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Biomedical subjects

B I Hirschowitz

Publications and source records attributed to B I Hirschowitz.

At least 19 recordsLinked to original sources
PubMed2002

Minor effects of Helicobacter pylori on gastric secretion and dose of lansoprazole during long-term treatment in ZE and non-ZE acid hypersecretors.

BACKGROUND: Helicobacter pylori infection may increase or decrease acid secretion and may augment proton pump inhibitor efficacy. Pepsin effects have not been reported. In Zollinger-Ellison syndrome (ZE) specifically, H. pylori has been reported to decrease acid. AIM: To examine H. pylori effects on secretion and dose of medication in hypersecretors (basal acid output > 15 mmol/h) undergoing long-term treatment with individually optimized lansoprazole doses. METHODS: Sixty-five patients (47 ZE and 18 non-ZE), treated for > 3 months to 10 years, were tested every 6 months with endoscopy, gastric analysis and serum gastrin. RESULTS: Forty-three per cent were H. pylori-positive. Acid, pepsin and gastrin were not different between H. pylori-positive and H. pylori-negative patients before or during long-term lansoprazole treatment. Initially, H. pylori-positive patients required less lansoprazole than H. pylori-negative patients (68 +/- 6 vs. 96 +/- 8 mg/day), but after 3 years the doses converged (83 vs. 86 mg/day). The disappearance of H. pylori in 15 patients caused no significant changes in acid, pepsin, gastrin or lansoprazole dose in the following 4 years. CONCLUSIONS: H. pylori had no significant initial or long-term physiological or potential clinical effects on acid or pepsin secretion or gastrin in these acid hypersecretors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Questions regarding future research on aspirin and the gastrointestinal tract.

Despite great proven and potential benefits, aspirin also has adverse side effects on all parts of the gastrointestinal tract including ulceration, bleeding, perforation, and stenosis. Because of widespread and growing use, there is a need to understand and, if possible, prevent the adverse effects of aspirin while maintaining its benefits. This article is part of a report from a consensus meeting in 1999 on nonsteroidal anti-inflammatory drugs, and examines possible mechanisms of each of the risks of normal and low-dose aspirin use including areas of uncertainty. Based on these issues, we recommend studies that would further clarify the actions of aspirin. We also examine various strategies that might be used to prevent or mitigate adverse effects. Finally, we propose future research prospects in the search for a safer aspirin.

Animals↗
PubMed2001

Helicobacter pylori effects on gastritis, gastrin and enterochromaffin-like cells in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome acid hypersecretors treated long-term with lansoprazole.

BACKGROUND: Helicobacter pylori is said to cause atrophy of the gastric corpus and enterochromaffin-like cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. AIMS: To determine the effect of H. pylori infection on gastritis, enterochromaffin-like cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger-Ellison syndrome) or normal gastrin (non-Zollinger-Ellison syndrome) before and during long-term treatment with lansoprazole. METHODS: Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post-surgical Zollinger-Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later. RESULTS: H. pylori was present in corpus biopsies in approximately 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori-positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, enterochromaffin-like cell density or hyperplasia. Enterochromaffin-like cell density was twice as high in Zollinger-Ellison syndrome as in non-Zollinger-Ellison syndrome patients (241 vs. 126 cells/mm2, P < 0.001). Enterochromaffin-like cells remained normal in the non-Zollinger-Ellison syndrome hypersecretors regardless of H. pylori status. CONCLUSION: Corpus enterochromaffin-like cell increases were related to serum gastrin elevation, but neither H. pylori nor long-term treatment with lansoprazole alone or together had any effect on enterochromaffin-like cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long-term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Long-term lansoprazole control of gastric acid and pepsin secretion in ZE and non-ZE hypersecretors: a prospective 10-year study.

BACKGROUND: The majority of patients with Zollinger-Ellison syndrome require lifelong treatment with proton pump inhibitors. AIMS: To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors. METHODS: Sixty-three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger-Ellison syndrome and 17 non-Zollinger-Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long-term prospective study using lansoprazole. Sixty-one were studied every 3 months for 1 year and then every 3-6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger-Ellison syndrome patients. RESULTS: The dose of lansoprazole could not be predicted a priori from pre-treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was approximately 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from approximately 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger-Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non-Zollinger-Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. CONCLUSIONS: The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one-quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors for up to 10 years.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Study of outcome after targeted intervention for peptic ulcer resistant to acid suppression therapy.

