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W Fischbach

Publications and source records attributed to W Fischbach.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Plasma cholecystokinin level in chronic pancreatitis].

Secretion of pancreatic enzymes is inhibited in rats by the presence of intraduodenal proteases via inhibition of CCK release. The existence of a similar feedback mechanism in man is discussed controversially. Thus, in chronic pancreatitis (cP), which leads to a decrease of digestive enzyme secretion, increases in plasma CCK may be postulated. However, food induced CCK release may be impaired in cP due to maldigestion. We studied, therefore, the influence of food with or without addition of pancreatic extracts on plasma CCK in 16 male patients with longstanding cP. Plasma CCK was measured by bioassay using pancreatic rat acini prepared by collagenase digestion. Plasma samples were processed through SEP-PAK cartridges and assayed for CCK-like activity by comparing the bioactivity of samples with those of standard curves of CCK8. Plasma CCK was measured in 20 healthy controls and in cP prior and 7.5, 15, 30, 45, 60, and 90 min after the application of a test meal made out of milk, cream, eggs, and cacao. In addition CCK was measured in 10 of the same patients with cP on a separate day but with the addition of pancreatic extracts to the test meal. Basal plasma CCK levels were similar in both groups (control: 1.3 +/- 0.2 vs. cP: 1.5 +/- 0.3 pMol/l). Both groups showed a similar steep increase of postprandial CCK with maximal values seen between 7.5 and 30 min (control: 4.6 +/- 0.6 vs cP: 4.8 +/- 1.3 pMol/l). The addition of pancreatic extracts to the liquid meal in cP caused a statistically significant slight increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Role of pancreatic enzymes and their substrates in autodigestion of the pancreas. In vitro studies with isolated rat pancreatic acini.

Intrapancreatic activation of proteases is believed to play a major role in the pathogenesis of acute necrotizing pancreatitis. Several authors have questioned, however, the central role of trypsin in autodigestion of the pancreas. To clarify the direct effects of pancreatic enzymes and other related factors on acinar cells, we used the model of isolated pancreatic acini. Acini were prepared from male Wistar rats by collagenase digestion. Protein synthesis was measured by incubation of acini with [35S]methionine. Acini were resuspended thereafter in fresh buffer and further incubated for 30-90 min under various conditions [e.g., with pancreatic homogenates, ascites (from rats with pancreatitis induced by sodium taurocholate), pure pancreatic enzymes, and other factors]. The percentage of release of newly synthesized proteins into the culture medium was regarded as a biochemical parameter of cellular integrity. A morphologic score of cellular integrity was obtained via light microscopic evaluation of acini at the end of the various incubations by measuring the degree of cell lysis, loss of cell granules, ballooning, formation of vacuoles, and karyopyknosis. When normal [35S]methionine-labeled pancreatic acini were incubated with various factors, the percentage of release of labeled proteins into the medium was as follows: incubation with HEPES/Ringer's buffer, 1.8%; hemorrhagic pancreatic ascites, 3.8%; pancreatic homogenates, 2.0%; lipase, 1.8%; phospholipase A2, 3.0%; phospholipase A2 + lecithin, 3.2%; trypsin, 2.5%; 5% olive oil, 1.8%; ascites + olive oil, 78.3%; ascites + homogenized epididymal fat, 79.9%; lipase + olive oil, 32.0%; pancreatic homogenates + olive oil, 28.0%; diolein, 2.65%; and oleic acid, 62.9%. The cellular release of radiolabeled proteins showed an inverse correlation with cellular integrity as shown by light microscopy. We postulate that interstitial release of degradation products from triglycerides by lipase causes cellular disruption. Whereas phospholipase A2 and proteases do not seem to be very harmful in the early phases of cellular damage, lipase may play a major role in acute necrotizing pancreatitis.

Acute Disease↗
PubMed1988

[SCC antigen: a sensitive and specific tumor marker for squamous cell carcinoma?].

