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Biomedical subjects

A M Mauer

Publications and source records attributed to A M Mauer.

At least 91 records · Page 5Linked to original sources
PubMed1977

Recent advances in pediatric oncology.

There have been remarkable improvements in our knowledge of how to treat children with cancer and also in the results of treatment. Much of this improvement has come from careful and systematic clinical therapeutic studies. We have learned much about the natural history and some about the biology of childhood cancer. For the future it would seem that major advances are going to come not from clinical therapeutic trials but from combined laboratory and clinical research approaches. Chemotherapy will be the main stay of treatment for the foreseeable future. Immunotherapy may play some role as our knowledge of that modality improves. Basically, however, we need much more understanding of the biology of childhood tumors to effect significant answers in this disease area.

Age Factors↗
PubMed1977

Initial prognostic factors and lymphoblast-erythrocyte rosette formation in 109 children with acute lymphoblastic leukemia.

Bone marrow lymphoblasts from 109 children admitted with untreated acute lymphoblastic leukemia (ALL) were tested for spontaneous rosette formation with sheep erythrocytes. Twenty-six children (24%) had lymphoblasts that formed rosettes (E+). Of 13 initial clinical characteristics, 8 were significantly associated with E+ lymphoblasts: mediastinal enlargement (86% of patients E+), leukocyte counts over 100 X 10(9)/liter (65% E+), nodes greater than 2 cm in any diameter (65% E+), age over 5 yr (46% E+), hemoglobin over 8 g/dl (44% E+), hepatomegaly greater than 5 cm (38% E+), boys (35% E+), and lymph node enlargement outside of the cervical area (28% E+). Spleen size, initial platelet counts, and periodic acid-Schiff scores did not distinguish E+ from E- patients. Since few patients were black and few presented with central nervous system leukemia, the association of these two characteristics with E+ blasts could not be determined. A hierarchical classification scheme and a linear logistic regression model were used to define the patterns of characteristics associated with E+ lymphoblasts. The initial clinical characteristics and the poorer course of E+ patients suggest that ALL comprises at least two biologically and clinically distinct types. The E+ ALL may result from a leukemic transformation of a non-Hodgkin lymphoma.

Adolescent↗
PubMed1977

Pretreatment cytokinetic studies in 94 children with acute leukemia. Relationship to other variables at diagnosis and to outcome of standard treatment.

The relationship of the pretreatment bone marrow mitotic index (MI) and in vitro 3H-thymidine labeling index (LI) to other variables present at diagnosis and to the outcome of standard therapy was examined in a series of 94 children with acute leukemia (71 ALL, 23 AML). The range of observed values at diagnosis was extremely broad, from less than 1% labeled cells to more than 25%. The median LI% for all patients studied was 5.2%; the median MI% was 0.3%. The values for AML and ALL did not differ significantly despite older age, higher initial white blood cell (WBC) counts, and poorer response to therapy of AML patients. The initial MI and LI were positively correlated with each other, but unrelated to age or initial WBC count in either ALL or AML. However, the LI and MI were significantly higher (p less than 0.01) in the group of 10 children of 54 studied with ALL whose blasts formed spontaneous rosettes with sheep red blood cells at 37 degrees C. The initial LI and MI were not shown to be related to the likelihood of attaining a complete response or to the length of remission in either ALL or AML. There was thus no evidence that either the initial MI or LI% of marrow blasts was of any prognostic significance in children with acute leukemia.

Age Factors↗
PubMed1977

Correlation of cell kinetic and clinical response to chemotherapy in disseminated neuroblastoma.

Mitotic and labeling indices of bone marrow tumor cells were determined from patients with disseminated neuroblastoma. Although pretreatment values were variable, the median indices indicated that only a small proportion of tumor cells were proliferating. The pretreatment indices could not be correlated with presenting clinical features or with the response to chemotherapy. Studies were repeated after 7 daily doses of cyclophosphamide (150 mg/sq m) and serially after Adriamycin (35 mg/sq m) given on Day 8. Changes in the mitotic and labeling indices during the first course of therapy could be directly correlated with the clinical response as evaluated after 4 months of induction chemotherapy. In all patients who attained a complete or partial remission, an increase in these indices was observed after 7 days of cyclophosphamide. If this increase was associated with an observed kinetic effect of Adriamycin in the G1, S, and G2 phases of the cell cycle, a complete remission was attained. If, following Adriamycin, kinetic evidence of an effect was not present in all three phases of the cell cycle, only partial remission was attained. No clinical response to therapy was observed in those patients in whom the mitotic index and labeling index did not increase after 7 days of cyclophosphamide.

