abdominal obesity and coronary disease in thai men

A SURVEY OF AWARENESS, OPINION ANDREPORTED USE OF CLINICAL PRACTICEGUIDELINES (CPG) OF THE ROYAL COLLEGEOF ANESTHESIOLOGISTS OF THAILAND (NO. 158)

S. Pitimana-aree, K. Uerpairojkit, Y. Punjasawadwong, T.Virankabutra

Department of Anesthesiology, Siriraj Hospital, MahidolUniversity, Bangkok, Thailand; Department of Anesthesiology,Chulalongkorn University, Bangkok, Thailand; Department ofAnesthesiology, Chiang Mai University, Chiang Mai, Thailand;Department of Anesthesiology, Ramathibodi Hospital, MahidolUniversity, Bangkok, Thailand.

Key words : Anesthesia, Awareness, Guidelines, Opinions, Practice,Questionnaire

Background : Up to the present (2006), The Royal Collegeof Anesthesiologists of Thailand (RCAT) has proposed and revisedsix practice guidelines. For guidelines to achieve their objectives,anyone who gets involved needs to be aware of the guidelines, beable to accept, and adhere to them. Although the authors did introducetheir guidelines by several passive means, the authors have not yetascertained what the result were.

Objective : The primary objective of the present studywas to assess awareness, opinion, limitation, and reported use ofguidelines. The secondary objective was to limitation, and reporteduse of guidelines. The secondary objective was to identify factorsassociated with variation, agreement, and reported use of guidelines.

Material and Method : A cross sectional, self-reportsurvey study was conducted. An anonymouse questionnaire includingprepaid-addressed reply envelopes was mailed to 600anesthesiologists and 1,300 nurse anesthetists, nationwide, based onthe colleges list. The questions covered respondents generalcharacteristics : awareness, agreement, and reported use of the existingguidelines ; opinion on implementation media, which guidelines themembers need, their local guidelines, and the impact of guidelineson their practice. All data were extracted and reported usingdescriptive statistics. Multiple logistic regression was done to identifyfactors associated with an agreement with and a reported use of theguidelines.

Results : The overall response rate was 33.4% and nurseanesthetists had a higher response than anesthesiologists. Forty-sixpercent of the respondents were aware of the existing guidelines.This result corresponded to percentage of those who had read theguidelines (41%). Among the six existing guidelines, the least twoguidelines reported use of agreement with, were those for laboranalgesia and conscious sedation (23-285; 24-28%). The guidelinesfor spinal anesthesia received the most response (46%). Forrespondents who had read the guidelines, most of them 80% to 94%)rated the level of agreement and reported use as good to excellent.The respondents also rated the announcement of the guidelines duringthe annual meeting of the Royal College.

(Journal of the Medical Association of Thailand, 2007/90/9; 1853-1859)

BISPECTRAL INDEX IN ASSESSMENT OF 3%AND 4.5% DESFLURANE IN 50% N 2O FORCAESAREAN SECTION (NO. 159)

W. Ittichaikulthol, S. Sriswasdi, N. Prachanpanich, J.Watcharotayangul

Department of Anesthesiology, Faculty of Medicine RamathibodiHosptial, Mahidol University, Bangkok 10400, Thailand.

Key words : BIS, Bispectal index, Caesarean section, Desflurane

Background : To prevent awareness and uterine atonyamong parturients during general anesthesia of caesarean section,volatile anesthetic agents have been limited to 0.5 MAC in 50% N2O.This technique appeared to be inadequate to produce BIS values lessthan 60 in isoflurane and sevoflurane.

Objective : To assess BIS value during general anesthesiawith 3% and 4.5% desflurane in 50% N2O before delivery.

Material and Method : The parturients were blinded andrandomized in opaque envelopes to one of the two study groups.Seventy-two elective caesarean section ASA I-II parturients wereinduced and intubated with thiopental 4 mg/kg, succinylcholine 1.5mg/kg and were received either 3% or 4.5% desflurane in 50% N2Oto maintain general anesthesia. Both groups received rocuronium0.6 mg/kg for muscle relaxation. Morphine 0.1 mg/kg and midazolam0.06 mg/kg were administered after delivery.

Results : There were no differences in demographic datain both groups. The incidences of patients with a satisfactory BISscore (

Key words : Anesthesia, Awareness, Complication, Recall, Riskfactors

Background : The authors determined predictors of intra-operative recall of awareness in the Thai Anesthesia Incidents Study(THAI Study).

Objective : To study a multi-centered registry ofanesthesia in 20 hospital across Thailand.

Material and Method : Structured data collection formsof patients who underwent general anesthesia and experienced intra-operative recall of awareness between March 1, 2003 and February28, 2004, were reviewed by three independent anesthesiologists. Onecase of awareness was matched to four controls by age, gender, andlevel of hospitals. Univariate analysis (p < 0.1) and logistic regression(p < 0.05) identified characteristics associated with intra-operativerecall of awareness.

Results : Eighty-one cases were matched with 324 controlsin the nested case control study. From univariate analysis, risk factorswere cardiac surgery, cesarean delivery, upper abdominal surgery,IV anesthetics, depolarizing muscle relaxant, non-depolarizing musclerelaxant, and nitrous oxide (p < 0.1). The predictors frommultivariable logistic regression were cesarean delivery p < 0.001,OR 6.48 (95% CI 2.03, 20.71), and cardiac surgery p < 0.001, OR10.37 (95% CI 3.37, 31.89). Decreased risk was associated withintra-operative use of nitrous oxide p = 0.02, OR 0.42 (95% CI 0.20,0.88).

Conclusion : In the THAI Study, predictors of intra-operative recall of awareness were cesarean delivery and cardiacsurgery. Use of nitrous oxide attenuates the risk of awareness.


RISK FACTORS OF INTRAOPERATIVE OXYGENDESATURATION : A CASE-CONTROL STUDY OF152,314 ANESTHETICS (NO. 161)

S. Charuluxananan, S. Suraseranivongse, Y. Punjasawadwong

Department of Anesthesiology, Faculty of Medicine,Chulalongkorn University, Bangkok, Thailand; Department ofAnesthesiology, Siriraj Hospital, Mahidal University, Bangkok,Thailand; Department of Anesthesiology, Chiang Mai University,Chiang Mai; Department of Anesthesiology, RamathibodiHospital, Mahidol University, Bangkok; Prince of SongklaUniversity, Songkhla; Khon Kaen University, Khon Kaen;Clinical Epidemiology Unit, Faculty of Medicine, ChulalongkornUniversity, Bangkok; Department of Anesthesiology, Faculty ofMedicine, Chulalongkorn University, Rama IV Rd, Pathumwan,Bangkok 10330, Thailand.

Key words : Adverse events, Anesthesia, Case-control, Complication,Desaturation, Risk factors

Background : The present study was part of the ThaiAnesthesia Incidents Study (THAI Study) of anesthetic adverseoutcomes.

Objective : to determine factors related to intraoperativeoxygen desaturation(SpO2 < 85% or < 90% for more than 3 min).

Material and Method : During a 12-month period(February 1, 2003 January 31, 2004), a prospective multicenteredregistry of patients receiving anesthesia was conducted in 20 hospitalsacross Thailand. Anesthesia personnel filled up patient-related,surgical-related, and anesthesia related variables and adverseoutcomes including intraoperative oxygen desaturation. A case-control (1:4) study of patients with and without intraoperative oxygendesaturation in the THAI Study database was done. Univariate andmultivariate analysis were used to identify factors related tointraoperative oxygen desaturation. A p-value < 0.05 was consideredas significant.

Results : Among 152,314 patients without preanestheticdesaturation in the database, 328 cases of intraoperative oxygendesaturation were matched with 1,312 control patients withoutdesaturation. Variables that predict desaturation by multiple logisticregression were age less than 5 years old [OR 9.3 (95% CI 5.4-16.0)],ASA physical status 3,4,5 [OR 3.1 (95% CI 2.2-4.3)], history of upperrespiratory tract infection [OR 10 (95% CI 1.9-51.6)], history ofasthma [OR 2.9 (95% CI 1.0-9.5)], general anesthesia [OR 4.0 (95%CI 2.4-6.7)] duration of anesthesia 31-90 min [OR 1.9 (95% CI 1.2-3.0)], duration of anesthesia 91-150 min (OR 2.2 (95% CI 1.3-3.6)],and duration of anesthesia > 150 min [OR 2.0 (95% CI 1.2-3.4)].

Conclusion : Knowing the risk factors of intraoperativeoxygen desaturation helps improving personnel to improvepreanesthetic conditions and facilitate early detection as well asprompt treatment of intraoperative oxygen desaturation.

(Journal of the Medical Association of Thailand, 2007/90/1, 2359-2365)

THE THAI ANESTHESIA INCIDENTS (THAISTUDY) OF ANESTHETIC RISK FACTORSRELATED TO PERIOPERATIVE DEATH ANDPERIOPERATIVE CARDIOVASCULAR COM-PLICATIONS IN INTRACRANIAL SURGERY

(NO. 162)

P. Akavipat, W. Ittichaikulthol, L. Tuchinda, T. Sothikarnmanee,S. Klanarong

Department of Anesthesiology, Prasat Neurological Institute,Ministry of Public Health, Bangkok, Thailand; Department ofAnesthesiology, Ramathibodi Hospital, Mahidol University,Bangkok, Thailand; Department of Anesthesiology,Chulalongkorn University, Bangkok, Thailand; Department ofAnesthesiology, Khon Kaen University, Khon Kaen, Thailand;Department of Anesthesiology, Buddhachinaraj Hospital,Ministry of Public Health, Phitsanulok, Department ofAnesthesiology, Siriraj Hospital, Mahidol University, Bangkok,Thailand; Department of Anesthesiology, Prasat NeurologicalInstitute, Ministry of Public Health, Bangkok 10400, Thailand.

Key words : Anesthesia, Cardiovascular complication, Certifiedboard anesthesiologist; Intracranial surgery, Perioperative death, Riskfactor

Faculty of Medicine Ramathibodi Hospital70

Objective : To evaluate the correlations betweenanesthetic risk factors and perioperative cardiovascular complicationsas well as perioperative death within 72 hours.

Material and Method : This case controlled took the datafrom the Thai Anesthesia Incidents Study (THAI Study), a prospectivemulti-centered registry of anesthesia in Thailand. The authorsincluded all the patients who received intracranial surgery from 20hospitals throughout Thailand. The present study was divided intotwo groups and focused on anesthetic factors that possibly related toperioperative cardiovascular complications or perioperative death.The statistical analysis were Chi Square test and logistic regressionmodel with the statistical significance if p-value < 0.05 demonstratedin Odds ratio (OR) and 95% confidence interval.

