous reports of

Plasmodium infection, in which, hemoglobin

degradation resulting anemia had a good correlation

with severity of infection due to p. falciparum.17 In

present study, low hemoglobin may be due to

nutritional deficiency or increased blood loss inassociation with hemolysis of parasitized or non-

parasitized RBCs.



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In our present study, ESR was significantly raised in p.

vivax than in p. falciparum (75.18±6.42 mm/1st hour

vs. 68.78±7.79 mm/1st hour) as shown in other study

done by Hussain M M et al (82.19±5.1 mm/1 st hour vs.

77.79±4.5 mm/1st hour).14 Again, combination of low

hemoglobin and raised ESR, as shown in our study,

was highly significant hematological parameters in

predicting p. vivax malaria infection in endemic areas

in patients who are symptomatic, but false smear

negative or serologically negative due to very low

parasitemia, as shown in other studies done by Erhart

et al18 and Gerardin et al.19

Mean value of total WBC count was significantly low

in p. falciparum group as compared to p. vivax group

(6008.92±1393.56/cc vs. 6653.16±1999.01, p=0.00).

Commonly, the total WBC count is within normal

range20, 21, except, in a few studies, where there was

evidence of leucopenia. 21, 22 In our present study, in p.

falciparum group, there was also leucopenia, which

was also consistent with other Indian study done in

malaria endemic area, where there was also evidence

of leucopenia.23 In Panama22 and Turkey24, also there

were evidences of leucopenia in cases of p. vivax, p.

falciparum and dual infection.

In our present study, there was significant reduction

differential lymphocyte count in p. falciparum

((36.39±15.45) %, p=0.00) as compared to p. vivax(42.14±12.42) % and control group (44.13±15.87) %.

Usually, differential lymphocyte count in acute

malaria, varies with the increase or decrease in

differential WBC lines. Hence, in respect to

differential lymphocyte count, varying reports

(increase, decrease or normal) were observed in

different studies in case of acute malaria infection21.

According to recent literature, lymphopenia may occur

in non-immune adult21, 25 and in children in endemic

areas.17, 21

In the present study, though, the differentiallymphocyte count was within normal range, but, it was

in the low range of normal in p. falciparum group. The

factors responsible for transient lymphopenia are:

firstly, tissue distribution of lymphocytes26 from freely

flowing blood stream to the endothelial lining of the

blood vessels to adhere27, secondly, lymphocyte

destruction due to Fas-induced apoptosis. 28 Owing to

the high rate of lymphocyte destruction in p.

falciparum affected patients, both absolute and

differential count will be low.

29

This may explain whymean total lymphocyte counts was in lower range of

normal in p. falciparum group.

Usually, phagocytes (Neutrophil and macrophages)

and/or natural killer [NK] cells are the effector cells,

been activated as a result of an immune response to

blood borne pathogens. So, obviously, an early

pathological hall-mark in acute malaria is reticulo-

endothelial cell hyperplasia involving macrophages.21

Monocytosis was the constant hematological finding

in different studies of acute malaria17, 30-32 as well as, in

our present study, where significant monocytosis were

observed in both p. vivax and p. falciparum groups

[(10.10±2.17)%, vs. (13.59±6.80)%,], as compared to

control group[ (8.68±4.95)% p =0.01].

In our study, mean neutrophil count was within normal

range as compared to control group [p. vivax=

(42.67±21.02) %, p. falciparum= (46.39±18.18) %,

control group = (43.77±21.31) %], which was

consistent with the other study in India31, where 85%

of patients had normal Neutrophil count, as well as,

study done in Singapore.33 Though, few studies

demonstrated neutropenia27, which may be the result

of increased margination and sequestration of

neutrophils due to increased expression of cell

adhesion molecules [ICAM — 1 and VCAM — 1]

occurred in acute malaria. Some earlier studies

demonstrated neutrophilia also.17

Though our study showed no difference in eosinophil

count in p. vivax and p. falciparum [(3.01±4.19) %,(4.12±4.79) % ] as compared to control (2.92±7.1) %,

but few studies in the world34, showed evidence of

eosinopenia, whose significance was not explained.

But, during recovery, these patients showed rebound

neutrophilia34, which was explained as the result of

enhanced T-helper — 2 cell response, which occurred

during this period.

Now-a-days, lots of work have been going on

regarding the platelet hemostasis in acute malaria,

because of the fact that, complexes of platelet andcoagulation factors surround the flowing and

sequestrated parasitized RBCs and enclose vascular

endothelium.21 The different studies on acute malaria

in the world17,23, 31, 35, 36 showed that the magnitude of

thrombocytopenia varied according to species and

severity of infection. It was also shown that p. vivax

group was associated with severe thrombocytopenia

than p. falciparum group. Similarly, our present study

showed thrombocytopenia in p. vivax group was more

severe than that in p. falciparum group(161792.45±61165.62 /cc. vs.

181350.87±91122.45/cc), though the count was within



125


normal limit, as compared to control group

(251350.10±81315.62/cc). This thrombocytopenia

stimulates bone marrow to produce an increased

number of megakaryocytes, which ultimately produce

megaplatelets and leave the bone marrow to enter the

circulation; the stimulating factor being

thrombopoietin, a key platelet growth factor, which

was described in the study done by Cyril et al37. As a

result of increased number of megaplatelets, mean

platelet volume will be increased during acute malaria

infection.17, 23.

The pathophysiology of thrombocytopenia is

multifactorial. Firstly, splenic sequestration of RBC,

secondly, antibody mediated platelet dysfunction,

thirdly, release of adenosine diphosphate (ADP) as a

result of hemolysis of parasitized RBCs, fourthly,

abnormal megakaryocytosis, fifthly, invasion of

platelets by parasites, sixthly, phagocytosis of

platelets, seventhly, oxidative stress.21, 38

In our present study, MCHC was significantly reduced

in p. vivax group as compared to p. falciparum group

(34.18±1.62 g/dl. Vs. 35.47±1.48 g/dl, p=0.00), but,

only MCH were reduced in both groups as compared

to control group (p. vivax = 27.72±8.21 pg., p.

falciparum = 28.94±6.45 pg., control = 32.64±4.52

pg.). But, all the RBC indices were within normal

limits, which may be due to the following factors:firstly, low production of cytokines, secondly, less

endothelial cell activation; thirdly, milder changes in

coagulation profile, fourthly, diminished sequestration,

fifthly, decreased hemolysis in less severe malaria.

Our present study demoed significantly raised serum

creatinine level in p. vivax group as compared to p.

falciparum (0.94±0.57 mg/dl, vs. 0.71±0.45 mg/dl.,

p=0.00) and control group (0.71±0.25 mg/dl.). This

study was consistent with the study done by Ogdaboyl

E O et al39

and Delanghe J et al40

, in which, raisedcreatinine was seen in the Nigerian population. The

elevated serum creatinine is probably due to

ineffective filtration ability as a result of renal

functional impairment.

In our study, plasma glucose level was lower in p.

vivax group (93.8±18.67 mg/dl) as compared to p.

falciparum group (100.35±10.89 mg/dl) and control

group (98.25±11.92 mg/dl). This low blood glucose

levels as well as low hemoglobin level are the two

most reliable indicators and hematological parametersin predicting the presence of p. vivax malaria as shown

in other studies also18, 19.

CONCLUSION

Malaria infection was twice more common in males

than females. Younger age group was the victim of

plasmodium falciparum, whereas, plasmodium vivax

affected higher age group. Plasmodium vivax

affected patients were more anemic. The combinationof low hemoglobin, low fasting blood sugar and

significantly raised ESR is highly significant in

predicting severity of Plasmodium infection in patients

of malaria endemic areas, which was evidenced in our

present study. Lymphopenia was observed in

Plasmodium falciparum affected patients, whereas,

thrombocytopenia in Plasmodium vivax affected

patients, but, significant monocytosis was observed in

both groups. Significantly reduced MCHC was

observed in Plasmodium vivax groups, whereas, MCHwas reduced in both groups.

Conflict of interest: Nil.

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SI. The global distribution of clinical episodes of

Plasmodium falciparum malaria. Nature.

2005;434: 214-17

2. Yadav D, Chandra J, Dutta AK. Benign tertianmalaria: how benign is it today? Indian J. Pediatr.

2012;79(4): 525-27

3. Lathia TB, Joshi R. Can hematological parameters

discriminate malaria from non malarious acute

febrile illness in the tropics? Indian J. Med. Sci.

2004;58: 239-44

4. Barnish G, Bates I, Iboro J. Newer drug

combinations for malaria. BMJ. 2004;328: 1511-

12

5. Nadeem M, Ali N, Qamar MA. Hematological

findings in acute malarial infection list of authors

along with highest qualification and institute.

Biomedica. 2002;18: 62-65

6. Costa E T M, Avril M, Nogueira A, Gysin J.

Cytoadhesion of Plasmodium falciparum-infected

erythrocytes and the infected placenta: a two-way

pathway. Brazilian Journal of Medical and

Biological Research. 2006;39(12): 1525-36

7. Francisschetti I M B. Does activation of blood

coagulation cascade have a role in malaria

pathogenesis? Trends in Parasitology. 2008;24(6):

258-63



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8. Ghosh K, Shetty S. Blood coagulation in

falciparum malaria — a review. Parasitology

Research. 2008;102(4): 571-76

9. Clark LA, Budd AC, Alleva LM, Cowden WB.

Human malarial disease: a consequence of

inflammatory cytokine release. Malaria Journal.

2006;5:85

10. Haldar K, Mohandas N. Malaria, eryrhrocytic

infection, and anemia. Hematology/The Education

Programme of the American Society of

Hematology. 2009;10:87-93

11. Price R N, Simpson J A, Nosten F. Factors

contributing to anemia after uncomplicated

falciparum malaria. Am. J. Trop. Med. Hyg.

2001;65: 614-22.

12. Ndao M. Diagnosis of parasitic diseases: old and

new approaches. Interdisciplinary Perspectives on

Infectious Diseases. 2009; Article ID 278246.

13. Muwonge H, Kikomeko S, Sembajjwe LF, Seguya

A, Namugwanya C. How reliable are

Hematological Parameters in predicting

Uncomplicated Plasmodium falciparum Malaria in

an Endemic region? ISRN Tropical Medicine.

2013; Article ID 673798.

14. Hussian MM, Sohali M, Abhishek K, Raziuddin

M. Investigation on Plasmodium vivax infection

influencing the host factors in tribal dominant andmalaria endemic population of Jharkhand. Saudi J

Biol Sci. 2013;20(2): 195-203

15. Weatherall DJ, Miller LH, Baruch DI, Marsh K,

Doumbo OK, Casals-Pascual C. et al. Malaria and

the red cell. Hematology Am. Soc. Hematol. Educ.

Program. 2002;35-57

16. Philips RE, Pasvol G. Anemia in Plasmodium

falciparum malaria. Baillieres Clin. Hematol.

1992;5: 315-30.

17. Maina RN, Walsh D, Gaddy C, Nongo G,Waitumbi J, Otieno L. Impact of Plasmodium

falciparum infection on hematological parameters

in children living in Western Kenya. Malar. J.

2010;9(suppl 3):S4

18. Erhart LM, Yingyuen K, Chuanak N, Buathong

N, Laoboonchai A, Miller RS. et al.

Hematological and clinical indices of malaria in a

semi-immune population of Western Thailand.

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19. Gerardin P, Rogier C, Ka AS, Jouvencel P,Brousse V, Imbert P. Prognostic value of

thrombocytopenia in African children with

falciparum malaria. Am. J. Trop. Med. Hyg.

2002;66: 686-91

20. Haroon H, Fazel PA, Naeem A, Mobin A, Naqvi

A, Makki K. Hide and seek hematological aspects

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Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132


&

Health Sciences




thDec 2013

Research article

NONLINEAR DYNAMIC ANALYSIS OF VOICE: A NORMATIVE STUDY IN THE INDIAN

POPULATION

Jacqueline B. Fernandes1, *Radish Kumar Balasubramanium

2, Arivudai Nambi Pitchaimuthu

2, Jayashree S. Bhat

3

1II MASLP,


3Professor & Head, Department of Audiology and Speech Language Pathology,

Kasturba Medical college (Manipal University), Mangalore, India.


ABSTRACT

Background: The aim of this study was to establish normative data for the Indian population using Nonlinear

dynamic analysis. In this study, correlation dimension, a measure of nonlinear dynamic analysis was performed for

normophonic young, middle aged and elderly voices. Materials and Methods: For this purpose, normophonic

young, middle aged and elderly individuals were selected without a history of voice/respiratory problems and

vocal abuse/ misuse. 60 participants were selected in each group. All of these individuals had a normal voice as

evaluated through GRBAS scale. Sound Recorder, on a computer desktop was used for voice recording and

“convert” code in MATLAB as well as D2.ini.writer software based on TISEAN package (Hegger, Kantz &

Schreiber, 1999) was used for the calculation of Correlation dimension (D2). Correlation dimension measures

were obtained for each participant, for both steady vowel phonations (/a/, /i/, /u/) as well as narration samples.

Results: The correlation dimension measures across the group revealed a significant main effect of the groups

indicating correlation dimension increases with increase in age. Conclusions: The application of nonlinear dynamic

measures in the assessment of voice is a novel venture and thus this study provides normative data for

correlation dimensions in the Indian population for future comparisons against the disordered voice samples.

Further studies are warranted to investigate the same in the clinical population. Also other nonlinear dynamic

analysis methods need to be investigated to obtain the normative data in the Indian population.

Keywords: Nonlinear dynamic analysis, Correlation dimension, Normophonic voice,

INTRODUCTION

Acoustic analysis does not appraise completely the

true nature of the underlying vocal fold function. Yet,

acoustic analysis is still used in the voice assessment

due to some level of correspondence between voice

production and voice acoustics. Though not perfect,

much can be inferred about the vocal physiology

based on the acoustic analysis. A normal voice signal

is said to be quasi periodic and must have very

minimal cycle to cycle variability in frequency aswell as amplitude. When the voice is periodic and/or

nearly periodic, measures such as Jitter and Shimmer

are reliable whereas they are unreliable in the case of

severely perturbed voices due to the difficulty in

identifying cycle boundaries. Due to this reason,

traditional measures such as jitter, shimmer have lost

their value in the assessment of aperiodic voices.

Nonlinear dynamic analysis endeavor to recognize

and explain the presence of ‘‘r ules’’ underlying the

random nature of a severely perturbed voices. Thisapproach considers the severely perturbed voices as

DOI: 10.5958/j.2319-5886.3.1.025



129


‘‘chaotic’’ in nature. Chaos theory believes that

erratic looking temporal behavior does not arise

randomly, but is deterministic in nature i.e., initial

condition(s) determines the end result based on some

law/rule.1

A potential advantage of this method,

when compared with traditional perturbation

measures of the voice signal, is the possibility of

objectively quantifying dysphonia severity without

the requirement of cycle boundary detection. Also,

non linear methods have the capability of analyzing

all the types of voice signal (periodic as well as

aperiodic voice). There are two most commonly

used nonlinear methods which include phase space

portraits and the subsequent computation of

correlation dimension.2

Usually, voice waveform data are entrenched in phase

space and then reconstructed using the method of lag

variables or delay coordinates.3

A periodic signal will

show a closed trajectory in phase space, with

increasing perturbation resulting in irregular or

chaotic trajectories.3-5

Though vocal fold vibration is

graphically represented as a trajectory in phase space

with time,2

further computation is required to

objectively quantify the complexity of the signal in

space.

Correlation dimension (D2) is one such measure that

quantifies the complexity of the signal by specifying

the number of degrees of freedom (ie, dimensions)

needed to describe a dynamic system like voice.5

If

the dynamics of a system can be determined to be low

dimensional, then a complex determinism may exist,

which is responsible for the observed signal profile.6

Alternatively, more complex the system, greater the

number of degrees of freedom are required to

describe its dynamic state, and the higher the

correlation dimension. These non linea r dynamic

methods have been analyzed in both pathological andnon pathological voice samples

5, 7-9 in several studies.

In the modern clinical outlook, its popularity is

limited. Also, there are no normative available in the

Indian context. Hence, the present study is an attempt

in this direction. Results of this study would guide the

speech language pathologist in a more efficient

assessment and management of voice disorders.

Aim of the study: To obtain a normative data for

voice using Non Linear Dynamic Analysis.

METHOD

This study followed a cross sectional normative

study design, with Non Random Convenient

Sampling. The institutional ethical approval was

obtained prior to the conduct of the study. Participants

were alienated into three different groups based on

age10

which are as follows:

Table 1: Age Range Classification10

AGE RANGE GROUP NAME18 – 40 Years Young Adults

41- 60 Years Middle Aged Adults

61 Years & Above Older Adults

Each group consisted of 60 individuals out of which

30 were females and 30 were males. All the

participants were normal healthy individuals

without any history of vocal abuse/misuse,

smoking, neurological, organic and non organic

vocal pathological conditions. All the participants

had a normal voice as evaluated perceptually by

three trained speech pathologists using the GRBAS

(Grade Roughness Breathiness Asthenia Strain)

scale.11

Prior to the study an informed consent was

obtained from all the participants.

Instrumentation: Sound Recorder, a computer device

was used for recording of the voices. A dynamic

microphone was used to record voice. Adobe

Audition (version 3.0) was used for noise reduction

from the samples. Correlation Dim ens ion was

ob tained by means o f M ATLAB (matrix

laboratory) developed by Math Works and

D2.ini.writer software based on TISEAN package.12

Procedure:

During the voice sample recording, the participants

were seated in a comfortable chair. All the voice

samples were directly recorded in Sound Recorder

using a dynamic microphone. The distance betweenthe microphone and the participant’s mouth was

constantly maintained at 10 cm. After a brief period

of familiarization, the participants were instructed to

phonate vowel /a/ at their habitual loudness and pitch

as if the vowel was a word in a conversation, and

were also instructed to avoid singing it. The task

was demonstrated to each participant and

instructions were repeated as and when required. The

task was repeated if the experimenter felt that the

voice produced did not sound like their habitual voiceproduction. The recordings were carried out in a



130


sound treated room in a single sitting for all the

participants. Similarly, a narration sample was also

recorded using the same set up. A common topic that

was maintained for narration was “home”.

Analysis: The pre recorded voice samples collected

for each participant was individually analyzed by

means of a code written using MATLAB. The

recorded voice samples were stored in “.wav” format.

The voice samples were then fed into MATLAB by

means of a “convert” code in order to transform it

into “.txt” file format. Once the “.txt” format was

obtained the file was then fed into a D2.ini.writer

based on the TISEAN package12

in order to obtain the

embedding dimension values. (Correlation

Dimension, D2). A total of 15 correlation dimension

values were obtained for each sample. The mean

values for every dimension were calculated in

order to obtain a normative range across the three

age groups as well as to compare the variation

amongst the three age ranges.

RESULTS

The present study was carried out with an aim to

obtain normative data for the acoustic analysis of

voice using Non Linear Dynamic Analysis. Age

related differences were analyzed using one way

ANOVA with bonferronis post hoc test.

Fig. 1: Mean dimension values for sustained vowel

/across the three groups.

The above figure depicts no significant change

amongst the three groups until the 7th

dimension at

p>o.05. However, a gradual increase in the mean

dimension values was observed in older adults beyond

the 8th

dimension at p<0.05. Young and middle aged

adults displayed similar profiles in the mean

correlation dimension values.

Fig. 2: Mean dimension values for narration across

the three groups.

The above figure indicates differences in the

correlation dimension values across the three

groups. Older adults showed a higher dimensionvalue in comparison to young adults at p<0.05. The

middle aged adults depicted a comparatively reduced

mean value when compared with younger and older

adults at p<0.05.

The results revealed significant differences for

phonation of vowel /a/, and narration at p < 0.05.

DISCUSSION

With the development of nonlinear vocal fold models,

studies have put forward the means of assessing

nonlinearity in the voice signal through various

methods. These methods provide quantifiable data

by considering the chaotic components in a voice

signal. Various nonlinear dynamic analysis methods

have been described in the literature. These include

the development of phase space portraits, attractors,

and the use of correlation dimension, all of which

have produced variable results. In the present study,

correlation dimension was used to characterize the

normal voice samples across adults and geriatric in

Indian population. Results of one way ANOVA

revealed that the correlation dimension measures

across the group revealed a significant main effect

of the groups i.e., as the age increases, correlation

dimension values increases. This suggests that as the

age increases, complexity in the laryngeal mechanism

also increases thereby providing chaos in the vocal

fold vibration.

Sulica reported that the age related anatomical

changes occurs in the laryngeal system such asdegenerative changes to the lamina propria and the



131


mucosal glands in the larynx, all of which results in

reduced production of laryngeal mucus which further

causes intermittent alteration in vocal fold vibratory

patterns thereby inducing changes in pitch, loudness

and quality as well.13

Thus, it can be stated that non

linearity is inherent in the laryngeal mechanism with

the presence of chaos in the voice production.

Higher correlation dimension values were reported in

systems that have more chaos or deterministic noise.

They suggest that the anatomical alterations in the

vocal mechanism that occur for any pathological

conditions result in higher values of correlation

dimension. Hence, we can opine that anatomical

alterations in the vocal mechanism that are exhibited

by aged individuals could be the underlying cause for

obtaining higher correlation dimension measures in

this study.14 Baken reported that the Fractal dimension

values are representative of the vibratory function of

the vocal folds.15

Baken considered vocal folds to be

oscillators whose movements if affected by means of

any change in the vocal mechanism be it due to aging

or organic pathology results in irregularity or chaos in

the regular oscillations of the vocal folds. This

irregularity in oscillation caused an increase in the

value of the fractal dimension.15

Alternatively, a study carried out by Nicollas et al16

in children aged 6-12 years using nonlinear dynamic

analysis reported that correlation dimension measure

decreased with increasing age in children. Their

results were attributed to several factors. The main

factor considered amongst them was the evolution of

the pediatric larynx.14,17

In support of this view, Eckel

et al17

reported that the subglottic airway rapidly

increases during the first 2 years and then follows a

linear mode. During the same period, fundamental

frequency decreases from 450 to 300 Hz, while

membranous vocal fold increase by 1 mm.Histologically, it is well known that the collagen

distribution in the vocal folds varies with age, with

large variations in collagen fiber type occurring

during the period between 6 years and mutation,

corresponding to the ‘‘pre mutation’’.18

These

histological changes, though not measured in the

present study would have contributed to increased

correlation dimension values in the older adults.

However, it is interesting to note that correlation

dimension values were more for young adults incomparison to middle aged adults. The explanation for

this was unclear.

Thus, nonlinear dynamic analysis of voice

provided a quantifiable data on the age related

changes in the voice production. It was evident that

as the age increases, complexity of dimensions also

increases with the decreased predictability of geriatric

voices. This effect was pronounced in both phonation

as well as the narration samples. Thus, it can be

considered as a useful tool in the assessment of voice.

However, it cannot replace the existing voice analysis

techniques available to the voice clinician. Yet, it

may add to the battery of voice assessment

procedures.

CONCLUSION

The application of nonlinear dynamic measures in the

assessment of voice is a novel venture and thus, this

study provides normative data for correlation

dimension in the Indian population for future

comparisons with disordered voice samples. The

correlation dimension measures across the group

revealed a significant main effect of the group

indicating that, correlation dimension values increases

with increase in age. Further studies are warranted to

investigate the same in the clinical population.

Moreover, another nonlinear dynamic analysis

methods need to be investigated to obtain the

normative data in the Indian population.

ACKNOWLEDGMENT: We thank our Dean,

Kasturba Medical College (Manipal University),

Mangalore for permitting us to carry out the study.

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3. Herzel H, Berry D, Titze IR, Saleh, M. Analysis

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5. Zhang Y, Jiang JJ, Wallace MS, Zhou L.

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6. Behrman A, Baken RJ. Correlation Dimension

of Electroglottographic data from healthy and

pathologic subjects. Journal of Acoustical Society

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7. Herzel H, Mende W, Wermke K. Bifurcation and

chaos in newborn infant cries. Physics Letters

A.1990;145:418 – 24.

8. Rahn DA, Chou M, Jiang JJ, Zhang Y. Phonatory

impairment in Parkinson’s disease: evidence from

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2009;23(6):647 – 52

10. Cichero J, Murdoch BE. Acoustic signature of

the normal swallow: characterization by age,

gender, and bolus volume. Annals of Otology

Rhinology and Laryngology. 2002;111: 623-32.

11. Hirano M. Clinical examination of voice. New

York: Springer verlag; 1981.

12. Hegger R, Kantz H, Schreiber T. Practical

Implementation of Nonlinear time series

methods: The TISEAN package, CHAOS: An

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13. Sulica L. Voice Medicine: The Ageing Voice.

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Amplitude: A first approach to Fractal Analysis

of Voice. Journal of Voice. 1994; 4: 185 – 97

16. Nicollas R, Garrel R, Ouaknine M, Giovanni

A, Nazarian B, Triglia, MJ. Normal Voice in

Children Between 6 and 12 Years of age:

Database and Nonlinear Analysis. Journal of

Voice. 2008; 22: 671-7517. Eckel HE, Koebke J, Sittel C, Sprinzl GM,

Pototschnig C, Stennert, E. Morphology of the

human larynx during the first five years life

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&

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thDec 2013

Research article

COMPARISON OF THE EFFECT OF MIME THERAPY VERSUS CONVENTIONAL THERAPY ON

THE SUNNYBROOK FACIAL GRADING SYSTEM IN PATIENTS WITH ACUTE BELL’S PALSY

*Mistry Gopi S1, Sheth Megha S

2, Vyas Neeta J

3

1Post graduate student,

2Lecturer,

3Principal, SBB College of physiotherapy, Ahmedabad, Gujarat, India

*Corresponding author email:[email protected]

ABSTRACT

Background: Facial resting symmetry and expressions are determinants of facial attractiveness & being a marker of

good health. Mime therapy is a combination of mime and physiotherapy and aims to promote symmetry of the face

at rest and during movement. The objective of this study is to compare the effect of Mime therapy and conventional

therapy on the facial functions in patients with acute Bell’s palsy. Method: The quasi-experimental study was

conducted at SBB College of physiotherapy. A convenience sample was taken consisting of 30 participants, 10 in

each group. Group A received Mime therapy. Group B, conventional therapy and Group C received home exercise

program. Facial symmetry at rest and movement was assessed through Sunnybrook facial grading scale (FGS) after

completion of 10 sessions to each group. At the end of treatment, response to treatment was assessed by the

Patient’s global impression of change scale (PGIC). Level of significance was kept at 5%. Result: Analysis of

variance was used to compare all outcomes. At the end of 10 sessions, scores on Sunnybrook FGS (p<0.001) and

PGIC (p<0.001) shows significant difference within and between groups. Post hoc Bonferroni test was used for

multiple comparisons. FGS shows significant differences between groups A&B (p<0.001) and groups A&C

(p<0.001). But no significant difference was seen between groups B&C(p=1.00). PGIC scale shows significant

differences between groups A&B (p<0.001) and A&C (p<0.001) but no significant difference was seen between

groupsB&C (p=1. 00). Conclusion: Mime therapy improves facial symmetry and functions more than conventional

therapy and home exercises in people with acute Bells’ Palsy. No difference was found between conventional

therapy and home exercise program.

Key words: Bell’s palsy, Mime therapy, Sunnybrook facial grading system, Patient’s Global Impression of changescale, electrical stimulation.

INTRODUCTION

The term Bells’ Palsy is defined as an idiopathic, acute

and unilateral paresis or paralysis of the face which

may be partial or complete occurring with equal

frequencies on right and left sides of the face.1

The

major cause of Bell’s Palsy is idiopathic, accounting

for 50% of all cases. Other few suggested causes are

exposure to cold, middle ear infections, dental andENT surgeries and traumatic.2

The problems faced in

acute phase of Bell’s palsy include difficulty in closing

the affected side eye, facial deviation to the unaffected

side, difficulty in drinking, eating and speaking along

with psychological problems and facial appearance is

the main concern in any phase of Bell’s palsy.2,4

Facial

palsy is classified according to House and Brackmann

score into 6 grades, where grade 1 is normal, grade 2

has slight dysfunction, grade 3 has moderatedysfunction, grade 4 has moderate to severe

dysfunction, grade 5 has severe dysfunction and grade

DOI: 10.5958/j.2319-5886.3.1.026



134


6 has total paralysis.3

Mime therapy consists of auto

massage, stretching with facilitation exercises,

relaxation, inhibition of synkinesis and coordination

and emotional expression exercises.4

A Cochrane review done by Teixeira LJ et al in

February 2011 has concluded that there is only very

low quality evidence that facial exercise reduces

sequel in acute cases.5

Facial symmetry is a

determinant of facial attractiveness, it is a marker of

good health and it influences interpersonal attraction.6,

7Bell’s palsy can dramatically affect, patients general

quality of life and expressions and interpersonal

communications. Patient’s with bell’s palsy suffer not

only the functional consequences of impaired facial

motion but also the psychological appearance of

skewed facial deviations.8Less evidences are available

for the effectiveness of mime therapy in improving

facial symmetry in acute phase management in Bell’s

palsy, so arises the need of the student. The objective

of this study is to assess and compare the effect of

Mime therapy and conventional therapy on the facial

symmetry and functions in patients with Bell’s palsy

in the early stage of paresis.

METHODOLOGY

A Quasi experimental study was conducted at SBB

College of physiotherapy and convenience sampling

was used. The study consisted of 30 participants, 10 in

each group. The study was carried out from June 2013

to October 2013. Inclusion criteria: Males and

f emales diagnosed with Bell’s palsy in the age group

of 18-70 years with acute onset (1-3wks) and no other

neurological deficit involving the face were included.

Exclusion criteria: Subjects with a history of surgical

intervention for the ear and facial nerve palsy, pain of

any other origin and non co-operative patients were

excluded. Materials used were powder, mirror,

standard electrical stimulator with accessories and

infra red lamp. Outcome measures used were 13-item

Sunnybrook facial grading system (SBFGS)8

and the

Patients' Global Impression of Change (PGIC) scale.9

SBFGS includes 3 components resting symmetry,

symmetry of voluntary movement and synkinesis.

Resting symmetry of 3 components are checked eye,

cheek (naso labial fold) and mouth. In symmetry of

voluntary movements there are 4 components for

standard expressions and grades are given according tothe symmetry during movements; in synkinesis again

there are 4 grades according to the amount of

synkinesis.

The study was reviewed & approved by the

Institutional Ethics Committee, SBB College of

Physiotherapy, V S General Hospital, Ahmedabad,

Gujarat.

Subjects were explained the procedure and purpose of

the study & written informed consent was taken.

After initial neurological examination the participants

were assigned randomly into three groups, Group A:

Mime therapy group, Group B: Conventional therapy

group and Group C: Home exercise group. Then

severity of the condition was measured by Sunnybrook

Composite Score (SBC) pre treatment and post

treatment.

Group A was given 10 sessions of Mime therapy

which included auto massage- effleurage and kneading

for 10 to 15minutes on both the sides of the face,

stretching exercises of the muscles of the affected side

followed by facilitation, specific low intensity

exercises to co-ordinate both the halves of the face,

active assisted exercises for affected side of the face,

exercises of mouth and eye with simultaneous

inhibition of synkinesis if present. A mirror was used

for biofeedback. Exercises to increase participants

awareness of lip movements such as a,e,i, o etc.

Group – B was given Electrotherapy (Conventional

therapy) for 10 Sessions. It included Infrared

radiations (up to 7 days from the date of onset) to

affected side followed by electrical stimulation

(Surged Faradic current) of affected muscles with 3

sets of 30 contractions for each nerve trunk. Exercise

program to all facial muscles was given as below.

Group – C was a control group. They were given 10

Sessions of home exercise program including,

massage, facial muscle exercise program in front of

mirror, 5-6 times in a day and home advices.Level of significance was kept at 5%.

RESULTS

Analysis of results was done with SPSS version 16.0.

ANOVA (Post Hoc Bonferroni test) was used to

analyze the difference in facial symmetry post

intervention in 30 patients with acute Bell’s palsy. The

mean age of the participants was 44.1 years in group

A, 46.2 years in group B and 41.9 years in group C.

There were 6 females and 4 males in groups A and Band 5 males and 5 females in group C.



135


Post hoc analysis of SBFGS showed that there was

statistically significant difference between group A

and B (p<0.001) and Group A and C (p<0.001) but no

significant difference between group B and C

(p=1.00). Post hoc analysis of PGIC showed there was

statistically significant difference between group A &

B (p<0.001) and group A & C (p<0.001) but no

significant difference between group B & C (p=1.00).

Table 1 show that differences in mean Sunnybrook

Composite (SBC) scores in all three groups is

statistically significant. (p<0.001)

Table 1: Comparison of mean composite score of SBFGS (Mean ± SD)

Variable Group A Group B Group C F value p value

SBC(Pre) 38.5±14.5 33.6±15.79 38.5±12.31

11.935 <0.001**

SBC(Post) 86.2±6.81 53.8±12.79 60.9±19.5

SBC(Diff) 48.2±15.31 23.0±10.88 23.4±13.06

**- Very significance, SBC- Sunnybrook composite score

Table 2: Comparison of total score of PGIC (Mean ± SD)

Groups Mean±SD F value p value

A 6.60±0.699

33.498 <0.001**

B 3.70±0.675

C 4.00±1.15

**-very significance

DISCUSSION

The present clinical trial was conducted to study the

effect of Mime therapy on facial symmetry in patients

with acute Bell’s palsy. The SBFGS used to evaluate

severity of facial nerve paresis, included three

components resting symmetry, voluntary movements

and synkinesis.10

In the present study, asymmetry has reduced in all

three groups but more in a Mime therapy group than

others. This improvement may be because massage

improves circulation and maintains muscle properties.

Visual feedback has shown to control muscle activities

in facial muscles.11

Also miming demands highly

refined sense of body and muscle control. A study

done by Ryan J, 2009 has concluded that massagedone in mime therapy has shown to create new growth

and increase production of collagen and connective

tissue in facial muscles and restore facial muscle

action.12

Study done on mime therapy efficacy in

patients with long term facial nerve paresis shows that

mime therapy improves facial symmetry13

. In

accordance with a study of Cronin and Steenerson

(2003) biofeedback by surface electromyography

results revealed improvement in facial symmetry.14

Ahmad SJ and Rather AH (2012) did a prospectivestudy of physical therapy in facial nerve paralysis and

found that physiotherapy in the form of electrotherapy

and facial exercises has an effective role in the early

management of peripheral facial paralysis.15

Because the effectiveness of therapeutic changes

differs greatly among patients, it is essential that

effectiveness of trials directly measure patient related

improvement and satisfaction with treatment.15

The

PGIC is patient-reported, and asked the subject to

“indicate how you feel now, compared to how you felt

before receiving treatment in this study” on a 7-point

scale.

