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Biomedical subjects

W Schepp

Publications and source records attributed to W Schepp.

At least 55 records · Page 3Linked to original sources
PubMed1995

Comparative trial of pantoprazole and ranitidine in the treatment of reflux esophagitis. Results of a German multicenter study.

In 249 patients with acute symptomatic reflux esophagitis grade II and III (Savary-Miller classification), we compared the efficacy and safety of pantoprazole, a newly developed proton pump inhibitor given at a once-daily dose of 40 mg, with a standard dose of the H2 receptor antagonist ranitidine (150 mg b.i.d.) in a randomized, double-blind, multicenter study. Complete healing was achieved after 4 and 8 weeks of therapy (protocol-correct) in 69 and 82% (pantoprazole) and 57 and 67% (ranitidine), respectively (p = 0.054 at 4 weeks and p < 0.01 at 8 weeks). The predominant symptoms of gastroesophageal reflux, i.e., heartburn and acid eructation, were more effectively reduced in pantoprazole- than in ranitidine-treated patients. The frequency of adverse events was low and did not differ between the two treatment groups. We conclude that pantoprazole is superior to ranitidine in the acute treatment of reflux esophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Pantoprazole versus omeprazole in the treatment of acute gastric ulcers.

BACKGROUND: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase. METHODS: The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, double-blind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n = 146) or omeprazole 20 mg (n = 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed. RESULTS: After 4 weeks, complete ulcer healing was seen in 88% of protocol-correct patients given pantoprazole and in 77% given omeprazole (between-group difference P < 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention-to-treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain-free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks. CONCLUSION: Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Comparison of pantoprazole versus omeprazole in the treatment of acute duodenal ulceration--a multicentre study.

METHODS: In this randomized, double-blind, multicentre study, the proton pump inhibitors pantoprazole and omeprazole were compared in patients with active duodenal ulcers. Two hundred and seventy-six protocol-correct patients received either pantoprazole 40 mg (n = 185) or omeprazole 20 mg (n = 91), once daily for 2 or 4 weeks, depending on the progress of ulcer healing. RESULTS: Rates of complete ulcer healing after 2 weeks were 71% in patients given pantoprazole and 74% in patients given omeprazole. After 4 weeks the figures were 96% and 91%, respectively. These differences were not significant. There was no significant difference in ulcer pain prior to treatment, and 85% of the pantoprazole group and 86% on omeprazole were pain-free after 2 weeks (not significant). The time until complete pain relief with pantoprazole or omeprazole, based on data from diary cards, was not significantly different (P > 0.05, Uleman's U-test). Both treatments were equally well tolerated. Changes in routine laboratory parameters were minimal in both groups. CONCLUSION: Pantoprazole was shown to be a highly-effective and well-tolerated treatment for acute duodenal ulcer. Pantoprazole 40 mg and omeprazole 20 mg were equally effective with respect to ulcer healing and pain relief, and have similar adverse event profiles.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Cholestasis induced hyperthyroidism after liver transplantation.

We report the case of a 68-year-old woman who underwent liver transplantation because of hepatitis-C-induced cirrhosis. She developed iodine-reduced hyperthyroidism postoperatively in temporal relation with cholestatic jaundice. Hepatic biopsies revealed moderate intrahepatic cholestasis and mild lobular inflammatory infiltration with some eosinophils. No histological evidence of acute graft rejection or reactivated hepatitis was found. Treatment with methimazole markedly reduced the serum parameters of cholestasis which, after subtotal thyroidectomy, returned to normal. Liver function recovered, as confirmed by repeated aminopyrine breath tests.

Aged↗
PubMed1995

Pantoprazole and ranitidine in the treatment of acute duodenal ulcer. A multicentre study.

