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Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 199 records · Page 11Linked to original sources
PubMed1988

Pancreatic trophism following colectomy in rats: the potential role of gastrointestinal hormones.

It has been shown that the large bowel contains substances with a potential to inhibit exocrine pancreatic function. Following large bowel removal in rats, there is an increase of pancreatic weight, digestive enzyme concentration, and secretion capacity in vitro. To evaluate the role of various GI hormones in the exocrine pancreatic adaptation following colectomy, we measured plasma cholecystokinin (CCK), neurotensin, glucagon, and insulin after meal stimulation. The test meal was applied via a transabdominal gastric tube in eight colectomized Wistar rats after a median of 18 days following surgery. Ten rats with a gastric tube without previous bowel surgery served as controls. After large bowel removal, there was impaired glucose tolerance and attenuated plasma insulin secretion. Baseline plasma glucagon levels were increased after colon removal, whereas the total postprandial glucagon release was decreased. Baseline and postprandial neurotensin values were comparable in both the experimental and control animals. Baseline and postprandial CCK plasma levels were intensely increased in the colectomized rats. It is assumed that the baseline and postprandial CCK pattern in rats after subtotal colectomy is responsible for exocrine pancreatic adaptation.

Animals↗
PubMed1988

Role of nutrients in pancreatic adaptation with implication of cholecystokinin release.

The exocrine pancreatic function is adapted to the composition of nutritional substrates. Dietary constituents activate specific neural mechanisms and the release of gut peptides operating on pancreatic enzyme synthesis and secretion. Cholecystokinin (CCK) released by dietary protein and by protease inhibition stimulates protease synthesis in the pancreas and promotes pancreatic growth. The interplay between changes in dietary protein content and increased plasma CCK released by a synthetic protease inhibitor (Foy 305) confirm the essential role of the nutritional support of protein to enable the display of pancreatic adaptation.

Animals↗
PubMed1988

Gut peptide-mediated adaptive response of the exocrine pancreas.

The gastrointestinal system is substantially involved in the regulation of exocrine pancreatic secretion, and it is therefore not surprising that intestinal diseases have been shown to affect exocrine pancreatic function. In rat experiments gastrectomy, truncal vagotomy, and subtotal colectomy stimulated pancreatic growth and altered pancreatic enzyme composition. Focusing on two main hormones supposed to be involved in the regulation of pancreatic adaptation, we studied basal and stimulated gastrin and cholecystokinin (CCK) pattern after the operative procedures. After total gastrectomy basal CCK values were unchanged, whereas postprandial CCK plasma values and the integrated postprandial CCK release were significantly increased. After subtotal colectomy CCK levels, both basal and postprandial, were significantly increased. In both of these conditions gastrin levels were either decreased (total gastrectomy) or unchanged (subtotal colectomy). CCK may therefore be the major humoral candidate to promote the observed pancreatic adaptive response. After truncal vagotomy CCK values remained unchanged, whereas basal and postprandial gastrin was significantly increased. Gastrin may be a candidate involved in the stimulation of pancreatic trophism after vagisection.

Adaptation, Physiological↗
PubMed1988

[Diagnostic strategies of the pancreas].

Once a diagnosis of acute pancreatitis is established, it is necessary to discriminate between the edematous-interstitial and the necrotizing course of the disease, to detect early infection and to determine the extent of necrosis by angiography and CT. After diagnosis of chronic pancreatitis it is imperative to ascertain the severity by endoscopic retrograde cholangio-pancreatography (ERCP), the impairment of function by the secretin-pancreozymin test as well spread to neighbouring organs. Beginning with the clinical picture, pancreatic carcinoma can be detected with great reliability by ERCP, contrast CT, tumor markers and fine-needle aspiration.

Acute Disease↗
PubMed1988

Human monoclonal anti-idiotypic antibodies as an epitope vaccine against pancreatic carcinoma.