The cost of the treatment is low as along with therapy

at physiotherapy center, home program is an integral

part of the treatment.9

So mime therapy is a good

choice of treatment for people with bell’s palsy.Thus Mime therapy can be used in the treatment of

people with acute Bell’s palsy to get improvement in

facial asymmetry within a shorter period of time.

Limitations of the study are that subjects were not

followed up for a longer period of time.

Randomization was not done. Home exercise protocol

was not supervised.

CONCLUSION

Mime therapy improves facial symmetry and functionsmore than conventional therapy and home exercises in

people with acute Bells’ Palsy. No difference was



136


found between conventional therapy and home

exercise program.

Conflict of interest: Nil

REFERENCES

1. Murakami S, Mizobuchi M, Nakashiro Y, Doi T,

Hato N, Yanagihara N. Bell’s Palsy and herpes

simplex virus: identification of viral DNA in and

oneurial fluid and muscle. Ann Intern Med 2006;

124(1):27-30

2. Leo LJ. Effectiveness of Mime therapy to improve

facial symmetry in acute Bell’s palsy patients- A

Randomised controlled trial. American journal of

physical therapy 2012;24(3):245-47.

3. Cederwall E, Olsen MF, Hanner P,Fogdestam I.

Evaluation of physiotherapeutic treatmentinterventions in Bell’s Palsy. Physiother theory

Pract. 2006;22:43-52

4. Buerskens CHG, Heymans PG. Mime therapy

improves facial symmetry in patients with long-

term facial nerve paresis. Australian Journal of

Physiotherapy 2006; 52: 177-83

5. Teixeira LJ, Soares BG, Vieira VP, Prado GF.

Physical therapy for Bell s palsy (idiopathic facial

paralysis). Cochrane Database Syst Rev 2008; 3:

CD006283.6. Fink B and Penton-Voak. Evolutionary

psychology of facial attractiveness. Current

Directions of Psychological Science 2002;1:154-

58

7. Heymans PG. The impact of facial paresis:

Psychological mechanism. In Buerskens CHG et

al (Eds) The Facial Palsies, Utrecht: Australian

Physiotherapy Association 2006;335-56.

8. John K Niparko, Lawrence R Lustig. Clinical

neurology; Diagnosing and Managing Disorders of Hearing, Balance and the Facial Nerve. Informa

Health Care. 2003;23:245-47

9. Turk DC, Dworkin RH, Allen RR. Core outcome

domains for chronic pain clinical trials:

IMMPACT recommendations. Pain.

2003;106(3):337 – 45

10. Buerskens CHG, Heymans PG. Patients with

facial nerve paresis: Description of outcomes.

American Journal of Otolaryntology 2004;25:394-

400

11. Shafshak TF. The treatment of facial palsy from

the point of view of physical and rehabilitation

medicine. Eura Medicophys.2006; 42:41-47

12. Joyce Ryan, Microcurrent facial: An electrical

current to restore facial muscles. April 17,2009.

13. Hu WL, Ross B, Nedzelski J. Reliability of the

Sunnybrook Facial Grading System by novice

users. J Otolaryngol 2001; 30:208-11.

14. Cronin GW, Steenerson RL. The effectiveness of

neuromuscular facial retraining combined with

electromyography in facial paralysis rehabilitation.

otolaryngol Head Neck Surg 2003;128:534-38

15. Ahmad SJ and Rather AH. A Prospective Study of

Physical Therapy in Facial Nerve Paralysis

experience at a Multispecialty Hospital of Kashmir

2012;15(2):145-48



137

Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143


&

Health Sciences

www.ijmrhs.com Volume 3 Issue1(Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 26

thAug 2013 Revised: 13


thDec 2013

Research article

CARDIOVASCULAR RESPONSES DURING DEEP WATER RUNNING VERSUS SHALLOW

WATER RUNNING IN SCHOOL CHILDREN

Anerao Urja M1, Shinde Nisha K

2, Khatri S M

3

1Postgraduate student,


3Principal, Department of Cardio-respiratory Physiotherapy,

College of Physiotherapy, Pravara Institute of Medical Sciences, Pravara Medical Trust, Loni.

*Correspondence author email: [email protected]

ABSTRACT

Overview: As the school going children especially the adolescents’ need workout routine; it is advisable

that the routine is imbibed in the school’s class time table. In India as growing number of schools provide

swimming as one of the recreational activities; school staff often fails to notice the boredom that is caused

by the same activity. Deep as well as shallow water running can be one of the best alternatives to

swimming. Hence the present study was conducted to find out the cardiovascular response in these

individuals. Methods: This was a Prospective Cross-Sectional Comparative Study done in 72 healthyschool going students (males) grouped into 2 according to the interventions (Deep water running and

Shallow water running). Cardiovascular parameters such as Heart rate (HR), Saturation of oxygen (SpO2),

Maximal oxygen consumption (VO2max) and Rate of Perceived Exertion (RPE) were assessed. Results:

Significant improvements in cardiovascular parameters were seen in both the groups i.e. by both the

interventions. Conclusion: Deep water running and Shallow water running can be used to improve

cardiac function in terms of various outcome measures used in the study.

Keywords: Deep water running, Shallow water running, cardiovascular responses.

INTRODUCTION

The importance of regular physical exercise, as part of

therapy in everyday life, has a favorable influence on

the important parameters of the cardiovascular system.

A number of studies have also shown that regular

physical exercise can decrease risk of the development

of many cardiovascular diseases and also other health

problems of both adults as well as children.1

People

who are physically active live longer. Regular exercise

reduces the risk of dying prematurely.2

Recommendations for appropriate amounts of

physical activity for the young population, including

school-age youth, have been developed by several

organizations and agencies. Although recent reviews

have summarized the benefits of regular physical

activity on the health of youth and its potential for

reducing the incidence of chronic diseases that are

manifested in adulthood, a more systematic approach

is indicated.1-9

These reports present results of a

systematic evaluation of evidence dealing with the

effects of regular physical activity on several health

and behavioral outcomes in school-age youth, with the

goal of developing a recommendation for the amount

DOI: 10.5958/j.2319-5886.3.1.027



138


of physical activity deemed appropriate to yield

beneficial health and behavioral outcomes.

According to the current worldwide survey, childhood

and adolescent health problems are one of the top five

problems in the world in the year 2012.3

They also

identified that this health issue is important not only

for the health care industry but also for the health of

the children as they mature into adults. The health

industry has recognized this problem and is beginning

to mobilize with new programs aimed specifically at

children. Numerous health risks have been associated

with adolescent overweight, including hypertension,

respiratory disease, several orthopedic disorders,

diabetes mellitus and elevated serum lipid

concentrations.4, 5

Development of specialized

physical activity programs are necessary as school

systems face the reality of cutting programs, such as

physical education and recess, to spend more time

preparing for the standardized tests and examinations.

Also; due to recent advances in technology; video

games and gaming consoles have become more

popular than outdoor sports activities thus; limiting

the regular physical exercise.

Current recommendations indicate that school-aged

youth should participate daily in 60 minutes or more

of moderate-to-vigorous physical activity that is

appropriate and enjoyable; and involves a variety of

activities including resistance training, aerobic

activities such as swimming, bicycling, running and

jogging.1, 3, 10

Program developed should be such that

it helps boys and girls develop competence and

confidence in their abilities to engage in different

types of physical activities. Fitness professionals who

incorporate such training into kid-friendly classes and

personal training sessions need to understand and

appreciate the physical and psychosocial perspective

of children and adolescents.11

Therefore, programdesign considerations for developing successful

programs should be such that regular participation in a

training program has the potential to positively

influence many health and fitness measures.

As the school going children especially the

adolescents’ need workout routine; it is advisable that

the routine is imbibed in the school’s class time table.

In India as a growing number of schools provide

swimming as one of the recreational activities; school

staff often fails to notice the boredom that is causedby the same activity. Deep as well as shallow water

running can be one of the best alternatives to

swimming. If the program is supervised and well

taught it can be beneficial for both physical as well as

psychological perspectives in the growth of the

children. But; the change following the water running

that would occur in terms cardiovascular parameters is

still unidentified are not expressed. The evidence

shows that there are many benefits of both deep water

running and shallow water running. Since there were

no prior studies performed to compare both the above

groups; hence, it’s very important to study the changes

in the cardiovascular responses and document them.

Hence; the aim of the study was to compare

cardiovascular responses after deep water running and

shallow water running. Accordingly the hypotheses

were formulated.

METHODS

There were 100 students who were screened for age,

symptoms, and/or risk factors for any medical

contraindications to exercise or any risk for disease.

After finding their suitability as per inclusion and

exclusion criteria were requested to participate in the

study.8 students did not meet the inclusion criteria.

The students were randomly selected for the study

with the use of random table numbers. Thus, out of 92

students 72 were selected to participate in the study.

These 72 students were explained about the study and

intervention. A written informed consent form

previously approved by the Institutional Ethical

committee (IEC) was obtained and was signed by the

School Principal and each student. The 72 students

participated in the study. The demographic data for

each student was filed. Pre treatment assessment of

HR; SpO2, RPE, VO2max were done.

In group A(N=35) students were receiving Deep

Water Running. It takes place in water deep enough

for students to be submersed to the neck. The use of

flotation aids, such as a buoyancy belt was used to

suspend the student so a lack of ground contact occurs

during the exercise. In Group B (N=37) students were

receiving Shallow Water Running. It was performed

in shallow water typically below the xiphoid level,

where students run/walk propelling themselves

through the water.12

Both the interventions were given for the duration of 6

weeks (3 times/ week) for 45minutes. At the end of 6weeks post test measurements of the students were



Anerao et al.,

taken. Data was collected and r

students completed the study. The

on the 1st

day of the intervention and

intervention for each participant.

RESULTS

The results of the study were anal

increase or decrease in Heart Rate,

and comparison was made between

day of the treatment. Statistical anal

GraphPad InStat (Trial version) s

were entered into an excel spreadsh

Table 1: Table showing demogr

Demographics

Age (years)

Height (mts)

Weight (kgs)

BMI(kg/m )

Fig.1.The following graph shows t

18th

day.

Table.2: Showing mean differenc

inference

Outcome Measure MEAN D

Group A

Heart Rate(b/m) 6.12±3.47

SpO2 0.4±0.14

RPE 4.06±0.63

VO2max(ml/kg/min) 16.41±4.3

The difference between parametsers

1 and on day 18were found to be ex

for HR (p= <0.0001) and RPE

VO2max (p=<0.0001), very signi

(p=0.0058). This indicates that th

0

20

40

60

80

100

Group A

Day1

79.37 80

98.14

5.6

40.1

Int J Med Res Healt

ecorded. All the

ata was recorded

on the 18th

day of

lyzed in terms of

O2max, RPE, SpO2

the first and 18th

lysis was done by

ftware. The data

eet, tabulated and

subjected to statistical

measures such a mean

test of significance suc

were utilized to analy

concluded to be statisti

and highly significan

significant with p>0.0

compare the difference

and post-intervention

‘t’ test was used to co

two groups i.e. the con

study group (Group B).

aphic data

roup A Group B

16.51+ 1.269 16.40+ 1.11

1.5+ 0.0943 1.57+ 0.064

4.17+ 6.853 52.10+ 4.40

2.12+1.773 21.02+ 1.32

e mean of parameters of participants in grou

e of outcome measures in Group A and G

IFFERENCE t df P

Group B

6.108±1.70 0.018 70 0.9851

0.27±0.11 4.338 70 <0.0001

4.22±0.55 1.142 70 0.2575

2 18.69±4.45 2.202 70 0.0310

for DWR on day

tremely significant

(p=<0.0001) and

ficant for SpO2

interventions in

form of Deep water ru

effective in improving

terms of Heart rate, Sp

The difference between

and on day 18 were fou

Group B Group A Group B

Day18

.173.25 74

98.37 98.54 98.64

5.67 1.5 1.45

39.77

56.51 58.

139

h Sci. 2014;3(1):137-143

analysis. Various statistical

, standard deviation (SD) and

as paired and unpaired ‘t’ test

e the data. The results were

cally significant with p <0.05

t with p < 0.001 and not

. Paired ‘t’ test was used to

s of scores on pre-intervention

ithin a single group. Unpaired

pare differences between the

trol group (Group A) and the

6

8

3

A and group B on 1st

day &

roup B and their Statistical

Inference

Not Significant

Highly Significant

Not Significant

Significant

nning in school children was

cardiovascular parameters in

2, RPE, and VO2max.

parameters for SWR on day 1

nd to be extremely significant

46Heart rate

SpO2

RPE

VO2max



140


for HR (p= <0.0001) and RPE (p=<0.0001), VO2max

(p=<0.0001), and SpO2 (p=0.0004). This indicates that

the interventions in form of Shallow water running in

school children was effective in improving

cardiovascular parameters in terms of Heart rate,

SpO2, RPE, and VO

2max.

The results between SWR and DWR on day 18 were

not significant in improving VO2max (p=0.2032), RPE

(p=0.5090), SpO2 (p=0.3224), HR (p=0.2253). This

indicates that both the interventions in form of Deep

water running and Shallow water running in school

children were effective in improving cardiovascular

parameters in terms of Heart rate, SpO2, RPE, and

VO2max.

The results of mean differences of the outcome

measures indicate that both Deep Water running and

Shallow water running improve Heart rate and RPE

similarly. The VO2max is improved more in Deep

Water running as compared to Shallow Water Running

and SpO2 is best improved during Shallow Water

Running as compared to Deep Water Running.

DISCUSSION

The study conducted in Loni; to compare Deep water

running to Shallow water running. It is also believed to

be the first study in India to compare the two water

running techniques in hydrotherapy. This study titled

cardiovascular responses in deep water running versus

shallow water running in school children was

performed in school boys aged between 15 to 19 years.

This population was chosen to generalize the results

for this age group. This study was conducted at

Pravara swimming pool, Loni, was completed in the

month of November 2012. The results of the study

indicated that the intervention in the form of Deep

water and shallow water running in school children

was effective in improving cardiovascular parametersin terms of Heart rate, Spo2, RPE, and VO2max and

were also comparable to other studies.

In a study by Chu KS et al in 200213

measured

maximal physiological responses to Deep-Water and

Treadmill Running in Young and Older Women, they

observed Lower HRmax values in DWR for both age

groups (p < .05). Another study by Town GP and

colleagues14

concluded that HRmax values for SWR and

DWR were 88.6% and 86% of TMR, respectively. In a

Comparative study the authors Michaud et al15

foundthat heart rate were significantly greater (p < 0.05) for

treadmill running. These results when compared with

the present study; the mean heart rate of participants

during Shallow water running and deep water running

at the end of the study were 73.25+2.201 and

74.13+3.66 respectively.

Authors noted that heart rate has been reported to

decrease during head-out water immersion exercise

compared with air.16-19

The mechanism responsible for

the lower heart rate during immersion is the

redistribution of blood volume from the periphery to

the central region. The increased hydrostatic pressure

of the water, concomitant with peripheral

vasoconstriction to reduce heat loss forces peripheral

blood into the thorax. This results in an enhanced

venous return and a decreased stroke volume while

maintaining cardiac output.17

The possible explanation

for reduction of heart rate in this present study was in

accordance with an explanation given by Sophie

Heywood.20

According to Sophie Heywood; the

hydrostatic pressure which is depth dependent; there is

increased stroke volume and cardiac output. The

Cardiac output (CO) is the product of Stroke volume

(SV) and Heart rate. Thus, during water immersion it

is found that heart rate is reduced.20

The hydrostatic

pressure causes an immediate increase in venous

return, right atrium pressure and, hence, stroke

volume. Increased stroke volume allows for the

maintenance of cardiac output with lower HR as stated

by Christie et al. in 1990.18

A reflex response of the

cardiovascular system to the cold receptors in the skin

could also have contributed to the depressed HR in the

water as the water temperature of 32.5 C is slightly

lower than thermo-neutral for the resting condition.21

This study showed extremely significant difference

between the SpO2 in SWR group at the start of the

study and SPO2 on at the end of the study (p<0.0001).

The mean SpO2 of participants in SWR at the end of the study was 98.54±0.5054. The difference between

the SPO2 in DWR group at the start of the study and

SpO2 on at the end of the study were very significant

(p<0.0001). The mean SpO2 of participants in DWR

on at the end of the study was 98.65 (SD= +0.4808).

These results are comparable with other studies.

Bishop et al.22

reported a higher O2 pulse during DWR

compared with TMR. Results of O2 pulse during

DWR was 4.34 and 3.81 during TMR (p<0.01). The

higher O2 pulse during DWR was largely a result of lower VO2 not that of higher HR.



141


The rate of perceived exertion measured in this study

was on the Borg’s (CR10) scale. In a study by authors

Hall et al studied the cardio-respiratory responses to

underwater treadmill walking in healthy females;

found that the Borg scale of perceived exertion(6-20)

showed that walking in water at 4.5 and 5.5 km/hr was

significantly harder than on land (p<0.001).23

It was

also concluded that walking in chest-deep water yields

higher energy costs than walking at similar speeds on

land.23

These responses were similar to the present

study. The difference between the RPE on at the start

of the study and RPE on at the end of the study were

extremely significant (p<0.0001) for both the groups.

The difference between the VO2max on at the start of

the study and Vo2max on at the end of the study were

extremely significant (p=<0.0001) for both the groups.

These results where comparable with a study by

Davidson K and McNaughton DK who examined the

ability of deep water running training to improve

cardiovascular fitness in a young sedentary population.24

Ten untrained female subjects were allocated into a

DWR and road running (RR) group. Subjects

underwent pre-test VO2max testing which was repeated

after each training program. Results indicated both

methods produced a significant increase in VO2max

compared with the pre-test without a significant

difference between the two.

Authors studied the intensity of exercise in deep-water

running and found that VO2 during the last session of

deep-water running (73% of maximum VO2) was not

significantly different from that of the treadmill hard

run (78%), but was significantly higher than that of the

treadmill normal run (62%).25

In a comparative study

it was found that peak oxygen consumption was

significantly greater (p < 0.05) for treadmill running.15

Although at a similar relative exercise intensity

treadmill running VO2, was significantly greater thandeep-water running. Several studies have shown that

maximal oxygen uptake (VO2max) attained during

treadmill running is lowered during DWR.16, 26-29

Town and Bradley in 1991 found that the highest

values reached for VO2 and HR were 73.5 and 86% of

VO2 max and HR max on land, respectively.28

A study

found VO2 and HR during DWR to be 86 and 91% of

those obtained on land.27

These findings are similar to

those reported in other studies.27, 30

Responses to sub

maximal exercise on the treadmill and when immersedto the neck have also been investigated.

30-32A study

reported lower HR during DWR than treadmill

running at any given VO2.30

Implications for practice: In the participants of this

study; it was found that both DWR and SWR serve as

effective tool in improving cardiovascular responses.

The above results point out that such form of exercise

if given as a form aerobic training may improve

cardiovascular indexes and so increases cardio-

respiratory endurance and parameters. The results also

indicate that both Deep Water running and Shallow

water running improve Heart rate and RPE similarly.

The VO2max is improved more in Deep Water running

and SpO2 is best improved during Shallow Water

Running so the intervention can be modified s per the

requirements of the participant.

In addition to benefits that physical activity has on

physical health and fitness, physical activity also has a

positive influence on academic performance and self-

esteem. Because of the protective and health benefits

of habitual physical activity, it is important that

children are physically active and that they continue

this behavior through adolescence into adulthood.

Aquatic therapy is justifiably a rapidly expanding,

beneficial form of rehabilitation. Understanding the

theory of water techniques is essential in implementing

an aquatic therapy program. The success of the

program depends on the pleasure and benefits

achieved by the patients. The environment should also

be conductive to family and social interaction that

ultimately encourages the compliance of long-term

exercise programs.

In the current study; all the boys who participated

successfully completed the study without missing a

single session with the same enthusiasm, eagerness,

zeal and keenness throughout the study. The goals

established at the initial and subsequent evaluations

were met as quickly and as sensibly as possible.Limitations of the study: Certain limitations of the

present study include small sample size, relatively

short term intervention, little follow up and the present

study has focused only on boys so the findings are

applicable to patients within this category only.

Suggestions for future research: Healthy school

going boys who were between the age group of 15 to

19 years were included in this study. Since the study

included regular participation for continuous 6 weeks

girls were not included for the same. Therefore; furtherstudy can be conducted to generalize the results for



142


female population. Also; this study was the first to

measure the cardiovascular parameters changes during

water running. Since the study was conducted in a

rural area, adequate instruments to measure VO2max;

were not available. Hence, future authors who are

interested in research can use a VO2max

analyzer for

their study. Moreover; as the above mentioned results

cannot be generalized to all the types of age groups in

both the genders; the same intervention must be

studied in another age group to see the effect of this

intervention in both the genders.

CONCLUSION

Thus accepting the alternate hypothesis and rejecting

the null hypothesis, we conclude that 6 weeks of

training given in terms of DWR and SWR is effective

in improving cardiovascular responses when measured

on PACER test, Borg’s Scale and Pulse oxymeter.

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causes in middle-aged men. Evidence from a 20-

year follow-up of the primary prevention study in

Goteborg. Ann Epidemiol. 1997;7(1):69-75.

2. Leitzmann MF, Park Y, Blair A, Ballard-Barbash

R, Mouw T, Hollenbeck AR, Schatzkin A. Physical

activity recommendations and decreased risk of

mortality. Arch Intern Med. 2007;167(22):2453-60.

3. Walter R. Thompson. Worldwide survey of fitness

trends for. ACSM’s Health & Fitness journal 2012,

15(6):9-18.

4. Gortmaker SL, Dietz WH Jr, Cheung LW.

Inactivity, diet and the fattening of America. J Am

Diet Assoc 1990; 90:1247-55.

5. Ramesh K Goyal, Vitthaldas N Shah, Banshi D

Saboo, Sanjiv pathak, Naveen Shah, Mukesh Gohel

et al Prevalence of Overweight and Obesity in

Indian Adolescent School Going Children: Its

Relationship with Socioeconomic Status and

Associated Lifestyle Factors. JAPI.2010; 58:151-

58.

6. Edu sports survey report 2012 view at

http://articles.timesofindia.indiatimes.com/2012-09

08/health/33018852_1_vitamin-d-deficiency-

lifestyle-obesity;

http://indiatoday.intoday.in/story/indian-kids-not-

involving-in-outdoor activities/1/154945.html;

http://www.dnaindia.com/academy/report_sports-

no-more-mere-childs-play_1711275.

7. Kapil U, Singh P, Pathak P, Dwivedi S, Bhasin S.

Prevalence of Obesity Amongst Affluent

Adolescent School Children in Delhi. Indian

Pediatrics 2002; 39:449-452.

8. Parekh A, Parekh M, Vadasmiya D. Prevalence of

overweight and obesity in adolescents of urban and

rural area of Surat,Gujrat. National Journal Of

Medical Research. 2012;2:( 3) 325-29.

9. Sedentary Lifestyle 2012 view at

http://articles.timesofindia.indiatimes.com/keywo

rd/sedentary-lifestyle/recent/5.

10. American College of Sports Medicine. ACSM’s

Guidelines for Exercise Testing and Prescription.

7th ed. Philadelphia: Lippincott Williams &

Wilkins, 2006.

11. Strong, W., R. Malina, C. Blimkie, Stephen R.

Danials, Rodney K. Dishman, Bernard Gutin et

al. Evidence based physical activity for school-

age youth. Journal of Pediatrics 2005;146(6) 732-

37.

12. Gappmaier E., Lake W, Nelson AG, & Fisher

AG. Aerobic exercise in water versus walking on

land: Effects on indices of fat reduction and

weight loss of obese women. The Journal of

Sports Medicine and Physical Fitness. 2006, 46:

564-69.

13. Chu KS, Rhodes EC, Taunton JE. Maximal

physiological responses to deep-water and

treadmill running in young and older women. J

Aging Phys Act 2002; 10: 306-13.

14. Town, G. P., S. S. Bradley. Maximal Metabolic

Responses to Deep and Shallow Water Running

in Trained Runners. Medicine and Science in

Sports and Exercise. 1991, 23 (2): 238-241.15. Michaud TJ, Rodriguez J, Andres FF, Flynn MG,

Lambert CP. Comparative Exercise Response of

Deep Water and Treadmill Running. Journal of

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Maximal physiological responses to deep and

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Levandoski SG, Kalkhoff RK, Hoffman MD,

Kalbflei Sch JH. Effect of increased central blood

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Physiological responses to treadmill and water

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144

Vidhya et al., Int J Med Res Health Sci. 2014;3(1):144-148


&

Health Sciences




thDec2013

Research article

A CADAVERIC STUDY ON ANATOMICAL VARIATIONS OF THE SUPERFICIAL PALMAR ARCH

Vidhya Ramakrishnan1, Anil kumar Reddy Y 2, Aruna. S3, Balaji Thotakura4, Suba Ananthi5

1,2 Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India.3 Department of Anatomy, Indira Gandhi Institute of Medical Sciences, Pondycherry, India4Department of Anatomy, Chettinad Hospital and Research Institute, Padur, Chennai, India


ABSTRACT

Background: The Superficial Palmar arch (SPA) is an anastomosis between the ulnar and radial artery in the palm.

Maximum contribution in the arch is by an ulnar artery and it is completed by superficial palmar branch of radial

artery or arteria princeps pollicis or arteria radialis indicis or median artery. The SPA develops as a terminal plexus

of axis artery which is later joined by median, ulnar and radial arteries as these arteries develop. Materials &

Methods: Present study conducted in the Department of Anatomy, Chettinad Hospital and Research Institute on 50

(28 right and 22 left) formalin fixed hands were used. The variations observed were classified as per Coleman and

Anson, 1961, classification of the superficial palmar arch. Results: As per Coleman and Anson classification,

complete arch of type A was seen in 43 hands (86%) and of type B in 3 hands (6%). In this study incomplete arch

was seen in 4 hands (8%, 1 right and 3 left), persistent median artery type H supplying the radial side of the palm

and digits was seen in only one hand (2%). Conclusion: The data regarding the study on variations of SPA is

helpful in crushing injury of hand, arterial grafting, and vascular trauma of the upper extremity.

Keywords: Superficial Palmar arch, Radial artery, Ulnar artery, Median artery, Coronary artery bypass graft

INTRODUCTION

A hand or manus is a prehensile, multi fingered body

part located at the end of upper limb or forelimb of

primates and some other vibrates used for both grossand fine motor skills. In order to perform its various

functions, it is richly supplied with blood vessels and

nerves1. The radial and ulnar arteries provide most of

the blood supply to the hands. Additional circulation

may come from the median artery or the interosseous

arterial system.

The superficial palmar arch (SPA) is an anastomosis

fed mainly by the ulnar artery. About a third of the

SPA are formed by the ulnar artery alone, a further

third are completed by the superficial palmar branchof the radial artery and a third by the arteria radialis

indicis, a branch of either arteria princeps pollicis or

the median artery2.

The radial and ulnar arteries form 4 circuits in thehand; anterior and posterior carpal arches at the level

of carpal bones, superficial and deep palmar arches at

the mid of palmar level3. Among these the superficial

and the deep palmar arches are the most important

circuits because they provide the principal blood

supply to all the structures in the hands. The SPA

develops as a terminal plexus of axis artery which is

later joined by median, ulnar and radial arteries as

these arteries develop4.

According to one of the extensive studies conductedon 1200 formalin fixed hands, by Coleman and Anson

in 1961, the variations in the SPA were classified as

DOI: 10.5958/j.2319-5886.3.1.028



145


complete and incomplete arches which were further

subdivided into various subtypes as follows3.

GROUP I – Complete Arch : Type A: classical radio

ulnar arch , Type B: Ulnar arch, Type C : mediano-

ulnar arch ,Type D: radio-mediano-ulnar arch, Type E:

ulnar artery & a branch from deep arch

GROUP II – Incomplete Arch : Type F: radial and

ulnar arteries without anastomosis, Type G; only ulnar

artery without supply to thumb and index finger, Type

H : ulnar and median arteries without anastomosis,

Type I: Median, radial and ulnar arteries without

anastomosis

Fig 1: Coleman and Anson classification

Hence the frequent anatomic variations encountered in

the formation of the SPA and increasing incidence of taking radial arterial grafts for coronary bypass

attracted the interest in checking its incidence.


For the current study 50 human cadaveric hands (28

right and 22 left) fixed in formalin (10%) solution,

hands in the Department of Anatomy, Chettinad

Hospital and Research Institute were used.

Macroscopic dissection of the palm was done

according Cunningham’s manual of practical anatomyand variations in the formation and branching pattern

of the SPA were studied, variation were noted and

compared with similar studies conducted previously.

OBSERVATION

Out of the 50 hands, complete arch was seen in 46

hands (24 right and 22 left) and incomplete arch in 4

hands. As per Coleman and Anson classification,

complete arch of type A was seen in 43 hands (86%)

and of type B in 3 hands (6%). Between the

incomplete arches, 3 were of type F (6%) and 1 was of

type H (2%) (Tab. 1)

Table 1: Incidence percentage of variations in the

current study

Arch type No. of hands Percentage

Complete arch 46 92Type A 43 86

Type B 3 6

Incomplete arch 4 8

Type F 3 6

Type H 1 2

Most of the arches seen in the current study were of

type A (Fig. 2), formed by the ulnar artery and

completed on the radial side either by the superficial

branch of the radial artery or princeps pollicis artery or

radialis indicis artery, branches of radial artery. Onlyulnar artery formed the arch (Fig. 3) in only 3 hands

and ulnar & radial without anastomosis (Fig. 4) in 3

hands. Persistent median artery supplying the radial

side of the palm and digits (Fig. 5) was seen in only

one hand.

Fig. 2: Complete arch, Type A – Classical radio

ulnar arch. (RA: Radial artery, UA: Ulnar artery)

Fig. 3: Complete arch, Type B – Ulnar arch . (UA:Ulnar artery)



146


Fig. 4: Incomplete arch, Type F – Radial and ulnar

arteries without anastomosis (UA: Ulnar artery, RA

: Radial artery).

Fig. 5: Incomplete arch, Type H – Mediano-ulnar

arch (2%), MA – Median artery, UA – Ulnar artery.

DISCUSSION

Advanced methods in Microsurgical techniques for the

reconstructing surgery of the hand and Upper

extremity and the choice of using a radial artery graft

during Coronary artery bypass grafting (CABG) have

necessitated the understanding of vascular architecture

in the palm.

Developmental the anomalies of blood vessels may be

due to: (i) The choice of unusual paths in the primitive

vascular plexuses. (ii) The persistence of vesselsnormally obliterated. (iii) The disappearance of vessels

normally retained. (iv) Incomplete development.

The normal arterial blood supply to the human hand is

well documented, although the vascular supply to the

hand and digits via the SPA is known to be variable

(Al-Turk & Metcalf, 1984; Iossifidis, 19954 , Ikeda et

al, 1988, Onderoglu et al, 19975). The systematic

arterial patterns of the hand were first described by

Jaschtschinski, 18976. Various anomalous patterns in

the arterial arches have been studied and various

classifications based on the contribution from the

formative branches, mainly superficial branches of the

radial artery and ulnar artery have been proposed by

various authors.

SPA was seen in all the 50 hands (100%) dissected (25

right, 25 left) unlike Brent et al7 (2010) who reported a

case of unilateral absence of the SPA in one hand he

observed. Complete arch was seen in 92% of the

hands (46, 22 left and 24 right) in the current study.

These results are similar to those reported by

MariosLoukas et al (2005)8, who observed the

presence of 90% complete arches in his study.

Although complete arches seem to be more prevalent,

as observed in the present study, in most of the studies

done by Coleman and Anson, 1961 (78.5%),

Suleyman et al, 2007 (75%) 9, Silvia et al, 2003 (60%)10, Nicolas et al, 2010 (58%) 11; some authors likeValeria et al, 2004 (47.5%) 12

and Elizabeth O’

Sullivan et al, 2002 (46.8%) 13 lesser incidence of

complete arches was reported.

The classical radio-ulnar arch formed by ulnar artery

and the superficial branch of radial artery or princeps

pollicis artery or radialis indicis artery (Coleman and

Anson, 1961, Type A) was seen in 43 hands (86%, 21

left and 22 right) in the current study unlike other

authors (Silvia et al, 2003, 67%; Suleyman et al, 2007,

40%; MariosLoukas et al, 2005, 40% and Colemanand Anson, 1961, 34%) who have reported a lesser

incidence of the same type.

The ulnar type of arch formed by the ulnar artery

alone (Coleman and Anson, 1961, Type B) was seen

in 3 hands (6%, 2right and 1 left) in the present study.

In comparison such an arch was more prevalent in

other studies such as Coleman and Anson, 1961, 37%;

Suleyman et al, 2007, 35%; MariosLoukas et al, 2005,

35%; Silvia et al, 2003, 23%.

In this study incomplete arch was seen in 4 hands (8%,1 right and 3 left) in par with Marios Loukas et al,

2005, who reported it in 10% of his study and unlike

other authors (Elizabeth O’ Sullivan et al, 2002,

53.2%; Valeria et al, 2004, 52.5%; Nicolas et al, 2010,

42%; Silvia et al, 2003, 40%; Suleyman et al, 2007,

25% and Coleman and Anson, 1961, 21.5%, who have

reported increased occurrence of the same (Fig. 6).



Vidhya et al.,

Fig. 6: Incomplete superficialCurrent study VsVarious authors

The most consistent incomplete ar

radial arteries without anastomosi

Anson, 1961, Type F), seen in 3 h

(6%, 2 left and 1 right hands). This

3.2% of the hands by Coleman an

20% of the hands by Suleyman e

33% of the hands by Silvia et al, 20

Fig. 7: Type F of incomplete sarch - Current study Vs Various a

Only one of Coleman and Anson,

median and ulnar arteries supplied

anastomosis, was observed in the c

left hand). Whereas Coleman an

3.8% of the same type and Silvia et

The other types of arches describe

Anson (Types C, D, E, G and I) we

the current study.

0%

10%

20%

30%

40%

50%

60%

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%30.00%

35.00%

Coleman &

Anson

1961

Suleyman

et al 2007

Silvia

20

Int J Med Res Health Sc

Palmar arch -

ch was ulnar and

s (Coleman and

ands in this study

type was seen in

Anson, 1961; in

t al, 2007 and in

3 (Fig. 7).

perficial palmar uthors

Type H, in which

the palm without

urrent study (2%,

Anson reported

al, 10 % ( Fig 8).

by Coleman and

re not observed in

Fig. 8: Various types

Coleman & Anson’s

CONCLUSION

The superficial and dee

rich anastomosis bet

Wounds of the palm bl

because of this anasto

artery or the SPA may

of the fingers, particul

anastomosis between th

arches.

