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Biomedical subjects

H Goebell

Publications and source records attributed to H Goebell.

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

Influence of the calcium antagonist nitrendipine on the hepatotoxic effect of cyclosporine A.

Calcium antagonists have a protective effect on different forms of nephrotoxicity due to cyclosporine A (CsA). The objective of the present study was to examine the influence of a calcium antagonist on the liver function in CsA-treated patients after kidney transplants. Different quantitative liver function tests were performed in six patients before and 3 months after administration of the calcium antagonist nitrendipine. Indocyanine green clearance (ICG-Cl) as a marker for hepatic blood flow and excretion showed a significant increase under nitrendipine. In addition, there was an improvement of the galactose elimination capacity. Although nitrendipine and lidocaine are both metabolized by the cytochrome P system, there was no reduction in lidocaine clearance. These results suggest an improvement of liver function under nitrendipine. Whether these findings alone are the expression of an improved liver blood flow or whether there is an additional hepatoprotective characteristic of the calcium antagonist nitrendipine cannot be determined.

Cyclosporine↗
PubMed1991

[Effect of pancreastatin on insulin secretion and the exocrine pancreas in rats].

Pancreastatin, a 49-amino-acid C-terminal amidated peptide, was isolated from porcine pancreas in 1986. It has been reported to inhibit insulin release and exocrine pancreatic secretion, but both these effects have been disputed. In the isolated perfused rat pancreas we therefore studied the effect of pancreastatin on insulin and exocrine pancreatic secretion. Neither basal exocrine pancreatic secretion, nor exocrine secretion stimulated by CCK-8, bombesin or secretin were affected by pancreastatin. 20 or 200 pM pancreastatin, however, significantly inhibited stimulated insulin release. We conclude that pancreastatin seems to be yet another inhibitory peptide, which--for unknown reasons--inhibits insulin release both in vivo and in vitro, but exocrine pancreatic secretion only in vivo.

Animals↗
PubMed1991

[Influence of the ileum on the regulation of gastrointestinal motility].

Under normal conditions a "physiologic malabsorption" and thus nutrients in the lower small intestine in the late postprandial state can be observed in humans. To study the effects of "physiologic" quantities of nutrients in the distal small intestine on upper gastrointestinal motor functions, 9 healthy subjects were intubated with an oro-ileal multi-lumen tube. The continuous perfusion of the duodenum with essential amino acids induced a fed motility pattern. In 12 out of 14 cases additional ileal perfusion with carbohydrates (60 kcal), but not with saline, converted the fed motility pattern to a pattern characteristic of the interdigestive state. These findings suggest that the ileum takes part in the late postprandial regulation of proximal gastrointestinal motor functions in humans.

Amino Acids, Essential↗
PubMed1990

Evaluation of the Crohn's Disease Activity Index (CDAI) and the Dutch Index for severity and activity of Crohn's disease. An analysis of the data from the European Cooperative Crohn's Disease Study.

In the European Cooperative Crohn's Disease Study a general documentation of clinical and laboratory data was made at the entry into the study in 452 patients. These patients were in different states of their disease from quiescent to very active. In all patients the Crohn's Disease Activity Index of Best (CDAI) and the Dutch Index of van Hees was calculated. Three gastroenterologists did a global clinical rating and a separate laboratory rating without knowledge of the indices. The ratings were then correlated with the indices in the individual patients. The clinical rating correlated well with the CDAI (r = 0.88) and less with the Dutch Index (r = 0.672). On the other hand the laboratory rating showed a better correlation with the Dutch Index (r = 0.742) than with the CDAI (r = 0.573). This demonstrates that the CDAI preferably is an estimate of the clinical severity of the disease and not of the activity of inflammation. Vice versa the Dutch Index is mainly reflecting the activity of the inflammatory process.

Colitis↗
PubMed1990

[Prevalence, causes and effects of increased iron storage in patients with kidney transplantation].

Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs-persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts.

Adolescent↗
PubMed1990

[Serology and culture diagnosis of Campylobacter jejuni infections].

Campylobacter jejuni is known today as one of the most common pathogens in acute infectious enteritis. In 77 patients serological testing by complement fixation as well as stool cultures were performed. A campylobacter jejuni infection was identified in 53% by culture and in 64% by serology, only in 17% the diagnosis was made with both methods. We conclude, that because of these data stool culture and serological testing should be used simultaneously. The complement fixation technique shows an increase in serum titer one to three weeks after beginning of the illness and a decrease in serum titer after four to eight weeks. For this reason it is an appropriate method for the identification of acute infections.

Antibodies, Bacterial↗
PubMed1990

Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion.

To study the effects of intraileal nutrients on human pancreatic secretion and gastrointestinal motility, nine healthy subjects were intubated with an oroileal multilumen tube for ileal perfusion, duodenal juice aspiration, and intestinal motility recording. The duodenum was perfused continuously with essential amino acids to induce submaximal stimulation of pancreatic enzyme secretion and fed motility pattern. Additional ileal perfusion with carbohydrate at quantities similar to those observed under physiological late postprandial conditions or fat at isocaloric loads significantly decreased pancreatic enzyme outputs by greater than 80% (P less than 0.001) compared with saline. Ileal carbohydrate or fat induced a duodenal motor activity front that migrated distally and was followed by reduced motility. In summary, ileal delivery of small quantities of nutrient markedly decreased endogenously stimulated pancreatic enzyme secretion in humans. This was associated with specific changes in fed intestinal motility that converted to patterns characteristic of the interdigestive state. Our findings suggest that the distal small intestine may participate in the late postprandial regulation of gastrointestinal function in humans.

