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Biomedical subjects

M S Mahaley

Publications and source records attributed to M S Mahaley.

At least 73 records · Page 4Linked to original sources
PubMed1980

Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery.

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

Aged↗
PubMed1980

Prediction of BCNU pulmonary toxicity in patients with malignant gliomas: an assessment of risk factors.

Symptomatic pulmonary disease occurred in 20 per cent of 93 patients with anaplastic gliomas being treated with carmustine (BCNU). An analysis of the variables has revealed a relation between the occurrence of pulmonary toxicity on the one hand, and the total cumulative dose of BCNU, the number of cycles over which the BCNU was administered, the history of lung disease, the patient's age, and the platelet-count nadir after the first course of BCNU on the other. An equation has been generated that allows prediction of pulmonary toxicity during the course of therapy with BCNU with 80 per cent accuracy. Pretreatment analysis of individual cases should allow safe use of BCNU and prevention of most of the serious pulmonary complications caused by this drug.

Adult↗
PubMed1980

Treatment of autochthonous rat brain tumors with fractionated radiotherapy. The effects of graded radiation doses and of combined therapy with BCNU or steroids.

The avian sarcoma virus-induced glioma model in rats was used to evaluate radiation dose response (survival curves), giving fractionated treatments to the whole head. Groups of 14 to 20 rats received total doses of 2300, 4600, or 5750 rads over 2, 4, or 5 weeks, respectively. Median group survival times were compared to controls and to each other. All doses of radiation significantly prolonged survival with reference to control. The 4600- and 5750-rad doses were significantly more effective than the 2300-rad dose. In another series of experiments, BCNU chemotherapy (10 mg/kg) was combined with 2300 and 4600 rads radiation therapy. Synergism of therapies was demonstrated. Methylprednisolone acetate (2 mg/kg twice weekly over 4 weeks) alone did not affect survival curves, and its combination with 4600 rads radiation therapy negated the prolongation of survival achieved with 4600 rads alone.

Animals↗
PubMed1979

Synergism between BCNU and irradiation in the treatment of anaplastic gliomas. An in vivo study using the avian sarcoma virus-induced glioma model.

The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.

Animals↗
PubMed1978

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Adolescent↗
PubMed1977

Immunobiology of primary intracranial tumors. Part 1: studies of the cellular and humoral general immune competence of brain-tumor patients.

Cellular and humoral immune parameters were evaluated in a series of brain-tumor patients, 42 with glioblastoma multiforme, 17 with other anaplastic gliomas, and 17 with meningiomas. A degree of anergy was found, which seems in the group as a whole to be proportional to the degree of anaplasia. In addition, serial bimonthyl testing in individual cases revealed further reduction in certain immune responses coincident with clinical decline.

Antibodies, Viral↗
PubMed1977

Immunobiology of primary intracranial tumors.

The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Guérin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon survival times. The most consistent prolongation of survival time was produced by triple therapy: BCG + intraperitoneally administered sarcoma cells + intravenously administered BCNU.

Alpharetrovirus↗
PubMed1977

Immunobiology of primary intracranial tumors. Part 3: Microcytotoxicity assays of specific immune responses of brain tumor patients.

Fifty-six in vitro microcytotoxicity assays were conducted on 30 patients with intracranial tumors at various times during the postoperative course. Significant specific cellular cytotoxic responses were found in nine of 56 assays, humoral cytotoxic responses in nine of 54 assays, and host effector cell-dependent, antibody-dependent cytotoxic responses in four of 28 assays. Variables that might influence the occurrence of cytotoxicity were studied, and the relationship of these findings to other immune parameters was discussed.

Adolescent↗
PubMed1977

Immunobiology of primary intracranial tumours. II. Analysis of lymphocyte subpopulations in patients with primary brain tumours.

Circulating peripheral blood lymphocyte subpopulations were analysed in patients with primary intracranial neoplasia. Patients with tumours of glial origin demonstrated a significant depletion of E-rosetting lymphocytes whereas the quantitative lymphocyte profiles of patients with non-glial brain tumours were normal. The number of immunoglobulin and Fe receptor-bearing cells was not significantly altered in any group of patients: however, the EAC-RFC subpopulation was increased in those with malignant gliomas. Two hypotheses are suggested to explain these observations: first, the presence of cross-reacting antibody between T cells and brain (glial) cells, and secondly, the proliferation of EAC-RFC in response to malignant degeneration.

