Biomedical subjects
Publications and source records attributed to M Levin.
A cannulation set has been designed for repeated short-term infusion of vesicant chemotherapeutic agents via the femoral vein. The major complication was thrombophlebitis in 2.1% of infusions. The procedure provides reliable venous access when therapeutic plans are changed or when the inability to provide catheter care makes an indwelling catheter unwarranted.
Exponentially growing L1210 mouse leukemia cells were incubated with Adriamycin (ADR) under hypoxic (95% N2:5% CO2) or euoxic conditions (95% air:5% CO2) for 1 hr at 37 degrees at a drug concentration ranging from 2.8 X 10(-8) to 2.8 X 10(-4) M, i.e., from levels attained clinically by bolus delivery to the high levels used as an i.p. drug dwell or experimentally, in in vitro conditions. High-pressure liquid chromatography analyses showed diminishing efficiency in drug uptake by the cells as the dose was increased. There were no significant differences between hypoxic and euoxic cells in drug uptake and metabolism. The frequency of DNA protein-associated single-strand breaks and DNA-protein cross-links per 10(6) nucleotides, detected by the alkaline elution technique, increased with the dose in the range of 2.8 X 10(-8) to 2.8 X 10(-6) M in both euoxic and hypoxic cells and declined thereafter. However, the number of DNA lesions relative to a normalized drug level declined steadily, starting with the 2.8 X 10(-7) M concentration. Concentrations greater than 2.8 X 10(-6) M of ADR induced still another type of lesion, direct DNA strand breaks, only in euoxic cells. The results indicate that a common mechanism of interaction between drug and DNA is present in hypoxic and in euoxic cells at low ADR, while an O2-dependent mechanism becomes operational in euoxic cells at high ADR levels.
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Bisantrene is a substituted anthracene derivative which preclinically demonstrated a spectrum of activity similar to that of doxorubicin but without associated cardiotoxicity. A Phase I evaluation of the drug has been performed using daily i.v. administrations for 5 days. Sixty courses of treatment were administered to 23 patients at doses from 2.5 to 90 mg/sq m/day. Courses were repeated at 4-week intervals. Dose-limiting toxicities were leukopenia and local cutaneous reactions. The leukopenia was dose related, noncumulative, and of brief duration. Local reactions occurred in 14 of 37 courses administered at doses greater than 60 mg/sq m and in 13 patients resulted in clinical cellulitis of the infused extremity. Gastrointestinal side effects were mild. No alopecia or cardiotoxicity was observed. Two mixed responses were obtained in patients with hypernephromas. Using a daily schedule for 5 days, approximately 40% more drug can be delivered per course than by single-day i.v. administration. However, with this schedule, local cutaneous reactions may prove additionally dose limiting. Phase II studies of Bisantrene in a daily i.v. schedule for 5 days are planned at a dose of 80 mg/sq m/day to be repeated every 4 weeks.
Screening for alcoholism and associated psychiatric disorders using preselected research criteria demonstrated an overall prevalence of alcoholism of 20% in 200 emergency department patients. The nighttime prevalence of alcoholism was 29%, while the daytime prevalence was 11%. The psychiatric disorders most frequently associated with alcoholism were primary affective disorder (depression) and antisocial personality. The alcoholics had chief complaints relating to trauma in 63% of the cases, vague neuropsychiatric complaints in 23% of the cases, and complaints directly related to alcohol in 8% of the cases. Screening for alcoholism and associated psychiatric illnesses is important in determining an overall treatment strategy for emergency patients.
The in vivo repair of ADR-induced cell damage was investigated in the DBA3 transplantable mouse lymphoma. After a single injection of 5 or 15 mg ADR/kg body weight into DBA/2J mice, the survival fraction of clonogens showed a 2.2- to 4.4-fold decrease at 12 or 18 hours post injection and returned to pretreatment levels within 6 hours. These changes were accompanied by the appearance and disappearance of DNA crosslinks and breaks. Because cell division and/or cell loss could not explain the return of clonogens to pretreatment level, the results strongly suggest repair of ADR damage in tumor cells in situ. Such an efficient repair mechanism, responding to a high toxic dose of ADR, constitutes a therapeutically unfavorable event that may contribute to drug resistance.
