Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

179 records · Page 10Linked to original sources

PubMed1984

[Stimulation of gastric acid secretion by sham feeding in patients with duodenal ulcer before and after selective proximal vagotomy].

Gastric acid secretion stimulated by sham feeding was measured in 12 patients with duodenal ulcer before and after highly selective vagotomy and compared with the results obtained from 7 healthy controls. In the ulcer patients sham feeding resulted in a higher stimulated secretion compared to normals. In addition after sham feeding the secretion fell slower to basal levels than in the control group. Highly selective vagotomy normalized these abnormalities. We conclude, that sham feeding might be a test applicable to patients after vagotomy to predict adequate reduction of acid secretion.

Duodenal Ulcer↗

PubMed1984

[Computer-assisted diagnosis and its application in pancreatic diseases].

The medical expert system CADIAC-2 based on fuzzy logic supports diagnostic decisions in the field of internal medicine. A medical knowledge base contains nosological descriptions of diseases. Given patient data, diagnostic decisions are made on the basis of the medical knowledge stored. Reasonings for the established diagnoses or diagnostic hypotheses are presented as well as plans for further examinations on the patient. Unexplained symptoms, signs or test results are also indicated. The usefulness of CADIAC-2 is demonstrated in a case study involving 38 patients with various pancreating diseases.

Diagnosis, Computer-Assisted↗

PubMed1984

[In vitro evaluation of the chemosensitivity of malignant gastrointestinal tumors by stem cell assay].

The Human Tumor Stem Cell Assay, originally described by Hamburger and Salmon, was shown to be a useful in-vitro technique for predicting response or lack of response in individual patients' tumors. In the present study 34 GI-tumors were assayed for evaluation of in-vitro growth characteristics and sensitivity-patterns to standard chemotherapeutic drugs as well as to recombinant interferon alpha-2(rIF). Sufficient growth for evaluation of anticancer drug activity (greater than 30 colonies/control plate) was obtained in 56% of specimens: 2/9 colorectal, 0/3 stomach, 0/3 pancreatic tumors and 1/4 hepatomas revealed a 50% (or more) decrease of TCFUs, that was considered the minimum for in-vitro efficacy. Our results suggest a very limited overall activity of rIF in gastrointestinal malignancies. Only 1 pancreatic cancer (of 18 evaluable specimens) showed a significant decrease of colony formation (70%), when 100 U of interferon/ml were added to the culture system.

Antineoplastic Agents↗

PubMedDate not supplied

Prevalence of microalbuminuria in maturity onset primarily non-insulin-requiring diabetes mellitus: effect of disease duration, glycemic control, and mean systemic blood pressure.

Because of the frequency of late cardiovascular complications in maturity onset non-insulin-dependent (Type II) diabetes mellitus, there have been few studies regarding nephropathy in this patient population. The authors have analyzed the prevalence of microalbuminuria and the nature of clinical manifestations associated with elevated albumin excretion rate (AER) in a large population presenting with Type II diabetes. Among 318 patients studied during 1986, pathologically elevated 24 h AERs were found in 59%. The rate of microalbuminuria among 205 Type I diabetic patients screened during the same interval was 43%. AER was found to be positively correlated with duration of disease (p less than 0.0008) and metabolic control as determined by measurement of glycosylated hemoglobin (HbA1c) (p less than 0.002). There was only a modest agreement between AER and mean systemic blood pressure. The high prevalence of microalbuminuria in Type II diabetic patients and its known association with increased mortality emphasize the need for long-term follow up studies in order to clarify whether elevated AER in this patient population is predictive for overt diabetic nephropathy.

Adult↗

PubMedDate not supplied

Coincidence of Crohn's disease and a high-risk gastrointestinal stromal tumor of the terminal ileum.

A 51-year-old male patient presented with characteristic radiologic features of Crohn's disease in the terminal ileum plus a large tumorous lesion in the right lower abdomen. Because of rapid crescent symptoms of bowel obstruction, the patient underwent surgery revealing a high-risk gastrointestinal stromal tumor (GIST) of the terminal ileum within an area of Crohn's ileitis. Whereas the association of chronic inflammatory bowel disease (IBD) and gastrointestinal adenocarcinoma is well known, other primary intestinal tumors are rare in these patients, particularly at the time of onset of clinical symptoms. This is the 3rd patient reported in the literature with a sarcoma complicating IBD, and in fact, the first description of the coincidence of Crohn's disease and GIST. Though the present case is likely to be a mere coincidence of two pathologically distinct entities (without any potential causal relationship), it should remind one of the possibility of small bowel 'Crohn's carcinoma' in patients with a sudden change in symptomatology as well as in those in whom intestinal obstruction fails to resolve with adequate therapy.

Crohn Disease↗

PubMedDate not supplied

Association between Helicobacter pylori infection and pancreatic cancer.

