[Ki-ras mutation--a specific and sensitive tumor marker for carcinoma of the pancreas?].
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Genes, ras↗
Biomedical subjects
G Adler
Publications and source records attributed to G Adler.
Fibrinogen in obesity before and after weight reduction.
Several studies have shown that obesity is associated with atherosclerosis. The reason may be that there is often a gathering together of risk factors for cardiovascular disease in obesity. Recently plasma fibrinogen level has been identified as an important cardiovascular risk factor. The aim of the study was to investigate fibrinogen levels in obesity before and after weight reduction. Obese but otherwise healthy patients with overweight problems were studied. 448 female patients (39.1 +/- 13.2 years, body mass index 38.7 kg/m2) and 136 male patients (39.4 +/- 12.8 years, body mass index 40.7 kg/m2) were examined after overnight fasting. Sixty patients (44 female, 16 male) were studied after 9.5 +/- 6.2 month of dieting (1200 kcal/day: 20% protein, 30% fat and 50% carbohydrates). The weight loss was 16.7 +/- 11.0 kg in the female and 16.2 +/- 6.7 kg in the male patients, and blood pressure, triglycerides, blood glucose and uric acid had declined. The fibrinogen level correlated with the body mass index, the waist circumference, the hip circumference and the waist to hip ratio. The fibrinogen level also correlated with insulin. A partial correlation of fibrinogen and insulin continued to exist after removing the linear effects of the other variables measured. After weight reduction, the level of fibrinogen was lower. In patients with extreme overweight and high fibrinogen levels, who reduced their BMI by 7.4 +/- 1.24 kg/m2, the weight loss correlated with the decrease in fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones.
In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities < 100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5 +/- 11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones < 20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P = 0.0567) and in group II from 6.5 ml to 20.2 ml (P = 0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
No study is an island: muscarinic control of gallbladder revisited.
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Gallbladder↗
Enhancement of hepatic glucose release and bile flow by the phosphodiesterase-III-inhibitor enoximone in the perfused rat liver.
The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the treatment of cardiac failure can be associated with hyperglycaemia. This phenomenon could be caused by hepatic events induced by PDI. The purpose of our study was to investigate the effects of the PDI enoximone on hepatic carbohydrate metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and lactate production, portal flow and bile flow were determined. Administration of enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid-independent bile flow in a dose-dependent manner. The PDI enhanced the glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from 9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol glucose/g/20 min). Furthermore, lactate production was significantly reduced by enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked or diminished by enoximone administration. In summary, it was shown that the PDI enoximone is able to enhance hepatic glucose production. Bile acid-independent bile flow was increased by the inhibition of phosphodiesterase-III. The effects of enoximone and glycogenolytic hormones on glucose release were synergistic. The vasoconstrictive action of catecholamines was reduced or completely prevented by enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and choleretic properties in the liver.
Animals↗
Cephalic phase of pancreatic polypeptide release: a valid test of autonomic neuropathy in diabetics?
We investigated pancreatic polypeptide (PP) release by chew and spit sham feeding as a test of autonomic function in 33 patients with diabetes mellitus (DM) and 24 age-matched healthy controls. Plasma samples were taken at nine 5-min time intervals, and PP plasma levels were determined by radioimmunoassay. Autonomic neuropathy (AN) was diagnosed and staged according to four standardized tests of cardiovascular autonomic function. The integrated PP response during sham feeding was decreased in DM patients (1067 + or - 397 vs. 2670 + or - 394 pg/ml/30 min; P < 0.05). The maximum increase of PP plasma levels was significantly different between the DM subgroups with AN (36 + or - 19 pg/ml; n = 13) and without AN (132 + or - 36 pg/ml; n = 20) but varied widely in healthy controls (219 + or - 29 pg/ml; range 20-460 pg/ml). A cutoff of maximum PP increase < 20 pg/ml (specificity 100%) resulted in only 46% sensitivity, while a cutoff < 160 pg/ml (sensitivity 100%) yielded 38% specificity for diagnosis of AN. The diagnostic value of the PP test for identifying individual patients against the variable reference range is therefore limited. Maximum PP increase < 20 pg/ml indicates AN, while maximum PP increase > 160 pg/ml excludes AN in diabetic patients.
Adolescent↗
Glycerol metabolism in patients with alcohol-induced liver cirrhosis.