BACKGROUND: Pantoprazole is a new substituted benzimidazole that inhibits the parietal cell H+,K(+)-adenosine triphosphatase. METHODS: Pantoprazole (40 mg) was compared with ranitidine (300 mg) in the treatment of acute duodenal ulcer. Two hundred and sixty-six patients with endoscopically diagnosed duodenal ulcers entered this multicentre, double-blind study. The primary efficacy variable was complete ulcer healing at 2 weeks; treatment then continued for a further 2 weeks if ulcers were unhealed. RESULTS: After 2 weeks 112 of 164 (68%) patients in the pantoprazole group had healed ulcers, compared with 36 of 81 (44%) taking ranitidine (p < 0.001). After 4 weeks the cumulative healing rates were 96% and 85% (p < 0.01). Improvement in ulcer pain was also significantly better with pantoprazole than with ranitidine (81% versus 62% with no pain at 2 weeks, p < 0.01). CONCLUSIONS: Pantoprazole is clinically superior to ranitidine in the treatment of acute duodenal ulcer, in terms of both healing and symptom relief.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Dermatomyositis as a complication of a metastatic melanoma-- case report and review of the literature].

In nearly 60% of men over 50 years of age, dermato-/polymyositis is induced by malignancies. Till now, 9 patients with melanoma-induced dermatomyositis have been reported in the literature. Here we report on a patient suffering from classic pelvic and pectoral girdle proximal weakness, typical heliotrope rash, increased serum CPK values, and biopsy-proven myositis, who died from metastasizing melanoma one year later.

Dermatomyositis↗
PubMed1994

Functional characterization of a muscarinic receptor stimulating gastrin release from rabbit antral G-cells in primary culture.

In previous studies carbachol-induced stimulation of gastrin release from antral G-cells in primary culture suggested the presence of muscarinic acetylcholine receptors on this cell type. Therefore, we attempted to pharmacologically characterize the muscarinic acetylcholine receptor subtype involved. Enzymatically isolated rabbit antral mucosal cells (0.8% G-cells) were separated by counterflow elutriation yielding a fraction (1.7% G-cells) that was placed in culture on collagen-coated well plates. After 24-36 h of culture 13.0 +/- 2.4% of total adherent cells were immunoreactive for gastrin as shown by immunocytochemical staining using the avidin-biotin complex method. In this preparation basal gastrin release ranged from 3.3 +/- 0.3 to 4.1 +/- 0.3% of total cellular content. Maximal gastrin release in response to the acetylcholine receptor agonist carbachol (10(-4) M) or the selective muscarinic receptor agonist arecaidine propargyl ester (10(-4) M) was 8.5 +/- 0.4% and 7.6 +/- 0.4% of total cellular content, respectively. The EC50 values were 3.7 +/- 0.5 x 10(-6) M carbachol and 1.8 +/- 0.4 x 10(-6) M arecaidine propargyl ester. At a concentration of 10(-6) M the non-selective muscarinic receptor antagonist atropine and the muscarinic M3 receptor preferring antagonist hexahydro-sila-difenidol (HHSiD; M3 > or = M1 > M2) completely inhibited gastrin release in response to carbachol (Ki values: 52 x 10(-9) M atropine and 29 x 10(-9) M HHSiD) and arecaidine propargyl ester (Ki values: 11 x 10(-9) M atropine and 13 x 10(-9) M HHSiD).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Exendin-4 and exendin-(9-39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7-36)NH2.

