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Biomedical subjects

M Büchler

Publications and source records attributed to M Büchler.

At least 145 records · Page 8Linked to original sources
PubMed1991

A randomized controlled trial of adjuvant immunotherapy (murine monoclonal antibody 494/32) in resectable pancreatic cancer.

In a prospective randomized multicentric trial, 61 patients from six hospitals with resectable pancreatic cancer were recruited between 1987 and 1989. All patients underwent a Whipple resection. Two weeks after surgery, the patients were randomized to be given either intravenous (IV) treatment with 370 mg (100 mg loading dose, 9 x 30 mg continuing within 10 days) of monoclonal antibody (MoAb) 494/32 (Behringwerke AG, Marsburg, Germany) or no additional anti-cancer treatment. This murine immunoglobulin (Ig) G1 antibody has been shown to strongly bind to human pancreatic cancer cells and to induce an antibody-dependent cellular cytotoxicity (ADCC). Both study groups were well matched with respect to age, sex, tumor staging, and grading. Six patients suffered from minor toxicity (vomiting and abdominal pain) after immunotherapy. Ten months after the end of the recruitment period, 65% and 53% of the patients in the treatment and control groups, respectively, had died. Of the living patients, 60% and 53% are alive with recurrent or progressive cancer disease. Median survival time was 428 days (range, 248 to 510 days) and 386 days (range, 296 to 509 days) in the treatment and control groups, respectively. The authors concluded that repeated IV treatment with the antibody 494/32 is not helpful in resectable pancreatic cancer. This study provides the first controlled data on passive immunotherapy in solid cancer.

Adult↗
PubMed1991

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency. 137 patients (84 males, 53 females, age 34-72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n = 24), moderate (n = 61) or severe (n = 38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190-1020 pg/ml for serum vitamin B12 and 2.4-16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512 +/- 48 pg/ml in mild, 493 +/- 52 pg/ml in moderate and 428 +/- 45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34 +/- 0.76 ng/ml in mild, 6.34 +/- 0.52 ng/ml in moderate and 7.45 +/- 0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Serum ribonuclease activity in the diagnosis of pancreatic disease.

The present study evaluated serum ribonuclease activity (SRA) in patients with inflammatory and neoplastic pancreatic diseases. RNase determination was carried out using t-RNA (T) from E. coli MRE 600 at pH 7.4 and polycytidylic acid (poly-C) (P) at pH 6.6 as RNA substrates with RNase A from bovine pancreas as reference enzyme. Healthy volunteers had a SRA of T: 160 +/- 12 and P: 482 +/- 24 ngeq/mL (mean +/- SEM (n]. In patients with acute interstitial pancreatitis (AIP), SRA was similar to healthy controls (T: 166 +/- 14; P: 474 +/- 30 ngeq/mL). Patients with acute necrotizing pancreatitis (ANP) had increased SRA (T: 278 +/- 49; P: 791 +/- 145 ngeq/mL, p less than 0.01, compared to controls). SRA values were also increased in patients with chronic pancreatitis (CP) with T: 224 +/- 15 ngeq/mL (p less than 0.01) and in patients with pancreatic carcinoma (PCA) with T: 331 +/- 35 (p less than 0.001 vs controls, p less than 0.01 vs CP). Increased SRA was detected in patients with renal insufficiency (T: 2576 +/- 195 ngeq/mL, p less than 0.001). Diagnostic discrimination between AIP and ANP was achieved in 69% using T-SRA (sensitivity 31%, specificity 88%), and in 78% using P-SRA (sensitivity 54%, specificity 92%). Discrimination between CP and pancreatic carcinoma was possible in 68% (sensitivity 67%, specificity 71%). The diagnostic value of serum RNase is limited because of its low sensitivity, but increased T-SRA above a cutoff of 250 ngeq/mL and increased P-SRA above a cutoff of 620 ngeq/mL are specific for detecting pancreatic necrosis in the absence of renal impairment. The kidney is a major site for SRA clearance.

Acute Disease↗
PubMed1991

PMN-elastase in comparison with CRP, antiproteases, and LDH as indicators of necrosis in human acute pancreatitis.

We analyzed the role of polymorphonuclear granulocytes (PMN)-elastase in predicting the prognosis of patients with acute pancreatitis in comparison with C-reactive protein (CRP), lactate dehydrogenase (LDH), and the two antiproteases alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M). Fifty-two patients with acute pancreatitis were subdivided according to morphological criteria into 29 patients with edematous pancreatitis and 23 patients with necrotizing pancreatitis. Within 5 days after the onset of acute pancreatitis, the accuracy rates for detecting necrotizing pancreatitis were 86%, 84%, 82%, 72%, and 69%, using cutoff levels of 120 mg/L for CRP, 120 micrograms/L for PMN-elastase, 270 U/L for LDH, 1.5 g/L for alpha 2-M, and 3.5 g/L for alpha 1-AT, respectively. The median peak value of PMN-elastase was reached on day 1 of acute pancreatitis in contrast to the median peak of CRP, which was at its highest between days 3 and 4. PMN-elastase represents a reliable indicator, comparable with CRP, for the staging of acute pancreatitis. The advantage of PMN-elastase over CRP appears to be its earlier increase and the greater dynamism of its serum course. Finally, the results suggest that CT scanning for the evaluation of the extent of intra- and extrapancreatic necrosis could be restricted to those patients with increased values of PMN-elastase and CRP.

Acute Disease↗
PubMed1991

LH-RH receptors in the human pancreas. Basis for antihormonal treatment in ductal carcinoma of the pancreas.