The sound knowledge

the palm is crucial in

hand and in amputation

radial artery for cor

preventing possible

surgery. Identifying the

its participation in the a

ligation of radial or ul

trauma.In addition, the identifi

arterial pattern of

ultrasonography, p

oximetric techniques

various surgical inter

present study gives

understand the vascula

and rare variations in th

et al

03

Current

study

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Type

A

Type

B

Type

C

Colem

147

i. 2014;3(1):144-148

f arches - Current study Vs

p palmar arches account for a

een arteries of the palm.

eed profusely but heal rapidly

osis. An injury in the ulnar

ompromise the arterial supply

arly if there is an insufficient

e superficial and deep palmar

about the vascular patterns in

microsurgical procedures of

s and in the choice of using the

onary bypass graft and in

complications during hand

presence of median artery and

rch completion is important in

nar artery in case of vascular

cation of any variation in the

the hand using Doppler

otoplethysomography and

cquires great importance in

entions in the hand.14 The

necessary information to

architecture and its common

hand.

ype

D

Type

E

Type

F

Type

G

Type

H

Type

I

n and Anson 1961



148


REFERENCES

1. Al-Turk M, Metcalf WK. A study of the

superficial palmar arteries using the Doppler

Ultrasound Flowmeter. Journal of Anatomy. 1984;

138:27 – 32

2. Susan Standring. Williams and Warwick Editors –

Grays Anatomy 38th Edition.

3. Coleman S, Anson J. Arterial pattern in hand-

based upon a study of 650 specimens. Surgery.

Gynaecology. Obstetrics, 1961; 409-24

4. Iossifidis. Aneurysm of the superficial palmar

arch. International Orthopaedics (SICOT). 1995;

19:403-404.

5. Onderoglu S, Basar R, Erbil KM, Cumhur M.

Complex variation of the superficial palmar arch –

case report. Surgical and RadiologyAnatatomy.1997; 19:123 – 25

6. Jaschtschinski SN. Morphology and topography of

the Arcusvolarissublimis and profundus of the

person. Anatomy notebooks. 1897; 7:161-88.

7. Brent AC, Paula Ferrada, Roger Walcott.

Demonstration of unilateral absence of the palmar

arch without collateral circulation. British Journal

of Surgery. 2006; 60: 652-55

8. Marios Loukas. Anatomical variations of the

superficial land deep palmar arches. FoliaMorphology.2005; 64( 2); 115-18

9. Süleyman Murat Tagil. Variations and clinical

importance of the superficial palmar arch. S.D.Ü.

TýpFak. Derg. 2007; 14(2):11-16.

10. Silvia. Morphologic variations of the

superficialpalmar arc. Acta Cir Bras. 2003;18(3):

46-49

11. Nicolás Ernesto Ottone. Analysis and clinical

importance of superficial arterial palmar irrigation

and its variants over 86 Cases. International

Journal of Morphology. 2010; 28(1):157-64

12. Valéria Paula, SassoliFazan. Superficial palmar

arch: an arterial diameter study. J Anat.

2004;204(4): 307 – 11.

13. Elizabeth O’Sullivan, Barry S Mitchell.

Association of the absence of palmaris longus

tendon with an anomalous superficial palmar arch

in the human hand. Journal of Anatomy. 2002;

202(2): 253.

14. Takkallapalli Anitha. Variations in the formation

of superficial palmar arch and its clinical

significance in hand surgery. Int J Biol Med Res.

2011; 2(2): 543-46



149

Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154


&

Health Sciences




thDec 2013

Research article

COMPARATIVE STUDY OF GONADOTROPIN LEVELS AND CLINICAL PRESENTATION IN

SURGICAL AND NATURAL MENOPAUSE

*Naik Raviraj R, Chandel Rittu S, Abichandani Leela G

Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai,

Maharashtra, India


ABSTRACT

Introduction: Menopause means complete stoppage of menses for last one year due to failure of follicular

activities of the ovaries. This can be determined by the various hormones secreted by ovary such as LH and

FSH. As these hormones are responsible for normal maintenance of basic ovarian function in reproductive

life; there occurs considerable alteration in their levels in menopause. Aims and Objectives :- 1] To study

and compare ovarian function by determining levels of LH and FSH in Surgical and Natural menopause. 2]

To study and compare ovarian function in Surgical and Natural menopause. Brief Methodology: - Case

study: - 50 women with surgical menopause between 45 – 50 years of age. Control study: - 50 women with

natural menopause between 45 – 50 years of age. Material & Methodolgy :- Fasting serum samples of all womenwith surgical and natural menopause were analysed for LH and FSH on Immulite 1000 chemiluminiscence

based analyser in special investigation lab. Summary of the Results :- Mean levels of LH and FSH were

higher in surgical menopausal women as compared to natural menopausal women. Women in surgical

menopause suffered from more vasomotor symptoms and cognitive decline as compared to women in natural

menopause group

Keywords: Surgical menopause, Natural menopause, LH, FSH, Chemiluminiscence

INTRODUCTION

Follicle stimulating hormone (FSH) and LuteinizingHormone (LH) is secreted by beta cells of the

adenohypophysis. FSH controls the ripening of

primordial follicles and in conjugation with LH

activates secretion of estrogen. FSH is suppressed by

estrogen secretion through a negative feedback

mechanism.1

In conjugation with FSH, LH activates

secretion of estrogen, brings about the maturation of

the ovum and causes ovulation. Following

ovulation LH produces luteinization of granulosa

and theca cells and initiate progesterone secretion.

LH also stimulates the secretion of testosterone

and androstenedione in ovarian stroma which

diffuses into follicular fluid and are aromatizedinto estradiol.

1Menopause is defined as that point

in time when permanent cessation of menstruation

occurs following loss of ovarian activity.2

It takes

12 months of amenorrhoea to confirm menopause.

Sixty million women in India are above the age

of 55 years . It is therefore important to address all

these menopause related impairment and apply

prophylactic measures so that these women can

have an enjoyable and healthy life.3

Menopause

normally occurs between the ages of 45 and 55

years ; the average being 47 years3. Surgical

menopause is the cessation of menses resulting

DOI: 10.5958/j.2319-5886.3.1.029



150


from surgical removal of the uterus, leaving one or

both ovaries, or the removal of both ovaries.4Women

who have undergone hysterectomy with ovaries

preserved will experience menopausal symptoms

because of hypoestrogenism caused by depletion of

oocytes. Hysterectomy is surgery to remove a

woman’s uterus. In physiological or natural

menopause, the ovaries gradually lose function,

secreting less hormones over time. With surgical

menopause, the loss of ovarian hormones happens

instantly with no adaptation time. The onset of

menopausal symptoms is therefore much quicker

and symptoms are usually more severe.6

Symptoms

associated with surgical menopause are often more

severe than with natural menopause, particularly

the vasomotor symptoms of hot flushes and night

sweats.6 Hot flushes are the most common

symptom of the climacteric and occur in 75% of

postmenopausal women in whom it is more common

after Hysterectomy.7

Hot flushes tend to last longer

and be more severe in women who have had a

surgically induced menopause.8

It is recognized

that hot flushes occur with the pulsatile release of

LH.9

The symptoms are characteristic of a heat

dissipation response , and consist of sweating on

the face , neck and chest as well as peripheral

vasodilation. 10 There is an acute rise in the skin

temperature of several degrees centigrade,11

a

transient increase in heart rate , fluctuations in the

electrocardiographic baseline and a pronounced

decrease in skin resistance.12

Tataryn IV et al13

conducted a study on LH , FSH and skin

temperature during the menopausal hot flush and

found positive correlation of simultaneous skin

temperature and circulating LH levels. These data

suggest that LH or the factors that trigger its

pulsatile release are related to the mechanismresponsible for the initiation of hot flushes.

Depressed mood is more common after a

hysterectomy, as it results in a greater frequency and

severity of vasomotor symptoms.14

It could be a

'domino effect' of vasomotor symptoms, causing sleep

disturbance and tiredness, which in turn precipitate

depression.15

Cognitive decline is directly related to

hot flushes in women who have undergone

hysterectomy, but natural menopause itself does

not necessarily result in significant cognitivedysfunction.

16During a hot flush , blood flow

decreases in the hippocampus , possibly impairing

memory and cognition.16

Such reductions in blood

flow may contribute to the decreased mental

clarity and short-term verbal memory problems

experienced by postmenopausal women.16

Symptoms

of menopause are irritability, mood swings, sudden

tears, anxiety, depression, memory lapses,

headaches, vaginal tissue atrophy that can lead to

more urinary tract or vaginal infections and

urinary incontinence, loss of skin tone and

osteoporosis. Other symptoms include heart

palpitations, insomnia, loss of libido, vaginal

dryness and painful intercourse, fatigue, weight

changes and difficulty in losing weight, itchy skin

and difficulty in concentrating.6

Aims & Objectives

1.To study and compare hormonal levels of LH ,

FSH in Surgical and Natural menopause.

2.To compare the symptoms like hot flushes and

cognitive decline in Surgical and Natural menopause.


Place of study: Special investigation laboratory of

Department of Biochemistry, Grant Medical College

& Sir JJ group of hospitals. Samples were collected

from female patients and staff of the hospital.

Study design: Prospective study. Institutional Ethical

Committee clearance was taken.

Study population: Present study includes 50 women

(cases) belonging to surgical menopausal group and

50 women (controls) belonging to Natural menopausal

group.

Ethics: Institutional Ethical Committee approval,

Informed consent were taken from all the women

included in the study.

Period of study: July 2011 – September 2013.

Inclusion criteria:

1. Women aging between 44 to 50 years who haveundergone Total Hysterectomy in past one to two

years.

2. Women aging between 44 to 52 years who were

experiencing natural menopause since past one to

two years.

Exclusion criteria - women with:

1. Hormonal intake in any form e.g.: Drugs,

Soyaflavons.

2. Endocrine disorder. eg: Hyperpituitarism.

3. Ovarian Tumors.Blood Sample Collection- 5 ml blood sample was

collected by venipuncture in plain tube. All blood



151


samples were centrifuged at 4500 revolutions per

minute for 5 minutes to obtain clear serum. Serum

samples are then stored between 2-80C before

analyzing on Immulite 1000 chemiluminiscence

machine.

Biochemical Analysis: All the hormonal parameters

(LH, FSH) were measured by Solid Phase

Competitive Chemilumniscent Enzyme Immunoassay.

The solid phase (bead) is coated with rabbit anti-

hormonal polyclonal antibody. The reagent contains

alkaline phosphatase conjugated to respective

hormone. This hormone-enzyme conjugate competes

with respective hormone in patients blood sample

for limited antibody binding sites on bead. The

excess sample and reagent are removed by centrifugal

wash. Finally chemiluminiscent substrate is added

to the bead and the signal is generated in

proportion to the bound enzyme. Fully automated

enzyme amplified chemiluminescent immunoassay

based Immulite 1000 analyzers was used.

Measurement of these blood hormonal parameters was

done by using commercial kits from Siemens Medical

Solutions Diagnostics, Los Angeles, CA, USA.

Statistical analysis: Numerical variables were

reported in terms of mean and standard deviation. An

independent (unpaired) sample t-test was used to

compare the difference of means for independent

quantitative variables following normal distribution.

Pearson chi-square test was used to test the

significance of qualitative variables like symptoms.

Variables showing P-value less than 0.05 were

considered to be statistically significant and less than

0.01 as very significant. The SPSS software was used

for data analysis.

RESULTS

The present study included 50 women with surgicalmenopause and 50 women with Natural menopause,

thus a total of 100 subjects fulfilling the inclusion

criteria were enrolled in this study.

Age at Menopause: In this study the mean age at

menopause in the study group was 46.76 years ± 1.43,

while that in the control group was 50.9 ± 0.83

years. On applying independent (Unpaired) sample t

– test, the difference in mean age at menopause

between two groups was found significantly

different at the 0.01 level of significance.

Table:1. Mean Age statistics of surgical and

natural menopausal.

Menopause N Mean Age at menopause ±

Standard Deviation (Years)

Surgical 50 46.76 ±1.437

Natural 50 50.9 ±0.839

Mean Difference= -4.14 Years

Table 2: Serum mean LH level of surgical and

natural menopausal females

Menopause LH[mIU/ml] FSH [mIU/ml]

Surgical 37.32±2.924 104.62± 12.952

Natural 22.96±4.389 66.4±9.216

P Value < 0.001 < 0.001

Note: Reference values in Postmenopausal women

LH: 11.3 – 39.8 mIU/ml, FSH 21.7 – 153 mIU/ml

LH: In this study the mean level of Luteinizing

hormone in study group was found to be 37.32±2.92

while that in control group was 22.96±4.38. On

applying independent (Unpaired) sample t – test, the

difference between mean LH levels in both the groups

was found to be very significant with P value < 0.001.

FSH: In this study the mean level of Follicle

stimulating hormone in the study group was104.62±12.95 while that in the control group was

66.4±9.21. On applying independent (Unpaired)

sample t – test, the difference in mean FSH level in

both the groups was found to be very significant with

P value < 0.001. (Independent Sample t test:- t value

17, df-88.49, P value <0.001)

Table 3: Clinical feature of surgical and Natural

menopause

Surgical

menopause

Natural

menopause

Mood Swings 32 (64%) 20 (40%)

Osteoporosis 35 (70%) 27 (54%)

Hot Flushes 44 (88%) 28 (56%)

Irritability 44 (88%) 28 (56%)

headache 30 (60%) 18 (36%)

Memory lapses 33 (66%) 18 (36%)

anxiety 34 (68%) 20 (40%)

depression 30 (60%) 20 (40%)

Sudden tears 31 (62%) 15 (30%)

Vaginal tissue

atrophy

35 (70%) 16 (32%)



152


Hot flushes: In the present study 88% of the women

in surgical menopausal group had hot flushes as

compared to only 56% of women in natural

menopausal group. On applying Pearson Chi-square

test, the frequency of hot flushes in surgical

menopause was significantly higher than that in

natural menopause with P < 0.001.

Mood Swings : In the present study 64% of the

women in surgical menopausal group had mood

swings as compared to only 40% of women in

natural menopausal group. On applying Pearson Chi-

square test, the frequency of mood swings in surgical

menopause was significantly higher than that in

natural menopause with P < 0.05. Women with hot

flushes are more likely to experience disturbed

sleep, depressive symptoms and significant

reductions in quality of life. Women in surgical

menopause suffer more from hot flushes thus are

more affected by mood swings. LH and FSH levels

were found to be significantly increased in surgical

menopause as compared to natural menopause.

Women belonging to surgical menopause group suffer

more from hot flushes and mood swings as compared

to women in the natural menopause group.

DISCUSSION

In the present study the mean age of the surgical

menopausal group was significantly lesser than that

of the natural menopausal group; which was well

supported by another study done by Ozdemir S et al.17

Ovarian function was indeed depressed in the

natural menopausal women but was still preserved

for 1 to 2 years after menopause.18

In the present study, serum LH and FSH levels

in the group of women within 2 years after

surgical menopause were significantly higher than

those in the group of natural menopausal womenat a comparable period after menopause. Similar

finding were suggested by Nobuaki Furuhashi et

al18

who reported significantly increased levels of LH

and FSH within 2 years after surgical menopause as

compared to their levels in natural menopause.

Similarly Edward.E et al19

also found a significant

increase in LH and FSH levels in surgical

menopause. Carina C.W. Chan et al20

found that

women with hysterectomy had significantly

elevated serum FSH level and lower stromalblood flow indices as compared to healthy natural

menopausal women. S.Muttukrishna et al21

reported

that ovarian inhibin A & B were cleared from

circulation within short period of surgical

menopause which was responsible for early rise

of FSH in surgical menopause.

The ovaries are the predominant source of Inhibin

A and B22

which are characterized for their

inhibitory effect on pituitary follicle-stimulating

hormone (FSH) secretion23

, by a negative feedback

regulation24,25

. It has been speculated that after

surgical menopause and the fall in inhibins ;

estradiol and progesterone stimulates increase in

the synthesis as well as secretion of FSH and

LH.21

It is well established fact that estradiol

demonstrate a direct pituitary site of estrogen

negative feedback on LH and FSH responsiveness

to GnRH but the effect of estradiol on FSH

responsiveness is greater than that on LH and this

effect is attenuated with aging and menopause.26

This negative feedback is disrupted in surgical

menopause because of abrupt deficiency of

estradiol which may also contribute to more

increase in levels of LH and FSH when compared

with natural menopause.27

In the present study the

percentage of surgical menopausal women

experiencing hot flushes , mood swings was

significantly higher than that of natural

menopausal women. Pearce J et al28 and Bachmann

GA et al29

reported similar significant difference in

hot flushes percentage between two menopausal

groups and concluded that hot flushes tends to last

longer and be more severe in women who have

had a surgically induced menopause. Nachtigall et

al30

reported that 100% of surgically menopausal

women had vasomotor symptoms, and 90% had

severe symptoms which lasted an average of 8.5

years after menopause. Another study done by

Tataryn IV et al13

found a positive correlation of simultaneous skin temperature and circulating LH

levels. So it may suggest that LH or the factors

that trigger its pulsatile release relate to the

mechanism responsible for the initiation of hot

flushes.13

Depressed mood is more common after

surgical menopause, as it results in a greater

frequency and severity of vasomotor symptoms.31

So

it could be a 'domino effect' of vasomotor symptoms,

causing sleep disturbance and tiredness, which in turn

precipitate depression.

15



153


CONCLUSION

LH and FSH levels were found to be significantly

increased in surgical menopause as compared to

natural menopause. Significant increases in the levels

of these hormones are seen in surgical menopause due

to sudden decline in the function of ovarian activity.These women suffer more from hot flushes, cognitive

decline and mood swings as compared to women in

the natural menopause group.

ACKNOWLEDGMENT

Technical help at special investigation laboratory, JJ

Hospital


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ms/Surgical%20Menopause.pdf.htm 1999

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women. Am J Obstet Gynecol 1999; 180: S312 –

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measurement of hot flushes. Am J Obstet Gynecol

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Muninathan et al., Int J Med Res Health Sci. 2014;3(1):155-160

may have spread (metastasized) to other parts of the

body from the original tumor. Chemotherapeutic drugs

elicit some toxicity towards normal cells also, that

limits its usage.

Paclitaxel is a naturally occurring antineoplastic agent

has shown great promise in the therapeutic treatment

of certain human solid tumors particularly in

metastatic breast cancer, skin cancer, lung cancer and

refractory ovarian cancer6. Paclitaxel's antitumor

activity was discovered in1960’s during a large scale

35,000 plants-screening program sponsored by the

National Cancer Institute (NCI), USA. Paclitaxel is a

most effective drug in skin cancer, it has several

important side affects particularly neutropenia,

peripheral neuropathy and hypersensitivity reactions7.

Myelo suppression or neutropenia is the principal dose

limiting toxicity of paclitaxel on all administration

schedules. It is undeniable that the need for new agents

with both improved activity and acceptable safety

profile is urgent. Nausea, vomiting, thrombocytopenia,

mucositis, decreased appetite and diarrhea are the less

common side effects of administration of paclitaxel.

Ongoing clinical trials suggest that combining

paclitaxel with other anticancer drugs may be an

effective treatment for patients with skin cancer.

Researchers are exploring ways to reduce the side

effects of treatment improve the quality of patients'

lives, and reduce pain.

The chemotherapeutic and antitumor activity

associated with garlic has been attributed to the

presence of various organosulfide-based active

compounds including Di Allyl sulfide6. A topical

application of Di allyl sulfide is the most promising

approach for treating skin tumors as it leads to a

localized effect at the desired site with minimal side

effects. Polycyclic aromatic hydrocarbons (PAHs)

are commonly occurring environmentalcontaminants and are widely distributed in the

environment as pollutants of air, water and soil8.

Benzo (a) pyrene is the most toxic compound of

PAHs.9

The purpose of the present study is to evaluate the

combined effect of Paclitaxel and Di allyl sulfide

against the DMBA induced skin carcinogenesis.


Chemicals: 7,12 Dimethyl benz (a) anthracene and Diallyl sulfide were purchased from Sigma chemical

company, USA. All the other chemicals used were of

analytical grade.

Animal care and housing: Male Wistar rats, 6-8

weeks of age and weighing 150-200g, were used. The

animals were procured from Central Animal House

Block, Meenakshi Medical College and Research

institute, Kanchipuran, Tamil Nadu, India and

maintained in a controlled environmental condition of

temperature and humidity on alternatively 12 h

light/dark cycles. All animals were fed standard pellet

diet (Gold Mohor rat feed, Ms.Hindustan Lever Ltd.,

Mumbai) and water ad libitum. This research work on

Wistar male rats was sanctioned and approved by the

Institutional Animal Ethical Committee

Experimental Design

The animals were divided in to six groups of 6 animals

each.

Group I animals served as control,

Group II as animals treated with DMBA (5 µg/kg of

body weight) per animal in acetone (100 µL), three

times a week for 28 weeks to induce skin cancer.

After tumor induction:

Group III animals were treated with Paclitaxel

(33mg/kg b.wt) once in a week for 4 weeks in intra

muscular.

Group IV animals were treated with garlic extract of

Di allyl sulfide (250µg/animal) for 30 days daily.

Group V animals were treated with both Paclitaxel and

Di allyl sulfide (as in group III and group IV) daily.

After the experimental period of 32 weeks, the animals

were sacrificed by cervical dislocation. Blood sample

was collected via cardiac puncture, and add 2-3drops of

EDTA anticoagulant.

The following Biochemical analysis was done:

1. Estimation of total white blood cells:

Enumerated by the method of John (1972)10

2. Differential Leucocyte count: By the method of

John (1972)10

3. Soluble immune complex was estimated by the

method of Seth and Srinivas (1981)11

4. Nitro blue tetrazolium (NBT) reduction test:

was carried out by the method of gifford and

malavista (1970)12

5. Neutrophil function test: By the method of

Wilkinson (1977)13

6. Ig G was quantitatively measured: by Tenant et al

(1979) 14



157


7. Phagocytic index: by the method of Wilkinson

(1977)13

.

8. Avidity index: by the method of Wilkinson

(1977)13

.

RESULTS

Immunocompetent cells : Fig. 1 represents the effect

of paclitaxel and Di allyl sulfide on the status of

immunocompetent cells in various experimental

groups. Group II cancer bearing animals show a

significant (p<0.001) decrease in the cell counts when

compared with group I control animals. Paclitaxel and

Di allyl sulfide treatment caused a significant decrease

in leucocytes (p<0.05), lymphocyte (p<0.01),

neutrophils (p<0.01), absolute lymphocyte count

(p<0.05) and absolute neutrophil count (p<0.05). Di

Allyl Sulfide along with paclitaxel treated group V

animals caused a considerable changes (p<0.001;

p<0.01) in cell count. However the effect was more

pronounced in the group VI animals treated with both

paclitaxel and Di allyl sulfide when compared with

group I control animals.

Fig 1: Effect of paclitaxel and Di allyl sulfide on the status of immunocompetent cells

Immune complexes: Fig. 2 depicts the effect of

paclitaxel and Di Allyl Sulfide on immune complexes

like phagocytic index, avidity complex, NBT

reduction and SIC in various experimental groups.

Group II cancer bearing animals showed a significant

(p<0.001) decrease in the immune complexes when

compared with group I control animals. Paclitaxel

treatment caused a significant (p<0.01; p<0.05)

decrease in the levels of immune complexes. Upon

paclitaxel and Di allyl sulfide treatment there found to

be a significant (p<0.001; p<0.01) increase in the

levels of immune complexes.

Fig 2: Effect of paclitaxel and Di Allyl Sulfide on immune complexes

Units - Total leucocyte count : cu mm x 10

2

; Lymphocyte : % ; Neutrophils : %; Absolute lymphocyte count :mm3 x 102



158


Immunoglobulins

Fig 3 display the levels of immunoglobulins like IgG,

IgA, and Ig M in various experimental groups. IgG

and IgM levels were decreased considerably (p<0.001)

in cancer bearing group II animals with an increase

(p<0.001) in IgA level when compared with group I

control animals. Upon paclitaxel treatment the levels

of IgG, IgM were significantly (p<0.05) decreased

where as IgA level was increased (p<0.01) in group III

animals. Di allyl sulfide along with paclitaxel treated

group V animals showed considerable alterations in

the levels of Immunoglobulins (p<0.001) when

compared with group II cancer bearing animals. In

group VI animals treated with both paclitaxel and Di

allyl sulfide show no significant changes when

compared with group I control animals.

Fig 3: Levels of immunoglobulins like IgG, IgA, and Ig M in various experimental groups.

DISCUSSION

Immunomodulatory activities: Chemotherapy

remains the major hope for the treatment of cancer and

is always associated with some degree of haemopoietictissue toxicity and immune suppression. Although

cancer itself is immunosuppressive, cytotoxic

antineoplatic therapy is the primary contributor to the

clinical immunodeficiency observed in cancer patients.

Severe leucopenia, thrombocytopenia alterations in

circulating platelets, white and red blood cells are the

main side effects of chemotherapy leading to the

decrease of chemotherapy dose or discontinuation of

treatment.15

The most common complication

associated with cytotoxic antineoplatic therapy occurs

with the onset of neutropenia.16

Though paclitaxel is a

potent anticancer agent the major limiting side effect is

myelosuppression. It induces troublesome neutropenia

of grade 3-4 with decrease in WBC count in more than

50% of the patients.

Abnormal content of immunoglobulin indicate the

concised humoral immunity and reduction in immune

response. Thompson et a.l17

have reported decreased

levels of IgG and IgM in skin cancer conditions. The

levels of IgG and IgM were also decreased in various

other cancerous conditions.18-20 IgA content alone was

found to be increased in the skin cancer bearing rats.

Chandy et al21

, have reported that the elevated serum

IgA levels may be due to the failure of clearancemechanism by the damaged liver. This indicates the

severity of liver damage which directly correlates with

the progression of the disease.

A significant alteration in the neutrophil functions has

been observed in all our study. The killing ability of

the neutroplil as indicated by the NBT reduction and

phagocytic ability of the neutrophils as indicated by

the phagocytic index and the avidity index has been

significantly decreased in the cancer bearing animals

which was further decreased upon treatment with

paclitaxel.

Soluble serum immune complexes serve as an

indicator of immune responses either due to presence

of excess antigens or antibodies. This may be due to

decreased antibody production during cancer.

Immunomodulation through natural or synthetic

substances may be considered as an alternative for the

prevention and cure of neoplastic diseases.22, 23

Flavanoids are polyphenol substances of plant origin,

having biological and antioxidative properties.24

Several reports have demonstrated the beneficial effect



159


of flavanoids in preventing toxicity of different

agents.25-27

Flavanoids display a remarkable array of biochemical

and pharmacologiocal actions some of which suggest

that certain members of this group of compounds

significantly affect the function of the immune system.

They also affect the function of enzyme system

critically involved in the immune system. Di allyl

sulfide contains organo sulfur compounds that play a

very important role in scavenging free radicals. In our

study also Di allyl sulfide exhibited positive effect on

the immune system which can be attributed to its

flavanoid content. Ali et al. (2000) have reported that

Di allyl sulfide stimulates immune response in rats.

Mesbah Lahouel28

have reported the effect of Di allyl

sulfide on haemotoxicity of chemotherapeutic drugs.

Considering the possible mode of antitumor action of

Di allyl sulfide it is likely that it could be mediated by

immunomodulatory activity of Di allyl sulfide. The

present study has given the hope that Di allyl sulfide

can confer in the reduction of side effects due to

chemotherapeutic agents and may be used in humans

in future.

CONCLUSION

From the present study, the effect of Paclitaxel- DAS

combination proved to be effective chemotherapeutic

agent against DMBA induced skin cancer in wistar

rats compared to that of paclitaxel or Di allyl sulfide

confirmed analyzing the total white blood cells,

Differential leukocyte count, Soluble immune

complex, neutophil function tests, IgG, IgM, IgA

levels and Phagocytic , Avidity indexs in blood

samples

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Rajesh et al., Int J Med Res Health Sci. 2014;3(1): 161-164


&

Health Sciences




thDec 2013

Research article

A STUDY ON EARLY DETECTION OF CHANGES IN VISUAL PATHWAY DUE TO DIABETES

MELLITUS BY VISUAL EVOKED POTENTIAL

Rajesh Kumar1, Sundararajan D

2, Rajvin Samuel Ponraj

3, M Srinivasan

4




4Professor, Department of Ophthalmology,

Meenakshi Medical College and Hospital, Kancheepuram, Tamil Nadu, India


ABSTRACT

Electrical potentials have been recorded by surface Evoked Potentials namely the Somatosensory Evoked Potential,

Auditory Brainstem Response and Visual Evoked Potential [VEP]. Visual conduction disturbance can be evaluated

by these instruments. A mass response of cortical and possibly subcortical may be represented, visual areas to visual

stimuli. Diabetic patients without a past history of cerebrovascular accidents diagnosed with Non- Proliferative

Diabetic retinopathy[DR] with a best corrected visual acuity at least 6/9.This study was done to assess whether a

delay in VEP latency observed in diagnosed type II DM patients could be ascribed to dysfunction of the retinal or

post retinal structures or by both. It is to find out whether the VEP latencies are altered in diabetes or not, if altered

and to correlate duration of the diabetes mellitus with visual evoked potential changes. Visual evoked potentials are

useful as a non invasive investigatory method in establishing central nervous system neuropathy developing in

diabetes. This study clearly shows that changes in VEP may be detected in diabetics before the onset of retinopathy.

Future studies should be focused on evaluation of the time that elapses between the appearance of the first

detectable pathologic electrophysiologic changes and the first ophthalmoscopically detectable retinal changes in

patients with Diabetes Mellitus [DM].

Keywords: Pattern reversal, Photostress, electrodes.

INTRODUCTION

Electrical potentials that occur in the cortex afterstimulation of a sense organ, which can be recorded by

surface electrodes, are known as Evoked Potentials

[EP]. e.g. Somatosensory Evoked Potential (SEP),

Auditory Brainstem Response (ABR) and Visual

Evoked Potential (VEP).

A change has been observed over time with the

clinical use of Electric potentials. There have been

advances in imaging technology, especially in

magnetic resonance imaging (MRI), have reduced the

use of EP testing in clinical practice. MRI largelyremains an imaging, structural, or anatomic test and

therefore gives more accurate information about

structural problems. EP testing assesses functionalityand thus supplies information about the physiology of

a certain anatomic pathway, providing much less

spatial or localizing information than MRI does.1

These electric potentials are used in the detection of

anterior visual conduction disturbance. A mass

response of cortical and possibly subcortical may be

represented, visual areas to visual stimuli.2,3 VEP

affection is related to age of onset of diabetes and

glycemic control. Any abnormalities in the visual

pathway can be detected with the help of VEP

much prior to appearance of visual symptoms orchanges in fundus examination.

4

DOI: 10.5958/j.2319-5886.3.1.031



Rajesh et al.,

These equipments permit on

structures which help in visual

conduction.5

Evaluation of bioel

the retinal layers is done wi

electroretinographic

signals with patterned stimuli (P

The aim of this study is to evaluate t

abnormalities in diabetic patients w

and with non-prolierative diabetic re

and to determine abnormal fr

investigate the relationship betwe

such as duration of diabetes and d

control.

Fig 1: Visual evoked potential3

Aim & Objectives

Aim: Aim of this work is to assein VEP latency observed in diagn

patients could be ascribed to dysfun

or post retinal structures or by both.

Objectives: 1. To find whether the

are altered in diabetes or not. 2. To

of the diabetes mellitus with visual

changes.


Experimental design: A cross secti

Subjects: Patients were selected f

of Ophthalmology Department of

College & Hospital, Kanchipura

consent and ethical committee cle

taken for this study.

Inclusion criteria:

1. No past history of cerebrova

2. Diabetic patients with durati

3. Non- Proliferative Diabetic r

4. Best corrected visual acuity

Exclusion criteria:

Int J Med Res Health Sci

sectioning of

pathway neural

ectric activity of

th the help of

RG)6.

he visual pathway

ithout retinopathy

tinopathy (NPDR)

equency and to

n other variables

gree of metabolic

ss whether a delay osed type II DM

ction of the retinal

VEP-PR latencies

correlate duration

l evoked potential

nal study.

om the outpatient

eenakshi Medical

. An informed

arance have been

scular accidents

on of 1-10 years.

etinopathy

at least 6/9

1. Cataract, 2. Gla

any evidence of optic

system disease 5. Prolif

General examination a

General examination

Ophthalmology and

Cerebrovascular diseas

Optic nerve pathology a

Visual evoked poten

pattern reversal stimul

Study Group: The st

Group I, Group II and

Group I: 40 normal a

were selected as control

Group II: 40 subject

retinopathy, with durati

year to 10 years

Group III: We evaluat

with non-proliferatve

diabetes varying from 1

In this study waveform

100 and N 75 and amp

the parameters. Visual

Diopsys Nova Compan

on the scalp as shown i

stimulus is rarely use

within and across subje

utilize alternate light

respectively. These sq

equal are then presente

screen.

Fig 2: Placement of El

used: 1.Frontal (FP2), 2

(C2) electrodes6

Statistical Analysis:

sample t test") was u

between control and dia

of variance (ANOVA)

VEP latencies and ampl

different level of glyce

162

. 2014;3(1): 161-164

ucoma 3. Vitreous opacities or

atrophy 4. Peripheral nervous

rative diabetic retinopathy

nd systemic examination:

as done in the Department of

a detailed history of

es, Cataract, Glaucoma, any

nd TB was taken.

tials were recorded using

ation

dy groups were divided into

roup III.

ge and sex matched subjects,

group.

s with DM Type II without

on of diabetes varying from 1

d 40 subjects with DM type II

retinopathy with duration of

year to 10 years.

pattern latencies which are P

litude of VEP were chosen as

voked Potential used from the

with the electrodes placement

n Fig 2: The diffuse light flash

due to the high variability

cts. The checkerboard patterns

nd dark squares and stripes,

uares and stripes which are

one at a time via a computer

ectrodes, Scalp electrodes was

. Occipital (O2), 3. Grounding

Student‘t’ test (Independent

sed for comparison of VEP

betes group. One way analysis

was used for comparing the

itude with duration of DM and

ic control



10


RESULTS

Table 1: Tabulation comprising 40 patients studied over period of 10 years

No. of

SubjectsAge Duration of DM

Group I 40 49.13 ± 4.52 -

Group II 40 52.70 ± 3.87 4.00 1.76

Group III 40 53.33±4.39 5.47 ± 2.25

Table 2: Comparison of P100 latency, N75 latency of Visual Evoked Potential

No. of Subjects P100 latency (ms) N75 latency (ms) P value

Group I 40 93.82 ± 2 67.46 ± 5.28 < 0.0001*

Group II 40 100.30 ± 4.91 70.76 ± 6.77 < 0.0001*

Group III 40 107.30 ± 4.54 73.81 ± 4.58 < 0.0001*

* The mean difference is significant at the < 0.05 level

Table 3: Comparison of Amplitude of Visual Evoked Potential between the groups

No. of

SubjectsAmplitude (v) p value

Group I 40 7.52 ± 1.18<0.0001*

Group II 40 3.61 ± 1.24

Group III 40 2.77 ± 1.56


Table 4: Relationship of various glycemic levels of Diabetes Mellitus with Visual Evoked Potential Latency

(P100).

