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Biomedical subjects

K R Hande

Publications and source records attributed to K R Hande.

108 records · Page 6Linked to original sources
PubMed1979

Presence of 2,4-diamino-N10-methylpteroic acid after high-dose methotrexate.

Assay of plasma methotrexate has been established as important to its safe use. We have investigated the specificity of 2 assay procedures for methotrexate: the competitive dihydrofolate reductase binding assay (CRBA) and the radioimmunoassay (RIA). The RIA of plasma methotrexate resulted in consistently higher values than the CRBA, with greater differences at later measurement times. A compound that strongly cross-reacts in the RIA, but not the CRBA, has been identified in plasma and urine of patients on high-dose methotrexate therapy, and appears to be the carboxypeptidase cleavage product (2,4-diamino-N10-methylpteroic acid) on the basis of chromatographic and ultraviolet spectral properties. Although this compound is present as a minor contaminant in commercial methotrexate preparations, quantitative assessment of urinary excretion suggests that in man a major portion of the compound is derived from methotrexate metabolism.

Biological Assay↗
PubMed1979

Thirty-six-hour preoperative high-dose methotrexate infusion in patients with squamous carcinoma of the head and neck.

Twenty 36-hour infusions of high-dose methotrexate were given preoperatively to 10 patients with head and neck cancer. Plasma methotrexate levels of greater than 1 X 10(-5) M were maintained for 36 hours and declined with primary and secondary plasma half-lives of 1.7 and 9.2 hours following the end of the infusion. Toxicity of this infusion regimen was minimal (10% incidence of significant (WBC less than 2000/mm3) myelosuppression; no renal toxicity) and all patients underwent surgical resection within 3 weeks of therapy without obvious increase in operative complications. Four of ten patients responded to chemotherapy. Further comparison of the therapeutic efficacy of this prolonged preoperative infusion regimen with surgery alone or schedules employing conventional doses or 6-hour infusions of high-dose methotrexate appears warranted.

Aged↗
PubMed1979

Ara-C metabolism: implications for drug resistance and drug interactions.

Clinical studies of resistance to cytosine arabinoside have not produced agreement as to the specific biochemical lesions responsible for altered sensitivity, although experimental and clinical work supports the concept that a decreased ability to generate ara-CTP must be the ultimate effect of this lesion. 3-deazauridine, an inhibitor of CTP synthetase, was found to enhance ara-CTP production in murine tumor cells, and in the present study, was shown to inhibit deamination of ara-C at both the nucleoside and nucleotide level. Enhanced ara-CTP formation was observed in cells lacking cytidine deaminase (L1 210 and HL60), indicating that 3-deazauridine inhibition of deoxycytidylate deaminase may be important in this drug interaction.

3-Deazauridine↗
PubMed1979

Hyperxanthinemia interferes with serum uric acid determinations by the uricase method.

Serum xanthine concentrations as high as 148 mg/L were noted after treatment of a patient with Burkitt's lymphoma who was receiving allopurinol. These markedly above-normal values for xanthine led to spuriously low values for serum uric acid as measured by the uricase method. Rapid tumor lysis in patients who are receiving allopurinol may lead to marked hyperxanthinemia, which in turn may obscure hyperuricemia in such patients when the uricase method is used for uric acid analysis. In such situations, uric acid concentrations should be measured by the phosphotungstate colorimetric assay.

Adult↗
PubMed1978

Diffuse histiocytic lymphoma involving the gastrointestinal tract.

The results of staging and treatment of 18 patients with diffuse histiocytic lymphoma involving the gastrointestinal tract are summarized. Widespread disease (Stage IV) was found in the majority (72%) of patients after rigorous staging, indicating the relative rarity of localized gastrointestinal lymphoma and the resulting need for systemic therapy in most of these patients. Chemotherapy combined with surgical resection and/or radiation therapy produced complete remissions in only 5 of 18 patients (28%). Patients failed to achieve complete remission due to 1) tumor resistance to drug therapy (46% of treatment failures), and 2) massive intestinal hemorrhage or bowel perforation secondary to tumor necrosis (38% of treatment failures). These findings indicate the need for more active chemotherapeutic regimens and for measures aimed at preventing complications such as bowel perforation or hemorrhage, possibly by combining surgical resection of bowel lesions with systemic chemotherapy.

