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Biomedical subjects

B M Mehta

Publications and source records attributed to B M Mehta.

At least 37 records · Page 2Linked to original sources
PubMed1981

Osteogenic sarcoma: eight-percent, three-year, disease-free survival with combination chemotherapy (T-7).

Sixty-one patients were treated with combination chemotherapy (T-7) for biopsy-proved, fully malignant, osteogenic sarcoma (OS) of the extremity. Chemotherapy consisted of the combination of bleomycin, cyclophosphamide, and dactinomycin, followed in 2 weeks by vincristine and high-dose methotrexate (HDMTX) given in doses of 8 g/m2 for adolescents and 12 g/m2 for children 12 years old or younger with citrovorum factor rescue. The HDMTX was administered weekly for 4 weeks. One week following the 4 HDMTX treatments, adriamycin (ADR) was given at a dose of 90 mg/m2 for 2 days. Two weeks after the ADR, 2 additional doses of HDMTX were given before surgery. Thirty-eight of the 61 patients were referred before amputation and underwent preoperative chemotherapy for approximately 3 months. After surgery, chemotherapy was resumed. Of the 61 consecutive patients with primary OS entered in the T-7 protocol, 54 (88%) remained free of disease for more than 8 to over 35 months (median 18+ mo), with a projected 3-year disease-free survival in excess of 80%. Of the 38 receiving T-7 chemotherapy before surgery, 28 demonstrated a near complete or complete lack of viable tumor cells on examination of the resected primary tumors. All 28 are surviving free of disease. Nine of the 10 patients less than 12 years of age remain free of disease from over 12 to more than 35 months (median 24+ mo). A significant increase in disease-free survival in the younger patients could presumably be attributed to the use of 12 g HDMTX/m2 in that age group. The prognostic value of the effect of preoperative chemotherapy on the primary tumor is statistically highly significant. These data indicated that preoperative chemotherapy with the proper dose of HDMTX would be valuable in all patients with OS.

Antineoplastic Agents↗
PubMed1981

Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor).

Forty-three patients, ranging in age from 7 to 30 years (median age, 17 yr), with primary osteogenic sarcoma (OS), confirmed by biopsies and with no evidence of metastatic disease at the time of diagnosis, received T-7 chemotherapy for an average of 4 months before surgery, including high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR) (median, 7 courses), and 1 course each of bleomycin, cyclophosphamide, and dactinomycin, and adriamycin. At the time of definitive surgery, the surgical specimen showed a good histologic response to chemotherapy (grade III or IV response) in 29 (67%) of 43 patients and a poor histologic response (grade I or II response) in 14 (33%) of 43 patients. Among those who responded well, no patient relapsed, as all received a complete course of preoperative and postoperative chemotherapy for more than 5 to over 28 months after the initiation of treatment (medium, 13 mo). Among those who responded poorly, 6 of 14 patients relapsed with pulmonary metastases (a thoracotomy was beneficial to 1), 4 of 6 patients are alive with disease, and 1 patient died of progressive disease. On retrospective analysis, we observed that good and poor responders did not differ in the distribution of sex, age, race, primary site of disease, or histologic subtype of OS. An elevated alkaline phosphatase level that returned to normal under preoperative chemotherapy indicated a good response. Neither the 24-, 48-, and 72-hour serum MTX levels nor the fluid intake and urinary output during 3 days that followed HDMTX with CFR correlated significantly with tumor response. Based on our studies with this form of therapy, we concluded that the response of OS to preoperative chemotherapy is of prognostic value.

Adolescent↗
PubMed1980

A double-blind controlled trial of mianserin and amitriptyline in depression.

A double-blind trial was carried out in 47 patients with depression to compare the effectiveness of 30 mg mianserin, 60 mg mianserin and 50 mg sustained-release amitriptyline, each given as a single dose at night over a period of 4 weeks. Hamilton Rating Scale scores showed significant, progressive improvement from Week 1 with all three regimens. Although the differences between the groups were not significant, the greatest improvement occurred after 60 mg mianserin daily and the order of effectiveness was consistent for various Hamilton Rating Scale items. Patient self-assessment, using visual analogue scales, gave similar results to the Hamilton Rating Scale with significant, progressive improvement in all groups. Once again, a consistent order of effectiveness was evident with most of the items, the greatest improvement being noted with 60 mg mianserin daily and the least with 30 mg mianserin daily. There was a considerable reduction in the number of reports of symptoms recorded before the trial during treatment in all groups. The only increase in symptoms possible drug-related was of blurred vision in patients receiving amitriptyline.

Adolescent↗
PubMed1980

Leukoencephalopathy following high-dose iv methotrexate chemotherapy with leucovorin rescue.

Seven patients with bone or soft tissue sarcomas but without metastatic CNS disease developed a chronic leukoencephalopathy after high-dose (8000-15,000 mg/m2) iv methotrexate (MTX) chemotherapy with leucovorin (LV) rescue. Approximately 12 MTX-LV treatments were administered over a 3-7 month period. None of the patients had cranial irradiation. The syndrome usually began several months after the initiation of chemotherapy with subtle personality changes followed by a progressive dementia, focal seizures, pseudobulbar palsy, spastic quadriparesis, and stupor. Computerized tomographic scans revealed diffuse white matter hypodensity in five patients and atropic changes in five patients. Serum MTX concentrations were elevated in four of six patients prior to several MTX-LV treatments, suggesting that MTX persisted in tissues for a long time. Abnormally high levels of MTX were detected in the cerebrospinal fluid of all four patients several days after an MTX-LV treatment, at a time when their encephalopathy was most severe. Pathologic brain material was obtained from three patients and revealed a spectrum of abnormalities. The syndrome observed in our patients clinically resembles the one described in children with acute lymphatic leukemia who received cranial irradiation and large cumulative amounts of low-dose (12-20 mg/m2) systemic MTX without LV.