The diagnostic value of serum concentrations of squamous-cell carcinoma (SCC) antigen was evaluated on 48 untreated patients with squamous-cell carcinoma of the lung or oro-maxillo-facial region. To test for specificity SCC antigen was also looked for in 55 patients with various other epithelial neoplasms, in 18 with inflammatory lung disease, and in 43 with liver and 34 with renal function abnormalities. The sensitivity rate of SCC antigen in squamous-cell carcinoma of the lung was 53%, in carcinoma of the oromaxillofacial region 34%. Both groups differed significantly from all other groups, except for patients with abnormal renal function more than half of whom had raised serum concentrations. The proportion of false-positive SCC values was 11% each for patient with inflammatory lung disease and other epithelial neoplasias, and 7% for patients with abnormal liver function. SCC is not a specific marker for squamous-cell carcinoma. Its clinical value probably lies mainly in monitoring the course of such tumours.

Antigens, Neoplasm↗
PubMed1988

Tissue concentrations of CEA and CA 19-9 in the carcinogenesis of colorectal carcinoma exemplified by the adenoma-carcinoma sequence.

To study the behavior of the tumor-associated antigens CEA and CA 19-9 in colorectal carcinogenesis, exemplified by the adenoma-carcinoma sequence, their tissue concentrations were measured in adenomas of different size and histology and compared with those found in normal colonic mucosa and carcinoma. Both in the case of monoclonal and polyclonal CEA assay, significantly higher concentrations were found in the adenoma tissue as compared with normal mucosa. Carcinomas revealed, on average, an even higher tissue CEA level, but the concentrations measured showed considerable scatter. In the adenoma group, the villous lesions and those with severe cellular atypia were characterized by markedly higher CEA concentrations, reflecting their special position in the adenoma-carcinoma sequence. In the case of CA 19-9, too, an increase in tissue concentrations from normal mucosa through adenoma to carcinoma was observed. In contrast, among the adenomas of different histologies and dysplasia no differences were observed. These findings fit with the concept of the adenoma-carcinoma sequence which, in our opinion, represents a suitable model for studying the significance of tumor-associated antigens in the carcinogenesis of colorectal cancer and its precursors.

Adenoma↗
PubMed1988

Influence of "calcium2+-channel blockers" on exocrine pancreatic secretion by isolated rat acini.

Cytoplasmic Ca2+ is regarded as an intracellular messenger for acetylcholine- and cholecystokinin (CCK)-stimulated pancreatic enzyme secretion. We investigated in the in vitro model of isolated rat pancreatic acini whether or not Ca2+-channel blockers are able to inhibit Ca2+-mediated enzyme secretion. Isolated rat pancreatic acini were prepared via collagenase digestion. The effect of various Ca2+-channel blockers on amylase secretion stimulated by various secretagogues was monitored. Verapamil, but not nitrendipine, dose-dependently reduced CCK8- and carbachol-stimulated enzyme secretion. Higher doses of either CCK8 or carbachol could not reverse the inhibition caused by verapamil. Amylase secretion stimulated by the ionophore A23817 was not altered by verapamil. Verapamil augmented enzyme secretion stimulated by secretagogues which work through cAMP as second messenger. 3H-N-methylscopolamine- and 125I-Bolton-Hunter-CCK8-binding to pancreatic acini was dose-dependently inhibited by verapamil, but the inhibition curves did not parallel the inhibition curves with unlabeled receptor agonists. Thus, the impairment of exocrine pancreatic amylase secretion by verapamil is probably not due to its known "Ca2+-channel" blocking abilities in other tissues but is rather caused by noncompetitive effects on the level of muscarinic receptors and receptors for CCK.

Amylases↗
PubMed1988

Comparison of 99Tcm-HMPAO and 111In-oxine labelled granulocytes in man: first clinical results.