OBJECTIVE: Different factors might affect outcome in ulcers resistant to antisecretory therapy. The aim of the study was to define the odds of resistant ulcers being associated with NSAID use, and/or Helicobacter pylori (H. pylori) infection, or neither. METHODS: A total of 80 patients with resistant peptic ulcers were prospectively followed after targeted intervention for a mean follow-up of 39.5+/-6.9 months. RESULTS: NSAID use was involved in 24 cases (14 with and 10 without concomitant H. pylori infection), H. pylori alone was involved in 44, and 12 patients had neither factor present. Of the NSAID group, resistant ulcers healed in patients who stopped taking NSAIDs. Those continuing to use NSAIDs (10 of 24; 41.6%) had either persistent ulceration or ulcer complications despite H. pylori eradication and omeprazole therapy. Of the H. pylori group, infection eradication induced ulcer remission in most patients, but those with persistent infection and a small subset of H. pylori eradicated patients (16.6%) had persistent/recurrent ulceration. Of the 12 refractory patients with neither NSAID use nor H. pylori infection, three had persistent ulceration but nine were controlled with antisecretory agents. Other factors (e.g., smoking or acid hypersecretion) were not associated with final outcome after targeted intervention of H. pylori infection and NSAID use. CONCLUSIONS: With current antiulcer therapies, NSAID use is the main, but not the exclusive, factor leading to intractability and complications in refractory ulcers. In a subset of resistant ulcers, neither the presence of H. pylori nor use of NSAIDs are involved. In this study, despite specific therapeutic intervention, 22.5% of patients with resistant ulcers had continuing ulcer problems.

Adult↗
PubMed1999

Prospective evaluation of ranitidine bismuth citrate-based triple therapy for the treatment of Helicobacter pylori infection.

BACKGROUND: There is a need for effective and inexpensive therapy for Helicobacter pylori with good patient compliance. AIM: To evaluate a simplified twice daily schedule for treating H. pylori. METHODS: Patients infected with H. pylori (positive by CLO- and 13C-urea breath tests [UBT]) and not previously treated with anti-H. pylori therapy were treated with ranitidine bismuth citrate (RBC) and two inexpensive antibiotics (metronidazole, tetracycline) twice daily for 14 days in an open-label study. Eradication was established by a negative UBT 4 weeks after ending therapy. RESULTS: Twenty men and 30 women (age 54+/-14 years, range 26-74) were included in the study. Five patients were prematurely withdrawn (side-effects 2, took additional antibiotics 2 and surgery 1) and one patient was lost to follow-up; therefore, 44 (88%) patients completed the H. pylori eradication protocol. Per protocol (PP) cure rate was 82% (36/44 patients, 95% CI: 68-95%), and intention-to-treat cure rate was 72% (36/50 patients, 95% CI: 58-82%). Five patients (10%) developed side-effects during therapy, most commonly nausea (3 patients). Four weeks after the end of treatment, 78% (PP) of patients were symptomatically improved. CONCLUSIONS: A 2-week course of twice-daily RBC-based triple therapy was well tolerated, eradicated H. pylori in 72% (ITT) and 82% (PP) of patients, respectively, and relieved symptoms in 78%.

Adult↗
PubMed1999

Toxicity of NSAIDs in the stomach and duodenum.

NSAIDs are widely used for analgesic, anti-inflammatory and anti-thrombotic indications. Such use carries the risk of gastrointestinal complications (1% over 6 months) which NSAIDs may promote from both ulcerous and nonulcerous lesions. Symptoms are poor predictors of serious lesions and complications, which may occur without previous symptoms. NSAIDs also delay healing of peptic ulcers, even to the extent of intractability, and may cause recurrence after gastric surgery. Prophylactic therapy is indicated in high-risk patients (age > 60 years, previous ulcer history, high dose, concomitant use of corticosteroids or anticoagulants). Misoprostol, omeprazole and high-dose famotidine have been shown to reduce the occurrence of both gastric and duodenal ulcers in NSAID users. At present, the role of Helicobacter pylori in NSAID-induced gastroduodenal lesions is controversial and there is no agreement in considering the organism as a risk factor and indicating its eradication in NSAID users.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Association of obesity with hiatal hernia and esophagitis.