Exendin-4 is a novel peptide from Heloderma suspectum venom which is 53% homologous with glucagon-like peptide-1 GLP-1-(7-36)NH2, a stimulant of cAMP-dependent H+ production in rat parietal cells. It was the aim of the present study to determine whether this effect of GLP-1-(7-36)NH2 is shared by exendin-4, and whether the responses to either peptide are blocked by exendin-(9-39)NH2, a competitive specific exendin receptor antagonist. In enriched rat parietal cells H+ production was measured indirectly by [14C]aminopyrine accumulation. cAMP production was determined by radioimmunoassay. [125I]GLP-1-(7-36)NH2 was prepared using chloramine T followed by high pressure liquid chromatography (HPLC) purification. Exendin-4 (10(-12) - 10(-8) M) stimulated [14C]aminopyrine accumulation in a concentration-dependent manner (EC50 = 7.6 x 10(-11) M). At the maximally effective concentration (10(-9) M) exendin-4 was as effective as GLP-1-(7-36)NH2 reaching 70-80% of the response to 10(-4) M histamine. Likewise, exendin-4 (10(-11) - 10(-7) M) stimulated parietal cell cAMP production up to 2.8-fold. Maximal stimulation by exendin-4 of [14C]aminopyrine accumulation was not affected by ranitidine (10(-4) M), but was concentration-dependently reduced by exendin-(9-39)NH2 (10(-11) - 10(-7) M). At the maximal concentration, exendin-(9-39)NH2 completely abolished the responses to 10(-9) M exendin-4 and to 10(-9) M GLP-1-(7-36)NH2 while not altering stimulation by 10(-4) M histamine. Binding of [125I]GLP-1-(7-36)NH2 to enriched parietal cells was displaced by exendin-4 (Ki = 4.6 x 10(-10) M) as well as by exendin-(9-39)NH2 (Ki = 4.0 x 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1994

RUDER--a prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. RUDER Study Group.

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A review of treatment of duodenal and gastric ulcers--pantoprazole vs. omeprazole.

The efficacy and safety of pantoprazole in the treatment of duodenal and gastric ulcers has been compared with that of the first proton pump inhibitor omeprazole in two (previously reported) clinical studies. Pantoprazole (40 mg/day) administered orally was an effective and well-tolerated treatment for both indications. Pantoprazole was as effective as omeprazole (20 mg/day) and had a similar safety profile. For gastric ulcers, the healing rate with pantoprazole was superior to that with omeprazole at 4 weeks.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture.

Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter gastrin secretion. We have used primary cultures containing canine antral G-cells to study the cellular actions of prostaglandins on gastrin secretion, comparing the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, and forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin release, PGE2 did not inhibit the response to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was reversed and, in contrast, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting that endogenous somatostatin produced an inhibitory tone in these cultures and excluding the possibility that PGE2 acted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1994

Stimulation of rat parietal cell function by histamine and GLP-1-(7-36) amide is mediated by Gs alpha.

It was the aim of the present study to determine in rat parietal cells whether Gs alpha, the stimulatory subunit of adenylate cyclase, mediates adenosine 3',5'-cyclic monophosphate (cAMP)-dependent parietal cell function in response to histamine and glucagon-like peptide 1 (GLP-1)-(7-36) amide. Cytoplasmic membrane from enriched (83 +/- 5%) rat parietal cells were incubated for 30 min with 30 microCi/ml [32P]NAD+ and 40 micrograms/ml preactivated cholera toxin (CT), a pharmacological tool for activation of Gs alpha. Subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography revealed [32P]ADP ribosylation of Gs alpha represented by three proteins with molecular masses ranging from 42 to 45 kDa. In intact parietal cells, CT (10(-12)-10(-8) M) caused marked stimulation of [14C]aminopyrine accumulation and cAMP production confirming the functional importance of Gs alpha in regulation of H+ production. Identical membrane preparations were preincubated (2 h, 4 degrees C) in parallel with and without RM/1, a rabbit polyclonal anti-Gs alpha-antibody. Subsequently, adenylate cyclase was stimulated by histamine, GLP-1-(7-36) amide, CT, or forskolin. At a 1:10 dilution, the antiserum completely abolished adenylate cyclase activity in response to maximal concentrations of histamine, GLP-1-(7-36) amide, and CT while reducing forskolin stimulation by only 22.0 +/- 4.9%. At 1:50, RM/1 reduced responses to histamine, GLP-1-(7-36) amide and CT by 20-30% but failed to inhibit forskolin-stimulated enzyme activity. At 1:100, the antiserum was ineffective versus all stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Rat parietal cell receptors for GLP-1-(7-36) amide: northern blot, cross-linking, and radioligand binding.