The in vitro and in vivo behaviour of 99Tcm-HMPAO (hexamethylpropyleneamineoxime) (n = 12) and 111In-oxine (n = 11) labelled granulocytes, isolated by density-gradient centrifugation (Metrizamide/plasma gradients), was compared in patients with suspected inflammatory diseases. The in vitro elution of both labels and the viability of the labelled cells (99Tcm, 98.5%; 111In, 96.5%) was comparable but the labelling efficiency was different (99Tcm, 44 +/- 13%; 111In, 72.5 +/- 5.5%). In vivo, the lung (t1/2 max: 7.7 min), liver and spleen perfusion patterns were nearly identical; the image quality for detail in 99Tcm scans was superior to 111In images. The blood disappearance curves of 99Tcm and 111In were comparable. In the small number of patients examined all infections could be diagnosed correctly, without false-positive or false-negative results. Disadvantageous is the renal excretion of 99Tcm complexes (3+% over 20 h) with kidney and bladder activity from the beginning of the study. The biliary excretion in half of the patients (n = 6) with unspecific positive small and large bowel visualization and the late intestinal excretion also render the diagnosis more difficult. The recommended best imaging times for abdominal and retroperitoneal inflammations are 30 min to 2 h after injection. Late scans in septic prosthetic joints have disproportionate long acquisition times. As a potential cell labelling compound, 99Tcm-HMPAO has a promising future in comparison to 111In scans because of the good availability of 99Tcm, the image quality and the lower radiation exposure to the patient when lower activities for the early diagnosis of abdominal inflammatory diseases are reinjected.

Colitis, Ulcerative↗
PubMed1988

Radiolabelled granulocytes in inflammatory bowel disease: diagnostic possibilities and clinical indications.

Radiolabelled granulocytes in chronic inflammatory bowel diseases (CIBD) are able to diagnose the disease extent and assess the disease activity. It may be performed with 111In oxine- and 99Tcm hexamethylpropyleneamineoxime (HMPAO)-labelled cells. The granulocyte scan localizes inflamed bowel segments with an accuracy comparable with radiology and endoscopy including biopsy of the bowel (r = 0.95; P less than 0.001). The specificity of the scan for diseased segments is near 100%, the sensitivity 92%. A three-phase white blood cell scan (imaging: 0.5, 4, 20 h post injection) allows differentiation of diseased bowel segments from abscesses and fistulas. False positive results are possible in necrotic carcinomas. The 99Tcm HMPAO scan shows rapid renal and delayed biliary and intestinal excretion of tracer. In this way diagnostic problems arise in the small pelvis. Because of the intestinal and biliary excretion, early images should be obtained (0.5-2 h post injection). Later scans with 99Tcm HMPAO are of minor importance. The disease activity can very specifically be assessed by the determination of the percentage faecal 111In excretion (96 h faecal collection). Active and non-active diseases can be clearly differentiated. We found no correlation with the subjectively influenced Crohn's disease activity index (CDAI) (r = 0.25; P greater than 0.05), but good correlations with the Dutch Index (van Hees: r = 0.67), ESR (r = 0.69), serum albumin (r = -0.54) and orosomucoid (r = 0.65). The percentage faecal excretion correlates well with the histologically estimated leucocytic bowel infiltration. Because of the intestinal 99Tcm HMPAO excretion the determination of faecal excretion is pointless in 99Tcm studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocytes↗
PubMed1987

Do size, histology, or cytology of colorectal adenomas and their removal influence serum CEA?

Based on the adenoma-carcinoma sequence the authors studied whether determination of serum carcinoembryonic antigen (CEA) provided any conclusions concerning malignant transformation of a colorectal adenoma. In 32 patients with single or multiple adenomas, serum CEA did not differ from 119 healthy individuals. In 43 percent, a decrease of CEA could be observed after polypectomy, while it increased in 22 percent or remained unchanged in 35 percent. No correlation was found between adenoma volume and serum CEA. There was a tendency toward a higher serum CEA level in patients with villous adenoma as compared with those with tubular structure. CEA concentrations were independent from the degree of cellular atypia, but polypectomy was followed by a decrease of serum CEA in villous adenoma or of moderate cellular atypia, reflecting a possible influence on production or shedding of CEA by these subtypes of adenoma. The results indicate, therefore, that serum CEA is not able to recognize the malignant potential of colorectal adenoma.

Adenoma↗
PubMed1987

Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors.

Adolescent↗
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↗
PubMed1987

Leucocyte elastase in chronic inflammatory bowel diseases: a marker of inflammatory activity?

