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Biomedical subjects

F Stöckmann

Publications and source records attributed to F Stöckmann.

At least 37 records · Page 2Linked to original sources
PubMed1991

Antral Helicobacter pylori-like organisms in different states of gastric acid secretion.

The frequency of Helicobacter pylori (H.p.) infestation in antral mucosa and the presence of gastritis were investigated in different states of gastric acid secretion. Biopsies were stained by the Warthin-Starry technique and hematoxylin-eosin. Antral H.p. was found in similar frequencies in Zollinger-Ellison syndrome (n = 17; profound acid hypersecretion, associated with duodenal ulcer disease in most cases) and the same number of age-matched controls (35% in each group) whereas H.p. could be detected in 31 out of 33 duodenal ulcer patients (94%). The incidence of H.p. infestation in H2-blocker refractory reflux oesophagitis was low (24%). Treatment of peptic lesions with omeprazole (drug-induced hypochlorhydria) led to a reduction or disappearance of H.p. in 7 out of 10 H.p.-positive patients whereas none of 19 primarily H.p.-negative patients became infected with H.p. during prolonged omeprazole therapy. It is concluded that (1) development of duodenal ulcers (as in gastrinomas) does not necessarily require H.p., and (2) at least in some patients H.p. is reduced in antral mucosa by omeprazole.

Adolescent↗
PubMed1991

Treatment of gastrointestinal endocrine tumours with interferon-alpha and octreotide.

This paper reports on the results of two controlled therapeutic trials on patients with endocrine tumours of the gastrointestinal tract. Seventeen patients were treated up to 18 months with recombinant interferon-alpha 2c (2 x 10(6) IU/m2 s.c. daily) and 16 patients are treated in an ongoing study with octreotide (3 x 200 micrograms daily). Objective response (greater than 50% reduction of hormone secretion) was observed in one of 15 evaluable patients on IFN-alpha and in 12 of 16 patients on octreotide. Reduction of tumour size was not observed in these two trials. However, the majority of patients had stable tumour size during IFN-alpha and octreotide treatment despite progressive disease before. Subjective improvement due to reduction of symptoms such as flushing, diarrhea, and dermatitis was significantly more frequent after octreotide than after IFN-alpha. Of five endocrine tumour patients with progressive disease on IFN-alpha, three responded to subsequent treatment with octreotide while one had stable disease and one progressed. Two cases are reported from the authors' series of patients treated with octreotide before start of these trials. Complete remission of the tumour by low-dose (2 x 100 micrograms daily) octreotide was observed in one carcinoid patient. This remission has now lasted for four years. In one patient with liver metastasis of a VIPoma, who had become resistant to streptozotocin, his watery diarrhoea is now completely controlled with 100 micrograms octreotide s.c. every second day.

Aged↗
PubMed1990

Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients.

In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.

Adenoma, Islet Cell↗
PubMed1990

Camostate (FOY-305) improves the therapeutic effect of peritoneal lavage on taurocholate induced pancreatitis.

The effect of peritoneal lavage with the addition of camostate to the lavage fluid on the outcome of taurocholate pancreatitis in rats was studied. Camostate is a low molecular weight protease inhibitor which has been developed recently. Peritoneal lavage was performed for 12 hours and camostate was added to the lavage fluid in five concentrations. At 0.1 mg/ml the survival rate increased significantly (11 of 20 v controls 4 of 20, p less than 0.05); the maximal effect was observed at 0.2 mg/ml, and no effect was seen at 0.01 and 0.05 mg/ml. Adverse effects occurred at 0.5 mg/ml. The addition of 0.1 mg/ml camostate significantly reduced the acidosis in arterial blood: mean (SD) pH 7.30 (0.035) v controls 7.23 (0.054) (n = 9, p less than 0.01) and arterial base excess: -15.4 (1.26) mmol/l v controls: -17.4 (2.51) mmol/l (n = 9, p less than 0.05). There was no difference, however, in plasma amylase activity and in the histological degree of specific tissue damage to the pancreas. A combination of intravenous camostate and lavage with the addition of camostate to the lavage fluid yielded a significantly improved survival compared with treatment with intravenous camostate alone (10 out of 16 animals v intravenous camostate alone, two out of 16, p greater than 0.01). We conclude that lavage with camostate significantly improves the prognosis of severe necrotising pancreatitis in rats.

