Biomedical subjects

P Schein

Publications and source records attributed to P Schein.

6 recordsLinked to original sources

PubMed1978

Fanconi syndrome associated with cephalothin and gentamicin therapy.

A case is reported of Fanconi syndrome and nonliquric renal failure, following a brief course of cephalothin and gentamicin, in a patient with diffuse histiocytic lymphoma. These drugs, especially when used in combination, have been associated with nephrotoxicity manifested as acute tubular necrosis and altered proximal tubular function, but biochemical evidence for generalized proximal tubular dysfunction has not been accurately defined. Thus far, only two other antibiotics, degraded tetracycline and streptozotocin, have been implicated in producing an acquired Fanconi syndrome.

Bacterial Infections↗

PubMed1978

Phase I studies on chlorozotocin.

A phase I investigation of chlorozotocin, a new-water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty-three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose-dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t1/2S of 3, 15, and 30 min. The concentration of N-nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N-nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.

Adolescent↗

PubMed1978

Immunological and plasma protein changes in cancer patients following a single plasmapheresis.

Serial serum protein determinations and immunological monitoring were performed prior to and following a single 4 to 5 liter plasma exchange in 10 patients with disseminated cancer. The most consistent changes were observed for two initially elevated alpha globulins, acid glycoprotein and haptoglobin, which declined rapidly in all patients 1 hour after plasmapheresis and began to rise again as early as 24 hours post-plasmapheresis to reach initial levels by 72 hours. Among the immunological parameters T and B cell counts, and phytohemaglutinin-induced lymphocyte transformation showed little change. In 4 out of 10 patients C3 levels dropped at 1 hour post-plasmapheresis and continued to decline to 24 hours, suggesting that consumption of C3 possibly by macrophages may have occurred. In view of our earlier reports that repeated plasmapheresis induced partial tumor regressions in patients with disseminated cancer and that these regressions may have been related to depletion of immunosuppressive serum proteins, it is suggested that to maintain levels of these rapidly renewed proteins at a minimum for as long as possible, it is most appropriate to perform plasmapheresis every 48 hours rather than every 72 or 96 hours as was the case in the earlier study.

Adult↗

PubMed1977

A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea.

Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA. DNase treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU.

Alkylation↗

PubMed1975

Advanced diffuse histiocytic lymphoma, a potentially curable disease.

Twenty-seven patients with advanced diffuse histiocytic lymphoma (reticulum-cell sarcoma) were treated with combination chemotherapy utilising nitrogen mustard (or cyclophosphamide), procarbazine, vincristine, and prednisone. Elven (41%) achieved a complete remission and only one of these has had a recurrence of tumour. The remaining ten complete responders were free of all evidence of tumour when last seen 26-105 months from the end of treatment. In contrast, all non-responders or partial responders have died. An interpretation of published survival data suggests that this virulent disease evolves quickly and is usally rapidly fatal if treatment is unsuccessful. Survival free of disease beyond 2 years from the end of treatment may be considered tantamount to cure. This definition of cure, previously applied only to patients treated with radiotherapy, seems applicable to patients who acheive complete remissions with modern drug treatment.

Administration, Oral↗

PubMed1975

Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides, and related disorders.

Substantial evidence has accumulated to indicate not only that mycosis fungoides and the Sézary syndrome are closely related malignancies, but to suggest that they are part of a larger spectrum of cutaneous lymphomas. The neoplastic cells of these disorders have membrane features of thymus-derived (T) lymphocytes, a characteristic tissue distribution (skin infiltration, marrow sparing, localization in T-cell regions of lymphoid tissue), and distinctive morphology. For these reasons, we suggest that these lymphoproliferative disorders be grouped together as "cutaneous T-cell lymphomas". The anergy noted in patients of this group with leukemia probably is related to both decreased percentages of normal T cells and presence in the serum of macrophage migration inhibitory activity. Leukapheresis has been particularly effective in the management of selected patients. The homogeneous T-cell populations in the patients with leukemia also provide important opportunities to study many aspects of lymphocyte physiology that are of broad biologic significance.

Cell Membrane↗