Results : From the 7,430 patients, there were 63 patients(0.85%) with perioperative cardiovascular complication. TheAmerican Society of Anesthesiologists (ASA) physical status 3-5 (OR5.77, 95% cI 2.33-14.27) and the absence of anesthesiologists (OR2.19, 95% CI 1.06-4.54) had statistical correlation with thecardiovascular complication. Eighty-four patients (1.13%) who diedwithin 72 hours post operatively were found. The ASA physical status3-5 (OR 10.14, 95% CI 3.42-30.02), the emergency circumstance(OR 3.55, 95% CI 1.31-9.60), and the absence of endtidalcarbondioxide monitor (OR 2.27, 95% CI 1.26-4.09) had statisticalcorrelation with the perioperative death.

Conclusion : Predictors of perioperative cardiovascularcomplications in intracranial surgical patients were ASA physicalstatus 3-5 and absence of certified board anesthesiologists. Riskfactors of perioperative death were ASA physical status 3-5,emergency condition, and absence or no monitoring of capnometer.


THE THAI ANESTHESIA INCIDENTS STUDY(THAI STUDY) OF AMBULATORY ANESTHESIA :PART I: METHOD, GEOGRAPHIC DISTRIBUTIONAND POPULATION (NO. 163)

S. Srisawasdi, Y. Punjasawadwong, T. Werawatganon, W.Pengpol

Department of Anesthesiology, Ramathibodi Hospital, MahidolUniversity, Bangkok, Thailand; Department of Anesthesiology,Chiang Mai University, Chiang Mai, Thailand; Department ofAnesthesiology, Chulalongkorn University, Bangkok, Thailand;Division of Anesthesia, Rajburi Hospital, Rajburi, Thailand;Department of Anesthesiology, Maharaj NakhonsithammarajHosptial, Nakhonsithammaraj, Thailand; Department ofAnesthesiology, Phramongkutklao College of Medicine, Bangkok,Thailand; Department of Anesthesiology, Chiang Mai University,Chiang Mai 50200, Thailand.

Key words : Ambulatory, Anesthesia, Outpatient

Background : There is a continuing trend to have moreelective surgical operations performed on an outpatient basis.

Objecitve : To determine the proportional distribution ofanesthetic procedures performed in ambulatory elective surgery atdifferent levels of hospitals across Thailand.

Material and Method : A prospective and descriptivestudy was conducted at 20 hospitals comprising seven universities,five regional, four general and four district hospital across Thailand.Consecutive outpatients who were undergoing elective surgicaloperation were included and their relevant data were selected andextracted for summary by using descriptive statistics.

Results : From the database of 118,027 anestheticsperformed for elective surgical operation 7,786 (6.6%) wereoutpatients. According to this, 7,016 (90.1%) were practiced inuniversity hospitals, 656 (8.4%) in regional or tertiary hospitals, 71(.9%) in general or provincial hospitals, and 43 (0.6%) in districthospitals. The frequency of the ambulatory anesthesia was higher inhospitals in the central region, especially in university hospitals inBangkok than in other regions. The majority of cases (86%) receivedtheir initial preanesthetic evaluation in the operating room while 12%were evaluated at the outpatient office. About 28% of the casespresented with pre-anesthetic abnormal conditions. The relativelycommon pre-anesthetic diseases were hypertension, diabetes mellitus,anemia, arrhythmia, and asthma.

Conclusion : From the results of the present study, theauthors have concluded that the rate of expansion of ambulatoryanesthesia in Thailand is relatively slow, and varies according to thetype of hospital and its geographic region. This indicates furtherstudies should be formally conducted to determine factors affectingthe practice of ambulatory surgery in Thailand. A large proportionof patients receive initial pre-anesthetic evaluation in the operatingroom on the day of surgery. This indicates that a system of pre-anesthetic evaluation should be set up for outpatients such as a pre-anesthetic care clinic should be set up for outpatients.


THE THAI ANESTHESIA INCIDENTS STUDY(THAI STUDY) OF MORBIDITY AFTER SPINALANESTHESIA : A MULTI-CENTERED REGISTRYOF 40,271 ANESTHETICS (NO. 164)

S. Charuluxananan, S. Thienthong, M. Rungreungvanich, T.Chanchayanon

Department of Anesthesiology, Chulalongkorn University,Bangkok, Thailand; Department of Anesthesiology, Khon KaenUniversity, Khon Kaen, Thailand; Department of Anesthesiology,Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;Department of Anesthesiology, Prince of Songkla University,Songkhla; Department of Anesthesiology, Siriraj Hospital,Mahidol University, Bangkok, Thailand; Department ofAnesthesiology, Faculty of Medicine, Chulalongkorn University,Rama IV Rd, Pathumwan, Bangkok 10330, Thailand.

Key words : Complication, Desatur, Nerve injury, Spinal anesthesia,Total spinal block

Background : The present study was part of the ThaiAnesthesia Incidents Study (THAI Study) of anesthetic adverseoutcomes.

Objective : Study complications after spinal anesthesia.

Mahidol University Annual Research Abstracts, Vol. 35 71

Material and Method : During the 12 month period(March 1, 2003 February 28, 2004), a prospective multicentereddescriptive study was conducted in 20 hospitals comprised of sevenuniversity, five tertiary, four general and four district hospitals acrossThailand. Anesthesia personnel filled up patient-related, surgical-related, and anesthesia-related variables and adverse outcomes of allconsecutive patients receiving anesthesia on a structured data entryform. The data were collected during pre-anesthetic, intra-operative,and 24 hr post operative period. Adverse event specific forms wereused to record when these incidents occurred. Data were reviewedby three independent reviewers and analyzed to identify contributingfactors by consensus.

Results : This was registry of 40,271 spinal anestheticsfrom 172,697 anesthetics. The incidence of total spinal anesthesia,neurological complications, suspected myocardial ischemia, orinfarction and oxygen desaturation per 10000 spinal anesthetics were3.48 (95% CI 1.66 5.30), 1.49 (95% CI 0.30 2.68), 2.73 (95% CI1.12 4.35) 0.99 (95% CI 0.39 - 2.56), and 6.46 (95% CI 3.98 -8.94) respectively. This was not different to the incidence in othercountries. Risk factors of oxygen desaturation were shorter in height[OR 0.95 (95% CI 0.92 0.97); p < 0.001], higher ASA physicalstatus [OR 3.37 (95% CI 1.98-5.72); p

Results : WHtR was most strongly associated with CHDevents in Thai men. The age-ajusted hazard ratio for those in thehighest, compared with the lowest, third was 2.89 (1.37, 6.11).Although WHtR had the largest area under the receiver operatingcharacteristic curve (AUC) with the optimal cut-off estimated to be0.51 (sensitivity, 55%; specificity, 61%), no statistically significantdifference (p > 0.10) was found between the AUC for WHtR andthat for the other three indices.

Conclusion : WHtR is, marginally, the best of the fourindices considered to predict CHD events in Thai men. Copyright 2007 NAASO.

(Obesity 2007/15/4; 1036-1042)

INTIMATE PARTNER VIOLENCE AMONGWOMEN IN SLUM COMMUNITIES IN BANGKOK,THAILAND (NO. 167)

W. Aekplakorn and R. Kongsakon

Department of Community Medicine, Faculty of MedicineRamathibodi Hospital, Mahidol University, Bangkok 10400,Thailand.

Introduction : This study aims to describe the prevalenceof intimate partner violence and associated factors among marriedwomen in slum communities in Bangkok.

Methods : A cross-sectional survey was carried out. Atotal of 580 married women aged 15 years or older were randomlysampled from seven slum communities in Bangkok. Information onage, education, occupation, income, family size, alcohol use, andexperience of partner violence were interviewed. Logistic regressionwas used to identify risk factors associated with the violence.

Results : The prevalence of intimate partner violence was27.2 percent. Most of the violent episodes were triggered either byfactors related to the couples personal character, such as having abad temper (89.9 percent) and being grumpy (83.5 percent), orcircumstantial factors, such as financial problems (74.7 percent) andsuspicions of adultery (28.5 percent). 12 percent of the abuse weremoderate violence and 34.2 percent were severe violence. The factorsassociated with partner violence included a young age group (youngerthan 35 years) with adjusted odds-ration (OR) of 3.13 (95 percentconfidence interval [CI] 1.33-7.34) compared to those aged 55 yearsor older ; inadequate income for family expenses (OR 1.97, 95 percentCI 1.20-3.22); and regular alcohol use (OR 3.72, 95 percent CI 2.02-6.89).

Conclusion : Intimate partner violence was commonlyfound in slum communities and is strongly related to thesocioeconomic status, personality characteristics and alcoholconsumption of the couples.

(Singapore Medical Journal 2007/48/8; 763-768)

LOGISTIC REGRESSION ANALYSIS TO PREDICTMEDICAL LICENSING EXAMINATION OFTHAILAND (MLET) STEP1 SUCCESS OR FAILURE

(NO. 168)

S. Wanvarie and B. Sathapatayavongs

Department of Community Medicine, Faculty of MedicineRamathibodi Hospital, Mahidol University, Department ofInternal Medicine, Faculty of Medicine Ramathibodi Hospital,Bangkok 10400, Thailand.

Key words : Basic science, National test, Prediction

Introduction : The aim of this paper was to assess factorsthat predict students performance in the Medical LicensingExamination of Thailand (MLET) Step1 examination. The hypothesiswas that demographic factors and academic records would predictthe students performance in the Step1 Licensing Examination.

Materials and Methods : A logistic regression analysisof demographic factors (age, sex and residence) and academic records[high school grade point average (GPA), National University entranceexamination score and GPAs of the pre-clinical years] with the MLETStep1 outcome was accomplished using the data of 117 third-yearRamathibodi medical students.

Results : Twenty-three (19.7%) students failed the MLETStep1 examination. Stepwise logistic regression analysis showed thatthe significant predictors of MLET Step1 success/failure wereresidence background and GPAs of the second and third pre-clinicalyears. For students whose sophomore and third-year GPAs forstudents from urban and rural backgrounds to pass the examinationwere estimated from the equation (2.35 vs 2.65 from 4.00 scale).

Conclusions : Students from rural backgrounds and/orlow-grade point averages in their second and third preclinical yearsof medical school are at risk of failing the MLET Step1 examination.The should be given intensive tutorials during the second and thirdpre-clinical years.

(Annals of the Academy of Medicine Singapore, 2007/36/9; 770-773)

NURSES IN PRIMARY CARE AND THE NURSEPRACTITIONER ROLE IN THAILAND (NO. 169)

S. Hanucharurnkul

Department of Community Medicine, Faculty of Medicine,Ramathibodi Hospital, Bangkok, Thailand. E-mail :[email protected]

Thailand supports a system of universal health carecoverage and promotes a system of primary care. Effective andefficient primary health care can improve health through increasingaccess and thereby reducing inequities. Nurses are key providers ofprimary care services, particularly in remote areas and play animportant role in improving the heath and well-being of the Thaicommunity.

