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Biomedical subjects

J Mössner

Publications and source records attributed to J Mössner.

At least 127 records · Page 7Linked to original sources
PubMed1995

A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: a multicentre trial.

BACKGROUND: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase. AIM: To compare pantoprazole 40 mg with omeprazole 20 mg as once daily dosing in the treatment of reflux oesophagitis (grades II and III). METHODS: This double-blind, randomized, multicentre study included 286 patients. Patients were reendoscoped after 4 weeks, and continued to receive a further 4 weeks of treatment if they were not healed at this time. RESULTS: After 4 weeks of treatment, complete healing occurred in 126/170 (74%) patients in the pantoprazole group and in 67/86 (78%) patients in the omeprazole group (per-protocol analysis). At 8 weeks, the corresponding healing rates were 153/170 (90%) and 81/86 (94%). The differences between the treatment groups were not significant (P = 0.57 and 0.34). Improvement in the principal symptoms of reflux oesophagitis was also very similar between the treatment groups, with 59% and 69% at 2 weeks, and 83% and 86% at 4 weeks, respectively, being free from any individual symptom. Both treatments were well tolerated. CONCLUSIONS: This study has shown pantoprazole and omeprazole to be similarly effective and well tolerated in the treatment of mild to moderate reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

[Sense and nonsense in the treatment of exocrine pancreatic insufficiency].

Application of pancreatic digestive enzymes is indicated in cases of a quantitatively decreased exogenous secretion or an asynchronous secretion of enzymes with regard to the duodenal passage of chyme. A clear indication for therapy is a proven steatorrhea, a relative indication loss weight of and/or uncharacteristic abdominal discomfort in patients with proven pancreatic disease, i.e. chronic pancreatitis. Uncharacteristic abdominal discomfort alone, which is regarded as a consequence of 'maldigestion' without proven pancreatic disease, is not an indication for therapy. To prevent a destruction of exogenously applied lipase by gastric acid and to enable a synchronous gastroduodenal passage of the enzymes together with food, acid-protected micropellets or -tablets with an ideal diameter around 1.4 mm containing high amounts of lipase are requested. In cases of anacidity i.e. gastrectomy or type-A gastritis, lipase rich 'conventional' enzymes applied as granulate are sufficient. Combinations (pancreatic enzymes with bile acids) or fungal lipases have either more side effects (diarrhea) or are less efficient when compared to porcine enzymes. Acid-resistant microbial lipases may be useful in the near future. Application of pure proteases or pancreatic enzymes with high concentrations of proteases as treatment of pain in chronic pancreatitis ('negative feedback regulation') are a rather expensive form of treatment when compared to analgetics and are probably ineffective.

Cholecystokinin↗
PubMed1994

A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Effect of 5-fluorouracil on secretion and synthesis of pancreatic digestive enzymes: studies in isolated pancreatic acini and perfused pancreas derived from normal rats and from rats with acute necrotizing pancreatitis.

5-Fluorouracil (5-FU) has been claimed to have beneficial effects in human pancreatitis because of its ability to inhibit protein synthesis and secretion. However, the effect of 5-FU has not been studied in the pancreas of animals in more detail and the data in human pancreatitis are mostly derived from uncontrolled studies. Thus, we studied potential short-term effects of 5-FU on protein synthesis and secretion in isolated pancreatic acini from normal rats and from rats with sodium taurocholate-induced pancreatitis. Furthermore, we used the isolated perfused pancreas, damaged by taurocholate, to study whether arterial perfusion with 5-FU has any beneficial effects. When pancreatic acini were incubated with various concentrations of 5-FU, CCK-8-stimulated amylase secretion was not altered. Furthermore, 5-FU had no short-term effects on protein synthesis. Protein synthesis and secretion was already markedly depressed in isolated pancreatic acini derived from rats with sodium taurocholate-induced pancreatitis. 5-FU did not further decrease protein synthesis or secretion. Retrograde injection of sodium taurocholate in the main pancreatic duct of the isolated perfused pancreas resulted in a steep increase of amylase and lipase in the portal effluate. Arterial perfusion with 5-FU had no influence on enzyme release into the portal blood. We may conclude that our data, derived from experimental pancreatitis in rats, do not encourage investigation of the effect of 5-FU, an anticancer drug with possibly toxic side effects, in human pancreatitis.

Acute Disease↗
PubMed1993

DNA mapping of colorectal neoplasms: a flow cytometric study of DNA abnormalities and proliferation.

