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Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 19 recordsLinked to original sources

[Lemierre's syndrome with splenic abscesses].

A week after onset of a pharyngo-tonsillitis a previously healthy 23-year-old man developed high fever (41.4 degrees C), leukocytosis (12,200/microliters) with marked shift to the left, thrombocytopenia (86,000/microliters) and increased transaminases (GOT 83 U/l, GPT 113 U/l). Chest x-ray film suggested intrapulmonary abscesses with left-sided pleural effusion. The suspected diagnosis of "post-tonsillitis" septicaemia (Lemierre's syndrome) was confirmed by demonstrating anaerobic, fusiform, gram-negative bacteria (Fusobacterium nucleatum and necrophorum) in several blood cultures. Despite antibacterial treatment (amoxicillin/clavulanic acid, imipenem/cilastatin, clindamycin) he had recurrent pain referred to the kidney region and persisting fever. Repeated ultrasound and radiological examinations revealed new foci in the spleen, which were enlarging. Laparotomy with splenectomy performed on day 17 after the begin of treatment confirmed multiple splenic abscesses, but abscess pus and splenic tissue were sterile. After altogether 6 weeks of antibiotic treatment, finally with chloramphenicol, the patient was discharged in a good general state.

Abscess

Nonparallel patterns of circadian pancreatic and biliary secretions in fasting rats.

We compared the circadian patterns of pancreatic and biliary secretions in fasting rats. For this purpose, indwelling plastic catheters were placed in 10 male Wistar rats (300-320 g) for the collection of biliary and pancreatic secretions. After small samples were taken for analysis, pancreatic and biliary secretions were recirculated into the duodenum by an additional connecting system. The rats were adapted to an inverse night-day cycle by artificial light during the night (8 PM-8 AM) and by darkroom housing at daytime (8 AM-8 PM). During a 24-h fasting period, samples of bile (100 microL) and pancreatic juice (20 microL) were taken every hour for determination of the following parameters: pancreatic and biliary flow rate, protein, amylase, lipase, trypsin, and bile acid output. Peak pancreatic flow rate (1.96 +/- 0.05 mL/h.kg) was achieved toward the end of the dark period at 7 PM. A significant increase of pancreatic secretion could be achieved merely by turning the lights off, a significant decrease by turning the lights on. Similar circadian patterns were found for pancreatic protein, amylase, and lipase output with peak secretions at 7 PM. An increase of nearly 5x was found between minimal (15.64 +/- 0.65 mg/h.kg) and maximal (72.43 +/- 2.83 mg/h.kg) pancreatic protein output. The amplitude was highest for amylase; peak amylase output (13740 +/- 832 U/h.kg) was about 18-fold above minimal output (758 +/- 44.3 U/h.kg). Conversely, the peak of trypsin concentration in pancreatic juice (1095 +/- 17.8 U/mL) occurred during the light period when flow rates were lowest.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Role of octreotide in the prevention of postoperative complications following pancreatic resection.

Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

Double-Blind Method

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.

Adult

The role of oxygen radicals in experimental acute pancreatitis.

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby, it seems that these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals still remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences depended 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

Changes in peptidergic innervation in chronic pancreatitis.

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

Adult

Treatment of duct carcinoma of the pancreas with the LH-RH analogue buserelin.

Thirty-six patients (21 male, 15 female) with ductal pancreatic cancer were treated with the long-acting synthetic luteinizing hormone releasing hormone (LH-RH) analogue buserelin. All patients had advanced tumor stages (stage II: 7 patients; stage III: 11 patients; stage IV: 18 patients). A monthly follow-up including clinical status, computed tomography scan, or ultrasonography and the tumor markers carcinoembryonic antigen (CEA) and H carbohydrate antigen 19-9 (CA19-9) was carried out. There were no severe side effects apart from impotency in men and hot flashes and outbreaks of perspiration in three patients. No partial or complete remission was seen. Twenty-six patients showed tumor progression with a median survival time of 4 months (range 0.5-11 months). In 10 patients a "no change" evaluation with a median survival time of 10 months (range 8-17 months) was registered. In only two of these patients there was no increase in the serum tumor markers CA19-9 and CEA during this time. In conclusion, LH-RH analogue treatment cannot be recommended in this selected group of patients suffering from advanced tumor stages of pancreatic cancer.

Adult

Inhibition of human exocrine pancreatic secretion by the long-acting somatostatin analogue octreotide (SMS 201-995).

The new long-acting somatostatin analogue octreotide (SMS 201-995) was investigated for its influence on secretagogue-stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U.kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 micrograms/h in a placebo-controlled randomized double-blind crossover trial. Duodenal juice samples were collected in 10-min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions. During secretin stimulation, amylase was inhibited between 41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and bicarbonate between 0 and 31% with 5, 20 and 80 micrograms/h octreotide. During secretin and ceruletide stimulation, amylase was significantly inhibited by 84%, 78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and bicarbonate by 25%, 11%, 19% with 5, 20, and 80 micrograms/h octreotide, respectively (all decreases P less than 0.05). The long-acting somatostatin analogue octreotide was confirmed to be a potent inhibitor of stimulated human exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide was achieved at a dose of only 5 micrograms/h. This finding may be of value in the planning of therapeutic studies with octreotide.

Adult

Standards in monitoring acute experimental pancreatitis.

Animal models are helpful and irreplaceable tools in studying etiological factors and the pathogenesis of acute pancreatitis. For the comparability of the results, standards in monitoring of acute experimental pancreatitis are necessary. In this article an overview about different models of acute experimental pancreatitis and their severity are given. We also describe obligatory and facultative standard parameters in monitoring of acute experimental pancreatitis.

Acute Disease

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