The impact of pseudomembrane formation on the outcome of Clostridium difficile-associated disease.

PURPOSE: Although pseudomembranes are the hallmark manifestation of Clostridium difficile-associated diarrhea (CDAD), there are scant data specifically addressing their impact on the clinical outcome. We investigated whether the formation of pseudomembranes predicts a worse CDAD outcome. METHODS: CDAD patients hospitalized during 2010 underwent sigmoidoscopy and were followed prospectively. In addition, all hospitalized CDAD patients in the period 01/2000-12/2009 who underwent lower endoscopy were retrospectively identified and their charts reviewed. Patients with detectable pseudomembranes on endoscopy were compared to those in whom pseudomembranes were absent. Thirty-day mortality and a composite outcome comprised of mortality within 30 days of diagnosis, admission to the intensive care unit (ICU), colectomy, peritonitis, hemodynamic instability, or respiratory insufficiency were addressed. Additional clinical outcomes used for comparison between the two groups were 60-day mortality, duration of hospitalization, and the failure of metronidazole and vancomycin. RESULTS: A total of 117 CDAD patients (mean age 62.9 ± 19 years) who underwent lower endoscopy were included; 46 with pseudomembranes and 71 without. Seven out of the 46 patients with pseudomembranes died within 30 days compared to 9/71 in the non-pseudomembrane group [odds ratio (OR) 1.2, 95% confidence interval (CI) 0.4-3.6, P = 0.8]. Similarly, there was no correlation between the occurrence of pseudomembranes and the rate of the composite adverse outcome (P = 0.6). In contrast, acute renal insufficiency (OR 15, 95% CI 3.2-72, P < 0.001) and hypoalbuminemia (OR 5.7, 95% CI 1.8-18, P = 0.002) were both independently predictive of a severe clinical outcome. CONCLUSIONS: Our findings suggest that the presence of pseudomembranes is not associated with an adverse outcome in CDAD patients.

Fibrotest or Fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C.

Non-invasive modalities to estimate fibrosis stage are desirable in hepatitis C-infected haemophilia patients. Previous studies found a high rate of significant fibrosis both by Fibrotest (FT) and Fibroscan (FS) in these patients. To estimate liver fibrosis and to assess the concordance between FT and FS in hepatitis C-infected haemophilia patients. FT and FS were performed at different laboratories and were unaware of the results of the alternative test. Three successive liver stiffness measurements (LSM) were performed at different sites on the liver. Two-validated algorithms were used to improve evaluation of fibrosis by non-invasive methods. Fifty-seven hepatitis C-infected haemophilia patients were evaluated by FT and FS. Acquisition of LSMs was not feasible in two patients: obesity--one, surgical scars--one. Fibrosis stage > or=F2, > or =F3 or =F4 were estimated in about a half, about a third and in 15-20% of the evaluated patients by FS and FT respectively. The corresponding concordance rates and kappa score for fibrosis stage > or =F2, > or =F3 or =F4 between FT and FS were 62%, 69%, 85% and 0.24, 0.32, 0.44 respectively. Using the two aforementioned algorithms, additional 14 patients could be reliably estimated for fibrosis stage > or =F2. High proportion hepatitis C-infected haemophilia patients were estimated with significant or advanced stages of liver fibrosis using both tests. Nevertheless, the agreement between modalities was only fair and improved with more advanced stages of fibrosis. Practical algorithms for the accuracy of FT and FS may improve reliable evaluation of fibrosis in this population.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Treatment of hepatitis C in patients with haemophilia - the Israeli National Hemophilia Center experience.