BACKGROUND: There is some evidence that neoplastic development and progression evolve through a multistep process associated with hyperproliferation and genetic alterations. Therefore, changes of proliferation and of cellular DNA content within the adenoma-carcinoma sequence were studied. METHODS: Using a "mapping" procedure, 12 adenomas and 18 carcinomas were analyzed flow cytometrically and histologically. In addition, normal mucosa adjacent to and distant from the tumors was assessed in the same way. RESULTS: Of 59 adenomatous fractions, 35.6% (n = 21) were aneuploid, whereas the incidence of aneuploidy was 63.5% (54/85) in the carcinomatous sites. Additional tetraploidies were identified in 5 (8.5%) and 13 (15.3%) adenomatous and carcinomatous samples, respectively. Cell proliferation, as determined by the percentage of S-phase cells, was significantly (P < 0.001) higher in the carcinomatous specimens (14.8% +/- 0.8%; mean +/- SEM) than in the adenomatous ones (8.1% +/- 0.7%). It decreased to normal mucosa adjacent to (5.1% +/- 0.5%) and distant (5.3% +/- 0.6%) from the neoplasms. DNA mapping of the tumors revealed both distinct regions and extended areas of aneuploidy and tetraploidy. There is evidence from the mapping data that aneuploid populations arise at a single focus of the adenoma and expand over large areas before a subpopulation of cells acquires the capacity of invasion. CONCLUSIONS: These data showing consecutive DNA content abnormalities within the colorectal adenoma-carcinoma sequence provide support for genomic instability and clonal evolution as important events of tumorigenesis and progression.

Adenoma↗
PubMed1993

Role of phospholipase A2 in pancreatic acinar cell damage and possibilities of inhibition: studies with isolated rat pancreatic acini.

Phospholipase A2 (PLA2) has been postulated to play an important role in the pathogenesis of acute pancreatitis. To study the mechanism through which PLA2 may cause cellular damage, we used an in vitro model of isolated rat pancreatic acini prepared by collagenase digestion. Newly synthesized proteins were labeled by [35S]methionine. Cellular destruction was measured by the degree of release of radiolabeled proteins. Incubation of pancreatic acini with PLA2 alone caused only minor damage when very high concentrations of this enzyme were used. However, when acini were incubated with PLA2 in combination with its substrate, lecithin, cells were destroyed in a time- and concentration-dependent manner. Incubating cells with pancreatic homogenates and lecithin caused damage only when there had been prior activation of homogenates with either trypsin or enterokinase. The damage could be simulated by incubating acini with pure lysolecithin. Alcohol and cerulein did not further increase the destruction caused by PLA2 and lecithin. When acini were incubated with supernatants from another set of acini to which oleic acid had been added, a similar degree of damage resulted as compared with acini incubated with oleic acid alone. However, adding PLA2 to supernatants from acini preincubated with fatty acids significantly increased the degree of cellular necrosis. The destruction by PLA2 and lecithin was inhibited by albumin but could not be inhibited by gabexate mesilate, nafamostat mesilate, or cytidine diphosphocholine. We conclude that PLA2 could play a role in pancreatic acinar cell damage, especially in the spread of cellular necrosis within the organ, provided that its substrate, lecithin, is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Is there a place for pancreatic enzymes in the treatment of pain in chronic pancreatitis?

According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. However, we have demonstrated in healthy volunteers that intraduodenal application of porcine pancreatic extracts does not inhibit but rather stimulates pancreatic enzyme secretion. This is probably due to the high protein content of porcine pancreatic extracts which may overwhelm a potential inhibitory effect of proteases. In a prospective placebo-controlled, double-blind, multicenter study to investigate the effect of acid-protected porcine pancreatic extracts on pain in 43 patients with chronic pancreatitis, pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between the two treatment arms. The pancreatic extract that we have used in our study neither inhibits pancreatic enzyme secretion nor is it very efficient in lowering pain in chronic pancreatitis.

Abdominal Pain↗
PubMed1992

Malignant lymphomas of the upper gastrointestinal tract. Results of a prospective study in 103 patients.

BACKGROUND: There is a discrepancy between the incidence of gastrointestinal involvement by malignant lymphomas, as established in postmortem studies, and the rareness of the corresponding clinical diagnosis. METHODS: Therefore, the authors performed routine upper gastrointestinal endoscopic examination, within the framework of the usual staging examinations, in 103 consecutive patients with newly diagnosed Hodgkin disease (n = 21) and non-Hodgkin lymphoma (n = 82). RESULTS: One patient with Hodgkin disease (4.8%), 11 of 40 patients (27.5%) with non-Hodgkin lymphoma of low-grade malignancy, and 11 of 42 (26.2%) of those with highly malignant non-Hodgkin lymphoma showed involvement of the gastric and/or duodenal mucosa, as diagnosed with esophagogastroduodenoscopy. Of the 22 patients with non-Hodgkin lymphoma, 9 had involvement of other mucosa-associated lymphoid or epithelial tissue. In two patients with Stage III, two with Stage II, and two patients with presumptive Stage I disease, the disease was reclassified as Stage IV. Because of gastrointestinal involvement, treatment for two patients was changed from radiation therapy to chemotherapy and another two patients had gastric resections so that possible treatment-related complications could be avoided. CONCLUSIONS: In light of these results and the fact that a major basis for the therapeutic strategy for malignant lymphomas is tumor stage, routine esophagogastroduodenoscopic examination within the framework of the usual staging examinations is recommended. In individual cases, this procedure may be of decisive importance in the therapeutic approach to and prevention of complications.

