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Biomedical subjects

M Scher

Publications and source records attributed to M Scher.

12 recordsLinked to original sources

Enhancement of differentiation and cytotoxicity of leukemia cells by combinations of fluorinated pyrimidines and differentiation inducers: development of DNA double-strand breaks.

We have previously shown that pretreatment of mouse erythroleukemia (MEL) cells with the fluorinated pyrimidines 5-fluorouracil (FUra) or 5-fluorodeoxyuridine (FUdR) followed by the differentiation inducer hexamethylene bisacetamide (HMBA) greatly enhanced the magnitude of their differentiation and caused extensive cell death. We have now extended these studies to address the mechanism that may be responsible for this enhancement and have also examined a human leukemic cell line (HL-60) for its sensitivity to this combination cytotoxic-differentiation therapy. We found that in HL-60 cells, pretreatment with FUdR, but not FUra, followed by 1.2% dimethylsulfoxide (DMSO) led to an 8 to 10-fold enhancement of cell death as compared to FUdR alone. When all-trans-retinoic acid (ATRA) was used instead of DMSO, the enhancement of differentiation and cytotoxicity was 5-fold. The percent of cells induced to differentiate was dependent on the concentration of both FUdR and ATRA. In HL-60 cells resistant to ATRA-induced differentiation, the combination of FUdR and ATRA did not result in enhanced cytotoxicity. Leucovorin (LV), a compound known to enhance the inhibitory effect of FUra or FUdR on DNA synthesis, increased the effectiveness of the cytotoxic-differentiation therapy, whereas thymidine inhibited its effectiveness. This suggests that inhibition of DNA metabolism may be an integral part of the differentiation-enhancing cytotoxic mechanism. To further explore inhibition of DNA synthesis, DNA was extracted under alkaline or neutral conditions from 3H-thymidine-labelled cells that were treated with FUra/LV and HMBA individually or in combination. The emergence of single and double-strand DNA breaks was monitored by agarose gel electrophoresis. In parallel to the enhancement of cytotoxicity, the combination treatment (FUra/LV followed by HMBA) also produced a 2.5-3-fold increase in the DNA breaks when compared to the same effect obtained by the agents applied individually. Thus, we propose that DNA degradation may be the mechanism responsible for the enhanced loss of cell viability. In summary, we report here an approach which is targeted to increasing the death rate of leukemic cells through the combined use of low doses of cytotoxic drugs and differentiation inducers.

Cell Differentiation

The effects of prenatal alcohol use on the growth of children at three years of age.

In this prospective study of substance use during pregnancy, women were interviewed in their 4th and 7th prenatal months, and women and children were assessed at 24 hr, 8, 18, and 36 months postpartum. Data are presented on the outcome of 519 children at age 3. At 3 years, children who were exposed prenatally to alcohol were smaller in weight, length, and head circumference. They also had an increased number of minor physical anomalies. These effects were found even after controlling for nutritional and environmental factors. The persistence of growth effects at age 3 suggests that children exposed to alcohol prenatally may have a diminished capacity for growth.

Body Height

Effect of prenatal alcohol exposure on growth and morphology of offspring at 8 months of age.

In this prospective study of alcohol and other substance use during pregnancy, a cohort of women was interviewed at each trimester of pregnancy and when the offspring were 8 months of age. Data are presented concerning the outcome for 461 infants. A significant relationship was found between alcohol use during pregnancy and the growth and morphology of the offspring at the 8-month follow-up observation. Alcohol use during the second and third trimesters of pregnancy and continuous use of alcohol throughout pregnancy were significantly related to lower weight, length, and head circumference in the exposed infants at the follow-up observation. A significant increase in the risk of minor physical anomalies and fetal alcohol effects was also predicted by prenatal alcohol exposure.

Adolescent

Carbamazepine adjunct for nonresponsive psychosis with prior hallucinogenic abuse.

Some patients diagnosed as schizophrenic report persistent polymodal hallucinosis following a period of extensive hallucinogenic drug abuse unrelieved by the usual antipsychotic drugs. In this open study, carbamazepine (Tegretol, an anticonvulsant) was administered to three patients with polymodal hallucinosis which had failed to diminish on antipsychotic drugs alone. All three patients showed a marked to complete reduction in symptomatology.