Treatment with pegylated interferon (Peg-IFN) and ribavirin, now the standard of care, has been shown to achieve sustained viral response (SVR) in up to 60% of patients with hepatitis C (HCV). Studies of response to this combination in HCV-infected haemophilia patients are scarce. The aim of the study was to report the results and safety of interferon/ribavirin treatment in HCV and HCV-/HIV-infected patients at the Israeli National Hemophilia Center. A retrospective observational cohort study was conducted on haemophilia patients infected with HCV or HCV/HIV. Patients received combination of Peg-IFN and ribavirin. Few were still treated with standard interferon. The primary end-point was sustained viral response (SVR). The secondary end-point was safety, with emphasis on increased bleeding episodes. Some 18/43 (42%) HCV mono-infected haemophilia patients achieved SVR. Relapse occurred in 14 (33%), while 11 patients (25%) were non-responders. SVR was achieved among 17/37 (46%) naïve patients receiving Peg-IFN and ribavirin. Among patients with genotype-1, SVR was achieved in 12/36 (33%) and 11/30 (37%) in the whole group and Peg-IFN treated naïve patients, respectively. In HCV/HIV co-infected patients only 1 patient achieved SVR. Severe anaemia occurred in 14/50 (28%) patients, four received erythropoietin. None maintained stable haemoglobin levels. Two patients had significant bleeding episodes. In our cohort of haemophilia patients, SVR was achieved in a lower than expected rates. A relatively high relapse rate in the HCV mono-infected patients and a very high non-response rate in the HCV/HIV co-infected patients were observed as anticipated. Anaemia was a major side effect and the use of growth factors seemed unrevealing.

Clinical trial: randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis.

BACKGROUND: Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema. AIM: To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam. METHODS: In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index > or = 4] were randomized to receive 2 x 1 g/30 mL low-volume (n = 163) or 2 x 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI < or = 4) at the final/withdrawal visit (per-protocol). RESULTS: 330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems. CONCLUSIONS: Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation.

Proof-of-concept study of the Aer-O-Scope omnidirectional colonoscopic viewing system in ex vivo and in vivo porcine models.

BACKGROUND AND STUDY AIMS: The limited angle of view of standard colonoscopes means that lesions can be missed. A multidirectional viewing system (OmniVision) has been developed recently and has been incorporated into the Aer-O-Scope (GI View Ltd., Ramat Gan, Israel), a disposable, self-propelling, and self-navigating colonoscope. The objectives of this study were to qualitatively assess the sensitivity of this viewing system in an ex vivo porcine polyp induction model, and to demonstrate its feasibility and safety in live pigs. MATERIALS AND METHODS: For the ex vivo part of the study, six red metal beads of various sizes were randomly sewn into the mucosa of an unfolded, 2-meter-long porcine colonic segment. Seven passages of the Aer-O-Scope were video-recorded separately and blindly reviewed by six experienced gastroenterologists. The sensitivity of the Aer-O-Scope to detect beads of various sizes was calculated. For the in vivo experiment, in a repeated-measure study, nine female domestic pigs were examined with the Aer-O-Scope with the OmniView optics, followed immediately by examination with standard optical colonoscopy in order to assess the integrity of the colonic mucosa. RESULTS: In the ex vivo study the sensitivity of the Aer-O-Scope was 97.6% (CI 94.0%-100%) for any bead (i. e. any "polyp"). The rate of polyp detection was similar for the six endoscopists, and was consistent for all bead sizes. The average false-positive rate was 0.3% polyps per run (SD 0.61%). The mean time taken for the video assessment was 8.0 minutes (SD 4.0 minutes). In the in vivo experiments with the Aer-O-Scope, both the front-viewing and omnidirectional-viewing systems were functional in all cases. The colon in front of the optical capsule was well distended and a complete and meticulous inspection of the entire colonic mucosa was performed in all the pigs. There were no adverse events. CONCLUSIONS: The OmniVision system allows for a highly sensitive inspection of the colonic mucosa without the need for tip manipulation. Clinical studies are warranted in order to validate these results in humans.

The feasibility and risk of early colonoscopy in acute diverticulitis: a prospective controlled study.

BACKGROUND AND STUDY AIM: Following acute diverticulitis, colonoscopy is advised to rule out malignancy. Commonly, the colonoscopy is postponed to avoid the potential risk of perforation. In a previous pilot, noncontrolled study, we showed that early colonoscopy is feasible in patients with acute diverticulitis. This randomized controlled trial compared early and late colonoscopy in hospitalized patients with acute diverticulitis. PATIENTS AND METHODS: 154 patients diagnosed with acute diverticulitis were hospitalized between January 2004 and June 2006. Of these, 35 patients were excluded because of either free perforation or pericolic air on computed tomography (CT), and another 18 because they had undergone colonoscopy in the previous year. The remaining 101 patients were offered the possibility of participating in the study, with random allocation to either early in-hospital colonoscopy or late colonoscopy, 6 weeks later. Randomization was refused by 15 patients, and 86 were included in the study. RESULTS: 45 patients were randomly allocated for early colonoscopy and 41 for late colonoscopy. Three and 10 did not present for the examination, in the early and late group respectively. The cecum could not be reached in eight and three patients from the early and late groups, respectively. The colonoscopy revealed polyps in five patients, two in the early group and three in the late group. No malignancy was detected. There were no complications in either group. CONCLUSIONS: Early colonoscopy in acute diverticulitis is feasible and safe in the absence of pericolic air on CT, and has greater compliance. However, no added value is apparent compared with the CT scan currently used.

