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Biomedical subjects

S McIntosh

Publications and source records attributed to S McIntosh.

At least 55 records · Page 3Linked to original sources

Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leukemia of childhood.

Two groups of children with refractory acute lymphoblastic leukemia were treated with a regimen of methotrexate (MTX) and asparaginase (Asn'ase) based on studies of the effect of MTX in vitro on human lymphoblasts exposed to Asn'ase. Induction therapy in 12 children produced 4 complete remissions, 3 partial remissions, and 5 failures. Responsiveness to Asn'ase seemed necessary for successful induction with the drug combinations. Maintenance therapy in 18 children produced a median hematologic remission of 31 weeks (range 3-85 weeks). During remission, 2 children developed central nervous system leukemia and 2 died of infection. The mean maximally tolerated dose of MTX was 361 mg/m2. The results of this trial suggest therapeutic synergy in maintenance therapy and the capability of Asn'ase to attenuate MTX toxicity.

Adolescent↗

High dose cytosine arabinoside (HDARAC) in refractory acute leukemia.

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.

Acute Disease↗

Chemotherapy as an adjunct in the initial management of cerebellar medulloblastomas. A preliminary report.

Eight consecutive children with biopsy-proven cerebellar medulloblastoma were treated with a combination of whole neuraxis radiation and prolonged chemotherapy using vincristine and cyclophosphamide. There was no evidence of tumor recurrence in the follow-up period, which ranged from 16 months to 7 years and 8 months following diagnosis. Morbidity associated with this regimen has been infrequent and easily reversible.

Administration, Oral↗

Antibody-mediated acquired sideroblastic anemia: response to cytotoxic therapy.

A 5 1/2-yr-old child developed severe anemia with erythroid hypoplasia and 50% ringed sideroblasts in his bone marrow. A serum inhibitor of erythropoiesis was demonstrated, utilizing syngeneic and autologous bone marrow in a plasma-clot culture system. The IgG fraction of the patient's serum effected similar suppression of erythroid colony formation. Prednisone therapy was ineffective, but following treatment with cyclophosphamide, normal erythropoiesis was established, ringed sideroblasts disappeared, and his serum no longer inhibited erythropoiesis in vitro. Cyclophosphamide was discontinued, and the patient has remained hematologically normal. This patient is an example of antibody-mediated sideroblastic anemia successfully treated with a cytotoxic drug.

Anemia, Sideroblastic↗

Fanconi's anemia: the preanemic phase.

Anticipation of Franconi's anemia prior to the development of overt marrow aplasia may prevent some morbidity and mortality from infectious and hemorrhagic complications. A presumptive diagnosis was made in a firstborn child and radial anomalies, small size, elevated fetal hemoglobin, intermittent excessive chromosome breakage and elevated T-antigen expression in fibroblasts infected with Simian virus 40. Serial studies may help identify infants and young children at risk to develop this type of constitutional marrow hypoplasia.

Anemia, Aplastic↗

Double primary cancers in 2 young sibs, leukemia in another, and dextrocardia in a fourth.

Two brothers developed multiple primary neoplasms in childhood; one had glioblastoma and non-Hodgkin's lymphoma at age 11 years, and the other brain tumor and acute leukemia at six years. A third brother died with myelogenous leukemia at thre years, and a fourth with cyanotic congenital heart disease at 11 weeks. Each child also had at least one hamartomatous lesion of the skin. The clinical features suggested von Recklinghausen's neurofibromatosis or other inherited cancer syndrome, but laboratory studies identified no markers of susceptibility to familial neoplasia.

Acute Disease↗

Methotrexate hepatotoxicity in children with leukemia.

Percutaneous liver biopsy was performed on seven children with acute lymphocytic leukemia who had received maintanance chemotherapy with high-dose intravenous methotrexate for 1 1/2 to 2 1/2 years. Portal fibrosis was found in four of the seven children and in an additional patient treated with oral methotrexate. Serial tests of liver function and 99mtechnetium-sulfur-colloid scans did not accurately identify children with hepatic fibrosis. Clinical evidence of liver disease was not seen.

Adolescent↗

Intracranial calcifications in childhood leukemia. An association with systemic chemotherapy.

Children with acute lymphocytic leukemia were examined for evidence of intracranial calcifications with roentgenograms of the skull and computerized tomography. Of 39 children in their initial complete remission, ten were found to have subcortical cerebral calcifications. Significant associations were found between the presence of cerebral calcifications and systemic treatment with large cumulative doses of methotrexate.

Adolescent↗

Prospective analysis of bone changes in treated childhood leukemia.

Serial knee radiographs were obtained from 58 children with leukemia. Leukemic bone changes were found in approximately half of those radiographed at the time of diagnosis but were consistently absent in children older than 10 years. The bone abnormalities persisted for as long as 10 months after treatment was started and did not occur or reappear at the time of relapse. Dense metaphyses simulating the appearance of lead poisoning developed in 20 of 58 patients during chemotherapy.

Antineoplastic Agents↗

Chronic neurologic disturbance in childhood leukemia.

Twenty-three leukemic children were studied prospectively to detect chronic effects of therapy. All patients received CNS prophylaxis, including 2400 R cranial irradiation, and intermittent maintenance therapy with intravenous methotrexate, cyclophosphamide and cytosine arabinoside. Neurologic symptoms were observed in 12 patients, all of whom had intermittent limping and mild incoordination, between the 10th and 18th month of maintenance therapy. Five of the 12 sustained seizures and four of these had subsequent abnormalities in motor, perceptual, behavioral or language development. Three school-aged children have learning disability and perceptual-motor defects. Studies of CSF folate and MTX content are presented but not helpful in delineating the etiology of these neurologic symptoms.

Adolescent↗

Prospective study of sickle cell anemia in infancy.

Twelve infants with sickle cell anemia identified in the course of a cord blood screening program have been followed prospectively for up to three years of age. The development of hemolytic anemia paralleled the postnatal decline in fetal hemoglobin and was evident in all infants by 12 weeks of age. Vasoocclusive episodes occurred in more than half the infants and seven aplastic crises were documented in four patients. Febrile illnesses were common and one of the twelve infants developed pneumococcal sepsis. This study also demonstrated that functional asplenia is an acquired defect in sickle cell disease. The onset of functional asplenia was documented with splenic scans in six of the nine infants followed for more than one year after birth. There have been no deaths in this series.

Anemia, Aplastic↗

Erythropoietin excretion in the premature infant.

Urinary erythropoietin was determined sequentially in four premature infants throughout their period of physiologic anemia. After the first day of life, no erythropoietin was found, even though there was a marked fall in hematocrit. Among seven premature infants with severe respiratory disease, three excreted elevated amounts of erythropoietin. Premature infants appear able to respond to hypoxia by increasing erythropoietin production. In the absence of hypoxia, however, diminution of erythropoiesis in the early weeks of life is not accompanied by elevated excretion of erythropoietin.

Anemia↗