In 109 patients with chronic diarrhea colonic biopsies were examined for the presence of specific microorganisms. A positive result was obtained in 48% of patients with ulcerative colitis, 50% with Crohn's disease, 21% with non-specific colitis and 36% with non-specific proctitis. Chlamydiae were found most frequently in all groups. Obligate enteropathogenic bacteria were isolated in only three cases of nonspecific colitis. Of the facultatively enteropathogenic organisms Klebsiella and Pseudomonas aeruginosa were isolated in 31% and 24%, respectively, of patients with ulcerative colitis, in 21% and 7% of patients with Crohn's disease, and in 10% and 6% of patients with non-specific colitis. Whereas chlamydial proctitis is a well-known disease, the results of this study point also to a possible pathogenic role of chlamydiae in the proximal colon. Facultatively enteropathogenic organisms causing acute diarrhea might have aetiologic relevance in some cases of chronic non-specific colitis.
The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (+/- SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10 +/- 0.07 and 0.50 +/- 0.20 micrograms/ml, respectively) and SZ (0.12 +/- 0.14 and 0.67 +/- 0.14 micrograms/ml, respectively). Urinary excretion of total AS (5-AS + AcAS), too, was similar (192 +/- 70 and 179 +/- 79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21 +/- 0.22 micrograms/ml; AcAS 0.83 +/- 0.40 micrograms/ml) and in 5 healthy volunteers (5-AS 0.28 +/- 0.14 micrograms/ml; AcAS 1.10 +/- 0.43 micrograms/ml). Urinary recovery of total AS averaged 20 +/- 6% (patients) and 27 +/- 10% (volunteers).(ABSTRACT TRUNCATED AT 250 WORDS)
Flumazenil, a new and specific benzodiazepine antagonist that appears to be free of intrinsic pharmacologic action, is extensively metabolized by oxidative processes and represents a high-clearance drug. Consequently, it could be anticipated that hepatic disease affects the elimination and oral bioavailability of flumazenil. Therefore, the pharmacokinetics of flumazenil was evaluated in eight patients who had moderate cirrhosis and in eight age-matched healthy volunteers after a single oral dose (30 mg) and after an intravenous dose (2 mg). The mean half-life (t1/2) was 0.8 versus 1.4 hours (p = 0.003) and total plasma clearance was 1201 versus 705 ml per minute (p = 0.009) for control subjects versus patients with cirrhosis. Bioavailability increased from the normal 28% to 65% (p = 0.001) in patients with hepatic dysfunction. Routine liver tests did not correlate with the elimination of flumazenil in individual patients. It can be concluded that elimination of flumazenil is impaired in patients who have stable alcoholic cirrhosis. Despite the relative wide margin of safety of flumazenil, somewhat lower doses could be effective in such patients if long-term oral use is anticipated.
Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.
A randomized controlled trial was performed to evaluate in Crohn's disease the clinical efficacy and safety of a higher dose of a new slow-release preparation of mesalazine (500 mg tablets). Twenty-four patients created with 3 g m esalazine/day were compared with 26 patients treated with sulfasalazine (3 g/day) and methylprednisolo n e ( initially 40 mg). All patients h ad active Crohn's disease diagnosed by endoscopy, sonograph y and radiology. Patients were ch aracterized before en try into the study and at two, fou r, e ight and 12 weeks of treatment by activity indices according to Best and van Hees, as well as by erythrocyte sedimentation rate, thrombocyte count, Broca index and serum a lbumin. All clinical and laboratory parameters were well matched for the two groups o f patients. During treatment with mesalazine and sulfasalazine/methylprednisolone, clinical remission could be observed in 20 of 24 patients (83%) and 23 o f 26 patients (88%), respectively. There was no difference between the two groups except for a s lightly high e r increase of the Broca index in the combined treatment group. S ide effects were reported in three (12.5% ) and six (23%) patients treated with mesalazine and sulfasalazine/methylprednisolone, respectively. In conclusion, oral mesalazine at a dose of 3 g/day was effective in active C ro hn's disease and was well tolerated by the patients. Can J Gastroenterol 1990;4(1):13,18Key Words: Crohn's disease, Mesalazine, Prednisolone, Sulfasalazine Efficacite clinique de la mesalazine orale dans la maladie de Crohn RESUME: Un essai clinique randomise a ere effeccue afin d'evaluer l'innocuite et l'efficacite d'une dose elevee d'une n o uve lle preparation de mesalazine a liberation lente (comprimes de 500 mg) administree clans la malad ie de C ro hn.Vingc-quatre patients traites par mesalazin e (3 g/jour) Ont ere compares a 26
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