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Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 145 records · Page 8Linked to original sources
PubMed1988

Acute oliguria associated with chlorprothixene overdosage.

The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis.

Acute Disease↗
PubMed1988

[Interferon therapy in multiple myeloma].

Natural leukocyte interferon and recombinant interferon alpha-2 have effected remission rates between 10 and 20% in the treatment of multiple myeloma. Response rates have been higher in untreated patients than in relapsing or primarily refractory cases. Patients with slowly proliferating tumors, early tumor stage or IgA-monoclonal protein seem to show increased sensibility to interferon as compared to patients without those characteristics. First trials using combined interferon chemotherapy regimens suggest that the toxicity associated with this treatment modality remains acceptable. At present, however, one cannot definitely decide whether and to which degree the combination therapy will improve the response rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Chemotherapy of advanced pancreatic cancer with 5-fluorouracil, doxorubicin and high-dose methotrexate].

The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.

Adult↗
PubMed1987

Search for improved culture conditions for clonogenic growth of human colorectal cancer cells in vitro.

In order to analyze and define potentially better growth conditions for colonic stem cell proliferation, we chose four established human colorectal cancer cell lines that differed in biologic cell properties. We studied variables of standard cloning conditions including culture medium, serum supplement, solidifying agent, addition of specific growth factors and use of capillaries as an alternative culture vessel. While modulation of serum concentration as well as use of various standard formulations of culture base media did not result in a reproducible increase of plating efficiencies (PEs), a significant increase in colony formation (when compared to the conventional assay procedure) was achieved; by use of 0.3% agarose or boiled agar as semisolid matrix and by culturing of cells in enriched 'GMF medium'. Specific growth factors, such as EGF or glucagon resulted in "occasionally better" in vitro growth. This suggests a retention of the ability of cells in culture to respond to physiologic regulators of growth. To verify and extend these initial results obtained with continuous cell lines, growth enhancing modifications of the original cloning technique were subsequently applied to in vitro growth of 15 human colorectal cancer specimens obtained directly from patients. Specimens that grew 30 or more colonies under standard plating conditions displayed a more than two-fold increase in PEs which was reproducible for the two specific variables mentioned above, but the overall success rate of the assay could not be improved. In addition to the possibility that several deficient basic requirements for achieving optimal environmental conditions for colonic stem cell growth have not been defined, we believe a major reason for failing to improve the number of drug-assayable specimens is related to an inherent interneoplastic diversity in terms of growth requirements of human colorectal malignancies.

Cell Line↗
PubMed1987

VAD protocol for treatment of advanced refractory multiple myeloma.

Twenty-three patients with advanced refractory multiple myeloma were treated with a combination chemotherapeutic regimen consisting of four-day continuous infusion of vincristine and doxorubicin plus intermittent high-dose dexamethasone (VAD). All patients included in the study were heavily pretreated with cytostatics and radiotherapeutic measures, and generally presented in poor general condition. In 3 of the 16 evaluable patients (18%) a response, and in 7 patients (44%) an improvement as defined by a reduction in tumor mass by more than 50% was achieved. Six patients had progressive disease. Evaluation of survival for responders (15 mos) versus non-responders (2 mos) by the landmark method seems to confirm the relative therapeutic efficacy of the VAD protocol in refractory multiple myeloma. The somewhat inferior response rate as well as the occurrence of considerable toxicity in several cases (when compared to the recent M. D. Anderson trial) may be related to differences in clinical features and pretreatment status of the two studies' population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Medical expert and consultation systems: review and examples for their use].

After a general introduction into the area of medical expert and consultation systems, a survey about different types of medical expert systems is given. The different objectives and modes of application of medical expert systems are presented and explained in detail. In the second part of this paper, the applicability of computer systems for fully automated interpretation of hepatitis serology findings in the clinical laboratory and for aiding differential diagnosis in internal medicine is described. With the examples given, it is demonstrated that expert systems for clinical decision aid can be of great benefit for the physician in the hospital or the doctor's office.

Antibodies, Viral↗
PubMed1987

[Progress in experimental chemotherapy of colorectal cancer].