Review article: capsule endoscopy - are all small intestinal lesions Crohn's disease?

Capsule endoscopy is the gold-standard examination for the diagnosis of Crohn's disease (CD) of the small intestine. Its incremental yield over other imaging modalities is above 30%. It is important to keep in mind that over 10% of healthy subjects demonstrate mucosal breaks and erosions in their small intestinal mucosa. Thus, one should refrain from diagnosing CD based on the existence of a few erosions and ulcers of the small intestine. Such erosions and ulcers may in fact be the result of non-steroidal anti-inflammatory drug intake and other pathological conditions such as lymphoid hyperplasia, lymphoma and radiation enteritis. Non-steroidal anti-inflammatory drug intake should, therefore, be excluded as a cause prior to relating the presence of lesions to CD. Misdiagnosis of CD may be harmful to the patient because if unresponsive, intensification of therapy may occur and occasionally an unnecessary operation may be performed. At the same time, the patient may also be deprived of the appropriate therapy for the treatment of their condition.

Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.

BACKGROUND: Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. AIM: To compare the therapeutic efficacy, tolerability and safety, and patient's preference of budesonide foam vs. budesonide enema. METHODS: Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) were eligible for this double-blind, double-dummy, randomized, multicentre study. They received 2 mg/25 mL budesonide foam and placebo enema (n = 265), or 2 mg/100 mL budesonide enema and placebo foam (n = 268) for 4 weeks. Primary endpoint was clinical remission (clinical activity index < or = 4) at the final/withdrawal visit (per protocol). RESULTS: A total of 541 patients were randomized--533 were evaluable for intention-to-treat analysis and 449 for per protocol analysis. Clinical remission rates (per protocol) were 60% for budesonide foam and 66% for budesonide enema (P = 0.02362 for non-inferiority of foam vs. enema within a predefined non-inferiority margin of 15%). Both formulations were safe and no drug-related serious adverse events were observed. Because of better tolerability and easier application most patients preferred foam (84%). CONCLUSION: Budesonide foam is as effective as budesonide enema in the treatment of active ulcerative proctitis or proctosigmoiditis. Both budesonide formulations are safe, and most patients prefer foam.

Typhoid hepatitis with immunoglobulins and complement deposits in bile canaliculi.

Documented typhoid fever in a 26-year-old patient was complicated by acute hepatitis with unusually profound jaundice. Liver biopsy revealed focal cell necrosis, mononuclear cell infiltration. Kupffer cell proliferation, and mild cholestasis. Immunofluorescent studies of the liver biopsy revealed deposits of IgG, IgA, IgM, and C3 in the bile canaliculi, suggesting a role for damage by immune complexes in typhoid hepatitis.

Cancer family syndrome of Lynch.

This report describes a family in whom eight cancers (six colonic and two endometrial) occurred in seven relatives. The colonic cancer was diagnosed in five of the six affected patients at an unusually young age, had a predilection for the proximal colon, and was of the mucinous type in four patients. Polyposis was not found in any colon. The occurrence of cancer in this kindred is characteristic of the "cancer family syndrome" of Lynch.

Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn's disease.