FBG

(mg/dl)

No. of

Subjects

P100 latency

(ms)

Amplitude (v) p value

<126 25 97.81 ± 4.25 4.35 2.04

> 0.0001*126-145 20 103.60 3.07 2.92 1.39

>145 35 108.40 3.70 3.28 1.90


Table 5: Analysis of P100 Latency in regard with different durations of Diabetes Mellitus:

Duration (yrs) No. of Subjects P100 latency (ms) Amplitude(ms) p value<3 28 96.31 6.38 5.54 1.61 < 0.0001*

3 –

7 28 102.29 1.72 3.30 0.98 < 0.0001*7 – 10 24 105.79 2.92 1.83 0.45 < 0.0001*


Relationship between duration of diabetes and VEP

latency and amplitude: Among the subjects, the

duration of type II diabetes mellitus was found to be

between 1 year and 10 years with a mean of 4.73 ±

1.42 years. The subjects were distributed into 3 groups

based on the duration of diabetes - Subjects > 3 years,

3 – 7 years and < 7 years duration of diabetes mellitus.

Amplitude of VEP and duration of diabetes: The

mean P100 – N145 amplitude was significantly

reduced with the increasing duration of diabetes.

(p.value <0.05)

DISCUSSION

Peripheral and central neuropathy in diabetic patients

can be determined by Electrophysiological

investigations. Many patients who were clinicallyexamined showed a decrease of nerve conduction

velocity.



164


In our study it appears that pattern stimulated VEP

(P100 and N75 latencies) in people with diabetes

mellitus shows a distinct prolongation of the latency

period which could be explained with findings of

Karlica et al.3

In our study VEP latencies and amplitude was

correlated with duration of diabetes and we found

there was a significant changes in VEP. This could be

explained from the basis of poor metabolic control,

diabetes duration, dislipidemia and diabetic

nephropathy and the probable physiological

mechanism could be that VEP abnormalities for both

eyes is associated with parasympathetic autonomic

neuropathy and the hyposthetic form of lower-limb

sensory neuropathy.

The mean N75 latency, P100 latency and P100-N145

amplitude were prolonged in those with HbA1c >7%

but the difference were not statistically significant.

CONCLUSION

Visual evoked potentials are useful as a non invasive

investigatory method in establishing central nervous

system neuropathy developing in diabetes.

This study clearly shows that changes in VEP may be

detected in diabetics before the onset of retinopathy.

This study also shows that the VEP changes may be

related to the poor control and long duration of the

disease, both of which were associated with significant

VEP latency prolongation and decreased amplitude.

Thus VEP measurement is essential for the detection

of pre retinopathy changes and has the potential to

reduce DM complications.

Furthermore, it can be performed whenever a patient

with diabetes without retinopathy shows a worsening

of metabolic control, to evaluate the impairment of

visual pathways. It is important to emphasise that,

when tight metabolic control is achieved, theseabnormalities disappear, suggesting that VEP

impairment is only functional and completely

reversible.

Future studies should be focused on evaluation of the

time that elapses between the appearance of the first

detectable pathologic electrophysiologic changes and

the first ophthalmoscopically detectable retinal

changes in patients with DM.

REFERENCES

1. Marco Alessandrini, Vincenzo Parisi, Ernesto

Bruno, Pier Giorgio. The relationship with visual

pathways function , Impaired saccadic eye

movement in diabetic patients: Documenta

Ophthalmologica 1999;99: 11-20

2. Andrew BE, Jane G Boggs. Clinical Utility of

Evoked Potentials. Journal name. 2010;vol:pgnos

3. Dobrila Karlica, Davor Galetovi, Milan Ivanisevi,

Veselin Skrabi, Ljubo Znaor and Darija Juri.

Visual Evoked Potential in the Detection of

Prediabetic Form of Diabetic Retinopathy in

Patients with Diabetes- Mellitus. Antropol.

2010;34(2): 525-29

4. Samahy RM, Matter AM, Nassef, Osman AF.

VEP in children and adolescents with type l

diabetes mellitus. Pediatric Diabetes, 2010,Suppl.

14: 35

5. Vincenzo Parisi, Luigi Uccioli, Giovanna

Monticone, Leoluca Parisi, Gianluca Manni,

Daniel Ippoliti, etal., Electrophysiological

assessment of visual function in IDDM patients.

Electroencephalography and clinical

Neurophysiologjy. 1997;104, 171 -79

6. Vincenzo Parisil, Luigi Uccioli. Visual

electrophysiological responses in persons with

type l diabetes. Diabetes/Metabolism Research and

Reviews, 2001; 17: 125:18



165

Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170


&

Health Sciences




thDec 2013

Research article

EFFECT OF 30°AND 60° HEAD UP TILT ON CARDIOVASCULAR RESPONSES IN NORMOTENSIVE

AND HYPERTENSIVE INDIVIDUALS

*Badwe AN1, Soodan KS

2, Kulkarni NB

3, Latti RG

4


3Professor,

4Professor & HOD, Department of Physiology, Rural Medical College, Pravara

Institute of Medical Sciences, Loni, Rahata, Ahmednagar, Maharashtra, India2

Ex-Principal Rural Medical College, Pravara Institute of Medical Sciences, Loni, Rahata, Ahmednagar,Maharashtra, India

*Corresponding author email: [email protected], Mob: +91-9096035553

ABSTRACT

Since 50 years, head up tilt table testing is being used by physiologists and physicians for different purposes. Many

investigators have studied the effect of head up tilt at a specific angle on cardiovascular and autonomic functions in

healthy individuals and reported usefulness of HUT in assessing the integrity of cardiovascular and autonomic

functions. In present study effect of 30° and 60° head up tilt is studied on cardiovascular parameters (systolic blood

pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial blood pressure (MAP), heart

rate/min (HR), rate pressure product (RPP)) in normotensive and hypertensive individuals. METHODS: Effect of

30° and 60° head up tilt on cardiovascular parameters was studied in normotensive (n=50) and hypertensive

individuals (n=50) aged 15-70 years. Blood pressure and heart rate were determined by using electronic blood

pressure apparatus. RESULTS: 30° and 60° HUT produced decrease in SBP, PP, MAP and increase in DBP, HR,

RPP in both groups. The results were significant at selected different time intervals. The changes produced by 60°

HUT were more significant than 30° HUT. The changes produced in the hypertensive group were more prominent

than normotensive group. In conclusion significant changes in HR and RPP in hypertensive individuals indicated

more myocardial oxygen consumption and myocardial work at both angles of HUT.

Keywords: Hypertensive, head up tilt, cardiovascular parameters

INTRODUCTION

Since 50 years, head up tilt table testing is being used

by physiologists and physicians for different purposes.

This includes effect of head up tilt (HUT) on heart rate

and blood pressure changes in posture, for modeling

responses to haemorrhage, as a technique for

evaluating orthostatic hypotension, as a method to

study haemodynamic and neuroendocrine responses in

congestive autonomic dysfunction and hypertension,

as well as tool of drug research.1-6

Many investigators have studied the effect of head up

tilt at a specific angle on cardiovascular and autonomic

functions in healthy individuals and reported

usefulness of HUT in assessing the integrity of

cardiovascular and autonomic functions.7,8

From literature survey conducted, it is found that,

there are few studies conducted to study the effect of

head up tilt on cardiovascular responses in

hypertensive individuals. The studies conducted so far,

have studied the effect of head up tilt mainly on

cardiovascular parameters such as Systolic blood

pressure (SBP), Diastolic blood pressure (DBP), heart

rate variability (HR), Cardiac output (CO).9-10

Hence

in the present study we decided to study the following

objectives in selected hypertensive patients from the

DOI: 10.5958/j.2319-5886.3.1.032



166


Medicine department and the Family Medicine

Department of Pravara Rural Hospital, Loni.

Objectives:1. To study the effect of 30° and 60° head

up tilt on cardiovascular parameters

2. Comparison of investigated parameters in

normotensive group and hypertensive group

MATERIALS AND MEHTODS

It was a case control study conducted in the

department of Physiology at Rural Medical College,

Pravara Institute of Medical Sciences. The male

subjects selected for the study were between the age

group of 20-70 years (n=100) and were grouped in two

groups as:

1. Normotensive (control group n=50)

2. Hypertensive (Study group n=50)

Control group: Age matched normotensive healthy

subjects were selected as control and were selected

from clerical, teaching staff and students of our

institute, who fulfilled following criteria, were

included as control subjects in the study:

• No signs of cardiac, vascular or neurological

involvement

• No history of diabetes mellitus, hypertension

• No history of drug treatment

• No history of systemic illness

Their normal blood pressure status was considered

according to guidelines of, Seventh Report of the Joint

National Committee (JNC7)11

on Prevention,

Detection, Evaluation and Treatment of high blood

pressure and Indian Hypertension Guidelines II, 2007

with optimal value as <120/<80 mm Hg and further

variations in systolic blood pressure was considered in

the range of 120-139 mmHg.Diastolic blood pressure

variation was considered in the range of 80-89 mmHg.

Study group (Hypertensive): Study group included

the hypertensive patients attending to Medicine

department and the Family Medicine Department of

Rural Medical College on outpatient basis.

Hypertensive subjects suffering from major illness

such as severe diabetic condition, congestive heart

failure, coronary artery disease, arrhythmias were

excluded from the study.

Same type of exclusion criteria was used for inclusion

of normotensive subjects in the proposed study. The

study protocol was approved by the Institutional

Research Ethical Committee.In this group also patients were between the age group

of 20-70 years with diagnosed hypertension (i.e.,

history of hypertension less than 1 year).Hypertensive

subjects were considered as, having systolic blood

pressure of 140-159 mmHg and diastolic blood

pressure of 90-99 mm Hg (Grade I hypertension =

According to Joint National committee VII and Indian

Hypertension Guidelines II, 2007).11-14

These subjects were under treatment or on blood

pressure lowering medication with controlled

hypertension (target blood pressure value 140/90) at

the time of study. Their hypertensive status was

determined by consulting physician of Medicine

department and Family Medicine department.

METHODS

All subjects were called by appointment in the

laboratory, 2 hours after light brake fast in the morning(09.00am-12.00pm). Subjects were instructed not to

consume caffeinated beverage and to avoid smoking

before 12 hours of the test. Subjects were informed in

detail about study protocol and written consent was

obtained before the study.

Before beginning of the test, anthropometric

characteristics such as height (cm), weight (Kg), body

mass index (BMI, Kg/m2), percent fat (%), fat mass

(FM, kg), fat free mass (FFM, kg) were recorded in all

subjects.

Percent fat (%), fat mass (FM, kg), fat free mass

(FFM, kg) parameters were determined by method of

measurements of girth as described by McArdle et al.15

Subjects were made to lie comfortably on tilt table for

20 minutes in the supine position. Three straps were

applied at the level of knee, waist and head. After 20

minutes of rest baseline cardiovascular parameters

(SBP, DBP, PP, MAP, HR/MIN, RPP) were recorded

at 1,5,10 minutes of interval by using digital blood

pressure monitor (Digicheck, Japan).

Thereafter subjects underwent gradual head up tilt at

30°, 60° angles of tilt with the speed of 5°/Sec. During

head up tilt manoeuvre passive head up tilt protocol

was followed only for 10 minutes. Tilt table with foot

board was used in the study to support body weight.

The following sequence of recording was followed.

1. Basal: 20 minutes of rest on tilt table in supine

position2. After 30° HUT

3. After 60° HUT

Cardiac parameters were recorded immediately after1,5,10 minutes of HUT. Between each HUT the



167


subject was tilted back to horizontal position and

allowed to rest for 10 minutes.

Statistical analysis: For each parameter of both

groups-mean and standard deviation (SD) were

calculated. To find any significant change the data was

analyzed for the same group by applying Student t –

test and between two groups by applying unpaired t-

test. The P values less than 0.05 (P<0.05) were

considered as statistically significant.

RESULTS:

Table:1. Anthropometric characteristics of subjects

Parameter Normotensive Hypertensive

Age(yrs) 35.72±1.88 49.28±1.94

Height (cm) 163.86±1.01 164.74±1.10

Body weight kg 55.26±1.20 65.56±1.71

BMI (Kg/m2) 20.81±0.48 24.21±0.57

% Fat 23.89±1.01 31.10±1.05

Fat Mass (Kg) 13.47±0.67 21.02±1.18Fat Free Mass (Kg) 41.76±0.92 43.94±0.82

Values are Mean ± SE

Higher values of anthropometric characteristics were

recorded in hypertensive individuals as compared to

control group, which were non significant (Table: 1).

All results are presented graphically for better

understanding of the effect produced by both angles of

head up tilt in both study groups.

Table: 2. Effect of 30°, 60°head up tilt on cardiovascular parameters in normotensive

Parameter Basal 30°HUT 60° HUT

1 Min 5 Min 10 Min 1 Min 5 Min 10 Min

SBP 121.4±1.66 117.44±1.80*‡‡‡ 118.42±2.03‡‡‡ 119.64±1.79‡‡‡ 116.94±2.13* 121.84±1.78 117.66±2.14*

DBP 76.26±1.30 77.04±1.30‡‡‡ 77.22±1.21‡‡‡ 78.1±1.57 78.8±1.43 80.26±2.25 80.54±1.58*PP 45.88±1.29 40.4±1.64*** 41.2±1.70* 41.7±1.71* 38.34±1.66*** 40.24±1.90* 37.4±1.67***

MAP 91.51±1.60 90.43±1.79 89.53±1.82 90.24±1.80 91.49±1.51‡‡‡ 93.09±2.31‡‡‡ 92.88±1.62‡‡‡

HR/MIN 75.6±1.60 78.14±1.79*††† 80.52±1.82***††† 79.6±1.80*††† 89.24±2.01*** 91.56±1.93*** 89.62±2.56***

RRP 9.0±2.74 9.09±2.30 9.48±2.59* 9.72±1.16** 10.43±0.31***††† 11.35±0.41***††† 10.64±0.33***†††

Values are Mean ± SE. Pressure values are in mmHg. Basal values are before tilt. SBP: systolic blood pressure,

DBP: diastolic blood pressure, PP: pulse Pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min

RPP: rate pressure. (Paired t – test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly

significant, Comparison between 30° and 60° head up tilt: †P<0.05significant, ††P<0.01 highly significant

†††P<0.001 very highly significant, Unpaired t test: ‡P<0.05 significant, ‡‡P<0.01 highly significant ‡‡‡<0.001

very highly significant)

Normotensive: 30° HUT caused minimal and

significant decrease in SBP after 1 min of HUT. After

1 minute of tilt, there was minimal decrease in SBP,

which remained insignificantly lower than basal value

for a total duration of 10 minutes of HUT.

DBP showed a marginal increase than basal value after

1 minute of HUT and remained almost constant

throughout the 10 minutes duration of HUT.

PP registered very highly significant decrease

(P<0.001) in its value than the basal value after 1

minute of tilt and showed a further significant decrease

(P<0.05) at 5 and 10 minutes of HUT.

MAP (=DBP+1/3 PP) showed insignificant decrease

after 1 minute of HUT and the same pattern was

continued for 5 and 10 minutes of HUT.

HR also registered increase in its value, which was

more than basal value. This change was significant

after 1minute (P<0.05) and at 5 (P<0.001), 10

(P<0.05) minutes of HUT.

RPP showed a marginal insignificant increase in its

value after 1 minute of HUT, however after 5 (P<0.01)

and 10 (P<0.001) minutes of HUT, RPP registered a

significant increase in its value.



168


60° HUT: 60° HUT produced more significant

changes in cardiovascular parameters as compared to

30° HUT. SBP decreased significantly (P<0.05) after 1

and 10 minutes (P<0.05) of HUT. Insignificant

increase was observed at 5 minutes of HUT, than basal

value.

DBP registered a marginal insignificant increase at 1

and 5 minutes of HUT, however at 10 minutes of HUT

significant (P<0.05) increase in DBP was recorded. PP

registered significant decrease at 1(P<0.001),

5(P<0.05), 10(P<0.001), minutes of HUT. This

decrease was lower than basal value. MAP showed

insignificant decrease in its value after 1,5,10 minutes

of HUT. HR registered very highly significant

(P<0.001) increase as compared to basal values

throughout the duration of 10 minutes of HUT. RPP

also recorded very highly significant (P<0.001)

increase in its value as compared to basal values

throughout the duration of 10 minutes of HUT

Table: 3 Effect of 30° and 60°head up tilt on cardiovascular parameters in hypertensive

Parameter Basal 30°HUT 60° HUT

1 Min 5 Min 10 Min 1Min 5 Min 10 Min

SBP 140.4±3.59 141.72±2.48 142.48±2.70† 140.5±2.58† 137.4±3.04‡‡‡ 136.58±3.83†‡‡‡ 132.62±3.49†‡‡‡

DBP 93.84±1.99 93.92±2.54 96.36±1.99 96.48±1.84 95.58±1.74‡‡‡ 95.00±1.92‡‡‡ 4.14±1.70PP 49.78±2.15 45.50±1.99 45.88±2.00* 43.9±2.56* 6.66±2.90 3.78±1.99** 0.68±1.96***

MAP 109.33±2.16 111.25±1.81 111.65±2.02 111.03±1.73 100.60±3.18* 109.56±2.11‡‡‡ 107.71±1.78‡‡‡

HR/MIN 75.48±1.96 75.80±2.31 76.82±1.78†† 79.82±1.95** 84.26±1.74***†††‡ 83.72±1.85***†††‡ 84.80±2.33***††‡

RRP 10.7±0.36 10.98±0.38††† 10.82±0.39 10.84±0.38 11.74±0.43*** 11.58±0.40* 11.40±0.41*

Values are Mean ± SE .Pressure values are in mmHg. Basal values are before tilt.SBP: systolic blood pressure,

DBP: diastolic blood pressure, PP: Pulse pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min,

RPP: rate pressure product. (Paired t – test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly

significant, Comparison between 300

and 600

head up tilt : †P<0.05significant, ††P<0.01 highly significant

†††P<0.001 very highly significant, Unpaired t test: ‡P<0.05 significant, ‡‡P<0.01 highly significant ‡‡‡<0.001

very highly significant)

Hypertensive: All cardiovascular parameters recorded

in hypertensives registered increase its value, as

compared with normotensives at 30°and 60° HUT at

different time intervals.

30° HUT: SBP registered a marginal insignificant

increase in its value than the basal value after 1and 5

minutes of HUT. After 10 minutes of HUT decline in

SBP was observed and returned to baseline values.

DBP also registered a marginal insignificant increase

in its value than basal value after 1 minute of HUT andthis insignificant increase was followed for 5 and 10

minutes of HUT.

PP showed an insignificant increase after 1 minute of

HUT and increase at 5 and 10 minutes of HUT, was

found to be more significant (P<0.05) than basal value.

MAP recorded insignificant increase in its value after

1,5,10 minutes of HUT

HR recorded initially decrease in its value as

compared to basal value, however at 10 minutes of

HUT significant (P<0.01) increase in HR wasobserved. RPP recorded a marginal insignificant

increase than basal value after 1,5,10 minutes of HUT.

60°HUT: HUT SBP decreased insignificantly and

remained lower than basal value during 1, 5, 10

minutes of HUT.

DBP recorded a marginal increase in its value than

basal value at 1,5,10 minutes of HUT

PP recorded insignificant decrease after 1 minute of

HUT, however this decrease was significant at 1

minute (P<0.01) and 10 minutes (P<0.001) of HUT

than initial basal value. MAP registered a significant

increase in its value after 1minute (P<0.05) of HUT.MAP showed further a marginal decrease at 1

and 5 minutes of HUT, than basal value. HR recorded

a highly significant increase (P<0.001) at 1,5,10

minutes of HUT. RPP also registered very highly

significant (P<0.001) increase in its value after 1

minute of HUT and remained significant (P<0.05)

increased at 5 and 10 minutes of HUT.

DISCUSSION

In the present study, we studied effect of 30° and 60°HUT on cardiovascular parameters in normotensive

and hypertensive subjects.



169


Normotensive: SBP, PP and MAP parameters

decreased, while DBP, HR/MIN, RPP increased

gradually as the angle of HUT increased. At 30° HUT

changes recorded in SBP, PP, HR/MIN, RPP were

significant.

Similarly same pattern of decrease in SBP, PP, and

MAP was observed in normotensive at 60° HUT and

significant pattern of increase in DBP, HR/MIN, and

RPP was observed. Except decrease in MAP other

findings of our study agree with the study conducted

by Vijayalaxmi et al15

.It is important to note that,

autonomic functions vary with ageing16

and

parasympathetic17

is also reduced, since our subjects

were selected from different age group (20-70 yrs). In

normotensive subjects, significant fluctuations were

not observed, since, during the initial phase of HUT

intact autonomic activity18 stabilized the

cardiovascular parameters during the total duration of

HUT.

Hypertensive: In hypertensive individuals, SBP, PP,

MAP showed decrease at 300

and 600

HUT. Similarly

DBP, HR/MIN, RPP showed increase in their value at

both angles of HUT. However, these changes were

more significant at higher angle of 60° HUT, in both

groups.

MAP is dependent on heart rate (HR), stroke volume

(SV) and total peripheral resistance (TPR), which can

be correlated as MAP=HR X SVX TPR. During HUT,

changes like pooling of blood in lower parts of the

body and low carotid pressure in the carotid sinus

occur.19

These gravity induced changes produced decreases in

venous return, stroke volume, pulse pressure, mean

arterial pressure which cause tachycardia and

vasoconstriction, due to baroreceptor reflex20

. In this

upright posture increase in heart rate and peripheral

resistance regulate blood pressure. This mechanism ismore effective in younger individuals than older ones

in maintaining blood pressure in upright posture.21

This was the major factor to cause a decrease in SBP,

PP and MAP during HUT.

Increase in HR, as reported by other studies is tilt

dependent, which remained elevated throughout the

period of HUT. However, this increase in HR may be

due to increase in sympathetic stimulation and

withdrawal of vagal tone, which is the prominent

finding in hypertensive.

22

HUT 30° and 60° produced an increase in RPP in both

groups, but this increase was more in the hypertensive

group than normotensive group. HUT of 60° produced

a more significant increase in its value throughout the

duration of HUT. The increase in RPP was caused due

to increase in SBP and HR.RPP (Robinson Index) was

expressed as RPP= SBP X HR X10-3. 23

RPP indicates

myocardial oxygen consumption and cardiac work in

normal subjects as well as patients with heart

diseases.24

It also indicates onset of ischaemia in

patients undergoing surgery or the onset of coronary

pain during exercise.25,26

Higher values of RPP

recorded in hypertensive than normotensive indicate

more oxygen consumption, coronary blood flow and

more myocardial work.

CONCLUSION

The results of this study indicate a significant effect of

HUT on cardiovascular parameters in hypertensive

group. It is worth noting that, significant changes in

HR and RPP in hypertensive individuals indicated

more myocardial oxygen consumption and myocardial

work at both angles of HUT. These are more

prominent at higher angles of HUT than the lower

angle of HUT.

REFERENCES

1. Severe K, Lefrandt, Nordby G, Os I. Autonomicfunction in hypertensive and normotensive

subjects. Hypertension 2001; 37:1351-56

2. Chakko S, Muligtapang RF, Huikuri HV.

Alterrations in heart rate variability and its

circardian rhythm in hypertensive patients with

left ventricular hypertrophy free of coronary artery

diseases. American Heart Journal 1993;126:1364-

72.

3. Guzzeti S, Piccgluger E, Casati R. Sympathetic

predominance in essential hypertension: a study

employing spectral analysis of heart rate

variability. J Hypertens 1988;6:711-17.

4. Singh JP, Larson NG, Tuji H. Reduced heart rate

variability and new onset hypertension: The

Framingham heart study. Hypertension

1998:77:93-297.

5. Huikuri HV, Ylitalo A, Pikkujamsa SM. Heart rate

variability in systemic hypertension. Am J Cardiol.

1996;77(12): 1073-1077.

6. Pikkujamsa SM, Huikuri HV, Airaksinen KE.

Rate variability and baroreflex sensitivity in

hypertensive subjects with and without metabolic



170


features of insulin resistance syndrome. Am J

Hypertens 1998;11:523-31.

7. Vaz M, Kulkarni RN, Rodrigues D, Shetty PS.

Immediate heart rate responses to head up tilt in

healthy human subjects: response characteristics

and variability. Indain J Physiol Phramacol

1993:37(4):323-27.

8. Jahan N, Deepak KK, Kaushal Navita, Paudel BH.

Effect of graded head up tilt on parasympathetic

reactivity. Indain J Physiol Phramacol

1996:40(4):309-17.

9. James MA, Robinson G T, Potter JF. The effect of

systemic blood pressure on cardiovascular reflexes

in elderly subjects.Clinical Physiology

2008:21(1):67-76.

10. Wahbha MMAE, Wilson , Hainsworth R.

Cardiovascular response to upright tilting in

hypertensive patients with and without renal

impairment and before and following nisoldopine

treatment. Br. J. Clin. Pharmac 1990;29:733-39.

11. Guidelines sub committee. 1993 Guidelines for the

management of mild hypertension:memorandum

from a World Health Organization/ International

Society of Hypertension meeting.J Hypertens

1993;11:905-918.

12. Joint National Committee on prevention, detection

and treatment of high blood pressure .The sixth

report of the Joint Committee on prevention,

detection and treatment of high blood

pressure.(JNC VI). Arch Intern Med 1997;157:

2413-46.

13. Chobanian AV, Bakris GL, Black AR. Joint

Committee on prevention, detection and treatment

of high blood pressure. National Heart, Lung and

Blood Institute, National high blood pressure

programme coordinating committee. Seventh

report of the Joint Committee on prevention,detection and treatment of high blood pressure.

Hypertension 2003;42:1206-52.

14. Shah Siddharth, convenor. Practical guidelines for

physicians: Indian hypertension guidelines 2007.

Supported by unrestricted educational grant Pfizer,

India. Website address

15. McArdle W, Katch F, Katch V. Body composition

assessment. In Exercise Physioloy: energy,

Nutrition and Human Performance.5th

Ed,Lippincott Williams and Wilkins,Baltimore:2001:772-776.

16. Collins KJ, AN Exton-Smith. Functional changes

in autonomic responses with ageing. Age and

Ageing 1980:9:17-24.

17. Vita GP, Calabro R, Toscano. Cardiovascular

reflex test: Assessment of age adjusted normal

range. J. Neural Sci 1986;75:263-74.

18. Guyton AC, Hall JE. Nervous regulation of the

circulation and rapid control of arterial pressure. In

T.B of Medical Physiology.11th

Ed ,Saunders,

Philadelphia. 2006:204-14.

19. Neto JAN, Gallo L, Manco JC. Mechanism of

tachycardia on standing: Studies in normal

individuals and in chronic changes in heart

patients. Cardiovas Res. 1980;14:541-50.

20. Florica V, Kem DC. Plasma norepinephrine, blood

pressure and heart rate response to graded change

in body position. Aviat Space Environ Med

1985;56:1166-71.

21. Luutonen S, Antila K, Errko M. Haemodynamic

response to head up tilt in elderly hypertensive and

diabetic. Age and ageing 1995;24(4):315-20.

22. Langewitz W, Ruddel H, Schachinger H. Reduced

parasympathetic cardiac control in patients with

hypertension at rest and mental stress. Am Hear J

1994;127:199-204.

23. Pepper MG, Crawley BE.Technical note:

Calculation and display of the rate/pressure

product during anaesthesia using binary rate

multipliers. Med and Bio. Eng and

Comput.1985;23:187-89.

24. Globel FL, Nordstrom LA, Nelson RR. The rate

pressure – product as an index of myocardial

oxygen consumption during exercise in patients

with angina pectoris. Circulation 1978;57:549-56

25. Cokkinos DV, Vorodis ES. Constancy of pressure

product in pacing induced angina pectoris. British

Heart Journal 1976;38:39-42.26. Robinson BF. Relation heart rate and systolic

blood pressure to the onset of pain in angina

pectoris. Circulation 1967;35:1073-80.



171

Darshana Bennadi, Int J Med Res Health Sci. 2014;3(1):171


&

Health Sciences




thDec 2013

Letter to Editor

PEDAGOGY TO ANDRAGOGY

Darshana Bennadi

Senior Lecturer, Dept. of Public Health Dentistry, Sree Siddhartha Dental College and Hospital, Tumkur, India.

Corresponding author email: [email protected]

Dear Sir,

I would like to congratulate Muneshwar JN, Mirza

Shiraz Baig, Zingade US, Khan ST for highlighting a

very important issue regarding the teaching methods

for health care professionals.1

Study has proved the

Chinese proverb: “If I hear, I forget; if I see, I

remember; if I do, I know”. Along with this I want to

focus little on “podcast” as new teaching method.

At present, education trend have changed from

pedagogy to andragogy i.e. from a teacher-centered

learning to a student-centered learning. These methods

of education trends have identified many different

learning styles as well. So, now it has become

necessary for educators to train themselves to

upcoming teaching methods.2

Many new teaching methods are evolving in the

current electronic world. In which Podcasts as a

supplement to live lectures is one of the teaching

method, which have been adopted by many

universities. Podcasting is user friendly, where

information is recorded, then uploaded to a website or

published through programs like iTunes and made

accessible to students. The file can then be played on a

computer or digital player.3,4

Recently many studies have been conducted using

podcast as a new aid and its effectiveness. Studies

have shown that audio podcasts as an effective aid for

review before exams, enhancing student performance;

acceptability and perceived utility of podcasts was

good among students. Introduction of podcasts in the

beginning will offer the students a lot of flexibility inlearning, with regard to place and time.

4

Podcasts as a supplement to live lectures as teaching

method has open up for future research to assess their

utility on a long-term basis so as to pave the way for

introducing podcasts as one of the teaching method.

REFERENCES:

1. Muneshwar JN, Mirza Shiraz Baig, Zingade US,

Khan ST. A questionnaire based evaluation of

teaching methods amongst MBBS students. Int J

Med Res Health Sci.2013;2(1):19-22

2. Poonam Kharb, Prajna Paramita Samanta,

Manisha Jindal, Vishram Singh. The Learning

Styles and the Preferred Teaching – Learning

Strategies of First Year Medical Students. Journal

of Clinical and Diagnostic Research. 2013;7(6):

1089-92

3. Burns TM. The forecast for podcasts: sunny skies

but not necessarily with clear visibility.

Neurology. 2007; 68(15):E19-20.4. Kalludi SN, Punja D, Pai KM, Dhar M. Efficacy

and perceived utility of podcasts as a

supplementary teaching aid among first-year

dental students. AMJ 2013; 6(9): 450-57

DOI: 10.5958/j.2319-5886.3.1.033



172

Deepanjali, Int J Med Res Health Sci. 2014;3(1):172-175


&

Health Scienceswww.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 4th Dec 2013 Revised: 18th Dec 2013 Accepted: 21st Dec 2013

Review article

EMERGING ROLE OF VITAMIN D IN HEALTH

*Deepanjali Lomte

Associate Professor, Department of Pharmacology, Dr.Vasantrao Pawar Medical College, Hospital & Research

Centre, Nashik, Maharashtra, India.


ABSTRACT

Vit. D is a steroid prohormone. It is synthesized in the skin under ultra – violet light exposure. Traditionally, Vit.D3,

cholecalciferol and calcitriol were known to have a role only in calcium and bone mineral metabolism. This article

takes an account of the current view on the impact of Vit D deficiency on human health. Research has now shown

the indisputable role of Vit D in prevention/treatment of some cancers, osteoporosis, rheumatoid arthritis, multiple

sclerosis, tuberculosis, hypertension, and diabetes mellitus. In addition lower maternal Vit. D levels are associated

with Pregnancy Induced Hypertension (PIH), suggesting that Vit. D deficiency may be a modifiable risk factor for

PIH. Greater awareness of the problem of a high prevalence of vitamin D inadequacy is required among researchers,

clinicians, and patients. Special efforts on the medical and social fronts are necessary to combat this preventable

epidemic of vitamin D deficiency.

Keywords: Vitamin D, 25-Hydroxyvitamin D, PIH, Pregnancy, Hypervitaminosis D, Cholecalciferol, Calcitriol.

INTRODUCTION

Vitamin D is more important nutrient for health.

Vitamin D is actually a hormone rather than a vitamin.

Despite its discovery 100 years ago, Vit D has

emerged as one of the most controversial nutrients and

prohormones of the 21st century, and a lot of research

has been in place on this molecule. Traditionally,

Vitamin D was viewed as a permissive factor incalcium and bone mineral metabolism. It works with

the Parathyroid hormone (PTH), acts on the kidneys,

bone & intestine and influences gene expression. The

research leads us to newer therapies with newer

concepts.1

Research has now shown Vit D's indis-

putable role in both inherent and adaptive immunity.

Vit D is a Steroid prohormone and it is synthesized in

the skin under ultra-violet light exposure. 7-

Dehydrocholesterol present in the skin absorbs UV

light over wavelengths of 290-300 nm [UVB] tosynthesize Vit D3. Synthesis in the skin epidermis

takes place over several days; the quantity (intensity)

and quality (appropriate wavelength) of sunlight are

both important this biosynthesis can be inadequate due

to poor dietary intake, absorption, or poor exposure to

sunlight [UVB]. The deficiency can occur because of

fat malabsorption, anticonvulsant use, chronic kidney

disease and obesity and is seen in high-risk groups like

elderly women, dark-skinned people, people fromareas with a thick layer of ozone, women using

sunscreen lotions, and people from urban areas.2

In urban and polluted areas, the UV light of 290-300-

nm wave length gets filtered out; hence, skin may not

get enough of this light. Therefore, there is a high rate

of Vit D deficiency even among the urban population.

Hence, foods and dietary supplements are necessary.

Cod liver oil, salmon and sardines, fortified milk, egg,

fortified yogurt, mushrooms, fortified soy products,

oysters, and fortified cereals are rich sources of Vit D.Activation of Vitamin D: It takes place in the

following manner:1

DOI: 10.5958/j.2319-5886.3.1.034



173


Fig 1: Activation of Vitamin D

Under situations of minimal exposure to sunlight, a

specific recommendation of a daily supplement of 400

IU (10 µg) is retained for the Indian population. RDA

for pregnant women is 200 IU per day and themaximum safe daily dose is 2,000 IU. Due to

increased deficiency screening for vitamin D levels is

important for most individuals. A serum concentration

of 25 (OH) D is the best indicator of vitamin D.