Acute Disease↗
PubMed1990

Acute and chronic effects of cyclosporine A on pancreatic polyamine metabolism and pancreatic adaptation.

The present study was designed to investigate the effects of acute and chronic application of the immunosuppressive agent cyclosporine A (CsA) on pancreatic polyamine metabolism as well as pancreatic growth of rats in vivo. Seven to ten animals per group were treated with either the synthetic trypsin inhibitor camostate (FOY-305, 200 mg/kg b.wt. p.o. twice a day), CsA (10 mg/kg b.wt. p.o. once a day), camostate plus CsA, or oil as control, and animals were killed after 8 h, 1, 5 and 14 days. Feeding of camostate resulted in a significant increase of the measured parameters in the following time-course: cholecystokinin (CCK), 8 h; ornithine decarboxylase (ODC), 8 h: putrescine, 8 h; S-adenosylmethionine decarboxylase (SAM-DC), 1 day; pancreatic weight, 1 day; protein content, 5 days; spermidine, 5 days; RNA, 5 days; and DNA, 14 days. Simultaneous treatment with CsA resulted in a significant inhibition of camostate-induced increases in ODC, SAM-DC as well as putrescine and spermidine and furthermore caused a nearly complete inhibition of the increase of all trophic parameters, while CCK plasma levels were not altered. Counterregulatory mechanisms to maintain the intracellular polyamine pool as known after application of specific inhibitors of enzymes of the polyamine metabolism (i.e. DFMO) were not observed. Therefore we conclude that CsA does not directly interact with the polyamine metabolism, but rather with the second messenger system or any other intracellular mechanism, that is activated after stimulation with CCK before the polyamine metabolism is induced.

Acetyltransferases↗
PubMed1989

Effect of a long-acting somatostatin analogue (octreotide) on circulating tachykinins and the pentagastrin-induced carcinoid flush.

Cutaneous flushing was provoked in seven patients with metastatic carcinoid tumours and the carcinoid syndrome by an intravenous injection of pentagastrin (0.6 micrograms.kg-1 body weight). The patients were studied before and 1 h after a subcutaneous injection of the long-acting somatostatin analogue octreotide 50 micrograms (Sandostatin). The severity of the carcinoid flush in all the patients was reduced by administration of the analogue. The rise in facial temperature was 1.3 (0.3) degree C before and 0.8 (0.2) degree C after octreotide. Six patients responded to pentagastrin with a rise in the circulating neurokinin A-like immunoreactivity (NKA-LI) and five patients with a rise in circulating substance P-like immunoreactivity (SP-LI). No cutaneous flushing or rise in tachykinin concentration was observed in healthy subjects (n = 6) after injection of pentagastrin. The rise in NKA-LI in the patients was decreased by 61 (14)% and the rise in SP-LI by 54 (13)% after octreotide. Although flushing still occurred, the tachykinin response in two patients was completely abolished. The data demonstrate that the release of tachykinins from carcinoid tumours during pentagastrin-induced flushing is subject to partial inhibition by octreotide. However, the occurrence of a flush in some patients in the absence of a detectable rise in circulating tachykinins indicates that the latter peptides cannot be the sole causative agent of the carcinoid flush.

Aged↗
PubMed1989

Dose-dependent inhibition by cyclosporine A of the induction of pancreatic ornithine decarboxylase (ODC) in rats.