Adolescent↗
PubMed1979

Informal patients detained.

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Commitment of Persons with Psychiatric Disorders↗
PubMed1979

Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol or carcinomatous meningitis.

Intracarotid (i.c.) hyperosmolar mannitol enhances central nervous system (CNS) penetration of intravenous (i.v.) methotrexate (MTX) in normal adult rats. A fivefold augmentation in the CSF:serum and ipsilateral brain:serum MTX concentration ratios was observed 1 hour after drug administration. Intravenous mannitol had no such effect. Rats with meningeal carcinomatosis have a partial defect in blood-brain barrier function, and the CSF:serum MTX concentration ratio was 4.6 times higher in these animals than in normal rats prior to mannitol therapy. Intracarotid hyperosmolar mannitol further augmented the blood-brain barrier permeability to intravenous MTX. Intracarotid mannitol increased the therapeutic effect of MTX, since rats with meningeal carcinomatosis that received i.v. MTX and i.c. mannitol experienced a slight enhancement in survival.

Animals↗
PubMed1977

[Serum methotrexate determination by microbiological assay in patients receiving high-dosage methotrexate (author's transl)].

Microbiological assay according to Burchenal (modified by Mehta) is used for the determination of the serum methotrexate (MTX) level. Fifty cycles of high-dose MTX therapy were monitored in 11 patients with osteogenic sarcoma. The results showed close correlation with the clinical course of the therapy. The serum level of MTX was elevated in patients with symptoms of toxicity.

Bone Neoplasms↗
PubMed1977

High-dose methotrexate with citrovorum factor rescue for the treatment of central nervous system tumors in children.

Eleven patients with brain tumors recurrent after surgery and radiation therapy were treated with high-dose methotrexate (MTX) (300-500 mg/kg) with citrovorum factor rescue (CFR). MTX was given as an iv infusion over 4 hours followed 2 hours later by oral CFR (10 mg every 6 hours X 12). MTX levels were measured in the serum, lumbar cerebrospinal fluid (CSF), and ventricular CSF at 0, 4, 12, 24, 48, and 72 hours from the start of the MTX infusion. MTX concentrations of greater than 10(-6) M were measured in the CSF over a period of 24 hours after the iv infusion. Peak CSF concentrations reached were greater than 10(-5) M. After the response to high-dose MTX with CFR was evaluated, vincristine (1.5 mg/m2) and a nitrosourea (methyl-CCNU or BCNU) were added to this treatment regimen. Two of four patients with recurrent pontine glioma and five of seven patients with recurrent medulloblastoma had favorable objective responses to treatment. It is suggested that high-dose MTX with CFR be cautiously considered for the primary treatment of intracranial neoplasms in children with the hope of increasing the cure rate for children with malignant brain tumors.

Brain Neoplasms↗
PubMed1977

Microbiologic assays of cancer chemotherapeutic agents.

Among various assay methods available for the study of drug distribution kinetics in cancer chemotherapy, a method that determines the drug in its active form is the most desirable. The microbiologic assay method, with its rapid, simple, and inexpensive procedures, fulfills such a requirement. Besides the two commonly used chemotherapeutic agents, methotrexate and cytosine arabinoside, microbiologic assays are available for other chemotherapeutic agents, such as 6-mercaptopurine, 5-fluorouracil, actinomycin D, adriamycin, and daunorubicin. Assays have been developed for citrovorum factor and 5-methyltetrahydrofolate in the presence of high levels of methotrexate. With the introduction of combination chemotherapy, microbiologic assay methods using resistant mutants, sensitive to a single drug but resistant (either due to mutation or due to culture conditions) to all other drugs involved in the combination, could well be the most efficient for the study of distribution kinetics. Several such assay methods employed in our laboratory are discussed.

Antineoplastic Agents↗
PubMed1977

A microbiologic disc assay for 5-methyltetrahydrofolate in the presence of methotrexate.

High-dose methotrexate-citrovorum factor rescue regimens are used extensively for the treatment of human malignancies. Since the rescue agent citrovorum factor is rapidly converted to 5-methyltetrahydrofolate, it is desirable to follow the distribution kinetics of both of these coenzymes to assess the selective therapeutic effectiveness of the regimen. The assay methods using methotrexate-resistant strains of Lactobacillus casei ATCC 7469 (LC/A), Streptococcus faecium var. durans ATCC 8043 (SF/A), and Pediococcus cerevisiae ATCC 8081 (PC/A) have been developed to determine the concentrations of 5-methyltetrahydrofolate and other folates in the presence of methotrexate. Since LC/A determines the total folates, SF/A deterimines the total folates except 5-methyltetrahydrofolate, and PC/A by our procedure determines only the most stable form of reduced folates, citrovorum factor, the quantitation of both 5-methyltetrahydrofolate and citrovorum factor can very easily be achieved by differential assays. This report describes the determination of as low as 10 ng/ml of 5-methyltetrahydrofolate in the presence of as high as 500 microgram/ml of methotrexate. The assay method described here is currently used in studying the pharmacokinetics of 5-methyltetrahydrofolate in patients with meningeal neoplasms.

Biological Assay↗
PubMed1977

Perilymph penetration of methotrexate in cats.

The perilymph of the inner ear has recently been suggested as a site of frequent leukemic or lymphomatous infiltrates. Experimental evidence supports the existence of barrier mechanisms and explains the attenuated entry of several substances, including chemotherapeutic agents, from either the cerebrospinal fluid or blood into theperilymph. The present study describes the attenuated entry of methotrexate into the perilymph compartment of experimental animals following intrathecal or iv administration.

Animals↗
PubMed1975

Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections.

The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.

Adolescent↗