(Contemp Nurse, 2007/26/1; 83-93.)


PREVALENCE AND MANAGEMENT OF DIABETESAND ASSOCIATED RISK FACTORS BY REGIONSOF THAILAND : THIRD NATIONA L HEALTHEXAMINATION SURVEY 2004 (NO. 170)

W. Aekplakorn, J. Abbott-Klafter, A. Premgamone, B. Dhanamun

Department of Community Medicine, Department of Medicine,Ramathibodi Hospital, Mahidol University, Thailand; PopulationHealth, University of Queensland, Brisbane, QLD, Australia;Setting Priorities Using Information on Cost-effectiveness(SPICE) Project, Ministry of Public Health, Bangkok, Thailand;Community Medicine, Khon Kaen University, Khon Kaen,Thailand; Preventive and Social Medicine, ChulalongkornUniversity, Bangkok, Thailand; Public Health, MahidolUniversity, Thailand; Epidemiology Unit, Prince of songklaUniversity, Hat Yai Thailand. Nursing, Chiang Mai University,Chiang Mai, Thailand.

Objective : The aim of this study was to determine theprevalence of diabetes and impaired fasting glucose (IFG) and theirassociation with cardiovascular risk factors and to evaluate themanagement of blood glucose, blood pressure, and cholesterol inindividuals with diabetes by geographical regions of Thailand.

Research Design and Methods : With the use of astratified, multistage sampling desing, data from a nationallyrepresentative sample of 37,138 individuals aged < 15 years werecollected using questionnaires, physical examination, and bloodsamples.

Results : The prevalence of diabetes and IFG weighted tothe national 2004 population was 6.7% (6.0% in men and 7.4% inwomen) and 12.5% (14.7% in men and 10.4% in women),respectively. Diabetes was more common in urban than in rural menbut otherwise prevalence was relatively uniform across geographicalregions. In more than one-half of those with diabetes, the diseasehad not been previously diagnosed, although the majority of thosewith diabetes were treated with oral antiglycemic agents or insulin.The prevalence of associated risk factors was high among individualswith diabetes as well as those with IFG. Two-thirds of those withdiabetes and concomitant high blood pressure (130/80 mmHg) werenot aware that they had high blood pressure, and > 70% of thosewith diabetes and concomitant high cholesterol (total cholesterol 6.2mmol/l) were not aware that they had high cholesterol.

Conclusions : The prevalences of diabetes and IFG wereuniformly high in all regions. Improvements in prevention, diagnosis,and treatment of diabetes and associated risk factors are required ifthe health burden of diabetes in Thailand is to be averted. 2007by the American Diabetes Association.

(Diabetes Care, 2007/30/8; 2007-2012)

TABACCO AND HAZARDOUS OR HARMFULALCOHOL USE IN THAILAND : JOINTPREVALENCE AND ASSOCIATIONS WITHSOCIOECONOMIC FACTORS (NO. 171)

W. Aekplakorn, M.C. Hogan, S. Tiptaradol, S. Wibulpolprasert

Department of Community Medicine, Faculty of Medicine,Ramathibodi Hospital, Mahidol University, Bangkok 10400,Thailand; Setting Priorties using Information on Cost-Effectiveness (SPICE) Project, 2nd Floor, Medical Department(5th Building), Ministry of Public Health, Tiwanon Road,Nonthaburi 11000, Thailand; School of Population Health,University of Queensland, Level 2, Public Health Building,Herston Road, Brisbane, QLD 4006, Australia, Institute forHealth Metrics and Evaluation, University of Washington, 1616Eastlake Avenue E, Suite 300, Seattle, WA 98201, USA; Food andDrug Administration, Ministry of Public Health, Tiwanon Road,Nonthaburi 11000, Thailand; Health Technical Office, Office ofthe Permanet Secretary, Ministry of Public Health, TiwanonRoad, Nonthaburi 11000, Thailand.

Key words : Tobacco smoking, Alcohol drinking patterns,Socioeconomic status

This study estimates the individual and joint prevalenceof cigarette smoking and alcohol misuse, and examines the associationbetween these risks and socioeconomic factors in Thailand. The self-reported data on cigarette and alcohol use are from a 2004 nationallyrepresentative cross-sectional survey of 39 290 individuals aged 15and over. Substantially more men than women were current smokers(45.8% vs. 2.3%; p < 0.001) as well as harmful (5.4% vs. 0.9%, p T) in intron 3 of the gamma-aminobutyric acid(GABA) receptor alpha3 subumit (GABRA3) gene possessed the mostsignificant difference in allele frequency (27% in THPP case and 5%in controls, P = 0.007). Actual allele frequency obtained fromgenotyping in each individual were very similar to the estimatedfrequency from the pools (28% in THPP and 2% in controls, and P =0.0002). Nearby DNA sequences of GABRA3 were sequenced andan additional two SNPs were found (A > C at exon 1 and G > T of rs12688128). Allele A of rs750841 and allele G of rs 12688128 inintron 3 were predominantly found in THPP with significant geneticrelative risk of 19 (P < 0.002; 95% CI 2.4-151.6).

Conclusions : Whole-genome scanning on pooled DNAprovides an accurate, useful screening tool for elucidating geneticunderpinnings of THPP. SNPs at intron 3 of GABRA3 are found tobe associated with THPP.

(Clin Endocrinol (Oxf) 2007/Oct 24)

ASSOCIATION OF GENETIC VARIATIONS NEARP2 PROMOTER OF THE HEPATOCYTE NUCLEARFACTOR 4 GENE AND INSULIN SECRETIONINDEX IN THAIS (NO. 182)

W. Jongjaroenprasert. S. Chanprasertyothin, A. Kongsuksai, P.Bunnag

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand;Research Center, Ramathibodi Hospital, Mahidol University,Bangkok, Thailand.

Key words : Asian diabetes, Association study, Insulin secretion,SNPs, Type 2 diabetes

This study was aimed to assess the association of the twosingle nucleotide polymorphisms (SNPs) near P2 promoter(rs1884614 and rs2144908) of hepatocyte nuclear factor-4 (HNF4A)with insulin secretion index and type 2 diabetes in Thais. Participantswere categorized into three groups; unrelated type 2 diabetes (N =219), prediabetes subjects (N = 228) and normal glucose tolerantcontrols (N = 203). Homeostasis model assessment was calculatedfor individual insulin secretion and insulin sensitivity index.Genotyping of both SNPs was done by allele-specific PCR technique.Difference of SNP allele frequencies between groups were computedusing the 2-statistic. Multivariate regression analysis was performedto determine the effect of SNPs on insulin secretion index. Theclinical features of all groups were similar. We demonstrated genotypeTT at rs1884614, BMI, and waist circumference were significantlyassociated with insulin secretion index (P = 0.023) but not withdiabetes phenotype. 2007 Springer-Verlag.

(Acta Diabetologica 2007/44/4; 227-232)

BERIBERI OUTBREAK AMONG COMMERCIALFISHERMEN, THAILAND 2005 (NO. 183)

P. Doung-Ngern, S. Kesornsukhon, J. Kanlayanaphotporn, S.Wanadurongwan

Bureau of Epidemiology, Department of Disease Control, ThaiMinistry of Public Health, Nonthaburi, Thailand; Srivichai 5Hospital, Samut Sakhon, Thailand; Division of Nutrition andBiochemical Medicine, Ramathibodi Hospital, MahidolUniversity, Bangkok, Thailand; Bureau of Epidemiology,Department of Disease Control, Ministry of Public Health,Nonthaburi 11000, Thailand.

In April 2005, The Tahi Bureau of Epidemiologyinvestigated a reported outbreak of beriberi among commercialfishermen in Maha Chai, a port city in the Gulf of Thailand. Theobjective of this study was to verify the diagnosis of beriberi inaffected individuals, describe the possible outbreak, ascertain riskfactors, and provide prevention and control measures. We interviewedill persons and treating doctors, and reviewed medical records toconduct a descriptive study. A probable case was defined as acrewmember of Ship A with one of the following : leg edema scrotaledema or ascites, dyspnea, chest discomfort, chest pain, extremitynumbness, or extremity weakness. Confirmed cases were those withclinical criteria and laboratory findings consistent with thiaminedeficiency. The outbreak started in early March 2005, and continueduntil March 31, 2005. Ship A had 28 crewmembers (four Thai, 24Myanmar). Overall, there were 15 probable cases (attack rate 53.6%with three confirmed and 12 probable cases). Only three were testedfor Vitamin B1 deficiency. All cases were male. With a median ageof 28 years (range 20-45). Fourteen of the 15 cases were Myanmarand one Thai. Due to limited resources, the crew ate only seafoodand polished rice for almost two months prior to symptoms.Symptoms included edema (60%), chest discomfort (54%), anddyspnea (27%). Two persons died while on board the ship (casefatality 13%). The total time at sea for Ship A was 18 months,including a five-month delay in docking due to licensing problems.

(Southeast Asian Journal of Tropical Medicine and Public Health2007/38/1; 130-135)


BLADDER SUBSTITUTION BY ILEAL NEO-BLADDER FOR WOMEN WITH INTERSTITIALCYSTITIS (NO. 184)

W. Kochakarn, P. Lertsithichai and W. Pummangura

Division of Hematology, Department of Medicine, Faculty ofMedicine Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand.

Objective : To report our experience with cystectomy andileal neobladder for women with interstitial cystitis (IC).

Materials and Methods : Thirty-five female patientstreated during 2000-2005 with the mean age of 45.9+/-4.4 years wereincluded in this study. All of them had experience surprapubic painwith irritative voiding symptoms and were diagnosed as having ICbased on NIDDK criteria for at least 2 years. Conservative treatmentshad failed to relieve their symptoms; and therefore all of them agreedto undergo a bladder removal. For cystectomy, the urethra was cut0.5 cm below the bladder neck, proximal to the pubourethral ligament,leaving the endopelvic fascia intact. An ileal segment of 65 cm wasused to create the neobladder with the Studers technique.

Results : All patients presented good treatment outcomewith regard to both diurnal and nocturnal urinary control withoutany pain. Quality of life using the SF-36 questionnaire showedsignificant improvement of both physical health and mental health.Spontaneous voiding with minimal residual urine was found in 33cases (94.3%), and the remaining 2 cases (5.7%) had spontaneousvoiding with residual urine and were placed on clean intermittentcatheterization (CIC). Twelve out of 30 cases with sexually activeability had a mild degree of dyspareunia but without disturbance tosexual life.

Conclusion : Bladder substitution by ileal neobladder forwomen who suffer from IC can be a satisfactory option after failureof conservative treatment. Resection of the urethra distal to thebladder neck can preserve continence and allow spontaneous voidingin almost all patients.

