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W Fischbach

Publications and source records attributed to W Fischbach.

At least 91 records · Page 5Linked to original sources
PubMed1993

DNA mapping of colorectal neoplasms: a flow cytometric study of DNA abnormalities and proliferation.

BACKGROUND: There is some evidence that neoplastic development and progression evolve through a multistep process associated with hyperproliferation and genetic alterations. Therefore, changes of proliferation and of cellular DNA content within the adenoma-carcinoma sequence were studied. METHODS: Using a "mapping" procedure, 12 adenomas and 18 carcinomas were analyzed flow cytometrically and histologically. In addition, normal mucosa adjacent to and distant from the tumors was assessed in the same way. RESULTS: Of 59 adenomatous fractions, 35.6% (n = 21) were aneuploid, whereas the incidence of aneuploidy was 63.5% (54/85) in the carcinomatous sites. Additional tetraploidies were identified in 5 (8.5%) and 13 (15.3%) adenomatous and carcinomatous samples, respectively. Cell proliferation, as determined by the percentage of S-phase cells, was significantly (P < 0.001) higher in the carcinomatous specimens (14.8% +/- 0.8%; mean +/- SEM) than in the adenomatous ones (8.1% +/- 0.7%). It decreased to normal mucosa adjacent to (5.1% +/- 0.5%) and distant (5.3% +/- 0.6%) from the neoplasms. DNA mapping of the tumors revealed both distinct regions and extended areas of aneuploidy and tetraploidy. There is evidence from the mapping data that aneuploid populations arise at a single focus of the adenoma and expand over large areas before a subpopulation of cells acquires the capacity of invasion. CONCLUSIONS: These data showing consecutive DNA content abnormalities within the colorectal adenoma-carcinoma sequence provide support for genomic instability and clonal evolution as important events of tumorigenesis and progression.

Adenoma↗
PubMed1993

Role of phospholipase A2 in pancreatic acinar cell damage and possibilities of inhibition: studies with isolated rat pancreatic acini.

Phospholipase A2 (PLA2) has been postulated to play an important role in the pathogenesis of acute pancreatitis. To study the mechanism through which PLA2 may cause cellular damage, we used an in vitro model of isolated rat pancreatic acini prepared by collagenase digestion. Newly synthesized proteins were labeled by [35S]methionine. Cellular destruction was measured by the degree of release of radiolabeled proteins. Incubation of pancreatic acini with PLA2 alone caused only minor damage when very high concentrations of this enzyme were used. However, when acini were incubated with PLA2 in combination with its substrate, lecithin, cells were destroyed in a time- and concentration-dependent manner. Incubating cells with pancreatic homogenates and lecithin caused damage only when there had been prior activation of homogenates with either trypsin or enterokinase. The damage could be simulated by incubating acini with pure lysolecithin. Alcohol and cerulein did not further increase the destruction caused by PLA2 and lecithin. When acini were incubated with supernatants from another set of acini to which oleic acid had been added, a similar degree of damage resulted as compared with acini incubated with oleic acid alone. However, adding PLA2 to supernatants from acini preincubated with fatty acids significantly increased the degree of cellular necrosis. The destruction by PLA2 and lecithin was inhibited by albumin but could not be inhibited by gabexate mesilate, nafamostat mesilate, or cytidine diphosphocholine. We conclude that PLA2 could play a role in pancreatic acinar cell damage, especially in the spread of cellular necrosis within the organ, provided that its substrate, lecithin, is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

[How are tumor markers used in diagnosis and in after-care of gastrointestinal cancers? Results of a nation-wide German survey].

To obtain appropriate information about the present use of tumor-associated antigens (TAA) in diagnosis and follow-up of gastrointestinal carcinomas, an inquiry into 102 German university and non-university hospitals was performed. 97 answers to ten standardized questions were available for evaluation. TAA are generally used in gastrointestinal carcinomas by 98.5% and 92.6% of internists (i) and surgeons (s), respectively. Preoperatively, serum concentrations of TAA are determined in 63.9% (i) and 84% (s) of gastric carcinomas. The corresponding rates in colorectal carcinomas are 93.8% and 92.6%. TAA are a routine part of postoperative care in 68.8% (i) and 76% (s) of gastric and in 100% (i) and 96.2% (s) of colorectal cancers. Interest is almost exclusively focused on CEA and CA 19-9. Other tumor associated antigens are rarely investigated in these diseases. Increasing serum concentrations of TAA induce intensive diagnostic procedures in 82.4% and 95.7% of internists and surgeons. However, an indication for a second-look operation solely based on increasing TAA concentrations is only seen by 30.6% of internists and 37% of surgeons. In gastric cancer the course of TAA concentrations is used for determining the effects of chemo- or radiotherapy in 36.4% (i) and 71.4% (s). The corresponding rates for colorectal carcinomas vary between 66.6% (i) and 80% (s). The results of this nation-wide inquiry confirm the wide use of CEA and CA 19-9 in gastrointestinal carcinomas. There are obvious differences with respect to diagnostic or therapeutic consequences based on postoperatively increasing serum levels of TAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Malignant lymphomas of the upper gastrointestinal tract. Results of a prospective study in 103 patients.

