PubMed Health⌕ Search

Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 91 records · Page 5Linked to original sources
PubMed1994

Oxygen radicals in experimental acute pancreatitis.

Oxygen free radicals mediate an important step in the initiation of experimental acute pancreatitis. These reactive oxygen metabolites are generated at an early stage of the disease. However, the source of the enhanced production of oxygen radicals still remains unclear. Experimentally, the effectiveness of scavenger treatment varied from one model to another, the differences depending on the experimental model and not on the form of pancreatitis that was induced. In most studies the experimental animals were pretreated before inducing acute pancreatitis. This does not mirror clinical reality, since patients are admitted to the hospital after the onset of the disease. It was shown in cerulein-induced pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damage after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. Initial indirect observations also suggest that in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damage. Well-defined controlled clinical trials involving patients suffering from acute pancreatitis are therefore needed to validate the role of oxygen radicals in this disease.

Acute Disease↗
PubMed1994

Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis.

Chronic pancreatitis is characterized by proliferation of the extracellular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this study we analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic pancreatitis (n = 8) and control pancreas (n = 7) by northern blot analysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromelysin) and TIMP-1 were not detectable in chronic pancreatitis and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhanced in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels could not be correlated to the histologically detectable degree of inflammation and fibrosis or to the total amount of deposited collagen protein, which was high in all chronic pancreatitis tissue samples as determined by a standard colorimetric procedure. Increased steady state levels of transcripts encoding extracellular matrix proteins or extracellular matrix degrading proteases may thus reflect the activity of processes involved in the remodeling of the gland during chronic inflammation. The precise role of overexpression of MMP-2 and its inhibitor TIMP-2 will have to be elucidated in further studies.

Chronic Disease↗
PubMed1993

Differential inhibition by cyclosporins of primary-active ATP-dependent transporters in the hepatocyte canalicular membrane.

The distinct ATP-dependent transporters for taurocholate, leukotriene C4, and daunorubicin, studied in rat liver canalicular membrane vesicles, are sensitive to inhibition by cyclosporin A and its non-immunosuppressive analog PSC 833. Ki values for cyclosporin A were 0.2, 3.4 and 1.5 microM for the transport of taurocholate, leukotriene C4, and daunorubicin, respectively. The corresponding Ki values for PSC 833 were 0.6, 29, and 0.3 microM. Both inhibitors were competitive with respect to the three substrates. The cyclosporins serve as new and potent tools to interfere with different potency with the distinct ATP-dependent export carriers in the hepatocyte canalicular membrane.

Adenosine Triphosphate↗
PubMed1993

Regional specificities in the distribution, chemical phenotypes, and coexistence patterns of neuropeptide containing nerve fibres in the human anal canal.

Despite the pivotal clinical significance of the human anal canal, little is known about its total and specific innervation. This study assessed the comparative distribution and histotopology of nerve fibres immunoreactive for neural markers and a variety of regulatory active neuropeptides in the human anal canal by light microscopic immunohistochemistry. Depending on the epithelial zone and region of the anal canal, the neural elements were differentially immunoreactive for the pan-neural marker protein gene product 9.5, the catecholamine marker tyrosine hydroxylase, the neuroendocrine marker chromogranin A, and various neuropeptides. Protein gene product 9.5-immunoreactive nerve fibres were ubiquitously abundant in the anal canal. In the anal transitional zone, ectopic epithelial types were supplied by the same pattern of peptidergic nerves as the respective type of epithelium in normotopic location. In the dermis of the squamous zone and in the perianal epidermis, unusual distribution patterns of nerve fibres, referred to as areas of high nerve fibre density, were encountered. Double immunohistochemistry revealed region-specific coexistence patterns of neuropeptidergic nerve fibres, and novel peptide coexistence patterns were detected in anal nerve fibres. Subsets of nerve fibres formed close spatial relationships with chromogranin A-positive neuroendocrine cells, most frequently in the anal transitional zone. Chromogranin-A positive cells were shown to be present in the epithelium of perianal eccrine sweat glands. The differential distribution, peptide phenotypes and coexistence patterns of different nerve fibre populations in the human anal canal may reflect topospecific regulatory functions of neurally released neuropeptides in health and disease.

