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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 181 records · Page 10Linked to original sources
PubMed1981

A radioimmunoassay for 5-methyltetrahydrohomofolate.

A radioimmunoassay for 5-methyltetrahydrohomofolate has been developed by using antibody induced in rabbits by 5-methyltetrahydrohomofolate-bovine serum albumin conjugates. The labeled drug was prepared by condensing it with [3H]histamine or [125I]histamine. The assay employing either isotope was simple and reproducible and had identical sensitivities. The specificity of the antibody was characterized by comparing the effectiveness of various related compounds in displacing labeled 5-methyltetrahydrohomofolate from the binding site of the antisera. At concentrations up to 1000 microgram/ml, homofolate acid, tetrahydrohomofolic acid, folic acid and methotrexate showed no competition for the binding. 5-methyltetrahydrofolic acid and 5-formyltetrahydrofolic acid cross-reacted with the antisera; the concentrations producing 50% binding inhibition were 2.8 and 24 microgram, respectively, as compared to 0.01 microgram for 5-methyltetrahydrohomofolate. The assay can be used for measuring the drug in plasma and tissues. This study supports its usability for clinical pharmacologic studies.

Animals↗
PubMed1981

Pharmacology of pentamethylmelamine in humans.

A rapid, specific high-pressure liquid chromatographic assay was used to study the pharmacology of pentamethylmelamine in 21 patients (28 infusions) receiving 80 to 1500 mg/sq m. In patients with normal liver function, pentamethylmelamine was rapidly cleared from the plasma with a terminal half-life of 2.2 hr. Abnormal liver function tended to correlate with increased half-life and reduced total clearance. In addition, increased neurological toxicity was associated with hepatic abnormalities. The N2,N2,N4,N6-tetramethylmelamine, N2,N4,N6-trimethylmelamine, dimethylmelamine, and monomethylmelamine metabolites were detected in plasma. The terminal plasma half-lives of these metabolites increased with decreasing number of methyl group. With liver dysfunction, the plasma clearance of these metabolites also decreased and central nervous system toxicity increased. Although the antitumor activity of pentamethylmelamine is thought to be mediated by the intermediate hydroxymethyl metabolites produced by hepatic microsomal oxidation or by the formaldehyde generated, the neurological toxicity appears to depend upon the pharmacokinetics of the drug and its demethylated metabolites.

Altretamine↗
PubMed1981

Role of intravenous hyperalimentation as an adjunct to intensive chemotherapy for small cell bronchogenic carcinoma.

Forty-nine patients with small cell bronchogenic carcinoma (23 limited and 26 extensive disease) received their first two of three courses of intensive remission induction chemotherapy with (21 patients) or without (28 patients) intravenous hyperalimentation (IVH). The chemotherapy included six remission induction courses with ECHO (epipodophyllotoxin VP-16-213, cyclophosphamide, hydroxydaunorubicin, oncovin), followed by six courses of maintenance with PRIME (procarbazine, ifosfamide, methotrexate). Prophylactic brain irradiation (3000 r/2 weeks) was given to all patients and those with limited disease received chest irradiation (5000 r/5 weeks) at the completion of ECHO. Thus far, all 30 patients who have completed three courses of ECHO have responded with complete (70% CR) or partial (30% PR) remissions. The CR rate was higher for patients receiving IVH (85% vs 59%, P = 0.25). Myelosuppression was pronounced and predominantly in the form of neutropenia. Median lowest neutrophil counts were zero during each of the three courses of ECHO and lasted a median of 5 days at levels less than 500/mm3. Major infections occurred in 21% of courses. The administration of IVH did not ameliorate the hematologic, gastrointestinal, and infectious morbidity of ECHO chemotherapy. However, it resulted in preservation of body weight (P less than 0.01) and improved skin reactivity to a battery of six skin antigens (P = 0.03). The administration of intensive therapy with ECHO +/- IVH was well tolerated and resulted in high CR rates in patients with small cell bronchogenic carcinoma. The administration of IVH was most helpful in preventing severe weight loss and augmenting response to a battery of skin antigens. The long term survival effects of these observations are yet to be determined.

Adult↗
PubMed1981

Treatment of patients over 50 years of age with acute myelogenous leukemia with a combination of rubidazone and cytosine arabinoside, vincristine, and prednisone (ROAP).