BACKGROUND: Oral methotrexate and folic acid are partly absorbed by a common intestinal transporter. AIM: : To determine the relative bioavailability of oral low-dose methotrexate administered with and without concomitant folic acid vs. subcutaneous administration in patients with stable Crohn's disease. METHODS: Ten patients were randomized to receive their regular maintenance dose of methotrexate (15-25 mg) for three consecutive weeks: orally, orally with 5 mg folic acid or subcutaneously. Blood samples were drawn at specified intervals during 24 h, and methotrexate levels were determined by fluorescence immunoassay. Areas under the curve extrapolated to infinity (AUC infinity ) were compared between the three routes. RESULTS: The geometric mean AUC infinity values (95% confidence intervals) were 360 nmol x h/L (301-430 nmol x h/L), 261 nmol x h/L (214-318 nmol x h/L) and 281 nmol x h/L (209-377 nmol x h/L) per milligram of methotrexate administered for subcutaneous, oral and oral with folic acid administration, respectively (P < 0.05 and P < 0.01 for oral with folic acid and oral vs. subcutaneous administration, respectively). The geometric mean relative bioavailabilities (95% confidence intervals) were 0.73 (0.62-0.86) and 0.77 (0.60-0.99) for oral and oral with folic acid administration, respectively (difference not significant). CONCLUSIONS: In patients with stable Crohn's disease, the oral bioavailability of methotrexate is highly variable and averages 73% of that of subcutaneous administration. Concomitant folic acid has no significant effect on the bioavailability. Dose adjustments based on individual pharmacokinetic assessment should be considered when switching patients from parenteral to oral therapy.

Coincidence of sarcoidosis and amyloidosis.

Amyloidosis was diagnosed in a patient with sarcoidosis. There was no evidence of any other disease known to be associated with amyloidosis. The joint occurrence of amyloidosis and sarcoidosis appears to be extremely rare, and to our knowledge, this is the second such patient to be reported. Whether the association of the two diseases in this patient represents a causal relationship remains an open question.

The I1307K APC polymorphism: prevalence in non-Ashkenazi Jews and evidence for a founder effect.

A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (approximately 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

The effect of chronic captopril administration on hepatic blood flow of the rat.

The effect of chronic captopril administration on indocyanine green (ICG) clearance and hepatic extraction has been studied in the rat using the intact liver for ICG clearance and the isolated perfused liver for ICG extraction. The captopril was added to the drinking water to give a calculated daily intake from 0-45 mg kg-1. Hepatic clearance of ICG was dose related from 16.5 +/- 2.4 (control) to 7.2 +/- 1.6 mL min-1 kg-1, respectively. The hepatic extraction of ICG was not significantly different (37 +/- 6%) from the control value in groups on 4 and 45 mg kg-1 daily. Since ICG clearance and extraction are dependent on hepatic blood, a change in ICG clearance without a change in the extraction reflects a similar change in the hepatic blood flow. This remained unchanged at daily captopril intakes of 1 and 4 mg kg-1 and decreased when the daily intake was 10 mg kg-1 or higher. If these results in the rat are applicable to man, the chronic administration of therapeutic doses of captopril (0.5-2 mg kg-1) will not affect the hepatic blood flow.

The role of short-term multilumen duodenojejunal manometry in patients with intestinal motor dysfunction.

Short-term duodenojejunal manometry, using a multilumen perfused tube, was performed in 12 patients with symptoms of motor dysfunction, 6 patients with irritable bowel syndrome and predominant diarrhea and 6 patients with chronic constipation. Ten healthy individuals served as controls. The durations, in minutes, of the various phases of the migratory motility complex in the three groups were: phase I: 24.4 +/- 22.1, 26.9 +/- 17.3, and 27.2 +/- 18.5; phase II: 86.7 +/- 25.2, 132 +/- 93, and 73.1 +/- 40.8, and those of phase III: 6 +/- 2.5, 6.8 +/- 5, and 6.4 +/- 1.7, respectively. The differences between patients and controls were not statistically significant. Variables of contractions of phase III in the different groups were: frequency (per minute): 10.9 +/- 0.8, 10.7 +/- 0.4, and 11.3 +/- 0.4; Summation of amplitudes per minute: 205.2 +/- 55.7, 288 +/- 57.9, and 337.8 +/- 76.5; Mean amplitude (mm Hg): 19.1 +/- 4.2, 28.6 +/- 5, and 33.5 +/- 7.1, respectively. Results in the patient groups were not significantly different from controls. Short-term duodenojejunal manometry was normal in patients with irritable bowel syndrome and in those with chronic constipation.

The effect of culture results for Helicobacter pylori on the choice of treatment following failure of initial eradication.