Aged↗
PubMed1993

Enhanced expression of the type II transforming growth factor beta receptor in human pancreatic cancer cells without alteration of type III receptor expression.

We have recently found that human pancreatic adenocarcinomas exhibit strong immunostaining for the three mammalian transforming growth factor beta (TGF-beta) isoforms. These important growth-regulating polypeptides bind to a number of proteins, including the type I TGF-beta receptor (T beta R-I), type II TGF-beta receptor (T beta R-II), and the type III TGF-beta receptor (T beta R-III). In the present study we sought to determine whether T beta R-II and T beta R-III expression is altered in pancreatic cancer. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas exhibited a 4.6-fold increase (P < 0.01) in mRNA levels encoding T beta R-II. In contrast, mRNA levels encoding T beta R-III were not increased. In situ hybridization showed that T beta R-II mRNA was expressed in the majority of cancer cells, whereas mRNA grains encoding T beta R-III were detectable in only a few cancer cells and were present mainly in the surrounding stroma. These findings suggest that enhanced levels of T beta R-II may have a role in regulating human pancreatic cancer cell growth, while T beta R-III may function in the extracellular matrix.

Adenocarcinoma↗
PubMed1993

CA 494--a new tumor marker for the diagnosis of pancreatic cancer.

In 59 patients with ductal pancreatic cancer the monoclonal antibody (MAb) BW 494, which detects the CA 494 glycoprotein antigen, was analyzed in comparison with the reference tumor markers CA 19-9 and CEA. Eighty-one patients with non-pancreatic malignancies of the gastrointestinal (GI) tract, 95 with chronic pancreatitis, 124 with benign non-pancreatic GI diseases, 30 with diabetes mellitus (type I or type II) and 114 healthy blood donors served as controls. The sensitivity of pancreatic cancer was 90%, 44% and 90% for CA 19-9, CEA and CA 494, respectively. In chronic pancreatitis, as the most important control population for pancreatic cancer, the specificity was 85%, 72% and 94% for CA 19-9, CEA and CA 494, respectively.

Adolescent↗
PubMed1993

Assessment of the fibrogenetic activity in chronic pancreatitis. The role of circulating levels of extracellular matrix components.

Determination of circulating levels of extracellular matrix components has been proposed as a reliable method to assess the activity of fibrogenetic processes. Therefore, we aimed to analyze circulating levels of laminin, fibronectin, and procollagen III peptide (PIIIP) in patients with chronic pancreatitis (CP) and to correlate them with the morphological and functional stage, and duration of the disease. Thirty patients with CP and 18 healthy controls were studied. Serum PIIIP concentrations (RIA), but not fibronectin (RID) and laminin (RIA), were abnormally high in 8 patients with CP. No correlation was found between circulating levels of extracellular matrix components and both functional and morphological stage and duration of CP. Nevertheless, patients with elevated serum PIIIP levels tend to have a more advanced CP (morphological and functional changes) than those with normal levels after a similar duration of the disease. We hypothesize that whereas functional and morphological findings reflect the cumulative effect of chronic inflammation on the pancreas, serum PIIIP concentrations would reflect the activity of the fibrogenetic process within the gland at the time of sampling. The results shown in the present study may be considered a starting point for longitudinal studies that examine the relationship between serum PIIIP or other markers for fibrogenetic activity and evolution of CP.

Adult↗
PubMed1993

Free fatty acids in serum of patients with acute necrotizing or edematous pancreatitis.