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The effects of Adriamycin derivatives on L1210 mouse leukemia cells were studied with the DNA alkaline elution assay. The exposure of exponentially growing cells to approximately equitoxic concentrations of N-trifluoroacetyladriamycin-14-valerate (13.8 microM) and its metabolites, N-trifluoroacetyladriamycin (9.0 microM) and N-trifluoroacetyladriamycinol (43.7 microM), for 1 hr in vitro resulted in a high frequency of protein-associated DNA breaks and DNA-protein cross-links. These effects were comparable to those observed with Adriamycin (2.8 microM) and with adriamycinol (26.9 microM). In contrast to Adriamycin and its metabolite adriamycinol, N-trifluoroacetyladriamycin-14-valerate and its two major metabolites do not bind to DNA. Despite the absence of this direct interaction, N-trifluoroacetyladriamycin-14-valerate and its metabolites produce alterations in DNA comparable with the effects of intercalating agents. No evidence for conversion of N-trifluoroacetyladriamycin-14-valerate to Adriamycin or adriamycinol was found in L1210 cells. The similar effects on DNA macromolecules, observed between intercalating and non-DNA-binding anthracyclines, are consistent with the concept that mechanisms other than direct interaction with DNA play a role in the toxic effects of these compounds.
We report here the case of a man who presented with nonspecific clinical symptoms and was found to have abnormal liver function tests and large filling defects on liver scan. At autopsy, a primary histiocytic lymphoma of the liver was found. The liver is frequently involved secondarily by lymphoma; primary hepatic lymphoma however however is rare, only five cases haveing been previously reported.
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Two hundred adults presenting to the emergency room of an urban general hospital were interviewed by a standardized technique to evaluate the existence of a current or previous psychiatric illness. Half of the subjects presented between 8:00 a.m. and 4:00 p.m. (daytime group), and 100 presented between 12:00 a.m. and 8:00 a.m. (nighttime group). In the nighttime population 65% were judged to have current or past psychiatric illnesses. In the daytime population only 36% had current or past psychiatric illnesses. The differences between the 2 populations was highly significant. Fewer than 10% of the 200 patients presented with neuropsychiatric symptoms in their chief complaints.
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Gentamicin sulfate was given to rabbits for four weeks in two dosage regimens, either 4 or 8 mg/kg subcutaneously twice a day. Two of the seven animals in each group regained nearly normal renal function after a transient rise in the level of serum creatinine, but the remainder developed severe renal failure leading to the death of all but one of these rabbits. None of the animals showed significant hyperglycemia, buy glycosuria appeared in all and was significantly correlated with the extent of renal damage. These findings demonstrate gentamicin-induced derangement of proximal tubular function and thus amplify the previously demonstrated histologic changes due to the drug. When the drug was administered twice daily, there was marked nephrotoxicity in rabbits given dosages of gentamicin only slightly higher than those employed clinically.
In the Tri-State Leukemia Survey, the history of diseases in 605 adult male leukemia cases 15 years and older and in 668 adult male population controls was examined. These diseases occurred at least 1 year before leukemia was diagnosed. The data were based on respondents' answers that the disease was diagnosed by a physician; the respondent was either the subject or his spouse. Of 30 diseases studied, 7 showed an excess among the patients with leukemia: infectious hepatitis, eczema, psoriasis, diabetes, arthritis and rheumatism, heart disease, and ankylosing spondylitis. Mumps had a lower reported occurrence among the cases, whereas pneumonia was less frequent in acute lymphatic cases than in population controls. Three diseases occurred significantly less in controls than in persons with specific histologic types of leukemia. Our data revealed a more frequent history of herpes zoster (shingles) in chronic lymphatic leukemia, more hives in acute chronic myeloid cases, and meningitis in acute myeloid leukemia. When we only considered the patients' responses, more of them admitted having had acne than did our controls. The remaining diseases--childhood viral diseases, infectious mononucleosis, smallpox, typhoid fever, dysentery, scarlet fever, tuberculosis, asthma, hay fever, and goiter did not occur more frequently in cases than in controls. The findings were consistent with evidence from previous laboratory and clinical studies. The increased occurrence of infectious hepatitis in our case series is consistent with the findings of other studies showing an increased frequency of Australia antigen in patients with hepatitis, leukemia, and Down's syndrome.
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A new case of the fetal gigantism-renal hamartomas-nephroblastomatosis syndrome is described, in which a Wilms' tumor occurred. It is considered that this observation provides strong evidence for the interrelationship between renal dysplasia and renal neoplasia.