LH-RH-, estrogen-, and progesterone-receptor binding was measured in the human pancreas of patients with ductal pancreatic cancer (n = 23) and chronic pancreatitis (n = 15), and of organ donors (n = 11). Receptor analysis was determined by incubation of the homogenized tissues with estrogen, progesterone, and the LH-RH analog buserelin labeled with iodine-125. Only one biopsy (9%) from normal pancreas had an LH-RH-receptor concentration greater than 3 fmol/mg membrane protein. LH-RH binding levels greater than 3 fmol/mg were detected in 67% of patients with chronic pancreatitis and in 57% of patients with pancreatic cancer. Progesterone levels greater than 15 fmol/mg membrane protein were found in 36% of normal pancreas, in 27% of chronic pancreatitis, and in 17% of pancreatic cancer cases, respectively. The highest concentration of estrogen receptors (greater than 15 fmol/mg membrane protein) was seen in normal pancreas (73%). The increase in LH-RH-receptor concentration in chronic pancreatitis and pancreatic cancer seems to be unspecific, but might be of benefit for antiproliferative treatment in pancreatic cancer.

Adult↗
PubMed1991

Carboxylic ester hydrolase. A sensitive serum marker and indicator of severity of acute pancreatitis.

When using clinical criteria, both falsely positive and falsely negative diagnoses of acute pancreatitis (AP) are often made. Based on a clinical study, elevated serum levels of the pancreatic lipolytic enzyme carboxylic ester hydrolase (CEH) was recently suggested to be a highly specific marker of acute pancreatitis. To determine the sensitivity of the test for AP, a study on patients with the diagnosis set objectively was necessary. In the present study, AP was diagnosed by contrast-enhanced computed tomography in 64 patients, and histopathological examination of tissue removed at laparotomy in 18 of them. By these criteria, 42 patients suffered from acute interstitial pancreatitis (AIP), and 22 patients from necrotizing pancreatitis (NP). Based on the CEH concentrations in the first serum sample obtained in each patient, the sensitivity of CEH for pancreatitis was 98%. From the second day after admission, CEH levels in patients with NP were significantly higher than in patients with AIP. Furthermore, in patients with NP, CEH values remained at a raised level for the following 10 d, whereas a significant decrease of CEH values was noted in patients with AIP. In contrast, total serum amylase activities were higher in patients suffering of AIP than in patients suffering of NP during the observation period. We conclude, that the sensitivity of the CEH test is very high for AP. CEH concentrations remaining at a high level are suggestive of NP, whereas diminishing CEH levels are suggestive of AIP.

Acute Disease↗
PubMed1990

Serum phospholipase A2 in patients with multiple injuries.

Catalytic phospholipase A2 activity (CA-PLA2) and the concentration of immunoreactive pancreatic PLA2 (IR-PLA2) were measured in serum samples from 12 patients with multiple injuries (median Injury Severity Score: 41). CA-PLA2 was increased in all patients and positive correlations were found between the extent of the increase of CA-PLA2, mortality, and impairment of pulmonary function. IR-PLA2 values were slightly increased in the serum of nine patients with multiple injuries. Of these nine patients, eight had an additional blunt abdominal trauma. On the other hand, no relationship was found between IR-PLA2 and CA-PLA2 values. This finding was confirmed by immunoadsorption experiments with an antiserum to human pancreatic PLA2, which demonstrated that the increased serum levels of IR-PLA2 were not responsible for the increased CA-PLA2 values. The results suggest the existence of at least two immunologically different phospholipase A2 enzymes in sera of patients with multiple injuries.

Adolescent↗
PubMed1990

Effects of TRH on pancreatic growth and secretion in rats.

Thyrotropin-releasing hormone (TRH) has been shown to be scattered throughout the gastrointestinal tract. High concentrations of TRH are reported in the pancreas of animals and humans. The present study was designed to investigate the pattern of pancreatic adaptation following chronic TRH administration in rats. Ten male Wistar rats were injected daily at 8.00 and 16.00 h with TRH (total dose of 6 mg/kg of body weight/day) via a chronic gastric fistula. Ten pair-fed control animals were injected with a saline solution. After 10 days, the rats were killed after an overnight fast; pancreatic wet weight, DNA, protein, amylase, trypsin, and lipase content were determined. Blood TRH levels were measured using a specific RIA (TRH antiserum K2B7, normal range of 30-80 fmol/ml). TRH increased pancreatic wet weight (+70%, p less than 0.01), DNA content (+83%, p less than 0.01), and protein content (+42%, p less than 0.05). Pancreatic enzyme concentrations (U/mg of DNA) were decreased (amylase, -81%; trypsin, -47%; lipase, -59%, p less than 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p less than 0.01) but the relative amount of basal and stimulated amylase discharge (% of total) was not influenced by TRH. Blood TRH levels were significantly increased (324 +/- 53 vs. 48 +/- 6 fmol/ml, p less than 0.01) 12 h after the last TRH administration. These data indicate that chronic TRH administration in rats induces pancreatic hyperplasia but decreases the pancreatic concentration of digestive enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1990

Oxygen free radicals in acute pancreatitis of the rat.

This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed.

Acute Disease↗
PubMed1990

Duodenum-preserving resection of the head of the pancreas--an alternative to Whipple's procedure in chronic pancreatitis.

Duodenum-preserving resection of the head of the pancreas is a low-risk operation for patients with chronic pancreatitis. Subtotal resection of the head of the pancreas does not result in a significant diminishment in the exocrine and endocrine functions of the pancreas. Owing to the limited nature of the intervention, hospital and late mortality rates are low. More than 80% of the patients with CP have experienced long-lasting relief of pain after this procedure. In comparison with the Whipple operation duodenum-preserving resection of the head of the pancreas spares the patient a gastrectomy, a duodenectomy, and resection of the extrahepatic bile duct.

Anastomosis, Surgical↗