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Biomedical subjects

H Friess

Publications and source records attributed to H Friess.

At least 343 records · Page 19Linked to original sources
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↗
PubMed1989

Cholecystokinin influences pancreatic trophism following total gastrectomy in rats.

In rats, total gastrectomy (TG) has been shown to induce pancreatic hyperplasia and increased tissue concentrations of pancreatic trypsin and amylase, whereas lipase concentration was decreased. We performed total gastrectomy with the additional insertion of a duodenal tube in 17 rats. A central venous catheter was placed after 3 wk. The control groups consisted of sham-operated rats with a gastrotomy plus duodenal tube and a group of rats with only a duodenal tube. The rats received meal stimulation with a 6 mL liquid diet (3 mL oil, 2 mL amino acid solution, and 1 mL glucose) via duodenal tube upon recuperation. Blood samples were taken before as well as 5, 15, 30, and 60 minutes after the meal and analyzed for insulin, pancreatic glucagon, gastrin, and CCK by specific RIA techniques. Glucose tolerance was found to be impaired after total gastrectomy. Though insulin release was delayed compared to the controls, the integrated postprandial output was unchanged. The pancreatic glucagon release after the meal increased 83% in TG rats, compared to control rats. The baseline and postprandial gastrin values diminished 70% compared to control animals. Neither group exhibited a postprandial increase in gastrin levels. TG led to an increased postprandial CCK output of 72% compared to controls. The trophic changes of rat exocrine pancreas following total gastrectomy, therefore, could be based on an elevated postprandial release of CCK.

Animals↗
PubMed1989

Role of phospholipase A2 in human acute pancreatitis.

In a prospective clinical trial, 85 patients with acute pancreatitis, including 50 with acute interstitial-edematous pancreatitis and 35 with necrotizing pancreatitis, were recruited. Serum pancreatic immunoreactive phospholipase A2 (IR-PLA2), serum phospholipase A catalytic activity (CA-PLA), and serum phospholipase A2 catalytic activity (CA-PLA2) were determined daily between day 1 and day 10 after the onset of the disease. The serum course of IR-PLA2 values for patients with acute interstitial-edematous pancreatitis was comparable to that for patients with necrotizing pancreatitis. In contrast, the determination of CA-PLA and of CA-PLA2 specific activity in the serum revealed a high differentiation between patients with interstitial edematous and those with necrotizing pancreatitis. The overall accuracy for differentiating patients with necrotizing pancreatitis from those with the interstitial-edematous type was 79% for CA-PLA and 77% for CA-PLA2 (cut-off level: CA-PLA, 15 U/L, day 1-5; CA-PLA2, 3.5 U/L, day 1-5). Patients with pancreatitis-associated pulmonary complications showed significantly higher CA-PLA and CA-PLA2 values in the serum. This study demonstrates the role of serum catalytic phospholipase A2 in human acute pancreatitis where the development of pancreatic necrosis and pulmonary failure is concerned.

Acute Disease↗
PubMed1989

[Therapy of pancreatic carcinoma with the monoclonal antibody BW 494/32: first clinical results].

In a phase-I clinical trial the monoclonal antibody BW 494/32 was administered to 18 patients with advanced pancreatic cancer of ductal origin. This murine immunoglobulin mediates an ADCC. The majority of patients tolerated this treatment without any side effects. There were no tumor remissions. 12 patients showed a progression of their pancreatic carcinoma after therapy. A stable course of the disease was observed in 6 patients for at least 3 months after therapy.

Aged↗
PubMed1988

[Immunotherapy of advanced pancreatic carcinoma with the monoclonal antibody BW 494].