PURPOSE: In order to determine whether infection with Helicobacter pylori might be associated with pancreatic adenocarcinoma, we performed a study to compare the H. pylori seroprevalence rate between patients with pancreatic carcinoma and matched control subjects. PATIENTS AND METHODS: Blood samples from 92 patients with histologically confirmed diagnosis of pancreatic adenocarcinoma admitted to our hospital between January 1994 and July 1995 were analyzed for the presence of IgG antibodies against H. pylori by a commercially available enzyme-linked immunosorbent assay. Thirty patients with gastric cancer, 35 patients with colorectal cancer, and 27 healthy volunteers served as controls. In addition to these serological analyses, tumor specimens from 20 patients with pancreatic adenocarcinoma were microscopically investigated for the presence of H. pylori. RESULTS: 65% of pancreatic cancer patients and 69% of those with gastric cancer were found to be seropositive, while only 45% of the other controls tested positive. Statistical analysis revealed no difference in seropositivity between the cohort of patients suffering from pancreatic and gastric cancer. The rate of seropositivity was more prominent, however, in pancreatic cancer patients when compared with those suffering from colorectal cancer combined with normal controls (p = 0.035), with an odds ratio of 2.1 (1.1-4.1). Microscopic evaluation of human pancreatic cancer specimens showed no evidence for the presence of H. pylori. CONCLUSION: Our data suggest an association between H. pylori infection and pancreatic cancer. Despite demonstration of a positive relationship and its physiological plausibility, larger prospective studies are needed to confirm our preliminary findings and to assess H. pylori as a potential carcinogenic risk factor.

Adenocarcinoma↗

PubMedDate not supplied

Mitomycin C, vinorelbine, carboplatin plus granulocyte-macrophage colony-stimulating factor for treatment of advanced non-small cell lung carcinoma.

BACKGROUND: The therapeutic potential of chemotherapy in the treatment of recurrent or metastatic non-small cell lung carcinoma (NSCLC) seems modest. Thus, the search for novel agents and combination regimens with a superior therapeutic index has a high priority. The present combination regimen consisting of mitomycin C, vinorelbine, carboplatin and granulocyte-macrophage colony-stimulating factor (GM-CSF) was chosen because of the known activity of these agents in NSCLC and their potential drug synergism without (nonhematologic) cross-toxicity. To prevent/counteract neutropenia that was assumed to represent the dose-limiting toxicity, the hematopoietic growth factor GM-CSF was routinely adminstered. The objective of our trial was to determine the antitumor efficacy and tolerance of this combination regimen in patients with advanced NSCLC. PATIENTS AND METHODS: Forty consecutive patients with nonresectable, measurable NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination chemotherapy regimen consisting of mitomycin C 8 mg/m2 on day 1, vinorelbine 40 mg/m2 on days 1 and 21, and carboplatin 250 mg/m2 on days 1 and 21; GM-CSF 5 microg/kg was administered subcutaneously on days 2-8 and 22-28. Treatment cycles were repeated every 6 weeks. All patients are evaluable in terms of toxicity and response assessment. A total of 123 courses was administered. RESULTS: Objective tumor response was notes in 16 patients (40%; 95% confidence interval 24.9-56.7%), including 3 (7.5%) complete and 13 partial responses. There was no change in 12 (31.5%) patients, and 12 had progressive disease. Median duration of response was 6 (range 3-15) months, the median time to progression for all patients was 6.2 (range 1-17.5) months, and the projected median survival time was 8.7 (range 1-23.3) months; the 1-year survival rate was 27.5%. Myelosuppression was the most frequently encountered adverse reaction; WHO grade 3 or 4 granulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%, respectively. Other toxicities were generally mild to moderate, and always fully reversible. CONCLUSION: With a 40% major response rate and disease stabilization in one additional third of our patients, this drug combination seems to have significant activity against advanced metastatic NSCLC. Due to its subjective tolerance and ease of administration, further investigation of this regimen in the palliative-intent care setting seems warranted.

Adult↗

PubMedDate not supplied

Evaluation of clinical efficacy of new medical treatments in advanced colorectal cancer. Results of a workshop organized by the EORTC GITCCG. European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group.

During the last few years several factors have contributed to an increasing change in the medical treatment of advanced colorectal cancer. Among them are the more general acceptance of the impact of chemotherapy on quality of life and survival in first as well as in second-line treatment, the introduction of new drugs and the definition of novel endpoints which can roughly be defined as "patient benefit". For this reason the European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Cooperative Group (GITCCG) felt it was appropriate to organize a workshop with experts from different countries and national groups to discuss in depth several aspects concerning the treatment of patients with advanced colorectal cancer.

Clinical Trials as Topic↗

PubMedDate not supplied

Red blood cell partitioning of the [6S]- and the [6R]-isomer of N5-formyltetrahydrofolic acid.

The in vitro interaction of the [6S]- and [6R]-stereoisomers of CHO-THFA with human RBCs was investigated in the (therapeutically comparable) concentration range from 1.0 to 12.5 micrograms/ml. Both compounds are bound to RBCs with a kRBC ranging from 0.13 to 0.75 for [6S]-CHO-THFA and from 0.06 to 0.33 for [6R]-CHO-THFA, respectively. The interaction of the [6S]-form with RBCs is about two times higher than of the [6R]-form. Incubation of CHO-THFA with RBCs over 24 h showed an accelerated disappearance from the test solution for [6R]-CHO-THFA with a mean t1/2 of 49.9 h in compare to t1/2 = 58.2 h for the [6S]-enantiomer. The results indicate that RBCs may play a major role for the pharmacokinetics and metabolism of CHO-THFA and may act as an intravasal depot especially for [6S]-CHO-THFA.

Binding Sites↗

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↗