Gastrointestinal events related to the use of non-steroidal anti-inflammatory drugs: some clinical and economic aspects.
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Biomedical subjects
Publications and source records attributed to R Eliakim.
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BACKGROUND: At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD). AIM: To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD. PATIENTS: Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied. METHODS: Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated. RESULTS: Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD.
Open-access endoscopy has recently gained popularity in referring patients for endoscopic procedures. Retrospective (looking into patients' medical files) and prospective studies (using 2 different questionnaires, and evaluating a selection system) were conducted, comparing the efficacy of open-access endoscopy for patients referred by either family practitioners or gastroenterologists. In the retrospective study, 673 patients (mean age 48.8 years, male-58%) underwent upper gastrointestinal endoscopy. The main indications for upper endoscopy were epigastric pain (71%), heartburn (18%) and vomiting (13%). Severe endoscopic findings were not different between the study groups. Normal or mildly abnormal findings were diagnosed in 75% of patients in both groups. In the prospective study, 361 patients were referred for upper endoscopy (mean age 50.2 years, male-58%). Although there were significantly (p < 0.01) fewer normal and more mild endoscopic findings in the patients referred by gastroenterologists, as compared with family practitioners, there was no difference in the clinically significant (severe) endoscopic findings. Previous ulcer, smoking, gender, age and nocturnal pain were predictive for severe endoscopic findings. There was a linear correlation between the severity of the scoring system and the endoscopic findings. The results of the present study, which reveal nonsignificant differences in the indications for and the findings of endoscopies, indicate that selection of patients for endoscopy can be safely done by family practitioners. In order to reduce the number of referred patients with no gastrointestinal pathology, a better scoring system to detect at-risk patients should be developed.
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BACKGROUND & AIMS: Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis. The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a randomized, double-blind multicenter trial. METHODS: Patients with active ulcerative colitis who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study. Methotrexate (12.5 mg) or placebo was added to their treatment once weekly for 9 months. RESULTS: Sixty-seven patients were included (methotrexate, 30 patients, placebo, 37 patients). The proportion of patients entering first remission (methotrexate, 46.7%; placebo, 48.6%), the time to reach first remission (methotrexate, 4.1 +/- 1.9 months; placebo, 3.4 +/- 1.7 months), as well as the proportions of patients having a relapse after first remission (methotrexate, 64.3%; placebo, 44.4%) were not significantly different between the two groups. The mean Mayo Clinic score, the mean monthly steroid dose, and the proportion of abnormal laboratory results during the study were also similar. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis.
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BACKGROUND: Surfactant-like particles, normal products of the human enterocyte, are released into the lumen and secreted into blood. AIMS: To assess their role as markers for mucosal functional integrity, this study examined their content in biopsy specimens and serum of patients with duodenal ulcer disease, compared with non-diseased control subjects. PATIENTS: Endoscopic biopsy specimens were taken 1-2 cm from areas of active inflammation or ulcer (peptic ulcer patients) or just beyond the duodenal bulb (normals) in 35 consecutive subjects. METHODS: After staining for phospholipid, extracellular and intracellular particles were counted on transmission electron micrographs of coded specimens. Serum was obtained from 24 patients, and densitometry of the 59 kDa band detected on western blot by antiserum against human jejunal particle was measured. RESULTS: Normal duodenum (n = 15) contained more particles (44 (4.7)) particles/block, mean (SD) than active duodenal ulcer (n = 13, 17 (3.9)) or gastritis/duodenitis patients (n = 4, 9 (2.7)). Three patients examined after healing of duodenal ulcers showed abundant particles (n = 3, 67 (2.2)). Similarly, the 59 kDa band was decreased in serum of patients with active peptic ulcer disease (n = 11, 0.25 (0.04) absorbance units) compared with normal patients (n = 10, 0.40 (0.03)) or healed ulcers (n = 3, 0.62 (0.04)). There was good correlation between morphological mucosal particle abundance and particle protein content of serum assayed from the same patients (r = 0.831). These changes were independent of Helicobacter pylori status. CONCLUSION: The mucosal and serum content of surfactant-like particles may reflect general mucosal integrity of the enterocytes from which they are derived.
The objective of this part of the first cross-section of the longitudinal study of a cohort of 70 year olds in Jerusalem was to survey the gastrointestinal symptoms and signs of this heterogeneous population and thus contribute to the knowledge of the development of gastrointestinal diseases in this age group. A total of 605 persons replied to a home-visit questionnaire gathering data on socioeconomic and migration variables. Later on, 463 of these attended an examination at the Geriatric Research Institute where an in-depth anamnesis and physical examination were conducted. A battery of biochemical and hematologic blood tests were performed as well as urine analysis, ECG, and pulmonary function tests. At 3 year follow-up, the interviewed subjects, subjects examined in the hospital, and the control group consisting of 70 year olds who were not examined, were compared. By the measures of disease-specific mortality and hospital morbidity, the three groups were found to be similar, demonstrating that the sample population does represent the total Jerusalem 70-year-old population. This paper describes the symptoms, signs and laboratory results of the gastrointestinal part of this study. Up to a third of the subjects complained of upper gastrointestinal symptoms, most prominent of which was heartburn. Almost 10% of subjects complained of abdominal pain occurring at least once a week, but less than 1% noted left lower quadrant pain. There was a direct association between upper abdominal pain and symptoms of ischemic heart disease. The second part of this study, which began in 1996, will provide additional information regarding the natural history of these complaints.