The effect of cyclosporine A (CsA) and alpha-difluoromethylornithine (DFMO) on the camostate-induced increase in pancreatic ornithine decarboxylase (ODC) activity and polyamine biosynthesis has been studied in vivo. Six hours after application of the synthetic trypsin inhibitor camostate (200 mg/kg b wt orally) pancreatic ODC activity increased about 140-fold and putrescine concentration about ninefold. CsA inhibited the elevation of both parameters in a dose-dependent manner. CsA pretreatment for 3 d with doses of 7.5, 10.0, and 12.5 mg/kg b wt orally once a day and consecutive CsA blood levels 24 h after the last CsA application of 751 +/- 62, 968 +/- 70, and 1,395 +/- 79 ng/mL, respectively, resulted in a complete inhibition of the camostate-stimulated increase in pancreatic ODC activity and putrescine concentration in vivo. DFMO (2% in drinking water and additionally 300 mg/kg b wt intraperitoneally at 8 AM, 12 noon, and 4 PM) inhibited the increase in both, ODC activity, and putrescine, significantly in an equipotent degree as 2.5 mg CsA/kg b wt, whereas higher doses of CsA proved to be more effective than DFMO in the chosen subtoxic dose. In all cases, no significant changes in pancreatic spermidine and spermine concentration, DNA and protein content, or pancreatic and body weight were observed. It is concluded that CsA in doses used for immunosuppression in clinical practice is a very potent and more effective inhibitor of ODC activity and polyamine synthesis in vivo than DFMO. This ODC inhibitory effect of CsA is a further detail to elucidate the up to now incompletely understood mechanisms of action of this immunosuppressive agent.

Animals↗
PubMed1989

The effect of cyclosporin A on rat pancreatic B-cell: interaction with the calcium-antagonist diltiazem.

Cyclosporin A (CyA) was fed to male Wistar rats in a dose of 5, 10 or 50 mg/kg b.wt. for 7 days. In another experimental procedure 10 mg/kg b.wt. CyA was given for 7 days combined with Diltiazem (DIL) 6.25 mg/kg b.wt. once daily ip. Glucose stimulated insulin secretion from the isolated perfused pancreas was investigated in these animals. Total insulin secretion (ng/50 min) was not affected after feeding 5 mg/kg b.wt. CyA, but was significantly decreased with 10 and 50 mg/kg b.wt. CyA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. CyA during the initial peak (0-10 min) but not during the second peak (10-50 min), whereas after 10 and 50 mg/kg b.wt. CyA both peaks nearly reached base-line levels. DIL markedly increased the initial peak (0-10 min) after feeding CyA 10 mg/kg b.wt., whereas the second peak was not affected. Our results demonstrate a toxic effect of CyA on the pancreatic B-cell, which might be partly abolished by calcium-antagonists.

Animals↗
PubMed1989

Impairment of stimulated insulin release from the isolated perfused rat pancreas by cyclosporine pretreatment.

Cyclosporine was fed to male Wistar rats in a dose of 5, 10, or 50 mg/kg b.wt. for 7 days, and the effect on insulin secretion from the isolated perfused pancreas was investigated. Dose-dependently plasma insulin and pancreatic insulin content decreased while whole-blood CsA levels increased. An increase in blood glucose was only observed after feeding 50 mg/kg b.wt. CsA resulting in whole-blood CsA levels of 7735 ng/ml. Glucose (20 mM)-stimulated total insulin secretion (ng/50 min) was not affected during feeding 5 mg/kg b.wt. CsA, but was significantly reduced after feeding 10 or 50 mg/kg b.wt. CsA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. during the initial peak (0-10 min) but not during the second peak (10-50 min), whereas after 10 or 50 mg/kg b.wt. CsA both peaks were markedly reduced. The arginine (20 mM) and the arginine (20 mM)-plus-glucose (20 mM) stimulated insulin secretion was less affected after feeding 10 mg/kg b.wt. CsA than after stimulation with glucose (20 mM) alone. The addition of CsA to the perfusate did not influence glucose-stimulated insulin release from normal rat pancreas. Our results demonstrate a toxic effect of CsA on the pancreatic beta cell that is dose dependent and possibly influences both insulin secretion and biosynthesis.

