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Biomedical subjects

A M Mauer

Publications and source records attributed to A M Mauer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Clinical studies of docetaxel (Taxotere) and concomitant chest therapy.

The administration of concomitant chemoradiotherapy has been shown to increase local and regional control of non-small cell lung cancer. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has single-agent activity in non-small cell lung cancer, as well as radiation-enhancing potential in preclinical studies. Therefore, its investigation with concomitant radiotherapy in the clinical setting is justified. Since the clinical interactions of docetaxel and concomitant chest radiotherapy have not been previously described, we initiated a phase I study with the goal of determining the maximum tolerated dose of docetaxel and the optimal schedule for its administration during a standard course of radiation therapy to the chest, in addition to defining the dose-limiting toxicities of this regimen. This report describes the design and preliminary results of this study.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Dosing of oral etoposide normalized for body surface area.

The objective of this clinical and pharmacological study was to determine whether any pretreatment parameters were associated with pharmacological or toxicity parameters after prolonged oral etoposide. Therefore, the relationships between patient characteristics and etoposide concentrations and hematological toxicity were evaluated. Sixty patients with advanced non-small cell lung cancer were treated with etoposide 50 mg/m2/day p.o. for 21 consecutive days and cisplatin 100 mg/m2 i.v. on day 1. Complete blood counts and etoposide plasma concentrations were obtained weekly. Etoposide was measured by high-performance liquid chromatography. The input variables were age, gender, race, weight, weight0.66, weight0.75, height, body surface area, performance status, albumin concentration; and total etoposide dose. The outcome measures were etoposide concentration; nadir values (white blood cells, neutrophils, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells; and graded toxicity. No significant correlations were found in 49 fully evaluable patients between any of the input and outcome variables. Among the outcome variables, significant correlations were found between etoposide concentration and the logarithmic transformation of the nadir blood counts. If any of the input variables were significantly correlated to etoposide concentrations or toxicity variables, it would be possible to suggest another predictor variable besides body surface area. As long as treatment is not modified for etoposide concentrations, dosing of oral etoposide must still rely on estimates of body surface area.

Administration, Oral↗
PubMed1994

Cytotoxic effects of alpha- and gamma-interferon and tumor necrosis factor in human bladder tumor cell lines.

We investigated the activity of alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN) and tumor necrosis factor-alpha (TNF-alpha) in a panel of ten human bladder tumor cell lines. All cytokines were tested at concentrations of 100-10,000 U/ml in a clonogenic assay system. We found that alpha-IFN was active against five of the ten lines while gamma-IFN was only active against one line. TNF was active against five of the ten lines. Maximum synergisms were obtained between the alpha-IFN and TNF, occurring in nine of the ten cell lines. We conclude that alpha-IFN and TNF are active as single agents and synergistic when used together in vitro in human bladder tumor cell lines.

Cell Division↗
PubMed1993

Adult and childhood acute lymphocytic leukemia: are they different diseases?

Age has long been recognized as an important factor in predicting response to treatment for acute lymphocytic leukemia (ALL). Specifically, the results of treatment of childhood ALL have been far superior to the treatment of what appears to be the same disease in adults. However, from an analysis of the clinical and biological prognostic factors known to be predictive in childhood ALL, there is a striking difference in their distribution in adults with ALL. It appears that there is a special form of ALL seen in children of some populations with a peak incidence of three to seven years. This treatment responsive leukemia appears to be different clinically, biologically, and epidemiologically from adult ALL.

Adult↗
PubMed1993

Cocaine-induced platelet defects.

BACKGROUND AND PURPOSE: Numerous studies have demonstrated an association between acute cardiac events, cerebrovascular accidents, and cocaine use. The underlying mechanisms leading to these complications have not been well defined. Using various in vitro model systems, it has been reported that cocaine, up to or greater than an order of magnitude of the lethal dose, causes either inhibitory or proaggregatory effects on platelet function. METHODS: To address these reported discrepancies, we examined the effect of cocaine and its carrier on the activation and aggregation of human platelets in vitro. RESULTS: We found that cocaine inhibited platelet aggregation when platelets were challenged with ADP, collagen, or arachidonic acid. This inhibition was due to a direct effect on fibrinogen binding to the activated platelet. Cocaine also caused the dissociation of preformed platelet aggregates. At these same concentrations, cocaine did not inhibit agonist-mediated increases in cytosolic calcium or inhibit platelet shape change, suggesting that its effect on platelet aggregation was a selective process and not due to a total destruction of platelet function. Interestingly, the organization of the cytoskeleton of activated platelets, a secondary event critical to cell receptor clustering and clot retraction, was disrupted by cocaine treatment. In addition, alterations in platelet protein electrophoretic patterns were observed on preincubation of platelets with cocaine. CONCLUSIONS: We conclude that cocaine may have a direct inhibitory effect on the ability of platelets to participate in thrombus formation. The contribution of this effect as an underlying mechanism of sudden death in cocaine abusers is unknown.

Adenosine Diphosphate↗
PubMed1993

Pharmacodynamics of prolonged oral etoposide in patients with advanced non-small-cell lung cancer.