In the course of a phase I study monoclonal antibody BW 494 was injected i.v. at a dose of 180-340 mg to 18 patients with advanced ductal pancreatic carcinoma. The murine IgG1-antibody is directed against a pancreatic carcinoma-associated glycoprotein. The antibody inhibits the functions of human pancreatic carcinoma cells. Diffuse muscle pain, which disappeared spontaneously, was noted by two patients 14 days after injection. Other side-effects were anaphylactoid reactions in two patients 12 and 19 days, respectively, on repeat antibody infusions. This event led to changes in the administration schema so that the total amount was given within ten days, after which there were no further allergic side-effects. Terminal antibody half-life was 47.8 h (initial half-life 0.2 h). Human anti-mouse antibodies in all eight patients tested for them developed within two to three weeks of the end of treatment. There were no tumour remissions. Progression of the tumour after treatment occurred in 12 patients (67%). In five patients the course was stable for at least three months after treatment, i.e. unchanged clinical status, unchanged tumour extent (CT), and stable tumour markers (CEA, CA 19-9) in serum. One female patient with a T3N1M0 carcinoma has so far lived for 16 months in full employment. The results justify the use of the monoclonal antibody in future controlled trials.

Aged↗
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

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↗
PubMedDate not supplied

The penetration of antibiotics into human pancreas.

In order to analyse the penetration of two antibiotics (mezlocillin and metronidazole) which cover the spectrum of microorganisms involved in pancreatic infection, we determined their concentration in pancreatic tissue, juice and cyst fluid in 16 patients undergoing pancreatic surgery. In addition, the external pancreatic fistula fluid of one patient was analysed for antibiotic concentration and bacterial counts during a seven-day treatment with mezlocillin, metronidazole and netilmicin (i.v.). Antibiotic concentrations were determined by HPLC between 16 and 210 (median 74) min after i.v. administration of 4 g mezlocillin and 500 mg metronidazole, respectively. The median concentration of mezlocillin was 23.2 (range: 3.1-37.4) mg/kg, 15.9 (range: 4.2-55.0) mg/l and 9.9 (range: 5.2-14.8) mg/l in pancreatic tissue, juice and cyst fluid, respectively. The median concentration of metronidazole was 5.1 (range: 1.8-13.0) mg/kg, 8.5 (range: 3.6-16.2) mg/l and 1.2 (0.9-1.4) mg/l in pancreatic tissue, juice and cyst fluid, respectively. From the fistula patient, seven different bacteria were cultured (five aerobic and two anaerobic isolates); their concentration in fistula fluid ranged from 10(5) to 10(7) CFU/ml. The bacteria sensitive for mezlocillin and metronidazole disappeared after four days of i.v. treatment, whereas the two isolates sensitive for netilmicin showed continuous growth seven days after i.v. treatment. The peak concentrations for mezlocillin, metronidazole and netilmicin in the fistula fluid were 6.8 mg/l, 5.6 mg/l and less than 0.1 mg/l, respectively.

Adenocarcinoma↗
PubMedDate not supplied

Penetration of ciprofloxacin into the human pancreas.

The aim of this study was to determine the concentrations of ciprofloxacin in human pancreatic tissue and juice. Concentrations were measured by high-pressure liquid chromatography (HPLC). Two hundred mg of ciprofloxacin were administered as a short i.v. infusion (30 min). The median ciprofloxacin concentrations 140 min (median) after the start of infusion in pancreatic tissue as well as in pancreatic juice were 0.9 mg/kg (mg/l). The penetration ratio was 1.0 for pancreatic tissue and 0.83 for pancreatic juice. With regard to the minimal inhibitory concentrations (MIC) for the respective bacteria, ciprofloxacin seems to be an appropriate drug for the treatment of septic complications in necrotizing pancreatitis. Future clinical trials are necessary to prove this assumption.

Adult↗
PubMedDate not supplied

Studies of pancreatic cancer utilizing monoclonal antibodies.

