Showing papers by "St. Jude Children's Research Hospital published in 1975"
TL;DR: Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL.
Abstract: A study was performed to evaluate the clinical and histopathologic characteristics of a distinctive degenerative lesion within the central nervous system (CNS) of children with acute lymphocytic leukemia (ALL). Of the 231 patients in this study, 13 were found to have specific degenerative changes in telencephalic white matter. Morphologically, the principal changes consisted of diffuse reactive astrocytosis and multiple, noninflammatory necrotic foci, often containing varying amounts of mineralized cellular debris. Clinical features common to all patients with this leukoencephalopathy were: 1) cranial irradiation of 2000 rads or more and 2) methotrexate administered systemically after irradiation. Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL. Age at time of irradiation, bacterial infections, nutrition, and CNS leukemia were not causally related to the development of this disease. This study suggests that chemotherapeutic agents may diffuse through the blood-brain barrier following CNS irradiation of 2000 rads or more.
459 citations
TL;DR: Findings indicate that brain adenylate cyclase required an activator for activity and that this activator is functionally identical to the protein activator of phosphodiesterase (J.B.C. 249: 4943–4954, 1974).
339 citations
TL;DR: Two neuropsychologic studies were performed to determine the long-term effects of "prophylactic" cranial or craniospinal irradiation on the psychologic and neurologic functions of children with acute lymphocytic leukemia.
Abstract: Two neuropsychologic studies were performed to determine the long-term effects of "prophylactic" cranial or craniospinal irradiation on the psychologic and neurologic functions of children with acute lymphocytic leukemia. In a prospective study, 34 patients with leukemia who received either craniospinal irradiation or cranial irradiation combined with intrathecal methotrexate were evaluated by standardized neurologic and psychologic examinations before and after irradiation. Their performance was compared with that of 27 controls who received irradiation to parts of the body other than the cranium. In a retrospective study, 11 patients with leukemia receiving prophylactic craniospinal irradiation and 12 controls with the disease not receiving such therapy were followed from the second year after either irradiation or the initial hematologic remission. Eighteen months after irradiation in the prospective study and four years after irradiation in the retrospective study, no noteworthy neurologic or...
167 citations
TL;DR: One hundred and forty‐nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents.
Abstract: One hundred and forty-nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, ediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.
165 citations
TL;DR: The results showed that the more massive or extensive the disease at diagnosis, the poorer the outcome and patients with excellent responses to therapy were found with each factor of poor prognosis.
Abstract: The relationship of a variety of initial features and the outcome of therapy was analyzed for 363 children with acute lymphocytic leukemia (ALL). All had entered "total therapy" studies between 1962 and 1971. The standard for comparing outcome of therapy was whether patients with a given feature attained or exceeded the median duration of complete remission, hematologic remission or survival for the group. The results showed that, in general, the more massive or extensive the disease at diagnosis, the poorer the outcome. Factors associated with a significantly poorer prognosis included: initial leukocyte count above 100,000/mm; spleen enlargement greater than 5 cm; mediastinal involvement and early CNS involvement. Children over 10 years old at diagnosis and Negro children also had a poor prognosis. From another viewpoint features were examined for patients who attained at least 3 years of continuous complete remission. This confirmed some earlier findings and, in addition, showed that children under 2 years of age at diagnosis or with hepatomegaly over 5 cm were less likely to attain this goal. With the exception of early CNS involvement, however, patients with excellent responses to therapy were found with each factor of poor prognosis. Two major factors were not analyzed because their relationship to prognosis is generally accepted: therapeutic differences and acute nonlymphocytic leukemia.
158 citations
TL;DR: The surface composition of thrombasthenic membranes by the lactoperoxidase iodination technique is investigated and a low concentration of glycoprotein II is found, and other molecular differences are found.
