A1280 AGA ABSTRACTS

5847

LOSS OF PLASMIDS FROM HELICOBACTER PYLORI UPONCONVERSION TO COCCOID FORM.Darren Morton. Karna D. Bardhan, Rotherham Gen Hosp, Rotherham ,United Kingdom.

INTRODUCTION In certain culture conditions the bacilliary morphologyof fl. pylori (HP) modifies to a coccoid structure. This alteration mayrepresent a step in the transmission of the infection, though has yet to besuccessfully recovered by culture . Earlier , we demonstrated a clear reduc­tion in DNA-associated fluorescence upon coccoid transformation (Gas­troenterology 1998:114;G0961). and an alteration in genus specific DNAmelting point (Gut 1999:44;W34I ). We have now investigated if carriageof plasmids, found in helical HP strains, is affected during conversion tococcoid bacterial form. METHODS 100 consecutive HP strains, wereisolated on solid media (bioMerieux Ltd. UK), for analysis in this study.Strains which initially demonstrated plasmids were further processed toproduce parallel cultures aged 3, and 18 days old. Gram stain microscopywas used to confirm the morphology of the HP cells after the prolongedincubat ion period. Bacterial plasmid DNA was extracted from helical andcoccoid parallel cultures using standard methods then visualised and sizedafter electrophoresis . RESULTS 36 (36%) of HP strains carried one ormore plasmids. Plasmid sizes ranged from 1.45-7.8MDa. 13 (36%) strainscarried a single plasmid; 9 (25%) carried 2 plasmids; 2 (6%)carried 3plasmids; 10 (27%)carried 4 plasmids and 2 (3%)strains carried 5 or 6plasmids each. Repeated culture showed plasmid carraige was stable how­ever, after coccoid conversion no plasmids could be extracted from anyplasmid bearing strain. CONCLUSIONS The range of plasmid sizes ex­tracted from the strains under test was broad. though generally small. Uponcoccoid conversion these HP strains appeared to lose all plasmid DNA.Although no function has been assigned to these plasmids, it is reasonableto assume that their loss may have a significant effect on bacterial strainsurvival. Loss of plasmid DNA during coccoid conversion appears tomirror the previously demonstrated loss of chromosomal DNA, suggestin§the same mechanism of DNA loss may be responsible. Th" work was su pporte

bv ,II f' Hardhan Research & Edu cation Trus t (BR ET)

5848EPINEPHRINE INJECTION FOR ENDOSCOPIC HEMOSTASISIN PATIENTS WITH BLEEDING PEPTIC ULCERS: A RETRO­SPECTIVE STUDY.Karim B. Muhammad , Amir Sherwani , Mark Welfare, Roger Barton,Irving Cobden, Seamus B. Kelly, North Tyneside Gen Hosp, Newcastle,United Kingdom.

Aim: To determine the outcome of endoscopic hemostasis using epineph­rine injection in patients with bleeding peptic ulcers, in terms of: initialhemostasis, clinical rebleed, second injection, requirements for emergencysurgery. blood transfusion, hospital stay and mortality . Background : En­doscopic hemostasis is now a well established first line treatment forbleeding peptic ulcers, with surgical intervent ion being reserved for thosewho continue to bleed or rebleed . Epinephrine injection for endoscopichemostasis has a success rate up to 98%. Simplicity, low cost and avail­ability, with reduced risk of tissue injury and decreased incidence ofrecurrent bleeding make it an ideal choice for treatment. Methods: Aretrospective study reviewed the results of epinephrine injection in 116patients (M:F= 72:44) with actively bleeding peptic ulcers, admitted to ateaching hospital between 1994 and 1999. Endoscopy was performedwithin 24 hours in 86 patients (71.6%). 38 patients (32.8%) were shockedon admission and were resuscitated prior to endoscopy . Results: Patientshad a mean age of 69 years(range 22-77 years). Ninety three patients wereaged ;,:,60 years and twenty five patients were aged ;,:,80 years. Seventypatients (60.4%) had severe systemic disease and 63 patients (54.3%) werelaking aspirin or non-steroidal anti-inflammatory drugs or both. Thirtyeight patients (32.8%) were shocked on admission. Endoscopy findingsincluded: 6 spurters (5.2%), 27 oozing vessels (23.3%), 49 visible vessels(42.2%), 20 adherent clots (17.2%),9 flat pigmented spots (7.8%) and 2clean based ulcers (1.7%). Initial endoscopic hemostasis was achieved in109 patients (94%). Clinical rebleed ing occurred in 26 patients (22.4%).Fourteen patients (12.1%) required a second injection and twenty patients(17.2%) required surgery. Ninety nine patients (85.3%) required bloodtransfusion (mean 5.3 units). The mean hospital stay was 14 days. Twentyone patients (18.1%) died in hospital. The mean age of the patients whodied was 78 years. Conclusion : The study confirms that epinephrine injec­tion is highly effective in stopping actively bleeding peptic ulcers. Highermortality, longer hospital stay and surgery could be attributed to old ageand severe systemic disease in our series of patients.

5849CORRELATION BETWEEN H. PYLORI GENOTYPE AND ALCO­HOL DEHYDROGENASE ACTIVITY.Ranadev Mukherjee, Nasar Sabra, Amel Ahmed, Sai L. Chandaran, AnmRahman, Mitra Tavakolli, Cornell R. Allen. Hassan Ashktorab, Duane T.Smoot. Howard Univ, Washington, DC.

