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Biomedical subjects

S B Murphy

Publications and source records attributed to S B Murphy.

At least 163 records · Page 9Linked to original sources

Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia.

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.

Adenosine Deaminase Inhibitors↗

Levels of 2'-deoxycoformycin, adenosine, and deoxyadenosine in patients with acute lymphoblastic leukemia.

2'-Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase, has recently undergone Phase I clinical trials and has been found to be therapeutically active in acute lymphoblastic leukemia. In this report, levels of dCF in plasma, plasma concentrations of adenosine and deoxyadenosine, and urine levels of deoxyadenosine were measured in leukemic patients undergoing treatment with dCF during a Phase I clinical trial. dCF was administered i.v. at a dose of 0.25 to 1.0 mg/kg (7.5 to 30 mg/sq m) for 3 consecutive days. Plasma drug levels of 2 to 6 microM were observed following the third dose of dCF, and drug accumulation occurred only at the 1-mg/kg dosage. In this limited series of patients, the plasma concentrations of adenosine and deoxyadenosine and the urine concentrations of deoxyadenosine did not show an obvious correlation with dCF dose, therapeutic response, or toxicity.

Adenosine↗

A randomized trial of combined modality therapy of childhood non-Hodgkin's lymphoma.

From 1975 to 1978, 69 children with non-Hodgkin's lymphoma were staged and treated in a randomized protocol to determine the contribution of involved-field radiotherapy (IF-RT) to an effective drug regimen in Stages III-IV and the efficacy of prophylactic treatment of the central nervous system with cranial irradiation and intrathecal methotrexate in Stage II-IV. Induction therapy for Stages I-II was vincristine, prednisone, cyclophosphamide and IF-RT (3000-3500 rad). Stages III-IV received the same three drugs plus adriamycin, and were randomized to received or not receive IF-RT. The complete remission rate was 88%. After randomization to receive CNS prophylaxis or not, all children received oral mercaptopurine and methotrexate for 18 months. The two-year actuarial estimate of disease-free survival for all responders is 55% and is significantly influenced by stage. (Ninety percent disease-free survival for Stages I-II, versus 38.8% for III-IV, P less than .05). We observed no benefit but added toxicity from IF-RT in Stages III-IV. Efforts at CNS prophylaxis in high-risk children are warranted, since only 1 of 18 children randomized to receive prophylaxis developed CNS disease as the site of first relapse, whereas 4 of 16 receiving no prophylaxis did so.

Adolescent↗

Nonglaucomatous cavernous degeneration of the optic nerve. Report of two cases.

The globes from two elderly women who underwent enucleation for malignant melanoma of the choroid showed cavernous degeneration of the optic nerve. Both individuals had prominent optic cups and a strong family history of severe cardiovascular disease; one patient also had mild anemia and substantial arteriosclerotic heart disease. Neither patient showed any clinical or histologic evidence of glaucoma. It is proposed that cavernous degeneration of the optic nerves in some patients may represent an aging change associated with generalized arteriosclerosis. Individuals with large optic cups may be more at risk of developing this condition.

Aged↗

Predicting the success of cataract surgery.

Fifty-four elderly patients with cataracts were tested with a questionnaire and a series of visual-motor learning and performance tasks immediately before, 7 weeks after, and 16 weeks after cataract surgery. The goal was to learn whether postoperative performance and questionnaire responses could be predicted from the preoperative tasks. Twenty-two elderly people without diagnosed cataracts did the same tasks at comparable intervals to establish normal performance levels and reliabilities. The amount of activity before surgery (walking, shopping, gardening, sewing, etc.) and the ability to learn a new visual-motor coordination were positively correlated with successful recovery as assessed by several measures including spontaneously expressed satisfaction.

Aged↗

Follicular (nodular) lymphoma in childhood: a rare clinical-pathological entity. Report of eight cases from four cancer centers.