BACKGROUND: There is a discrepancy between the incidence of gastrointestinal involvement by malignant lymphomas, as established in postmortem studies, and the rareness of the corresponding clinical diagnosis. METHODS: Therefore, the authors performed routine upper gastrointestinal endoscopic examination, within the framework of the usual staging examinations, in 103 consecutive patients with newly diagnosed Hodgkin disease (n = 21) and non-Hodgkin lymphoma (n = 82). RESULTS: One patient with Hodgkin disease (4.8%), 11 of 40 patients (27.5%) with non-Hodgkin lymphoma of low-grade malignancy, and 11 of 42 (26.2%) of those with highly malignant non-Hodgkin lymphoma showed involvement of the gastric and/or duodenal mucosa, as diagnosed with esophagogastroduodenoscopy. Of the 22 patients with non-Hodgkin lymphoma, 9 had involvement of other mucosa-associated lymphoid or epithelial tissue. In two patients with Stage III, two with Stage II, and two patients with presumptive Stage I disease, the disease was reclassified as Stage IV. Because of gastrointestinal involvement, treatment for two patients was changed from radiation therapy to chemotherapy and another two patients had gastric resections so that possible treatment-related complications could be avoided. CONCLUSIONS: In light of these results and the fact that a major basis for the therapeutic strategy for malignant lymphomas is tumor stage, routine esophagogastroduodenoscopic examination within the framework of the usual staging examinations is recommended. In individual cases, this procedure may be of decisive importance in the therapeutic approach to and prevention of complications.

Adolescent↗
PubMed1992

Influence of various nutrients and their mode of application on plasma cholecystokinin (CCK) bioactivity.

CCK is known to be a major endocrine stimulant of the exocrine pancreas. However, the influence of various compositions of nutrients and their mode of administration on plasma CCK is still not clear. We therefore studied plasma CCK after either oral or intraduodenal administration of various solid and liquid diets. Plasma CCK was measured by bioassay. Nine healthy male volunteers received three different isocaloric diets via intraduodenal perfusion (1 kcal/ml; 300 ml/90 min). Diet A consisted of low-molecular oligopeptides (energy: protein 18%, fat 22%, carbohydrates 60%); diet B was a high molecular diet enriched with fat and fiber (protein 15%, fat 30%, carbohydrates 55%, fiber 1 g/100 ml); and diet C was a high molecular diet, poor in fat and fiber-free (protein 14%, fat 7%, carbohydrates 79%). All diets caused a rapid increase in plasma CCK, followed by a slow decrease. The highest CCK plasma values were achieved with diet B (8.4 +/- 1.6 pM); diets A and C led to similar, rather low plasma CCK values (A: 5.0 +/- 0.7 pM). Another five volunteers received the above-described liquid diets orally. Integrated CCK plasma values were similar for all oral liquid diets studied and not different from those seen after intraduodenal administration of the high-molecular high-fat diet B. Oral administration of a solid diet (ten volunteers) comparable to diet B in calories and nutrient composition caused a rather small and delayed increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.

Animals↗
PubMed1992

Comparison of different treatment modalities in experimental pancreatitis in rats.

Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate), and albumin under different conditions in rats were investigated. (a) Isolated pancreatic acini were incubated with pancreatic homogenates and triglycerides or lecithin with or without albumin and the degree of cellular destruction quantitated. (b) Taurocholate was injected into the pancreatic duct of isolated pancreas and the organ continuously perfused with either FUT, THL, or albumin. Organ damage was evaluated by measurement of pancreatic enzymes in the portal effluence. (c) Necrotizing pancreatitis was induced in vivo via retrograde taurocholate injection. FUT, THL, or albumin was applied either intravenously or injected into the pancreatic parenchyma. (a) Albumin prevented the cellular damage caused by both fatty acids and lysolecithin. (b) THL was ineffective, FUT lowered the release of pancreatic enzymes into the portal effluence, and albumin was most effective. (c) Albumin prevented the development of panlobular necrosis and lowered the degree of extrapancreatic fat necrosis. Albumin, via its ability to bind detergents, may have therapeutic implications.

Albumins↗
PubMed1992

[Drug therapy of chronic inflammatory bowel disease--reliable standards and new developments].