The Emerging Roles of Vit D: It is now considered

important in cell differentiation, proliferation, and

immune function. It is an important factor in

prevention/treatment of some forms of cancer,

osteoporosis, rheumatoid arthritis, multiple sclerosis,

hypertension, cardiovascular disease, obesity, psoriasis,and psychiatric diseases. The role of vitamin D in

pregnancy is also taking new dimensions.

Vit. D and Pregnancy: Maternal Vit.D deficiency is

common during pregnancy and throughout gestation.

If a women is Vit. D deficiency, it leads to a number

of serious health problems likes poor bone

mineralization in infants, low birth weight baby and

other adverse pregnancy outcomes.3-5

There are

different deficiency levels. The risk of rickets

increases significantly when the total circulating

25(OH)D falls below 10 ng/mL (25 nmol/L), whereas

cathelicidin mRNA expression as a marker of immune

function continues to be suppressed until 25(OH)D

circulating levels reach at least 20 ng/mL (50

nmol/L).6

The recently revised Institute of Medicine's (IOM)

2010 criterion for Vit D deficiency of total circulating

25(OH) D is <20 ng/mL (50 nmol/L), Optimal serum

concentrations of 25(OH) D3 are at or above 30 ng/mL

(>75 nmol/L), and Vit D toxicity is present when

levels are at or above 150 ng/mL (374 nmol/L).7

Rates of deficiency of Vit D are more with women

who have darker pigmentation and women who have

limited access to sunlight, through limited outdoor

activity.8Vit D deficiency exists in a higher percentage

in obese women. Women including pregnant women,

with a BMI >30, are at increased risk of Vit D

deficiency.8

The adipose tissue serves as a repository

for Vit D that does not get into the circulation.

As per recent guidelines Recommended Daily

Allowance (RDA) of Vit. D during pregnancy is 200-

400 IU/day and more than 2,000 IU/day has been toxic

not just to the pregnant women but to the any one. As

per recent research, higher dosages of Vit D are not

just safe during pregnancy, but increased dosage may

actually reduce the risk of complications.

In a study, 500 women who were at least 12 weeks

pregnant took 400, 2000, or 4000 IU of Vit D per day.

The women who took 4,000 IU were less prone for

preterm labour or infections during pregnancy. Vit D

intoxication is extremely rare and easy to treat.

Pregnant women who get too little Vit D are more

likely to develop PIH (Pregnancy induced

hypertension) and are also more likely to require a

Cesarean section. They concluded that giving 4,000 IU

a day to pregnant women may not only improve birth

outcomes but also does not cause toxicity.9

Pregnant women with a serum level of 25-OH Vit D

<75 nmol/L are considered to be Vit D3 deficient.10

Until recently, it was thought that Vit D deficiency

was common only in high-risk women (women with

dark skin and those with minimal exposed skin), but it

is quite high even in low-risk women.

All women therefore should be offered testing for Vit

D status in early pregnancy and recommended

supplementation if deficient.11

Women with a 25-OH Vit D3 <75 nmol/L are

considered Vit D deficient and should have a dietaryassessment for calcium intake. They should receive a

higher dose up to 1000 IU. They should be offered

retesting at 28 weeks of pregnancy. If the higher dose

of Vit D does not improve the serum Vit D levels, then

malabsorption syndrome (such as celiac disease)

should be ruled out or else the patient may be non-

compliant.

Pregnant women should have enough Vit D at the time

of delivery to insure sufficient Vit D levels in their

baby for the first 4-6 months of life.The transplacental passage of maternal 25-OH Vit D3

is the sole source of Vit D in the developing fetus.



174


Therefore, infants are wholly dependent on their

mother for their Vit D status. Infants born to Vit D-

deficient mothers will be Vit D deficient and hence

will require supplementation in the form of

cholecalciferol bolus (50,000 IU) dose orally. The

obstetricians must understand the importance of

vitamin D supplementation to pregnant and nursing

mothers, which will go a long way in preventing

rickets.

Emerging Role of Vitamin D in Other Diseases: The

role of Vit D in osteoporosis and muscle weakness is

indisputable. But, there is a recent trend to give a

higher dose of Vit D to prevent the osteoporotic

fracture.

In a placebo controlled study, oral Vit.D (700-800

IU/d) with or without calcium supplementation was

given to elderly persons. The results show that there

was statistically significant (23-43%) reduction in risk

of a hip fracture and any non-vertebral fracture.12-15

Multiple sclerosis is an autoimmune disease which is

more prevalent in temperate climates than the tropics

and is also seen much more commonly in women. It is

associated with lower serum vitamin D levels, and Vit

D supplementation may have a preventive role in

multiple sclerosis.

The protective role of optimal Vit.D status and lower

risk of cancer has been reported in many studies.

Seven decades ago, Pellers and etal first time reported

that sunlight exposure may reduce the risk of cancer.16

In another study it has been reported that when the

concentration of 25 OH Vit.D > 32 ng/ml, there was

50% reduction in breast and colorectal cancer.17-18

The

higher the Vit D level, the lower the risk of cancer.

Vitamin D acts as an immunosuppressant in

rheumatoid arthritis as well.

Vit.D has a preventive role in development of diabetes

mellitus. Pittas AG and et al studied on high dosage of calcium and Vit.D over 2-4 years in 83779 women

with no history of diabetes. In this study for group one

calcium >1200 mg/day and Vit. D >800 IU/day was

given. For group two calcium <600 mg/day and Vit.

D <400 IU/day was given. The results show that in

group one there was 33% lower risk of type 2 diabetes

as compared to group two.19

In another study in

Finland over 31 years Vit. D in a dose of 2000 IU/day

was administered to 10366 children during their first

year of life and result show that the risk of type 1diabetes reduce by 80%.

20

Tuberculosis is associated with lower Vit D levels.

Before the antikoch's treatment was available, high

dosages of Vit D were given to patients. We see this

disease in urban areas in women with a specific

dressing style which prevents adequate sunlight

exposure.

Adverse Effects of Vit D Therapy: The primary

toxicity associated with Calcitriol is to increase

intestinal calcium and phosphate absorption, along

with the potential to mobilize osseous calcium and

phosphorus concentrations.

Hypervitaminosis D is treated by immediate

withdrawal of the vitamin, a low calcium diet,

administration of glucocorticoids and vigorous fluid

support. Forced saline diuresis with loop diuretics for

hypercalcemia is useful. With this plasma Ca2+

concentration fall to normal and Ca2+ in soft tissue

tends to mobilize. Conspicuous improvement in renal

function occurs.1

CONCLUSION

To summarize, Vit D deficiency is highly prevalent

and contributes to women's health greatly. Getting too

little vitamin D is worse than getting too much. Newer

reports are changing our ideas about the optimal Vit D

status and the role of Vit D in health, especially in

relation to modern chronic diseases affecting women.

It must be remembered that some populations are still

very much under treated, and pregnancy-associated

complications can be reduced with correction of the

deficient state.

In spite of the close relation of vitamin D to human

health, vitamin D deficiency is not widely recognized

as a problem by doctors and patients. Greater

awareness of the problem of a high prevalence of

vitamin D inadequacy is required among researchers,clinicians and patients. Women in the underprivileged

sections, both in urban and rural India, are battling

inadequate resources, multiparty, imposed customs of

clothing, and social vulnerability of the fairer sex

which coupled with the urban environmental decay

will continue to pose the threat of Vit D deficiency.

Special efforts on the medical and social fronts are

necessary to combat this preventable epidemic of

vitamin D deficiency.



175


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randomized clinical trial of safety and

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10. National Institute for Health and Clinical

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Healthy Pregnant Women. NICE Clinical

Guideline 62, London. 2009

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supplementation: a meta-analysis of randomized

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years on hip fractures in elderly women. BMJ.

1994:308:1081-82

15. Lips P, Graafmans WC, Ooms ME. Vitamin D

supplementation and fracture incidence in elderly

persons: a randomized, placebo-controlled clinical

trial. Ann Intern Mcd. 1996:124;400-06

16. Peller S, Stephenson CS. Skin irritation and cancer

in the United States Navy. Am J Vied Sci. 1937;

194:326-33

17. Lappc JM. Travers-Gustafason D, Davies KM.

Vitamin D and calcium supplemcnlation reduces

cancer risk: results of a randomized trial. Am J

Clin Nutr. 2007:85:1586-91

18. Dembrow M. High vitamin D: Rx for cancer

prevention? Clin Advisor. 2007;10:54-57

19. Pittas AG, Dawson-Hughes B, Li T. Vitamin D

and calcium intake in relation to type 2 diabetes in

women. Diabetes Care. 2006:29:650-56

20. Hypponen E, Laara E, Reunanen A.. Intake of

vitamin D and risk of type 1 diabetes: a

birthcohort study. Lancet. 2001;358: 1500-03



179

Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182


&

Health Sciences



rdOct 2013 Accepted: 18

thNov 2013

Case report

KIMURA’S DISEASE: A RARE CASE REPORT

*Nagarekha Kulkarni

Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India


ABSTRACT

Introduction: Kimura’s disease is of unknown etiology. Case report: This report describes an interesting case of

Kimura’s disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple

cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated

with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles

with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells.

Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect

the Kimura’s disease.

Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia

INTRODUCTION

The history of Kimura’s disease dates back to 1937

when HT Kimm and C Szeto first described about it.1

Kimura et al in the year 1948 was the pioneer to

describe the microscopic features of the disease.

Hence, the disease is recognised by his name.1

This

disease is seen in young Asian males and the cause of

this rare entity is not known. Only 200 cases are

reported since its histological description and

sporadic in the rest of the world.2 Clinically the

disease presents as swelling in the head and neck

region characterised by eosinophilia in blood and

tissue with marked elevated serum immunoglobulin E

(IgE) levels.3

This report describes a rare case of

Kimura’s disease in a 18 years old male who

presented with parotid swelling

CASE REPORT

An 18 years old male presented to the ENT outpatient

department with the swelling on the left side of the

face below the left ear. It was sudden in onset and

progressed gradually to attain the size of 12X10cms.

There was no past history of prolonged fever, cough,

loss of weight and loss of appetite. He was non-

alcoholic and non-smoker. The family history was

unremarkable. On palpation the swelling was diffuse,

non-tender, firm, multiple over left parotid region

The swelling was measuring 12x10cms, mobile, skin

over the swelling was pinchable and hyperpigmented.

Other groups of the lymph nodes were not enlarged.

There was no hepatosplenomegaly. Bilateral ear and

facial nerve examination were within normal limits.

The vital signs and laboratory investigations were

normal except there was eosinophilia and elevated

IgE levels as shown in table-1. Neck ultrasonography

revealed enlarged parotid gland with altered

echotexture, multiple enlarged pre and post auricular

lymphnodes. Fine needle aspiration biopsy revealed

features of reactive lymphadenitis. After a course of

antibiotics the swelling was excised and sent for thehistopathological examination. He was treated with

DOI: 10.5958/j.2319-5886.3.1.036



180


levofloxacin, acclofenac, cetrizine and B- complex

tablets.

The specimen was received in the histopathology

section. Macroscopic examination revealed a well

circumscribed mass measuring 12X8X5cms. External

surface was unremarkable and cut section showed

grey white homogenous areas as shown in figure - 1.

The specimen was processed routinely in the

histopathological section and the sections were

stained with haematoxylin and eosin stain (H/E).

Microscopic examination revealed the architecture of

the lymph nodes with numerous follicles showing

hyperplastic feature with germinal centers. Many

eosinophils and plasma cells were present in the

interfollicular area. Also seen are perifollicular

fibrosis, prominent blood vessels with endothelial

proliferation and mild hyaline change as shown in

figure 2. The diagnosis of Kimura’s disease was

made.

Table 1: Shows vital signs and laboratory findings

Vital Signs: Pulse Rate: 86/minute, Blood Pressure: 130/80 mm of Hg, Respiratory Rate: 28/minute

Temperature: 38.5oc

Laboratory Investigations:

Hb%: 11.8g/dl (normal:12.5-14.5g/dl)RBC Count: 3.8millions/cmm (normal:4.5-5.5millions/cmm)

Haematocrit: 34% (normal: 35% to 45%)

WBC Count: 9800 cells/cmm (normal: 4000 to 11,000/cmm)

Differential Count: Neutrophils: 65%, Lymphocytes: 23%, Eosinophils: 10%, Monocytes: 02%

Basophils: 00%

Bleeding Time-3 minutes 30 seconds (Normal:2-6minutes)

Clotting Time-4 minutes 30 seconds (Normal: 2-8minutes)

Absolute eosinophil count: 600 cells/cmm (Normal:40-440cells/cmm)

Serum IgE:4.4mg/dl (Normal: 0.01 – 0.04 mg/dl)

Stool tests: negative for parasites

Random Blood Sugar: 90mg/dl (normal: 80 to 110mg/dl)

Blood Urea: 19mg/dl (normal: 5 to 25mg/dl)

Serum Creatinine: 0.8mg/dl (normal: 0.8 to 1.2mg/dl)

Serological Investigations: HIV-1 & 2:Negative , HBsAg : Negative

Routine Urine Examination: Albumin: Nil, Sugar: Nil, Urine micro: 1-2 pus cells/HPF

Table 2: Shows the difference between kimura’s disease and angiofollicular hyperplasia with eosinophilia1

Kimura’s disease Angiofollicular hyperplasia with eosinophilia

Young man (2nd

-3rd

decade) Middle aged woman (3rd

-5th

decade)

Oriental WesternerVoluminous subcutaneous mass, adenopathy,

salivary gland involvement

Subcutaneous or dermal cervical papules or nodules;

overlying skin is erythematous or pigmented; rare

adenopathies

Follicular hyperplasia, eosinophil infiltration of

interfollicular and perivascular zones with abcess

formation and lysis, postcapillary venule

proliferation

Same aspect. Histiocytoid vessels with particular

endothelial cells (different sized nuclei and protrusion

into the vessel lumen)

Elevated total IgE, hypereosinophilia, benign

pathology

No increase in IgE, hypereosinophilia. Benign form of a

group of vascular proliferation diseases ranging from

hemangioendothelioma to epitheloid angiosarcoma



181


Fig 1: Cut section of the specimen showing

homogenous grey white areas.

Fig 2: Showing the microscopic picture of

Kimura's disease 40X(H/E).

DISCUSSION

Kimura’s disease is a chronic inflammatory condition

where in the etiology may not be established. Hence,

there was a misconception between this disease and

angiolymphoid hyperplasia with eosinophilia

(ALHE). But later it was proved that they were two

separate disorders. Autoimmune/allergic response

was seen in Kimura’s disease as against benign

vascular hyperplasia in ALHE.4

There is no age preponderance to this disease.

However 2nd

and 3rd

decade have been reported in

many literature, which also collaborates with the

present case.5

Won Jun Choi et al reviewed 54

patients and found that the mean age of the patients

was 33.1 years with head and neck region being more

commonly involved5. Other areas to be involved are

kidneys, orbit, ears, spermatic cord and median

nerve.5

Clinical differential diagnosis should include

chronic inflammatory disorder of the salivary glands,

granulomatous gland disease (cat-scratch disease,

sarcoidosis) and autoimmune disease (Sjogren’s

syndrome), benign and malignant lesions of the gland

and cysts should be differentiated. However the

following conditions like lymphoma, metastasis,

ALHE, Langerhans cell histiocytosis, florid follicular

hyperplasia, Castleman’s disease, drug reaction,

dermatopathic lymphadenopathy, parasitic

lymphadenitis and allergic granulomatosis of Chung

and Strauss are to be considered in differential

diagnosis.3

Laboratory analysis showed peripheral blood

eosinophilia and increased serum total IgE

concentration. There was no proteinuria. Regional

lymphadenopathy, peripheral blood eosinophilia and

increased IgE levels are commonly seen in Kimura’s

disease, but not in ALHE. Renal involvement is

found in half the patients of Kimura’s disease. Yuen

et al 6 reported that renal involvement is about 60%.

Table-2 reveals the differences and similarities

between Kimura’s disease and ALHE.1

Surgical excision of the lesion is the first line therapy.

Corticosteroids therapy is partly unsuccessful.

Radiation and cytotoxic therapy has to be considered

for the refractory lesions which do not respond to

surgery. Cetrizine (histamine [H-1] receptor blockers)

induced a complete remission in a corticosteroid

dependent patient within 2 months of treatment.

CONCLUSION

This rare case report underlines the importance of

taking into account Kimura’s disease when there is

eosinophilia in the peripheral blood and swelling in

the head and neck region.

ACKNOWLEDGEMENT

I thank the Director, Principal, Head of the

Department & all staff members of the Department of

Pathology & ENT, VIMS, Bellary for their support &

encouragement to prepare this report.

REFERENCES

1. Larroche C, Bletry O. Kimura’s disease.

Orphanet encyclopedia. February 2005:

http://www.orpha.net/data/patho/GB/uk-

kimura.pdf

2. Veerendra Kumar, Salini, Savida Haridas.

Kimura’s disease: An uncommon cause of

lymphadenopathy. Indian J Med Paediatr Oncol.

2010;31(3):89-90.



182


3. Savage NW, Vucicevic Boras V. Unilateral

intraparotid swelling: a case report of Kimura’s

disease and review of differential diagnosis. Case

reports in Otolaryngology. 2013;3:

http://dx.doi.org/10.1155/ 2013/ 795921.

4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas

C. Epitheloid hemangioma (angiolymphoid

hyperplasis with eosinophilia) in the oral mucosa

: a case report and review of the literature. Oral

Oncology. 1999;35(4):435-38

5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang

Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An

unusual clinical presentation of Kimura’s disease

occurring on the buttock of a five year old

boy.Ann Dermatol. 2010;22(1):57-60.

6. Yuen HW, Goh YH, Low WK, Lim- Tan SK.

Kimura’s disease: a diagnostic and therapeutic

challenge. Singapore Med J. 2005;46:179-83.



179



&

Health Sciences



rdOct 2013 Accepted: 18

thNov 2013

Case report

KIMURA’S DISEASE: A RARE CASE REPORT

*Nagarekha Kulkarni

Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India


ABSTRACT

Introduction: Kimura’s disease is of unknown etiology. Case report: This report describes an interesting case of

Kimura’s disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple

cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated

with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles

with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells.

Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect

the Kimura’s disease.

Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia

INTRODUCTION

The history of Kimura’s disease dates back to 1937

when HT Kimm and C Szeto first described about it.1

Kimura et al in the year 1948 was the pioneer to

describe the microscopic features of the disease.

Hence, the disease is recognised by his name.1

This

disease is seen in young Asian males and the cause of

this rare entity is not known. Only 200 cases are

reported since its histological description and

sporadic in the rest of the world.2 Clinically the

disease presents as swelling in the head and neck

region characterised by eosinophilia in blood and

tissue with marked elevated serum immunoglobulin E

(IgE) levels.3

This report describes a rare case of

Kimura’s disease in a 18 years old male who

presented with parotid swelling

CASE REPORT

An 18 years old male presented to the ENT outpatient

department with the swelling on the left side of the

face below the left ear. It was sudden in onset and

progressed gradually to attain the size of 12X10cms.

There was no past history of prolonged fever, cough,

loss of weight and loss of appetite. He was non-

alcoholic and non-smoker. The family history was

unremarkable. On palpation the swelling was diffuse,

non-tender, firm, multiple over left parotid region

The swelling was measuring 12x10cms, mobile, skin

over the swelling was pinchable and hyperpigmented.

Other groups of the lymph nodes were not enlarged.

There was no hepatosplenomegaly. Bilateral ear and

facial nerve examination were within normal limits.

The vital signs and laboratory investigations were

normal except there was eosinophilia and elevated

IgE levels as shown in table-1. Neck ultrasonography

revealed enlarged parotid gland with altered

echotexture, multiple enlarged pre and post auricular

lymphnodes. Fine needle aspiration biopsy revealed

features of reactive lymphadenitis. After a course of

antibiotics the swelling was excised and sent for thehistopathological examination. He was treated with

DOI: 10.5958/j.2319-5886.3.1.036



181


Fig 1: Cut section of the specimen showing

homogenous grey white areas.

Fig 2: Showing the microscopic picture of

Kimura's disease 40X(H/E).

DISCUSSION

Kimura’s disease is a chronic inflammatory condition

where in the etiology may not be established. Hence,

there was a misconception between this disease and

angiolymphoid hyperplasia with eosinophilia

(ALHE). But later it was proved that they were two

separate disorders. Autoimmune/allergic response

was seen in Kimura’s disease as against benign

vascular hyperplasia in ALHE.4

There is no age preponderance to this disease.

However 2nd

and 3rd

decade have been reported in

many literature, which also collaborates with the

present case.5

Won Jun Choi et al reviewed 54

patients and found that the mean age of the patients

was 33.1 years with head and neck region being more

commonly involved5. Other areas to be involved are

kidneys, orbit, ears, spermatic cord and median

nerve.5

Clinical differential diagnosis should include

chronic inflammatory disorder of the salivary glands,

granulomatous gland disease (cat-scratch disease,

sarcoidosis) and autoimmune disease (Sjogren’s

syndrome), benign and malignant lesions of the gland

and cysts should be differentiated. However the

following conditions like lymphoma, metastasis,

ALHE, Langerhans cell histiocytosis, florid follicular

hyperplasia, Castleman’s disease, drug reaction,

dermatopathic lymphadenopathy, parasitic

lymphadenitis and allergic granulomatosis of Chung

and Strauss are to be considered in differential

diagnosis.3

Laboratory analysis showed peripheral blood

eosinophilia and increased serum total IgE

concentration. There was no proteinuria. Regional

lymphadenopathy, peripheral blood eosinophilia and

increased IgE levels are commonly seen in Kimura’s

disease, but not in ALHE. Renal involvement is

found in half the patients of Kimura’s disease. Yuen

et al 6 reported that renal involvement is about 60%.

Table-2 reveals the differences and similarities

between Kimura’s disease and ALHE.1

Surgical excision of the lesion is the first line therapy.

Corticosteroids therapy is partly unsuccessful.

Radiation and cytotoxic therapy has to be considered

for the refractory lesions which do not respond to

surgery. Cetrizine (histamine [H-1] receptor blockers)

induced a complete remission in a corticosteroid

dependent patient within 2 months of treatment.

CONCLUSION

This rare case report underlines the importance of

taking into account Kimura’s disease when there is

eosinophilia in the peripheral blood and swelling in

the head and neck region.

ACKNOWLEDGEMENT

I thank the Director, Principal, Head of the

Department & all staff members of the Department of

Pathology & ENT, VIMS, Bellary for their support &

encouragement to prepare this report.

REFERENCES

1. Larroche C, Bletry O. Kimura’s disease.

Orphanet encyclopedia. February 2005:

http://www.orpha.net/data/patho/GB/uk-

kimura.pdf

2. Veerendra Kumar, Salini, Savida Haridas.

Kimura’s disease: An uncommon cause of

lymphadenopathy. Indian J Med Paediatr Oncol.

2010;31(3):89-90.



182


3. Savage NW, Vucicevic Boras V. Unilateral

intraparotid swelling: a case report of Kimura’s

disease and review of differential diagnosis. Case

reports in Otolaryngology. 2013;3:

http://dx.doi.org/10.1155/ 2013/ 795921.

4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas

C. Epitheloid hemangioma (angiolymphoid

hyperplasis with eosinophilia) in the oral mucosa

: a case report and review of the literature. Oral

Oncology. 1999;35(4):435-38

5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang

Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An

unusual clinical presentation of Kimura’s disease

occurring on the buttock of a five year old

boy.Ann Dermatol. 2010;22(1):57-60.

6. Yuen HW, Goh YH, Low WK, Lim- Tan SK.

Kimura’s disease: a diagnostic and therapeutic

challenge. Singapore Med J. 2005;46:179-83.



183

Amarjeet et al., Int J Med Res Health Sci. 2014;3(1):183-185


&

Health Sciences




thNov 2013

Case report

SCOLIOSIS CORRECTION IN CHILDREN-ANAESTHETIC CHALLENGE: A CASE REPORT

* Amarjeet D Patil1, Sivashankar KR

2, Arpan Sashankar

3, Shikha A Malhotra

4, Nitin Kapoor

5, Charu Sudan

6


2Professor & Head,


4,5,6Resident, Department of Anaesthesiology,

MGM Medical College and Hospital, Kamothe, Navi Mumbai, India


ABSTRACT

Kyphoscoliosis is a challenging surgery to surgeons but even more challenging to anaesthesiologist to give

anaesthesia and maintain it throughout the surgery and post operative pain relief and ventilation. Here we are

describing the case of 3 years old male child weighing 9kg for surgical correction of spine deformity with

instrumentation.

Keywords: Scoliosis, Children and Anaesthesia

INTRODUCTION

Scoliosis is defined as a curvature in the vertebral

column from side to side and kyphosis is a curvature

from anterior to posterior.1

Kyphoscoliosis can be

congenital, idiopathic or postural. Surgical correction

is usually attempted from the age of 10. Advances in

paediatric anaesthesia and expertise of the surgeons

are allowing this correction to be attempted at the

very early stage. Positioning of the infant for surgery,

gross fluid shifts and manipulation of neural

structures pose a challenge to the anaesthesiologist.

Surgical correction with instrumentation in a boy of nine kilos is described in this paper.

2,3

CASE REPORT

Nine kgs, 3 years, boy was admitted in our tertiary

care hospital, MGM Medical College & Hospital,

Navi Mumbai, for surgical correction of deformity of

spine since one year. Clinical examination revealed

no other congenital anamoly and cardiorespiratory

system not deranged apart from the positional change.

Radiological findings revealed the extent of angulation of the vertebral column in all directions.

The child was planned for surgical correction with

instrumentation with complete preaparedness for

invasive monitoring and replacement of blood and

blood products.

Fig 1: Pre-operative X-ray of patient AP & Lateral

views

TECHNIQUE4

The infant was assessed, prepared, premedicated as

per standard protocol.5

Intravenous induction,

intubation with non depolarizing blocking agents was

resorted to once the peripheral iv line was secured.

Central line (Rt internal jugular canulation 4.5 fg) and

DOI: 10.5958/j.2319-5886.3.1.037



184


left radial artery canulated Positioning of the infant

for surgery was supplemented by cotton bundles apart

from standard bolsters. Proper eye padding given.6

Standard monitoring of oxygen saturation, end tidal

carbon dioxide (EtCO2), invasive blood pressure

(IBP), central venous pressure (CVP) and urine

output was being done, neuromuscular monitoring

was not possible because the instrument was

defective on that day.7

Anaesthesia was maintained with intermittent

neuromuscular blocking agents, inhalational

anaesthetic and opiod analgesia. We took care to

avoid hypothermia by warming mattress,warm

fluids.8

Surgery was uneventful for 480 minutes.9

Elective postoperative mechanical ventilation was

done for 24 hours.10

Fig 2: Post operative X-ray AP view

Fig 3: Post operative X-ray AP & Lateral view

DISCUSSION

Very few cases have been reported of infants below

10 kgs undergoing surgical correction and

instrumentation of gross Kyphoscoliosis. Positioning

of the child should be preferably with 9 poster

frame.11 We had resorted to cotton bundles for the

same, canulation of Internal jugular vein and radial

artery in children needs experienced hands. Proper

monitoring of effects of gross fluid shifts is

mandatory along with correction of the same.

Monitoring of spinal cord functions could not be done

in this surgery. No complications were noticed in the

form of brachial plexus injury and ocular changes or

air embolism.

CONCLUSION

With clinical experience of the Anaesthesiolgist,

expertise of the surgeon, surgical correction of

kyphoscoliosis even in children is possible now-a-

days12-14

.

ACKNOWLEDGEMENT

We would like to extend our heartfelt gratitude to the

Department of Orthopedics, Department of

Pediatrics, Radiology and Physiotherapy.

REFERENCES

1. Weinstein SL, Dolan LA, Spratt KF, Peterson

KK, SpoonamoreMJ, Ponseti IV. Health and

function of patients with untreated idiopathic

scoliosis. A 50 year natural history study. JAMA

2003; 289:559-67.

2. Michael AE, Davandra Patel. Contin Educ

Anaesth. Crit Care Pain 2006;6 (1): 13-16.

3. Ogilvie JW, Winter RB, Bradford DS, Lonstein

JE, Ogilvie JW, eds. Historical Aspects of

Scoliosis. Moe’s Textbook of Scoliosis and other

Spinal deformities 3rd Edition. WB Saunders

Company. Philadelphia, USA, 1995; 1-4.

4. Salem MR, Klowden AJ, Gregory GA, ed.

Pediatric Anesthesia. Anesthesia for Orthopedic

Surgery Churchill Livingstone, New York, USA,

2002; 617-61.

5. Standards, Guidelines, Statements and Other

Documents. www.asahq.org

6. Myers M, Hamilton SR, Bogosian A, Smith CH,

Wagner TA. Visual loss as a complication of



185


spine surgery: A review of 37 cases. Spine 1997;

22:1325-29.

7. Ramirez N, Richards BS, Warren PD, Williams

GR. Complications after posterior spinal fusion

in Duchenne’s muscular dystrophy. J Pediatr

Orthop 1997; 17:109-14.

8. Sessler DI. Mild perioperative hypothermia. N

Engl J Med 1997; 336:1730-37.

9. Tsirikos AI, Chang W, Dabney KW, Miller F.

Comparison of one stage versus two stage

anteroposterior spinal fusion in pediatric patients

with cerebral palsy and neuromuscular scoliosis.

Spine 2003; 28:1300-05.

10. Rawlins BA, Winter RB, Lonstein JE.

Reconstructive spine surgery in pediatric patients

with major loss in vital capacity. J Pediatr Orthop

1996; 16:284-292.

11. Winter RB, Lonstein JR, Herkowitz H, Garfin

SR, Balderstone RA, Eismont FJ, etal., Juvenile

and Adolescent Scoliosis. Rothman-Simeone,

The Spine 4th

Edition. WB Saunders Company,

Philadelphia, USA, 1999; 325-72.

12. Wazeka AN, DiMaio MF, Boachie-Adjei O,

Oheneba MD. Outcome of pediatric patients with

severe restrictive lung disease following

reconstructive spine surgery. Spine 2004; 29:528-

534

13. Merola A, Haher T, Brkaric M. A multicenter

study of the outcomes of the surgical treatment

of adolescent idiopathic scoliosis using the

Scoliosis Research Society (SRS) outcome

instrument. Spine 2002; 27:2046-2051.

14. Shapiro G, Green DW, Fatica NS, Boachie-Adjei

O. Medical complications in scoliosis surgery.

Curr Opin Pediatr 2001; 13: 36-41.



186

Krishna et al., Int J Med Res Health Sci. 2014;3(1):186-189


&

Health Sciences




ndNov 2013

Case report

AGGRESSIVE ANGIOMYXOMA PRESENTING AS HUGE BROAD LIGAMENT TUMOR- A RARE

CASE REPORT

*Krishna Mandade1, Kashika singh

1, Aptulkar

2, Angarkar

3, Bhavthankar DP

4

1Junior resident, Department of OBGY,

2Asso. Prof, Department of Surgery,

3Professor, Department of Pathology,

4Prof & Head, Department of OBGY, Pravara Rural hospital Loni, Maharashtra, India.


ABSTRACT

Aggressive angiomyxoma was first described in 1983 by Steeper and Rosai, and fewer than 150 cases have been

reported in the world medical literature. Aggressive angiomyxoma is a rare mesenchymal tumor occurring

predominantly in the pelvic-perineal region of females of age group 30 to 50 yrs. These tumors are benign and often

reach too large dimensions before becoming clinically symptomatic. We report such a case presented as broad

ligament tumor, a very unusual presentation. Patient underwent laprotomy and tumor was successfully excised.

Keywords: Aggressive angiomyxoma, Pouch of Douglas.

INRTODUCTION

Aggressive angiomyxomas (AA) are rare, slow

growing benign tumors which are, predominantly,

located on the perineum of reproductive age

women.1,2

These lesions are characterized as soft,

non-encapsulated tumors with finger-like

projections infiltrating the surrounding soft tissues.

The tumour presents as a large multilobular or

polypoid mass or swelling. It is important to

diagnose this condition because a tumor is locallyinfiltrative and surgery is usually the first line of

treatment, radical surgery with wide margins and

long-term follow-up is advised.3

CASE

40 yrs female came to OPD with complain of pain in

abdomen, difficulty in passing stools and urine and

feeling of abdominal mass since 2 months in OPD of

Pravara Rural Hospital, Loni. Dist. Ahmednagar in

Maharashtra in India.Mass associated with pain and bowel complain was

initially small and gradually progressed to present size.

There was no history of fever, cough, cold, nausea,

vomiting, and bleeding per-vaginal, apparent weight

loss. Last menstrual period was 10 days back.

Past menstrual history was regular with cycle and

flow and there were no clots and no dysmenorrhea.

Patient was Para 2 Live 2. Both were full term

normal deliveries & history of tubal ligation done 15

yrs back.

Past, personal and family history was insignificant.On examination, general condition of the patient was

good and vitals were stable. No peripheral

lymphadenopathy and other signs of malignancy

found.

Per abdomen: Non tender abdominal mass felt

corresponding to 24-26 weeks; oval, on Rt. side of

lumbar spine, arising from pelvis, slightly mobile, firm

in consistency, around 20*15cm. Rt. iliac fossa

completely obliterated.

Per vaginal examination: Uterus normal size, firm,mobile, separately felt from the mass which was felt in

Rt. Adnexa.

DOI: 10.5958/j.2319-5886.3.1.038



Krishna et al.,

Rt. Adnexa was fixed; bogginess fel

Fornix was relatively free.

Per Rectal examination: large

anteriorly free from rectal mu

obliterated & mass compressing rect

All hematological investigations w

investigation reports were within nor

USG suggestive of a large tumor o

arising from Rt. Adnexa. Ovaries se

tumor on Transvaginal sonogra

Uterus of normal size with nor

ovaries.

Tumor with some cystic and some

in between. On Color Doppler vasc

Fine needle aspiration cytology (F

of Tumor cells cytologically bl

spindled, ovoid or stellate appea

nuclei and evenly dispersed chrom

MRI evaluations could not be

affordability. CA125 levels was 9IU.

On the basis of the clinical pictur

review patient diagnosed as large

ligament tumor.

Exploratory laprotomy under Ge

performed. Large whitish shiny tum

cm drawn out of peritoneal cavity

from Rt. Adnexa of the uterus an

peduncle in POD and also in the

noted.

With combined surgical approac

completely by securing bowel, bladd

Along with the tumor uterus with

which were observed to be norma

conventional method of Hysterect

achieved completely with moder

loss. No remnants of tumor left.

Fig 1: Tumor attached to broad li

Int J Med Res He

t in Rt. fornix, Lt.

firm mass felt

cosa, POD was

al lumen.

ere done and the

mal limits.

f size 21*20*8cm

n separately from

hy examination.

al ecotexture of

hyper lucent areas

larity set in.

