Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CI-986 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)- thione-2-hydroxy-N,N,N-trimethylethanaminium salt) is a novel anti-inflammatory compound classified as a dual inhibitor of cyclooxygenase and 5-lipoxygenase. Studies were undertaken to characterize the preclinical toxicology of the compound. CI-986 was administered to rats for 2 weeks (0, 50, 250, 750, and 1500 mg/kg) or 13 weeks (0, 20, 250, 500, and 1000 mg/kg), dogs for 2 weeks (0, 50, 150, and 500 mg/kg) or 13 weeks (0, 20, 100, and 200 mg/kg), and to monkeys for 2 weeks (0, 50, 250, and 1000 mg/kg). No drug-related deaths resulted. Mild clinical signs of toxicity were noted in rats given doses of 250 mg/kg and above. Drug-related emesis and diarrhea were absent at the low dose in the dog and monkey but increased in incidence and severity at higher doses. Severe clinical signs in monkeys (emesis and diarrhea) necessitated the lowering of the top dose to 500 mg/kg/day (administered b.i.d.) during the second week of the monkey study. Slight decreases (< 23%) in serum protein and/or albumin were noted in all studies at the higher doses. A dose-related increase in alkaline phosphatase was noted in both dog studies, with no other drug-related effect on clinical pathology parameters. A gastric ulcer occurred in one rat administered 500 mg/kg CI-986 for 13 weeks. Gastrointestinal ulcers were not noted at any other dose in rats or at any dose in dogs or monkeys. A dose-related eosinophilia of glandular stomach submucosa was noted in rats after 2 and 13 weeks of drug administration but not in dogs or monkeys. In the 2-week rat study, mean combined sex plasma drug concentrations monitored 2 hr after dose on Day 14 were 0.59, 1.10, 2.64, and 3.43 micrograms/ml for the 50, 250, 750, and 1,500 mg/kg dose groups, respectively. In the 2-week dog studies, maximum plasma drug concentrations on Day 10 or Day 11 were achieved within 2 hr of dose with mean combined sex Cmax values of 0.73, 2.05, and 2.62 micrograms/ml for the 50, 250, and 750 mg/kg groups, respectively. Hepatic microsomal induction characterized by increased microsomal protein, increased microsomal cytochrome P450 content, and increased p-nitroanisole O-demethylation activity was noted in dogs and monkeys but not rats. CI-986 was well tolerated in rats and dogs at the doses employed and in monkeys at doses up to 500 mg/kg (b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Subacute and subchronic toxicology studies of CI-986, a novel anti-inflammatory compound. 831 60

Among the factors involved in the pathogenesis of gastric ulcer, the reduced clearing capacity of the stomach seems to play an important role. On this basis, cisapride, which improves gastrointestinal motility, enhances gastric emptying, and prevents duodenogastric reflux, may be effective in the treatment of the gastric ulcer. We randomly allocated 60 consecutive patients, with uncomplicated antral gastric ulcer (diameter 5-25 mm), into three groups of treatment: cisapride 20 mg b.i.d. (C), ranitidine 150 mg b.i.d. (R), cisapride 20 mg b.i.d. + ranitidine 150 mg b.i.d. (C+R). Endoscopic examination with biopsy specimens was performed on admission, after 4 weeks and (if ulcer not healed) after 8 weeks of therapy. Three patients were lost to follow-up (two in C and one in C+R), and three were withdrawn, due to malignant ulcer (one case in R) or to side effects (one case of diarrhea in C, one case of headache in C+R). Healing rates at 4 weeks were 41.1% in C, 52.6% in R, and 50.0% in C+R; at 8 weeks they were 88.2% in C, 89.4% in R, and 94.4% in C+R. Though the lack of a placebo arm makes final considerations difficult, the results were similar in all three groups, with no evident differences. In conclusion, therapy with cisapride appears as effective as H2-blocker alone or combined treatments in healing benign gastric ulcer.
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PMID:Effectiveness of cisapride in gastric ulcer. Results of a double-blind randomized trial versus ranitidine and versus cisapride plus ranitidine. 840

