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Biomedical subjects

D M Levine

Publications and source records attributed to D M Levine.

At least 55 records · Page 3Linked to original sources

Validity of physicians' self-reports of cardiovascular disease risk factors.

To determine the accuracy of self-reported risk factors in 78 physicians, self-reported information was compared to findings on a standardized examination. Measured weight (r = 0.98), height (r = 0.95), body mass index (r = 0.96), systolic blood pressure (SBP) (r = 0.72), and diastolic blood pressure (DBP) (r = 0.60) were highly correlated with self-reported values (all P < 0.0001). Mean self-reported SBP and DBP did not differ from measured values; measured weight was 1.5 kg greater and measured height 1.4 cm less than self-reported values (both p < 0.0001). Regression of measured on self-reported values indicated excellent agreement except for DBP and heart rate. Differences between measured and self-reported values were not associated with a variety of variables except for a greater difference in SBP at higher levels of SBP. None of the 60 self-reported nonsmokers had expired carbon monoxide levels greater than 10 ppm. These results indicate that physicians' self-reports of height, body mass index, SBP, and smoking are extremely accurate and suitable for research purposes.

Aged↗

Randomized, double-blind, placebo-controlled, two-period crossover clinical trial of psyllium fiber in children with hypercholesterolemia.

A randomized, double-blind, placebo-controlled, crossover clinical trial was designed to test the efficacy of psyllium fiber in lowering elevated low-density lipoprotein cholesterol (LDL-C) levels in children 5 to 17 years of age. Subjects with LDL-C levels > 2.84 mmol/L (110 mg/dl) after at least 3 months of a low total fat, low saturated fat, low cholesterol diet were enrolled. Two ready-to-eat cereals, with water-soluble psyllium fiber (6 gm/day) and without, were prescribed for 4 to 5 weeks each, with an intervening 2-week washout phase. Reported compliance rates exceeded 80% in the 20 subjects who completed the study. Mean initial total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride values were 5.23, 3.60, 1.18, and 2.22 mmol/L, respectively. Comparison of the mean changes (from baseline) in lipid values after the two periods of cereal consumption revealed no statistically nor clinically significant differences in total cholesterol, LDL-C, or high-density lipoprotein cholesterol values. Triglyceride levels, however, increased 0.68 mmol/L (26 mg/dl; p < 0.05) after the control cereal in comparison with the psyllium cereal. No significant differences were noted in the children's dietary intake (assessed by 7-day diet records) during the two study periods. Measures of growth (height, weight, and skin-fold thicknesses), and blood vitamin (folic acid; vitamins A, D, and E) and mineral (iron, zinc, and calcium) levels were not affected. In this study, psyllium fiber had no additional lowering effect on total cholesterol or LDL-C levels in children who were already following low total fat, low saturated fat, low cholesterol diets.

Adolescent↗

A randomized trial of ethics education for medical house officers.

We report the results of a randomized trial to assess the impact of an innovative ethics curriculum on the knowledge and confidence of 85 medical house officers in a university hospital programme, as well as their responses to a simulated clinical case. Twenty-five per cent of the house officers received a lecture series (Limited Intervention or LI), 25 per cent received lectures and case conferences, with an ethicist in attendance (Extensive Intervention or EI), and 50 per cent served as controls. A post-intervention questionnaire was administered. Knowledge scores did not differ among the groups. Confidence regarding ethical issues was significantly greater in the aggregate intervention group (3.9 on a 1 to 5 scale) compared to the control group (3.6). Confidence regarding procedural issues related to ethics was significantly higher for the EI group than for the controls (4.0 v 2.8). Responses to a simulated case showed that significantly fewer house officers in the EI group would intubate a patient for whom such therapy would be futile (EI = 57 per cent, LI = 87 per cent, Controls = 82 per cent). We conclude that ethics education can have an impact on house officers' confidence and their responses to a simulated case, and that the EI was more effective than the LI. Such results have implications regarding the implementation of ethics education during residency.

Baltimore↗

Agonistic effects of tyrphostins on human peripheral mononuclear cells.

Tyrosine kinases of the src family, p56lck and p59fyn, were implicated in the transduction of signals via the T-cell receptor complex. These kinases are negatively regulated by phosphorylation of a carboxyl-terminal tyrosine residue. Tyrphostins are synthetic low molecular weight compounds that selectively inhibit different protein tyrosine kinases. We report here on the agonistic and antagonistic effects of tyrphostins on human peripheral blood mononuclear cells (PBM). At low concentration, the tyrphostins enhanced glucose uptake and maximal stimulation was attained at a concentration characteristic for each of the tyrphostins used. Higher concentrations were less effective. The tyrphostins AG126 and AG183 were also found to enhance IL-2-induced cytotoxicity in human PBM in a biphasic manner. In contrast, the tyrphostin AG17 markedly inhibited IL-2-induced cytotoxicity at low AG17 concentration and no stimulation was observed. The tyrphostins tested had selective effects on [3H]thymidine incorporation induced by the mixed lymphocyte culture and different agents. The most potent inhibitor was AG17. Tyrphostins also affect cytokine secretion by human PBM. AG126 and AG183 enhanced TNF-alpha secretion and this effect was more prominent in the presence of IL-2. AG126 enhanced IFN-gamma, IL-1, and IL-6 production in PBM that were costimulated with the stress stimuli heat shock and phenylarsine oxide. The stimulatory effects of the tyrphostins on cytokine secretion and induction of cytotoxicity might be interrelated. The agonistic and antagonistic effects of tyrphostins on lymphocyte functions may have therapeutic potential.