AC): suggestive

nd and have a

rance with ovoid

atin. CT scan and

done due to no

.

e and Ultrasound

Rt. Sided Broad

eral anesthesia

or nearly of 20*20

which was arising

its extension as

ischiorectal fossa

Tumor excised

er and ureters.

bilateral ovaries

l removed by the

my. Haemostasis

ate intraoperative

gament seen.

Fig 2: External ap

extension of tumor.

Post-op was uneventf

11gm%. Patient dischar

Histopathology gross: mass measuring 22*20

of body of uterus.

hemorrhagic areas. Tum

globular 8.5*7*3cm at

uterus near Cervix. An

5cm noted on the poster

Fig 3: Cut Surface of t

Section from tumor s

composed of numerous

large blood vessels set i

Stroma shows collag

muscle bundles.

The Tumor cells cyt

spindled, ovoid or st

nuclei and evenly disper

Stroma is distinctly myx

187

lth Sci. 2014;3(1):186-189

earance with pedunculated

ul. Repeat haemogram was

ged on 10th

Post operative day.

Shiny white brown Tumor 7cm arising from lateral Wall

ut surface: Myxomatous &

or is extended as pedunculated

tached to the lower side of

other extended mass 9 *7*2.

ior aspect of the Uterus.

umor.

how sparsely cellular tumor

haphazardly arranged small to

myxoid stroma.

n fibrils, scattered smooth

logically bland and have a

llate appearance with ovoid

sed chromatin.

oid.



188


Fig 4: Section from pelvic mass showing varying

sized blood vessels surrounded by cells with ovoid

to spindle nuclei & a myxoid stroma (H & E x 280).

DISCUSSION

Aggressive angiomyxoma is a rare tumor of

mesenchymal origin first described in 1983 by Steeper

and Rosai.

The age distribution is wide, with the peak incidence

at 31 to 35.4

Female to male ratio of slightly more than

6:1 . The size may vary from 1-60 cm.5

On gross examination it is rubbery and white or soft

and gelatinous. The tumor presents as a large

multilobular or polypoid mass or swelling.5

Locally infiltrative but non-metastasising; that may

present as a vulval mass, vaginal polyp, bartholin or a

vaginal cyst, ovarian cyst, etc. These lesions are

characterized as soft, non-encapsulated tumours with

finger-like projections infiltrating the surrounding soft

tissues.6

The tumor grows slowly, and its benign

nature is suggested by the histology and by the fact

that it shows no tendency to metastasize. However it

usually tends locally to recure.6

The rarity of this

condition makes the preoperative diagnosis fairly

difficult, It has been also related to hormonal activity

which explains female dominance.7

The diagnosis can be made considering the clinical

presentation aided by ultrasound, CT or MRI shows a

hypodense mass with translevator extension,

displacing rather than invading the pelvic organs.

FNA reduces the diagnostic possibilities but

histopathology alone gives the definite diagnosis.8

Differential diagnosis:

Benign: myxolipoma, myxoid neurofibroma and

myxoid leiomyoma to myxofibrosarcoma, myxoid

variant of liposarcoma, leiomyosarcoma.Malignant: fibrous histiocytoma and botryoid

rhabdomyosarcoma.

The distinctively striking vascular component in

aggressive angiomyxoma helps in ruling out most of

the above mentioned neoplasms as differentials.

The optimal treatment for AA is wide local excision

with tumor free margin, as this tumor is locally

invasive and tends to infiltrate deep into pelvic soft

tissues.9

Pre-operative knowledge of tumor extent is important

in determining surgical approach and MRI features of

AA are characteristic.9

Recurrence is local and reported in 36-72%.

This surgery is challenging because of the infiltration

and the difficult dissection and value of extensive

surgical resection to obtain clear margins has been

questioned.10

In the past, most authors advocated wide

excision even if genitourinary and digestive tract

resections were necessary.

Radiotherapy and chemotherapy may not have much

role due to the low mitotic activity seen.

GnRH agonist and tamoxifen have been used

successfully in few patients.11

The response can be assessed by clinical assessment,

patient's symptomatology and radiographic findings.

Because of the abdominal and pelvic organ

manipulation, hospital stays are generally longer, and

patients are at higher risk of developing problems such

as deep venous thrombosis and pulmonary embolism

while they await the return of bowel function after the

procedure.

There are many unanswered questions about treatment

and follow-up strategies for this rare disease; because

this tumor is slow growing and is often symptomatic

only when the tumor is large, radiographic follow-up

is best.

CONCLUSION

Although a rare diagnosis, aggressive angiomyxoma

can present with unusual features. Detailed

radiological examination is helpful in suspecting the

problem, but histology is the gold standard for

diagnosis. It should be distinguished from benign

myxoid tumors with low risk of local recurrence.

Therefore, recurrence of tumor may be avoided by

wide local excision which is curative and prognosis of

such tumor is good.



189


REFERENCES

1. Steeper TA, Rosai J. Aggressive angiomyxoma of

the pelvis and perineum: report of nine cases of a

distinctive type ofgynaecologic soft tissue

neoplasm. Am J Clin Pathol 1983; 7:453

2. Chan YM, Hon E, Ngai SW, Ng TY, Wong LC.

Aggressive angiomyxoma in females: is radical

resection the only option? Acta Obstet Gynecol

Scand 2000;79(3): 216-20.

3. Wiser A, Korach J, Gotlieb WH, Fridman E.

Importance of Accurate Preoperative Diagnosis in

the Management of Aggressive Angiomyxoma:

Report of Three Cases and Review of the

Literature,” Abdominal Imaging. 2006;31(3):383-

86.

4. Gungor T, Zengeroglu S, Kaleli A, Kuzey GM.

Aggressive angiomyxoma of the vulva and vagina.

A common problem: misdiagnosis. Eur J Obstet

Gynecol Reprod Biol 2004; 112: 114 – 16.

5. Fetsch JF, Laskin WB, Lefkowitz M, Kindblom

L, Meis-Kindblom JM. Aggressive

angiomyxoma. A clinicopathologic study of 29

female patients. Cancer 1996; 78: 79 – 90.

6. H. Adwan, P.D Kamel and G. Glazer, “ A Solitary

Encapsulated Pelvic Aggressive Angiomyxoma,”

Annals of The Royal college of Surgeons of

England, vol. 86, No. 6, November 2004, pp. W1-

W3.

7. Htwe M, Deppisch LM, Saint-Julien JS. Hormone-

dependent, aggressive angiomyxoma of the vulva.

Obstet Gynecol 1995; 86(4 Pt 2): 697-99.

8. Amezcua CA, Begley SJ, Mata N, Felix JC,

Ballard CA. Aggressive angiomyxoma of the

female genital tract: a clinicopathologic and

immunohistochemical study of 12 cases. Int J

Gynecol Cancer 2005; 15: 140-145.9. Kaur A, Makhija PS, Vallikad E, Padmashree V,

Indira HS. Multifocal aggressive angiomyxoma: a

case report. J Clin Pathol 2000; 53: 798 – 99.

10. Siassi RM, Papadopoulos T, Matzel KE.

Metastasizing aggressive angiomyxoma. N Engl J

Med 1999;341:1772.

11. Behranwala KA, Thomas JM. 'Aggressive'

angiomyxoma: a distinct clinical entity. Eur J Surg

Oncol 2003; 29(7):559-63.



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&

Health Sciences




thNov 2013

Case report

ANGIOMYOLIPOMA OF A KIDNEY: A CASE REPORT

*Manish Shah, Mrunal N. Ketkar, Sudhir J. Kothari, Shilpa S. Patankar, Ravi M. Swami

Department of Surgery, Bharati Hospital and Research Centre, Pune Satara road, Dhankawdi, Pune, Maharashtra,

India


ABSTRACT

Angiomyolipoma is a rare benign tumour of the kidney. They are composed of abnormal vasculature, smooth

muscle and adipose elements. They may be associated with Tuberous sclerosis. The unilateral presentation is

uncommon. Angiomyolipoma is presented as an enlarge lump in the abdomen may mimic malignant lesion such as

renal cell carcinoma, yet malignancy has to be ruled out. The diagnosis of this condition may not be straight forward

with imaging alone. Excision is recommended for definite histopathological diagnosis (in symptomatic patients) and

to prevent the potential risk of haemorrhage and malignancy. A case of benign giant Angiomyolipoma is presented

here because of its uncommon occurrence.

Keywords: Angiomyolipoma , Unilateral, Kidney

INTRODUCTION

Angiomyolipoma is a rare benign tumour of the

kidney. It is found in approximately 45-80% of

patients with tuberous sclerosis and are typically

bilateral and asymptomatic. In patients without

tuberous sclerosis, renal angiomyolipomas can be

unilateral and tend to be larger.1Angiomyolipoma is a

benign clonal neoplasm consisting of varying amounts

of mature adipose tissue, smooth muscle, and thick-walled vessels. It is most likely derived from the

perivascular epithelioid cells, and its growth may be

hormone dependent. It shows female predominance

and rarity before puberty.2

It may mimic renal cell

carcinoma. Diagnosis is done with the help of

ultrasonography, CT scan and histology.

CASE REPORT

A 75 yr. an old woman from rural area presented with

lump in right side of the abdomen that the patient hadnoticed 1 year previously. (Bharati Hospital). The

lump had gradually increased in size over a period of

time. She had complaints of pain since 1 day. On

examination, she was anaemic (8.3gm %) with large

retroperitoneal lump that occupied right side of

abdomen, the lump was firm in consistency and

tender. She had no lymphedema or other palpable

lymph node. Ultrasonography revealed a well defined

echoic lesion noted of size 14.6 X 8.7 cm, associated

with upper pole of the right kidney extending upto the

epigastric region and midline on right side. CT scanrevealed a large well defined mass lesion showing

density with peripheral soft tissue component seen in

right hypochondriac and right lumbar region

measuring 13 X 11 X 10 cm. The mass is seen in

medial to pancreas and (Inferior vena cava) displacing

it superolaterally. Superiorly mass extending to liver

and inferiorly to the right iliac fossa. The mass

completely encasing right kidney and displacing it

inferiorly, most likely liposarcoma. (figure 1) A

malignant tumour was suspected based on the imaging

and clinical features. In view of above finding and

pain, malignancy needed to be ruled out. The patient

underwent surgery and tumour was excised intact

DOI: 10.5958/j.2319-5886.3.1.039



191


(figure 2). Its weight was 1800 grams. A nephrectomy

was done due to inability to differentiate it from renal

cell carcinoma. 4 units of blood were transfused

preoperatively and in addition 3 units were given

(blood group AB positive) She made an uneventful

recovery. An angiomyolipoma was confirmed by

histopathological assessment. Post operatively, a

single large well circumscribed an encapsulated firm

mass measuring 20 X 15 X 9 cm weight 1800grams.

The cut section appears yellowish brown with areas of

hemorrhage (figure 3). Microscopy- tumour showed

mature adipocytes, separated by fibrohyalinisedseptae

showing vascular proliferation and area of smooth

muscle cell in bundles (figure 4).

Fig 1: CT scan showing lesion

Fig 2 : Intra operative photograph

Fig 3 : Specimen showing renal Angiomyolipoma.

Fig 4: Histopathology - Angiomyolipoma

DISCUSSION

Angiomyolipoma is a rare benign tumour of the

kidney. It is found in approximately 45- 80% of

patients with tuberous sclerosis and are typicallybilateral and asymptomatic with F: M predominance

of 2:I. The mean age of presentation is 30 years. In

contrast, of the 60 -70% of patient with AML who do

not have tuberous sclerosis present later in life, during

5th

or 6th

decade and this tumour can be unilateral and

tend to be larger than those associated with tuberous

sclerosis. Tuberous sclerosis is an autosomal dominant

disorder comprising adenoma sebaceum, mental

retardation and epilepsy .1

Angiomyolipoma consists of varying amount of

mature adipose tissue, smooth muscle and thick walled

vessels. It is mostly likely derived from perivascular

epitheloidcell. Extrarenal occurrence have been

reported in hilarlymphatics, retroperitoneum and liver

and direct extension into the venous system.2

On diagnostic imaging, it may mimic a malignancy.

On ultrasonography, it gives a well circumscribed,

highly echogenic often associated with shadowing. On

CT scan, well defined mass is seen (confined by a

value of -20 to-80 Hounsfield units).2

Differential diagnosis for this are subtypes of sarcoma

including fibrosarcoma, leiomyosarcoma, liposarcoma

and renal cell carcinoma.3

Positive immunoreactivity

for HMB-45 is characteristic for angiomyolipoma and

can be used to differentiate it from sarcoma.4, 5

The patient with tumour with intermediate features or

calcification should be managed proactively because

the likely diagnosis in most such cases is renal cell

carcinoma. Patients with isolated lesions less than 4

cm, can be followed up with a yearly CT scan or

Ultrasonography to define the growth rate and clinicalsignificance. Similarly, Patients with asymptomatic or

mildly symptomatic lesions greater than 4 cm should

Blood

vessel

Fat

Smooth

Muscle

Angiomyolipoma



192


be followed up with semiannual ultrasonography.

Patients with lesions greater than 4 cm with moderate

or severe symptoms (bleeding or pain) should undergo

surgical intervention either in the form of tumour

excision with or without nephrectomy, renal-sparing

surgery or renal arterial embolization.2

Complications are as follows, Retroperitonal

hemorrhage, hematuria, hypovolemic shock,

hypertension, abscess formation.

CONCLUSION

Angiomyolipoma is a rare tumour of the kidney.5

They

may be confused with malignant tumours especially

when the presentation is unilateral. CT Scan and

ultrasonography helps in diagnosis. Symptomatic

patient requires surgical intervention.

REFERENCES

1. Smith and Tanagho’s. General urology. McGraw-

Hill & Lange. 18th

ed. Chapter 22: 330-31,.

2. Campbell - Walsh Urology. Renal Tumours. WB.

Saunders; Philadelphia, PA. 9th edition.Chapter-

47:1578-80

3. Steiner MS, Goldman SM, Fishman EK, Marshall

FF. The natural history of renal angiomyolipoma.

J Urol. 1993, 150:1782-86.4. De la Cruz Ruiz M, Rivero M, Fernandez DL.

Giant renal angiomyolipoma. Arch EspUrol 1999;

52: 381 – 5

5. Hostis HL, Deminiere C, Ferriere JM. Renal

angiomyolipoma: a clinicopathologic,

immunohistochemical, and follow-up study of 46

cases. Am J Pathol 1999; 23: 1011 – 20.



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Amit et al., Int J Med Res Health Sci. 2014;3(1):193-194


&

Health Sciences




thNov 2013

Case report

RIGHT SIDED CONGENITAL DIAPHRAGMATIC HERNIA: A RARE CASE REPORT

*Amit Narkhede1, Shrikhande DY

2, Prasant Nigwekar

3, Santosh Yadav

1, Haresh Kasodariya

1

1PG Student,

2Professor and Head,

3Asso. Professor, Department of pediatrics, Rural Medical College, Pravara

Institute of Medical Sciences (DU), Loni, Maharashtra, India


ABSTRACT

A diaphragmatic hernia is defined as a communication between abdominal and thoracic cavity with or without

abdominal contents in the thorax. The true incidence of Congenital diaphragmatic hernia is 1 in 5000 live births

while right side diaphragmatic hernia (15%) is rare comparing to left side diaphragmatic hernia (85%) because

liver plugs the opening. Congenital diaphragmatic hernia typically refers to Bochdalek form, other forms are rarer.

Despite advances in neonatal intensive care, congenital diaphragmatic hernia is associated with high mortality and

morbidity. The posterolateral right congenital DH is a rare diaphragmatic defect. Females are twice affected than

that of males. The symptoms are non characteristic and patients with this disease maybe without symptoms for a

long period. The main tool for diagnosis of congenital DH is radiography. Surgical correction is required.

Keywords: Right sided congental diaphragmatic hernia, Posterolateral, Liver plugs at right side

INTRODUCTION

A diaphragmatic hernia is defined as a

communication between abdominal and thoracic

cavity with or without abdominal contents in the

thorax. Right side diaphragmatic hernia (15%) is rare

comparing to left side diaphragmatic hernia (85%)

because liver plugs the opening. Congenital

diaphragmatic hernia typically refers to Bochdalek

form, other forms are rare. The posterolateral right

congenital DH is a rare diaphragmatic defect.

Females are twice affected than that of males. The

symptoms are non characteristic and patients with this

disease maybe without symptoms for a long period.1

CASE REPORT

A male neonate, born in a private hospital to non-

consanguineous parents 36th

week of gestational

age, preterm, appropriate for gestational age (birth

weight 2300 gms, was brought to our hospital on 1

day of life with complaints of respiratory distress and

noisy breathing. Patient had tachypnea, grunting, air

entry absent over the right hemithorax along with

Peristaltic sounds heard over right hemi thorax. Chest

X ray shows Presence of bowel loops and liver in

the right hemi-thorax. Left lung showed nearly

complete expansion, Arterial Blood gas analysis

showed features of respiratory acidosis, other

investigations were within normal limits. The

neonate was referred to neonatal surgical unit for

surgical correction, after stabilization.

DOI: 10.5958/j.2319-5886.3.1.040



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Amit et al., Int J Med Res Health Sci. 2014;3(1):193-194

Fig 1: Chest X ray shows Presence of bowel loops

and liver, in the right hemi-thorax. Left lung

showed nearly complete expansion

DISCUSSION

A diaphragmatic hernia is defined as a

communication between abdominal and thoracic

cavity with or without abdominal contents in the

thorax. The true incidence of Congenital

diaphragmatic hernia is 1 in 5000 live births.1

Right-

sided diaphragmatic hernia (15%) is rare, compared

to left-sided diaphragmatic hernia (85%) because

liver plugs the opening. Congenital diaphragmatic

hernia typically refers to Bochdalek form, other forms

are rarer.2

Malformation of diaphragm allows the

abdominal organs to push into proper lung formation

despite advances in neonatal intensive care;

congenital diaphragmatic hernia is associated with

high mortality and morbidity due to two

complications namely pulmonary hypoplasia and

pulmonary hypertension.2

The posterolateral right

Congenital Diaphagmatic Hernia is a rare

diaphragmatic defect. Females are twice affected than

that of males.1

Newborns with CHD often have

severe respiratory distress which can be life

threatening unless diagnosed and treated early.3,4 Thesymptoms are non characteristic and patients with this

disease maybe without symptoms for a long period.

The main tool for diagnosis of congenital DH is

radiography. Surgical correction is required. ECMO

has been used as a part of treatment strategy in some

hospitals.3

CONCLUSION

Diaphragmatic hernia is the congenital anomaly that

manifests itself since birth in the form of severerespiratory distress. Suspicion of the condition and

early diagnosis is necessary in such situation; surgical

correction is the treatment modality.


REFERENCES

1. Akhil maheshwari and waldermar A carlo.

Diaphragmatic hernia. Nelson textbook of

pediatrics,19th

edition,:594-96

2. George BM. Report of a Case Strangulated Right-

Sided Diaphragmatic Hernia. AMA Arch Surg.

195,72(2):273-74.

3. Bryner BS, Kim AC, Khouri JS, Drongowski

RA, Bruch SW, Hirschl RB et al., Right-sided

congenital diaphragmatic hernia: high utilization

of extracorporeal membrane oxygenation andhigh survival. J Pediatr Surg. 2009;44(5):883-7.

4. Christopher VVM, Canino JE, Jules RC, James

JR. Congenital Right Diaphragmatic Hernia.

Misericordia Hospital Philadelphia, Penna

congenital right diaphragmatic hernia associated

with Thorax. Thorax. 1950;5:133



195

Muthubabu et al., Int J Med Res Health Sci. 2014;3(1):195-196


&

Health Sciences


stOct 2013 Revised: 18


thDec 2013

Case report

CAPILLARY HEMANGIOMA OF THE COLUMELLA OF NOSE

*Muthubabu K, Sakthivel M, Srinivasan MK, Kalpana G, Twinkle Radhakrishnan, Ancy Anthony

Dept. of ENT, Meenakshi Medical College and Research Institute, Kanchipuram, Tamilnadu, India


ABSTRACT

Capillary hemangioma is a common condition but a capillary hemangioma arising from the columella of the nose is

rare. Here we report a 24 year old man who presented with a pedunculated swelling in the nasal columella. This was

excised. Histopathological examination showed features suggestive of capillary hemangioma, the case was

presented here due to rare occurrence in the nasal columella. Patients present with epistaxis and cosmetic

alterations. Wide excision and cauterization of the base gives excellent results.

Keywords: Columella, capillary hemangioma.

INTRODUCTION

Capillary hemangioma arising from the columella of the nose is rare. Capillary haemangiomas can occur

anywhere in the nasal cavity and has even been

reported in the ethmoids.1

Congenital lesions of

capillary haemangioma have been reported in

children.2

Capillary haemangiomas can grow in size to

produce nasal obstruction, hence earlier surgical

intervention is advisable.3

Frequent nose picking with

fingers has been cited as etiological factor. Cryo

application is one modality of treatment.5

Wide

excision and cautery is the treatment of choice.

CASE REPORT

A 24 year old person presented with complaints of

swelling hanging from the nose of one month duration.

He gave history of frequent nose picking with his

fingers. To start with the swelling was small in size

and has attained the present size (fig 1). He gave

history of bleeding from the mass at times. It was not

painful. He was also bothered about the cosmetic

alteration. On examination a reddish pedunculated

mass was seen arising from the columella of the noseon the right side. The stalk was narrow. The size of the

mass was about 2 cms. It was nontender, bled on

touch, hanging and freely mobile. Anterior rhinoscopywas done. The septum, turbinates and nasal mucosa

was found to be normal. Postnasal space was normal.

Under Local anaesthesia, infiltration with 2%

xylocaine in the columella of nose around the mass

was done. The pedunculated mass was excised

completely and the base was cauterized with bipolar

cautery. A wide excision of the mass was done. The

specimen was sent for histopathology which

confirmed capillary hemangioma ( fig 2&fig 3). The

wound was sutured with 3 – 0 chromic catgut. There

was no recurrence on follow up.

Fig 1: Capillary hemangioma arising from the nasal

columella.

DOI: 10.5958/j.2319-5886.3.1.041



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Muthubabu et al., Int J Med Res Health Sci. 2014;3(1):195-196

Fig 2: Photomicrograph showing lobular arrangement of

thinned out capillaries lined by plump endothelium and

thinned out squamous epithelium. (10 X)

Fig 3: Photomicrograph showing proliferation of

thinned out capillaries lined by plump endothelial cells.(40 X)

DISCUSSION

Capillary hemangiomas are benign tumours arising

from the vascular tissues of skin and mucosa. They are

made up of small capillaries which are normal in size

but more in number. These tumours may be either flat

to the skin, raised or protrude out as a nodule. In our

case the hemangioma protruded out as a nodule. They

are usually typically bright red in colour. Large

capillary hemangioma arising from the nasal columella

has been rarely reported.6

Adult capillary

hemangiomas have also been reported in the upper

eyelid.7

In the nasal cavity, cases with capillary

hemangioma involving the middle turbinate8

and in the

nasal septum has also been identified.9

Previous nasal

trauma and nose picking has been implicated as

possible etiological factors.4

In our case the cause of

the capillary hemangioma could be his persistant nose

picking habit. Small tumours like the one reported

here can be easily excised and the base cauterized. An

argon laser has also been considered by some for the

removal of this hemangiomas.10

CONCLUSION

Capillary hemangiomas are a common tumour. But

occurrence in the nasal columella is rare. Patientspresent with epistaxis and cosmetic alterations. Wide

excision and cauterization of the base gives excellent

results.

REFERENCES

1. Swapan K Gosh, Rajkumar Chathurvedi.

Capillary haemangioma of the ethmoid. Indian

Journal of Otolaryngology. 2004; 56(2): 148-49

2. Nedev P. Lobular capillary haemangioma of the

nasal cavity in children. Trakia Journal of Sciences. 2008; 6(1): 63-67.

3. Milton Waner, Julie Kastenbaum, Kathrin Scherer.

Haemangiomas of the nose – Surgical

management using modified subunit approach.

Arch Facial Plast Surg 2008; 10(5):329-334.

4. Puxeddu R, Berlucchi M, Ledda GP, Porado G,

Farina D, Nicolai P. Lobular capillary

hemangioma of nasal cavity. Ann J Rhinol. 206 ;

20 (4): 480 – 4.

5. Mohammed Maqbool, Suhail Maqbool. Tumours

of the nose and paranasal sinuses. Textbook of ear

nose and throat diseases 2013; Chapter 38, page

169.

6. Bora H, Bandyapadhyay SN, Sinha R, Bhuria R,

Mukherjee S, Das KK,Mukherjee PB. Large

capillary hemangioma arising from the nasal

columella: A case report. Journal of Indian

Medical Association 2001; 99(5):269 – 70.

7. Robert JP, Thomas I, Warner, Heather AD, Potter,

Daniel M, Albert. Adult capillary hemangioma.

Archives of ophthalmology 2012;130 (8):999

8. Kartaran H, Uraldi C, Arl N, Aktas D. Lobular

capillary hemangioma of the middle turbinate .

Acta otolaryngol 2006; 126: 442 – 444.

9. Ayotunde J Fasunla, Oluwatasin S Adebola,

Clement A Okolo ,Adereni AA. Nasal septal

lobular hemangioma in West Africa sub region ; A

case report. Case journal 2009 ; 2 : 8952.

10. Lemarchand VF. Indications for laser in the

treatment of capillary hemangioma.

J.Mal.Vasc.1992:17(1) 41 –

3.



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&

Health Sciences




thDec 2013

Case report

DELTO-PECTORAL FLAPS FOR SECONDARY DEFECTS FOLLOWING EXCISION OF

RECURRENT PAROTID TUMORS: CASE SERIES

*Adedeji Taiwo O1, Tobhi James E

1, Olaosun Adedayo O

1, Oseni Oyeniran G

2, Idowu Julius A

1, Olaitan Peter B

2

1Department of Ear Nose and Throat, Ladoke akintola University of Technology Teaching Hospital, Osogbo

2Department of Surgery, Ladoke akintola University of Technology Teaching Hospital, Osogbo


ABSTRACT

Background: Extensive infiltration of the skin by parotid gland tumors often lead to the surgeon seeking various

options that will lead to good cosmetic appearance and reduced donor site morbidity. Materials and Methods: This

is a report of two patients with extensively enlarged parotid tumors with associated skin loss and depth that was

difficult to close. Consent/permission was obtained from the patients. The case notes of the patients were reviewed

and it shows that apart from local tissues and skin grafts, delto-pectoral flaps could come handy. Outcome is

reported in this report. Results: Two patients who had a deltopectoral flap cover of their defects following excision

of huge parotid tumors involving the infiltration of the overlying skin are reported in this study. There was good

aesthetic outcome with minimal and acceptable donor site morbidity. Conclusion: Delto-pectoral flaps should beconsidered an option in covering defects following parotid tumour excision.

Keywords: Recurrent parotid tumours, Delto-pectoral flaps, Secondary defects, Cosmesis

INTRODUCTION

Parotid gland tumors are not common.1-3

Generally,

salivary gland tumors represent about 1-3% of head

and neck tumours.2

In our environment, it constitutes

1.7% of head and neck tumours3. Seventy eight to

eighty percent of parotid tumours are benign.2, 3

Parotid tumours elicit considerable medical interest

because of their multifaceted clinical presentation,

varied histological appearances and the associated

difficulties in predicting their prognosis.1,3

In most

cases, therapy consists of parotidectomy and adjuvant

therapy – mainly radiotherapy which is reserved for

cases with malignancies.2

Surgical intervention varies

from limited excision to extensive parotidectomy with

facial nerve sacrifice with or without neck dissection2.

Factors that influence surgical therapies include facial

nerve invasion, tumour extension, histological

characteristics and positive limits of the tumor.2

The recurrent parotid gland tumor is a challenge to

both the patient and the surgeon. Factors responsible

for tumor recurrence include histological grade, extent

of the tumour, invasion of adjacent structures and poor

surgical technique. Recurrence is more common in

malignant tumors4

but in pleomorphic adenoma (a

benign tumour), if the capsule ruptured during

removal, tumour may implant and cause recurrence.4

Management of recurrent parotid tumour is

challenging.4

There is a need for wide surgical

excision4

and facial nerve as well as the surrounding

soft tissues including skin sacrifices is inevitable.

Wide defects are therefore produced necessitating a

flap cover or a skin graft. The significant depression

created by complete tumour excision is a source of

concern for the patient about cosmesis and challenge

to the doctor about its closure.

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198


Various options available for repairing the defect

include fat grafts, sternocleidomastoid muscle rotation

flaps, cellular dermal graft and free vascularized facial

graft.4

The deltopectoral flap is a useful, reliable and

versatile regional flap that can be used in selected

circumstances for major head and neck

reconstruction.5

This article reports two cases of

recurrent parotid gland tumours that were managed by

the use of deltopectoral flaps in repairing the defects

created following wide surgical excision.

CASE NO 1

A.I. was a 69yr old male Nigerian referred from a

private hospital on account of left sided parotid

swelling. Progressive left sided parotid swelling

noticed about a year prior to presentation. No

associated swelling in other parts of the body, no pain

and no facial weakness. Examination at presentation

showed left sided parotid swelling which measured

6cm x 8cm in its widest dimension. It was firm, non

tender with no associated parapharyngeal /

oropharyngeal extension and no facial nerve

involvement.

Full blood count, electrolyte and urea and chest

radiograph were normal. An ultrasound revealed a

cystic mass 4.5cm x 4.7cm in widest dimension. Fine

needle aspiration for cytology suggested a benign

lesion. Patient had superficial parotidectomy under

general anesthesia. Findings at surgery were a cystic

mass about 6x6cm which contained sero-sanguinous

fluid. Patient was noticed to have developed House

and Brachman grade II facial palsy. Histology of the

tumour showed adenoid cystic carcinoma on account

of which he was referred for radiotherapy and

discharged to clinic but was lost to follow up.

He however re-presented two years later on account of

2 months history of recurrent parotid swelling withassociated pain and worsening of facial weakness.

Examination revealed 8cm x8cm left parotid swelling,

firm, non tender and no differential warmth. There was

grade III facial palsy. Full blood count, electrolyte and

urea, chest radiograph and clotting profile were

normal. He had a total parotidectomy. Operative

findings were tumour with a cystic cavity that had

infiltrated the root of zygoma, facial nerve, posterior

wall of external auditory canal and ramus of the

mandible. There was a big cavity of about 6 cm depthcreated. A deltopectoral flap was then designed and

raised and de-epithelialised and the distal part turned

over to fill the defect. This was transferred under the

skin of the lateral neck. The result was functionally

and cosmetically accepted by the patient.

Fig 1: Huge left parotid tumour infiltrating the skin

and ear lobule.

Fig 2: Case 1 at surgery (filling the defect with

delto-pectoral flap)

Fig 3: Post operative appearance

CASE NO 2

A 73yr old widow who presented on account of left

sided progressive parotid swelling of five years

duration. No associated swelling in other part of the

body, no history of pain, trauma or facial weaknessand no alteration in the size of the tumour during food

intake. Examination revealed an elderly woman with



199


12x 11cm left sided parotid mass, firm, non tender and

no differential warmth. Full blood count, electrolyte

and urea and chest radiograph were normal,

electrocardiograph showed left ventricular

hypertrophy, neck ultrasound revealed a non

homogenous mass with multi-septated cystic masses

measuring 10x20mm. Fine needle aspiration for

cytology was suggestive of pleomorphic adenoma. She

had superficial parotidectomy. Findings at surgery

were multi-nodular cystic mass about 25x18cm in its

widest dimension. Histology of the tumour showed

adenoid cystic carcinoma on account of which she had

54 cGy of radiotherapy. Three years later, patient

represented with 6 months history of recurrence. The

recurrence was associated with pain, facial weakness,

and ulceration and bleeding. Examination revealed an

elderly woman with a left parotid mass about 16x8cm

in widest dimension which had involved lobule of the

ear with a central area of ulceration. Full blood count,

electrolyte and urea, and chest radiograph were

normal. She had total parotidectomy. Operative

findings were multi-nodular masses which had

invaded the lobule of the ear and infiltrated the

branches of the facial nerve and associated facial

weakness. (Fig 4). A wide defect of 10 x 12cm) was

created. (Fig 5). Delto-pectoral flap of 24cm length

and 8cm width was designed, raised and partly de-

epithelialised. It was transferred by tunneling

subcutaneously into the defect. It covered the defect

completely and healed perfectly. The result was

functionally and aesthetically acceptable to the patient

Fig 4: Extensive recurrent left parotid tumor

infiltrating the skin and ear lobule

Fig 5: Defect after excision

Fig 6: Postoperative appearance of case 2.

DISCUSSION

The delto-pectoral flap remains a useful, reliable, and

versatile regional flap that can be used alone or in

combination with other flaps in selected circumstances

for major head and neck reconstruction5. It has

provided an excellent source of thin and pliable tissue

that form appropriate source of donor tissue for

reconstruction of limited defects of the pharynx,

esophagus, and skin of the neck 6. The flap has become

the most commonly used pedicle regional flap for head

and neck reconstruction while providing coverage for

most defects of the head and neck from the scalp andskull base to the cervical region and hypopharynx

7. It

continues to play an important role in head and neck

reconstruction, reflecting its versatility, reliability, and

ease of harvest7. The current reports show the

versatility of this flap in covering secondary defects

from parotidectomy especially in our environment

where patients present rather late with tumours that

may leave a defect that may not close directly. While

Microvascular procedure might have given a better

result, facility for this is often not available in mostdeveloping countries. This flap therefore comes handy

in managing this difficult and extensive defect



200


especially with the attending cosmetic problem that

might arise following the use of inappropriate tissue

for the closure.

Head and neck surgeries present unique challenges

because of the variety of functions that head and neck

are responsible for, including speech, swallowing,

sensation, oral continence, airway protection and facial

expression. Deformities of the head and neck region

can have devastating effects on the appearance and

function of the patient and are among the most

disabling and socially isolating defects with significant

impact on the patient’s quality of life. Reconstruction

of such defects continues to be an extremely

demanding challenge for surgeons who aim to restore

form and function with minimal surgical morbidity.

These reconstructive surgeries must always be

performed in a way that preserves these functions as

much as possible. The surgery may be done to restore

function, improve cosmetic appearance, or a

combination of both.

In the cases presented here, both function and

aesthesis were preserved with the flaps-one covering

the wide defect smoothly and the other occluding a

depth created by the excision of the tumors.

Gardiner et al.8

reported three cases of recurrent head

and neck carcinoma viewed as challenging

reconstructive problems because of the extent of the

extirpative surgery necessary and the substantial risk

of complications that would be associated with

previous treatment techniques. They showed that

myocuteneous flaps were quite versatile and useful in

head and neck reconstructive process8. Hurvitz et al.