The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.
Journal Article↗
Effects of glucagon-like peptide-1 (GLP-1) in RINm5F insulinoma cells. Stimulation of insulin secretion, insulin content, and insulin receptor binding.
Glucagon-like peptide-1 (GLP-1) is the major incretin hormone from the distal small intestine which stimulates basal and glucose-induced insulin secretion. Using the rat insulinoma cell line RINm5F (Gazdar et al. 1980) we investigated the effects of GLP-1 on insulin secretion, insulin content, and insulin receptor binding. During a 1 hour incubation, GLP-1 [1 nM] stimulated insulin secretion 2-fold (p < 0.01 vs controls). Incubating RINm5F for 24 h with GLP-1 [1 nM], a 1.6-fold higher cellular insulin content was observed (p < 0.01 vs controls). Moreover, GLP-1 induced a 2-fold higher capacity and a 15-fold higher affinity of 125I-insulin binding on the cell surface (p < 0.01 vs controls). Glucagon, known as a potent stimulator of insulin secretion, yielded a similar effect only in 1,000-fold higher concentrations, whereas the intracellular insulin content as well as insulin receptor binding was not increased. Taken together, in RINm5F insulinoma cells GLP-1 potently stimulates insulin secretion and insulin content, and improves insulin receptor binding.
Animals↗
Neurohormonal control of human pancreatic exocrine secretion.
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Acetylcholine↗
Supramaximal secretagogue stimulation enhances heat shock protein expression in the rat pancreas.
Heat shock or stress proteins (HSPs) are synthesized by various cell types in response to different metabolic insults (e.g., hyperthermia). Although the function of HSPs is not fully understood, they are believed to be an evolutionary conserved intracellular defense mechanism. In an attempt to characterize the autoprotective potential of pancreatic acinar cells, we investigated the regulation of HSPs of the 70-kD family and the small HSP ubiquitin in vitro and in vivo during supramaximal cerulein stimulation. Infusion of the secretagogue cerulein induces a mild edematous form of pancreatitis in vivo and is characterized by a marked disturbance of the intracellular transport and segregation of enzymes. Synthesis of HSP70 mRNA is upregulated in isolated pancreatic lobules by either cerulein (100 nM) or hyperthermia (42 degrees C for 60 min). In contrast, expression of ubiquitin mRNA was not altered by either secretagogue treatment or hyperthermia. This heat shock-like response of pancreatic acinar cells could be reproduced in vivo: Pancreatitis was induced in male Wistar rats by intravenous infusion of supramaximal doses of cerulein (10 micrograms/kg/h). Analysis of mRNA expression revealed a significant upregulation of HSP70 RNA during supramaximal secretagogue stimulation. mRNA levels encoding for ubiquitin remained unchanged. Western blot analysis demonstrated that the transcriptional upregulation of HSP70 in vivo was reflected on the protein level. This study demonstrates that the marked intracellular disturbance observed in secretagogue-induced pancreatitis is associated with enhanced expression and synthesis of a major stress protein. Given the autoprotective potential of HSPs, this upregulation may indicate a self-defense mechanism of pancreatic acinar cells in experimental pancreatitis.
Animals↗
Correlation of nucleolar organizer regions with secretory and regenerative process in experimental cerulein-induced pancreatitis in the rat.
Silver staining of nucleolar organizer regions (AgNORs) demonstrates loops of DNA that transcribe ribosomal RNA. Their number and size have been attributed to rDNA transcription activity involved in protein synthesis and thus associated with proliferation. The exact relationship among proliferation, protein synthesis, and expression of AgNORs is, however, not yet well established. We therefore investigated AgNORs in an experimental model of cerulein-induced rat pancreatitis. During secretory stimulation with maximal doses of cerulein (0.25 micrograms/kg/h) for 12 h, AgNOR number and size per nucleus as well as 3H-thymidine label index did not change, although there was a marked increase in pancreatic volume flow, up to 150%, and of protein synthesis rate, up to 180% of the control levels. In contrast, after infusion of supramaximal doses of cerulein (5.0 micrograms/kg/h), AgNOR and 3H-thymidine label values rose significantly, with a distinct peak at day 3 after induction of pancreatitis. Most interestingly, AgNOR number and size were elevated 12 h before DNA replication started as determined by 3H-thymidine incorporation. At the same time intracellular protein synthesis proved to be decreased approximately 30-50% compared to controls. Our data confirm that AgNOR is a marker of proliferation that reflects regulatory events in the cell cycle earlier than 3H-thymidine incorporation. Here we demonstrate for the first time that this phenomenon is independent of the total intracellular protein synthesis rate.