Abstract: THE platelet plasma membrane contains several proteins of different molecular weights. Three of these proteins stain for carbohydrate with periodic acid–Schiff reagent and have been termed glycoproteins I, II and III (molecular weights 150,000, 124,000 and 106,000, respectively)1,2. It has been suggested that the bleeding tendency observed in Glanz-mann's thrombasthenia results from abnormalities of the platelet membrane3–6. Nurden and Caen7 showed that glycoprotein II was absent in a crude membrane fraction isolated from thrombasthenic platelets. We have now investigated the surface composition of thrombasthenic membranes by the lactoperoxidase iodination technique2 and found a low concentration of glycoprotein II, and other molecular differences.
142 citations
TL;DR: The progressive improvement in the prognosis of acute lymphocytic leukemia has been a result of the more efficient use of chemotherapeutic agents, particularly the use of combinations of agents, but further studies are needed to improve the efficacy and reduce the toxicity of therapy.
Abstract: The progressive improvement in the prognosis of acute lymphocytic leukemia has been a result of two major developments: 1) the more efficient use of chemotherapeutic agents, particularly the use of combinations of agents and the discovery that agents effective at one stage of disease may be inappropriate at another stage, and 2) the prevention with irradiation of central nervous system relapse. As many as one-half of children with this disease may enjoy long-term leukemia-free survival. However, further studies are needed to improve the efficacy and reduce the toxicity of therapy. This paper reviews the evolution of some of these studies.
111 citations
TL;DR: With the longer remissions and survivals now commonly observed, a concerted effort is needed to minimize side effects while trying to improve further the efficacy of therapy.
Abstract: An overview is presented of the improvements in the prognosis of acute lymphocytic leukemia due to combined modality therapy. With the best available regimens, approximately 50% of these children have remained leukemia-free for 5 years or more. Because of these results, there is growing concern for the quality of survival and for the side effects of therapy. A case in point is a completely unexpected side effect in a current study. Nonleukemic leukoencephalopathy has developed in 8 of 20 children given intravenous methotrexate, 50-80 mg/m2 per week, as the sole agent following remission induction and CNS therapy. Thus, with longer remissions and survivals now commonly observed, a concerted effort is needed to minimize side effects while trying to improve further the efficacy of therapy.
99 citations
TL;DR: Within the employed limits of dosage, small quantities of podophyllum were as effective as larger quantities in potentiating the response to Ara-C and the epipodophyllotoxins, VM- 26 and VP 16–213.
84 citations
TL;DR: It is concluded that Sendai virus morphogenesis does not require HN as a structural element or any function supplied by HN, and other consequences of the mutation were marked lessenings of cytopathology and cell protein synthesis inhibition during infections at nonpermissive temperature.
83 citations
TL;DR: Although the activities of the enzyme and the activator paralleled one another on a subcellular basis, they varied from tissue to tissue and during ontogenetic development of the tissues, which suggests variability may be a result of cellular heterogeneity or multiple forms of phosphodiesterase.
TL;DR: While most of the affected children suffered a mild transient illness, 1 patient died as a result of bladder hemorrhage, and the doses of cyclophosphamide received by these children ranged widely and did not correlate with the severity of the cystitis.
Abstract: The records of 314 children with acute lymphocytic leukemia (ALL) were reviewed to determine the frequency, clinical and laboratory features; contributing factors; and prognosis of cyclophosphamide-induced hemorrhagic cystitis. Twenty-five well-documented cases of hemorrhagic cystitis were identified. While most of the affected children suffered a mild transient illness, 1 patient died as a result of bladder hemorrhage. The doses of cyclophosphamide received by these children ranged widely and did not correlate with the severity of the cystitis. The frequency of this complication did not differ significantly with sex, age or route of administration. However, cystitis was over twice as frequent in black children as in white. Nineteen of 25 cases occurred in the spring and summer months. The group of affected children did not differ significantly from a matched control group in terms of total drug dosage received, incidence of systemic toxicity, mean urine specific gravity, or overall survival.
