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Biomedical subjects

A M Mauer

Publications and source records attributed to A M Mauer.

At least 19 recordsLinked to original sources

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

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

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

A reappraisal of the results of stopping therapy in childhood leukemia.

We examined the results of stopping therapy in children with acute lymphocytic leukemia. Of 639 patients in eight consecutive "total therapy" studies, 278 (44 per cent) had all treatment stopped, usually after 2 1/2 years of complete remission. About one fifth (55 of 278) of this group have relapsed, mainly in the bone marrow. The relapse rate for the first year off therapy was higher than that for the next three years (0.16 vs. 0.04, P less than 0.01). The life-table estimates of the four-year relapse rates were 0.24 for all patients and 0.22 for patients receiving adequate central-nervous system prophylaxis. Boys had a higher relapse rate than girls (0.33 vs. 0.15 P less than 0.01). None of the 79 patients who remained in complete remission for at least four years off therapy have yet relapsed. Acute lymphocytic leukemia appears curable in over one third of all newly diagnosed patients who receive treatment for approximately 2 1/2 years.

Antineoplastic Agents

Kinetic studies of cells in childhood leukemias.

A review of cell kinetic studies in acute childhood leukemia with a comparison of leukemic transformation of non-Hodgkin's lymphoma is presented in this paper. Leukemic cell populations have a longer cell cycle than their normal cell counterparts. The cell populations are comprised of proliferating and resting fractions and are capable of self-maintaining growth. Growth regulation is determined primarily by the size of the proliferating cell population or growth fraction. The growth fraction can vary as to site of disease, the clinical phase, following chemotherapeutic perturbation, and most importantly is related to the specific tumor cell type. Within a specific type of leukemia there is considerable variability of proliferative activity at time of diagnosis, but this variability bears no relationship to the subsequent clinical course. Those leukemias, such as the E rosette-positive form of lymphocytic leukemia characterized by rapid tumor growth and large tumor bulk, are also associated with tumor cell populations having larger growth fractions than standard lymphocytic leukemia. There is evidence for growth regulation of leukemic cell populations on systemic, regional, and, perhaps most importantly of all, intrinsic cell levels. It is this area of growth regulation for these tumor cell populations which currently needs the greatest research attention.

Acute Disease

Treatment of acute leukaemia in children.

As can be seen, there are many problems yet to be solved in the development of optimal therapy for acute leukaemia in children. For patients with ALL we must be able to identify clearly the standard and the varieties of high risk patients. For the patient with standard risk features life expectancy is long and therapy regimens must be designed to provide optimal control of the disease with minimal short and long-term toxicity. For patients with the high risk features of those varieties of ALL associated with poor prognosis methods must be found to circumvent the problem of early acquisition of drug resistance by the leukaemic lymphoblasts. For children with AML the results of remission induction regimens must still be improved to match those obtained in ALL. The major problem awaiting solution, however, is the maintenance of remission once obtained. As disease-free survival in AML is improved then consideration of CNS prophylaxis and the timing of cessation of therapy must be considered.

Acute Disease

Factors leading to delay in the diagnosis and affecting survival of children with head and neck rhabdomyosarcoma.

Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions. These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy. There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy.

Adolescent

Current treatment of acute leukemia.

For patients with ALL we must be able to identify clearly both standard and high-risk patients. For standard-risk patients in whom life expectancy is long, therapy regimens must be designed to provide optimal control with minimal short- and long-term toxicity. For patients with high-risk ALL, methods must be found to circumvent the problem of early acquisition of drug resistance by the leukemic lymphoblasts. For patients with AML, more work must be done to improve the results of remission induction. But the major problem for these patients is the maintenance of a remission once it is obtained. Perhaps one of the critical factors in AML is the interrelationship of normal and leukemic marrow elements in therapy response. Disease-free survival time must be improved before considerations of CNS prophylaxis and cessation of therapy can be approached.

Bone Marrow Transplantation