OBJECTIVE: Although weight loss is commonly recommended for symptoms of gastroesophageal reflux, a relationship between excessive body weight and esophageal reflux has not been established. The aim of this study was to determine whether obesity is associated with the presence of a hiatal hernia (HH) and/or an endoscopic diagnosis of esophagitis. METHODS: Retrospective case control studies were done using 1389 patients who underwent gastric analysis and upper GI endoscopy between 1974 and 1995. After excluding patients with Zollinger-Ellison syndrome, 189 cases of esophagitis with 1024 controls were identified. In a separate analysis of the database, 151 cases of HH with 1053 controls were also identified. Patients were classified by body mass index (BMI) as: thin (BMI <20 kg/m2), normal (BMI 20-25), mildly obese (BMI 25-30), and obese (BMI >30). RESULTS: Excessive body weight was significantly associated with the presence of HH, the probability of HH increasing with each level of BMI (p < 0.01), as well as with esophagitis (OR 1.8; 95% CI 1.4-2.1). HH was independently associated with esophagitis (OR 4.2 95% CI 2.9-6.1); when controlled for the effect of HH, the association between BMI and esophagitis diminished but remained significant. In the population as a whole, for the presence of esophagitis multiple logistic regression indicates BMI and hiatal hernia were significant factors but gender and race did not appear to be. CONCLUSIONS: Excessive body weight is a significant independent risk factor for hiatal hernia and is significantly associated with esophagitis, largely through an increased incidence of hiatal hernia. Whites are more likely to have the combination of esophagitis and hiatal hernia than are blacks.

Body Mass Index↗
PubMed1999

Minimizing the risk of NSAID-induced GI bleeding.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) have definite indications and can offer relief for many conditions, many patients have severe gastrointestinal problems after taking them. Physicians should prescribe these drugs more selectively and advise patients to limit their use of over-the-counter NSAIDs. For patients at high risk who need an NSAID, a prophylactic drug or a cyclooxygenase 2-selective NSAID can decrease the risk.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer.

BACKGROUND & AIMS: Postsurgical ulcer recurrence is a challenging problem. The aim of this study was to define the role of aspirin in postsurgical ulcers. METHODS: We studied 30 patients with postsurgical ulcer and aspirin abuse. Preoperatively 13 had stenosis, 7 bleeding, and 7 perforation or penetration; 18 had undergone vagotomy and 11 gastrectomy. RESULTS: Of 30 patients, 15 admitted long-term aspirin use (1-4 g/day), whereas 15 denied use but had positive salicylate blood levels (15.1 +/- 2.25 mg/100 mL; >1 mmol/L). Gastrin or gastric secretion was normal in the 24 patients tested. On follow-up, 3 (10%) healed after surgery (all stopped taking aspirin), whereas 27 continued and had new ulcers; 12 (44%) developed stenosis, and 6 (23%) developed bleeding. A second operation was required in 16 patients who had continued aspirin abuse, which was surreptitious in 10 (63%). Thirteen of these 16 had recurrent ulceration (7 [43%] with stenosis and 1 with bleeding); 1 died and 2 stopped taking aspirin and healed. A third operation was required in 8 patients. All had continued aspirin abuse (75% surreptitiously), and all again had relapses (3 with stenosis); 1 underwent an unsuccessful fourth operation, and 3 died. CONCLUSIONS: With continued aspirin abuse, recurrent ulceration is the rule, and complications, especially stenosis, are common. Surreptitious aspirin abuse, if discovered, is a clear contraindication to elective ulcer surgery, because aspirin-abuse ulceration is incurable by gastric surgery.

Aspirin↗
PubMed1997

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Anti-Ulcer Agents↗
PubMed1997

Zollinger-Ellison syndrome: pathogenesis, diagnosis, and management.