Since 1985, 150 patients with pancreatic ductal adenocarcinoma have been treated with the monoclonal antibody BW 494 in four different multicentric trials in Germany. The antibody recognizes a human pancreatic cancer associated antigen and mediates an antibody dependent cellular cytotoxicity (ADCC) in vitro, when human mononuclear cells are coincubated as effector cells. In patients with at advanced unresectable pancreatic cancer there where two phase-I-studies finished in 1987 and 1989, respectively, and one uncontrolled phase-II-study finished in 1988. In 1987, we started a controlled randomized trial in patients with resectable (Whipple) pancreatic cancer, which will be finished in 1990. There were no major side effects if the intravenous antibody application was restricted to a 10-d treatment protocol (up to 370 mg given in 10 different dosages). Human anti-mouse-antibodies could be demonstrated in all patients investigated for within 4 wk after immunotherapy. In patients with advanced pancreatic cancer (n = 87), monoclonal antibody treatment did not induce significant response rates. There was stable disease in 1/3 to 1/2 of the patients lasting three months or longer. Therapeutic success may be expected in patients with minor tumor burden.

Animals↗
PubMedDate not supplied

Duodenum-preserving pancreatic head resection: Long-term results.

Early and late results from 298 patients with chronic pancreatitis who were surgically treated by means of duodenum-preserving pancreatic head resection (DPPHR) were prospectively analyzed. The aim of this operative procedure is to treat complications of chronic pancreatitis caused by inflammatory enlargement of the pancreatic head by decompressing the common bile duct, the pancreatic duct, the duodenum, and the retropancreatic intestinal vessels. End points of the study were early and late postoperative outcome. The follow-up period ranged from 1 to 22 years with a median follow-up of 6 years. In-hospital mortality was 1%, postoperative morbidity was 28.5%, and the rate of repeat laparotomy was 5.7%. Diabetes mellitus developed early in the postoperative period in six patients (2%). After a median follow-up of 6 years, late mortality was 8.9%. In the late follow-up period 88% of our patients were completely free of pain or had infrequent episodes and 63% were able to return to work. DPPHR might be considered as an alternative surgical technique in the treatment of chronic pancreatitis if the dominant lesion is in the pancreatic head.

Adult↗
PubMedDate not supplied

A review of various techniques of orthotopic liver transplantation in the rat.

Orthotopic liver transplantation (OLT) in rat is a demanding procedure, which has become a popular model to investigate various problems. Our aim was to review and analyze the various techniques of experimental OLT in the rat. A review of the literature revealed 30 techniques or technical modifications. Each modification represented a change or a simplification of the reconstruction method of five anatomical structures, which are cornerstones of a successful OLT: the suprahepatic inferior vena cava (SHVC), portal vein (PV), infrahepatic inferior vena cava (IHVC), hepatic artery (HA), and bile duct (BD). SHVC is anastomosed via microsuture or cuff. The PV anastomosis is performed by microsuture, cuff, or a microsuture-temporary splint technique. IHVC is reconstructed by a microsuture, cuff, or microsuture-temporary splint technique. Arterialization has been accomplished via microsuture (aortic segment, celiac segment, or aortic patch), cuff, splint, sleeve, or telescopic method. Nonarterialization of the graft has also been described. Methods for BD reconstruction include pull-through, telescopic, splint, and T-tube. Although a high level of microsurgical skill is the basic requirement in the microsuture technique which provides the most physiological situation and concomitantly reduces thrombosis, it increases anhepatic time compared to the cuff procedure. The learning curve of microsuture techniques is flat; beginners need much practice to become expert. The most physiologic techniques for anastomoses are preferred for long-term survival studies, while the faster techniques are options for short-term survival studies. Each research group must choose techniques according to study defined aims.

Animals↗
PubMedDate not supplied

Therapy for pancreatic cancer with a recombinant humanized anti-HER2 antibody (herceptin).

The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the clinical significance of that overexpression is uncertain. In the present study we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor growth in certain patients with those diseases. We quantified HER2 expression in various human pancreatic cancer cell lines and studied the bioactivity of this antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed in vitro in cell lines with high levels of HER2/neu expression. Cell lines with low levels of this protein did not respond significantly to the antibody. In vivo we studied two different pancreatic cancer cell lines in an orthotopic mouse model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa-2 tumor cell line, which expressed high levels of HER2/neu. These data suggest that Herceptin treatment of patients with pancreatic cancer who express high levels of the HER2/neu oncogene may be reasonable.

Adenocarcinoma↗