The intestinal peptide hormone glucagon-like peptide-1 (GLP-1) (7-36) amide is a potent stimulus of H+ production in isolated rat parietal cells, suggesting the presence of specific GLP-1-receptors on this cell type. Our aim was to characterize these receptors. Enzymatically isolated rat gastric mucosal cells (F0) were fractionated by counterflow elutriation, resulting in five fractions (F1-F5) according to increasing cell diameter and parietal cell content (3, 5, 4, 27, 81%). Additional density gradient centrifugation of F4 yielded enriched chief cells (74%; parietal cells: 1%; F6), whereas density gradient centrifugation of F5 almost purified parietal cells (97%; chief cells: 1%; F7). Northern blot of total cellular RNA from F0-F7 with a probe specific for the GLP-1-(7-36) amide receptor revealed two RNA species of 2.7 and 3.6 kb. These messages were present to some extent in small cells (F1, F2), much more pronounced in F5, abundant in F7, barely detectable in F3 and F4, and absent from F6. Cross-linking of 125I-labeled GLP-1-(7-36) amide to parietal cell membranes revealed a single 59-kDa band that was abolished by unlabeled GLP-1-(7-36) amide. Throughout fractions F1-F7 specific binding of 125I-GLP-1-(7-36) amide was correlated with parietal cell content (r = 0.99; P < 0.01) and H+ production ([14C]aminopyrine accumulation) in response to GLP-1-(7-36) amide or histamine (r = 0.96; P < 0.01). Binding was maximal in purified parietal cells (F7), whereas almost no binding was detectable in enriched chief cells (F6). In F7, Scatchard analysis revealed a single class of high-affinity binding sites (KD = 2.8 +/- 0.6 x 10(-10) M, Bmax = 6.8 +/- 1.4 fmol/10(6) cells, 4,096 +/- 793 receptors/parietal cells). The following half-maximal inhibition values were found for GLP-1-(7-36) amide and (1-37) and (1-36) amide: 6.6 +/- 0.9 x 10(-10), 1.4 +/- 0.7 x 10(-7), and 2.6 +/- 0.4 x 10(-7) M, respectively. Pancreatic glucagon, GLP-2, and oxyntomodulin, products of the proglucagon gene, were 3-4 log units less potent displacers while gastric inhibitory peptide, vasoactive intestinal peptide, and secretin were ineffective. We conclude that rat parietal cells are equipped with specific high-affinity receptors for GLP-1-(7-36) amide, which, in addition, are present in as yet unidentified small cells (F1, F2) but not in chief cells.

Aminopyrine↗
PubMed1993

[Pneumonia due to a rare atypical Mycobacterium in AIDS].

A 38-year-old man, HIV-positive for 6 years, developed fever and cough with deterioration in his general state. Chest radiography demonstrated an infiltration in the left upper lobe and computed tomography showed a septated cavity. Three bronchioalveolar lavages over 4 weeks recovered Klebsiella, Candida, Pseudomonas and Staphylococcus in the lavage fluid. Acid-fast rods were not found in any of the microscopic preparations. His clinical condition and the radiological findings deteriorated despite appropriate antibiotic administration. A further cavity occurred in the right upper lobe and the inflammatory infiltrations extended further. Although no acid-fast organism had been demonstrated, tuberculostatic treatment was begun (daily 300 mg isoniazid, 600 mg rifampicin, 900 mg streptomycin, 2 g pyrazinamide). His general condition and the radiological findings rapidly improved. Four weeks after culturing the lavage fluid atypical Mycobacterium xenopi was isolated. This case illustrates the difficulty of diagnosing an atypical mycobacterial infection. It takes time and effort, but it is of great importance because up to 50% of patients with AIDS contract such infection. Early and appropriate treatment will significantly improve quality of life and life expectancy.

AIDS-Related Opportunistic Infections↗
PubMed1993

In man histamine and muscarinergic mechanisms are essential mediators of acid secretion in response to synthetic human gastrin (1-17).