TL;DR: The anionic-exchange resin technique utilizing isotopically labeled cyclic AMP and an auxiliary enzyme, 5′-nucleotidase, for the assay of phosphodiesterase does not accurately measure the enzyme activity due to adsorption of the product (adenosine or guanosine) by the resin.
TL;DR: It is concluded that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.
Abstract: Summary.
The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 μm, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T- and B-cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)—a T-cell marker. E-rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T-cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.
TL;DR: Viremia was not related to the duration, type or number of drugs used in immunosuppression, nor to the hematologic status of leukemia, and leukopenia, neutropenia, total lymphocyte count, fourfold rise or fall in complement-fixing titer, and viruria had no consistent relationship to viremia or clinical CID.
TL;DR: A group of avian influenza viruses with hemagglutinin subunits related to those of the 1957 Asian influenza virus and possibly also toThose of the virus that caused the influenza epidemic in 1889 are postulated.
TL;DR: The results are encouraging in an otherwise high mortality situation and the proportion of patients achieving long-term tumor-free survival after surgery was encouraging.
TL;DR: The current status of Pneumocystis Carinii Pneumonitis is discussed in this paper, where the authors present a review of the state of the art in this area.
Abstract: (1975). Current Status of Laboratory Diagnosis of Pneumocystis Carinii Pneumonitis. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 6, No. 2, pp. 145-170.
TL;DR: It is concluded that the platelet antiplasmin and the serum antiplAsmin are very similar and may be useful in fibrinolytic therapy.
Abstract: Summary A low molecular weight antiplasmin has been detected in human blood platelets. The antiplasmin is dialysable and a similar material is present in normal plasma. A simple method for rapid isolation of the antiplasmin based on ultrafiltration is described. The inhibition of plasmin by these materials under different conditions has been studied. In the ultracentrifuge, both antiplasmins showed a single broad peak with an approximate sedimentation coefficient of 0.5S. Paper chromatography and paper electrophoresis indicated the isolated material to be heterogeneous. The individual components were isolated by paper chromatography and the antiplasmin activity was measured by the fibrin plate method. Preliminary studies on the fraction with maximal antiplasmin activity suggest that the inhibitory effect might be due to enzyme-inhibitor complex formation. Based on the present data, it is concluded that the platelet antiplasmin and the serum antiplasmin are very similar. This antiplasmin material may be useful in fibrinolytic therapy.
TL;DR: It is suggested that neither of these two activities but a third enzyme is responsible for the ultraviolet-irradiated DNA-specific endonuclease activity observed in crude cell extracts.
TL;DR: The effect of extensive iodination on mitochondrial membranes limits the amount of iodide which can be incorporated with the lactoperoxidase membrane-labeling procedure when this technique is used as a surface probe of mitochondrial membranes.
TL;DR: Inadequate postnephrectomy irradiation or infiltration of the liver by nephroblastoma cells appeared to be predisposing factors in the development of these reccurrences.
TL;DR: The data suggest that methotrexate reduces the rate of DNA replication by inhibiting chain initiation independently of chain elongation.
Abstract: The rate of DNA synthesis in cultures of human lymphoblasts decreased more than 80% within 30 min after the cells were exposed to methotrexate, a potent inhibitor of dihydrofolate reductase. Despite this rapid initial inhibition, DNA continued to be synthesized for at least an additional 6 h. The mode of this subsequent replication appeared to be semiconservative, as indicated by the buoyant density of 5-bromodeoxyuridine-substituted DNA in alkaline CsCl gradients. The growth rates of DNA chains in cells exposed to methotrexate were determined by sedimentation rate analysis in alkaline sucrose gradients. DNA synthesized during 2-min or 10-min pulses with labeled deoxycitidine in the presence of methotrexate had about the same sedimentation coefficient, 35 S, as controls. When methotrexate-treated cultures were pulse-labeled for 10 min and then chased for various times, DNA fragments of about 80 S accumulated. DNA synthesized in the presence of methotrexate was stable and elongated to bulk-size DNA after methotrexate inhibition of growth was removed by addition of thymidine and deoxycytidine. The data suggest that methotrexate reduces the rate of DNA replication by inhibiting chain initiation independently of chain elongation.
