Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

170 records · Page 10Linked to original sources

PubMedDate not supplied

Approach to a hospital-based application of a medical expert system.

CADIAG-2 is a data-driven fuzzy medical expert system built for computer-based consultation in internal medicine. It has been integrated into the medical information system WAMIS of the Vienna General Hospital. Through the integration, CADIAG-2 is able to access patient data and laboratory test results already collected in the central patient database of WAMIS. CADIAG-2 operates in two subsequent phases: (1) as an automatic screening procedure for detecting pathological states in the patient, for generating diagnostic hypotheses, and for proposing further useful examinations; and (2) as an on-line consultation system for the clinician to assist him in clarifying patients' disorders completely and in great detail. At present, CADIAG-2 is subject to extended clinical trials. There are four application areas: rheumatic diseases, pancreatic diseases, gall bladder and bile duct diseases and colon diseases. First results on the performance of CADIAG-2 based on the evaluation of about 500 cases were obtained. In this paper, the principal goals, main components and concepts of CADIAG-2, and the experience gained until now are discussed.

Artificial Intelligence↗

PubMedDate not supplied

Serum levels of vasoactive intestinal peptide (VIP) in patients with adenocarcinomas of the gastrointestinal tract.

BACKGROUND: VIP acts as a neuroendocrine mediator under physiological conditions, with an important role in water and electrolyte secretion in the gut. Recent findings suggest that VIP also promotes growth and proliferation of normal as well as malignant cells. We have investigated the VIP-serum levels in patients with pancreatic cancer and colonic adenocarcinoma as compared to healthy controls. This was accompanied by immunohistochemical investigations and in vitro experiments to further define the role of the peptide in pancreatic and colorectal cancer. MATERIALS AND METHODS: Serum levels of VIP were evaluated under standardized conditions in a total of 135 patients; 45 patients had metastatic colorectal cancer, 45 suffered from metastatic pancreatic cancer, and 45 healthy volunteers served as controls. Human pancreatic and colorectal carcinoma cell lines were incubated over 5 days with VIP in increasing concentrations. RESULTS: In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found, while patients with pancreatic cancer had a median level of 40.58 +/- 3.013 pg/ml (range, 6.9-102.4 pg/ml). In patients with cancer originating in the colon, however, a median serum level of 116 +/- 10.14 pg/ml (range, 51.6-487 pg/ml) was found. While no difference between healthy controls and patients with pancreatic cancer could be detected (p = 0.6381), a significant difference between patients with colorectal cancer and healthy controls (p < 0.0001) and patients with pancreatic cancer (p < 0.0001) was demonstrated. The median VIP-concentrations found in the patients sera for pancreatic and colonic tumor patient groups, 40 pg/ml and 115 pg/ml respectively, had no significant effect on the proliferation of PANC-1 and HT29, inhibited ASPC-1, BxPC3, COLO201 and HCT-15 cells, and stimulated the growth of one pancreatic (CAPAN-1) and one colonic (COLO320DM) cell line under these conditions. CONCLUSIONS: As opposed to pancreatic cancer and healthy controls, patients in our series had elevated serum VIP-levels. Further studies are warranted to evaluate whether VIP can be used as a tumor marker in this disease.

Adenocarcinoma↗

PubMedDate not supplied

In vitro drug sensitivity testing with agar-containing glass capillaries.

Capillary cloning has been shown to have advantages over conventional cloning of human tumor cells in Petri dishes. We have recently published in this Journal an optimization of the capillary method towards homogeneous colony distribution and high cloning efficiency. In the present study this modified capillary cloning system was investigated for its feasibility for drug sensitivity testing. For the human breast cancer cell line MDA-231 and the drug sensitive Chinese Hamster Ovary cell line CHO-AB as well as for its multidrug resistant mutant CHO-C5 a similar linear dose response effect was obtained with the capillary cloning system and with the Petri dish system. The capillary cloning system, however, was 2 to 4 fold more sensitive for the detection of cytotoxic drug effects. It was concluded that the optimized capillary cloning system is well suited for drug sensitivity testing.

Agar↗

PubMedDate not supplied

A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines.

Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.

Antineoplastic Agents↗

PubMedDate not supplied

Homogeneous growth of tumor cell colonies in agar containing glass capillaries.