The role played by Helicobacter pylori in the pathogenesis of peptic ulcer disease (PUD) is discussed, and the epidemiology, identification, diagnosis, eradication, and treatment of H. pylori infection are reviewed. Isolation of H. pylori from up to 100% of patients with duodenal ulcer and 80% of patients with gastric ulcer establishes a strong association between H. pylori and idiopathic PUD, although other factors also may be essential for the development of PUD. Invasive procedures for diagnosis of H. pylori infection include upper endoscopy and biopsy of gastroduodenal tissues followed by culture or the rapid urea test; noninvasive tests include the urea breath tests and serology. Although H. pylori is susceptible to a number of antimicrobials, eradication (as opposed to suppression) of this organism has been a major challenge. The most important predictive factor for clinical and microbiological efficacy is the pretreatment susceptibility of H. pylori to nitroimidazoles. Triple therapy with bismuth, metronidazole, and either amoxicillin or tetracycline has resulted in better clinical and microbiological outcomes than either monotherapy or dual therapy. Possible adverse effects of this regimen include nausea, vomiting, taste disturbance, and diarrhea. Anti-H. pylori therapy should be reserved for those patients who have recurrent symptomatic or intractable PUD. Currently, the regimen of choice includes bismuth, metronidazole, and either amoxicillin or tetracycline given for at least two weeks.
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PMID:Helicobacter pylori and peptic ulcer disease. 842 32

A case of itraconazole-induced hypokalemia with pulmonary aspergilloma is reported. A 68-year-old female who had been followed for rheumatoid arthritis, gastric ulcer and pulmonary aspergilloma was admitted to our hospital because of a cough, low grade fever and hemosputum. She was treated with itraconazole (100 mg/day) for pulmonary aspergilloma of the left upper lobe. Fifty seven days after starting the treatment, her serum potassium was 2.33 mEq/l. Since there was no history of diarrhea, vomiting or abuse of drugs known to cause hypokalemia, itraconazole- induced hypokalemia was suspected. Thirty one days after the discontinuation of the treatment with itraconazole, her serum potassium increased to 3.57 mEq/l without potassium supplement. The lymphocyte stimulation test for itraconazole was negative. This case suggests that serum potassium should be monitored in the patients treated with itraconazole.
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PMID:[A case of itraconazole-induced hypokalemia with pulmonary aspergilloma]. 858 96

We describe a 43-yr-old female with a giant gastric ulcer, refractory to medical treatment, that ultimately proved to be due to the mural form of eosinophilic gastroenteritis. The patient presented with a 6-month history of abdominal pain, diarrhea, and weight loss. Endoscopy showed a giant gastric ulcer, and biopsies revealed only chronic active ulcerative inflammation. The ulcer progressed on omeprazole therapy; therefore, a distal antrectomy with gastrojejunal anastomosis and bilateral vagotomy was performed. Pathology of the surgical specimen demonstrated the mural form of eosinophilic gastritis. To the best of our knowledge, this case is the first to demonstrate that refractory giant gastric ulcers may be a manifestation of the mural form of eosinophilic gastroenteritis.
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PMID:Eosinophilic gastroenteritis presenting as a giant gastric ulcer. 867 58

Endocrine active islet cell tumors of the pancreas are rare and become clinically evident mainly by symptoms of hormone over-production (hypoglycemia, gastric ulcer disease, diarrhea etc.). The tumors may occur sporadically or in connection with the familial MEN-I syndrome. Diagnosis is verified biochemically and does not need further localization studies. Localization studies are important, however, intraoperatively and in detecting persistent or recurrent tumor disease. Principally endocrine pancreatic tumors are excised selectively with exception of MEN-I patients and patients suffering from "Nesidioblastosis", where subtotal resections of the pancreas are indicated. In case of malignant metastatic endocrine pancreatic tumors palliative therapies (surgery, embolization, chemotherapy, therapy of hormone excess etc.) are demanded to improve the quality of life in these patients, since they may survive for years despite their tumor burden.
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PMID:[Endocrine pancreatic tumors]. 868 60

