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Biomedical subjects

A Imdahl

Publications and source records attributed to A Imdahl.

At least 19 recordsLinked to original sources

The influence of ischemic bowel wall damage on translocation, inflammatory response, and clinical course.

BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.

APACHE

Glycine-extended gastrin acts as an autocrine growth factor in a nontransformed colon cell line.

BACKGROUND & AIMS: The hypothesis that progastrin-derived peptides act as autocrine growth factors for colorectal carcinomas has generated considerable interest. However, the influence of autocrine gastrins on nontumorigenic colonic cells has not been investigated. This study tested the above hypothesis in the nontumorigenic, conditionally immortalized mouse colon cell line YAMC. METHODS: The effects of expression of antisense or sense gastrin messenger RNA, treatment with antibodies against progastrin-derived peptides, or treatment with gastrin receptor antagonists on YAMC cell proliferation were measured. RESULTS: YAMC clones expressing antisense gastrin messenger RNA had reduced levels of immunoreactive progastrin-derived peptides and a reduced rate of proliferation, relative to vector only-transfected cells. Glycine-extended gastrin17, but not amidated gastrin17, reversed the antisense-induced inhibition of proliferation and stimulated the proliferation of sense- or vector only-transfected cells. YAMC cells bound 125I-glycine-extended gastrin17 (Kd, 0.36 nmol/L, 1810 sites/cell), but not 125I-amidated gastrin17, and binding was unaffected by gastrin receptor antagonists including benzotript. Proliferation of all YAMC clones was partially inhibited either by an antibody selective for glycine-extended gastrin or by preincubation with benzotript, and the inhibitory effects were additive. CONCLUSIONS: YAMC cells use nonamidated progastrin-derived peptides as autocrine growth factors, partly through binding to an extracellular receptor selective for glycine-extended gastrin, and partly through an intracellular mechanism.

Animals

[Therapy outcome of patients with soft-tissue sarcoma: retrospective analysis for identifying independent prognostic factors].

The postoperative outcome of 108 patients with soft tissue sarcoma (STS) of the extremities, the retroperitoneum, or the trunk was investigated retrospectively to identify independent factors for the over all survival and local tumor control. Chi-square single factor analysis and a Cox model were used to identify independent postoperative risk factors. Single factor analysis revealed a significant correlation with negative effect on overall survival for the variables metastasis (p < 0.0001), chemotherapy (p < 0.0009), surgical procedures (0.001), tumor size > 10 cm (p < 0.003), localization (retroperitoneum, trunk) (p < 0.03), and grading (G3/G4) (p < 0.03). Local tumor control was significantly correlated with the variable tumor size > 10 cm (p < 0.01). The Cox model showed a significant negative impact on overall survival for the factors metastasis (p < 0.002), tumor size > 10 cm (p < 0.004), grading (G3/G4) (p < 0.005), and sex (male) (p < 0.008). For local tumor control the variables were age (p < 0.006), and surgical procedures (p < 0.01).

Adolescent

Comparison of laparoscopic handsewn suture techniques for experimental small-bowel anastomoses.

Laparoscopic techniques have only rarely been applied to procedures on the small bowel. A comparison of three handsewn intracorporeal anastomoses was carried out. Thirty pigs were divided into three groups, and a different technique was used in each group (SK, single knot; RS, running suture; CL, clip suture). Half of the animals had a relaparoscopy on day 4. The duration of the procedure was recorded, and the quality of anastomotic healing was assessed by morphological, radiological, mechanical, and biochemical examinations. The animals were sacrificed on postoperative day 14. The anastomoses in the SK group took significantly longer than in the RS or CL groups. The mean duration of relaparoscopy was 28 min. Bursting pressure values and hydroxyproline concentrations were without any significant difference. The SK and CL groups showed a good alignment of the layers and the RS showed necrosis and overlying mucosa. Most complications were noted in RS. The results demonstrate that manual small-bowel anastomoses can be performed laparoscopically. Single-knot and clip sutures are reliable techniques. The ongoing development of new instruments and the three-dimensional technique will basically improve the construction of intracorporeal anastomoses.