Adult↗
PubMed1978

High-dose methotrexate with citrovorum factor rescue in non-small-cell lung cancer.

Nineteen patients with non-small-cell carcinoma of the lung were treated with high-dose methotrexate and leucovorin rescue. Two partial responses (10.5%) were observed, lasting 13 and 17 weeks. Toxicity was acceptable. It is concluded that the occasional benefit of high-dose methotrexate with leucovorin rescue at this dose and according to the schedule described for these patients does not warrant further study.

Adult↗
PubMed1977

Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity.

To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drug's clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. After 375 infusions, 48 hour methotrexate levels fell within 2 standard deviations of the mean for nontoxic infusions, and myelosuppression did not occur. Methotrexate concentrations exceeded the range for nontoxic patients (mean +/- 2 standard deviations) after 20 infusions. Serious myelosuppression occurred after six of these 20 infusions, including five of 12 infusions associated with 48-hour drug concentrations above 9 X 10(-7) M. In seven patients with 48-hour concentrations above 9 X 10(-7) M, the absence of toxicity could be attributed to subsequent rapid clearance of the drug; four of these patients also received large doses of supplemental leucovorin (50 to 100 mg per square meter every six hours). Determination of methotrexate concentration in plasma thus identified patients at high risk of toxicity, a group that may benefit from supplemental leucovorin rescue.

Blood Cell Count↗
PubMed1976

Sepsis with a new species of Corynebacterium.

Sepsis with a previously undescribed species of Corynebacterium was documented in four patients. All patients had predisposing illness at the time of infection, three patients having leukemia in relapse and one having a porencephalic cyst and a ventriculoatrial shunt. The isolates from blood cultures had a characteristic metallic sheen when grown on blood agar. They were resistant to most antibiotics tested, including the penicillins, but were uniformly sensitive to vancomycin. Common biochemical characteristics, the metallic sheen, and the unusual antibiotic sensitivity pattern suggest that these isolates comprise a new species or group of closely related species of Corynebacterium that is capable of infection in man.

Adult↗
PubMed1971

Comparative production of interferon by human fetal, neonatal, and maternal cells.

Production of interferon was studied in fibroblasts cultured from human fetal, neonatal, and maternal tissue. Human fetal and maternal cells were paired to diminish genetic variability. Fetal cells displayed an increased response to two inducers of interferon, virus and synthetic double-stranded ribopolynucleotide. Fetal cells released 300-fold more interferon than maternal cells on exposure to poly rI:rC. This enhanced capacity for interferon production was consistent in cultures developed from fetal skin obtained between the 10th and 20th gestational week. The response was relatively stable, persisting in cells cultured for 18 generations (about 14 weeks). On infection with Newcastle disease virus, fetal cells produced, on the average, 4 to 6.5 times more interferon than maternal or neonatal cells. The virus was adsorbed with equal efficiency by each type of cell. Increased production is apparently independent of the rates of overall protein synthesis, since fetal and maternal cells have very similar rates of total protein synthesis.

Journal Article↗
PubMedDate not supplied

Cyclophosphamide, doxorubicin, and cisplatin in the treatment of advanced non-small cell lung cancer.

Fifty-four patients with non-small cell lung cancer were treated with a combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). A 35% response rate was seen, with a median survival of 380 days for the responders, compared to median survival times of 150 days for the nonresponders and 229 days for the group. Twenty-four percent of these patients had received prior treatment. All of the nonresponding patients had died by 438 days, whereas eight of 19 responders lived greater than 425 days. The survival curve the nonresponders was similar to that for a historical control group not given chemotherapy. These data indicate that this drug regimen has some efficacy in the treatment of non-small cell lung cancer.

Aged↗