Benzylidene Compounds↗

Hemin stimulation of cAMP production in human lymphocytes.

Hemin stimulates cAMP production in human peripheral blood mononuclear cells (PBMC). The kinetics are similar to that of hormone-induced cAMP generation, namely a rapid effect followed by a desensitization phase. Several experimental findings suggest that prostaglandins do not mediate this effect. First, macrophage depleted T and B cells purified by erythrocyte-rosetting were as responsive as unfractionated PBMC to hemin. Second, indomethacin, an inhibitor of prostaglandin synthesis, and meclofenamate, a prostaglandin E2 receptor antagonist, had no effect on hemin stimulated cAMP production. In addition, propranolol, a beta-adrenergic receptor antagonist, had no effect on hemin-stimulated cAMP production. We also examined structural analogues of hemin. Among the metalloporphyrins (Fe, Ni, Co, Zn and Sn) and protoporphyrin IX tested only hemin (Fe-protoporphyrin) was active in stimulating cAMP production. No correlation was found between the ability of metalloporphyrins to stimulate cAMP production and their ability to generate H2O2. The data indicate that hemin stimulates cAMP production by directly affecting lymphocytes and that prostaglandins do not mediate this effect.

Animals↗

Early predictors of career achievement in academic medicine.

OBJECTIVE: To identify early personal and scholastic factors that predict academic career choice and long-term career achievement among academic physicians. DESIGN: A longitudinal cohort study. PARTICIPANTS: Nine hundred forty-four male physicians who graduated from The Johns Hopkins University School of Medicine, Baltimore, MD, from 1948 through 1964. OUTCOME MEASURES: Career achievement outcomes included attained faculty rank in 1990 and the number of citations (20 to 24 years after graduation) to published work. RESULTS: Of the 944 physicians, 424 (45%) had chosen academic careers. Scholastic performance and research experience in medical school were independently associated with having chosen an academic career (P less than .001). Among academicians, higher attained rank in 1990 was independently associated with the following: (1) membership in Alpha Omega Alpha (relative risk [RR] = 4.94, P = .0001); (2) rank in the top third of the graduating class (RR = 2.68, P = .01); and (3) research experience in medical school (RR = 3.11, P = .0001). These three factors were also independently associated with more citations to participants' published work (P less than .05). CONCLUSION: These data suggest that scholastic performance and research experience during medical school predict career achievement in academic medicine over 20 years in the future.

Achievement↗

The effect of filtered-coffee consumption on plasma lipid levels. Results of a randomized clinical trial.

OBJECTIVE: --To determine the effect of filtered-coffee consumption on plasma lipoprotein cholesterol levels in healthy men. DESIGN: --Randomized controlled trial with an 8-week washout period followed by an 8-week intervention period during which men were randomly assigned to drink 720 mL/d of caffeinated coffee, 360 mL/d of caffeinated coffee, 720 mL/d of decaffeinated coffee, or no coffee. SETTING: --Outpatient clinical research center in a university medical center. PARTICIPANTS: --One hundred healthy male volunteers. OUTCOME MEASURE: --Changes in plasma lipoprotein cholesterol levels during the intervention period. RESULTS: --Men who consumed 720 mL of caffeinated coffee daily had mean increases in plasma levels of total cholesterol (0.24 mmol/L, P = .001), low-density lipoprotein cholesterol (0.17 mmol/L, P = .04), and high-density lipoprotein cholesterol (0.08 mmol/L, P = .03). No significant changes in these plasma lipoprotein levels occurred in the other groups. Compared with the group who drank no coffee the group who drank 720 mL/d of caffeinated coffee had increases in plasma levels of total cholesterol (0.25 mmol/L, P = .02), low-density lipoprotein cholesterol (0.15 mmol/L, P = .17), and high-density lipoprotein cholesterol (0.09 mmol/L, P = .12) after adjustment for changes in diet. CONCLUSION: --Consumption of 720 mL/d of filtered, caffeinated coffee leads to a statistically significant increase in the plasma level of total cholesterol, which appears to be due to increases of both low-density lipoprotein and high-density lipoprotein cholesterol levels.