Adult↗
PubMed1990

Characterization of the major form of cholecystokinin in human intestine: CCK-58.

Acid extracts of human intestines obtained from surgical samples or from organ donors contain cholecystokinin (CCK) immunoreactivity. From surgical samples, extracted and eluted quickly, greater than 75% of the CCK immunoreactivity eluted in the same region as purified canine CCK-58 during analytical reverse-phase high-pressure liquid chromatography (HPLC). A major portion of the CCK immunoreactivity from donor intestinal extracts also eluted in this region. This immunoreactivity has been purified from human intestinal extracts by a series of several reverse-phase and cation-exchange chromatographies. Amino acid and microsequence analysis showed that this immunoreactivity is human CCK-58. Tryptic digestion of purified human CCK-58 produced another immunoreactive form that eluted in the position of CCK-8 during analytical reverse-phase HPLC. The immunoreactivity of the trypsin-digested material was 2.6-fold higher than that of an identical sample of CCK-58 incubated without trypsin. Thus the carboxyl-terminal antibody used for radioimmunoassay cross-reacts greater than twofold less with human CCK-58. This diminished cross-reactivity would lead to an underestimation of the relative proportions of CCK-58 in tissue and plasma extracts. If CCK-58 is the major circulating form this diminished cross-reactivity would also lead to underestimations of the circulating levels of total CCK. Determination of human CCK-58 structure confirms that one of the major components of human CCK that expresses biological activity is CCK-58.

Amino Acid Sequence↗
PubMed1990

Molecular variants of cholecystokinin after endogenous stimulation in humans: a time study.

The time-dependent release of molecular variants of cholecystokinin (CCK) into the circulation was studied before and 1, 2, and 4 h after a test meal in six healthy volunteers. At each time period, 100 ml of blood were drawn in a manner to inhibit CCK degradation. Plasma was formed and CCK concentrated by Sep-Pak C18 cartridge chromatography. Molecular variants of CCK and gastrin were well separated from each other by high-performance liquid chromatography (HPLC). Molecular forms of CCK and gastrin were measured by radioimmunoassay using an antibody that requires the presence of the carboxyl-terminal phenylalanine amide for full recognition, implying that biologically active forms were detected. HPLC elution positions of gastrin forms were determined using a gastrin-specific antibody. Chromatographic separation of CCK from gastrin forms was complete, allowing separate integration of gastrin and CCK forms. Therefore no subtraction of gastrin-like immunoreactivity from CCK-like immunoreactivity (CCK-LI) was necessary and CCK-LI could be directly determined. Peaks of CCK-LI were integrated in the column eluates and the plasma concentrations were calculated. Total plasma CCK-LI rose from a value of 2.4 +/- 0.6 pM before the test meal to 6.4 +/- 0.8, 6.6 +/- 0.9, and 5.8 +/- 1.2 pM 1, 2, and 4 h postprandially. The major molecular forms released into the circulation eluted on HPLC in the position of CCK-58 and CCK-39 (which coelutes with CCK-33). Minor amounts were detected in the position of CCK-8. There was no significant difference in the relative proportions of the molecular forms released at the different time periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Action of neurotensin on meal-stimulated gastric acid secretion in the dog.

In six to nine mongrel dogs the effect of graded doses of intravenous neurotensin (188, 375, 750, and 1500 pmol/kg h) on acid secretion basally or stimulated by distention (by isotonic glucose), peptone (0.5, 1, and 4 g%), and pentagastrin was studied. Neurotensin did not affect acid secretion basally, stimulated by distention, or the maximal peptone dose. However, when submaximal doses (0.5 and 1 g%) of peptone were instilled in the stomach, neurotensin stimulated the secretory response to intragastric peptone. This effect was observed in doses of intravenous neurotensin which mimicked circulating neurotensin concentrations after a standard test meal. Thus, neurotensin could be considered a physiologic stimulant of acid secretion when protein is present in the stomach. The mechanism for this action of neurotensin is unknown but could be partly explained by an enhanced release of gastrin. The potentiating effect of neurotensin on peptone-stimulated acid secretion could play a major role in gastric secretory function of the dog.

Animals↗
PubMed1990

[Paralytic ileus as an initial manifestation of malignant VIPoma of the pancreas--case report with review of the literature].

A 57-year old patient with a paralytic ileus of unknown origin was admitted to the intensive care unit. Because of the laboratory findings with therapy resistant hypokalemia, hypercalcemia and metabolic acidosis a VIPoma was suspected. Therapy with somatostatin resulted in correction of laboratory abnormalities and in normalization of gastrointestinal motility. Plasma concentrations of VIP and PP were elevated, ultrasonography revealed a pancreatic tumor. Postsurgical examination of the removal tumor tissue confirmed the diagnosis of a malignant VIPoma. Clinical symptoms, laboratory findings with and without somatostatin-therapy and immunhistochemical properties are described.

