PubMed Health⌕ Search

Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 127 records · Page 7Linked to original sources

The closed duodenal loop technique.

The closed duodenal loop (CDL) technique, one of the first experimental models producing experimental acute pancreatitis, is described in this article. Since this model was published first by Pfeffer in 1957, it has undergone several modifications. The CDL method is an easily practicable and reproducible model to investigate acute hemorrhagic pancreatitis. In view of other available experimental models, the CDL technique has lessened in popularity.

Acute Disease↗

Role of oxygen radicals in experimental acute pancreatitis.

A growing body of evidence suggests that oxygen radicals are generated in all forms of experimental pancreatitis at an early stage of disease. Moreover, first indirect observations assume that also in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. The source of the enhanced production of oxygen radicals remains still unclear. Experimentally, the efficiency of scavenger treatment varies between three different models, whereby these differences depend more on the design of the experimental models than on the form of pancreatitis which was induced. Antioxidant treatment with radical scavengers should therefore interrupt these deleterious pathomechanisms or at least mitigate the damages normally seen. Most studies, however, pretreated the experimental animals before inducing acute pancreatitis, which does not mirror the clinical reality. Patients, however, are admitted after onset of the disease. Therefore, well-defined, controlled clinical studies are needed to validate the involvement of oxygen radicals in acute and chronic pancreatitis and the effect of scavenger treatment in patients with pancreatitis.

Acute Disease↗

Clinical relevance of experimental acute pancreatitis.

There are several well-standardized models of experimental acute pancreatitis such as the closed duodenal loop technique, cholecystokinin or cerulein stimulation, duct injection and diet-induced acute experimental pancreatitis. With regard to human acute pancreatitis, experimental models in animals have a considerable high clinical relevance if the subject of investigation concerns pathogenetic, morphological and diagnostic approaches to the disease; as regards the treatment modalities and causative therapy of acute pancreatitis, experimental models in animals up to now seem to be far away from the clinical situation and therefore these protocols have low clinical relevance. The reasons for this discrepancy are outlined in this paper.

Acute Disease↗

Acute pancreatitis: when and how to operate.

Patients with proved necrotizing pancreatitis should be treated in an intensive care unit. Surgical management of necrotizing pancreatitis is indicated if an acute abdomen or persistent or increasing signs of organ complications develop, such as pulmonary or renal insufficiency, cardiocirculatory dysfunction or metabolic disorders, and these do not respond to maximum intensive care treatment over at least 72 h. Besides these so-called non-responders to ICU treatment, operative management is clearly indicated in patients who develop signs of sepsis on the basis of a bacteriologically positive fine-needle aspiration of pancreatic necroses. In patients with minor necroses without any bacterial contamination and without extensive retroperitoneal fatty tissue necroses intensive care therapy can be successful without the necessity of a surgical intervention. The gold standard of surgical management of necrotizing pancreatitis is careful removal of necrotic tissue, drainage of bacterially infected area, elimination of the pancreatogenic ascites in order to prevent systemic spread of vasoactive and toxic substances and interruption of the inflammatory process. For the treatment of pancreatic necrosis we strongly support surgical debridement (necrosectomy), supplemented by postoperative closed continuous lavage of the lesser sac and the adjacent necrotic cavities. In 152 patients suffering from severe necrotizing pancreatitis the hospital mortality was 12.5% (19/152) by this surgical approach.

Acute Disease↗

Characterization of two phospholipases A2 in serum of patients with sepsis and acute pancreatitis.

Pancreatic phospholipase A2 and non-pancreatic ascitic phospholipases A2 were studied in sera of healthy individuals and of patients suffering from sepsis or acute pancreatitis. In gel filtration experiments, immunoreactive ascitic phospholipase A2, as determined in serum by a time-resolved fluoroimmunoassay, eluted either unassociated with an apparent M(r) of 10,000-14,000 or associated with proteins of high molecular mass. Catalytically active ascitic phospholipase A2 was associated with high molecular weight proteins. In acute pancreatitis the catalytically active and immunoreactive pancreatic phospholipase A2 eluted mainly as a protein of M(r) of 14,000. The results of the gel filtration experiments indicate that pancreatic phospholipase A2 is not associated with other proteins in human serum, whereas ascitic phospholipase A2 is associated with protein(s) of relative high molecular weight, or exists in different polymeric forms. We also purified phospholipase A2 from sera of healthy individuals by ion exchange chromatography and HPLC. The enzyme was homogenous, displayed an M(r) of approximately 13,500 as judged by SDS-polyacrylamide gel electrophoresis, and reacted with an antibody raised against ascitic phospholipase A2.

Acute Disease↗

Determination of pancreatic lipase by immunoactivation technology. A rapid test system with high sensitivity and specificity.