Bone Neoplasms↗
PubMed1976

Cell kinetics and chemotherapy in neuroblastoma.

The proliferative behavior of neuroblastoma cells in bone marrow was evaluated before and after perturbation by chemotherapy. The data presented indicated that the proliferating fraction of the tumor cells before therapy was small. In most of the patients, initial therapy with a non-cell-cycle specific agent increased the mitotic and labeling indices. If initial therapy was followed by a cell cycle-specific agent, variable kinetic responses were observed. Although the number of patients was small and the follow-up was short, there was a correlation between the clinical response and the kinetic changes induced by the chemotherapy. Evaluation of cell kinetic changes during the initial course of chemotherapy might identify early those patients who are unlikely to have a good clinical response. Similar studies in the evaluation of new drugs to aid in identifying agents that favorably change cell kinetics and thus therapy for children with neuroblastoma was urged.

Antineoplastic Agents↗
PubMed1976

Manipulation of the mitotic cycle in the treatment of acute myelogenous leukaemia.

A priming dose of cytosine arabinoside (Ara C) was given to 16 children and five adults with acute myelogenous leukaemia (AML) to synchronize leukaemia cells in the DNA synthesis (S) phase of the mitotic cycle. An infusion of this drug, which was continued for 12 h, was started at the time of partial synchronization and was repeated every 6-12 h until the bone marrow was very hypocellular. Complete remission was achieved in 12 of 16 children and in all adults. Two of the four children went into complete remission with the addition of two doses of daunorubicin or adriamycin. These results suggest that partial synchronization of cells in the S phase results in a therapeutic advanatage in the use of Ara C for induction of a remission of AML and that manipulation of the mitotic cycle, as monitored by kinetic studies, may be helpful in planning optimal schedules for drug administration.

Adolescent↗
PubMed1976

Evidence for recruitment and synchronization in leukemia and solid tumors.

In malignant cell populations which are sensitive to drug therapy it does not seem necessary to potentiate treatment with perturbation of the proliferative characteristics. However, in some relatively drug-resistant populations significant advantages can be obtained by recruiting resting cells into the drug-sensitive cell cycle. Further studies of growth-regulatory mechanisms for malignant cell populations may help a great deal in designing better methods of recruiting the resting cells back into active cell division. Synchronization of the dividing cells in a specificially drug-sensitive phase of the cell cycle is another method of potentiating chemotherapeutic effectiveness in relatively drug-resistant cell populations. The biochemical changes induced by sequential drug administration may be equally important in sensitizing the malignant cell to subsequent drug administration.

Antineoplastic Agents↗
PubMed1975

Current concepts of cell kinetics in the treatment of leukemia.

In a relatively brief time, considerable information has been accumulated concerning the relationship of the cell proliferation characteristics of acute leukemia and response to chemotherapy. Much remains to be learned, but we are now able to approach the problem of therapeutic regimen design based on observed patterns of in vivo cell response.

Antineoplastic Agents↗
PubMed1975

Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test.

The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidative metabolism. The oxidation of glucose-1-14-C by supernatant prepared from selectively depleted sera indicated that the neutrophil-stimulating factor(s) was generated through the alternate pathway of complement activation. The possibility that inulun had been ingested as a particle was ruled out by light microscopy and radiolabeling studies. The failure of neutrophils stimulated by the serum-inulun supernatants to migrate after exposure to a chemotactic agent suggested that the site of neutrophil-complement interaction was on the cell membrane. It is concluded from these results that biologically active fragments generated through the alternative pathway of complement activation can stimulate neutrophil metabolism in the absence of phagocytosis. Interaction of such fragments with circulating neutrophils in vivo and the subsequent metabolic activation of these cells is one explanation for the spontaneous reduction of nitroblue tetrazolium dye in vitro by neutrophils from patients with certain infections and inflammatory disorders.

Absorption↗