(Int Braz J Urol 2007/33/4; 486-92; discussion 492)

C.P. 1.07 EXERCISE INTOLERANCE AS A PRESEN-TATION OF ADULT ONSET NEMALINE (ROD)MYOPATHY (NO. 185)

C. Dejthevaporn and S. Phudhichareonrat

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand; PrasatNeurological Insitute, Pathology, Bangkok, Thailand.

We report a 48-year-lady who presented with one monthhistory of dyspnea on exertion and orthopnea. Her cardiovascularand pulmonary examinations were unremarkable. On retrospect, shehad a 4 year history of proximal lower limbs weakness with difficultyclimbing upstair and gripping. The weakness appeared to be worsenedfollowing viral infection. She had no prior history of swallowing andbreathing difficulty. However, she had noted frequent fall whilerunning since age 22 but she had never seeking any medical advice.

Her family history was unremarkable. On examination, she had higharch palate with mild facial weakness, symmetrical MRC grade 4/5weakness on deltoid, biceps, triceps, iliopsoas, quadriceps, hamstringand tibialis anterior. Other muscles as well as deep tendon reflexeswere normal. Her CK was 16 U/L. A needle EMG showed non-irritative myopathic pattern in the proximal and distal muscles of thearms and legs. Left vastus lateralis muscle biopsy shows someatrophic muscle fibre on H&E staining. Nemaline rod bodies in thesubsarcolemmal area were found on modified Gomeri Trichrome stainand on electron microscopic study.

(Neuromuscular Disorders 2007/17/9-10; 836-411)

CASE REPORT COMBINED HEPATOCELLULARAND CHOLANGIOCARCINOMA WITH SARCO-MATOUS TRANSFORMATION (NO. 186)

P. Boonsakan, O. Thangnapakorn, J. Tapaneeyakorn, S.Kositchaiwat

Division of Endocrinology and Metabolism, Department ofMedicine, Faculty of Medicine Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand.

Combined hepatocellular and cholangiocarcinoma withsarcomatous transformation was first recognized in RamathibodiHospital in 2005. This variant of carcinoma has been increasinglyreported particularly from Asian countries. Dedifferentiation of theepithelial component to various sarcomatous components is likelythe underlying mechanism. The causative factors ofhepatocarcinogenesis in Thailand include chronic viral hepatitis Bor C, exposures to aflatoxin B1 and nitrosamine(s) and occasionallysome certain nodular hepatocellular lesions due to arterialhyperperfusion. It is suggested that the recent change of the Thaipeoples life style to an increased consumption of fast foods containingfood preservatives especially nitrate or nitrite, the nitrosamineprecursor may allow heavy exposure(s) to the chemical carcinogen(s)i.e. nitrosamine(s) leading to sarcomatous transformation of thecarcinoma.

(Journal of the Medical Association of Thailand 2007/90/3; 574-80)

CHANGES IN HEART RATE VARIABILITYDURING CONCENTRATION MEDIATION (NO. 187)

S. Phongsuphap, Y. Pongsupap, P. Chandanamattha and C.Lursinsap

Department of Computer Science, Faculty of Science, MahidolUniversity, Bangkok 10400, Thailand; Health Care ReformProject, National Health Security Office, Nonthaburi, Thailand;Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand.

Key words : Heart rate variability, Autonomic nervous system,Meditation, Pattern recognition

This study aims at investigating chages in heart ratevariability (HRV) measured during meditation. The statistical andspectral measures of HRV from the RR intervals were analyzed.


Results indicate that meditation may have different effects on healthdepending on frequency of the resonant peak that each meditatorcan achieve. The possible effects may concern resetting baroreflexsensitivity, increasing the parasympathetic tone, and improvingefficiency of gas exchange in the lung.

(International Journal of Cardiology , In Press Corrected Proof/337)

CHARACTERIZATION OF ATYPICAL LYMPHO-CYTES AND IMMUNOPHENOTYPES OF LYMPHO-CYTES IN PATIENTS WITH DENGUE VIRUSINFECTION (NO. 188)

W. Jampangern, K. Vongthoung, A. Jittmittraphap, S.Worapongpaiboon

Faculty of Tropical Medicine, Mahidol University, Bangkok,Thaialnd; Faculty of Medicine Ramathibodi Hospital, MahidolUniversity, Bangkok, Thailand; B.M.A. Medical College, VajiraHospital, Bangkok, Thailand.

To characterize the immunophenotypes of lymphocytesin patients with dengue infection, we performed flow cytometricanalysis of peripheral blood mononuclear cells collected from 49dengue hemorrhagic fever (DHF), 25 dengue fever (DF), and 26dengue-like syndrome (DLS) cases. The mean total atypicallymphocytes in DHF (916.1 + 685.6 cells/ml). And DF (876.2 +801.9 cells/ml) were higher than those of DLA (310.5 + 181.4 cells/ml). An atypical lymphocyte count of 10% or higher was a goodindicator of dengue infection (sensitivity 50% and specificity 86%).Flow cytometric studies showed that the percentages of atypicallymphocytes correlated with those of CD19+B lymphocytes andinversely correlated with the percentages of CD69+ lymphocytes.The mean absolute counts of atypical lymphocytes and CD19+cellson the discharge day were significantly higher than those on theadmission day. Low percentages of TdT+cells were found in allgroups of patients. We concluded that atypical lymphocyte andCD19+ cell counts may be a useful diagnostic tool for dengueinfection and the recovery from the disease could be judged whennumbers of both cell types are significantly elevated.

(Asian Pacific Journal of Allergy and Immunolgy 2007/25/1; 27-36)

CLINICAL USE OF CLOPIDOGREL IN ACUTECORONARY SYNDROME (NO. 189)

R. Zambahari, O.H. Kwok, S. Javier, K.H. Mak, S. Piyamitr, H.Q.Tri Ho

Department of Cardiology, Institute Jantung Negara, KualaLumpur, Malaysia; Cardiac Catheterizationand InterventionCentre, Hong Kong Sanatorium and Hospital, Hong Kong;Makati Medical Center, Manila, Philippines; Gleneagles MedicalCentre, School of Mechanical and Aerospace Engineering,Nanyang Technological University, Singapore, Singapore,Ramathibodi Hopsital, Bangkok, Thailand; Emergency andReanimation Cardiology, Ho Chi Minh City Heart Institute, VietNam; Yunlin Branch Hospital, National Taiwan UniversityHospital, Taipei, Taiwan; Dr. Soetomo General Hospital, Jakarta,

Indonesia; Asia-Pacific Region Sanofi-Aventis; Department ofCardiology, Institut Jantung Negara, 145, Jalan Tun Razak,50400 Kuala Lumpur, Malaysia.

Several therapeutic approaches have been developed toimprove the outcome among patients with acute coronary syndrome(ACS). However, treatment with antithrombotic therapies such asoral glycoprotein IIb/IIa inhibitors has been limited by the lack ofefficacy and excess bledding complications. As the publication ofthe landmark study Clopidogrel in Unstable Angina to PreventRecurrent Events (CURE), the clinical benefit of early andintermediate-term use of combined antiplatelet agents clopidogrelplus aspirin- in non-ST-segment elevation myocardial infarction(NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoingpercutaneos coronary intervention (PCI) was further supported bythe PCI-CURE trial. Recently, the results of two major trialsClopidogrel as Adjunctive Reperfusion Therapy Thrombolysis inMyocardial Infarction 28, Clopidogrel and Metoprolol in MyocardialInfarction Trial established the pivotal role of clopidogrel in the otherspectrum of ACS-STEMI. Coupled with the results from previousmulticentre trials, these two studies provide a guide for the early andlong-term use of clopidogrel in the whole spectrum of ACS. A reviewsummarising the results of the recent clinical trials and a discussionon its implications for the clinical management of ACS is presented. 2007 The authors Journal comilation 2007 Blackwell PublishingLtd.

COMBINED LIVER-KIDNEY TRANSPLANTATIONIN A PATIENT WITH ACUTE LIVER FAILURECOEXISTING WITH ACUTE RENAL FAILURE

(NO. 190)

A. Sobhonslidsuk, B. Phakdeekitcharoen, S. Leelaudomlipi, P.Pootrakul

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University; Department of Surgery,Ramathibodi Hospital, Mahidol University; Department ofAnesthesiology, Ramathibodi Hospital, Mahidol University;Department of Pathology, Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand.

Key words : Acute liver failure, Acute renal failure; Cirrhosis; Kidneytransplantation, Liver transplantation

Acute renal failure (ARF) is common among patients withliver failure awaiting liver transplantation due to the increased waitingtime for available liver grafts and extended survival from improvedintensive care. The role of combined liver and kidney transplantation(LKT) in this situation is quite controversial. A case of acute liverfailure (ALF) complicated with ARF is reported. Non-A, non-Bhepatitis was the cause of ALF. He had hemodialysis for one monthbefore transplantation. Combined LKT was performed because ofprolonged pre-transplant hemodialysis and the potential of irreversiblerenal failure. Sevre impairment of both native kidneys was confirmedby renal scan at 6 months after transplantation. Combined LKT maybe needed for patients with acute liver failure complicated withprolonged acute renal failure.



COMPARISON OF ESSENTIAL TRACE ELEMENTSIN BLOOD OF PATIENTS RECEIVING RAMA-THIBODI STANDARD PARENTERAL NUTRITIONWITH RAMATRACE OR A COMMERCIALFORMULAR (NO. 191)

C. Roongpisuthipong, J. Chiaovit, S. Songchitsomboon and B.Chindavijak

Division of Nutrition and Biochemical Medicine, Department ofMedicine, Ramathibodi Hospital; Research Center, RamathibodiHospital, Faculty of Pharmacy, Faculty of Medicine, MahidolUniversity; Department of Medicine Ramathibodi Hospital,Mahidol University, Bangkok 10400, Thailand.

Key words : Chromium, Copper, Manganese, Ramatrace, Traceelements, Zinc.

Objective : Commercially intravenous trace elementproduct is very expensive compared to Ramatrace. Therefore, thepresent research was designed to compare the levels of zinc, copper,chromium and manganese in the blood of patients receivingRamathibodi Standard Parenteral Nutrition (STD) containing theRamatrace or the commercial product.

Material and Method : Two groups of patients receivingSTD were recruited. Group 1 (19) males and 11 (females) receivedRamatrace and Group 2 (19 males and 11 females) received acommercial product. Blood samples on day 0, day 3 and day 10were measured for zinc, copper, chromium and manganese levels byatomic absorption spectrophotometer (model 3100, Perkin Elmer).

Results : The present results showed that levels of zinc,copper, chromium and manganese were not significantly differentbetween the two groups. On day 0, day 3 and day 10, the levels ofzinc, copper and manganese in the blood of both groups weresignificantly increased (p < 0.05). Blood chromium levels of Group1 were significantly increased from day 0 (0.14 + 0.02 mg/dL) today 3 (0.23 + 0.02 mg/dL) but there was no significant differencebetween day 3 and day 10. In Group 2, the blood levels of chromiumfrom day 0 to day 10 were significantly increased.