Background: H. pylori is a gram negative bacterium which has beenassociated with chronic gastritis and peptic ulcer disease. Many virulenceassociated genes have been identified for H. pylori , including cagA, vacA,and iceA. However, it remains unclear how much they contribute to H.pylori induced cell injury. H. pylori also possesses an alcohol dehydroge-

GASTROENTEROLOGY Vol. 118 . No.4

nase (ADH), which converts alcohol to acetaldehyde, which could con­tribute to gastric cell injury, especially in alcoholic patients. The presentstudy was undertaken to correlate ADH activity in different H. pyloristrains with H. pylori cagA status, vacA subtype and bacterial cytotoxicity.Methods: Fresh H. pylori isolates from African American patients, endo­scoped at Howard University Hospital, were cultured on trypticase soy agarwith sheep's blood. Each isolate was subcultured once after selecting smallcolonies for further culture. DNA was isolated from subsequent cultures forPCR analysis for cagA status and vacA alleles. In addition, isolates weresonicated to obtain cytosolic protein, then centrifuged at lOO.OOOg at 4°C.The supernatant was then assayed for cytosolic ADH activity. Strains wereexposed to AGS cells overnight then assayed for sublethal cytotoxicity bymeasuring release of LDH into the culture medium. Results: The vacA s Igenotype was common in African Americans patients with upper G./.symptoms (90%). The vacA s2lm2 genotype was rare in African Ameri­cans patients at our institution (10%). The vacA sllml genotype is mostcommon in African American patients at our institution. H. pylori isolatesdisplayed a wide range of ADH activity, with some strains showing noactivity at all. Out of 18 strains tested for ADH activity, 12 were cagA-posand showed a mean ADH activity of 163 Ulng protein as compared with 6cagA-neg strains which showed an average activity of 146 U1ng protein.Also, there was no correlation between ADH activity and vacA alleles(s l ,s2,ml ,m2). There was a direct correlation between LDH release intoculture medium and ADH activity. Conclusion: At our institution thepredominant H. pylori genotype in African Americans is cagA-pos andvacA sl/ml, which differs from published reports in Vietnamese subjects(sllm2), Greeks (slim)) and Lebanese (s2/m2 and s2m)). These findingssuggest that H. pylori ADH activity does not correlate with cagA status orvacA subtype. However. we do find a trend for increased cytotoxicity instrains with high ADH activity. ADH activity may well contribute to H.pylori cytotoxicity, however. additional studies are needed.

5850INITIAL POTENCY OF LANSOPRAZOLE AND OMEPRAZOLE·MUPS ON PENTAGASTRIN·STIMULATED GASTRIC ACID SEeCRETION - A PLACEBO-CONTROLLED STUDY IN HEALTHYVOLUNTEERS.Peter Muller, Mehmet A. Goksu, Winfried Am Fuchs, Frank Schluter,Bernd Simon. Krankenhaus Salem, Heidelberg, Germany; Takeda PharmaGmbH, Aachen, Germany; Kreiskrankenhaus, Schwetzingen, Germany.

Aim: The purpose of this study was to compare the efficacy of differentdoses of lansoprazole and omeprazole-MUPS and to find equipotent dos­ages of the two proton pump inhibitors. Methods: 12 Hp-negative malesubjects entered this placebo-controll ed, six-way cross-over study. Duringthe dosing periods of two days durat ion, one of the following treatmentswas administered: 10 mg or 20 mg omeprazole-MUPS, or 7.5 mg or 15 mgor 30 mg lansoprazole , or placebo. The wash-out period between eachphase was one week. The treatment order was randomised . Pentagastrin­stimulated gastric acid secretion was determined by means of aspiration ofthe stomach contents in 15-min intervals between 12.5 and 14.5 hours afterdosing. The aspirated volume was titrated, the volume and the pH weredocumented . Acid output was calculated in mmoll15 min and expressed asa percentage of the placebo values. Results: Mean relative gastric acidsecretion is shown in the table as mean :t standard deviation. The two­sided 95% confidence interval for the mean is given in square brackets.Conclusion: Lansoprazole 15 mg and omeprazole-MUPS 20 mg haveabout the same potency to suppress pentagastrin-stimulated secretion ofgastric acid on the first two days. The potency of lansoprazole 30 mg ishigher than that of lansoprazoJe 15 mg and omeprazole-MUPS 20 mg.Neither the effect of lansoprazole 7.5 mg. nor that of omeprazole-MUPS 10mg, is clearly different from placebo on the first two days. The inter­individual variation of acid suppression is considerably higher after ome­prazole than after lansoprazole . The effect of lansoprazole is alreadypronounced on the first day, whereas the effect of omeprazole -MUPS issignificantly different from placebo only on the second day.

Mean relative (% ofpacebo) gastricacidsecretion rate. ITT analysis.

Drug Day 1 Day 2

Lansoprazole 7.Smg 109± 38[84; 133] 102± 43[75; 1301Lansoprazole 15mg 75± 37[52; 991 62 ± 37[38; 85]Lansoprazole 30mg 48± 35[26:7O] 37± 22[23; 50]Omeprazole-MUPS 10mg 92± 49[61; 123) 93± 55[58; 128)Omeprazole-MUPS 20mg 78± 49(47: 109] 56+ 48[24; 89]

5851

A COMPARISON OF THE ALKALINE REFLUX CHARAC­TERISITCS OF OESOPHAGITIS AND BARRETT'S OESOPHA­GUS.Frank R. Murphy. Dominic Foy, Christopher Sheen, Alan Macfarlane, PaulJ. Winwood, Royal Bournemouth Hosp, Bournemouth, United Kingdom.

It is generally accepted that Barrett ' s oesophagus is an acquired conditioncaused by chronic reflux of gastric, duodenal contents or both. Adenocar­cinomas complicating Barrett 's oesophagus usually have adjacent areas ofepithelium that show dysplasia . The trophic agent that promotes dyspla sticchange is unknown. Aim: To determine the amount of alkaline exposure in