BACKGROUND: Current treatment for the eradication of Helicobacter pylori in patients with peptic disease is based on the combination of antibiotic and anti-acid regimens. Multiple combinations have been investigated, however no consensus has been reached regarding the optimal duration and medications. OBJECTIVES: To assess the efficacy of two treatment regimens in patients with peptic ulcer disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal culture in patients failing previous treatment. METHODS: Ninety patients with established peptic ulcer and NUD (with previously proven ulcer) were randomly assigned to receive either bismuth-subcitrate, amoxycillin and metrnidazole (BAM) or lansoprasole, clarithromycine and metronidazole (LCM) for 7 days. Patients with active peptic disease were treated with ranitidine 300 mg/day for an additional month. RESULTS: Eradication failed in 8 of the 42 patients in the BAM group and in 2 of the 43 patients in the LCM group, as determined by the 13C urea breath test or rapid urease test (19% vs. 5%, respectively, P = 0.05). Five of these 10 patients were randomly assigned to treatment with lansoprazole, amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the other 5 patients were assigned to treatment with lansoprazole and two antibacterial agents chosen according to a susceptibility test. Eradication of H. pylori was confirmed by the 13C urea breath test. The same protocol (LAC) was used in all patients in the first group and in four of the five patients in the second group. The culture results did not influence the treatment protocol employed. CONCLUSIONS: Combination therapy based on proton pump inhibitor and two antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal culture testing for sensitivity of H. pylori to antibiotics is probably unnecessary before the initiation of therapy for patients with eradication failure.

Nimesulide-induced hepatitis and acute liver failure.

BACKGROUND: Nimesulide is a relatively new non-steroidal anti-inflammatory drug that is gaining popularity in many countries because it is a selective cyclooxygenase 2 inhibitor. Occasionally, treatment is associated with mild elevation of liver enzymes, which return to normal upon discontinuation of the drug. Several cases of nimesulide-induced symptomatic hepatitis were also recently reported, but these patients all recovered. OBJECTIVES: To report the characteristics of liver injury induced by nimesulide. PATIENTS AND METHODS: We report retrospectively six patients, five of them females with a median age of 59 years, whose aminotransferase levels rose after they took nimesulide for joint pains. In all patients nimesulide was discontinued, laboratory tests for viral and autoimmune causes of hepatitis were performed, and sufficient follow-up was available. RESULTS: One patient remained asymptomatic. Four patients presented with symptoms, including fatigue, nausea and vomiting, which had developed several weeks after they began taking nimesulide (median 10 weeks, range 2-13). Hepatocellular injury was observed with median peak serum alanine aminotransferase 15 times the upper limit of normal (range 4-35), reversing to normal 2-4 months after discontinuation of the drug. The remaining patient developed symptoms, but continued taking the drug for another 2 weeks. She subsequently developed acute hepatic failure with encephalopathy and hepatorenal syndrome and died 6 weeks after hospitalization. In none of the cases did serological tests for hepatitis A, B and C, Epstein-Barr virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings. CONCLUSIONS: Nimesulide may cause liver damage. The clinical presentation may vary from abnormal liver enzyme levels with no symptoms, to fatal hepatic failure. Therefore, monitoring liver enzymes after initiating therapy with nimesulide seems prudent.

Cimetidine and omeprazole do not affect cyclosporine disposition by the rat liver.

Cyclosporine has been used with increased frequency, occasionally in conjunction with cimetidine and omeprazole. The present study was undertaken to study a possible interaction between either of the two drugs and cyclosporine in the liver. The isolated perfused rat liver was used with recirculation of perfusate for 150 min. 6 experiments were performed with each of the following: cyclosporine alone, cyclosporine with cimetidine, and cyclosporine with omeprazole. Initial concentrations of cyclosporine, cimetidine and omeprazole were 600 micrograms/ml, 12.5 micrograms/ml, and 4.5 micrograms/ml, respectively. At 1 and 2 h of perfusion 1 micrograms of omeprazole was added to perfusate. Cyclosporine concentration was determined at 30 min intervals. Results at 150 min expressed as percentage of the initial concentration of cyclosporine were 59 +/- 3%, 55 +/- 6%, and 60 +/- 9% for cyclosporine alone, with cimetidine and with omeprazole, respectively. The elimination rate of cyclosporine by the liver did not change during the entire experiment with the addition of cimetidine or omeprazole. Thus, it is concluded that short administration of cimetidine or omeprazole will not affect cyclosporine metabolism by the liver.