Acute Disease↗
Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade.
The present study investigated how a cholinergic agonist modifies interdigestive motility and secretion of the upper gastrointestinal tract and how muscarinic and cholecystokinin receptor blockade interfere with this direct cholinergic stimulation. In eight healthy volunteers, gastrointestinal motor and secretory responses to bethanechol (12.5, 25, and 50 micrograms kg-1 h-1) with and without a background of atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1) were studied. Stepdoses of bethanechol caused a parallel stimulation of antroduodenal motility and gastropancreatic secretion (P < 0.01) without inducing a fed pattern. However, duration of phase I was shortened (P < 0.05). Only high doses of bethanechol enhanced gastrin (P < 0.05), cholecystokinin (P < 0.05), and pancreatic polypeptide (P < 0.01) release. Atropine completely antagonized motor and secretory responses to cholinergic stimulation. Loxiglumide left cholinergically stimulated motility and pancreatic enzyme secretion unaltered. With co-infusion of bethanechol and loxiglumide, PP release dropped by 63% (P < 0.01); gastric acid output, gastrin and CCK release increased by 56%, 16%, and 25%, respectively (P < 0.05). We conclude that stimulation by a cholinergic agonist preserves the interdigestive pattern. Low dose muscarinic receptor blockade abolishes cholinergic stimulation over the full dose range. Inhibition of somatostatin release would explain stimulation of gastrin release and gastric acid secretion with co-infusion of bethanechol and loxiglumide. Endogenous CCK appears to interact with direct cholinergic stimulation at the pancreatic PP cell and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth muscle cells.
Adult↗
Vasoactive mediators and the progression from oedematous to necrotising experimental acute pancreatitis.
Little is known about the pathophysiological factors that determine the clinical severity of acute pancreatitis. Because impairment of pancreatic circulation and oxygenation is associated with greater disease severity and morphological damage in experimental pancreatitis it has been suggested that various vasoactive mediators might participate in the progression from the oedematous to the necrotising variety of the disease. This study used an animal model of acute pancreatitis induced by intravenous caeruleint (10 micrograms/kg/h for up to six hours), which does not entail either haemorrhage or significant necrosis of the pancreas. This study considered whether the administration or the inhibition of either nitric oxide, bradykinin, or adrenergic mediators can convert this mild variety into haemorrhagic and necrotising pancreatitis. Neither nitric oxide nor catecholamines were involved in the progression from oedematous to haemorrhagic pancreatitis. Their substitution, activation, and inhibition all failed to change the severity of the disease process. Bradykinin alone seemed to be critically involved in the pathogenesis of pancreatic haemorrhage and necrosis. However, the inhibition of bradykinin and not its activation or substitution increased the severity of the disease.
Acute Disease↗
Disassembly of rat pancreatic acinar cell cytoskeleton during supramaximal secretagogue stimulation.
In vivo stimulation of the exocrine pancreas with concentrations of secretagogue in excess of a maximally stimulating dose causes a marked disturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, are involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal dose (10 micrograms.kg-1.h-1 for up to 6 h) intravenously in rats. To study the ultrastructural alterations of acinar cell microfilaments and microtubules by immunogold labeling, we used monoclonal antibodies directed against actin and beta-tubulin. As early as 30 min after the start of the secretagogue infusion we found a progressive disassembly of microtubules and microfilaments in exocrine cells. In immunoblot studies this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indicate that the earliest morphological events during supramaximal secretagogue stimulation of the pancreas involve the disassembly and degradation of microtubules and microfilaments. This cell biological phenomenon offers an explanation for the disturbances of segregation, transport, and exocytosis of digestive enzymes, which are known to be associated with supramaximal stimulation of the pancreas and experimental models of pancreatitis.
Actin Cytoskeleton↗
Effect of kinin inhibition in experimental acute pancreatitis.