Adult↗
PubMed1977

Neuropathology of tissues from patients treated by the Brain Tumor Study Group.

The histopathologic diagnoses in 718 brain tumor patients entered in the Brain Tumor Study Group were reviewed, as well as those for 53 of these patients who were reviewed, as well as those for 53 of these patients who were autopsied later. This review documented instances of progression of histologic analplasia. Of particular interest in the autopsied cases were several instances of extensive necrosis in white matter distant from persisting glioma following chemotherapy and radiotherapy. This observation suggested the presence of a structural and/or metabolic alteration in the diseased hemisphere that perhaps makes it more susceptible to further alterations secondary to the adjunctive therapy.

Adult↗
PubMed1977

Surface antigenic characteristics of human glial brain tumor cells.

The surface antigenic characteristics of human glial brain tumor (HGBT) cells were studied by complement-dependent cytotoxic antibody assays and indirect membrane immunofluorescence. Eight permanent, well-characterized cell lines derived from human gliomas were used for analysis with antisera raised by hyperimmunization of nonhuman primates (Macaca fascicularis) with glioblastoma multiforme tissue or established HGBT cells lines. Exhaustive absorption of these antisera to remove predominantly antispecies activity rendered HLA nonreactive "preabsorbed" antisera, which reacted with a large panel of gliomatous and nongliomatous human tumor cells; 1 carcinoma, 2 sarcomas, 2 melanomas, 1 neuroblastoma, and 8 HGBT cell lines. Four lymphoblastoid lines and 2 carcinomas were unreactive. After further absorption with a human osteogenic sarcoma cell line, the antisera demonstrated significant levels of reactivity for 8 tested HGBT cell lines and no longer reacted with the nongliomatous cultured tumor cells lines. Therefore, extensive absorption of nonhuman primate anti-human glioma sera removed all activity for the nongliomatous cell lines tested, but it left significant reactivity against a glial tumor cell line-associated antigen(s) present on all 8 human glioma cell lines tested.

Antibodies, Neoplasm↗
PubMed1976

Evaluation of mithramycin in the treatment of anaplastic gliomas.

A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 mug/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.

Adult↗
PubMed1976

Chiasmal syndrome due to intrasellar abscess.

A 43-year-old woman had diabetes insipidus and amenorrhea. There was panhypopituitarism on endocrine testing and visual field examination showed inexorably progressive loss to bitemporal hemianopsia. All radiographic findings were normal, but craniotomy disclosed the cause of this chiasmal syndrome to be an intrasellar abscess which, on culture, grew a Gram-positive anaerobe, Peptococcus. Intrasellar or pituitary abscess is rare, but it must always be considered in the differential diagnosis of the chiasmal syndrome, since loss of pituitary and visual function may occur much more rapidly than with the tumors most often responsible for this syndrome and since surgical cure is possible.

Adult↗
PubMed1975

Value of sequential postoperative brain scans in patients with anaplastic gliomas.

The authors analyze the postoperative course of 30 patients with anaplastic supratentorial gliomas to evaluate the usefulness of sequential brain scanning as an adjunct to clinical neurological examinations in the early detection of tumor recurrence. The correlation between sequential scanning and clinical evaluation was excellent; no examples of divergent resu;ts were seen. With the exception of scans made very early in the postoperative period or when postoperative scalp flap infections were present, initial postoperative scans were easily interpreted in terms of both the superficial (postcraniotomy) and parenchymal changes. The specific type of postoperative therapy (radiation therapy, chemotherapy, or both) could not be correlated with whether scan or examination ultimately changed first. However, analysis of original tumor location revealed that while sequential postoperative scanning offered no advantage over repetitive neurological examinations in the detection of recurrent tumor in the neurologically dominant left hemisphere, scan changes preceded examination changes in eight of 17 cases involving tumors of the neurologically nondominant right hemisphere.

Brain Neoplasms↗