Adult

Prenatal exposure to alcohol: effect on infant growth and morphologic characteristics.

In this prospective study of alcohol and other substance use during pregnancy, a cohort of 650 women was interviewed at each trimester of pregnancy. Data are presented concerning the status of 595 live singleton births. A relationship was demonstrated between prenatal maternal alcohol use and growth and morphologic abnormalities in the offspring. Low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were all found to be significantly correlated with exposure to alcohol during the first 2 months of the first trimester.

Abnormalities, Drug-Induced

Reviewing results of psychological tests in a patient group.

Believing that much helpful information from psychological test results was not being transmitted to patients, psychologists on a teaching ward at a Veterans Administration hospital began holding group sessions to explain the results of psychological tests to patients. Attendance was voluntary, but 96 per cent of the patients who were tested in a one-year period attended, an average of four or five each session. The psychologist described routine tests and how the results were used and then presented individual test results, giving practical illustrations of the findings and emphasizing patients' strengths and coping styles. Scores from questionnaires administered to patients after they completed the tests and at the end of the group session showed that their attitudes toward tests became more positive after the group session, and that they felt that hearing their own and others' test results had been helpful.

Hospitals, Veterans

Thrombocytopenia in the absence of leukopenia associated with the use of neuroleptics.

Thrombocytopenia, a fairly uncommon side effect of phenothiazine treatment, usually appears in the presence of a concommitant leukopenia. The authors report 1 patient in whom the illness appeared in the presence of a long known Beta thalassemia but without evidence of alteration in myeloid or lymphoid series. Platelet changes were seen in the presence of a butyrophenone and an aliphatic phenothiazine. A piperazine derivative was used without difficulty.

Adult

The use of student ratings in multiinstructor courses.

In this study the authors examined the efficacy of using student ratings of teaching effectiveness in multiinstructor courses. Specific issues addressed included student ability to identify differences in faculty teaching effectiveness, the consistency of student rating obtained immediately following each lecture with those obtained at the conclusion of the course, and the relationship between individual faculty ratings and overall course ratings. A random sample of students rated each of 14 lectures in a psychopathology course using a 13-item rating scale immediately after each lecture and again at the end of the course. Results indicated that differences in faculty teaching effectiveness are measurable, ratings of individual faculty are relatively stable over over time, and rating of individual faculty are separable from those of the course as a whole. Implications of this research for use of student ratings are also discussed.

Education, Medical

A model for the improvement of medical faculty lecturing.

The development of a program designed to improve the teaching effectiveness of faculty members of a new Introductory Psychopathology course at the University of Washington School of Medicine is described. Two consultants from the Office of Research in Medical Education worked closely with the faculty in designing the evaluation program during the preparation of the course. The literature on lecture effectiveness is reviewed, as are existing instructional evaluation instruments. The integration of this information and the needs of the involved faculty produced a lecture observation schedule designed to facilitate the observation of a lecture and the immediate feedback which followed each of the 15 lectures evaluated. The process of using this instrument to assist the faculty in self-improvement is discussed. While the specific evaluation method described may not be appropriate for all situations, it may serve as a model for the development of similar programs in other settings.

Evaluation Studies as Topic

Psychiatrist-wife-mother: some aspects of role integration.

Throughout her professional life the woman who chooses to combine the roles of psychiatrist, wife, and mother may find them not only compatible but complementary. If she can adopt a philosophy of life that permits her to function in these roles, and if those around her support her activities, she can perform with relative ease and proficiency. Her lifestyle must of necessity differ from that of her male colleagues, but differing lifestyles among members of a profession vitalize the field. A broad perspective is desirable, especially in a profession that deals with the emotional and mental lives of people. Married women and mothers afford such a broadened perspective to the field of psychiatry.

Family

Prenatal marijuana use and neonatal outcome.

In a longitudinal study of marijuana and other substance use during pregnancy, women were interviewed at each trimester of pregnancy. Growth parameters, morphological abnormalities and gestational age were assessed for the 519 liveborn singletons. There were few significant effects of marijuana use during pregnancy on birth weight, head or chest circumference, gestational age, or growth retardation after adjustment for covariates using a regression model for analysis. There was a small but significant negative effect of marijuana use during the first two months of pregnancy on birth length and a positive effect of marijuana use during the third trimester on birth weight.

Adult