Conclusion : In patients receiving STD, Ramatrace couldimprove the levels of zinc, copper, chromium and manganese as wellas the commercial product. This may be one way to reduce the costof treatment.


COMPARISON OF PREVENTION OF NSAID-INDUCED GASTROINTESTINAL COMPLICATIONSBY REBAMIPIDE AND MISOPROSTOL : ARANDOMIZED, MULTICENTER, CONTROLLEDTRIAL STORM STUDY (NO. 192)

S.H. Park, C.S. Cho, O.Y. Lee, J.B. Jun, S.R. Lin, L.Y. Zhou,Y.Z. Yuan

St. Marys Hospital, Catholic University of Korea, Seoul 150-713, South Korea, Hanyang University Hospital, HanyangUniversity, Seoul 133-792, South Korea; Third Hospital, Peking

University, Beijing 100083, China; Ruijin Hospital, ShanghaiSecond Medical University, Shanghai 200025, China; ChanghaiHospital, Second Military Medical University, Shanghai 2000043,China; Union Hospital of Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan 430022, China;Beijing China-Japan Friendship Hospital, Beijing 100029, China;Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;Ramathibodi Hospital, Mahidol University, Bangkok 10400,Thailand; Chonburi Hospital, Chonburi 20000, Thailand.

Key words : Clinical trial, Gastrointestinal tract, Misoprostol,NSAID, Rebamipide

Nonsteroidal anti-inflammatory drugs (NSAIDs) havegastrointestinal side effects such as dyspepsia, peptic ulcer,hemorrhage, and perforation. Misoprostol and PPIs have been usedto prevent NSAID-induced gastroduodenal injury. Rebamipideincreases gastric mucus and stimulates the production of endogenousprostaglandins. The prophylactic effect of rebamipide on NSAID-induced gastrointestinal complications is unknown. The aim of thisstudy was to compare NSAID-induced gastrointestinal complicationsin rebamipide- and misoprostol-treated groups. Patients wererandomized to two groups and took a conventional NSAID plusrebamipide or misoprostol for 12 weeks. Gastric mucosal damagewas evaluated by endoscopy at screening and the end of the study.The prevalences of active gastric ulcer were 7/176 (3.9%) in therebamipide group and 3/156 (1.9%) in the misoprostol group. Theprevalences of peptic ulcer were 8/176 (4.5%) in the rebamipide groupand 7/156 (4.4%) in the misoprostol group. The cumulativeincidences of peptic ulcer in the high-risk subgroup were 6/151 (4.0%)for rebamipide and 6/154(3.9%) for misoprostol. In conclusion,rebamipide prevented NSAID-induced peptic ulcer as effectively asmisoprostol in patients on long-term NSAID therapy. Rebamipidemay be a useful therapeutic option for the prevention of NSAID-induced gastrointestinal ulcer because of its therapeutic effect andsafety.

(Journal of Clinical Biochemistry and Nutrition 2007/40/2; 148-155)

CO-STIMULATORY MOLECULES ON PERI-PHERAL BLOOD MONONUCLEAR CELLS ANDTISSUE INFILTRATING CELLS OF SKIN WARTAND IN VITRO POKE WEED MITOGEN STIMU-LATION (NO. 193)

P. Phumeesat, S. Charuwichitratana and M. Vongsakul

Department of Microbiology, Faculty of Science, MahidolUniversity, Department of Medicine, Ramathibodi Hospital,Mahidol University; Department of Microbiology, Faculty ofScience, Mahidol University, Bangkok 10400, Thailand.

Key words : Co-stimulatory molecule, Immune cell competency, Skinwart

Background : Skin wart is a lesion caused by humanpapilloma viruses (HPVs) that can infect both male and female.

Objective : Quantify the number of CD28+, CD86+,CD152+ and in peripheral blood mononuclear cells (PBMCs) ofsubjects with skin wart. Identify CD86+ and cells in skin wartcryosections.


Material and Methods : Sixteen subjects with skin wartson face, hand, finger, knee, foot or plantar, both male and female,aged between 19-59 years-old, were recruited from RamathibodiHospital, Mahidol University, Bangkok.

Results : CD86 and CD152, on peripheral bloodmononuclear cells (PBMCs) of subjects with skin wart aresignificantly lower compared to controls. Tissue cryosection stainingfor CD86+ and cells showed no difference among subjects with skinwart and control. Proliferative response to poke weed mitogen ofsubjects with skin wart is significantly lower than control subjects.

Conclusion : There was no difference in the number ofsubjects positive for CD28 and CD86+ cell between normal and skinwart subject, but an increase in skin wart subjects with cells.


DASATINIB OR HIGH-DOSE IMATINIB FORCHRONIC - PHASE CHRONIC MYELOIDLEUKEMIA AFTER FAILURE OF FIRST-LINEIMATINIB : A RANDOMIZED PHASE 2 TRAIL

(NO. 194)

H. Kantarjian, R. Pasquini, N. Hamerschlak, P. Rousselot, J.Holowiecki

M.D. Anderson Cancer Center, Houston, TX, United States;Hospital de Clinicas de Cutritiba, Curitiba, Parana, Brazil;Hospital Israelita Albert Einstein, Sao Paulo, Brazi; HospitalSaint Louis, Paris Cedex, France; Katedra I Klinika HematologiiI Transplanatacji Szpiku, Katowince, Poland; RamathibodiHospital, Bangkok, Thailand; Szpital Specjalistyczny Im.Kopernika Klinika Hematologii, Lodz, Poland; NationalResearch Hematology Center, Moscow. Russian Federation;National Medical Center, Budapest, Hungary; CollegiumMedicum Uniwesytetu Jagiellonskiego, Krakow, Poland; KlinikaHematologii, academia Medyczna, Gdansk, Poland; St.Petersburg State Medical University, St Petersburg, RussianFederation; Moscow regon research clinical Institue, Moscow,Russian Center, Seattle, WA. United States; Divison ofHematology, Institute of Medial Veterinary Science, Adelaide,SA, Australia; Bristol Myers squibb, wallingford, CT, UnitedStates; Division of Hematology and Oncology, University College,of San Francisco School of Medicine, san Francisco, CA, UnitedStates : Departmentof Leukemia, University of Texas M.D.Anderson Cancer Center, POBox 30-1402, Houston, TX 77230-1420, United States.

Therapeutic options for chronic myelogenous leukemia(CML) resistant to 400 to 600 mg imatinib are limited. Escalatingimatinib doses may overcome resistance. Dasatinib, a significantlymore potent inhibitor of BCR-ABL, is safe and effective in thispopulation. Pateints with imatinib-resistant chromic-phase (CP) CMLwere randomized 2:1 to 140 mg dasatinib (n = 101) or 800 mgimatinib (n = 49). With a median follow up of 15 months, completehematologic responses were observed in 93% and 82% of paitnetsreceiving dasatinib and high-dose imatinib (P = .034), respectively.Dasatinib resulted in higher major cytogenetic response rates (52%)than high-dose imatinib (33%) (P = .023);this included complete

cytogenetic response in 40% and 16% (P = .004). Major molecularresponses were also more frequent with dasatinib (16% versus 4%; P= 0.038). Treatment failure (hazard ratio [HR], 0.16; P < 0.001) andprogression-free survival (HR, 0.14; P < 0.001) both favoreddasatinib. Superficial edema (42% versus 15%) and fluid retention(45% versus 30%) were more prevalent with imatinib; pleural effusionwas more common with dasatinib (17% versus 0%). Grade 3 to 4nonhematologic toxicity was minimal. Cytopenias were more frequentand severe with dasatinib. Dasatinib represents a safe and effectivetherapy for CP-CML resistant to conventional imatinib doses withimproved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib 2007 by The AmericanSociety of Hematology.

(Blood 2007/109/12; 5143-5150)

DECLINING PREVALENCE OF DRUG-RESISTANTTUBERCULOSIS AMONG HIV/TUBERCULOSISCO- INFECTED PATIENTS RECEIVING ANTIRE-TROVIRAL THERAPY (NO. 195)

S. Sungkanuparph, B. Eampokalap, S.Chottanapund, S.Thongyen

Faculty of Medicine, Ramathibodi Hospital, Mahidol University,Bangkok, Thailand; Bamrasnaradura Infectious DiseasesInstitute, Ministry of Public Health, Nonthaburi, Thailand;Departmentof Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand.

Key words : Antiretroviral therapy, Drug resistance, HIV, Prevalence,Tuberculosis

Background : Drug-resistant tuberculosis (DR-TB) is aserious threat in developing countries where the prevalence of bothHIV and TB are high. Antiretroviral therapy (ART) has been moreaccessible in these countries. The present study aimed to determinethe impact of ART on the prevalence of DR-TB among HIV/TB co-infected patients.

Material and Method : A retrospective cohort study wasconducted among HIV-infected patients with culture-proved TB from1999 to 2004. Susceptibilities of Mycobacterium tuberculosis toantituberculous drugs and rate of ART use were studied.

Results : There were 225 patients, mean age 35.8 yers,72.4% male and median CD4 44 cells/mm3. Patients who hadreceived ART increased from 18.5% in 1999 to 92.1% in 2004 (p 10 mlU/ml were definedas responders. There were 65 patients with a mean age of 39 + 8, 5years, 68% were females. Fifty-seven (88%) patients had receivedantiretroviral therapy for a mean(SD) duration of 26.1 (22.3) monthsand 75% of these had an HIV-1 RNA count < 50 copies/ml. Themean (SD) CD4 cell count and percentage at the time of vaccinationwere 345 (194) cells/mm3 and 16 (7%), respectively. Thirty patients(46%) were responders. Compared to non-responders, respondershad a higher mean CD4 cell count (p = 0.047) and a treand toward ayounger age (p = 0.052). On multivariate analysis, younger age (p =0.049) and higher CD4 cell count (p = 0.048) were predictors forsuccessful response to hepatitis B vaccination. Determination ofantibody levels after vaccination in HIV-infected patients iswarranted.

(Southeast Asian Journal of Tropical Medicine and Public Health2007/38/4; 680-685)

FLUORESCENCE IN SITU HYBRIDIZATIONMETHOD IN ISOLATED SINGLE NUCLEIEXTRACTED FROM PARAFFIN-EMBEDDEDHEPATOCELLULAR CARCINOMA TISSUES

(NO. 206)

A. Tantiwetrueangdet, R. Panvichian, P. Sornmayura, K.Pinpradap

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand;Department of Pathology, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand;Department of Surgery, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand.