9

reported that although defects of the head and neck

region present a challenge, successful cosmetic and

functional results have been achieved with both local

and free tissue flaps.

In the first of the cases presented in this article, delto-pectoral flap was designed, raised and de-

epithelialised. It was transferred by tunneling

subcutaneously into the defect to fill the cavity created

while in the second case, the flap with 24cm by 8cm

was designed, raised and partly de-epithelialised. It

covered the defect completely and healed perfectly.

Both results were functionally and aesthetically

acceptable to the patients. Delto- pectoral flap is

therefore useful in the reconstruction of defects and

restoration of cosmetic value to the patients followingsurgical excision of recurrent parotid tumours.

While the flap functions effectively for aesthesis and

function, the limitation of the flap is in the fact that it

was bulky and needed to be divided secondarily to

remove the bulkiness on the side of the neck in one of

the patients. This was in a woman with thick

subcutaneous fat. The second problem arose as a result

of the fact that the secondary defect was closed

directly and this led to about 2-3cm lift of the

ipsilateral breast compared to the contralateral side.

Although the 73 year old woman was satisfied and did

not bother about the disparity in the breasts as a result

of the flaps, caution is suggested in raising these flaps

in women. Indeed, this problem of lift and the

bulkiness that may need a second procedure must

always be explained to the patients. Deltopectoral

flaps are therefore part of the armamentaria that can be

considered for parotidectomy defects.

CONCLUSION

Delto-pectoral flaps should be considered an option in

covering defects following parotid tumour excision. It

is useful in the reconstruction of defects, restoration of

cosmetic value to the patients with minimal and

acceptable donor site morbidity.

REFERENCES

1. Somefun OA, Oyeneyin JO, Abdulkarrem FB, da

Lilly- Tariah OB, Nimkur LT, Esan OO. Surgery

of parotid gland tumours in Lagos: a 12 year

review. Niger Postgrad Med J. 2007; 14(1): 72-75.

2. Mag A, Cotulbea S, Lupescu S et al. Parotid Gland

Tumours. J Exp Med Surg Resear. 2010; 4: 259-

263.

3. Nzegwu MA, Ngozi NR, Ugochukwu AI et al. A

Review of Salivary Gland Neoplasm in Eastern

Nigeria for A Five- Year Period from January 1,

2000 to December 31st 2004. Adv in Bioresear

2011; 2(1): 28 – 32

4. Carrol WR, Morgan CE. Diseases of the Salivary

Glands. In Ballenger’s Otorhinolaryngology Head

and Neck Surgery, sixteenth edition (Snow JB,

Ballenger JJ eds) BC Decker Inc. Hamilton,

Ontario, 2003; 1441 – 1454.

5. Gilas T, Sako K, Razack MS et al. Major Head

and neck reconstruction using deltopectoral flap.

A 20 year experience. Am J Surg 1986; 152(4):

430 – 434.6. Mortensen M, Genden EM, Role of the island

deltopectoral flap in contemporary head and neck



201


reconstruction. Ann Otol Rhinol Laryngol. 2006

;115(5):361-364

7. Yang JY, Rosen MR, Keane WM. Flaps and

Grafts in the Head and Neck . In Ballenger’s

Otorhinolaryngology Head and Neck Surgery,

sixteenth edition (Snow JB, Ballenger JJ eds) BC

Decker Inc. Hamilton, Ontario, 2003; 972- 996.

8. Gardiner LJ, Ariyan S, Pillsbury HC.

Myocuteneous flaps for challenging problems in

head and neck reconstruction. Arch Otolaryngol.

1983; 109(6): 396- 399.

9. Hurvitz KA, Kobayashi M, Evans GR. Current

options in head and neck reconstruction. Plast.

Reconstr. Surg. 2006; 118(5):122e-133e.



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thDec 2013

Case report

RABIES: NEED FOR ACTIVE AND PASSIVE IMMUNISATION

G N S Sangeetha Lakshmi

Dept of General Medicine, Baptist Christian Hospital, Tezpur, Assam


ABSTRACT

Rabies is an acute highly fatal viral disease of the CNS caused by Lyssavirus Type-I. It has a long and variable

incubation period. It is a communicable disease of man that is always fatal. The combined administration of a single

dose of anti rabies serum with a course of vaccine, together with local treatment of the wound is the best specific

prophylactic treatment after exposure of man to rabies. Here, we report a case of rabies, who developed the disease

in spite of having taken three doses of anti rabies vaccine (Post exposure).

Keywords: Rabies Immunoglobulin, Human Diploid Cell Vaccine, Post-exposure Prophylaxis, Intra-dermal

Regimen.

INTRODUCTION

Rabies is a zoonotic disease of warm blooded

carnivore animals. It is transmitted to man usually by

bites or licks of rabid animals on broken skin and

mucous membrane.

Human Rabies is endemic in India. According to a

recent WHO estimate, 55000 deaths occur annually

due to human rabies globally 20,000 (36%) of which

occur in India.1

CASE REPORT

A female patient aged 55 years presented to the

Casualty of a secondary care hospital in Assam with

history of feeling feverish, headache, vomiting and

increased irritation since the morning of 29.05.2012.

She was admitted to the hospital with a provisional

diagnosis of Acute Sinusitis / Headache for evaluation.

At admission on physical examination vitals were

stable, mild frontal sinus tenderness was seen, and rest

of the systemic examination was normal. Complete

blood count, Random Blood Sugar, Serum Creatinine,

Serum Electrolytes, Liver Function Test, complete

Urine examination were within normal limit. Tests for

the peripheral smear of malaria and Rapid test for

Scrub Typhus was Negative. Chest-X-Ray and ECG

were within Normal limit.

After admission, in the ward she was found to be

reluctant to drink water. Further examination revealed

agoraphobia, hydrophobia and a healed wound on the

nasal bridge.

On reviewing history, the patient’s attendant revealed

that the patient had been bitten by a street dog on the

nasal bridge 2 weeks ago. The patient was taken to a

local physician and given HDC vaccine-Rabipur on ‘0’

day - 1st

dose, 3rd

day - 2nd

dose, 7th

day - 3rd

dose ;

post exposure. The 4th

dose was not taken, as the

patient developed symptoms of rabies two days prior

to the 4th

dose. The patient was however not RIG

advised.

The patient was well until 27.05.2012 (14 days after

the dog bite) doing all household work. The neither

relatives nor patient could tell about the fate of the

dog. A clinical diagnosis of rabies was made. The

DOI: 10.5958/j.2319-5886.3.1.043



203


patient was discharged on request and advised to go to

a higher Centre.

DISCUSSION

The prophylaxis of rabies is with an Anti rabies

vaccine and rabies Immunoglobulin. The Postexposure Prophylaxis depend on the category of the

wound.2

Approach to Post-exposure Prophylaxis (PEP):

Management of animal bite wound:

Wound Toilet: Rabies virus enters the human body

through a bite or scratch. An efficient wound toilet can

be done by prompt and gentle washing with soap and

flushing the wound with running water for 10 minutes.

Considering the importance of this step all clinics that

are likely to encounter patients with dog bites shouldhave wound washing facilities.

Passive immunization – rabies Immunoglobulin

(RIG): RIG should also be administered as passive

immunisation for immediate protection before the

development of immunity from the vaccine, It should

be given at the same time as the first dose of vaccine

and no later than 7 days after the first dose.2

Rabies

vaccine and RIG should never be administered at the

same site or in the same syringe.

Two types of Rabies antibody preparations areavailable: Human rabies immunoglobulin (HRIG) and

Equine rabies immunoglobulin (ERIG).

The recommended dose of ERIG is 40 International

units (IU) /Kg3

up to a maximum of 3000 IU2, ERIG

may be occasionally associated with anaphylaxis. A

skin test may be performed prior to the administration

of ERIG but WHO does not advocate skin sensitivity

test (SST) anymore.4

The recommended dose of HRIG

is 20 IU/Kg3

up to a maximum of 1500IU.2

Adverse

effect of HRIG includes local pain and low grade

fever.

The wounds should be infiltrated with RIG (if

anatomically feasible) and the remainder of the dose

should be given intramuscularly (IM) in the gluteal

region. If the exposure involves a mucous membrane,

the entire dose should be administered IM. With

multiple or large wounds, the RIG may need to be

diluted for adequate infiltration.

Active Immunisation – Anti rabies Vaccine: HDC

vaccines are mostly used as they are generally safe and

highly potent. All age groups of animal bite victims of

category II and III require the same number of

injections and dose per injection. The category III

exposures in addition require administration of rabies

immunoglobulin. The vaccination schedule

recommended for Post exposure Prophylaxis consist of

6 doses (1 ml each) on days 0, 3, 7, 14 and 28 and a

booster dose on day 90. Injections are given

intramuscularly (deltoid).2

Intra-dermal (ID) Regimens: The use of this route

leads to considerable savings in terms of the total

amount of vaccine needed for a full Post-exposure

vaccination. A vaccine which has been approved by

Drug Controller General of India (DGCI) for use by

intra-dermal route have to be used[2]

.The vaccines

used are same; however route, dose and site of

administration differ. The Regimen approved by DGCI

has updated Thai Red Cross schedule (2-2-2-0-2).2

Approach to a patient requiring RIG when none is

available: In circumstances when no immunoglobulin

is available greater emphasis should be given to proper

wound toileting followed by Essen schedule.2

RIG is life saving biologic in patients with severe

exposure to rabies, but scarce and expensive.

Worldwide less than 3% of risk exposure cases receive

RIG and it is often not injected into wounds.5,6

Fear of

anaphylaxis with ERIG and the cost of HRIG are the

main barrier. ERIG is indigenously produced, less

expensive, more widely available. ERIG should be

promoted as an ‘institutional product’7

and given by

trained persons in all first referral unit (FRU)

hospitals. The safety profile of ERIG is good in many

studies.8

Post exposure prophylaxis applied adequately

is highly effective in prevention of human disease but

its use is low in India (2.1%).9

The compliance to

vaccine in India is 40.5%.9

After recognition of a rabies exposure, when a patient

approaches a local physician, exposure has to be

assessed to see which category it falls into. The needfor RIG and active immunisation has to be stressed

and informed to the patient by the local physician. In

our case, the patient should have been administered

RIG along with the first dose of rabies vaccine or been

informed of the need to enable the patient to approach

a higher centre for the same.

Rabies can be confirmed in patients early in the illness

by antigen detection using immuno fluorescence of

skin biopsy, and by virus isolation from saliva and

other secretions. These tests are not available in ourhospital, therefore they were not done.



204


CONCLUSION

The approach to the management of rabies consists of

wound toilet, active and passive Immunisation should

be made available at the Primary Health Centres

(PHC) across the country.

As HRIG is expensive, ERIG can be used as it is less

expensive and more widely available. WHO has

recommended the use of intra-dermal (ID) route of

administration of HDC vaccine which not only reduces

the cost of Post-exposure Prophylaxis, but also allows

wider coverage in available quantity of vaccine?

This case shows the need for the combined

administration of RIG and Anti rabies vaccine in every

case of exposure of man to rabies. Every instance of

human exposure should be treated as a medical

emergency.

REFERENCES

1. Haniv J, Gdalenich M, Mimouni D, Gross E,

Shpilberg O. Successful post exposure rabies

prophylaxis after erronous starting treatment. Prev

Med 1999; 29(1): 28-31

2. National guidelines for rabies Prophylaxis and

Intra-dermal Administration of Cell Culture rabies

Vaccines – 2007.

www.ncdc.gov.in/Rabies_Guidelines.pdf

3. World Health Organisation 2005: WHO expert

consultation on rabies. First report (First Report

Edition), Geneva, WHO, 2005.

http://apps.who.int/iris/bitstream/10665/85346/1/9

789241209823_eng.pdf

4. Rabies Vaccines: WHO Position paper. Wkly

Epidemiol Record 2010; 85:309-20.

5. David Anderson. WHO guidelines dealing with

immunoglobulin use impede rabies prevention.

Asian Biomed. 2007; 1:103-7.

6. Association for Prevention and Control of Rabies

in India (APCRI), assessing the burden of rabies in

India: WHO Sponsored National Multi Centric

rabies Survey, 2004. http://rabies.org.in/rabies-

journal/rabies-06/SpecialArticle1.htm

7. Sudarshan MK, Ashwath Narayana DH, Ravish

HS. Is skin sensitivity test required for

administering equine rabies immunoglobulin ?

The National Medical Journal of India.

2011;24(2):80-82

8. Chawan VS, Tripathi RK, Sankhel L, FeravdesAC, Dastary GV Safety of equine rabies

immunoglobulin in Grade-III bites. Indian J

Community Med 2007; 32:73-74

9. Sudarshan MK. Assessing the burden of rabies in

India. WHO sponsored national multi-centric

rabies survey 2003. Final report August 2003.

Bangalore, Association for Prevention and control

of Rabies in India (APCRI), 2003.

10. Tapan Ranjan, Durga Madhab Sathapathy,

Ashiwini Kumar Pradhan. Safety of Equine rabies

Immunoglobulin into fingers and toes. Asian Bio

medicine. 2012;6(3):429-32.

11. Wilde H, Chutivongse S. Equine rabies

immunoglobulin : a product with a underserved

poor reputation. An J Trop Med Hyg.

1990;42(2):175-8.

12. Sudarshan MK, Madhusudan SN, Mahendra BJ,

Rao NS, Aswath Narayana DH Abdul Rahman S,

Assessing the burden of human rabies in India.

Results of a national multi-centre epidemiological

survey. Int J Infect Dis 2007, 11:29-35.



205

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&

Health Sciences

www.ijmrhs.com Volume 3 Issue(1 Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 11



thDec 2013

Case report

SPONTANEOUS NEPHROCUTANEOUS FISTULA IN TUBERCULOUS PYELONEPHRITIS: AN

UNUSUAL OCCURRENCE

Apoorv Sharma1, *Zeeshanuddin Ahmad

1, Arpan choudhary

1, Moolchand Songra

2

1MS Senior Resident, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India

2HOD and Professor, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India


ABSTRACT

Nephrocutaneous fistula has an uncommon incidence and occur usually as a complication of operative procedures

on kidneys, renal injuries (penetrating or iatrogenic), renal uroliths, renal tumors and chronic UTI with resultant

perirenal abscesses. The most common causes identified are renal calculi and chronic renal tuberculosis. We intend

to highlight a case of a woman aged 35years, complaining of watery discharge through the skin in the right lumbar

region for the past six months. A fistulogram was done which showed the passage of contrast dye in the collecting

system. The patient underwent a simple nephrectomy on the concerned side and recuperated without any

complication in the postoperative period.

Keywords: Kidney, Fistula, Renal tuberculosis, Nephrocutaneous.

INTRODUCTION

Spontaneous nephrocutaneous fistula (NCF) is a rare

condition. Majority develop secondary to

postoperative, trauma, chronic urinary tract infection,

renal stones1. Few cases as a complication of

xanthogranulomatous pylonephritis has also been

reported to the literature2, however occurrence of this

condition due to renal tuberculosis is a rare

phenomenon. The fistula may be internal (the fistulous

communication between kidney and adjacent viscera

like colon, duodenum, or jejunum) or external, like

nephrocutaneous fistula.3We report a rare case of

Spontaneous nephrocutaneous fistula due to renal

tuberculosis.

CASE REPORT

Complaints - A 35 year old female presented with

complaint of insidious onset watery discharge from her

right flank for 6 months. There was no history of loin

pain, back pain, lump in abdomen, fever, frequency of

urination or burning micturition at any time during the

course of illness. She never underwent any surgical

intervention in the past. There was also no history of

previous purulent discharge.

Examination -The physical examination revealed a

fistulous orifice in the skin on the right lumbar region

with surrounding induration. Examination of chest,

abdomen, spine and genitourinary systems was

unremarkable. There was no lymphadenopathy. On

examination watery discharge was of ammoniacal

smell. Culture and sensitivity of the discharge and

urine were sterile. X-ray chest, spine and KUB were

normal. Routine blood tests including renal functions

were normal and patient was not found diabetic.

Investigation - A fistulogram was done which showed

the passage of contrast dye in the right collecting

system travelling down freely up to the ureter andbladder (Figure 1). Excretory urography revealed

nonfunctioning right kidney with normal function

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206


opposite side. Ultrasound abdomen revealed small

right kidney with significant cortical loss and fistula

site biopsy was inconclusive.

Treatment- In view of non functioning right kidney,

nephrectomy was planned with excision of the fistula.

Intraoperatively shrunken, atrophic kidney was found

adhered to the surrounding tissue and perinephric fat

with caseous material filled in (Putty kidney). After

careful separation from surrounding tissue simple

nephrectomy was performed by excision of the entire

fistulous tract including skin and subcutaneous tissue.

Histopathology - Histopathological examination of

the specimen showed tuberculous pyelonephritis. The

postoperative period was uneventful. Patient was

started on antitubercular drugs and was discharged on

the seventh post-operative day.

Fig 1: Fistulogram showing passage of contrast agent to

the right collecting system freely up to the bladder

DISCUSSION

Spontaneous nephrocutaneous fistula without previous

surgical history is rare.4

Most of the cases reported in

the literature was associated with chronic UTI, renal

tumors, renal tuberculosis and nephrolithiasis. Patients

often overlook minor complaints of backache and

flank pain; such neglected cases often harbor an

underlying perinephric abscess5

that may lead to the

genesis of a spontaneous NCF. A review of literature

suggests renal calculus being the most common cause

followed by tubercular and xanthogranulomatous

pyelonephritis and reflux disease.6,7

However some

reports favor open surgical procedure being

commonest.8

Tuberculous pyelonephritis usually starts in renal

parenchyma and ureters and bladder are secondarily

involved. The mode of spread is hematogenous. Three

pathological stages have been described. At any stage,

when there is significant fibrosis and outlet

obstruction, the pus may find its way along the path of

least resistance-forming renocutaneous, reno-colic or

reno-pleural fistula. The case under discussion had

total outlet obstruction in proximal ureter due to

progressive fibrosis and obstruction causing atrophic,

putty kidney and renocutaneous fistula.

The clinical features related to renal tuberculosis are

variable and range from simple fatigue, anorexia and

weight loss, to the attacks of loin pain and haematuria.

Other features depend upon the stage of disease and

extent of involvement. Apart from routine

investigations, culture and sensitivity of urine,

abdominal ultrasound, fistulography, excretory

urography and DTPA renal scintigraphy are important

diagnostic tools.

Early changes are best detected by excretory

urography / pyelography while chronic changes are

evaluated with the help of ultrasound or CT scan. Plain

films are helpful in detecting lesions in the lungs and

areas of calcification in kidneys, adrenals and adjacent

lymph nodes. The standard treatment of

nephrocutaneous fistula is nephroureterectomy with

complete debridement of affected perirenal fat,

muscles, and subcutaneous tissue. The surgery is

followed by anti-TB regimen and long-term follow-up.

Classification of TB Pyelonephritis

I: Nondestructive (infiltrate) tuberculosis of kidney

II: Initial destruction (papillitis or small, by diameter

about 1 cm, single cavity);

III: Marked destruction (caverns or policavernosial

tuberculosis one of kidney segments);

IV: Total or subtotal destruction (policavernose

tuberculosis, tubercular pyonephrosis, calcification).

They distinguish three forms of tuberculosis:

tuberculoinfiltrative, ulcerous and scar.

CONCLUSION

We highlight here the rarity of spontaneous

nephrocutaneous fistula and renal tuberculosis as animportant differential diagnosis to be kept in mind in

the Indian scenario.



207


REFERENCES

1. Singer AJ. Spontaneous nephrocutaneous fistula.

Urology 2002; 60(6): 1109 – 10.

2. Biyani CS, Torella F, comford PA, Brough SJ.

Xanthogranulomatous pyelonephrins with bilateral

Nephrocutaneous fistulae. Urol Int 1997: 59: 46-

47.

3. Ansari MS, Singh I, Dogra PN. Spontaneous

nephrocutaneous fistula — 2 unusual case reports

with review of literature. Int Urol Nephrol.

2004;36:239 – 43.

4. Alberto A, Antunes, Adriano A, Calado, Evandro

F. Spontaneous nephrocutaneous fistula.

International Braz J Urol 2004; 30: 316-18.

5. Karfopoulos AS, Murray W, Stone FJ.

Nephrocutaneous fistula. J Med Soc NY 1981; 78:379.

6. Iseki T, Kawamura M. Spontaneous passage of

renal calculi through nephrocutaneous fistula due

to calculous pyelonephritis. Br J Urol 1987;

59(3): 285 – 86.

7. Lewi HJE, Scott R. Calculocutaneous sinus.

Urology. 1986;28:232 – 34.

8. Das S, Ching V. Nephrocutaneous sinus: a case

report. J Urol 1979; 122: 232.

9. Hargreave TB. The kidney and ureter. In: CusheiriA, Giles GR, Moosa AR, (edi). Essential surgical

practice, 3rd ed. Oxford. Butterworth- Heinemann;

1995:1487.



208

Veena et al., Int J Med Res Health Sci. 2014;3(1):208-211


&

Health Sciences


ndNov 2013 Revised:1 8


thDec 2013

Case report

CONGENITAL GIANT MELANOCYTIC NEVI – TIP OF THE ICEBERG

*Veena G1, Sathish Selva Kumar

2, Meenakshisundaram

3, Rajalakshmi V

4

1Senior Resident,



4Professor & HOD, Department of Pathology, ESIC

Medical college & PGIMSR , K. K. Nagar, Chennai.


ABSTRACT

Congenital Giant Melanocytic Nevus (CGMN), pigmented lesion present since birth, occurs in 1 % of infants

worldwide. Fifteen percent of CGMN are localized in the head and neck region and it can also have a bathing trunk

distribution. It grows proportionally to the size of the body as the child matures and grows with variation in colour

and surface texture. A 29 years old female presented to the Gynecology Out Patient Department for infertility. She

also had multiple large nevi of varying sizes present since birth. The lesion was distributed all over the body. She

also complained of sudden appearance of swellings at the back which were later excised and the histopathological

examination showed the presence of neural nevus involving the dermis and subcutaneous tissue. This case is being

reported for its rarity, the higher risk for melanoma transformation, its association with meningeal melanosis and

few benign / malignant tumors.

Keywords: Congenital, Nevi, Melanoma

INTRODUCTION

Melanocytic nevus refers to any congenital/acquired

lesion of melanocytes. They are common and they

present with numerous clinical and histologic types.

This variation in clinical and histologic presentations

necessitates thorough knowledge to differentiate from

malignant tumors. Congenital Giant Melanocytic

Nevus, classified according to the size of the nevus,1-4

are present since birth.1

These pigmented lesions are

to be followed up regularly because of their

association with melanoma transformation, meningeal

melanosis and few benign / malignant tumors.

CASE REPORT

A 29 years old female presented to Gynecology

Department for infertility. Incidentally, she brought

to the notice of the gynecologist about multiple

blackish lesions of varying sizes all over the body

since birth. She also complained of sudden

appearance of multiple nodules on her back of three

months duration. On examination multiple large

pigmented lesions were seen in the upper part of

chest, back and face. Few areas of the pigmented

lesions showed hair. The pigmented areas of the back

showed three nodules measuring 5x4cm, 7x5cm and

8x5cm each with wrinkled skin (Fig 1). All other

laboratory parameters were within normal limits. The

clinical differential diagnosis of the nodules was

neurofibroma. One of the nodules was excised and

sent for histopathological examination.

Gross – Specimen of skin with soft tissue mass

measuring 10x8x5 cm. The skin showed wrinkling

and hyperpigmentation. The cut section showed many

specs of black discoloration of less than 0.3 cm,involving the subcutis (Fig 2).

DOI: 10.5958/j.2319-5886.3.1.045



209


Microscopy -Sections showed structure of skin with

dermis showing interlacing fascicles of spindle

shaped cells with elongated nuclei interspersed with

collagen fibers, melanophages containing melanin

pigments (Fig 3). The skin appendages were also

surrounded by similar cells. Melanin bleach was done

and it confirmed that the pigments were melanin.

Immunohistochemistry showed positivity for HMB

45 and S 100 (Fig 4). Final diagnosis of congenital

giant melanocytic nevus was made.

Fig 1: CGMN involving the back, is hair borne.

Nodules are seen (arrow).

Fig 2: GROSS- Cut section shows multiple black

pigmented specs extending upto the subcutis.

Fig 3: a) epidermis and underlying dermis showing

melanocytes (100 X)

Fig 3 b): shows dermis with interlacing fascicles of

spindle shaped cells interspersed with collagen fibres

and theques of melanocytes (40 X)

Fig 4: Immunohistochemistry – a) Melanocytes showing

positivity for HMB 45 (100 X)

Fig 4: IHC – b) Melanocytes showing positivity for

S100 (100 X)

DISCUSSION

Melanocytes are of neural crest origin and they

migrate along nerves that emerge from the spinal cord

and merge with the skin. As they reach the skin, they

spread out evenly among the epidermal cells. These

melanocytes produce pigments, which protect the

skin from damage by the ultraviolet rays from the

sunlight. Congenital Melanocytic Nevi (CMN)



210


reflects a failure of the normal process of migration of

melanocytes into the skin. Instead of spreading out

evenly into the skin, many cells collect at the same

spot .

Majority of the CMN are sporadic as our case, but

few familial cases have also been reported.

Congenital melanocytic nevi are present at birth in

1% to 2% of newborns.1-3

Large CGMN are rare

occurring 1 in 20,000 to 1 in 500,000 newborns.1

CMN are classified according to their size, as small-

less than 1.5cm , medium 1.5-19.9cm and large -

more than 20 cm.1,3,4

Zeal LH et al recommended

defining CGMN as nevi covering 1% body surface

area in the face and neck and 2% elsewhere in the

body. . Hence our case according to this can be

classified as CGMN. The size is significant as it

determines the therapeutic options and risk for

malignancies.

CGMN can occur in both sexes4

with a slight female

predilection5. Majority of Congenital melanocytic

nevi, increase in size during first trimester of

pregnancy.5,6

Clinically the CMN are tan to brown, small,

uniformly pigmented, flat to elevated with well

defined, round borders. Giant melanocytic nevus is

darkly colored and well delineated from the normal

skin. Giant CMN are often covered with hair or

proliferative nodules.7

CGMN can occur at any site,

may involve whole extremity, scalp or the trunk and

may extend into the placenta. CGMN is associated

with meningeal or cerebral melanosis.

The majority of these patients lead normal life

without any complications. CGMN is at an increased

risk for the development of melanoma and is as high

as 5-7 % by age 60 years, and Arif et al suggested the

incidence as 2% to 31 % for melanoma

transformation.5,8

In another study, 70% of melanomas occur in patients with giant CMN before

puberty.5

Hence there is no age limitation for the risk

of melanoma transformation. The risk of melanoma

may be greater in those with giant congenital

melanocytic nevi with larger diameter.1,9

Another

study suggests multiple nevi alone or with associated

posterior midline location of large congenital

melanocytic nevi may be complicated by underlying

cranial or spinal leptomeningeal melanocytosis.10

Crowe et al

11

, in their study of 223 patients withneurofibromatosis found that 3 patients had extensive

CMN. Von Recklinghausen in his monograph

described 1 of 28 patients as having giant CMN. Few

benign conditions like diffuse lipomatosis,

hamartomas, hemangiomas, lymphangiomas,

mastocytomas, schwannomas, Von-Recklinghausen's

disease, vitiligo, structural brain malformations,

hypertrophy of skull bones, skeletal asymmetry,

hydrocephalus are associated with CGMN. The

explanation for these mixed neoplasms is that CMN

precursor cell, at least in some cases, is pluripotent

stem cell which has the capacity to give rise to

multiple cell types.12

Similarly malignant conditions

associated with CGMN are neuroectodermal tumors,

malignant melanoma (6% to 12%), neurocutaneous

melanosis, rarely rhabdomyosarcoma. One of the

syndromes known as Epidermal Nevus syndrome,

also known as Feuerstein syndrome/ Solomon's

syndrome, consists of extensive congenital nevi with

abnormalities of central nervous system (CNS),

musculoskeletal system, cardiovascular, genitourinary

and eyes.12

A study of 57 patients with CMN, suggests that

somatic mosaicism for NRAS codon 61 mutations in

a progenitor cell within the neuroectoderm cause

multiple CMN and neuromelanosis (including

nonmelanocytic CNS lesions).13

Treatment is usually to obtain an acceptable cosmetic

result to decrease the psychosocial inconvenience to

the patient and to minimize the risk of malignancy.

Curettage is an alternative to surgical excision if

performed in the first 2 weeks of life.14

Even after

complete removal of the nevi, the risk of malignancy

persists as the melanoma can occur at extracutaneous

sites, especially in CNS.5, 15

CONCLUSION

Long term follow up of the CGMN patients helps in

early diagnosis of malignant melanoma and variousbenign/malignant tumors. Regular follow up of the

patient with magnetic resonance imaging is essential

for early detection of CNS complications. Anxious

couples need to be counseled, as there is no risk

associated with pregnancies. This case reported for its

rarity and its associated complications.

REFERENCES

1. Mary Wu Chang, Vourc’h-Jourdain M.The Risk

for Melanoma in large, congenital melanocytic

nevi, J Am Acad Dermatol 2012,



211


www.jwatch.org/./risk-melanoma-large-

congenital-melanocytic-nevi.

2. Alper JC, Holmes LB. The incidence and

significance of birthmarks on a cohort of 4641

newborns, Pediatric Dermatology. 2012;1(1):58-

68

3. James WD, Berger TG. Andrews ’Diseases of the

skin: clinical Dermatology, Saunders Elsevier.

2006; 10th

edn ; Philadelphia, pg 678-79

4. Karthik Natarajan. Congenital Melanocytic Nevi :

Catch Them Early!. J Cutan Aesthet Surg.

2013;6(1) :38-40.

5. Bhagyalakshmi A. Giant Congenital Melanocytic

Nevus of Scalp: a rare case. International Journal

of Research in Medical Sciences. 2013;1(3):317-

19

6. Timothy McCalmont, Dirk M Elston.

Melanocytic Nevi. Updated Jun 3, 2013,

emedicine.medscape.com/article /1058445.

7. Price HN, Schaffer JV. Congenital Melanocytic

Nevi-when to worry and how to treat: Facts and

controversies. Clinics in Dermatology.

2010;28(3):293-302

8. Arif Turkmen, Ebopras, DaghanIsik, Mehmet

Bekerecioglu. Comparison of Classification

Systems for Congenital Melanocytic Nevi.

Dermatologic Surgery 2010;36:1554-62

9. Hale EK, Stein J, Ben- Porat L. Association of

melanoma and neurocutaneous melanocytosis

with large congenital melanocytic nevi- results

from the NYU-LCMN registry. Br J Dermatol.

2005;152(3): 512-17

10. Lovett A, Maari C, Decarie JC. Large congenital

melanocytic nevi and neurocutaneous

melanocytosis: one pediatric center’s experience.

J Am Acad Dermatol. 2009;61(5):766-74

11. Crowe FW. A Clinical,Pathological and Geneticstudy of multiple Neurofibromatosis.

Springfield,IL,Charles C Thomas,1956,p 181.

12. Fitzpatrick’s Dermatology in General Medicine.

Klaus Wolff. Melanocytic tumors, Benign

neoplasia and hyperplasia of melanocytes,1;7the

ed: C1099-1101.

13. Veronica A. Multiple Congenital Melanocytic

Nevi and Neurocutaneous Melanosis Are Caused

by Postzygotic Mutation in codon 61 of NRAS,

Journal of Investigative Dermatology. 2013;133,2229-36

14. Linda E . De Raev. Curettage of Giant Congenital

Melanocytic Nevi in Neonates. Arch Dermatol.

2002;138(7) 943-47

15. Marghoob AA, Schoenbach SP, Kopf AW. Large

Congenital nevi and the risk for the development

of malignant melanoma. Arch Dermatol

1996;132:170



212

Vandana et al., Int J Med res Health Sci. 2014;3(1):212-215


&

Health Sciences




stDec 2013

Case report

PRIMARY UROTHELIAL CARCINOMA OF PROSTATE: A RARE CASE REPORT

*Vandana Gangadharan

1, Geetha Prakash

2, Eswari V

3, Indhu Kannan

4

1Assisstant Professor,

2Professor and HOD,


4Post Graduate, Department of Pathology,

Meenakshi medical college, hospital and Research institute, Enathur, Tamilnadu, India


ABSTRACT

Primary urothelial carcinoma of the prostate is a rare clinicopathological entity which as a rule bears an

unfavourable prognosis. We report a case of a 75 year old male who presented with a history of voiding difficulty.

With a provisional diagnosis of Benign Prostate Hyperplasia both clinically and by needle biopsy a Trans Urethral

Resection was undertaken. Histopathology showed acini lined by malignant transitional epithelial cells with stromal

invasion. No primary in the bladder was detected on the investigation. A CK 7/ CK 20 copositivity on

Immunohistochemistry confirmed our diagnosis of Primary Urothelial Carcinoma of Prostate.

Key words: Urothelial, carcinoma, prostate, primary

INTRODUCTION

Transitional cell carcinoma of prostate is carcinoma of

urothelial origin. The reported incidence of prostatic

transitional cell carcinoma ranges from 21.8 – 36.7%

depending mainly on the manner of examination.1,2

Urothelial carcinoma of the prostate is rarely primary

and usually represents synchronous or metachronous

spread from carcinoma of bladder and urethra.3

The

frequency of primary urothelial carcinoma, ranges

from 1- 4% of all prostate tumours in adults.3,4 Mostpatients are older with a similar age distribution to

urothelial carcinoma of the bladder i.e. 45 to 90 years.4

The primary prostatic transitional cell carcinoma

involves the entire prostatic urethra particularly areas

near the verumontanum, the large prostatic duct and

nearby acini. They presumably arise from urothelium

lining the prostatic urethra and the proximal portion of

prostatic ducts. It has been postulated that these may

develop through a hyperplasia – dysplasia sequence,

possibly from reserve cells within the urothelium.5

Stephen et al6

also suggests that tumour originating in

the prostate may be the result of malignant

transformation of prostatic urothelium. On the other

hand secondary prostatic transitional cell carcinoma

mainly involves the bladder neck or posterior prostatic

tissue and results from the direct pagetoid spread of

urothelial carcinoma in situ or a direct pathologic

invasion of bladder urothelial carcinoma. However

whether primary or secondary transitional cell

carcinoma of prostate is believed to have a poor

prognosis.7

CASE REPORT

A 75yr old male patient presented with a 3 month

history of voiding difficulty, symptoms of nocturia and

very few episodes of dysuria. This was not associated

with significant anorexia or weight loss. No other

positive history was elicited. Serum PSA done was

within normal limits. Ultrasonography revealed

prostatic enlargement without any nodules.

DOI: 10.5958/j.2319-5886.3.1.046



213


Initial prostatic biopsy with a provisional diagnosis of

Benign Prostatic Hyperplasia reported focal acini

showing hyperplasia with low grade PIN changes.