Anastomosis, Surgical

Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas.

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Binding, Competitive

Radiation enteropathy.

PURPOSE: Radiation enteropathy presents a complex clinical picture which varies from case to case. Diagnosis and treatment require a thorough knowledge of the natural history of the condition and of the complications which are to be expected. PATIENTS AND METHODS: The pathogenesis, clinical picture, diagnosis and treatment of radiation damage to the gut are described. The progress of 90 patients operated on in the Chirurgische Universitätsklinik Freiburg is retrospectively evaluated. RESULTS: Haemorrhage, vomiting, diarrhoea and, occasionally, perforation are the signs of acute radiation enteropathy, which appears weeks or months after radiotherapy. Except for perforations, these can usually be treated conservatively. Chronic radiation enteropathy does not manifest itself until years after irradiation, with diarrhoea, obstruction and the development of fistulae. The acute ileus can often be relieved with decompression tubes. After localising the stenosis radiologically with a contrast medium, and improvement in the general condition, many cases require operative intervention. This usually consists of resection, the establishment of a bypass anastomosis or enterostomy. In 44% of the patients postoperative complications followed, with a mortality of 22%. The cause of the high complication rate is partly the poor general condition of the patient, and partly the radiation induced impairment in wound healing, which may lead to insufficiency of the anastomosis and the development of fistulae. CONCLUSIONS: The treatment of radiation enteropathy is a demanding task. Because of the high complication rate, it is generally wise to choose the least risky procedure.

Adult

[The value of CEA immunoscintigraphy for diagnosis of colorectal cancer and its metastases: results of a prospective study].

The importance of the CEA-immunoscintigraphy (IS; BW 431/26 Fa Behring) for the diagnosis of colorectal carcinoma and its metastases was determined in a prospective trial including 60 patients. The results were compared with results of the ultrasound, the CT-Scan and the Angio-CT. Patients suffered from a colorectal carcinoma (15), from a local tumor recurrence after bowel resection (10), from hepatic (39) and/or extrahepatic metastases (16). In 40 patients the diagnosis was confirmed by laparotomy. Regarding the detection of hepatic metastases the sensitivity and specificity of the Angio-CT were superior to the IS (0.86 and 0.63 vs. 0.78 and 0.45). Ultrasound and Angio-CT together revealed true positive results in 89.2%. The IS did not improve this rate. Regarding the detection of extrahepatic metastases the sensitivity and the specificity of the CT were slightly superior to the IS (0.59 and 0.87 vs. 0.47 and 0.28). However, the IS increased the rate of true positive results by 18.8% (US + CT 43.7%; +IS 62.5% true positive results). Due to these results the IS is not recommended as the method of choice to detect liver metastases. But in patients unfit for diagnostic laparotomy the IS may give additional information of the extrahepatic tumor stage.

Adult

[Perioperative risk factors in esophageal cancer: a retrospective study of independent variables].

The postoperative outcome of 127 patients with an esophageal carcinoma was investigated retrospectively, to identify independent factors for the perioperative mortality (hospital mortality). Chi-square single factor analysis was employed to test 35 independent variables, in a second analysis stepwise logistic regression was used to determine the factors correlating with the morality. In 41 patients the esophagus was resected by a thoraco-abdominal approach, in 86 by blunt dissection. The hospital mortality was 17.3%, the 30-day mortality 12.6%. Single factor analysis revealed a significant correlation with the variable smoking (p < 0.003), post-operative morbidity (p < 0.008), CEA (p < 0.02), time of operation (p < 0.02) and surgical procedures (p < 0.02). The influence of the surgeon's experience was significant. In the stepwise logistic regression the duration of operation (p < 0.0039), the surgical procedures (p < 0.016), and the units of blood (p < 0.03) were correlated with mortality. The logistic regression showed a significant increase of mortality for the thoracoabdominal approach with increasing duration of the operation. The estimation of survival time according to Kaplan and Meier revealed a significant correlation with the stage of the tumor, but not with the surgical procedure.