This paper describes the test characteristics and clinical relevance of a newly developed homogeneous enzyme immunoassay IMAC lipase test for the determination of serum pancreatic lipase. The method of determination is based on an immunoactivation technology and utilizes antibody fragments against human pancreatic lipase covalently bound to the marker enzyme horseradish peroxidase. The serum samples of 408 persons were investigated with this new assay. The within-run and day-to-day precision, the linearity, and the recovery of this immunoassay correspond to a very high degree to the requirements made of a modern immunological test. Comparison with an ELISA method resulted in a correlation coefficient of 0.971, whereby the IMAC lipase assay tended to register lower serum values. The serum range for the IMAC lipase test is 0-47 micrograms/L, based on a normal collective of 187 healthy controls. A sensitivity of 95.8% for the diagnosis of acute pancreatitis at a cutoff level of twice the upper normal range and a specificity of 99.3% at an efficiency of 99.8% can be given. The advantage of the IMAC lipase test method is its ability to be adapted to work on automatic laboratory analyzers.

Acute Disease↗

[The effect of duodenum-preserving pancreatic head resection on the endocrine pancreas function in patients with chronic head pancreatitis].

In a prospective clinical-experimental study, 15 patients with chronic pancreatitis operated consecutively due to severe pain were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th postoperative day, and three months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, somatostatin, and pancreatic polypeptide were determined. As indicated by the k-value, glucose tolerance improved postoperatively in 11 patients; two patients showed no change, and one patient was worse. Only one patient developed evident diabetes mellitus immediately postoperatively. The pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (2p less than 0.01). Duodenum-preserving pancreas head resection led to improvement of the glucose tolerance in the majority of patients; a deterioration was observed only in two cases.

Adult↗

[Free intraperitoneal tumors cells in pancreatic cancer--significance for clinical course and therapy].

Intraoperative peritoneal cytology was performed in 36 patients with pancreatic ductal adenocarcinoma. 12 patients (33%) showed malignant cells in the peritoneal cavity. In the further course these patients developed more non-local metastases and had a significantly shorter survival rate. Peritoneal carcinomatosis became evident in 75% of the patients with free cancer cells in contrast to only 14% of the patients without. Detection of free cancer cells was directly related to the histological tumor stage (TNM-system). Iatrogenic shedding of malignant cells by surgical tumor manipulation or needle biopsy was not observed. The technique of intraoperative peritoneal lavage with consecutive cytology and its possible effects on further treatment is discussed.

Adult↗

[The value of ultrasound and computerized tomography in detection of cystic changes in chronic pancreatitis].

Intra- or extrapancreatic pseudocysts (PP) are the most common local complication in chronic pancreatitis. Aim of this study was to investigate frequency, localisation and size of pseudocysts in patients with chronic pancreatitis by means of ultrasound (US) and computed tomography (CT). 155 patients (females 35, males 120) with chronic pancreatitis, that underwent simultaneous (within two weeks) CT and US examinations, from January 1982 to June 1989, were included in this study. Cystic lesions were detected in 62% by CT, in 52% by US. Sensitivity in detection of cysts based on intraoperative findings (gold standard) was 98% for CT and 94% for US. 80% of the pseudocysts were smaller than 6 cm. 46% were in the range from 2 to 66 cm and 34% were smaller than 2 cm. The most common localisation was the pancreatic head region (50%), 20 of 102 patients with chronic pancreatitis were found to have a direct communication of a pseudocyst with the ductal system by ERP. No specific clinical or laboratory pattern were associated with the presence of pseudocysts. Increased pancreatic serum amylase concentration was detected in 29% of patients with and in 27% of patients without pseudocysts.

Adolescent↗

TRH-immunoreactivity in chronic pancreatitis.

Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.

Adult↗

[Oxygen radicals and acute pancreatitis].

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences were depending on the experimental model and not on the form of pancreatitis which was induced. Most studies pretreated the experimental animals before inducing acute pancreatitis. This does not mirror the clinical reality, since patients are admitted to the hospital after onset of the disease. It was shown in Cerulein-pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damages after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. The first indirect observations also suggest that in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. Therefore, well-defined controlled clinical studies with patients suffering from acute pancreatitis are needed to validate the role of oxygen radicals in this disease.

Acute Disease↗

Antineutrophil cytoplasmic autoantibodies (ANCA) in acute pancreatitis.

Antineutrophil cytoplasmic autoantibodies, which are now considered reliable serological markers of acute necrotizing vasculitic diseases, were measured in 11 patients with acute necrotizing pancreatitis and 12 patients with acute interstitial pancreatitis. When tested by indirect immunofluorescence, none of the sera was positive for diffuse cytoplasmic staining, and none was positive for perinuclear staining of antineutrophil cytoplasmic antibodies. Also by the sensitive enzyme-linked immunosorbent assay, none of the sera was positive when purified alpha-granule fraction of granulocytes was used as an antigen. We can therefore conclude that neither the diffuse cytoplasm-reacting, nor the perinuclear form of antineutrophil cytoplasmic antibodies, is involved in cases of acute pancreatitis.

Acute Disease↗

[Surgical therapy of acute cholecystitis--advantages of early operation].