Key words : Fluorescence in situ hybridization (FISH), Formalin-fixed paraffin embedded tissues, Hepatocellular carcinoma, Isolatedsingle nuclei

Background : Genetic analysis using the fluorescence insitu hybridization (FISH) method applied to intact tissue sections offormalin-fixed paraffin embedded (FFPE) tissue is well known to berelatively difficult. The frequent technical problems includeunsuccessful hybridization as a result of poor probe penetration,excessive probe requirement, excessive background, auto-fluorescence, and overlapping or incomplete nuclei. These problemslead to absence or insufficiency of fluorescent signals, resulting inan inaccurate analysis. Formalin-fixed paraffin embedded tissue canbe analyzed either as intact tissue sections or as a suspension ofdisaggregated, but intact, nuclei. Intact tissue sections have theadvantage of preserved tissue architechture and morphology but havethe intrinsic disadvantage of poor probe penetration, overlapping orincomplete nuclei and auto-fluorescence, accordingly reducing theaccuracy of fluorescent signals evaluation.

Objective : To present the effective FISH method appliedto isolated of single nuclei and the procedures for isolation of a singlenuclei from formalin-fixed paraffin embedded tissues ofhepatocellular carcinoma.

Material and Method : Ten paraffin-embedded blocksof hepatocellular carcinoma tissues from the department of pathology,Ramathibodi hospital, Thailand were studied. Isolated single nucleiwere extracted from 10 sections of paraffin-embedded blocks ofhepatocellular carcinoma tissue and hybridized with alpha-satellitecentromeric DNA enumeration probes for chromosomes X (CEP X,spectrum green) and satellite III for chromosomes Y (CEP Y, spectrumorgane). The signal of, at least, 200 interphase nuclei were countedfrom each specimen.

Results : The efficacy of this method has been evaluatedin 10 formalin-fixed paraffin embedded tissue of hepatocellularcarcinoma. The results showed bright, planar and an easy to scoresignal.

Conclusion : FISH procedure described here isparticularly suitable for retrospective studies of genetic aberrationapplied to formalin-fixed paraffin embedded tissues.


G.P.4.03 DYSFERLINOPATHY IN THAI PATIENTSAND ITS UNUSUAL PATHOLOGICAL FINDINGS

(NO. 207)

S. Pongpakdee, V. Sopassathit, S. Phudhicharoenrat, U.Suthiponpaisan

Bhumibol Adulyadej Hospital, Neurology unit, Department ofMedicine, Bangkok, Thailand; Prasat Neurological Institue,Department of Neuropathology, Bangkok, Thailand; SomdejPrapinklao Hospital, Neurology Unit, Department of Medicine,Bangkok, Thailand; National Institute of Neuroscience, NationalCenter of Neurology and Psychiatry (NCNP), Department ofNeuromuscular Research, Tokyo, Japan; RamathithibodiHospital, Mahidol University, Division of Neurology, Departmentof Medicine, Mahidol University, Bangkok 10400, Thailand.

Background : Although dysferlinopathy is beingincreasingly recognized in limb-girdle muscular dystrophy and distalmyopathy, it has never been reported in Thailand.

Objective : To report the first three Miyoshi myopathypatients in Thailand together with interesting pathological findings.

Method : We studied the clinical features of two siblingsand one sporadic case from two unrelated non-consanguineousfamilies who presented with distal legs weakness. Muscle biopsywas performed in the probands in both analysis for dysferlin.

Results : All patients showed wasting and weakness ofmuscles of the calves. The muscle pathology in one patient showeddystrophic change and inflammatory cell infiltration which are oftenfound in dysferlinopathy, whereas the other showed numerous ringfibers in addition to variation in fiber size. Immunotochemical andWestern blot analyses demonstrated the absenc of dysferlin in bothmuscles. Dysferlinopathy is known to show a wide range ofabnormalities in myofibrillar alignment from nearly normal tomarkedly disorganized myofibrils showing lobulated fibers and/ormoth-eater fivers in addition to necrotid and regenerating process.However, prominent ring fibers have never been reported.

Conclusion : Dysferlinopathy seems to be infrequent inEurpoe. The observation that it is more prominent in Japan and themost common cause of limb-girdle muscular dystrophy advocatesthat it may actually be common in other Asian countries as well.Our report probably supports this notion and suggests the presenceof more patients with dysferlinopathy in Thailand. Pathologically,one of our cases was characterized by numerous ring fibers. Musclepathology with frequent ring fibers is seldom seen except in myotonicdystrophy although ring fibers themselves are not disease-specific.This report further widens the variety of dysferlinopathy musclepathology with prominent ring fibers.

(Neuromuscular Disorders 2007/17/9-10; 778-411)

GENETIC POLYMORPHISMS AND HAPLOTYPESOF DNA REPAIR GENES IN CHILDHOOD ACUTELYMPHOBLASTIC LEUKEMIA (NO. 208)

S. Pakakasama, T. Sirirat, S. Kanchanachumpol, U.Udomsubpayakul

Division of Allergy-Immunology-Rheumatology, Department ofMedicine Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand.

Background : Polymorphisms of DNA repair genes canalter protein structure and may impair DNA repair capacity. Defectsin repairing damaged DNA lead to genetic instability andcarcinogenesis. This study was performed to evaluate the effect ofthe polymorphisms of DNA repair genes on risk of childhood acutelymphoblastic leukemia (ALL).

Procedures : We genotyped polymorphisms of X-rayrepair cross-complimenting group I (XRCC1) codon 194 (Arg to Trp),280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosumgroup D (XDP) codon 312 (Arg to Gln), and 715 (Lys to Gln) in 108children with ALL and 317 healthy controls using PCR-RFLP method.


The allele, genotype, and haplotype frequencies of thesepolymorphisms were compared between cases and controls using Chi-square or Fishers exact test. PHASE computer software was used toanalyze estimated haplotypes of the XRCCl and XPD polymorphisms.

Results : The frequency of XRCCl 194Trp allele inpatients was significantly lower than that in controls (odds ratio (OR)0.67; 95% confidence interval (CI), 0.47-0.97). Individuals withXRCCI 194 Trp/Trp genotype had a significantly reduced risk ofALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCCIhaplotype B (194Trp-280Arg-399Arg) was significantly lower inchildren with ALL when compared to controls. The XRCC1 399Glnallele was associated with a significantly increased risk of ALL (OR1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotypeC (194Arg-280Arg-399Gln) was significantly higher in patients.There was no difference of allele frequencies of the XRCC1 280(Arg to His). XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) betweencases and controls.

Conclusion : The XRCC1 194Trp allele and haplotype Bshowed a protective effect against development of childhood ALL.In contrast, individuals with the XRCC1 399Gln allele and haplotypeC were associated with increased risk for this disease.

(Pediatr Blood Cancer 2007/48/1; 16-20)

GROWTH HORMONE TREATMENT IN ADOLES-CENT MALE WITH IDIOPATHIC SHORTSTATURE : CHANGES IN BODY COMPOSITION,PROTEIN, FAT, AND GLUCOSE METABOLISM

(NO. 209)

T.S. Hannon, K. Danadian, C. Suprasongsing and S.A. Arslanian

Division of Pediatric Endocrinology, Metobolism and DiabetesMellitus, Division of Weight Management and Wellness,Childrens Hospital of Pittsburgh, Pittsburgh, PA 15213, UnitedStates; Oneida Pediatric Group, Onedia, NY 13421, United States;Ramathibodi Hospital, Mahidol University, Bangkok 10400,Thailand; Childrens Hospital of Pittsburgh, 3705 5th Avenue atDeSoto Street, PA 15213, United States

Context : Cross-sectional observations show an inverserelationship between pubertal increase in GH and insulin sensitivity,suggesting that pubertal insulin resistance may be mediated by GH.

Objective : Our objectie was to assess longitudinally theeffects of short-term GH supplementation in adolescent males withnon-GH-deficient idiopathic short stature (ISS) on body composition,substrate metabolism, and insulin sensitivity. Children with ISS werestudied to simulate the pubertal increase in GH secretion.

Participants and Setting : Eight males with ISS (10.8 16.5 yr) were recruited from pediatric endocrinology clinics at anacademic medical center.

Study Design : Participants were evaluated in the GeneralClinical Research Center before and after 4 months of GHsupplementation (0.3 mg/kg/wk). Body composition was assessedwith dual-energy x-ray absorptiometry. Whole-body glucose, protein,and fat turnover were measured using stable isotopes. In vivo insulin

action was assessed during a 3-h hyperinsulinemic (40 mU/m2 +min)euglycemic clamp.

Results : GH supplementation led to 1) increase in hepaticglucose productionand fasting insulin levels, 2) increase in lean bodymass and decrease in fat mass, and 3) improvement in cardiovascularlipid risk profile. Plasma IGF-I levels correlated positively withinsulin levels.

Conclusions : Four months of GH supplementation inadolescent males with ISS is associated with significant bodycomposition changes and hepatic insulin resistance. Copyrigh 2007 by The Endocrine Society.

(Journal of Clinical Endocrinology and Metabolism 2007/92/8;3033-3039)

HAEMOGLOBIN HOPE IN A NORTHERN THAIFAMILY : FIRST IDENTIFICATION OF HOMOZY-GOUS HAEMOGLOBIN HOPE ASSOCIATEDWITH HAEMOGLOBIN H DISEASE (NO. 210)

T. Sura, M. Busabaratana, S. Youngcharone, R. Wisedpanichkij

Department of Medicine, Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand; Department of Paediatrics,Faculty of Medicine Siriraj Hospital, Mahidol University,Bangkok 10700, Thailand.

Key words : gloin, Haemoglobinopathy, Hb H, Hb Hope, Thailand,Thalassaemia

Haemoglobin (Hb) Hope [136(H14)Gly ->Asp(GGT ->GAT)] is one the unstable haemoglobin variants of the -globinchain, which is demonstrated in people of various ethnic backgrounds.Here we report a Thai female patient with clinical thalassaemiaintermedia since childhood. This patient had experienced neitherblood transfusion nor hospitalisatin. Hb Barts H and a large amountof Hb Hope were identified by high-performance liquidchromatography (HPLC) assay and the diagnosis of homozygous HbHope was definitely achieved by direct sequencing of exon 3 of -globin gene. Furthermore, we could identify that her brother carriedthe mutation of homozygous Hb Hope without abnormal globinchain involvement, and another family member had heterozygousHb Hope in association with 3.7 mutation, and both of them wereclinically silent. 2007 The Authors.

(European Journal of Haematology 2007/79/3; 251-254)

HEMOGLOBIN H DISEASE INDUCED BY THECOMMON SEA DELETION AND THE RAREHEMOGLOBIN QUONG SZE IN A THAI FEMALE :LONGITUDINAL CLINICAL COURSE,MOLECULAR CHARACTERIZATION, ANDDEVELOPMENT OF A PCR/RFLP-BASEDDETECTION METHOD (NO. 211)

T. Sura, O. Trachoo, V. Viprakasit, P, Vathesatogkit, A.Tunteeratum


Department of Medicine Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand; Department of Pediatrics,Ramathibodi Hospital, Mahidol University, Bangkok 10400,Thailand; Sirikit Medical Center, Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand; Department of Pediatrics,Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;Siriraj Thalassemia Res. Program/WHO Collaborating Ctr. Forthe Control of Hemoglobinopathies, Siriraj Hospital, MahidolUniversity, Bangkok 10700, Thailand.