We administered a combination of rubidazone, cytosine arabinoside, vincristine, and prednisone (ROAP) to 91 patients with acute myelogenous leukemia who were 50 yr of age or older. These patients had been identified in previous studies to be a group with a relatively poor prognosis. One-third of the patients had an antecedent hematologic disorder prior to treatment. Forty patients (48%) obtained a complete hematologic and clinical remission. A history of an antecedent hematologic disorder, male sex, and absence of Auer rods were adverse factors for achieving remission in this older population. More than half of the patients achieved remission in one course. The major cause of failure to obtain a remission was death due to infection, 40% of which were caused by fungi. Resistance to chemotherapy, although uncommon, was noted more frequently in patients with an antecedent hematologic disorder. Univariate and multivariate prognostic factor analysis was used to compare these patients with a historical control group treated with a program in which adriamycin was used instead of rubidazone (AdOAP). No significant difference in remission rate was detected. Cyclocytidine was used as a maintenance agent in this study, and while the median remission duration was only 37 wk, 30% of patients are expected to be in remission for 2 yr. Chemotherapy programs combining an anthracycline with cytosine arabinoside, given to older patients in similar fasion to younger patients will achieve remissions in one-half of a group of older patients. These remissions are of comparable quality to those of younger patients. Mathematical models derived from analysis of prognostic factors are of use in identifying patients likely to fail these programs who are in need of innovative approaches to treatment.

Aged↗
PubMed1981

Penetration of methylglyoxal bis(guanylhydrazone) into intracerebral tumors in humans.

Methylglyoxal bis(guanylhydrazone) (MGBG; NSC 32946) is currently being reevaluated for its clinical antineoplastic activity against both hematological and solid tumors. MGBG (100 to 200 mg/sq m) was administered by slow infusion over 3 hr to six patients during surgical resection of intracerebral tumors. Excised tumor tissue and plasma were assayed for MGBG by high-pressure liquid chromatography. In all cases, MGBG penetrated rapidly into brain tumor tissue. Viable tumor tissue contained greater concentrations of MBGB than did necrotic tumor tissue. In two patients with glioblastoma multiforme, MBGB concentrations in brain tumor tissue were five- to 19-fold higher than concurrent plasma samples. However, MGBG did not penetrate well into the cerebrospinal fluid of two patients with Ommaya reservoirs given i.v. MGBG (200 mg/sq m). The highest MGBG concentration in cerebrospinal fluid reached only 22% of the concurrent plasma levels. These studies suggest that MGBG may be a useful agent in the treatment of intracerebral tumors but may not be effective against meningeal leukemia and meningeal carcinomatosis.

Blood-Brain Barrier↗
PubMed1980

Percutaneous hepatic arterial infusion (HAI) of mitomycin C and floxuridine (FUDR): an effective treatment for metastatic colorectal carcinoma in the liver.

The response rate of metastatic colorectal carcinoma confined to the liver to HAI of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HAI to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m2 administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography, and radionuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of the these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5-FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapy-related complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment.

Adult↗
PubMed1980

Phase I-II trial of percutaneous intra-arterial cis-diamminedichloro platinum (II) for regionally confined malignancy.

Forty-nine patients with regionally confined recurrent malignancy were treated with intra-arterial cis-diamminedichloro platinum II in a Phase I-II trial. A safe starting dose of 120 mg/m2 was established. An overall response rate of 45% was noted with significant responses observed among patients with melanoma, sarcoma, breast carcinoma, and neuroblastoma. Side effects included transient renal and bone marrow toxicity as well as neurotoxicity and ototoxicity (6%), the latter usually with residual damage. The rational basis and advantages of treatment with intra-arterial cis-platinum are discussed.

Adolescent↗
PubMed1980

Sarcoma of the stomach: clinicopathologic study of 43 cases.

The records of 43 patients with histologically proved primary gastric sarcoma treated at M. D. Anderson Hospital and Tumor Institute between 1945 and 1975 were reviewed. Weight loss, abdominal pain, and hematemesis or melena were the most common symptoms, and palpable epigastric mass was the most common physical sign. Ninety-five percent of the gastric tumors were leiomyosarcomas. The median survival time and the five-year survival for the 29 patients who had curative gastrectomy were 33 months and 38%, respectively. Morphologic and histologic factors that adversely influenced the length of disease-free interval and survival following curative surgery included 1) primary tumor 8 cm or greater in diameter, 2) tumor extension to serosa of the stomach, and 3) low grade of differentiation of the primary tumor. Seventy-seven percent of recurrences in patients with curative tumor resection occurred within two years of resection of the primary. Of the 17 patients with advanced disease who received chemotherapy, two (15%) had objective tumor regression of greater a median survival time of eight months for patients who failed to respond. New approaches that may improve the results of treatment of gastric sarcoma are discussed.

Female↗
PubMed1980

Phase II study of 4'-(9-acridinylamino) methanesulfon-m- anisidide (AMSA) in metastatic melanoma.

A phase II study of AMSA in previously treated patients with metastatic malignant melanoma was conducted. The dose schedule of AMSA was 40 mg/m2/day for 3 days repeated at 3-week intervals. Among the 30 evaluable patients, one achieved a complete response, one a partial response, and four had minor responses. Side effects included mild nausea and vomiting and moderate degree of myelosuppression. AMSA has poor activity against previously treated metastatic melanoma.

Adult↗