Adolescent↗
PubMed1992

Influence of various nutrients and their mode of application on plasma cholecystokinin (CCK) bioactivity.

CCK is known to be a major endocrine stimulant of the exocrine pancreas. However, the influence of various compositions of nutrients and their mode of administration on plasma CCK is still not clear. We therefore studied plasma CCK after either oral or intraduodenal administration of various solid and liquid diets. Plasma CCK was measured by bioassay. Nine healthy male volunteers received three different isocaloric diets via intraduodenal perfusion (1 kcal/ml; 300 ml/90 min). Diet A consisted of low-molecular oligopeptides (energy: protein 18%, fat 22%, carbohydrates 60%); diet B was a high molecular diet enriched with fat and fiber (protein 15%, fat 30%, carbohydrates 55%, fiber 1 g/100 ml); and diet C was a high molecular diet, poor in fat and fiber-free (protein 14%, fat 7%, carbohydrates 79%). All diets caused a rapid increase in plasma CCK, followed by a slow decrease. The highest CCK plasma values were achieved with diet B (8.4 +/- 1.6 pM); diets A and C led to similar, rather low plasma CCK values (A: 5.0 +/- 0.7 pM). Another five volunteers received the above-described liquid diets orally. Integrated CCK plasma values were similar for all oral liquid diets studied and not different from those seen after intraduodenal administration of the high-molecular high-fat diet B. Oral administration of a solid diet (ten volunteers) comparable to diet B in calories and nutrient composition caused a rather small and delayed increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.

Animals↗
PubMed1992

Comparison of different treatment modalities in experimental pancreatitis in rats.

Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate), and albumin under different conditions in rats were investigated. (a) Isolated pancreatic acini were incubated with pancreatic homogenates and triglycerides or lecithin with or without albumin and the degree of cellular destruction quantitated. (b) Taurocholate was injected into the pancreatic duct of isolated pancreas and the organ continuously perfused with either FUT, THL, or albumin. Organ damage was evaluated by measurement of pancreatic enzymes in the portal effluence. (c) Necrotizing pancreatitis was induced in vivo via retrograde taurocholate injection. FUT, THL, or albumin was applied either intravenously or injected into the pancreatic parenchyma. (a) Albumin prevented the cellular damage caused by both fatty acids and lysolecithin. (b) THL was ineffective, FUT lowered the release of pancreatic enzymes into the portal effluence, and albumin was most effective. (c) Albumin prevented the development of panlobular necrosis and lowered the degree of extrapancreatic fat necrosis. Albumin, via its ability to bind detergents, may have therapeutic implications.

Albumins↗
PubMed1992

Immunoglobulin G (IgG), IgG1, and IgG2 determinations from endoscopic biopsy specimens in control, Crohn's disease, and ulcerative colitis subjects.

Acute exacerbations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease) are characterised by an increase in immunoglobulin G (IgG) positive cells in the mucosa, whereas uninflamed mucosa of inflammatory bowel disease patients displays only moderately increased or normal numbers of these cells. Previous data suggest that acute exacerbations of ulcerative colitis and Crohn's disease can be distinguished by different IgG subclass expression of mucosal immunocytes and a different IgG subclass production pattern of lamina propria lymphocytes. A procedure to obtain enough intestinal mononuclear cells from biopsy specimens to measure in vitro IgG and IgG1 production in control subjects and various patient groups has been established. IgG2 could be measured in Crohn's disease and ulcerative colitis only, as the concentrations in control subjects were below the sensitivity of the ELISA method. We found that IgG and IgG1 production correlated with the degree of local inflammation in both diseases, even in slightly inflamed mucosa, compared with control subjects. The proportion of IgG1 subclass was significantly increased in severely inflamed mucosa of both ulcerative colitis and Crohn's disease patients. A major difference between Crohn's disease and ulcerative colitis mucosa is apparent in mild or no inflammation. In Crohn's disease mucosa in remission, the IgG1/IgG ratio is comparable with that in controls, yet ulcerative colitis mucosa still displays significantly increased proportions of IgG1. In addition, the IgG2/IgG ratio is 0.12 in ulcerative colitis and 0.19 in Crohn's disease patients. The results show the dependence of local IgG and IgG1 production on the degree of inflammation and that an increase in subclass IgG1 in ulcerative colitis is present at all stages, including remission. These findings support the hypothesis that different immunoregulatory mechanisms are involved in Crohn's disease and ulcerative colitis. Environmental stimuli or genetic background may be responsible for the observed differences.

Biopsy↗
PubMed1992

Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial.

According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.

Adult↗