Biomarkers, Tumor↗
PubMed1990

[Effect of 1 week's administration of prednisone on gastric acid secretion and liberation of gastrin in healthy humans].

In a double-blind, randomized study we examined the effects of an oral administration of prednisone (60 mg/day for 6 days) or placebo on gastric acid output basally (BAO), in response to peptone meals 1%, 2%, 4% and 8%, 500 ml each) and to pentagastrin 6 micrograms/kg s.c. to determine maximal acid output, MAO) and on plasma gastrin levels in 14 healthy volunteers. Gastric acid output was measured by intragastric titration (pH 5.5). For gastrin determination we used a specific radioimmunoassay. Experiments were performed one day (day 0) before giving the drugs and one day (day 7) and one month (day 30) after finishing the treatment. Both groups were comparable in their gastric acid responses on day 0. Six days treatment with prednisone did not significantly alter BAO, MAO and the gastric acid response to peptone and pentagastrin. Also, one month after finishing the treatment there were no significant differences in gastric acid output. Both groups had similar plasma gastrin levels on each day. Prednisone did not significantly alter plasma gastrin levels. We conclude that a six-day treatment with prednisone does not alter BAO, MAO and gastric secretory responses to peptone nor release of gastrin in healthy human volunteers.

Administration, Oral↗
PubMed1990

[Risk factors in the etiology of Crohn disease].

So far the aetiology of Crohn's disease remains unclear. Besides a genetic predisposition a causal role of environmental factors has been taken into consideration within the last time period. A number of case-control studies have consistently reported about an increased consumption of dietary sugar in patients with Crohn's disease as compared with controls. Furthermore cigarette smoking and the use of oral contraceptive drugs have been shown to increase disease risk. While the role of the former can be regarded as established the role of the latter still remains controversial.

Cohort Studies↗
PubMed1990

Feedback regulation of human pancreatic secretion. Effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes.

To determine the effects of luminal protease inhibition on duodenal delivery and the intraluminal fate of pancreatic enzymes, six healthy subjects were intubated with an oro-ileal multilumen tube assembly. By using nonabsorbable markers, cumulative trypsin, chymotrypsin, lipase, and amylase activities were measured as delivered to duodenum, midjejunum, and distal ileum, with or without simultaneous duodenal perfusion of the protease inhibitor camostat at graded doses. Compared with saline, camostat (a) inhibited trypsin activity in the entire small intestinal lumen by up to 99%, and significantly reduced chymotrypsin activity by up to 89%; (b) significantly increased duodenal deliveries of lipase activity, amylase activity and volume; (c) did not influence plasma cholecystokinin concentrations; and (d) significantly increased jejunal and ileal deliveries of lipase but not amylase activity. Small intestinal transit and motility were not affected by camostat. In additional in vitro studies, camostat significantly reduced the spontaneous decline in lipase activity in fresh human duodenal juice incubated at 37 degrees C. These findings demonstrate that duodenal deliveries of lipase and amylase activities increase when intraluminal protease activity is decreased; they suggest that this increase is not caused by slower proteolytic destruction of enzyme protein but by stimulation of pancreatic secretion. Thus, luminal protease-mediated feedback regulation of pancreatic secretion may be operative in humans. Because plasma cholecystokinin concentrations were not affected, these effects may in part be independent of cholecystokinin. The data further suggest that proteolytic digestion plays a major role in the rapid loss of luminal lipase activity on small intestinal transit.

Adult↗
PubMed1989

[Calcium homeostasis and exocrine pancreas: physiological ans pathological interrelations].

Calcium homeostasis and exocrine pancreas interact on several levels under both physiologic and pathophysiologic conditions. (1) Calcium ions are important intracellular mediators of cholinergic and hormonal stimulation of the pancreatic acinar cell, and thus play a central role in the stimulus-secretion coupling of ecbolic pancreatic function. (2) The calcium concentration in pancreatic juice is lower than in the interstitial fluid: pancreatic juice calcium is composed of two fractions, one of which is secreted together with enzyme proteins and the other diffuses along paracellular pathways dependent on serum calcium. Disturbed calcium secretion in pancreatic juice can be observed even following slight pancreatic alteration; conversely, disturbed calcium secretion may be of importance in the pathogenesis of chronic calcifying pancreatitis. (3) Hypocalcemia is an important symptom of acute pancreatitis whose pathogenesis has not been fully elucidated. (4) On the other hand, pancreatitis complicates chronic and acute hypercalcemic syndromes though the pathogenic mechanisms is uncertain. Experimental chronic hypercalcemia in animal models causes characteristic pancreatic secretory changes and disturbs the diffusion barrier for calcium. Experimental acute hypercalcemia causes stimulation of pancreatic enzyme secretion and cholecystokinin release. In addition, extracellular calcium has a direct stimulatory effect on pancreatic acinar cells in vitro.

Acute Disease↗