Animals↗
PubMed1989

Influence of CCK antagonist L-364,718, pancreastatin (33-49) and a somatostatin analogue on camostate-induced rat pancreatic hypertrophy.

Since endogenous cholecystokinin (CCK) is released after oral administration of camostate, it has been suggested that camostate-induced pancreatic growth is mediated via circulating CCK. To test this concept, we investigated the effects of three potentially inhibitory substances on rat pancreatic hypertrophy caused by feeding of camostate over 2 weeks: (1) L-364,718, the novel specific highly potent nonpeptide CCK receptor antagonist, (2) octreotide (SMS 201-995), a potent long-lasting somatostatin analogue and (3) pancreastatin (33-49), the biologically active C-terminal fragment of the novel gastrointestinal peptide pancreastatin. Camostate feeding (200 mg/kg) once daily for 14 days induced a significant increase in pancreatic weight, total protein, trypsinogen and polyamine levels, whereas total amylase content was substantially diminished. Simultaneous oral or subcutaneous treatment with L-364,718 (0.3 mg/kg twice daily) completely suppressed all trophic effects of camostate. Octreotide (25 micrograms/kg twice daily s.c.) and pancreastatin (33-49) (10 micrograms/kg twice daily s.c.) did not change any trophic parameter. In case of octreotide it could be shown that two daily injections only partially suppressed elevated CCK levels. Pancreatic DNA and putrescine levels were slightly reduced in rats receiving the CCK antagonist alone. These results demonstrate that camostate-induced pancreatic hypertrophy in rats is caused by the release of endogenous CCK which may contribute to the maintenance of normal pancreatic DNA and putrescine concentrations.

Animals↗
PubMed1989

Quantitative studies of gastric endocrine cells in patients receiving long-term treatment with omeprazole.

A total of 36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with omeprazole 20-60 mg/day, for periods up to 3 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a mean of 81.5 to 206 pg/ml; a slight decrease was observed thereafter. There was no significant increase in the volume density of argyrophilic cells in the oxyntic mucosa. No clusters of endocrine cells were found in the oxyntic mucosa and no change of G-cell volume density occurred in the antral mucosa under therapy. Omeprazole therapy did not result in any changes in gastrin levels or oxyntic argyrophilic cells in the antrectomized patients. It is concluded that the moderate hypergastrinaemia observed during long-term omeprazole treatment in man does not induce hyperplasia of argyrophilic cells in the oxyntic mucosa.

Biopsy↗
PubMed1988

Circulating bradykinin-like immunoreactivity and the pentagastrin-induced carcinoid flush.

Bradykinin and structurally related peptides are potent vasodilators and a role for these kinins in the aetiology of the carcinoid flush has been proposed. Using an antiserum directed against the COOH-terminal region of bradykinin in radioimmunoassay, the concentrations of bradykinin-like immunoreactivity in extracts of peripheral blood were compared in patients with carcinoid syndrome (n = 11) and healthy subjects (n = 6). In the fasted state, the concentrations of bradykinin-like immunoreactivity in the patients (10 +/- 5 ng/l) were not significantly different from the concentrations in healthy subjects (6 +/- 3 ng/l). An intravenous injection of pentagastrin (0.6 micrograms/kg) provoked a flush of differing degrees of severity in all patients. In four patients, the flush was concurrent with large rises (277-, 26-, 11- and 10-fold over mean basal values) in bradykinin-like immunoreactivity that was resolved by high performance liquid chromatography into lysyl-bradykinin and bradykinin (approximate ratio 1:2). In two patients, small rises in immunoreactivity (2.4- and 1.7-fold) occurred after the flush and in the remaining five patients no rise in bradykinin-like immunoreactivity was measured. In the healthy subjects, the pentagastrin injection did not provoke a flush and no rises in bradykinin-like immunoreactivity were observed. The data support earlier results obtained using bioassays that the carcinoid flush in some patients is associated with the appearance in blood of bradykinin-related peptides. It has been shown, however, that these kinins cannot be the sole causative agent of the flush. It is suggested, therefore, that the aetiology of the flush is probably multi-factorial.