During therapeutic repetitive application of MAb BW 494 in pancreatic carcinoma patients, a human IgG anti MAb BW 494 response arose, which was analyzed on the B cell clonal level as well as in the serum of these patients 2-4 months after treatment. From 5 investigated patients 3 developed a polyclonal human IgG anti-idiotypic response in the serum and had B cells with the same specificity which could be immortalized by EBV transformation. Two out of 5 patients showed an anti-idiotypic and anti-isotypic polyclonal response which could be found on the B cell clonal level as well. The data indicated that the human IgG anti MAb BW 494 response was mainly anti-idiotypic.

Antibodies, Monoclonal↗
PubMed1988

[Necrosectomy and bursa lavage in necrotizing pancreatitis. Results of a prospective clinical study].

In a prospectively performed clinical trial a surgical management protocol including necrosectomy and postoperative local lavage of the necrosis cavity and the omental bursa was applied in 95 patients with necrotizing pancreatitis. In 80% of them severe organ failures occurred preoperatively, in spite of intensive care treatment. The median value of early prognostic signs of these patients was 4.5. Intraoperatively 59% showed extended pancreatic necroses and 66% an extension of the necroses into extrapancreatic tissue structures; in 42% bacteria were detected in the necrotic material. After necrosectomy the postoperative local lavage was performed for an average period of 25 days with 8 1 of lavage fluid per 24 hours in median. The average intensive care period came to 7.0 days, the average postoperative hospital time was 60 days. The hospital mortality amounted to 8.4%. The advantage of this management protocol including necrosectomy and postoperative local lavage lies in the continuous emptying of vasoactive and toxic substances, germs and necrotic material.

Acute Disease↗
PubMed1988

[Monoclonal antibodies in the therapy of non-resectable pancreatic cancers. Initial experiences].

In this study 34 patients with pancreatic cancer were treated postoperatively with monoclonal antibodies (MABs). The antibody BW 494/32 is directed against a membrane antigen of differentiated adenocarcinomas of the pancreas and mediates cellular cytotoxicity. The patients suffered from non resectable tumors, mostly with lymph-node or liver metastases. The patients received repeated doses of MABs over a time period from 5 to 14 days. The highest single dose was 100 mg, the highest cumulative dose 490 mg. At the moment 16 out of 34 patients are eligible for evaluation of tumor response. There was no complete or partial remission (reduction more than 50% of tumor volume). However, two patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in cat scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). 9 patients had progressive tumor disease in spite of MAB-treatment. Two to three weeks after antibody infusion most patients produce human anti-murine-antibodies, so that severe allergic reactions may occur, if the application is repeated.

Adenocarcinoma↗
PubMed1987

Tumor scintigraphy with 131I anti CEA monoclonal antibodies and F(ab')2 in colorectal cancer.

In 14 patients with proven local recurrence of colorectal cancer or metastases in liver and/or lungs, the sensitivity (SE) in detecting tumor sites was estimated in a single-blind study using conventional planar whole body scintigraphy. Nine patients received F(ab')2 and five received MAB by intravenous infusion over 30 min with a dose of 40-200 MBq after skin testing and thyroid blocking, scanning was performed 1-7 days later. All but one patient had elevated plasma CEA levels with a mean of 25.5 +/- 31.9 ng/ml. The scans were interpreted by two independent observers. In five of the nine patients receiving F(ab')2, the tumor site could be visualized, yielding a sensitivity of 55%. No tumor sites were identified with MAB. The highest tumor uptake was recorded in a patient with additional ovarian cancer with the activity accumulating in the ovarian cancer. The optimum time for imaging was 3 or 4 days after injection. There was no correlation between positive imaging and plasma CEA levels which ranged from 1.9 ng/ml to 100 ng/ml in the positive cases. The thyroid uptake on the sixth day was 0.68% +/- 0.2% of the total dose given despite thyroid blocking. Bone uptake of 131I was also observed, this was mild in four patients, moderate in three but high in one patient, especially on days one to four. Thus, only anti-CEA F(ab')2 seem to be of clinical interest for further evaluation in localizing colorectal cancer. Regarding the still low sensitivity of 55%, further improvement can be expected by gaining experience, using more appropriate isotopes such as 111In and SPECT. The estimated radiation side effects on thyroid and bone marrow are only modest.