Key words : Hb H disease, Hb Quong Sze, Hemoglobinopathy,Nondeletional thalassemia, Thalassemia

We report on a Thai patient who presented withhypochromic microcytic anemia, hepatosplenomegaly, and failureto thrive since 3 years of age. Hematological and hemoglobin (Hb)analysis were consistent with a clinical diagnosis of Hb H disease.However, no abnormal Hb fraction had ever been detected. Duringthe 20 years of follow-up, this patient experienced several episodesof hemolytic crisis, which worsened her anemia, necessitating bloodtransfusion. Recently, we identified Hb Quong Sze (Hb QS), a highlyunstable globin gene mutation affecting codon 125(CTG->CCG) of2 globin gene in trans with the commonents 0 thalassemia(-SEA)in the patient. This report highlights the clinical significance of HbQS in Southeast Asians, as previously almost all of the patientsdescribed with this variant were of Chinese origin. Springer-Verlag2007.

(Annals of Hematology 2007/86/9; 659-663)

HEMOSTATIC AND THROMOBOTIC MARKERSIN PATIENTS WITH HEMOGLOBIN E/-THALASSEMIA DISEASE (NO. 212)

P. Angchaisuksiri, V. Atichartakarn, K. Aryurachai, N. Archararit

Department of Medicine Ramathibodi Hospital, MahidolUniversity, Bangkok, Thailand; Department of Pathology,Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;Faculty of Medicine, Ramathibodi Hospital, Mahidol University,Bangkok, Thailand.

Increased frequency of thrombosis has been observed inpatients with hemoglobin E/-thalassemia (Hb E/-thal) disease,particularly those who have previously been splenectomized. Wecompared various hemostatic and thrombotic markers in blood from15 Hb E/-thal patients who were not splenectomized (NS), 15 whohad been splenectomized (S), and 15 normal controls (NC). Levelsof plasma thrombin-antithrombin, 2 thromboglobulin, C-reactiveprotein, tissue plasminogen activator antigen were significantly higherin the S group thanin either the NS or the NC groups, and levels ofprothrombin fragment 1.2 were significantly higher in the S than inthe NC group. Levels of plasminogen activator inhibitor-1 antigenwere significantly higher in the S than in the NS group. Levels ofprotein C, protein S, antithrombin, and fibrinogen were significantlylower in the S and NS groups were not statistically different fromNC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-gradeinflammation, endothelial cell injury, impaired fibrinolysis, anddecreased naturally occurring anticoagulants in splenectomized HbE/-thal patients. These changes may account for the increased riskof thrombosis in these patients. 2007 Wiley-Liss, Inc.

(American Journal of Hematology 2007/82/11; 1001-1004)

HUMAN POISONING IN THAILAND : THERAMATHIBODI POISON CENTERS EXPERIENCE(2001-2004) (NO. 213)

W. Wananukul, C. Sriapha, A. Tongpoo, U. Sadabthammarak

Ramathibodi Posion Center and Division of ClinicalPharmacology and Toxicology, Department of Medicine, Facultyof Medicine, Ramathibodi Hospital, Mahidol University,Bangkok, Thailand.

Objective : To identify poisoning and toxic exposurepattern, severity, and clinical outcome in Thailand during 2001 to2004.

Method : This is a prospective study. All inquires wereregistered, followed up, and verified. Interlocutors, poisons, patientsprofiles, severity, and medical outcome after exposure or poisoningwere analyzed.

Results : A total 14,428 events was suspected as humanpoisoning or exposure. After follow-up and verification, 98.9% wereconfirmed as poisoning or poison exposure. These involved 15,016patients and accounted for 6.0 per 100,000 populations per year. Thevast majority of calls (92.4%) were from physicians. Pesticides,household products, and pharmaceutical products were the mostcommon poisons involved in human exposure, which were 41.5%,19.5% and 18.9% respectively. Patients aged 0-6 years, teenagerand adults with 20-29 years of age had the highest rates of exposure,which were 33.0, 24.5 and 10.5 exposures per 100,000 per year,respectively. Unintentional accidental exposure is the major reasonof exposure in children, but intentional suicide was the main reasonof exposure in teenagers and adults. The death rate of all exposurewas 5.5%. Pesticides cause more severe clinical course and thehigherst death rate (10.0%).

Conclusion : Features of poisoning in Thailand weredifferent from those in Western countries. Pesticide poisoning wasthe major problem in Thailand. International suicide was the majorcircumstance of poison exposure in adults, but accidental exposurewas the major reason of exposure in children.

(Clinical toxicology (Philadelphia, Pa. 2007/45/5; 582-588)

IMPACT OF A NEW GUIDELINE FOR CENTRALVENOUS CATHETER CARE ON SEPSIS IN TOTALPARENTERAL NUTRITION : EXPERIENCE INRAMATHIBODI HOSPITAL (NO. 214)

C. Roongpisuthipong, V. Getupook and B. Chindavijak

Department of Medicine, Ramathibodi Hospital, MahidolUniversity; Faculty of Pharmacy, Ramathibodi Hospital, MahidolUniversity; Department of Medicine, Ramathibodi Hospital,Mahidol University, Bangkok 10400, Thailand.

Key words : Catheter, Guideline, TPN-related

Background : Total parenteral nutrition (TPN) is theessential treatment for hospitalized patients in whom normnal enteralnutrition is inadequate or not feasible. However, TPN-related sepsis


is the most serious and fatal complication of the treatment and thecatheter is the most common cause of infection. Therefore, theNutrition Support team in Ramathibodi Hospital has developed anew guideline for central venous catheter care for TPN patients andhas used it for at least a year.

Objective : Survey the current incidence of TPN-relatedsepsis in the hospital, the predisposion factors of the TPN-relatedsepsis and the pathogenic organisms of the sepsis.

Material and Method : Between July 1999 and February2000, 52 TPN treatments (catheter count) in 40 surgical and medicalpatients were prospectively recruited. Microbiological studies weredone in all cases of TPN-related sepsis.

Results : The incidence of TPN-related sepsis was 15%per catheter or 12.64/1000 catheter-days. Although no statisticallysignificant predisposing factors were found for the sepsis, somefactors such as postoperative TPN and short interval (< 2 days) forTPN line change (OR = 3.33, 95% CI = 0.33-30.34) showed a higherrisk for TPN-related sepsis. The most common pathogenic organismswere Coagulase-negative staphylococci, Candidia albicans, and gram-negatie bacteria. The organisms were found from hemoculture inseptic patients and were well correlated with those found in thecatheter line. Thus, the significant pathogenic role of Coagulase-negative staphylococci emphasizes the importance of aseptictechnique during catheterization.

Conclusion : The Ramathibodi guideline rendered supportfor a good policy to improve and standardize the TPN treatment.Along with a practical guideline, the well-trained and highlyresponsible personnel would also be crucial to avoid the infectiouscomplications.


IMPACT OF ANTIRETROVIRAL THERAPY ONTHE RELAPSE OF CRYPTOCOCCOSIS ANDSURVIVAL OF HIV-INFECTED PATIENTS WITHCRYTOCOCCAL INFECTION (NO. 215)

U. Jongwutiwes, S. Kiertiburanakul and S. Sungkanuparph

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand.

Background : Cryptococcosis is an opportunisticinfection with morbidity and mortality in HIV-infected patients.Impact of antiretroviral therapy (ART) on the relapse ofcryptococcosis and survival of HIV-infected patients withcryptococcosis has not been well established.

Methods : A retrospective cohort Study of HIV-infectedpatients with cryptococcosis during 1997-2005 was conducted.Relapse and survival rates with correspondeing risk factors weredetermined.

Results : There were 149 patients with a mean age of33.5 +/- 7.4 years and 57% were male. Median CD4 cell count was22 cells/mm(3). After exclusion of patients who died or were lost tofollow-up during the first two weeks, 127 patients were eligible for

the analysis of the effect of ART on relapse and survival rates. Of127 patients, 52 received ART. The demographic data between thetwo groups were similar. Median time of ART initiation aftercryptococcal diagnosis was 2.6 months. The most frequent ART usedwas NNRTI-based regimen (88.4%). Median CD4 change at sixmonths of ART was 97 cells/mm(3) and 87.9% achievd undetectableHIV-RNA. The cumulatie 75% survival (free) from relapse durationwas 10.4 months in no-ART group and 41.9 months in ART group (P< 0.01). The 75% survival from cryptococcal-related mortality inno-ART group was 6.4 months whereas > 54 months for ART group(P < 0.01). In Cox proportional hazard model, ART was the onlyfactor that associated with lower relapse and mortality rate (P < 0.01).

Conclusions : ART significantly reduced relapse andmortality rate from cryptococcosis in HIV-infected patients. ART isstrongly recommended in this population and should not be delayed.

(Current Hiv Research 2007/5/3; 355-360)

IMPACT OF DRUG-RESISTANT TUBERCULOSISON THE SURVIVAL OF HIV-INFECTED PATIENTS

(NO. 216)

S. Sungkanuparph, B. Eampokalap, S. Chottanapund, S.Thongyen

Faculty of Medicine Ramathibodi Hospital, Mahidol University,Bangkok 10400, Thailand; Bamrasnaradura Infectious DiseasesInstitute, Ministry of Public Health, Nonthaburi, Thailand;Department of Medicine Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand.

Objective : To determine the effect of drug-resistanttuberculosis (TB) on the survival of human immunodeficiency virus(HIV) infected patients in an area with a high prevalence of TB.

Design : Retrospective cohort study.

Results : Of 225 HIV-TB patients with a mean age of35.8 years, 72.4% were male. The median CD4 cell count at TBdiagnosis was 44 cells/mm3. Sixty per cent presented with extra-pulmonary TB (EPTB). Sixty-three (28%) patients were infectedwith Mycobacterium tuberculosis resistant to at least one durg;respectively 16.4%, 9.3%, 5.3% and 12.9% were resistant to isoniazid(INH), rifampicin (RMP), ethambutol and streptomycin, and 14(6.2%) had multidru-resistant TB (MDR-TB). During a medianfollow-up of 11.5 months, 4% died. From Kaplan-Meier analysis,INH resistance, RMP resistance and MDR-TB were associated withshorter survival (log-rank test, P < 0.005). Coxs proportional hazardmodel showed that MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1-64.9), not receiving antiretroviral therapy (ART) (HR 7.9; 95% CI1.5-43.1) and EPTB (HR 5.1%; 95% CI 1.9-25.9) were significantrisk factors for death.