TL;DR: Data indicate that CCRF-CEM cells have 10- to 20-fold more DHFR than required for cell division, which suggests that MTX inhibition of cell division resulted from the inhibition of DHFR.
TL;DR: Results show that CNP therapy provides an effective means of improving arterial oxygenation in spontaneously breathing older children, just as in neonates, without the need for endotracheal intubation, prolonged sedation, and muscle relaxants.
TL;DR: Findings indicate that the increase of phosphodiesterase is not accompanied by its activator and that the two proteins are controlled by separate genes.
TL;DR: Topical poly(I:C), as used in this study, was of no benefit in treatment of localized herpes zoster and neither the concentration nor the total dose of drug was related to the outcome of infection.
Abstract: Twenty-four children with cancer and localized herpes zoster were randomized to receive either topical polyinosinic acid-polycytidylic acid [poly(I:C)] or a saline placebo. Solutions containing 1.0 or 2.5 mg of drug per ml were applied to the lesions every 3 h, seven times a day for 7 consecutive days. Serial, standardized color photographs were used to evaluate the progression of lesions and maximum percentage of dermatome involvement. In patients receiving poly(I:C), the median days of new lesions after therapy was 2.0 days as opposed to 3.5 days in placebo-treated patients. This difference was not statistically significant. Moreover, the total median days of lesions and percentage of dermatome involvement were similar in both groups, as were complications. Neither the concentration nor the total dose of drug was related to the outcome of infection. We conclude that topical poly(I:C), as used in this study, was of no benefit in treatment of localized herpes zoster.
TL;DR: It was observed that complexing these receptors potentiates, rather than inhibits, platelet aggregation by thrombin or by adenosine diphosphate, and blocking of the thrombosthenin sites is necessary for sensitization of platelets.
Abstract: Summary The first step in thrombin-induced aggregation of blood platelets is binding of thrombin to specific receptors on the platelet membrane. Elucidation of the nature of this receptor in human platelets was attempted using radioactively labelled thrombin. In disc gel electrophoresis an extract of thrombin-treated platelets showed one peak of radioactivity near the origin. Gel filtration of the platelet extract through Sephadex G-200 showed mainly one protein peak at the void volume which contained radioactivity. After column fractionation the final isolate reacted with antiserum to thrombosthenin but did not react with antiserum to serum, fibrinogen or soluble platelet proteins. Gel electrophoresis of the reduced isolate in the presence of sodium dodecyl sulphate showed a pattern similar to thrombosthenin. To explore the possibility that thrombosthenin might be the receptor of thrombin, attempts were made to complex the receptor sites with thrombosthenin antibody or its univalent fragment. It was observed that complexing these receptors potentiates, rather than inhibits, platelet aggregation by thrombin or by adenosine diphosphate. Univalent fragment of antibody to albumin failed to cause this potentiation. Thus, blocking of the thrombosthenin sites is necessary for sensitization of platelets.
TL;DR: The differential increase of cAMP phosphodiesterase by B 2 cAMP and the disparate reduction of cGMP phosphodiedterase in the transformed cell suggest that the two enzymes are regulated separately.
TL;DR: Since the techniques employed were not helpful in preventing infection with cytomegalovirus in the immunosuppressed host, they have been discontinued at this hospital.
Abstract: Standard contagious isolation procedures were used for 83 patients with acute lymphocytic leukemia and serologic and/or cultural evidence of cytomegalovirus infection. The infection rate, as determined serologically, for 9 months before and 13 months during isolation procedures was not decreased. Since the techniques employed were not helpful in preventing infection with cytomegalovirus in the immunosuppressed host, they have been discontinued at this hospital.