We report the case of a patient in the Psychiatric Department who complained of progressive impairment of cerebral functions consistent with dementia, diarrhea and fecal incontinence in the last few months. His medical history included a Billroth II gastrectomy for gastric ulcer. Biochemical tests detected cobalamin deficiency, without megaloblastic anemia, and an abnormal Schilling test that was not due to intrinsic factor deficiency. Once other causes of cobalamin deficiency were ruled out, we considered it as a deficiency disease due to blind loop syndrome. Treatment with parenteral vitamin B complex and long term oral antibiotic therapy allowed the complete and permanent resolution of neurologic and digestive symptoms. We consider this case to be interesting because it shows the existence of curable dementias and the usefulness of taking into account bacterial overgrowth, usually underestimated, as an entity that can produce a variety of disorders.
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PMID:[Dementia caused by bacterial overgrowth in a patient with Billroth II gastrectomy]. 875 25

Pantoprazole is an irreversible proton pump inhibitor which, at the therapeutic dose of 40mg, effectively reduces gastric acid secretion. In controlled clinical trials, pantoprazole (40mg once daily) has proved superior to ranitidine (300mg once daily or 150mg twice daily) and equivalent to omeprazole (20mg once daily) in the short term (< or = 8 weeks) treatment of acute peptic ulcer and reflux oesophagitis. Gastric and duodenal ulcer healing proceeded significantly faster with pantoprazole than with ranitidine, and at similar rates with pantoprazole and omeprazole. The time course of gastric ulcer pain relief was similar with pantoprazole, ranitidine and omeprazole, whereas duodenal ulcer pain was alleviated more rapidly with pantoprazole than ranitidine. Pantoprazole (40mg once daily) showed superior efficacy to famotidine (40mg once daily) in ulcer healing and pain relief after 2 weeks in patients with duodenal ulcer in a large multicentre nonblinded study. In mild to moderate acute reflux oesophagitis, significantly greater healing was obtained with pantoprazole than with ranitidine and famotidine, whereas similar healing rates were seen with pantoprazole and omeprazole. Pantoprazole showed a significant advantage over ranitidine in relieving symptoms of heartburn and acid regurgitation. Reflux symptoms were similarly alleviated by pantoprazole and omeprazole. Preliminary results indicate that triple therapy with pantoprazole, clarithromycin and either metronidazole or tinidazole is effective in the treatment of Helicobacter pylori-associated disease; however, these findings require confirmation in large well-controlled studies. Pantoprazole appears to be well tolerated during short term oral administration, with diarrhoea (1.5%), headache (1.3%), dizziness (0.7%), pruritus (0.5%) and skin rash (0.4%) representing the most frequent adverse events. The drug has lower affinity than omeprazole or lansoprazole for hepatic cytochrome P450 and shows no clinically relevant pharmacokinetic or pharmacodynamic interactions at therapeutic doses with a wide range of drug substrates for this isoenzyme system. In conclusion, pantoprazole is superior to ranitidine and as effective as omeprazole in the short term treatment of peptic ulcer and reflux oesophagitis, has shown efficacy when combined with antibacterial agents in H. pylori eradication, is apparently well tolerated and offers the potential advantage of minimal risk of drug interaction.
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PMID:Pantoprazole. A review of its pharmacological properties and therapeutic use in acid-related disorders. 888 82

Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) almost invariably cause acute gastroduodenal injury and probably account for approximately 12,000 ulcer bleeding episodes and 1200 deaths per annum in the United Kingdom. Clinically significant intestinal toxicity is also recognized but less clearly defined. The main risk factors for NSAID-related peptic ulcer complications are age, past history, use of higher risk individual NSAIDs, drug dose, concurrent use of warfarin or corticosteroids. The underlying reason for NSAID use and Helicobacter pylori status is not clearly associated with increased risk. Whether NSAIDs cause drug-induced non-ulcer dyspepsia is also controversial. Acute injury occurs more readily with aspirin than with non-aspirin NSAIDs, and the spectrum of acute injury is of little value in predicting clinically significant end points in comparison with different NSAIDs. However, acute studies of co-prescribed protective agents are highly predictive of performance in clinical practice. Gastric mucosal integrity is maintained by the interplay of three protective networks: prostaglandin synthesis, nitric oxide synthesis and the activity of the enteric nervous system. Aspirin and NSAIDs act by inhibiting prostaglandin synthesis catalysed by two cyclooxygenase enzymes. Most existing NSAIDs are unselective and inhibit the activity of the constitutive cyclooxygenase (COX) 1 enzyme in the stomach as much as the cyclooxygenase (COX) 2 enzyme which is induced at sites of inflammation such as joint disease. There are, however, prospects for selective cyclooxygenase 2 inhibitors. Some NSAIDs, particularly aspirin, have additional topical toxicity, which may in part reflect mucosal trapping. Some data favor an effect of NSAIDs in inhibiting mitochondrial oxidative phosphorylation. The principal physiological mechanisms which are compromised by NSAID use are mucosal blood flow, secretion of mucus and bicarbonate and maintenance of a hydrophobic mucosal surface. Animal data suggest that polymorphonuclear leukocytes (PMNs) are important for acute damage though the relevance to humans has yet to be established. As well as damaging the mucosa, NSAIDs impair ulcer healing and are associated with reduced epithelial proliferation and evidence of diminished angiogenesis. An interaction between prostaglandins and growth factors, as well as the synthesis of antiproliferative products of arachidonic acid metabolism may be involved. Healing of NSAID ulcers by conventional doses of H2 antagonists is slow and H2 antagonists are poor at preventing gastric ulcer development or recurrence. These problems can be overcome by the use of more potent acid suppression. Misoprostol heals NSAID-associated ulcers, though whether healing is as fast as with non-NSAID ulcers has not been formally established. Misoprostol is effective prophylactic treatment but has a significant incidence of adverse events, particularly diarrhoea. Misoprostol has been reported to prevent ulcer complications, and in endoscopic studies has been superior as prophylaxis to standard dose ranitidine. Results of its efficacy compared to proton-pump inhibitors are awaited. For many patients appropriate management is avoidance of NSAIDs or use of less potent/toxic alternatives such as ibuprofen. Reductions in prescribing arising from a prior authorization scheme show that this can be achieved. For high-risk patients requiring continuing NSAID use co-prescription of omeprazole or misoprostol should be considered.
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PMID:Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. 889 49

Helicobacter pylori (H. pylori) is currently considered the most important exogenous factor in the genesis of gastritis and peptic ulcer disease. However, the optimum regimen for the eradication of H. pylori remains unclear. The purpose of this study was to evaluate the eradication rate of H. pylori, the side effects, and the patients' compliance with regard to various drug regimens. We also analyzed factors influencing the eradication of H. pylori. One hundred and eighty patients were included and divided into four groups: 42 patients (Group I) received tripotassium dicitrato bismuthate (240 mg b.i.d.), metronidazole (250 mg t.i.d.) and amoxicillin (500 mg t.i.d.) for 14 days; 55 patients (Group 2) received omeprazole (20 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 14 days; 36 patients (Group 3) were treated with omeprazole (20 mg b.i.d.), metronidazole (250 mg t.i.d.) and amoxicillin (500 mg t.i.d.) for 14 days; and 47 patients (Group 4) received omeprazole (20 mg q.d.) and amoxicillin (500 mg t.i.d.) for 14 days and then tripotassium dicitrato bismuthate (240 mg b.i.d.) and nizatidine (150 mg q.d.) for 14 days. The diagnosis of H. pylori was made by histology. The eradication of H. pylori was defined both by histology (H&E and Giemsa stain) and by rapid urease test (CLOR) showing negative for H. pylori 4 weeks after the completion of therapy. Of the 180 patients, 95 patients had non-ulcer dyspepsia, 40 patients had gastric ulcer and 45 patients had duodenal ulcer. The eradication rate of H. pylori was highest (89.3%) in Group 3, as compared with Group 1 (68.9%), Group 2 (65.4%), and Group 4 (48.9%). The eradication rate was significantly higher in Group 3 than in Groups 2 and 4 (p < 0.05). There was no significant difference in the eradication rate among clinical diagnosis, sex and age. But, in the conventional triple therapy (Group 1), the eradication rate was higher in male (78.6%) than in female (46.2%). The side effects in order, were nausea (22.1%), dizziness (19.5%), abdominal pain (11.6%) and diarrhea (97%), and there was no difference among the drug regimens. The compliance of the patients was good (more than 80% irrespective of drug regimen). On the basis of these findings, the side effects of the drugs seemed minimal, and the compliance of patients was good irrespective of the drug regimen. In conclusion, the triple therapy with omeprazole, metronidazole and amoxicillin was the most effective regimen and could be recommended for H. pylori eradication.
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PMID:Evaluation of therapeutic regimens for the treatment of Helicobacter pylori infection. 894 97


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