Aged↗
PubMed1987

[Immunohistochemistry in pancreatic cancer with new monoclonal antibodies].

Immunhistochemistry using hybridoma-derived monoclonal antibodies (MAb's) directed against tumor associated antigens offers new approaches to morphological diagnosis of tumors, e.g. for classification and typing of tumor subtypes with different prognosis. Before in-vivo application of monoclonal antibodies in man for diagnostic or therapeutic purposes the tissue distribution of the antibody should be determined immunhistochemically for assessment of antibody sensitivity and specificity. The binding capacity of the newly developed MAb BW 494/32 to pancreatic cancer tissues was therefore tested by immunhistochemistry, other benign and malignant intestinal and extraintestinal tissues served as controls. The MAb BW 494/32 showed positive immunoreactivity in all cases of ductal pancreatic adenocarcinomas grading I to II (sensitivity: 100%). In grading III carcinomas the target antigen was only accessible in half of the tested specimens. Specificity was limited by a mostly weak immunoreactivity with normal pancreas tissue in 36%, with acute inflamed tissue in 100%, with inflamed tissue in chronic pancreatitis in 71%. Extrapancreatic specificity was restricted by positive antibody binding to singular goblet cells of gastrointestinal epithelium. The well established antibody CA 19-9 was used for comparison. CA 19-9 showed about the same sensitivity of 88% (BW 494/32: 92%) for ductal pancreatic adenocarcinomas grading I to III. Specificity of CA 19-9, however, was comparable more restricted, as CA 19-9 showed a significant cross-reactivity with other gastrointestinal adenocarcinomas (5 out of 6 colorectal cancers, 3/6 gastric carcinomas, 1/3 carcinomas of the common bile duct), with some extraintestinal cancers (breast 60%, lungs 50%) and with other non-cancerous tissues of intestinal origin. According to the results of this study it is worthwhile to investigate the antibody BW 494/32 for possible applications in experimental immunodiagnosis and -therapy of pancreatic cancer.

Antibodies, Monoclonal↗
PubMed1987

Pancreatic abscess and infected pancreatic necrosis. Different local septic complications in acute pancreatitis.

Local septic complications in acute pancreatitis need to be exactly characterized and defined in order to develop improved concepts for their prevention, early diagnosis, and therapy. While up to now all local septic complications have been termed abscesses, the present study for the first time delineates the morphologic, clinical, and laboratory criteria needed to distinguish between two separate clinical entities: the infected necrosis (IN) and the pancreatic abscess (PA). IN is defined as a diffuse bacterial inflammation of necrotic pancreatic and peripancreatic tissue, but without any significant pus collections. On the other hand, the morphologic substrate of PA is a localized collection of pus surrounded by a more or less distinct capsula. IN becomes clinically evident during the early phase of acute pancreatitis (AP). The patients with IN present both the signs of sepsis and the laboratory findings of AP. Thus in these patients the most fulminant course of AP is observed; 51.8% and 35.7% of them have pulmonary or renal insufficiency, respectively. The mortality of the patients with IN is high and amounts to 32.1%. Pancreatic abscess, on the other hand, does not develop before the fifth week after onset of symptoms and after subsidence of the acute phase of pancreatitis. In these patients laboratory signs of AP-like amylasemia, hypocalcemia, hyperglycemia, and rise of LDH are rarely observed. Corresponding to the lack of pathophysiologic effects of AP per se, pulmonary and renal insufficiencies occur in only 33.3% and 16.7%, respectively, and mortality in these patients is 22.2%. While an abscess may readily be identified by computed tomography, the differentiation between IN and non-IN can be very difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1987

Serum elastase 1 in inflammatory pancreatic and gastrointestinal diseases and in renal insufficiency. A comparison with other serum pancreatic enzymes.