229 patients with an acute cholecystitis were operated on at the Surgical University Hospital of Ulm between 3/1982 and 6/1990. 42.3% of the patients were older than 70 years, the mean age being 64.3 years. 51.5% suffered from a complicated form of the disease. Intercurrent diseases were preoperatively found in 76%. Intraoperative complications of a technical nature occurred in 3.1%. The overall postoperative morbidity rate was 54%, with 9.4% of local problems, and showed a clear dependency on age and the number of preexisting risk factors. 31% had to undergo reoperation. The overall mortality rate was 2.6%, with a 0% mortality for patients under 65 years. The number of preexisting risk factors clearly correlated the period of hospitalisation, which was 16.1 days on average. In symptomatic gallstone diseases an early elective cholecystectomy should be strongly considered, especially in aged and multimorbid patients.

Acute Disease↗

[The diagnostic value of the amino acid absorption test in detection of a disorder of exocrine pancreatic function].

The amino acid consumption test (AACT) during exogenous stimulation with secretin and CCK was proposed as a sensitive and highly specific test for detection of exocrine pancreatic insufficiency. To further investigate the diagnostic value of this test we measured the AACT in comparison with the pancreolauryl serum test (PLT) in patients with chronic pancreatitis and in patients with gastrointestinal diseases but without pancreatic disease. A total of 48 patients, 23 patients with chronic pancreatitis (CP) and 25 patients with gastrointestinal diseases, were included in the study. Diagnosis of chronic pancreatitis was established by standardized morphological criteria in ultrasound, ERCP, CT, and was confirmed by surgery in 11 cases. The PLT was abnormal in 83% of patients with chronic pancreatitis and normal in 92% of the control subjects (diagnostic accuracy 88%). Basal amino acid concentration was comparable in patients with chronic pancreatitis and in control subjects (300 +/- 12 [symbol: see text] 325 +/- 16 mumol/l). The peak decrease of amino acids occurred after 30 min during combined stimulation with secretin and ceruletide and was not different between the two groups (CP: 11.2 +/- 1.7%, controls: 13.9 +/- 1.9% below basal values). With a 12% decrease of amino acids as cutoff, sensitivity was 74% and specificity 52% (diagnostic accuracy 63%). Integrated amino acid decrease did not show any significant differences between CP and controls (CP: 228 +/- 63% min, controls: 397 +/- 80% min). Determination of the individual amino acids serine, valine, histidine, and isoleucine could also not discriminate between patients with chronic pancreatitis and other gastrointestinal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The involvement of oxygen radicals in acute pancreatitis.

The purpose of this study was to assess the involvement of oxygen radicals in acute edematous and hemorrhagic pancreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 micrograms/kg/h) and by retrograde injection of 5% sodium taurocholate for 30 min, 3.5 h, and 12 h. At the end of the infusion and observation time, serum enzymes, conjugated dienes, and malondialdehyde in the tissue were measured. Moreover, the tissue samples underwent light microscopical examination. In cerulein pancreatitis, an interstitial edema and intravascular margination of granulocytes in the pancreatic gland were observed after 3.5 h. After 12 h, the histological evaluation revealed a pronounced zymogen degranulation, extensive tissue necrosis and migration of granulocytes into the tissue. Parallelly, amylase and lipase increased by 15 and 35 times, respectively. In contrast, conjugated dienes and malondialdehyde increased in cerulein pancreatitis and reached their highest level after 3.5 h and decreased to normal levels after 12 h. The development of the histological damages and serum enzyme levels with sodium taurocholate pancreatitis was similar as compared to the cerulein pancreatitis, however, the development was faster and more traumatic. Already after 3.5 h an extensive zymogen degranulation and cell necrosis was observed. Concomitantly, the amylase and lipase levels increased by 90 and 30 times, respectively. Treatment with superoxide dismutase (100,000 U/kg/h) and catalase (400,000 U/kg/h) prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue edema and inflammatory response were not affected in both models of acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Oxygen radicals in liver ischemia and reperfusion--experimental data.

The generation of free oxygen radicals is presumed as a substantial pathogenetic principle in reperfusion injury. Although demonstrated in gut, muscle and kidneys its role in liver reperfusion injury is still under investigation. In an experimental rat model of warm liver ischemia of 60 min and 8 h reperfusion electron resonance spectroscopy assessed the increased generation of free radicals in early reperfusion period, leading to a decrease of polyunsaturated free fatty acids in liver tissue within 15 min of reperfusion. Histologically, single cell death, local and patchy necrosis of hepatic lobuli could be observed after 8 h reperfusion (n = 6). These histologic signs of liver injury could be attenuated by administration of superoxide-dismutase in combination with catalase but not by allopurinol. Best results could be obtained by deferoxamine. This indicates that increased generation of free oxygen radicals in reperfusion is not caused by the known conversion of xanthine-dehydrogenase to -oxidase but is mediated by an increased generation of hydroxyl-radicals, which can be scavenged by deferoxamine.

Allopurinol↗