Showing papers by "St. Jude Children's Research Hospital published in 1974"

Efficacy of Trimethoprim and Sulfamethoxazole in the Prevention and Treatment of Pneumocystis carinii Pneumonitis

Abstract: A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with P. carinii pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After P. carinii pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of P. carinii infection.

The molecular biology of paramyxoviruses.

Abstract: This review evaluates possible mechanisms which regulate paramyxovirus protein and RNA syntheses. Evidence indicates that viral polypeptide abundances are specified at the transcriptional level. RNA replication and transcription are competing processes utilizing an encapsidated single-stranded RNA template. The requirement for capsid proteins in RNA replication suggests that these proteins are positive control elements for replication of paramyxovirus RNA.

Sendai Virion Transcriptase Complex: Polypeptide Composition and Inhibition by Virion Envelope Proteins

Abstract: Sendai virions, disrupted in 2% Triton X-100 in 1 M KCl, were separated into nucleocapsids and envelope proteins by centrifugation. The nucleocapsids, representing 46% of the virion proteins, had a buoyant density of 1.29 gm/cm3 in D2O sucrose. RNA-dependent transcriptase activity associated with them had a ninefold greater specific activity than transcriptase assayed in unfractionated detergent-disrupted virions. These enzyme-active nucleocapsids contained only two polypeptides, the largest virion polypeptide (molecular weight 75,000) and the nucleocapsid structure unit (molecular weight 60,000). Virion envelope proteins, either glycoproteins or nonglycosylated matrix protein, inhibited nucleocapsid-associated polymerase activity; brief heat denaturation abolished their inhibitory activity. Yeast RNA stimulated nucleocapsid-associated enzyme, suggesting that stimulatory polyanions act at the enzyme-template level.

Classification of chronic myelocytic leukemia in children.

Abstract: The present study was undertaken to define criteria for classification of chronic myelocytic leukemia in children and adolescents From April, 1963 through July, 1971, 18 patients were available for study Evaluation of the clinical, laboratory, and histopathologic features demonstrates three distinct subgroups: adult, juvenile, and familial chronic myelocytic leukemia Parameters of most value in this distinction are the level of the white blood cell count, presence of thrombocytopenia or thrombocytosis, the bone marrow myeloid to erythroid ratio, and the presence or absence of well-defined malpighian corpuscles in the spleen One patient with acute lymphocytic leukemia in remission manifested some unique features and may represent a fourth form of chronic myelocytic leukemia, resulting from previous chemotherapy or irradiation The use of chemotherapy has not significantly prolonged survival in our patients Two patients with familial chronic myelocytic leukemia are surviving in remission 9 years following splenectomy

The initial attack of acute rheumatic fever during childhood in North India. A prospective study of the clinical profile

Abstract: A prospective study was done to determine the clinical profile of first attacks of acute rheumatic fever in children in North India. Unlike other reports, the clinical profile described here closely resembles the spectrum prevalent in the West. Arthritis, the most common manifestation, was seen in 66.6% of the 102 patients, chorea in 20.7%, and carditis in 33.7%. Carditis was considered mild in 22 patients and severe in 12; a persistent elevation of sleeping pulse rate and mitral regurgitation was noted in each case. Patients with severe carditis also had significant cardiomegaly and apical mid-diastolic murmur. Two patients with severe carditis developed congestive heart failure; one of them had pericarditis as well. Murmur of aortic origin was not noted in this series. One patient with severe carditis died from the disease. Erythema marginatum was noted in two, both of whom had severe carditis. There were two instances of subcutaneous nodules, one with and one without carditis. The close similarity of t...

Binding of thrombin to human platelets.

Abstract: MUCH work has been carried out aimed at elucidating the mode of action of thrombin on platelets1–5. These studies were based on the assumption that hydrolysis of a protein by thrombin constitutes the primary event culminating in aggregation of platelets. Results of recent studies suggest that the primary step in this process might be binding of thrombin to a receptor site, triggering viscous metamorphosis of the platelets6,7. The processes of binding and proteolysis need not be mutually exclusive, however, binding may be followed by proteolysis. Here I present direct evidence of thrombin binding by human platelets and discuss some of its implications.