Serum elastase 1 has been evaluated in 115 patients with pancreatic and nonpancreatic gastrointestinal diseases and in 36 healthy controls. Increased serum elastase 1 values were found in all 27 patients with acute pancreatitis. If the diagnostic cutoff was established as the 2-fold increase above the upper normal range, sensitivity of elastase 1 (100%) was superior to pancreatic lipase (90%), immunoreactive trypsin (87%) and pancreatic amylase (78%). Specificity was 96% for elastase 1 at this cutoff. No distinction was possible between edematous and necrotizing acute pancreatitis on the basis of peak serum elastase 1 concentrations. Among 32 patients with chronic pancreatitis increased serum elastase 1 values were found in 22% and decreased values in 16% of patients, showing a striking parallelism to serum values of pancreatic lipase and immunoreactive trypsin. Specificity, established in controls and 49 patients with different gastrointestinal diseases, was 77% for elastase 1, 76% for immunoreactive trypsin, 83% for pancreatic lipase and 91% for pancreatic amylase. In addition, we investigated 21 patients with severe chronic renal diseases. In patients with renal insufficiency elastase was increased in 33%, comparable to the frequency of increased amylase and pancreatic amylase serum levels, whereas immunoreactive trypsin was increased in 95%. Immunoreactive trypsin showed a significant correlation to creatinin serum concentration, whereas the other enzymes did not.

Acute Disease↗
PubMed1987

Pancreatic morphology and function in relationship to pain in chronic pancreatitis.

The correlation of pancreatic pain and the degree of morphological and functional changes was prospectively investigated in 64 patients (45 males, 19 females) with chronic pancreatitis. All patients underwent clinical examination and diagnostic investigations by means of endoscopic retrograde pancreatography (ERP), computed tomography (CT) and exocrine pancreatic function test (secretin-ceruletide; SC). The individual tests were performed within 4 weeks in all patients. No significant correlation was found between the degree of pain and the severity of ERP and CT findings. Severe pain was found in 62% of patients with advanced ductal changes, and in 41% of patients with advanced parenchymal lesions. 58% of patients with severe pain had marked exocrine insufficiency. Ductal changes characterized by obstruction of the main pancreatic duct were most frequently associated with severe pain (58%). Less often, severe pain was associated with duct dilatation (34%) or with slight duct changes (26%). Among parenchymal lesions as revealed in CT, large cysts were most frequently related to severe pain (62%). A notable finding was that 89% of patients presenting with calcifications in CT still experienced pain and 39% of them had severe pain. The combined diagnostic approach is useful for the individual therapeutic management, but does not provide insight into the mechanisms of pain in chronic pancreatitis.

Adult↗
PubMed1987

Pancreatic trophism after truncal vagotomy in rats.

Thirty-two rats had truncal vagotomy either with or without pyloroplasty. After 2 or 4 weeks, respectively, the pancreas was excised and weighed. Measurements of amylase, trypsin, lipase, total protein, and DNA were obtained from the homogenated pancreatic tissue. Isolated pancreatic lobules were incubated with and without ceruletide (5 X 10(-10) g/ml) during a 60 minute period. Amylase values were determined four times in the incubation medium. Morphometry was performed by light microscopy analysis. There was a significant increase in pancreatic weight, DNA content, and trypsin concentration 2 weeks after vagotomy with and without pyloroplasty. These changes were accelerated after 4 weeks. DNA, amylase, and total protein concentrations were unchanged. Lipase concentration decreased 2 weeks after vagotomy and pyloroplasty, whereas at 4 weeks, it decreased in both experimental groups. The in vitro incubation study revealed a significantly decreased amylase discharge under basal conditions, whereas the stimulated amylase discharge was unchanged in both experimental groups compared with the control group. Morphometry did not detect differences in exocrine cellular size. We conclude that vagotomy in rats induces pancreatic hyperplasia, enzyme dissociation, and decreased basal amylase discharge in vitro.