The capillary cloning system has been shown to have advantages over conventional cloning of human tumor cells in Petri dishes. In the present study a further optimization towards homogeneous colony distribution and high cloning efficiency is described. For reasons of reproducibility the study focused on cell lines, i.e. three human linew (MDA-231, HT-29, L363) and one rodent line (CHO-AB). Major variables investigated were the gel length, the capillary tube diameter, the tube sealing and buffer system, and the cell number. Criteria for optimal tumor colony growth included homogeneous colony distribution along the gel, mean colony size and cloning efficiency. It was found that colony distribution as well as overall colony growth depended largely on the gel length, i.e. on the volume of tumor cell containing agar applied per capillary tube. The results showed that optimal tumor cell colony growth was achieved in 100 ul capillary tubes of 1.2 mm internal diameter filled with 30ul, yielding a gel length of 27 mm. Colony formation did not significantly differ between sealed and unsealed tubes, provided that HEPES buffer was added. It was concluded that, for practical reasons, sealing of tube ends and therefore utilization of HEPES buffer is not necessary. In a head to head comparison, cloning efficiency was equal or higher in capillary tubes than in Petri dishes. The capillary cloning system is an alternative for drug development as well as for predictive drug testing. Its major advantage is the utilization of fewer tumor cells.

Agar↗

PubMedDate not supplied

Experiences with continuous intraarterial administration of recombinant interferon alpha-2C (rIFN-alpha 2) for treatment of patients with advanced transitional cell bladder cancer.

The response of locally-advanced transitional cell carcinoma of the urinary bladder to intraarterial regional treatment with recombinant interferon alpha-2C (rIFN-alpha 2) was investigated. Patients received 4-weekly courses of i.a. continuous infusion of rIFN-alpha 2 (5 megaunits/24 hours administered into the a. iliaca interna via a subcutaneously implanted port-a-cath) alternating with 4 weeks i.m. treatment cycles (5 megaunits/day x 3 weekly). None of the 5 patients entered in the study showed evidence of objective tumor regression after a median of 4 i.a./i.m. treatment cycles. Constitutional, organ and local toxic effects were considerable even with that low-dosage schedule employed. The lack of efficacy and poor tolerance of the regimen suggest that i.a. administration of IFN is unlikely to yield an acceptable therapeutic index.

Aged↗

PubMedDate not supplied

In vitro evaluation of the anticancer drug modulatory effect of hyaluronidase in human gastrointestinal cell lines.

In an attempt to establish whether the combination of anticancer drugs with hyaluronidase would result in enhanced cytotoxicity, we have tested a range of 6 continuous cell lines against 4 different chemotherapeutic drugs with or without the addition of various concentrations of the enzyme. Measurement of cytotoxic drug effects has been performed using the Bactec system, a new semiautomated radiometric technique. In only 15 of a total of 144 experiments (11%) was a significant hyaluronidase-mediated potentiation of the single agents' activity seen. In the large majority of experiments, the antiproliferative effect of the combined treatment was classified as additive or subadditive, while in 23% it was antagonistic. Evaluation of the drug modulatory mechanism of hyaluronidase suggested that the combined drug-hyaluronidase effects were independent of the nature of the drug, the exposure mode and the concentration of the enzyme employed. Among the various tumor cell lines tested there was a marked heterogeneity in the sensitivity to the combined effect (P less than 0.0001). In summary, we have not been able to confirm the promising results of early reports of in vitro and in vivo enhancement of the cytotoxicity of antitumor agents by hyaluronidase. Our data emphasize the need for further controlled clinical studies in order to prove or disprove this new therapeutic approach.

Adenocarcinoma↗

PubMedDate not supplied

Phase II trial of recombinant interferon alpha-2C in metastatic renal cell carcinoma.

A total of 18 patients with advanced metastatic renal cell cancer were treated with recombinant interferon alpha-2C (rIFN alpha-2C) at daily doses of 10 X 10(6) IU by intramuscular injection. All patients had evaluable metastatic lung, liver, or abdominal disease as measured by radiographic or computerized tomographic scans. In 2 of the 18 patients an objective response (1 CR, 1 PR) with a duration of +28 and 12 months, respectively was achieved. A 25$ to 50$ decrease in tumor measurements (MR) was seen in 2 additional patients; in 3 cases a stabilisation of the disease (SD) was observed, whereas it progressed in 11. 3/4 responding patients (including MR) and all 3 cases with SD had measurable disease in the lungs as predominant site of metastatic disease. Additional clinical characteristics of patients exhibiting response or SD to IFN therapy included prior nephrectomy, favourable initial performance status and limited metastatic disease. No serious haematologic or irreversible organ toxic effects were attributed to interferon. Several patients, however, had constitutional symptoms, and major dose reductions due to CNS toxicity became necessary in two. Further studies are warranted to evaluate the use of interferons in combination with cytotoxic drugs or other biologic response modifiers.

Adult↗