The aim of the present study was a prospective evaluation of the predictive value of a new system as a primary screen for cytotoxic compounds with activity against cancer of the large bowel. Basically, this system consists of three human continuous colorectal cancer cell lines that have previously been shown to manifest in vitro responsiveness consistent with that known from clinical trials. Cytotoxic drug effects are measured by use of a new semiautomated radiometric technique (Bactec system). Among 22 investigational compounds, currently being investigated in phase I or early phase II clinical trials, we found that trimetrexate, DUP-785, didemnin-B, and flavone-8-acetic acid might be effective for treatment of patients with colorectal cancer.

Antineoplastic Agents↗
PubMed1986

Recombinant interferon alfa-2C versus polychemotherapy (VMCP) for treatment of multiple myeloma: a prospective randomized trial.

Forty-two previously untreated patients with multiple myeloma were entered in a prospective, randomised trial comparing recombinant interferon alfa-2C monotherapy with VMCP (vincristin, melphalan, cyclophosphamide and prednisolone). Both treatment arms were comparable for the stratification variables such as paraprotein type, stage of disease, and renal function. Rec. interferon effected 14% responses and 29% minor responses, while 57 and 32% of VMCP-treated patients achieved a pathologically documented remission (P less than 0.001). The time on initial treatment was significantly shorter in the IFN group (3.2 months) than in the VMCP group (7.6 months). In four patients in the IFN arm, primary treatment had to be changed according to progressive or severe stationary disease. Since all four patients responded to second line therapy (VMCP) no significant difference has been observed between the two groups in survival (median follow-up greater than 12 months). Despite this clear superiority of the conventional four-drug polychemotherapy, there was some suggestion that IFN might be particularly active in cases with low tumor-burden (stage I, II), and light-chain or IgA paraprotein type.

Adult↗
PubMed1986

In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay.

A human tumor cloning assay was utilized to evaluate the antineoplastic activity of the novel antitumor antibiotic fostriecin (CI-920). Initial screening with 10.0 mcg/ml continuous exposure against a variety of histologic tumor types resulted in 14/51 (27%) in vitro responses (defined as greater than 50% decrease in TCFUs). Further investigation of the compound was performed in 1-hr preincubation experiments. The in vitro response rate at a concentration of 1.0 mcg/ml (which was considered to correspond to a clinically achievable concentration) was 15/43 (35%). Response rates for specific tumor types included: 5/15 in ovarian cancer, 5/12 in breast, and 4/11 in human lung cancer. The impression of significant antitumor activity of the compound at this dose was further substantiated by comparing its in vitro activity with a variety of simultaneously tested standard anticancer agents. In addition, these data indicated the possibility of non-cross resistance of CI-920 to several established cytostatics. CI-920 is a compound with good in vitro activity which should be further developed for clinical trials.

Alkenes↗
PubMed1986

Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay.

The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.

Antineoplastic Agents↗
PubMed1986

[Prognosis of malignant tumors of the exocrine pancreas: effect of clinical and pathologico-anatomic variables on patient survival].

Survival patterns of 112 patients with histologically ascertained pancreatic cancer were analysed retrospectively in an attempt to determine the relationship to various clinical and pathologic-anatomic prognostic factors. Stage of disease, localisation of the primary tumor, as well as histologic grade were found to influence the patient's survival significantly. A limited anatomic involvement with tumor, localisation within the head of the pancreas, and high-grade differentiation were associated with an increased median survival. An evaluation of non-anatomic prognostic variables suggested a relative survival advantage for females, younger age groups, patients with favourable initial performance status and short symptom duration. There was no obvious relationship between survival and qualitative or quantitative indication of weight loss. In order to permit a critical evaluation of the value of any treatment program in pancreatic cancer, our observations reemphasize the need to define characteristics of patients under study.

Adult↗
PubMed1986

New screening system for selection of anticancer drugs for treatment of human colorectal cancer.