It is still controversial whether gastrin stimulates acid secretion by interacting with specific gastrin receptors on parietal cells or via endogenous mediators, e.g., histamine. Therefore, it was our aim to determine in healthy human volunteers (n = 14; 3 females, 11 males; age 23-28 years) the degree by which the specific histamine H2-receptor antagonist famotidine or the muscarinergic antagonist atropine block acid secretion in response to synthetic human gastrin (hG) (1-17). Famotidine was deliberately administered at a supramaximal dose (40 mg i.v. bolus) to reliably block any and all effects of endogenous histamine on the parietal cells. After an overnight fast famotidine or saline were injected i.v., and gastric secretions were collected via a nasogastric tube for the ensuing 60 min to assess basal secretion. Thereafter, hG (1-17) was infused for 60 min in randomized order at two different rates: 0.75 ng/kg/min resulting in postprandial plasma gastrin levels (55-66 pg/ml), and 1.5 ng/kg/min yielding supraphysiologic levels (110-136 pg/ml). Both rates increased basal acid secretion (meq/10 min) from 0.5 +/- 0.2 to 3.8 +/- 0.6 and 4.7 +/- 0.5, respectively. Famotidine abolished basal acid secretion and completely blocked acid and volume secretion in response to both hG (1-17) doses. After injection of famotidine both hG (1-17) doses resulted in plasma levels exceeding those in controls by 18-27 pg/ml. A similar increase (14-16 pg/ml) was observed after famotidine injection without simultaneous hG (1-17) infusion indicating that this increase was due to the release of endogenous gastrin when the acid feedback inhibition was blocked by famotidine. To study a potential additional role of cholinergic mechanisms the effect of atropine (7 micrograms/kg i.m.) on hG (1-17)-induced acid secretion was examined. Atropine reduced basal acid secretion from 0.8 +/- 0.1 to 0.1 +/- 0.08 meq/15 min. Similarly, the response to 0.75 ng/kg/min hG (1-17) was reduced by 72.9%. Basal gastrin release was not altered by atropine which, however, tended to increase serum gastrin levels during infusion of hG (1-17) by 16-24 pg/ml. We conclude that in man histamine and muscarinic mechanisms are essential mediators of gastrin-stimulated acid secretion. The present data argue against a significant direct effect of gastrin alone on human parietal cells but rather support potentiating interaction with histamine and cholinergic mechanisms.

Adult↗
PubMed1993

Pertussis toxin-sensitive inhibition of glucagon-like peptide 1-stimulated acid production by epidermal growth factor and transforming growth factor alpha in rat parietal cells.

We have recently shown that the intestinal hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is a cAMP-dependent stimulant of rat parietal cell H+ production. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are known to inhibit histamine-stimulated parietal cell function by reducing cAMP production in a pertussis toxin-sensitive manner. Pertussis toxin blocks Gi alpha, the inhibitory subunit of adenylate cyclase, thereby preventing inhibitors from acting via Gi alpha. Therefore, we used pertussis toxin as a tool to determine whether EGF and TGF alpha inhibit GLP-1-stimulated parietal cell function via Gi alpha. In enriched (76 +/- 4%) rat parietal cells [14C]aminopyrine accumulation and cAMP production were maximally stimulated by GLP-1-(7-36) amide (10(-8) and 10(-7) M, respectively) or by histamine (10(-4) and 10(-3) M, respectively). EGF and TGF alpha (10(-13)-10(-7) M) caused concentration-dependent inhibition of GLP-1-stimulated parietal cell function. Maximal inhibition (33% and 37% of the response to GLP-1-(7-36) amide was observed at 10(-8) M EGF and 10(-9) M TGF alpha, respectively. There was a close correlation (r = 0.83; P < 0.05; n = 7) between the inhibition by EGF and TGF alpha of [14C]aminopyrine accumulation and the fall in cAMP production in GLP-1-stimulated parietal cells. The identical concentrations of both growth factors which maximally reduced GLP-1-stimulated parietal cell function inhibited [14C]aminopyrine accumulation in response to histamine by approximately 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