Leucocyte elastase is a neutral proteinase which plays an important role in the pathogenesis of inflammatory disorders. Infiltration of bowel mucosa by neutrophil and eosinophilic granulocytes is a characteristic feature of chronic inflammatory bowel diseases. We studied plasma elastase in 44 patients suffering from Crohn's disease or ulcerative colitis. Plasma levels were significantly higher in these patients compared to 7 patients with non-inflammatory bowel diseases or 53 healthy controls. Elevated plasma levels were more often found in patients with active inflammation than in those with inactive disease. Elastase did neither correlate with leucocyte counts, serum albumin, ESR, alpha 1-proteinase inhibitor and orosomucoid nor with clinical indices or the faecal excretion of 111In-labelled granulocytes. In serial studies of 15 patients, elastase did not always run parallel to the disease activity. We conclude that plasma elastase does not reliably indicate the inflammatory activity in chronic inflammatory bowel diseases.

Adult↗
PubMed1987

Follow-up of moderately elevated serum CEA levels in "healthy patients".

In a retrospective analysis of 254 patients with a moderately elevated serum CEA level (3.6 to 10.0 ng/ml) a satisfactory explanation for the increased CEA level could not be identified in 42 patients despite intensive diagnostic procedures. The follow-up of these patients showed a decrease of CEA level in 28 patients (80%), returning to normal range below 3.5 ng/ml in 20 patients (57%). There was an increase of CEA level in 5 (14.3%) and no change in two patients (5.7%). Except one patient who died of an unknown cause, none of the other patients developed malignancy in a period up to 34 months. We conclude that a single elevated serum CEA level does not justify further diagnostic procedures if clinical signs of a disease are absent. Patients with increasing CEA levels should be checked more intensively, because in some cases a previously undetectable malignant disease may become evident.

Carcinoembryonic Antigen↗
PubMed1986

[Significance of neuron-specific enolase (NSE) in the diagnosis of bronchial carcinomas and neuroendocrine tumors].

The diagnostic significance of neuron-specific enolase in serum was examined in 54 patients with bronchial carcinoma and in 28 with neuroendocrine tumors. Control groups were 42 patients with epithelial and 39 with nonepithelial malignant neoplasms as well as 40 patients with benign pulmonary diseases. The sensitivity of neuron-specific enolase in small-cell bronchial carcinoma was 60% and increased to 87.5% in advanced stages ("extensive disease"). On the other hand, non-specific enolase showed an increase in only 13.8% of patients with other than small-cell bronchial carcinoma. The proportion of false-positive enolase values in non-malignant pulmonary diseases was 5%. Some endocrinal tumors (e.g. tumors of the APUD cell system) showed pathological serum concentrations in 7.1% of the cases only. 37.5% of epithelial malignant neoplasms had enhanced levels, but only 5.1% in nonepithelial neoplasms. Small-cell bronchial carcinoma is most probably present in patients with bronchial carcinoma and neuron-specific enolase serum concentrations above 25 micrograms/l.

Adenocarcinoma↗
PubMed1986

[Regulation of acinar cell receptors of the pancreas by peptides].

Peptides may act on the same receptor they regulate or on another receptor by causing regulations via receptor interactions. These receptor regulations include changes of receptor affinity and capacity. Receptor capacity is regulated by internalization, recycling, degradation, synthesis, and modification of bioavailability without migration of the receptor. Examples for those regulations, mostly based on experiments with isolated pancreatic acini from the rat, mouse, or guinea pig, are given. For the CCK receptor these examples include complex regulations of this receptor by CCK itself, bringing into discussion the hypothesis of negative cooperativity and the two-site receptor model, desensitization of the receptor by CCK, in vivo CCK influences on its receptor, and insulin receptor/CCK receptor interactions. For the insulin receptor the physiological significance of "up and down regulation" of this receptor by insulin itself is discussed. For the IGF receptors and the EGF receptor CCK-induced, Ca2+-mediated regulation of receptor internalization are another type of regulation with unknown physiological and pathophysiological significance. Finally CCK-induced, Ca2+-mediated regulation of somatostatin receptor capacity and affinity are mentioned. It is postulated that those regulations play an important role in influencing the biological effect of hormones and that knowledge about them may improve our understanding of pathophysiology.

Calcium↗