We report an evaluation of a new radiometric technique (BACTEC assay) as a potential screening system for cytotoxic compounds with activity against cancer of the large bowel. Exponentially growing cells of nine different human colorectal cancer cell lines were exposed to a variety of standard anticancer agents with or without documented clinical activity. Each drug was tested in a series of 1-h and continuous exposure studies utilizing three different concentrations. Antineoplastic effects were analyzed as a function of in vivo achievable serum concentrations, namely by a ratio of the concentration required to decrease cell growth to 10% of control to one-tenth of the peak plasma concentration in humans. Our results suggest that COLO 320DM, OM-1, and Ht-29 cells manifest responsiveness to anticancer drugs consistent with that noted in clinical studies with most agents tested. The radiometric technique provides several advantages for a screening system, including reproducibility, a good agreement with the cloning assay, speed, and low costs. The combined use of the BACTEC technique and the three colon cancer cell lines could prove useful as a screen for new anticancer compounds with activity in colorectal cancer.

Antineoplastic Agents↗
PubMed1986

Shortened platelet half-life in multiple myeloma.

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half-life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained--intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

Blood Platelets↗
PubMed1986

Model for estimation of clinically achievable plasma concentrations for investigational anticancer drugs in man.

A major problem related to in vitro testing of new investigational anticancer compounds is the lack of accurate pharmacokinetic data for the drugs in man. Based on the concept of a relationship between certain toxicologic endpoints in animal systems and maximally tolerated doses in man, we hypothesized that a comparable agreement might exist between these experimental animal toxicology data and clinically achievable peak plasma concentrations (PPCs). A retrospective analysis of the known data pairs of 28 commonly used cytotoxic compounds supports the existence of a reasonably good correlation between ip LD50 values (Pearson test) in nontumored mice and PPCs in man (r2 = 0.501; P less than 0.0001). Our data suggest that by use of the resultant statistical regression model a rational starting point can be selected for in vitro screening of entirely new agents for which human PPCs are not available. Additionally, application of this approach may also prove useful in relation to selecting in vitro doses for chemosensitivity assays intended for predictive correlation with clinical response in cancer patients.

Animals↗
PubMed1985

In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer.

The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02).

Antineoplastic Agents↗
PubMed1985

Acute encephalopathy associated with continuous vincristine sulfate combination therapy: case report.

Neurotoxicity is a well-recognized and commonly observed side effect associated with the use of vincristine sulfate in cancer chemotherapy. The clinical manifestations of vincristine neuropathy cover a wide spectrum of peripheral neurologic dysfunctions that have been described to be reversible and cumulative in most instances (1, 2). Paresthesias, loss of tendon reflexes, and progressive weakness are the most common clinical features (3, 4). Sensory impairment, cranial nerve palsies, gastrointestinal disturbances, and autonomic dysfunctions including atonic bladder, impotence, and orthostatic hypotension may occur (5). Acute CNS complications, usually presenting as generalized seizures, are extremely rare and only a few cases have been reported which were without underlying biochemical or structural abnormalities (1, 5-9). We describe the case of a woman with multiple myeloma, who developed fulminant encephalopathy following 4 days of continuous vincristine, adriamycin, and day 1-4 pulse dexamethasone (VAD) combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Weekly low dose doxorubicin monotherapy in metastatic breast cancer resistant to previous hormonal and cytostatic treatment.

Weekly low dose doxorubicin monotherapy was evaluated in heavily pretreated patients with metastatic breast cancer. 19 patients received 8-12 mg/m2 doxorubicin/week for a treatment period of up to 7 months until a progression of the disease occurred (mean number of weekly courses 15 +/- 8). In 2 of 17 evaluable patients, an objective response with a duration of 3+ and 5 months respectively was achieved. In 9 patients a stabilisation of the disease was observed (mean duration of DS 4 mos +/- 2), whereas the disease progressed in 6. The tolerance for this regimen was remarkable, with neither serious acute toxicity nor any signs of congestive cardiomyopathy even in those patients who were treated beyond a cumulative dose of 450 mg/m2. Weekly low dose doxorubicin monotherapy shows modest activity, but is devoid of severe toxicity in heavily pretreated patients with metastatic breast cancer. An increase in the therapeutic index was not observed.

Aged↗