Serum concentrations of free fatty acids (FFA) were assayed in 20 patients with acute necrotizing pancreatitis (ANP). Pancreatic and peripancreatic fat necrosis was verified on operation and/or by contrast-enhanced computed tomography. For comparison, 20 patients with acute edematous pancreatitis (AEP) were examined. On admission, FFA serum levels were 1.14 +/- 0.12 (SEM) mmol/L in ANP and, thus, significantly (p < 0.03) higher than in AEP (0.78 +/- 0.09 mmol/L). The two groups also differed in the later course: in ANP, the FFA values remained raised (d 5-11:0.86 +/- 0.13 mmol/L; p > 0.05 vs day 1), whereas in AEP, the FFA concentrations normalized within 1 wk (d 2-4:0.52 +/- 0.11 mmol/L; d 5-11:0.39 +/- 0.05 mmol/L; p < 0.05 vs day 1 and p < 0.01 vs ANP). Serum FFA correlated positively with C-reactive protein levels (rs = 0.42; p < 0.01), but has less discriminating potency between ANP and AEP. In AEP, the initial peak may correspond to the disease outburst itself and to unspecific stress. In ANP, the higher and sustained elevation of FFA may predominantly mirror the ongoing pancreatic parenchymal and extrapancreatic fat necrosis, and be pathophysiologically relevant, especially in view of significantly reduced serum albumin levels in ANP.

Acute Disease↗
PubMed1993

Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group.

BACKGROUND: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. METHODS: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. RESULTS: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups. CONCLUSIONS: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

Acute Disease↗
PubMed1993

Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival.

BACKGROUND: Transforming growth factor beta s (TGF-beta s) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-beta expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-beta expression in human pancreatic cancer. METHODS: The distribution of TGF-beta isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques. RESULTS: Immunohistochemical analysis showed the presence of TGF-beta 1 (47% of tumors), TGF-beta 2 (42% of tumors), and TGF-beta 3 (40% of tumors) in the cancer cells. The presence of TGF-beta 2 was associated with advanced tumor stage (P < 0.05). Furthermore, there was a significant correlation between the absence of TGF-beta s in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P < 0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells. CONCLUSIONS: These findings show that human pancreatic cancers show increased levels of TGF-beta isoforms and enhanced TGF-beta mRNA expression and suggest that the presence of TGF-beta s in pancreatic cancer cells may contribute to disease progression.

Adenocarcinoma↗
PubMed1993

Overexpression of HER2/neu oncogene in human pancreatic carcinoma.

The HER2/neu oncogene encodes a transmembrane protein that possesses intrinsic tyrosine kinase activity. Its overexpression has been associated with the malignant phenotype. In this study we examined HER2/neu expression in the normal and cancerous human pancreas. In the normal pancreas HER2/neu immunostaining was observed in acinar and ductal cells. HER2/neu immunoreactivity was expressed in 34 of 76 (45%) pancreatic carcinomas. There was a significant correlation between tumors with well-differentiated histology and HER2/neu expression. Northern blot analysis demonstrated HER2/neu mRNA expression in the normal pancreas and in situ hybridization confirmed its distribution in both acinar and ductal cells. In cancer tissues Northern blot analysis indicated that HER2/neu mRNA levels were elevated in 13 of 25 (52%) of the tumors in comparison with the normal tissues. In addition, in situ hybridization demonstrated a strong but heterogenous distribution of mRNA grains in these tumors. Southern blot analysis did not demonstrate HER2/neu gene amplification in any of the tumors. These data indicate that the HER2/neu protein is synthesized in the normal exocrine pancreas and is frequently overexpressed in well-differentiated adenocarcinomas of the pancreas as a result of increased HER2/neu mRNA levels.

Adult↗
PubMed1993

Possible association of c-Harvey-Ras-1 (HRAS-1) marker with autism.

We tested for an association between autism and genes coding for enzymes involved in monoaminergic metabolism and for a linked marker, c-Harvey-Ras-1 (HRAS 1), using restriction fragment length polymorphisms. We did not find evidence of an association between autism and genes coding for tyrosine hydroxylase, dopamine-beta-hydroxylase (DBH), and tryptophan hydroxylase. However, we report a positive association between autism and the locus containing the gene for HRAS-1.

Adolescent↗
PubMed1993

Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer.