Cessation of Therapy during Complete Remission of Childhood Acute Lymphocytic Leukemia

Abstract: To assess the need for prolonged therapy in acute lymphocytic leukemia in remission, we studied the course of 132 patients removed from therapy after two to three years of remission. The median period off therapy was 21 months, with a range of one month to 7.5 years. Of the patients removed from therapy, 21 have relapsed (16 per cent). Of the patients who relapsed, six had not received specific Central-nervous-system therapy. We conclude that (1) programs for treatment of childhood acute lymphocytic leukemia have resulted in an impressive number of long-term leukemia-free survivals even after cessation of all therapy, (2) the likelihood of relapse after therapy is stopped is greatest in the first year, (3) relapse was more frequent in patients who had not received Central-nervous-system irradiation, and (4) no other feature was found to predict whether relapse would occur after stopping therapy. (N Engl J Med 291:1230–1234, 1974)

Isolation and Characterization of Sendai Virus Temperature-Sensitive Mutants

Abstract: Ten temperature-sensitive mutants of Sendai virus, a paramyxovirus, were isolated and partially characterized. The mutants replicated in chicken embryo lung cells at 30 C, but not at 38 C; wild-type virus grew equally well at both temperatures. Complementation tests divided the mutants into seven groups. Six groups synthesized neither infectious virus nor RNA when incubated at 38 C from the beginning of infection. Temperature shift-up experiments demonstrated that three of these complementation groups were blocked in early steps required for RNA synthesis, but these gene functions were not needed throughout the replicative cycle. In contrast, the other three RNA-negative complementation groups were defective throughout the replicative cycle in functions required for virus-specific RNA synthesis. Only one mutant, which complemented all of the above, synthesized RNA but not infectious virus when placed at 38 C; the hemagglutinin of this mutant functioned only at the permissive temperature.

T- and B-lymphocytes and lymphoblasts in untreated acute lymphocytic leukemia.

Abstract: This study demonstrates in the peripheral blood and bone marrow of patients with untreated acute lymphocytic leukemia (ALL) the coexistence of two main subpopulations of lymphoid cells: 1) small lymphoid cells which bear the same surface markers as normal lymphocytes; and 2) blasts which in the majority of the patients lack these markers. The proportions of cells bearing different cell-surface markers were studied in 14 children with ALL at time of diagnosis. Thymus-dependent (T) cells were identified by spontaneous formation of rosettes with sheep erythrocytes, and thymus-independent (B) cells by immunofluorescence of surface immunoglobulins. Using these criteria we demonstrated small lymphocytes with T- or B-markers in the peripheral blood or bone marrow of all patients assayed. In contrast, in 10 of 14 children the blasts had no detectable markers. However, in 2 patients more than half of bone marrow blasts had T-cell surface receptors, and in another 2 the proportion of blasts forming rosettes was 2% and 17%. The initial blast cell count in peripheral blood was greater than 105/mm3 in both children with the higher proportion of T-lymphoblasts. An additional initial clininal feature in one of them was the presence of a large anterior mediastinal mass, probably thymus. After successful induction of remission there was an increase in the proportion of normal T-lymphocytes in the bone marrow of 9 children assayed. The results from this study suggest that the presence of T-lymphoblasts, which may be of thymic origin, is correlated with a more advanced disease at time of diagnosis.

Splenectomy and chemotherapy in acute myelocytic leukemia of childhood

Abstract: This study was undertaken to explore the therapeutic and diagnostic value of splenectomy for children with acute myelocytic leukemia (AML) in remission. Of 29 consecutive untreated patients entering the study, 19 attained complete remission with mercaptopurine, vincristine, and 6-azauridine. Chemotherapy during remission consisted of mercaptopurine daily and cytosine arabinoside weekly. Because remission lasted 2 months or less in 5 patients, they did not undergo splenectomy. Fourteen patients underwent splenectomy while clinically in complete remission. Splenectomy was tolerated well with no major complications. Gross abnormalities of the abdominal organs were found in 11 patients. Histologic leukemia was found in 12 patients, most often in the spleen. Negro children did not respond to therapy as well as Caucasian children. Central nervous system (CNS) leukemia terminated clinical remission in 7 of the 14 patients. Four patients remain in initial CNS and hematologic remission for 18 to 24 months, and four others remain in initial hematologic remission for 16 to 18 months. These results suggest that in children with AML, splenectomy may influence the activity of leukemia and prolong the duration of remission.