Conclusion : MDR-TB and EPTB substantially reducesurvival among patients co-infected with HIV and TB. Early detectionand optimal treatment of MDR-TB are crucial. ART significantlyprolongs survival and should be initiated in HIV-TB co-infectedpatients. 2007 The Union.

(International Journal of Tuberculosis and Lung Disease 2007/11/3; 325-330)


INCIDENCE AND RISK FACTORS OF MAJOROPPORTUNISTIC INFECTIONS AFTER INITIA-TION OF ANTIRETROVIRAL THERAPY AMONGADVANCED HIV-INFECTED PATIENTS IN ARESOURCE-LIMITED SETTING (NO. 217)

W. Manosuthi, A. Chaovavanich, S. Tansuphaswadikul, W.Prasithsirikul

Bamrasnaradura Infectious Diseases Insitute, Ministry of PublicHealth, Nonthaburi 11000, Thailand; Faculty of MedicineRamathibodi Hospital, Mahidol University, Bangkok 10400,Thailand.

Key words : Antiretroviral therapy, HIV, Immune reconstitution,Incidence, Opportunistic infections, Risk factors, Tuberculosis

Objective : To study incidence, risk factors, and impactof major opportunistic infections (Ols) after initiation of antiretroviraltherapy (ART).

Methods : A retrospective cohort study was conductedamong nave HIV-infected patients who were initiated ART duringJanuary 2003 December 2004. All patients were followed until 15months after ART.

Results : There were 793 patients with mean +SD age of35.2 +7.4 years and 56.3% male. Median (IQR) CD4 was 26 (9-78)cells/mm3. Of 793 patients, 61 (8%) patients developed 81 episodesof Ols after ART. These included tuberculosis (48.1%), CMV retinitis(19.8%). MAC infection (14.8%), PCP (9.9%), cryptococcosis(6.2%) and penicilliosis (1.2%). Overall incidence of new episodeof Ols after ART was 8.0% during the first year of ART. Probabilitiesof Ols at 1,2,3,6 and 12 months after ART were 2.6%, 4.0%, 5.3%,6.9% and 8.0% respectively. Baseline CD4 < 50 cells/mm3, malegender, and low body weight were associated with higher incidenceof Ols after ART (P < 0.05).

Conclusions : Most of new episodes of major Ols developwithin the first three months after ART. Tuberculosis is the mostfrequent Ols in this situation. The substantial increase of new episodeof Ols after ART was observed among HIV-infected patients withCD4 cell counts < 50 cells/mm3 at ART initiation. 2007 TheBritish Infection Society.

(Journal of Infection 2007/55/5; 464-469)

INCIDENCE AND RISK FACTORS OF NEVIRA-PINE-ASSOCIATED SKIN RASHES AMONGHIV-INFECTED PATIENTS WITH CD4 CELLCOUNTS < 250 CELLS/MU L (NO. 218)

W. Manosuthi, S. Sungkanuparph, S. Tansuphaswadikul, Y.Inthong

Department of Medicine, Menistry of Public Health,Bamarasnaradur Infection Dission, Nonthaburi, Thailand;Department of Medicine, Ramathibodi Hospital, MahidolUniversity, Bangkok 10400, Thailand.

The objective of the study was to determine cumulative incidenceand risk factors of nevirapine (NVP) associated rashes that lead toNVP discontinuation among HIV-infected patients with CD4 < 250cells/mu L. A retrospective cohort study was conducted amongantiretroviral-nave HIV-infected patients who had baseline CD4 .05) 2006 by the InfectiousDiseases Society of America. All rights reserved.

(Clinical Infectious Diseases 2007/44/1; 141-144)

NO DIRECT HEPATOTOXIC POTENTIALFOLLOWING A MULTIPLE-LOW DOSE PARAQUATEXPOSURE IN RAT AS RELATED TO ITSBIOACCUMULATION (NO. 229)

V. Podprasart, J. Satayavivad, S. Riengrojpitak, P. Wilairat, W.Wananukul

Graduate Program in Toxicology, Faculty of Science, MahidolUniversity, Bangkok 10400, Thailand; Department ofPharmacology, Faculty of Science, Mahidol University, Bangkok10400, Thaland; Department of Pagthobiology, Faculty ofScience, Mahidol University, Bangkok 10400, Thailand;Department of Chemistry, Faculty of Science, Mahidol University,Bangkok 10400, Thailand; Division of Pharmacology andToxicology, Department of Medicine, Faculty of Medicine,Ramathibodi Hospital, Mahidol University, Bangkok 10400,Thailand; Department of Medical Science, Ministry of PublicHealth, Bangkok 1100, Thailand.

Key words : Paraquat, Hepatotoxicity, Enzymes, Accumulation, CYP

Paraquat (PQ) is a well-known toxic bipyridyl herbicidecommonly used in agricultural countries. Pulmonary toxicity is themain cause of death but damage to other organs has also been reported.PQ is also classified as a direct hepatotoxicant following an acutehigh dose exposure. The evidence of multi-low dose toxicity of PQwas scarce. Therefore, the aim of this study was to examine theeffect of multiple low doses of PQ on the liver function andxenobiotic-metabolizing enzyme activities including CYP1A1, 2E1,and 3A4, and to correlate the effects with its tissue accumulation.PQ, at the dose range 4.0-6.0 mg/kg day, was subcutaneouslyadministered to male Wistar rats for seven consecutive days. Theprominent feature of toxic response was lung toxicity. Interestingly,PQ-treatment caused a dose- and time-dependent reduction of plasmatransaminase activity. Hypobilirubinemia and hypoalbuminemia werealso observed without significant alteration in the liver morphology.Of all the xenobiotic-metabolizing enzymes being studied, only theactivity of CYP1A1 related 7-ethoxyresorufin-O-deethylase wasreduced following the highest dose of PQ administration. Plasmaand tissue concentrations and accumulation of PQ analyzed by HPLCwere dose-dependent showing much higher concentration(approximately 13 times) in the lung than that in the liver whereas itwas undetectable in the plasma at the same time point. It can beconcluded that multi-low dose PQ might affect certain syntheticfunction of the liver or activity of some hepatic xenobiotic-metabolizing enzymes. Minimal PQ accumulation in the liver is oneof the explanations for the lack of cytotoxic hepatic injury in thisstudy. Plasma PQ concentration may not be a good marker ofexposure and toxicity after a prolonged exposure to PQ.

(Toxicology Letters 2007/170/3; 193-202)

OPTIONS FOR A SECOND-LINE ANTIRETRO-VIRAL REGIMEN FOR HIV TYPE 1-INFECTEDPATIENTS WHOSE INITIAL REGIMEN OF AFIXED-DOSE COMBINATION OF STAVUDINE,LAMIVUDINE, AND NEVIRAPINE FAILS (NO. 230)

S. Sungkanuparph, W. Manosuthi, S. Kiertiburanakul, B.Piyavong

Faculty of Medicine Ramathibodi Hospital, Mahidol University,Bangkok, Thailand; Bamrasnaradura Infectious DiseasesInstitute, Ministry of Public Health, Nonthaburi, Thailand;Division of Infectious Diseases, Department of Medicine, Facultyof Medicine Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand.

Background : A fixed-dose combination of stavudine,lamivudine, and nevirapine is extensively used as an antiretroviralregimen in developing countries because of its affordability.Virological failure with this regimen has become more common, anda second-line regimen needs to be prepared in the national program.

Methods : Genotypic resistance testing was conductedamong human immunodeficiency virus type 1 (HIV-1)-infectedpatients who experienced treatment failure with their firstantiretroviral regimen (a fixed-dose combination of stavudine,lamivudine, and nevirapine) during 2003-2005. Patterns of resistancmutations and options for a second-line regimen were studied.

Results : We studied 98 patients (mean age, 35.2 years),of whom, 63% were male. The median duration of antiretroviraltherapy was 20 months. The median HIV-1 RNA load at the time ofvirological failure detection was 4.1 log copies/mL. The prevalencesof patients with + 1 major mutation conferring drug resistance tonucleoside reverse-transcriptase inhibitors and nonnucleoside reverse-transcriptase inhibitors were 95% and 92% respectively. M184V wasthe most common nucleoside reverse-transcriptase inhibitor resistancemutation (observed in 89% of patients). Thymidine analoguemutations. K65R, and Q151M were observed in 37%, 6%, and 8%of patients, respectively. Patients with an HIV-1 RNA load of > 4log copies/mL at the time of treatment failure had higher prevalenceof thymidine analogue mutations (P = .041), K65R (P = .031), andQ151M (P = .008) mutations. The second-line regimen wasdetermined in a resource-limited setting where tenofovir andenfuvirtide are not available; the options were limited for 48% ofpatients.

Conclusions : After experiencing treatment failure witha fixed-dose combination of stavudine, lamivudine, and nevirapine,almost all patients have lamivudine and nonnucleoside reverse-transcriptase inhibitor resistance. The options for a second-lineregimen are limited for one-half of these patients. In resource-limitedsetting where availability of antiretroviral agents is limited, strategiesfor prevention of HIV-1 resistance are crucial. Early detection ofvirological failure may provide more options and better treatmentoutcomes. 2006 by the Infectious Diseases Society of America. Allrights reserved.

(Clinical Infectious Diseases 2007/44/3; 447-452)


OSTEOPOROSIS : THE ROLE OF GENETICS ANDTHE ENVIRONMENT (NO. 231)

B. Ongphiphadhanakul

Department of Medicine, Faculty of Medicine RamathibodiHospital, Mahidol University, Bangkok 10400, Thailand.

Osteoporosis is partly genetically determined. The geneticsof osteoporosis is polygenic in nature with multiple commonpolymorphic alleles interacting with each other and environmentalfactors to determine bone mass. A number of studies have attemptedto dissect the genetic factors responsible for the pathogenesis ofosteoporosis using genome-wide scanning and the candidate geneapproach. However, the results of such studies among differentpopulations have been mostly inconsistent, suggesting geneticheterogeneity of osteoporosis. It is likely that the cohort of genesindicating predisposition to the risk of osteoporosis may be differentamong populations with different ethnic backgrounds. The successfulidentification of susceptibility genes for osteoporosis should proveto be helpful in targeting preventive and therapeutic measures toindividuals at higher risk and to render the effort more cost-effective.Information with regard to genetic variations is also likely to be usefulin targeting preventive or therapeutic measures to subjects geneticallydetermined to have better responsiveness. Intestinal calciumabsorption is dependent on vitamin D receptor gene polymorphisms.Skeletal responsiveness to estrogen, particularly at lower doses, isrelated to polymorphisms in the estrogen receptor gene. Recently,circulating homocysteine levels have been shown to be associatedwith fracture risk. Folate and vit

abdominal obesity and coronary disease in thai men

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