Octreotide (SMS 201-995), a long-acting somatostatin analogue, has been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. We analyzed the efficacy of octreotide treatment in 22 patients (14 men, 8 women) with histologically verified ductal pancreatic cancer. All patients had advanced tumor stages (stage III: 13 patients; stage IV: 9 patients). Octreotide was given by self-administered subcutaneous injection (3 x 100 micrograms/day). When there was evidence of tumor progression, the dose of octreotide was increased to 3 x 200 micrograms/day. A monthly follow-up, including clinical status, CT scan or ultrasonography, and tumor marker carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 determination was carried out. There were no severe side effects apart from slight burning sensation at the injection site. No partial or complete remission was seen. Eighteen patients showed tumor progression with a median survival time of 17 weeks (range 3-42 weeks). In three patients a "no change" evaluation with a median survival time of 46 weeks (range 40-68 weeks) was registered. In these three patients the serum tumor markers CA 19-9 and CEA did not show an increase to more than twice the baseline value during this time. One patient discontinued the octreotide treatment because of tumor progression. The results of the analysis indicate that low-dose octreotide treatment is not effective in patient suffering from advanced tumor stages of pancreatic cancer.

Adenocarcinoma↗
PubMed1993

Ratios of different serum pancreatic enzymes in the diagnosis and staging of chronic pancreatitis.

The aim of this study was to define an optimum serum enzyme ratio for the diagnosis of chronic pancreatitis (CP) and for the evaluation of the stage of the disease. With this goal in mind, a simultaneous and interrelated analysis of different serum pancreatic enzymes was performed in 296 consecutive patients with clinically suspected CP. A total of 167 patients were finally diagnosed with CP and 129 with other digestive diseases (used as controls). Serum values of pancreatic amylase, lipase, immunoreactive trypsin, and their ratios were determined in every patient before final diagnosis was established. Stepwise logistic regression analysis was performed. As expected, abnormally low values of individual serum pancreatic enzymes in the diagnosis of CP were highly specific (92-98%) but very insensitive (20-32%). Their diagnostic usefulness was neither improved by calculation of their ratios nor by the use of multivariate logistic regression analysis. A low pancreatic amylase/lipase ratio correlated with advanced CP (p < 0.01), and had a high degree of accuracy (80.5%) in the evaluation of the stage of the disease (assessed by endoscopic retrograde pancreatography). In conclusion, while serum pancreatic enzymes have limited usefulness in the diagnosis of CP, the pancreatic amylase/lipase ratio could be a simple method for staging the disease.

Amylases↗
PubMed1993

Prevention of postoperative complications following pancreatic surgery.

Major pancreatic resection is still accompanied by considerable morbidity and even mortality. Complications which occur after pancreatic surgery are chiefly associated with exocrine pancreatic secretion, hence, the inhibition of exocrine pancreatic secretion perioperatively is a promising concept in the prevention of complications. The hormone somatostatin and its synthetic analogue octreotide have been shown to profoundly inhibit exocrine pancreatic secretion, particularly the secretion of proteases. In a randomized, placebo-controlled, multicenter double-blind trial we analyzed the potential role of octreotide in the prevention of postoperative complications after major pancreatic surgery. A significant reduction in complications such as fistula, abscess, fluid collection, sepsis, pulmonary insufficiency, and postoperative acute pancreatitis could be demonstrated in patients who received octreotide at 3 x 100 micrograms/day subcutaneously. Octreotide was particularly effective in patients undergoing Whipple resection for cancer.

Double-Blind Method↗
PubMed1993

Enzyme treatment after gastrointestinal surgery.

After gastrointestinal surgery, patients often suffer from maldigestion. The extent of this maldigestion syndrome depends on the type of surgical procedure performed. After total pancreatectomy, subtotal left resection, resection for chronic pancreatitis. Whipple operation with ductal occlusion, and total gastrectomy, patients need obligatory enzyme treatment. After partial pancreatectomy without duct occlusion or partial gastrectomy, enzyme treatment should be initiated when exocrine pancreatic insufficiency occurs.

Chronic Disease↗