Concurrent chemotherapy and radiation therapy in the treatment of childhood and adolescent Hodgkin's disease

Abstract: A treatment program of combination chemotherapy and concurrent radiotherapy was designed for children and adolescents with all stages of Hodgkin's disease. From September, 1967 to April, 1972, 49 patients with previously untreated disease were admitted to the study. They were given 12 weeks of initial chemotherapy in combination with simultaneous radiotherapy at a tumor dose of 3500 to 4000 R. For Stages II-IV chemotherapy was continued for 1 to 2 years. Forty-seven patients responded to therapy with complete remissions; two had no response. Of the patients responding, 40 have been in continuous complete remission for periods of 6 to 58 months, four have relapsed, and three have died in remission. Twenty-six patients have been off all therapy for periods of 4 to 54 months without evidence of active disease. In most instances complications of therapy including drug toxicity, infections and nutritional disturbances have been reversible by modification of chemotherapy and judicious supportive care. We conclude that combination chemotherapy and concurrent irradiation are tolerated by children and adolescents with Hodgkin's disease and result in a high frequency of complete remission. Results to date suggest that the majority of children, even those with advanced stages, will have lengthy complete remissions.

Fatal Bacillus cereus pneumonia and sepsis in a child with cancer.

Abstract: From the Infectious Diseases Service, St. Jude Children’s Research Hospital and the Laboratory of Clinical Bacteriology. Supported by General Research Support Grant RR05584, and Childhood Cancer Research Center Grant CA-08480, National Cancer Institute, from the National Institutes of Health and by ALSAC. * Correspondence to Sandor Feldman, M.D., Infectious Diseases Service, St. Jude Children’s Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, Tenn. 38101. PECIES of the Bacillus genus are motile, gram-positive, aerobic, spore-forming rods found widely in air, soil, water, milk, and feces.’ Except for the highly virulent Bccccillrcs anthracis, members of this genus are generally considered saprophytes or laboratory contaminants when isolated from clinical specimens. At times, however, Bacillus cereus has been implicated as the etiologic agent in pneumonia, 2.3 purulent pleuritis,~ ophthalmitis,’ food poisoning,6>7 meningitis,’ and bacteremia as a complication of hemodialysis.9 One case of fatal B. cereus pneumonia has been reported in a cancer patient.~ 2

Life span of erythrocyte membrane protein.

Abstract: IN most types of cells the protein constituents of the cytoplasm are constantly being degraded and synthesised1–6. When the proteins in these cells are labelled with a protein precursor, the label disappears from the protein with first order kinetics. The amount of any protein in the cell then is regulated by the rate of its synthesis and degradation, and recent work indicates the importance of this process as a regulatory mechanism in mammalian cells. In contrast, when haemoglobin, which comprises 90% of the protein of the mature mammalian erythrocyte, is labelled, it does not decay with first order kinetics, but survives for a finite period. It disappears from the vascular bed when the intact erythrocyte is removed from circulation. Thus, haemoglobin labels provide excellent material for studies of the life span of the red cell.7

Disseminated histoplasmosis and childhood leukemia.

Abstract: The course of histoplasmosis in patients with childhood leukemia is poorly understood. Past attempts to characterize the disease have relied on single case reports, without benefit of a series of patients with similar types of leukemia and chemotherapy. Described here are the clinical course of infection, laboratory findings, and therapy in six children with acute lymphocytic leukemia and disseminated histoplasmosis. A diagnosis of histoplasmosis was most commonly encountered during remission of the leukemia in patients presenting with fever, hepatosplenomegaly, variable chest roentgenogram findings, leukopenia, and/or neutropenia. Bone marrow cultures revealed the presence of Histoplasma capsulatum in each. All six children were treated with amphotericin B and recovered from the infection.

Micromethod for Determining Total Iron-Binding Capacity by Flameless Atomic Absorption Spectrophotometry

Abstract: Because of the large quantities of venous blood required, assays of total iron-binding capacity (TIBC) and serum iron are often omitted in diagnostic tests involving small children. As an alternative to the conventional method of assessing TIBC, we developed a micromethod based on flameless atomic absorption spectrophotometry (flameless AAS). Additionally, the standard microprocedure for determining serum iron was modified so that iron concentration could be estimated from the same iron standards used to calculate TIBC. With these procedures, only 20 µl of serum is required to prepare protein-free supernate for measurement of TIBC or serum iron with an atomic absorption spectrophotometer equipped with a graphite furnace and a recorder. The resulting TIBC, serum iron, and computed transferrin saturation values compared well with those obtained by conventional flame atomic absorption spectrophotometry. The correlation was statistically significant at the 99% confidence level. These flameless AAS micromethods provide an accurate and sensitive means of determining both TIBC and serum iron in a total of 40 µl of serum, a quantity easily collected from a fingertip puncture, and hence are appropriate for routine laboratory work in pediatric clinics and for large-scale nutrition surveys.