Eight cases of follicular lymphoma (FL) were found amount 318 children with non-Hodgkin's lymphoma seen in two decades in four large institutions (overall incidence: 2.5%). The children's ages ranged from 3 to 13 years (median 8). Four patients presented with localized peripheral lymphadenopathy, two with tumors of the digestive tract, two with disseminated disease. Five were tentatively classified as stage I or II and 3 as stage IV. The existence of other diseases responsible for lymphadenopathy could satisfactorily be exclued. All patients are alive after follow-up periods of 1 to 14 years from diagnosis (median 4). Morphologically, 5 lymphomas were mixed and 3 histiocytic. The growth pattern was "expansile" in the younger patients (3 to 9 years), and "infiltrative," as in the adult disease, in the three older children (11 to 13 years). The histiocytic cytology correlated with stage IV disease. FL in children appears to be different from both its adult counterpart and the diffuse childhood lymphomas. Differences with the former include the absence of tumors of poorly differentiated lymphocytic type, the higher frequency of stage I-II disease and the better prognosis. This last feature, as well as the higher frequency of peripheral node involvement and the absence of leukemic conversion or CNS disease, differentiates the follicular from the diffuse childhood lymphomas.

Adolescent↗

Histoplasmosis mimicking childhood non-Hodgkin lymphoma.

Cell surface markers are becoming increasingly important in the diagnosis of malignant lymphoid diseases. We present a case of pulmonary histoplasmosis with a pleural effusion. The differential diagnosis included non-Hodgkin lymphoma because the pleural fluid cells were cytologically identical to convoluted lymphoblasts; the cells also formed rosettes with sheep erythrocytes at 37 degrees C, suggesting that they were malignant thymus-derived lymphoblasts. Since cultures of pleural fluid were negative for bacteria and fungi, the correct diagnosis of histoplasmosis was made only after conventional histology identified Histoplasma capsulatum organisms in pleural nodules. Thus, until we have a better understanding of the significance of cell surface markers, we should continue to rely on conventional histology for the diagnosis of lymphomas.

Child↗

Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse.

Seventeen intravenous abusers of methadone underwent clinical, roentgenologic and physiologic assessment. Two complained of dyspnea on exertion and two had cor pulmonale. Of 15 patients whose fundi were examined, nine had talc particles in their retinal vessels. The chest roentgenograms of seven showed a diffuse pin-point micronodular pattern and two of the seven also manifested volume loss, one with coalescence of opacities simulating progressive massive fibrosis. Twelve patients had some degree of pulmonary dysfunction, 10 with lowered steady state diffusing capacity and 11 with decreased flow rates (FEV1 and MMF). There was no hyperinflation, but two showed an increase in residual volume. Corticosteroid therapy was attempted on two and was ineffective. Necropsy on the one patient who died revealed severe pulmonary fibrosis and talc granulomas in lungs, liver, kidneys and lymph nodes.

Adult↗

Kinetic studies of cells in childhood leukemias.

A review of cell kinetic studies in acute childhood leukemia with a comparison of leukemic transformation of non-Hodgkin's lymphoma is presented in this paper. Leukemic cell populations have a longer cell cycle than their normal cell counterparts. The cell populations are comprised of proliferating and resting fractions and are capable of self-maintaining growth. Growth regulation is determined primarily by the size of the proliferating cell population or growth fraction. The growth fraction can vary as to site of disease, the clinical phase, following chemotherapeutic perturbation, and most importantly is related to the specific tumor cell type. Within a specific type of leukemia there is considerable variability of proliferative activity at time of diagnosis, but this variability bears no relationship to the subsequent clinical course. Those leukemias, such as the E rosette-positive form of lymphocytic leukemia characterized by rapid tumor growth and large tumor bulk, are also associated with tumor cell populations having larger growth fractions than standard lymphocytic leukemia. There is evidence for growth regulation of leukemic cell populations on systemic, regional, and, perhaps most importantly of all, intrinsic cell levels. It is this area of growth regulation for these tumor cell populations which currently needs the greatest research attention.

Acute Disease↗

Talc retinopathy.

We observed talc particles in the retinal vessels of nine out of 17 addicts to intravenous methadone. The retinopathy was found in patients who had injected more than 9,000 tablets. In seven the chest roentgenograms showed a diffuse micronodular pattern which progresses to resemble massive pulmonary fibrosis and is associated with severe disability. The ophthalmologist must recognize this entity since he may be the first to identify drug abusers who inject oral medications containing talc. Early detection and counselling may prevent the severe pulmonary complications.

Adult↗

Histiocytosis X: abnormal cerebrospinal fluid cytology in extrahypothalamic central nervous system involvement.

The clinical course and long-term survival of a patient with acute disseminated histiocytosis X and extrahypothalamic CNS involement were presented. The clinical significance of histiocytes appearing in the CSF cocomitant with the onset of this neurologic syndrome was discussed. Detailed cytologic examination of the CSF in patients with histiocytosis X and CNS involvement was recommended.

Cerebellar Ataxia↗