The standard therapy of ulcerative colitis and Crohn's disease is based on the treatment with corticosteroids, sulfasalazine and 5-aminosalicylic acid (mesalazine). Depending on the localization and the extent of bowel inflammation these drugs are given topically (proctosigmoiditis, left-side colitis) or systemically (total and subtotal colitis). Azathioprin and metronidazole are considered to be reserve drugs (the latter one having proven to be effective only in Crohn's disease). During the last years, the efficacy of several new agents has been investigated. At present, their routine administration cannot be advised. The clinical usefulness of new topical corticosteroids showing both high antiinflammatory effect and no or at least minor systemic side effects is promising.

Adrenal Cortex Hormones↗
PubMed1992

[Tertiary gummatous syphilis of the liver--an unexpected disease today. Report of two cases].

Today the luetic hepatitis and gummata of liver are very rare manifestations of a tertiary syphilis because of the antibiotic therapy. Therefore a luetic involvement of liver is a most unexpected and at first mostly misinterpreted finding. In the both represented cases foci in the liver were present, which were suspicious for a metastasizing malignoma and set off the search for an unknown primary tumor. In liver biopsies no malignant process was seen, but necroses with a granulomatous reaction at the border were found which were classifiable definitively only after serological investigations as gummata of liver. Especially by the presence of an additionally reactive hepatitis in the remaining liver parenchyma, possibly with some sarcoid-like granulomas, a tertiary gummatous syphilis should be taken into consideration. The regression of gummata in sonography and computertomography as well as the return to normal of the laboratory findings are important parameters in the follow-up to confirm the diagnosis under antibiotic therapy. The described cases stress the importance that even today the tertiary lues should be taken into consideration by liver foci of unknown origin and should be excluded serologically.

Biopsy↗
PubMed1992

[Risk of cancer in chronic inflammatory bowel diseases].

This article summarizes the data concerning cancer risk in chronic inflammatory bowel disease. Cancer risk of ulcerative colitis and Crohn's disease is highly dependent on the duration of the disease, extent of bowel inflammation, and probably also of the age at onset of the disease. Cancer development follows the dysplasia-carcinoma-sequence. Diagnosis of premalignant changes is the basis for follow-up studies in ulcerative colitis as suggested here.

Cell Transformation, Neoplastic↗
PubMed1991

[Tertiary syphilis with liver gummata].

Sonography revealed multiple echo-poor lesions in the liver of a 51-year-old man with nonspecific symptoms (fatigue, drop in performance, pressure sensation in the upper abdomen), increased blood sedimentation rate (68/110 mm) and evidence of cholestasis (gamma-GT 126 U/l, alkaline phosphatase 444 U/l, leucine-aminopeptidase 64 U/l). Under the diagnosis of liver metastases the primary tumour was looked for. These investigations and a fine-needle biopsy having proved unsuccessful, laparoscopy was performed. The biopsies so obtained showed whitish yellow, tight elastic structures indicating gummas of the liver in tertiary syphilis. Treponema-specific IgM antibodies in serum characterized active syphilis requiring treatment. Administration of antibiotics (penicillin 1 mega U daily i.m.; because of allergy replaced after four days by erythromycin 2 g daily for six weeks) resulted in complete normalization of all biochemical findings and, some time later, regression of the gummas. The patient has now been symptom-free for three years. This case illustrates the need even to-day of including syphilis in the differential diagnosis of unclear space-occupying lesions of the liver.

Biopsy↗
PubMed1991

Influence of exogenous application of pancreatic extracts on endogenous pancreatic enzyme secretion.

The existence of negative feedback inhibition of human pancreatic enzyme secretion by proteases is controversially discussed. We have recently demonstrated that jejunal application of porcine pancreatic extracts, in a dose commonly used to treat digestive insufficiency, stimulated rather than inhibited, human pancreatic enzyme secretion. We have now studied the influence of duodenal application of high concentrations of either pure trypsin or porcine pancreatic extracts with trypsin-equivalent activity, on human pancreatic enzyme secretion. Twenty-three male volunteers were intubated with a gastric tube and a two-lumen jejunal tube to collect secretions separately via the first and third tubes and to perfuse either pure trypsin or porcine pancreatic extracts distal to the pylorus via the second tube. PEG-4.000 was continuously perfused via the second tube to correct for losses of volume. Volunteers received PEG alone during the first hour, phenylalanine during the second, PEG alone again during the third, and either phenylalanine together with trypsin or porcine pancreatic extracts during the fourth h. Activities of lipase, amylase, and chymotrypsin were measured in 15-min fractions. In addition, human lipase secretion was measured with an enzyme immunoassay, which does not crossreact with porcine lipase. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay, which utilizes amylase release by isolated rat pancreatic acini. Perfusion of the duodenum with phenylalanine caused a statistically significant stimulation of enzyme secretion. This stimulation could be inhibited by high concentrations of pure trypsin. In contrast, application of porcine pancreatic extracts, which contained the equivalent activity of trypsin, caused further increases of lipase secretion when compared to phenylalanine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