The patient was followed with Trans Urethral

resection of prostate which revealed prostatic acini

with adenomatous hyperplasia and a focus of ducts

lined by malignant transitional epithelial cells with

mitotic figures and areas of necrosis and stromal

invasion. – suggesting Transitional cell carcinoma of

prostate.

Fig 1: Urothelial Carcinoma Prostate 40x

Fig 2: High grade cytological features (40x)

Fig 3: Cytokeratin 7 positivity (40x)

The urinary bladder was evaluated with clinical andultrasonography to rule out secondary TCC prostate

from a bladder primary carcinoma. This turned out to

be negative. Immunohistochemisty with CytoKeratin

7 (CK 7) and Cytokeratin 20 (CK 20) was positive

while Prostate Specific Antigen (PSA) was negative

which confirmed our diagnosis.

DISCUSSION

Prostate cancer is one of the most common cancers in

men. Prostatic cancer occurs microscopically in up to

50% men by the age of 50 and almost all men aged 80

years showed some microscopic evidence of prostate

cancer.8

Besides the garden variety of prostatic

adenocarcinoma many variants and a wide histological

spectrum have been described. These include

mucinous carcinoma, neuroendocrine carcinoma,

sarcomatoid carcinoma, squamous cell carcinoma,

urothelial carcinoma etc.3

Primary urothelial carcinoma of prostate is rare with

an incidence ranging from 1-4%3,4

and arises either

from prostatic urethra or from the urothelial lining of

the larger periurethral prostatic ducts.9

Patients usually

present with symptoms of haematuria, urinary

obstruction or prostatitis as was seen in our case.3,10

Wadhwa et al11

describes an atypical case presenting

as bleeding per rectum due to a rectal ulcer. Digital

rectal examination is abnormal in the majorityof cases

but is rarely the presenting sign.10 Clinically urothelial

carcinoma of prostate may be mistaken for nodular

hyperplasia or prostatitis which was the provisional

diagnosis in our case too.3

Serum prostate specific

antigen (PSA) which is the cornerstone in the

diagnosis of prostatic adenocarcinoma is not elevated

in primary urothelial carcinoma of prostate (< 4

ng/dl).3

Radiological findings can overlap and play

limited role in the diagnosis of unusual neoplasms of

prostate including urothelial carcinomas.12

Most cases

are diagnosed by TUR or less often by needle biopsy.13

TURP is preferred due to more false negative reports

with needle biopsy as seen in our case as well.

However, in all suspected cases of primary urothelial

prostate cancer the possibility of secondary

involvement from an apparent or occult bladder

primary must be excluded. This may require random

biopsies of urinary bladder mucosa.14

Histologically the diagnostic criteria for primary

prostatic urothelial carcinoma are identical to those for

urothelial cancer of the bladder; most cancers aremoderately or poorly differentiated and usually

associated with prominent chronic inflammation.



214


Squamous metaplasia is rare.3

They may be seen to

spread by invasion of prostatic stroma initially. Local

spread beyond prostate gland as well as metastasis

may occur.10

Distinguishing urothelial carcinoma from

prostatic adeno carcinoma is clinically important

because of the oestrogen unresponsiveness of the

former.3

Prostatic adenocarcinoma may respond to

hormonal therapy and cystoprostatectomy may not be

needed. Diagnosis also determines the stage for

prognostication.15

Urothelial Carcinoma is usually

distinguished from poorly-differentiated Prostatic

AdenoCarcinoma by its histopathological

characteristics (Fig 1) including the presence of solid

nests of cells associated with dense or abundant

cytoplasm and striking nuclear pleomorphism, with the

absence or rarity of glandular lumina. The serum free

PSA level is a main marker for prostate

adenocarcinoma screening15

.In difficult cases IHC

may be mandatory. The sensitivity and specificity of

PSA are high in prostate cancer, at 100% sensitivity.

In poorly-differentiated prostate cancer and PAC, the

expression levels of PSA may reach 85 – 95%. PSA is

the oldest and most commonly used

immunohistochemical marker to identify cancers of

prostatic origin.16

CK7 and CK20 are also useful

markers to distinguish PAC from UC. Bassily et al17

studied the expression of CK7 and CK20 in PAC and

UC, and estimated their usefulness for distinguishing

between the two tumors. In the prostatic and metastatic

tumors, neither was positive for the markers. However,

61% of the UC cases were positive for CK7 and

CK20.

CONCLUSION

Primary urothelial carcinoma is a rare type of prostatic

carcinoma which as a rule bears an unfavourable

prognosis. As a primary tumor it makes only 1-4 % of

tumors of the prostate. It originates in the poorly

differentiated reservoir cells of the prostatic

periurethral ductus which explains why diagnosis is

most often obtained in advanced stages thus limiting

its management to radical surgery. Its distinction from

prostatic adenocarcinoma is pertinent for both

treatment and prognostication. Thus Transitional Cell

Carcinoma should be considered as a differential

diagnosis in cases with obstructive symptoms and

normal PSA.

REFERENCES

1. Lerner SP, Shen S. Pathologic assessment and

clinical significance of prostatic involvement by

transitional cell carcinoma and prostate cancer.

Urol Oncol. 2008; 26(5):481-85

2. Shen SS, Lerner SP, Muezzinoglu B, Truong LD,

Amiel G, Wheeler TM. Prostatic involvement by

transitional cell carcinoma in patients with bladder

cancer and its prognostic significance. Hum Pathol

Jun 2006; 37(6):726-34

3. Bostwick DG, Eble JN (eds): Urologic surgical

pathology. St Louis Mosby, 2000 Pgno

4. Greene LF, O’Dea MF, Dockerty MB. Primary

transitional cell carcinoma of prostate. J Urol

1976; 116:235-37

5. Karpas CM, Moumgis B. Primary transitional cellcarcinoma of the prostate: possible pathogenesis

and relationship to reserve cell hyperplasia of

prostatic periurethral ducts. J Urol 1969;101:201-

05

6. Stephen W. Hardeman and Mark S Soloway.

Transitional cell carcinoma of prostate :

Diagnosis, staging and management. World J

Urol. 1988;6:170-74

7. Varghese SL, Grossfeld GD. The prostatic gland :

malignancies other than adenocarcinomas. RadiolClin North America 2000; 38 : 179-202

8. Cho JY. Prostate In: Kim S H editor. Radiology

Illustrated: Uroradiology. Philadelphia, P

A:Saunders, 2003:571-606

9. Pickup M, VanTH, Der Kwast. My approach to

intraductal lesions of the prostate gland. J clin

Pathol 2007;60(8):856-65

10. David J Grignon. Unusual subtypes of prostate

cancer. Modern Pathology. 2004;17:316-27

11. Wadhwa P, Mandal AK, Singh SK, Goswami AK,

Sharma SC, Joshi K et al., Primary transitional cell

carcinoma of the prostate presenting as a rectal

ulcer. Urol Int. 2004; 72(2):176-77

12. Chang JM, Lee HJ, Lee SE, Byun SS, Choe GY,

Kim Sh etal., Unusual tumours involving the

prostate : radiological – pathological findings.

British journal Of Radiology.2008;81: 907-15

13. Oliai BR, Kahane H, Epstein JI. A

clinicopathologic analysis of urothelial carcinomas

diagnosed on prostate needle biopsies. Am J surg

pathol 2001;25:794-801



215


14. Young RH, Sringley JR, Amin MB. Variants of

prostatic adenocarcinoma, other primary

carcinomas of prostate and secondary carcinoma.

In: Tumours of the prostate gland, seminal

vesicles, male urethra and penis. Armed forces

institute of pathology: Washington D C, 2000,217-

55

15. Xiaoqing Yang, Chen Xu, Jianing Guo, Chunrui

Yang, Yuming Yang, and Ruifa Han.

A novel

subtype of primary prostatic adenocarcinoma : A

case report. Oncol Lett. 2013; 6(5): 1303 – 06

16. Epstein JI., PSA, PAP as immunohistochemical

markers in prostate cancer. Urol Clin North Am.

1993;20:757 – 70

17. Bassily NH, Vallorosi CJ, Akdas G, Montie JE,

Rubin MA. Coordinate expression of cytokeratins

7 and 20 in prostate adenocarcinoma and bladder

urothelial carcinoma. Am J Clin Pathol.

2000;113:383 – 88



Tanvi et al.,

disorder. The boy had previously

one general practitioner for stunte

misdiagnosed as malnutrition.

We did a complete ophthalmologi

examination of the child alo

investigations which revealed t

mucopolysaccharidosis type VI (

On ophthalmological examination w

to be 6/36 and 6/60 in the right

respectively. Best corrected vision

eyes with a refractive error of +

+1.00/-1.50 X 105o

in right (RE)

respectively. On external examinati

biomicroscopy, patient had bilateral

haze (Fig 2) with reduced central

corneas. Corneal topography with

(Wavelight AG, Germany) showe

flattening (Fig. 3) with a kerat

follows: RE -K1: 39.6D K2: 40.2

K2: 40.4D. Intraocular pressur

applanation tonometer was 16 and

right and left eyes respectively.

thickness noted was 555µm and 52

On electrophysiological testing, the

(ERG) showed a bilateral reduc

photoreceptors especially cones.

tomography (OCT) of the retinal ne

macula was within normal level.

On systemic evaluation the child

signs of MPS, namely stunted

deformity with skeletal dy

demonstrated on X-ray (Fig

involvement with non-rheumatic

cardiac valves which was co

echography. Urine was

mucopolysaccharidosis and a confi

was done by assessing the arylsullevels in the blood

3. Spectrophoto

para nitro catchecol sulphate and

using 4-methyl umbelliferone show

aryl sulphatase B 12.6 nmol/hr/mg (

Int J Med Res Health Sci. 2

visited more than

growth but was

ical and systemic

ng with blood

he diagnosis of

aroteaux-Lamy).3

e found the vision

and the left eye

was 6/9 in both

.75/-1.00 X 55o,

and left (LE) eye

on with slit lamp

l diffuse epithelial

convexity of the

Allegro Oculyzer

d central corneal

metry values as

, LE -K1: 39.3D

(IOP) with an

18mm Hg in the

Central corneal

0µm respectively.

electroretinogram

ed sensitivity of

ptical coherence

rve fibre layer and

showed the most

growth, skeletal

tosis multiplex

4), and cardiac

affection of the

nfirmed by 2D

positive for

rmatory diagnosis

hatase B enzyme etric assay using

flurimetric assay

ed a low level of

ormal-115-226).

Fig 1: Stunted growt

(Photograph taken aftefather)

Fig 2: Subepithelial

examination (cloudy c

Fig 3: Corneal to

lattening

Fig 4: X-ray showin

with short, broad met

217

14;3(1):216-219

with coarse facial features

consent from of the patient’s

haze seen under slit lamp

rnea)

ography showing central

skeletal dystosis multiplex

carpals and phalanges

SUBEPITHELIAL DEPOSITS

SEEN AS CLOUDING



218

Tanvi et al., Int J Med Res Health Sci. 2014;3(1):216-219

DISCUSSION

Maroteaux- Lamy syndrome (mucopolysaccharidosis

type VI) is a disorder of lysosomal storage. It is

characterised by a defect in the production of the

enzyme arylsulphatase B. This causes abnormal

deposition of the GAG, dermatan sulphate. Themucopolysaccharidoses are caused by a specific

deficiency of lysosomal enzymes which lead to the

deposition of glycosaminoglycans in various organs in

the body. This may give rise to a wide spectrum of

clinical phenotypes.

The deposition of the GAG is seen in many organs and

tissues in the body. Patients with the severe form of

MPS I, MPS II and MPS VI present early to the

clinician, as their respiratory, cardiac and skeletal

deformities make the diagnosis straight forward. Incase of mild forms of MPS I, MPS III, MPS IV,

careful examination may reveal the corneal clouding

and thereafter a paediatric reference is often made. The

deposition of GAG within the layers of the cornea

gives it a cloudy appearance.2

Detailed

ophthalmological examination often becomes difficult

owing to the corneal opacification, thickening and due

to the physical and mental capabilities of most

patients.

MPS VI may present as a wide spectrum of clinicalfeatures, but all the affected children are intellectually

normal. This was true in our case which prompted the

child to complain about his poor vision. Individuals

with Maroteaux- Lamy disease have short stature,

coarse facial features, restrictive joint problems and

hepatosplenomegaly. Some other features include

middle ear disease, sensorineural deafness, upper

airway problems and cardiomyopathy.

Ocular findings in MPS VI are progressive increased

corneal opacification and corneal thickening. Patients

may however present with clear corneas. Raised IOP

and both acute and chronic angle closure glaucoma

have been reported in MPS VI.4

Optic nerve

involvement in the form of swelling and optic atrophy

has also been seen.5, 6

However among the various

MPS syndromes, Maroteaux- Lamy disease has a less

severe phenotype with mild skeletal deformities and a

longer lifespan. Since the ocular findings are

progressive in nature, the role of the ophthalmologist

becomes paramount. The increased life span of these

children due to the advent of the bone marrow

transplant and the enzyme replacement therapy has

widened the scope for their ocular treatment.7

Our case was unique due to isolated ophthalmological

symptoms. On examination, we found the other signs

suggestive of MPS VI and then further reference was

made.8

The child had a normal intellect with coarse

facial features and skeletal deformities. Cardiac

involvement was seen however the respiratory system

is unaffected at this time. Ocular involvement with

corneal opacification with corneal flattening was seen.

On investigation delayed cones response was seen on

ERG testing suggesting a retinopathy.9

The child

needs to be tested on a regular basis for any

development of glaucoma4, worsening of the corneal

clarity or other complications which may reduce his

quality of life and require appropriate treatment.

CONCLUSION

Mucopolysaccharidoses are a complex group of

diseases which are rare and difficult to diagnose as

well as treat. The patient may present to any specialty

of medicine due to its varied presentation. It becomes

imperative on the clinicians part that a careful and

meticulous examination is done which can help

diagnose this disease. Ophthalmological involvement,

although rare as an initial finding, should definitely be

kept in mind when facing a case of

mucopolysaccharidosis.

REFERENCES

1. Muenzer J. The mucopolysaccharidoses: a

heterogeneous group of disorders with variable

pediatric presentations. J Pediatr 2004;144(5

Suppl): 27-34

2. Ashworth JL, Biswas S, Wraith E, Lloyd IC. The

ocular features of the mucopolysaccharidoses.

Eye.2006;20 :553 – 63

3. Lehman TJA, Miller N, Norquist B, Underhill L,

Keutzer J. Diagnosis of the

mucopolysaccharidoses. Rheumatology 2011;50

(Suppl 5):v41-v48

4. Cantor LB, Disseler JA, Wilson FM 2nd. .

Glaucoma in the Maroteaux-Lamy syndrome. Am

J Ophthalmol 1989;108:426-30

5. Ashworth JL, Biswas S, Wraith E, Lloyd IC.

Mucopolysaccharidoses and the eye. Surv

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6. Summers CG, Ashworth JL. Ocular manifestations

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&

Health Sciences

www.ijmrhs.com Volume 3 Issue 1 (Jan-Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886Received: 9



thDec 2013

Case report

SYNCHRONOUS OCCULT METASTASISING DUODENAL CARCINOID AND OVARIAN MUCINOUS

CYSTADENOCARCINOMA – MULTIPLE PRIMARY MALIGNANCIES IN THE SAME PATIENT

*Devadass Clement W1, Sridhar Honnappa

1, Aarathi R Rau

1, Sharat Chandra

2

1Department of Pathology, M.S. Ramaiah Medical College, Bangalore, India

2Department of Surgical Oncology, M.S. Ramaiah Medical College, Bangalore, India


ABSTRACT

Gastrointestinal carcinoid tumors are uncommon neuroendocrine tumours that may be associated with synchronous

or metachronous primary tumours of other histological type, most frequently colorectal adenocarcinomas. Primary

ovarian mucinous adenocarcinomas have been reported to coincide with few other ovarian tumours and minority of

these tumours may occur in association with Lynch syndrome. However association of duodenal carcinoid with

ovarian mucinous adenocarcinoma is distinctly unusual and, to our knowledge, has not been previously described.

We report a case of occult metastasising duodenal atypical carcinoid that was incidentally detected during surgical

intervention performed for left ovarian mucinous cystadenocarcinoma in a middle aged female. The carcinoid

tumour was Stage IIIB with regional nodal metastasis and the ovarian tumour was Stage IA with low grade

histology.

Key words: Duodenal carcinoid, multiple primary malignancies, synchronous tumours.

INTRODUCTION

Synchronous and metachronous “Multiple primary

malignancies” (MPM) are relatively rare with an

overall occurrence rate between 0.73% to 11.7%.1-3

About 20-29% of small intestinal carcinoid tumours

(CT’s) are associated with synchronous or

metachronous primary non-carcinoid tumours, with

colorectal adenocarcinomas being the commonest.4, 5

Primary ovarian mucinous carcinoma have been

reported in conjunction with other ovarian tumors like

teratoma, Brenner tumour, and Sertoli-Leydig cell

tumour and some occur in the setting of Lynch

syndrome.6

However the simultaneous occurrence of

duodenal CT, which is rare, and ovarian mucinous

cystadenocarcinoma, which according to recent studies

constitutes only 3% all ovarian cancers, in the samepatient is unusual. We present a case of metastasising

duodenal CT that was incidentally detected during

treatment of ovarian mucinous cystadenocarcinoma in

middle aged female.

CASE REPORT

A 40 year old female presented with pain and mass per

abdomen of one year duration. She also complained of

progressively increasing intermittent episodes of

respiratory distress, diarrhoea, palpitations and weight

loss. She denied history of prolonged therapy with H2

blockers and family history of malignancies.

Abdominal examination revealed firm lobulated

central pelvic mass. Abdomino-pelvic computed

tomography revealed a large complex cystic ovarian

mass [Figure 1]. A complete digestive tract endoscopy,

chest X-ray and gastric and colonic biopsies were

normal. Laparotomy showed a left ovarian tumour, the

frozen sections of which revealed mucinous

DOI: 10.5958/j.2319-5886.3.1.048



221


adenocarcinoma. In addition an area of intramural

thickening was present in D1 duodenal segment with

associated serosal puckering, omental adhesions and

enlarged adherent sub-pyloric nodes suggestive of

metastasis/implants. The paraaortic lymphnodes were

also enlarged. A clinical FIGO Stage IIIC was

assigned and total abdominal hysterectomy, bilateral

salpingoophorectomy and pelvic lymphadenectomy,

omentectomy, appendicectomy and sampling of

duodenal serosal nodularity, sub-pyloric and paraaortic

nodes was performed.

Fig 1: Abdomino-pelvic computed tomography showing

a large complex cystic ovarian mass.

Pathological findings: Gross examination revealed a

tensely cystic, bosselated left ovarian mass, measuring

23x18x10 cm with intact capsule and multilocular

mucoid cut surface with mural ragged solid and

nodulocystic areas exhibiting foci of necrosis and

haemorrhage [Figure 2]. Microscopy revealed a well

differentiated mucinous cystadenocarcinoma with

expansile pattern of invasion, grade 1 (Universal

grading system) [Figure 3].

Fig 2: Multiloculated left ovarian mass with mural

ragged solid and nodulocystic areas (O), enlarged

subpyloric nodes (SP) with greater omental adhesions

(GO) and unremarkable appendix (A).

Fig 3: A- Ovarian mucinous adenocarcinoma with

architecturally complex papillary cystic areas, B-

Expansile pattern of invasion; C- Glandular formations

lined by disorderly epithelium exhibiting moderate

nuclear atypia (x400 H&E).

The pathological examination of the uterus, right

ovary, bilateral fallopian tubes, bilateral pelvic and

paraortic lymphnodes, appendix and peritoneal

washings revealed no significant abnormality.

The microscopy of the duodenal serosal nodularity

revealed a histologically different tumour composed of

organoid formations of relatively monotonous

cuboidal cells exhibiting stippled chromatin and

mitotically active nuclei (4-5/10HPF) consistent with

Neuroendocrine tumour, grade II (Atypical carcinoid)

[Figure 4]. This was further confirmed byimmunohistochemistry which revealed positive

staining of pan-cytokeratin and chromogranin in the

tumour cells with a 40% Ki67 index [Figure 5]. The 3

subpyloric lymphnodes isolated revealed metastasis of

the neuroendocrine tumour (pN1)

Fig 4: A- Subpyloric lymph node (LN) with metastatic

carcinoid tumour (CT); B- Duodenal serosal nodule

showing Atypical carcinoid; C- Atypical carcinoid

showing monotonous cells exhibiting stippledchromatin and mitotically active nuclei (arrows) (x400

H&E).



222


Fig 5: Duodenal tumour showing A- positivity for

Pan Cytokeratin; B- positivity for Chromogranin; C-

Nuclear positivity for Ki-67 [x400].

Further, extensive sampling of the ovarian tumourfailed to reveal any teratomatous/ carcinoid

component.

A final diagnosis of Left ovarian mucinous

cystadenocarcinoma, pT1aG1 pN0 pM0, TNM/FIGO

Stage IA with synchronous duodenal Neuroendocrine

tumour, grade II, TNM Stage IIIB was made.

DISCUSSION

CT’s are relatively uncommon slow growing

neuroendocrine tumours, derived fromenterochromaffin cells, that are capable of secreting

vasoactive substances and 73-85% of these tumours

occur in the gastrointestinal tract (GIT).7

Duodenal

carcinoids are rare , accounting for < 2% of all GIT

carcinoids, with an annual incidence of 0.07/100,000.5

About 91% have metastasis at time of detection

presumably because they are difficult to diagnose and

majority are asymptomatic and behave in an indolent

form.5

Clinical features are varied and depend on the

anatomic location, tumour size and metastasis andmajority are incidentally detected.

8They may present

as carcinoid syndrome with cutaneous flushing,

diarrhoea palpitations, abdominal pain and

bronchospasm. G-cell tumours followed by D-cell

tumours account for majority of duodenal CT’s, the

former may occur with multiple endocrine neoplasia

type 1 and the latter may occur with neurofibromatosis

type 1. Unlike their midgut and hindgut counterparts,

proximal duodenal CT are less well characterized and

exhibit variable biological course necessitatingindividualised treatment strategy for each patient.

9

In the present case the patient had palpitations,

diarrhoea and respiratory distress, all of which were

attributed to the huge ovarian tumour. The duodenal

CT was detected incidentally during the surgical

treatment of the associated ovarian malignancy.

CT’s may be associated with other synchronous

primary malignant tumours. Berner M et al reported

that out of 270 GIT CT’s analysed 7.8% had

synchronous primary malignancy, two thirds of which

were colorectal adenocarcinomas and 80% of which

were detected during the treatment of the other

associated malignancy.10

Mullen et al reviewed 24

duodenal CT’s and found that 38% had synchronous

or metachronous non-carcinoid malignancies, 77.8%

of which were adenocarcinomas.9

Associated ovarian

malignancies were not detected in these studies. We

describe the first case, to our knowledge, of a duodenal

CT and a simultaneous ovarian mucinous

cystadenocarcinoma.

The mechanisms involved in the occurrence of MPM

have not been fully explained. Genetic susceptibility,

failure of immunological surveillance and exposure to

carcinogens has been implicated.1, 2, 4

Some authors

have hypothesised that CT’s produce growth factors

which may determine neoplastic transformation or

influence tumour growth at other sites.4

It has been reported that prognosis of patients with

synchronous CT’s and non-carcinoid tumours is

determined by the stage of the non-carcinoid tumour

rather than the CT.10

This probably is applicable for

those cases wherein the CT component is non-

metastasising.4, 5

In the present case the ovarian

malignancy was well differentiated and FIGO stage I,

with an excellent prognosis and 5 year survival rate of

95%.6

The CT had regional node metastasis with Stage

III B, and logically will determine the survival of this

patient. The five year survival rate for CT’s with onlylocal spread is 88% in contrast to 25% for those with

metastasis.5

Combined curative resection is the treatment of choice

for synchronous MPM.1, 2

However, in this case a

second malignancy was not suspected pre-operatively.

Pancreaticoduodenectomy is the subsequent treatment

in the management, which will be done after she

recovers from the first surgery.

CONCLUSION

The possibility of MPM should always be considered

in the pre-operative evaluation. The association of



223


CT’s with colorectal adenocarcinomas and ovarian

mucinous adenocarcinomas with other primary ovarian

tumours and Lynch syndrome have been described.

As the management may differ in the finding of a

second primary, we should not limit ourselves to these

known associations. The clinicians should be aware of

this rare entity so that pre planned stage specific

treatment may be delivered resulting in better

outcome.

REFERENCES

1. Irimie A, Achimas-Cadariu P, Burz C, Puscas E.

Multiple Primary Malignancies- Epidemiological

Analysis at a Single Tertiary Institution. J

Gastrointestin Liver Dis 2010;19:69-73

2. Anania G, Santini M, Marzetti A, Scagliarini L,

Vedana L, Resta G, et al. Synchronous primary

malignant tumours of the breast, caecum and

sigma. Case report. G Chir 2012;33:409-10

3. Demandante CG, Troyer DA, Miles TP. Multiple

primary malignant neoplasms; case report and a

comprehensive review of the literature. Am J Clin

Oncol 2003;26:79-83

4. Gurzu S, Bara T Jr, Bara T, Jung I. Synchronous

intestinal tumours: aggressive jejunal carcinoid

and sigmoid malignant polyp. Rom J Morphol

Embryol 2012;53:193-96

5. Gao L, Lipka S, Hurtado-Cordovi J, Avezbakiyev

B, Zuretti A, Rizvon K, et al. Synchronous

Duodenal Carcinoid and Adenocarcinoma of the

Colon. World J Oncol 2012;3:239-42

6. Soslow RA. Mucinous Ovarian Carcinoma:

Slippery business. Cancer 2011; 117:451-53

7. Babovic-Vuksanovic D, Constantinou CL, Rubin

J, Rowland CM, Schaid DJ, Karnes PS. Familial

Occurrence of Carcinoid Tumors and Asssociation

with Other Malignant Neoplasms. CancerEpidemiol Biomarkers Prev 1999;8:715-19

8. Erbil Y, Barbaros U, Kapran Y, Yanik BT,

Bozbora A, Ozarmaoan S. Synchronous Carcinoid

Tumour of the Small Intestine and Appendix in the

Same Patient. West Indian Med J 2007;56:187-89

9. Mullen JT, Wang H, Yao JC, Lee JH, Perrier ND,

Pisters PWT, et al. Carcinoid tumours of the

duodenum. Surgery 2005;138:971-78

10. Berner M. Digestive carcinoids and synchronous

malignant tumors. Helv Chir Acta. 1993;59:757-66



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Magdalene Int J Med Res Health Sci. 2014;3(1):224-227


&

Health Sciences




stDec 2013

Case report

SYNCHRONOUS POORLY DIFFERENTIATED GASTRIC ADENOCARCINOMA WITH GASTROINTESTINAL

STROMAL TUMOR: A CASE REPORT

Magdalene K. F.

Professor in Pathology, Sree Narayana Institute of Medical Sciences, Chalaka, Kerala, India


ABSRACT

Gastrointestinal stromal tumor (GIST) is categorized as a mesenchymal tumor. In the abdomen more than half occur

in the stomach. Adenocarcinoma is the most common epithelial malignancy of stomach comprising over 90% of all

gastric cancers. The simultaneous occurrence of both these tumors together is rare. This is an interesting case report

of a 54 year old lady with synchronous occurrence of GIST and poorly differentiated adenocarcinoma of intestinal

type. A brief review of literature is done regarding the reported cases and proposed hypothesis.

Keywords: Poorly differentiated carcinoma, GIST, Synchronous

INTRODUCTION

The most common gastric tumors are epithelial tumors. Adenocarcinomas constitute the most common type of

epithelial gastric tumors. Gastrointestinal stromal tumors (GIST) are non epithelial tumor which can occur in the

stomach. In the gastrointestinal tract 1% of all malignancies1, 2

and 5.7% of sarcomas3

are accounted by GIST. GISTs

and adenocarcinomas have two separate histogenesis. It is extremely rare for the co-existence of GIST and

adenocarcinoma. GISTs have been reported in the literature to coexist with tumors of different histogenesis such as

adenocarcinomas, carcinoids, MALT lymphomas and Burkitt’s lymphomas4,5,6

, as well as with different mesenchymal

tumors.7-13

Here is a case report of a 54 year old lady with poorly differentiated adenocarcinoma and synchronous

gastrointestinal stromal tumor which was incidentally detected.

CASE REPORT

A 54 year old lady was admitted with vomiting,

following food intake, of 3weeks duration. There was

associated abdominal discomfort and belching. She

gave a history of loss of appetite and weight loss

which was of 3 months duration. On general

examination the patient was emaciated and pale. The

systemic examination was unremarkable. Blood

routine was normal except for the low hemoglobin

level (5gm%). Urine routine was normal.

Ultrasonograghy showed diffuse thickening of the

gastric pyloric antral wall.

Oesophagogastroduodenoscopy showed multiple

ulcerations with hypertrophied margins in the lesser

curvature and antrum and the impression was gastric

outlet obstruction. Endoscopic biopsy done showed

microscopic features of a poorly differentiated

carcinoma. A lower radical gastrectomy was done and

the specimen was received in the histopathology lab.

An ulcerating infiltrating neoplasm measuring

30x25mm was detected in the lesser curvature adjacent

to which another nodular firm grey white

mesenchymal neoplasm measuring 25x20mm was also

DOI: 10.5958/j.2319-5886.3.1.049



225


noted [Figure1]. The microscopy of the ulcerating

tumor showed features of a poorly differentiated

intestinal type adenocarcinoma [Figure 2]. The tumor

was infiltrating the full thickness of the gastric wall

and extended to the serosal fat of the lesser curvature.

Four out of nine lymph nodes showed evidence of

metastasis.

Fig 1: Ulcerating infiltrating gastric carcinoma in the

lesser curvature of stomach (blue arrow) with adjacent

nodular firm grey white gastrointestinal stromal tumor

(red arrow)

Fig 2: Microscopy of poorly differentiated intestinal type

adenocarcinoma in the gastric wall (H&E X 10x)

Fig 3a: Microscopy of circumscribed submucosal

spindle cell gastrointestinal stromal tumor (H&E X 10x)

Fig 3b: Microscopy of gastrointestinal stromal tumor

showing the sheet- like and fascicular arrangement of

spindle shaped cells (H&E X 40x)

The adjacent nodular firm white neoplasm showed

microscopic feature of a submucosal spindle cellmesenchymal neoplasm which was circumscribed. A

fascicular and sheet like arrangement of plump spindle

shaped cells were noted [Figure 3a,b]. Mitotic activity

was less than 5/50 HPF. No areas of necrosis were

found. Based on the mitotic count of less than 5/50

HPF and size of the tumor less than 5 cm, the

histological diagnosis was GIST-low risk type.

Immunohistochemical markers were advised for

confirmation of GIST.

Immunohistochemical markers were done for the

identification of origin of the tumors. The

mesenchymal neoplasm was CD 117 (c-kit protein)

moderately to strongly positive demonstrating a

combined membranous and diffuse cytoplasmic

staining pattern. Additionally, CD 34 protein was

observed to be membranous stain positive, whereas S-

100, desmin and SMA demonstrated negative or very

weak reactivity. The poorly differentiated intestinal

type adenocarcinoma was cytokeratin positive. A final

report of synchronous poorly differentiated intestinal

type adenocarcinoma and GIST (low risk type) was

arrived. Since intestinal type adenocarcinomas could

be due to Helicobacter pylori they were searched in the

gastric mucosa but were not detected microscopically.

The resected gastric margins and omentum were free

of neoplasm. The postoperative course was uneventful.

Following surgery the patient received adjuvant

chemotherapy, but unfortunately died of progressive

disease 16 months later.



226


DISCUSSION

GIST was named in the earlier literature as

leiomyomas, schwannomas, leiomyosarcomas and

leiomyoblastomas. Electron microscopy and

immunohistochemical stains recognized it as a distinct

entity.14 Mazur and Clark 15 introduced the term GIST

in 1983.

The synchronous occurrence of GIST and gastric

carcinomas are rare. A few reports of simultaneous

presence of poorly differentiated adenocarcinoma and

GIST have been reported.7-13

Most of the

adenocarcinomas were detected after endoscopic

biopsies. GIST was diagnosed as an incidental finding.

No high risk types of GIST have been reported in

association with gastric carcinoma .The tumors were

mostly less than 5cm.Recently Karahan N et al.16

havereported in a neurofibromatosis type-1 patient with

development of simultaneous multiple GIST and

signet ring cell carcinoma. The synchronous

occurrence of these two tumors has excited many and

it raises the question as to why they occur together.

The reason for the simultaneous origin of GIST and

adenocarcinoma may be due to coincidence. Gene

mutations were another reason that was proposed.

Recently Yan Y et al17

conducted molecular analysis

and clinicopathological profile of KIT/PDGFRA inboth these tumors. No relationship was obvious

according to this study.

H. pylorus is another cause that may be considered. H.

pylori can cause simultaneous development of gastric

carcinoma and lymphoma7.

Such a relationship with

GIST is not proved yet. In the present case study no H.

pylori could be detected.

Another hypothesis is the role of carcinogenic agent. It

may act on neighboring tissues and may lead to the

development of tumors in the same organ with

different histogenesis.18, 19

CONCLUSIONS

The synchronous occurrence of a GIST with gastric

carcinoma is rare, and little is known about this

association. Coexisting GISTs are in most cases small,

asymptomatic tumors and are detected incidentally

during surgery for gastric carcinomas. Hence

specimens should be handled cautiously to detect

associated lesions. Since most of the cases were poorly

differentiated adenocarcinomas further studies are

needed to know whether the associated GIST

influenced the differentiation of the tumor. Molecular

studies are also further needed to explain the

simultaneous development of tumors of different

histogenesis.

Disclosure of conflicts of interest: The author

declares that there is no financial relationship with anyorganization in this case study and that there is no

conflict of interest.

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stromal tumors: clinical profile, pathogenesis,

treatment strategies and prognosis. J

GastroenterolHepatol 2005;20:818-24.

2. Eisenberg BL, Judson I. Surgery and imatinib in

the management of GIST: emerging approaches to

adjuvant and neoadjuvant therapy. Ann SurgOncol

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3. DeΜatteo RP, Lewis JJ, Leung D. Two hundred

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patterns and prognostic factors for survival. Ann

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4. Sailors JL, French SW. The unique simultaneous

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cases. Turk J Gastroenterol 2004;15:187-91.

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case report. J Pak Med Assoc 2006;56:184-86.

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Fano R: Synchronous occurrence of epithelial and

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Arch Pathol Lab Med 2000;124:682-86.

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EvangelosTsiambas, Andreas Karameris,

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Tumor in the Stomach: A Case Report. J

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