PURPOSE: This study was undertaken to investigate the pharmacodynamic relationship between etoposide drug levels on 21-day oral treatment courses and hematologic toxicities in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-two patients with stage IIIB or IV NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days in combination with cisplatin 100 mg/m2 on day 1. Treatment was repeated every 28 days for up to six courses. Patients had not received previous chemotherapy and had a performance status of 0 to 2. Patients were monitored weekly while on treatment for compliance with oral etoposide and toxicity, including complete blood cell counts, and a blood sample before the daily etoposide dose (drug trough levels). Etoposide concentrations were measured in the plasma by high-performance liquid chromatography (HPLC). RESULTS: Three patients achieved a complete response (CR) and 10 patients a partial response for an objective response rate of 41% (95% confidence interval, 24% to 58%). The median survival was 4 months (range, 1 to 23). Neutropenia was dose-limiting, and two patients died of neutropenic sepsis. Pharmacodynamic correlations for drug concentrations and hematologic toxicities were available for 27 patients and a total of 76 treatment courses, and correlations were significant for graded hematologic toxicity and nadir counts of leukocytes, neutrophils, hemoglobin, and platelets. The grade of infection (77 courses) was also related to drug levels. Using data from 27 initial courses, a pharmacodynamic model was developed to estimate the nadir leukocyte or neutrophil count (WBCn, ANCn) based on the pretreatment count (WBCp, ANCp) and the etoposide concentration (Ec) as follows: WBCn = 0.35 (1 + WBCp x e-1.12 x Ec) and ANCn = 0.32 (1 + ANCp x e-2.47 x Ec). CONCLUSION: Etoposide concentrations are related to the resulting hematologic toxicities. It is possible to predict nadir counts in the first course by a pharmacodynamic model. The above equations need to be validated prospectively and may be useful in future studies of prolonged oral etoposide.

Administration, Oral↗
PubMed1992

Assessment of lumiaggregometry for research and clinical laboratories.

Platelet aggregometry is often used to help diagnose storage pool disease (SPD-reduced amounts of granule nucleotides) and release defects (abnormal release of granule nucleotides). The general assumption that normal aggregation patterns are sufficient to rule out the diagnosis of one of these disorders has been invalidated by the recent publication of two papers describing patients with clinical bleeding, prolonged bleeding times and normal aggregation patterns in spite of defective release. The lumiaggregometer provides a tool for measuring platelet release and aggregation simultaneously. This paper presents a standardized, reproducible method for the use of the lumiaggregometer based on a "standard curve". Data obtained during the development of the procedure are presented including normal ranges of release at different concentrations of agonists, release measured in intrinsic disorders as well as in patients on aspirin, and values for release relative to varying platelet counts. A monoclonal antibody (anti-p24/CD9; MAb7) which activates platelets similarly to thrombin and may be a useful reagent for distinguishing SPD and release defects is also introduced.

Adenosine Triphosphate↗
PubMed1987

Detection of small cell lung cancer bone marrow involvement by discontinuous gradient sedimentation.

Marrow involvement by small cell lung cancer (SCLC) is detected in 10-23% of patients at initial diagnosis by marrow aspirate and biopsy techniques. To improve the detection and potentially monitor marrow involvement by SCLC we have attempted to concentrate malignant cells with clonogenic potential on a discontinuous density gradient (DDG). The bone marrow from 43 patients with SCLC (36 with histologically negative marrow aspirates and biopsies) were separated on a Ficoll-based DDG. Samples were also separated by conventional Ficoll-diatrizoate (FD) (density, 1.077) gradient sedimentation. The cellular interphase from three fractions (F X) corresponding to specific densities 1.050 (F X 1), 1.055 (F X 2), and 1.060 (F X 3) as well as cells separated by Ficoll-diatrizoate (F X FD) centrifugation were isolated and 2.5 X 10(5) cells from each fraction were cultured in 2 ml of 0.3% agar in McCoy's media with 10% fetal calf serum, 2.5 micrograms transferrin, 1 microgram insulin, and 1% penicillin-streptomycin. Colony growth was assessed after 14 days of culture at 37 degrees C and 6% CO2. Tumor colony growth was seen in eight of 36 (22%) patients with histologically negative marrows as well as in four of seven (57%) patients with known involvement. Mean colony growth per 2.5 X 10(5) cells for all 12 patients was 4.3 colonies for F X 1; 8.8 for F X 2; and 2.7 for F X 3. In contrast mean growth from the F X FD was 1.0 colonies. Cells with clonogenic potential could be demonstrated from F X 2 and F X 3 in seven of 12 and eight of 12 patients, respectively; in F X FD four of 12 patients had tumor growth. We conclude that separation of marrow samples by DDG concentrates malignant cells with clonogenic potential at least 8-fold compared to FD separation and that the sensitivity of the clonogenic assay in detecting marrow involvement by SCLC is enhanced by DDG sedimentation.

Biopsy↗
PubMed1987

The concept of cure in pediatric oncology. Altered realities.

Defining cure for a child with cancer is not simple. Such terms as "long-term disease-free survival" or "no evident disease" are expressions of our current clinical inadequacies. An equally important problem, however, is that the disease and its treatment are frequently associated with sequelae that prevent complete restoration of baseline health status or that alter subsequent growth and developmental patterns. This article describes the nature of cures that have been achieved for childhood cancer and reassesses current treatment goals, taking into consideration altered realities of survival. Tasks remaining include the construction of medical treatment regimens that minimize acute and late effects, the design of intervention strategies to reduce the psychological and social impact of the disease on children and families, and the modification of society's attitudes so that cancer survivors are more accepted in the community.

Acute Disease↗