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Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 109 records · Page 6Linked to original sources
PubMed1993

Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas.

The actions of transforming growth factor-beta isoforms as potent regulators of growth and differentiation have led to the examination of their presence in the human pancreas. The cellular localization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 was assessed in the normal human pancreas by using immunohistochemical and in situ hybridization techniques. Although cytoplasmic immunoreactivity for TGF-beta 1, TGF-beta 2, and TGF-beta 3 was found in islet cells, acinar cells, and ductal cells, a differential immunostaining pattern for TGF-beta isoforms was observed. In the endocrine pancreas, the islet cells demonstrated diffuse cytoplasmic immunostaining for TGF-beta 1, TGF-beta 2, and TGF-beta 3. However, only TGF-beta 2 and TGF-beta 3 exhibited an intense pattern of immunostaining in a few endocrine cells. Most of the positive islet cells coexpressed insulin. In contrast, in the exocrine pancreas, a greater number of acinar cells showed immunoreactivity for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3. In the ductal cells, all three TGF-beta isoforms showed a similar intensity and pattern of immunostaining and were observed more frequently in the smaller distal ductules than in the larger pancreatic ducts. TGF-beta 1 and TGF-beta 3, but not TGF-beta 2, immunostaining was detected strongly in the smooth muscle cells and weakly in the endothelial cells of the blood vessels, whereas the fibroblasts of the interstitium were completely negative. In situ hybridization revealed that mRNA encoding all three TGF-beta isoforms colocalized with their respective proteins in islets, acinar cells, and ductal cells. In contrast, mRNA expression was absent in the smooth muscle cells and endothelium of the vessels. These results suggest that TGF-beta isoforms may act by both autocrine and paracrine mechanisms in the pancreas. The differential pattern of expression observed for each TGF-beta isoform implies unique roles for these proteins in the regulation of the endocrine and exocrine pancreas.

DNA Probes↗
PubMed1993

Complications of acute pancreatitis and their management.

Severe acute pancreatitis remains a disease with high hospital mortality. In the period from 1991 to 1992, several articles dealt with the complicated form of acute pancreatitis. There is no question that necrosis of the pancreas and fatty tissue in the peripancreatic spaces and particularly secondary infection of necrosis are the most important prognostic factors for these patients. Indications for surgery and the efficacy of conservative treatment of acute pancreatitis (including interventional measures) have not been clearly determined. Most surgeons would elect to operate on a patient with multiorgan failure caused by infected necrosis, however. Another major question is the type of surgery to be performed: closed continuous lavage of the lesser sac and retroperitoneal cavities, staged relaparotomy, or open packing. This review concentrates on articles pertaining to complicated acute pancreatitis in humans.

Acute Disease↗
PubMed1993

Clinical utility of the serum pancreolauryl test in diagnosis and staging of chronic pancreatitis.

Indirect pancreatic function tests are frequently used in the clinical routine as complementary tools for the diagnosis of chronic pancreatitis (CP) because of their noninvasiveness and simplicity. We analyzed the clinical efficacy and routine application of a modified serum pancreolauryl test (PLT) in the diagnosis and staging of CP. We studied a total of 90 patients with CP diagnosed by endoscopic retrograde pancreatography and 54 patients with extrapancreatic gastrointestinal disorders as controls. Sensitivity and specificity of the serum PLT in the diagnosis of CP were 82% and 91%, respectively, using a value of 4.5 micrograms/ml as cutoff. In the diagnosis of patients with mild to moderate morphological changes of CP, the sensitivity of the serum PLT (52%) was improved by the concomitant analysis of serum pancreatic amylase in a logistic model (70%). Serum PLT closely correlated with the degree of pancreatic ductal abnormalities (p < 0.001), and showed a sensitivity of 81% and specificity of 89% in the staging of CP (mild-moderate vs. marked CP; cutoff 2.5 micrograms/ml). We conclude that the modified serum PLT is a reliable test which should be considered as a first-line option for the diagnosis and follow-up of patients with CP.

Amylases↗
PubMed1993

Surgical strategies in acute pancreatitis.

The most important diagnostic step in the management of patients with acute pancreatitis is to discriminate between interstitial-edematous and necrotizing pancreatitis. Measurement of C-reactive protein or PMN-elastase is useful in detecting the necrotizing course of acute pancreatitis. While patients with acute edematous pancreatitis can be treated on a regular ward, patients with a necrotizing course should be treated in the ICU. Surgical decision-making in necrotizing pancreatitis should be based on the extent of necroses found by contrast-enhanced CT, and on the development of septic signs due to bacterial infection of the necroses. Information about the latter can be obtained by a bedside ultrasound-guided fine needle aspiration and bacteriological examination of the aspirate. Patients with no organic complications and with focal necrosis should be treated conservatively, while patients with persistent organic insufficiencies or progressive multiple organ failure despite maximum intensive care are candidates for surgical therapy. The procedure of choice in necrotizing pancreatitis is the careful removal of necrotic tissue (necrosectomy) followed and supplemented by a postoperative regimen for the continuous evacuation of further necrotic debris. Hospital mortality rate has been reduced to less than 20% by this procedure.

Abscess↗
PubMed1993

Pancreatic necrosis: an early finding in severe acute pancreatitis.

Despite the clinical importance of pancreatic necrosis in the course of acute pancreatitis, little is known about when it develops. Serum C-reactive protein (CRP) is a reliable parameter with a high deduction rate for pancreatic necrosis. We analyzed 199 patients with acute pancreatitis. The development of pancreatic necrosis was ascertained by a daily measurement of serum CRP in 45 patients with contrast-enhanced computed tomographic-proven necrotizing pancreatitis. In all 45 cases, the criteria for pancreatic necrosis were satisfied within the first 4 days of the onset of symptoms. This indicates that pancreatic necrosis is an early finding that develops within hours.

Acute Disease↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