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Biomedical subjects

R T O'Brien

Publications and source records attributed to R T O'Brien.

15 recordsLinked 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

Enterovirus inactivation in soil.

The inactivation of radioactively labeled poliovirus type 1 and coxsackievirus B 1 in soils saturated with surface water, groundwater, and septic tank liquor was directly proportional to temperature. Virus persistence was also related to soil type and the liquid amendment in which viruses were suspended. At 37 degrees C, no infectivity was recovered from saturated soil after 12 days; at 4 degrees C, viruses persisted for at least 180 days. No infectivity was recovered from dried soil regardless of temperature, soil type, or liquid amendment. Additional experiments showed that evaporation of soil water was largely responsible for the decreased recovery of infectivity from drying soil. Increased rates of virus inactivation at low soil moisture levels were also demonstrated.

Adsorption

Structural changes associated with poliovirus inactivation in soil.

The loss of infectivity of poliovirus in moist and dried soils was a result of irreversible damage to the virus particles. The damage included (i) dissociation of viral genomes and capsids and (ii) degradation of viral ribonucleic acid (RNA) in the soil environment. Under drying conditions, capsid components could not be recovered from the soils. Further studies in sterile soils indicated that, under moist conditions, the viral RNA was probably damaged before dissociation from the capsid. However, in sterile, dried soil, RNA genomes were recovered largely intact from the soil. These results suggest that polioviruses are inactivated by different mechanisms in moist and drying soils.

Adsorption

Structural and compositional changes associated with chlorine inactivation of polioviruses.

Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.

Capsid

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

Iron burden in sickle cell anemia.

Total body iron burden was estimated by two indirect methods in 23 patients with sickle cell anemia. Concentrations of serum ferritin correlated directly and significantly with age of the patients. Eleven of 15 patients under 20 years of age had normal levels of serum ferritin. Deferoxamine-induced urinary excretion of iron was considerably less than that reported in patients with thalassemia major who were receiving regular blood transfusions. These data imply that patients with sickle cell anemia generally do not acquire excessive iron burdens during the first two decades of life. The risks of transfusional hemosiderosis in patients with sickle cell anemia who are included in hypertransfusion programs are discussed.

Adolescent

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

Inactivation of polioviruses and coxsackieviruses in surface water.

Inactivation rates of polioviruses 1 and 3 and coxsackieviruses A-13 and B-1 were determined in situ in the Rio Grande in southern New Mexico, using membrane dialysis chambers. Inactivation of the viruses was exponential, and the rates of inactivation were apparently affected principally by the water temperature. Stability of the viruses in river water differed, with poliovirus 1 and coxsackie B-1 being most stable. Typically 1-log reductions of infectivity at water temperatures ranging between 23 and 27 degrees C required 25 h for poliovirus 1, 19 h for poliovirus 3, and 7 h for coxsackie virus A-13. At water temperatures of 4 to 8 degrees C, the log reduction times for poliovirus 1 and coxsackievirus B-1 were 46 and 58 h, respectively. Results obtained with labeled poliovirus 1 and coxsackievirus B-1 and with infectious ribonucleic acid indicate that inactivation was due to damage to viral ribonucleic acid. Virus-inactivation rates were also affected by heat sterilization of river water, indicating the presence of a heat-labile or volatile inactivating factor. The inactivating factor in Rio Grande water was apparently present at a constant concentration over a 1-year period.

Enterovirus

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

Gas chromatographic presumptive test for coliform bacteria in water.

A gas chromatographic procedure which shows promise as a presumptive test for coliform bacteria in water is described. Total coliform bacteria concentrations were determined from the incubation times at 37 C required for ethanol to be produced. Fecal coliform densities were determined in a similar manner at 44.5 C. The culture medium was filter sterilized M-9 salts supplemented with 1% lactose, 0.1% Casamino Acids, and 0.1% yeast extract. Best results were obtained when the initial total coliform concentrations were 5 per ml or higher and when fecal coliform concentrations were 50 per ml or higher. Minimum detection times at these concentrations were 9 and 12 h, respectively.

Chromatography, Gas