Aged↗
PubMed1988

Long-term omeprazole treatment in man: effects on gastric endocrine cell populations.

36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with 40-60 mg of omeprazole daily for periods between 1 and 2 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a medium level of 81.5 to 206 pg/ml, a slight decrease was seen thereafter. In 10 patients investigated before the start of the treatment and after 1 and 2 years, the volume density of argyrophilic cells in the oxyntic mucosa increased from 0.43 +/- 0.08 to 0.91 +/- 0.14% during the first year; this change was statistically significant. No further increase was observed thereafter. No such difference could be demonstrated between a larger group of 18 patients investigated before and after 1 year of treatment with omeprazole (0.806 +/- 0.1 vs. 0.93 +/- 0.08%) and between a larger group of 22 untreated patients and 17 patients treated for 17-24 months with omeprazole (0.73 +/- 0.1 vs. 0.86 +/- 0.09%). The volume density of argyrophilic cells found in 8 patients with gastrinoma amounted to 1.37 +/- 0.22%. No clusters of endocrine cells were found in omeprazole-treated patients. The D cell volume density in the antral mucosa decreased significantly during the first months of treatment, but steadily increased thereafter to reach pretreatment values after 17 months. There was no change in G cell volume density under therapy. No changes in gastrin levels or oxyntic argyrophilic cells were observed in the antrectomized patients. It is concluded that the hyperplasia of argyrophilic cells observed in some patients during long-term omeprazole treatment is mediated by hypergastrinaemia.

Female↗
PubMed1988

[Treatment of gastrointestinal neuroendocrine tumors with the somatostatin analog octreotide (Sandostatin)].

Somatostatin, a 14 amino acid peptide hormone, is a potent inhibitor for secretion of gastrointestinal hormones from endocrine cells. The clinical use of somatostatin for treatment of endocrine gastrointestinal tumours was limited due to its short half-life (2-3 min). Octreotide (Sandostatin), a long-acting somatostatin analogue, has been developed for subcutaneous use with an elimination half-life of about 45 min. This offers a new way of long-term treatment for patients with endocrine gastrointestinal tumours. The effect of octreotide in various forms of these diseases and its importance for the possible inhibition of tumour growth are described.

Apudoma↗
PubMed1988

Effects of single and combined infusions of human biosynthetic proinsulin and insulin on glucose metabolism and on plasma hormone concentrations in euglycaemic clamp experiments.

Euglycaemic clamp experiments with single or combined infusions of human biosynthetic proinsulin and insulin were performed in 6 healthy, normal weight subjects in order to assess the possibility of antagonistic, additive, or synergistic effects on whole body glucose metabolism. Insulin (i: 2.02 pmol x kg-1 x min-1) or proinsulin (p: 9.26 pmol x kg-1 x min-1) were infused under euglycaemic clamp conditions over 240 min. After 120 min, the infusion rates were doubled (protocols ii and pp), or proinsulin (protocol ip) or insulin (protocol pi) infusions were added. After 240 min of infusing insulin or proinsulin alone, euglycaemia was maintained for an additional 60 min period without hormone infusions to measure the decay of hormone concentrations and of effects on glucose metabolism. Effects on glucose uptake were measured as the glucose infusion rate necessary to maintain euglycaemia. IR-insulin, IR-proinsulin, IR-C-peptide and IR-glucagon were determined by specific radioimmunoassays. After 240 min, similar steady state glucose infusion rates were reached for all protocols (mean +/- SEM, mg x kg-1 x min-1: ii: 10.6 +/- 1.0; ip: 9.1 +/- 0.4; pi: 10.0 +/- 0.9; pp: 8.4 +/- 0.7). The infusion rate with proinsulin alone (pp), however, was significantly smaller than with insulin alone (ii), indicating a somewhat lower effectiveness of the proinsulin dose employed. With all protocols, nonesterified fatty acid and IR-glucagon concentrations were decreased to a similar extent. Steady state hormone concentrations were reached within 30 min of each infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