Adenocarcinoma

Lectin histochemical investigations of fetal cultivated pancreatic tissue.

The terminal glycoproteins of fetal, cultivated (7-12 days), and adult nondiabetic and diabetic pancreatic tissues (Balb c, C3h mice) were investigated by lectin histology (peanut-, phytohemagglutinin, wheat germ agglutinin, Ulex europeus I, concanavalin A and Ricinus communis agglutinin, PaP method +/- neuraminidase). Anti-insulin and -glucagon were used to identify islet cells. S-100 antibody showed dendritic reticulum cells, anti-IAK proved MHC II antigens (C3h). Cultured tissue was partly incubated with anti-IAK and complement for lysis of MHC II antigens. On the 19th gestational day fetal pancreatic tissue did not bind peanut agglutinin, Phytohemagglutinin, or wheat germ agglutinin, whereas concanavalin A and Ricinus communis were weakly bound. Terminal fucose residues were not expressed by C3h fetal islet cells in contrast to Balb c. Following neuraminidase digestion peanut agglutinin and phytohemagglutinin were strongly bound, indicating sialic acid-substituted terminal glycoproteins. Cultivated tissue (Day 7) bound all investigated lectins (except Ulex europeus I in C3h mice), indicating maturation of islet cells. In spite of the peak of insulin concentration in the medium we observed a faint binding of anti-insulin and investigated lectins following 12 days of cultivation. This indicates a disorder of terminal glycoprotein synthesis at this point. There was no difference in lectin binding patterns of adult nondiabetic islet cells compared to the cultivated tissue (7 days), but no Ulex europaeus I binding of the adult Balb c mice was observed. S-100 binding decreased during the cultivation period as dendritic reticulum cells became destroyed by cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Serum gastrin level in patients with colorectal adenoma or carcinoma].

During the last years interest has focused on the trophic effect of gastrin in colorectal carcinomas. Some reports indicated an increased serum level of gastrin in patients with colorectal adenomas or carcinomas. In a prospective study in 261 patients submitted to colonoscopy fasting serum gastrin concentrations were determined. 91 patients served as control, 89 patients had one or more adenomas, 55 patients suffered from a colorectal carcinoma, 17 had a benign, postoperative stenosis of the colon, and 9 had a chronic inflammatory bowel disease. All patients fulfilled the following criteria: No regular drug intake, no previous gastric or small bowel operation, no known ulcer disease, no abnormalities in serum calcium, creatinine, triglycerides, cholesterol and blood urea. Mean gastrin level was 86.63 +/- 23.8 pg/ml in the control, 84.57 +/- 25.1 pg/ml in the adenoma group and 84.6 +/- 24.4 pg/ml in the carcinoma group. No difference of serum gastrin levels were observed regarding sex, age, tumor stage and localisation.

Adolescent

[Diagnosis and management of lower gastrointestinal hemorrhage. Retrospective analysis of 233 cases].

In a retrospective analysis the diagnostic procedure was evaluated in patients with acute lower gastrointestinal bleeding. Bleeding sources were localized distally to the ligament of Treitz in 233 patients (1979-1988). Patients with hemorrhoidal bleeding were not included. Following exclusion of an upper gastrointestinal bleeding the diagnostic procedure was initiated with a recto-/colonoscopy. Lesions were detected in 77% of the treated patients (n = 136). Angiography localized the bleeding in 68%, in combination with colonoscopy the identification of the bleeding source reached 86.5% in the treated patients. Following scintigraphy the bleeding source was determined in 89.7% of these patients. The sensitivity of colonoscopy (0.93) was superior to the angiography (0.78) and to the scintigraphy (0.75). Apart from neoplasms and adenomas angiodysplasia and Meckel's diverticula were the most common sources of the bleeding in patients who underwent operation. In 61 patients endoscopic therapy was performed, however, 6.5% of these patients had to be operated on later because of persistent bleeding. All together 79 patients underwent operation, 31 for bleeding and 48 for other reasons. 12 patients died, 6 of them were operated on for the bleeding, the other for neoplasms.

Adolescent

Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells.

Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.

Animals