Amylases↗
PubMed1987

Fluorescein dilaurate serum test: a rapid tubeless pancreatic function test.

The value of a modified fluorescein dilaurate (FDL) serum test for the detection of pancreatic exocrine insufficiency was investigated in 89 patients with and without pancreatic disease. This test modification with fluorescein serum determination following metoclopramide (10 mg) and secretin (1 U/kg) i.v. injection appeared efficacious in a pilot study in six healthy volunteers. Individual peak fluorescein serum concentration was achieved within 180 min after the test meal in 96% of all subjects studied. Peak fluorescein serum concentration within this time period allowed the best discrimination between normal and abnormal pancreatic function. Sensitivity in detection of chronic pancreatitis was 86% (38 of 44 patients) when the lower normal fluorescein serum concentration was considered 4.5 micrograms/ml (this value corresponds to mean - 2 SD). The specificity of this test in detecting chronic pancreatitis was 100% when healthy controls were considered, but fell to 78% when patients with different gastrointestinal disorders, including those with secondary pancreatic insufficiency, were included. The correlation between serum and urinary fluorescein determination was significant (r = 0.61; p less than 0.01). Duodenal bicarbonate output/h after secretin also showed a significant correlation with peak fluorescein serum concentration (r = 0.79; p less than 0.001).

Adolescent↗
PubMed1987

Sepsis indicators in acute pancreatitis.

Twenty-one routine clinical and laboratory data in 161 patients with necrotizing pancreatitis (NP) undergoing surgical treatment were analyzed. The necrotic tissue at operation was bacterially infected in 41% of the patients. The goal of the study was to evaluate whether there was any special clinical feature in cases of an infection. The parameters were recorded during 48 h after admission as well as during 48 h before operation, and the frequencies submitted to both a univariate and a multivariate analysis (logistic regression model). In the period after admission, patients with infected necrosis significantly more often had a rectal temperature greater than 38.5 degrees C (p = 0.001). Before operation (i.e., after maximum conservative treatment), four findings were significantly related to an infection: rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, hematocrit less than 35% (all p = 0.0001), and paO2 less than 60 mm Hg (p = 0.001). The multivariate analysis, which calculates and quantifies the mutual influence of factors, showed a combination of three findings (rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, and hematocrit less than 35%) to be related to necrosis infection before operation. All three criteria in a patient imply a probability of infection of 83%. It is noteworthy that the sepsis indicators were equally distributed in patients with focal, extended, or subtotal/total infected necrosis, but correlated with the necrosis extent in sterile necrotizing pancreatitis. Moreover, all parameters not related to the pancreatic infection [e.g., hyperglycemia, hypocalcemia, rise of lactic dehydrogenase (LDH), and the white blood cell count] correlated with the three necrosis categories.

Acid-Base Imbalance↗
PubMed1987

Adaptive changes in rat exocrine pancreas following subtotal colectomy.

Subtotal colectomy was performed in 17 rats. After 2 or 4 weeks the entire pancreas was excised and isolated pancreatic lobules were incubated for 60 min in Krebs-Ringer-Hepes solution either with or without addition of ceruletide (5 X 10(-10) g/ml). Amylase was determined every 15 min in the supernatant medium. Amylase, trypsin, DNA and total protein were measured in homogenized pancreatic tissue. Morphology was performed via light-microscopy analysis. Two weeks after subtotal colectomy we found an increase in pancreatic wet weight, enzyme and protein content, cellular size and secretion capacity in vitro, whereas DNA concentration in relation to pancreatic tissue weight in grams decreased. These changes pointed to pancreatic hypertrophy. Four weeks after surgery, pancreatic wet weight, enzyme content and DNA content as well as in vitro amylase discharge increased, whereas cellular size remained unchanged compared to controls and sham-operated rats. These changes were indicative of pancreatic hyperplasia.

Adaptation, Physiological↗