Zollinger-Ellison syndrome (ZES) involves hypergastrinemia produced by gastrin-secreting tumor(s) of the pancreas or duodenum. Estimated to occur in 0.1-3 per million of the United States' population, the actual prevalence may be higher because ZES is often undetected with routine testing. ZES should be suspected in patients who present with persistent or complex duodenal or postsurgical ulcer, especially if accompanied by esophagitis, diarrhea, weight loss, and/or liver metastases. Twenty percent of ZES patients have multiple endocrine neoplasia type I, some of whom may also have elevated levels of serum calcium and a family history of ZES. Diagnostic tests include fasting serum gastrin concentration, gastric secretion analysis, with, if necessary, secretin stimulation of serum gastrin. Complete surgical tumorectomy for cure is impossible in as many as 70-90% of patients with ZES, who then require long-term medical therapy to reduce acid exposure. Basal acid output needs to be maintained at < 5 mEq/h for uncomplicated ZES and at < 1-2 mEq/h for complicated ZES or postgastrectomy. Proton pump inhibitors (omeprazole, lansoprazole) with careful clinical monitoring provide safe and effective acid control in patients with ZES.

Combined Modality Therapy↗
PubMed1996

Gastric secretion of acid and pepsin in patients with esophageal stricture and appropriate controls.

Most cases of esophageal stricture are associated with acid/peptic reflux esophagitis. While patients with strictures commonly have disordered lower esophageal sphincters and poor clearance and neutralization mechanisms, it is not known whether they also have abnormal gastric secretion. This study examined fasting, basal, and stimulated acid and pepsin secretion. With an endoscopic diagnosis of esophagitis, patients with stricture (< 12.5 mm) were matched for age, sex, concurrent gastrointestinal disease (duodenal ulcer, N = 9), Zollinger-Ellison syndrome (N = 6), and postgastric surgery state (N = 5), as well as the absence of ulcer disease (non-DU, N = 37). Fasting, basal, and pentagastrin-stimulated acid and pepsin secretion were measured. Overall, the 57 stricture patients had the same acid and pepsin secretion as their matched controls with esophagitis; the same was true for each of the subgroups (ZES, DU, non-DU, and postsurgical). Stricture patients weighed less and had a lower body mass index (P < 0.01). Patients with esophageal peptic stricture have the same acid and pepsin output as control patients matched for sex, age, background gastrointestinal disease, and the presence of esophagitis.

Endoscopy, Digestive System↗
PubMed1996

Gastric acid and pepsin secretion in patients with Barrett's esophagus and appropriate controls.

The objective of this study was to determine whether gastric secretion of acid and pepsin is different in the subset of esophagitis patients who also have Barrett's esophagus. Basal and stimulated gastric secretions were studied for 1 hr in the unstimulated state and 1 hr after pentagastrin 6 microg/kg subcutaneous injection. Because Barrett's patients are predominantly male, the 30 patients were matched with patients who had esophagitis, but not Barrett's, for sex (26 men, 4 women) and age as well as for background gastrointestinal disease (duodenal ulcer in 10, no ulcer disease in 17 and Zollinger-Ellison hypersecretors in 3). Patients with Barrett's weighed more than controls (P < 0.05). Acid and pepsin output in the basal and stimulated state were no different in Barrett's and their appropriately matched controls. Overnight fasting residue--volume, pH, acid and pepsin concentrations, and bile content--were also alike. The severity of esophagitis or prevalence of esophageal ulcer or stricture was not different between those with and without Barrett's and in neither was the grade of esophagitis related to acid or pepsin output. It is concluded that Barrett's esophagus patients do not have gastric secretions different from appropriately matched controls with esophagitis alone. When present, esophagitis due to reflux in Barrett's epithelium should be treated on its merits by appropriate reduction of acid exposure.

Barrett Esophagus↗
PubMed1996

Long-term treatment with lansoprazole for patients with Zollinger-Ellison syndrome.

BACKGROUND: Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression. METHODS: Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells. RESULTS: Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered. CONCLUSION: Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.

2-Pyridinylmethylsulfinylbenzimidazoles↗