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Biomedical subjects

H Friess

Publications and source records attributed to H Friess.

At least 19 recordsLinked to original sources
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

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.

The epidermal growth factor (EGF) receptor is activated by both EGF and transforming growth factor-alpha (TGF-alpha). Using immunohistochemical and immunoblotting techniques we now report that the EGF receptor, EGF, and TGF-alpha are found in both pancreatic acini and ducts in the normal human pancreas, and that all three proteins are expressed at higher levels in human pancreatic cancer tissues. Using in situ hybridization techniques, we also report that the mRNA encoding the EGF receptor, EGF, and TGF-alpha colocalize with their respective proteins. Northern blot analysis of total RNA indicates that, by comparison with the normal pancreas, the pancreatic tumors exhibit a 3-, 15-, and 10-fold increase in the mRNA levels encoding the EGF receptor, EGF, and TGF-alpha, respectively. Furthermore, by in situ hybridization, there is a marked increase in these mRNA moieties within the tumor mass. These findings suggest that EGF and TGF-alpha may participate in the regulation of normal pancreatic exocrine function, and that overexpression of the EGF receptor and its two principal ligands may contribute to the pathophysiological processes that occur in human pancreatic cancer.

Adult↗
PubMed1992

[The diagnostic value of the amino acid absorption test in detection of a disorder of exocrine pancreatic function].

The amino acid consumption test (AACT) during exogenous stimulation with secretin and CCK was proposed as a sensitive and highly specific test for detection of exocrine pancreatic insufficiency. To further investigate the diagnostic value of this test we measured the AACT in comparison with the pancreolauryl serum test (PLT) in patients with chronic pancreatitis and in patients with gastrointestinal diseases but without pancreatic disease. A total of 48 patients, 23 patients with chronic pancreatitis (CP) and 25 patients with gastrointestinal diseases, were included in the study. Diagnosis of chronic pancreatitis was established by standardized morphological criteria in ultrasound, ERCP, CT, and was confirmed by surgery in 11 cases. The PLT was abnormal in 83% of patients with chronic pancreatitis and normal in 92% of the control subjects (diagnostic accuracy 88%). Basal amino acid concentration was comparable in patients with chronic pancreatitis and in control subjects (300 +/- 12 [symbol: see text] 325 +/- 16 mumol/l). The peak decrease of amino acids occurred after 30 min during combined stimulation with secretin and ceruletide and was not different between the two groups (CP: 11.2 +/- 1.7%, controls: 13.9 +/- 1.9% below basal values). With a 12% decrease of amino acids as cutoff, sensitivity was 74% and specificity 52% (diagnostic accuracy 63%). Integrated amino acid decrease did not show any significant differences between CP and controls (CP: 228 +/- 63% min, controls: 397 +/- 80% min). Determination of the individual amino acids serine, valine, histidine, and isoleucine could also not discriminate between patients with chronic pancreatitis and other gastrointestinal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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

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↗
PubMed1989

Serum phospholipase A2 in intensive care patients with peritonitis, multiple injury, and necrotizing pancreatitis.

To study the source and role of circulating phospholipase A2 (PLA2) catalytic activity we monitored the serum from patients with necrotizing pancreatitis (n = 8), diffuse peritonitis (n = 6), and multiple injuries (n = 11). Immunoreactive PLA2 serum protein concentration was analysed using a fluoroimmunoassay based on an antibody against human pancreatic PLA2. Serum PLA2 catalytic activity was analysed using a radiochemical method based on a substrate with tritiated palmitic acid in beta position. In necrotizing pancreatitis immunoreactive PLA2 and PLA2 catalytic activity both increased. Obviously, in necrotizing pancreatitis the major part of serum catalytic activity stems from the pancreas. In patients with diffuse peritonitis and multiple injuries, as a rule, immunoreactive phospholipase A2 serum concentration appears to be within the normal range. In contrast, in these patients we demonstrated high serum catalytic PLA2 activity comparable to that in necrotizing pancreatitis. The source of catalytic PLA2 activity in peritonitis and multiple injuries seems not to be the pancreas. There was a correlation between pulmonary insufficiency and serum PLA2 catalytic activity in patients with necrotizing pancreatitis, peritonitis, and multiple injuries.

Acute Disease↗
PubMed1989

Long-term effect of growth promoting conditions on the exocrine pancreas of rats.

Pancreatic adaptation following prolonged exposition to growth promoting conditions (protease inhibitor feeding, B II subtotal gastrectomy, subtotal colectomy) was studied in rats. Fifty male Wistar rats were divided into 5 groups: controls (n = 10), sham-operated (n = 10), low dose protease inhibitor feeding (n = 10), B II subtotal gastrectomy (n = 10), and subtotal colectomy (n = 10). After 4 mo a significant increase in pancreatic wet wt and DNA content was observed in rats after protease inhibitor feeding (p less than 0.01), B II gastrectomy (p less than 0.01), and subtotal colectomy (p less than 0.05). Pancreatic total protein and lipase content were significantly increased in these three groups. Amylase and trypsin content increased after feeding the protease inhibitor (p less than 0.01) and following B II subtotal resection (p less than 0.01) but were unaffected after subtotal colectomy. Comparing the long-term effects (4 mo) with our previously published short-term data (4 wk) under the same experimental conditions, pancreatic trophism after 4 mo is less pronounced but characterized by a change in the enzyme composition with an increase in pancreatic lipase content.

Adaptation, Physiological↗