OBJECTIVES: The recommended evaluation of adult patients presenting with iron deficiency anemia (IDA) includes the performance of colonoscopy and esophagogastroduodenoscopy. IDA is a common feature in patients with celiac disease and, in several, may be the only presenting sign. The performance of small bowel biopsy (SBB) for the evaluation of celiac disease as the cause of IDA is not routinely recommended. The aim of the present study was to determine the yield of SBB performed during routine endoscopy of adults with IDA. METHODS: We prospectively studied 93 patients with IDA. Three control groups were included: 23 patients with steatorrhea, 37 patients with idiopathic diarrhea, and 9 patients in whom SBB was performed for miscellaneous indications. RESULTS: Eleven patients with IDA and two patients with steatorrhea had SBB findings compatible with celiac disease. None of the patients from the other two groups had similar findings. Two patients with IDA, who were later diagnosed to suffer from celiac disease, presented: one with occult blood in the stool and the other with rectal bleeding. Subgroup analysis of patients with IDA revealed that patients with celiac disease were younger, had significantly more episodes of diarrhea, lower mean hemoglobin level, and longer duration of anemia than those without celiac disease. Other mucosal abnormalities were found in a substantial number of patients with celiac disease: esophagitis, gastritis, duodenitis, hemorrhoids, and colitis. CONCLUSIONS: A substantial number of adult Israeli patients who present with IDA are found, on SBB, to have mucosal abnormalities compatible with the diagnosis of celiac disease. The presence of esophagitis, gastritis, or duodenitis on esophagogastroduodenoscopy, or other abnormalities on colonoscopy, do not exclude the coexistence of celiac disease. Celiac disease should be included and routinely looked for in the differential diagnosis of adult patients with IDA.
Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.
Capsaicin-sensitive afferent neurons are involved in maintaining the integrity of the gastrointestinal mucosa. These neurons are closely apposed to mast cells and could, therefore, lead to their activation. In the present study, the role of capsaicin-sensitive neurons in the pathogenesis of experimental colitis and the possible involvement of mast cells and nitric oxide were evaluated. Rats were treated with capsaicin subcutaneously, 20, 30, and 50 mg/kg, on three consecutive days, a regimen shown to ablate primary afferent neurons. Colitis was induced two weeks later by flushing 2 ml 5% acetic acid into the proximal colon. Control rats received saline, acetic acid, or capsaicin alone. Another group of rats received ketotifen (100 micrograms/100 g body wt x 2/day) intragastrically 48 hr prior to damage induction and thereafter. Rats were sacrificed 24 hr after damage induction, the colon isolated, damage assessed, explants were organ-cultured for 24 hr for determination of nitric oxide generation, and mucosa extracted for determination of leukotriene B4 generation and nitric oxide synthase activity. Significant increases in colonic weight, nitric oxide synthase activity, and nitric oxide and leukotriene B4 generation accompanied the near tripling of acetic acid-induced damage in capsaicin-pretreated rats. Ketotifen pretreatment significantly decreased the macroscopic damage and the increase in colonic weight. The protection provided by ketotifen was accompanied by a significant decrease in leukotriene B4 generation and nitric oxide synthase activity (80%).(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative cultures were carried out on samples from gastric juice obtained from 12 ambulatory patients with esophagitis before and one month after omeprazole therapy. An increase in the number of patients in whom gastric juice was culture-positive, as well as an increment in the bacterial counts were noted. The spectrum of microorganisms isolated from gastric juice was identical to the normal flora of the oral cavity, mainly alpha-hemolytic streptococci, corynebacteria, and Candida species. Thus, the counts of organisms within gastric contents are simply a reflection of swallowed oral microflora that were able to survive due to the less acidic environment.
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TEMPOL, a cyclic nitroxide stable radical blocks biological damage by breaking chain reactions through termination reaction with free radicals, and by inhibiting the catalytic effect of transition metals. This study tested its protective effect on two models of experimental colitis as free radicals play an important part in their pathogenesis. TEMPOL was given intragastrically immediately after induction of colitis with acetic acid or trinitrobenzene sulphonic acid (TNB) and mucosal damage was assessed one, three, or seven days later. Cellular partition of TEMPOL was determined by electron paramagnetic resonance spectroscopy. In vitro experiments showed that TEMPOL immediately penetrates colonic mucosa and, following its intragastric administration, it persists in both gastric and colonic mucosa for several hours. Intragastric administration of TEMPOL, 0.5 g/kg/bw, immediately after intracaecal administration of 5% acetic acid significantly decreased mucosal lesion area, myeloperoxidase activity, and leukotriene B4 and C4 generation when assessed 24 hours after damage induction. Intragastric administration of TEMPOL, 0.5 g/kg/bw, immediately after intracolonic administration of 30 mg TNB in 0.25 ml 50% ethanol, and once daily thereafter, significantly decreased mucosal lesion area assessed after one, three, and seven days, having no effect on LTC4 generation and affecting colonic weight, myeloperoxidase activity, and LTB4 generation only sporadically. In conclusion, TNB and acetic acid induced colitis can be pharmacologically manipulated by TEMPOL. TEMPOL may be beneficial in the treatment or prevention of inflammatory bowel disease.
A 38-year-old woman presented with iron-deficiency anemia in 1983. Eight years later, she developed classic symptoms of celiac disease, ie, diarrhea, weight loss, and diminished appetite. New noninvasive blood tests and the ease with which small bowel biopsies can be achieved are having an impact on the clinical pattern of the disease. This report includes a discussion of anemia as the presenting sign of celiac disease and a review of the literature.
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