Activation of the endogenous kinin system is a consistent observation in acute pancreatitis and has repeatedly been implicated in the pathophysiology of the disease. We have studied the effect of a potent bradykinin antagonist on the onset and development of acute pancreatitis in four unrelated animal models. Pancreatitis was induced in rats by either supramaximal stimulation with caerulein, intraductal injection of sodium taurocholate, or pancreatic duct ligation with secretin infusion, and in mice by feeding a choline-deficient, ethionine-supplemented diet. The potent, long-acting bradykinin antagonist HOE-140 was administered subcutaneously (0.1 mg/kg every 5 h). Effective kinin inhibition had no effect on pancreatitis-associated mortality, the extent of morphological damage and inflammation, or the intracellular distribution of lysosomal hydrolases. Pancreatic edema was only reduced in caerulein-induced pancreatitis, the only model in which edema formation was paralleled by increased vascular permeability. We conclude that, contrary to previous suggestions, kinins do not play a predominant role in the development of acute pancreatitis. Their participation is strictly limited to vascular events and does not involve the early cell biological alterations in pancreatic acinar cells.
Acute Disease↗
[Endoscopic and surgical therapy of hemorrhagic duodenal and stomach ulcer].
The aim of this prospective clinical study was to evaluate whether a combination of the endoscopic hemostasis together with fibrin sealing and consecutive conservative therapy could reduce the frequency of recurrent bleedings, thus the number of operations without adversely influencing the prognosis of the disease. 134 patients admitted to the surgical and medical hospital of the University of Ulm between 1/1990 and 1/1992 with bleeding gastroduodenal ulcers took part in this study. All patients were treated endoscopically by hypertonic saline solution plus epinephrine and fibrin sealant. If initial endoscopic hemostasis was not achieved patients were operated within 6 h after admission. Patients with successful initial endoscopic hemostasis were treated conservatively and underwent control endoscopy after 24 and 48 h. In 23 patients the initial endoscopic hemostasis was not successful, they had to be operated immediately. In 111 patients endoscopic hemostasis was achieved, 20% of these patients had acute bleeding ulcers (Forrest Ia, b), 66% showed stigmata of fresh bleedings (Forrest-IIa bleeding). Primary endoscopic hemostasis was achieved in 85.6% of all patients treated, 14.4% of patients (n = 16) developed a recurrent bleeding during the observation period verified by gastroscopy. Half of these patients had an acute bleeding at the first gastroscopy (Forrest-Ia, Forrest-Ib bleeding). Recurrent bleeding became apparent between day 1 and 6 after admission to the hospital. Two patients refused surgical intervention, the other 14 were operated immediately.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Imaging methods in diagnosis of chronic inflammatory bowel diseases].
In diagnostic imaging of chronic inflammatory bowel diseases, endoscopy and radiologic techniques are used complementarily. For primary evaluation, endoscopy has greater impact, and radiologic techniques are restricted to the assessment of the small bowel. In acute and chronic complications, cross-section methods are superior because extraenteric lesions can be detected precisely. By means of fast sequences and development of gastrointestinal contrast media, magnetic resonance imaging is of increasing value because multiplanar sections can be performed and irradiation risk can be avoided.
Diagnosis, Differential↗
Diagnostic value of fine-needle puncture of the gallbladder: side effects, safety, and prognostic value.
Bile sampling without the risk of contamination by pancreatic and duodenal secretions and avoiding unpredictable influences of general anesthesia during biliary surgery on biliary analytics are feasible with percutaneous puncture of the gallbladder. In 207 patients with gallstones, gallbladder puncture was performed under local anesthesia with a 22-gauge spinal needle under continuous real-time ultrasound guidance. Bile samples were investigated for biliary lipids and nucleation time. Complete aspiration of gallbladder bile could be achieved in all patients without complications such as bleeding, bile leak, or inflammation. Of these patients, 11.6% reported mild abdominal problems, 3.4% required analgetics, and in 1.0% biliary colics were observed. Elective cholecystectomy was performed in 1 patient. Of the bile samples, 10.1% were contaminated with bactobilia. Biliary lipids, cholesterol saturation index (CSI), total lipid concentration (TLC), and bacteriological contamination were independent of gallstone number, whereas patients with solitary gallbladder stones exhibited a significantly longer nucleation time (NT) in comparison with those with multiple stones. In patients with gallstones, fine-needle puncture of the gallbladder represents an important diagnostic procedure and can be performed within minutes without major side effects if performed by an experienced sonographer.
Adult↗