Adult↗

The quality of mercy. Caring for patients with 'do not resuscitate' orders.

OBJECTIVE: To assess (1) the effect of an ethics education intervention for medical house officers on practices surrounding "Do Not Resuscitate" (DNR) orders and (2) the association of DNR care with patient diagnosis and demographic variables. DESIGN: A 1-year randomized, controlled trial. SETTING: An urban, university teaching hospital. PARTICIPANTS: Eighty-eight internal medicine house officers. INTERVENTION: House officers were arbitrarily assigned to four "firms." One firm was randomized to an extensive ethics education intervention (EI), one to a limited intervention, and two served as controls. MAIN OUTCOME MEASURES: Charts of patients with DNR orders were reviewed for compliance with the hospital's DNR policy, which instructs that when DNR orders are written there should be (1) an attending signature, (2) documentation of reasons, (3) appropriate consent, and (4) attention to 11 concurrent care concerns (CCCs) (eg, the appropriateness of intubation, tube feedings, hospice). RESULTS: Thirty-nine charts were reviewed before the intervention and 57 after. The number of CCCs per DNR order fell among patients cared for by controls (1.9 to 1.0, P less than .05) and rose among patients cared for by the EI group (0.9 to 3.8, P less than .05). Compliance with the DNR policy varied among patients with differing diagnoses. "Do Not Resuscitate" orders were signed less frequently (P = .01) for patients with the acquired immunodeficiency syndrome (AIDS) (65%) compared with patients who had other diagnoses (85%) or malignancy (91%). Similarly, appropriate consent was recorded for 59% of patients with AIDS, 83% of others, and 85% of those with malignancy (P less than .05). The number of CCCs per DNR was 0.7 for AIDS, 1.4 for others, and 2.4 for malignancy (P less than .05). In multivariate regression analysis, house officer ethics education and patient diagnosis, but not patient gender, age, race, or insurance status, were predictors of the number of CCCs per DNR. CONCLUSIONS: (1) An extensive ethics education intervention can improve care for DNR patients, especially with respect to CCCs. (2) In this setting, quality of care for DNR patients varied systematically with diagnosis. These results have implications for the design and implementation of ethics education programs.

Baltimore↗

Automated measurement of lipoprotein(a) by immunoturbidimetric analysis.

Immunoturbidimetric analysis of lipoprotein(a) in plasma or serum was developed for use on the Roche COBAS FARA II and COBAS MIRA clinical chemistry analyzers. The components of the assay are: (1) buffer consisting of 2.25% polyethylene glycol in phosphate-buffered saline, 0.2% gelatin, and a surfactant; (2) fractionated goat anti-human lipoprotein(a) IgG; (3) five standards with lipoprotein(a) concentrations ranging from 0.05 to 1.0 g/l; (4) two controls with concentrations of approximately 0.2 and 0.5 g/l. The analyzer delivers sample and buffer, incubates the reaction mixture at 37 degrees C for 5 min, delivers neat lipoprotein(a) antibody, and incubates for an additional 10 min. The lipoprotein(a) concentration of samples is calculated by the COBAS DENS (Data Evaluation for Non-linear Standard Curves) option by fitting the standard curve values to a four-parameter logit-log curve model. Total imprecision results (CV%) for the FARA II and MIRA were under 11% (NCCLS protocol EP5-T). The assay is linear beyond the highest calibrator to 2.6 g/l. No interference was observed for plasminogen up to 2.3 g/l, apolipoprotein B up to 4.36 g/l, hemoglobin up to 10 g/l, bilirubin up to 4.0 g/l, and triglycerides up to 4.36 g/l. Comparison with a double monoclonal ELISA used at the Northwest Lipid Research Laboratories yielded: R = 0.970, slope = 1.013, and y-intercept = 0.00009 (n = 37). Comparison with a commercially available ELISA kit for lipoprotein(a) yielded: r = 0.987, slope = 1.243, and y-intercept = 0.024 (n = 40). This assay provides rapid, accurate, and precise screening of lipoprotein(a) in serum or plasma.

Antibody Formation↗

The effect of lipoproteins on human glioblastoma growth in vitro.

Experiments were performed using an established human glioblastoma cell line to determine the effect of lipoproteins on regulating their growth. It was found that synthetic and natural human high density lipoproteins (HDL) were effective in inhibiting tumor cell growth in a nontoxic, dose-dependent manner, and that the LD50 was 10-fold lower than that for normal rat astrocytes grown under identical conditions. In the presence of the antioxidant, glutathione, essentially all of the growth-inhibiting properties of HDL could be reversed suggesting that oxidized lipids from the HDL interacting with the plasma membranes of the glioblastoma cells were responsible for the growth-inhibiting effect observed. The markedly lower concentration of HDL required to inhibit glioblastoma cells in culture compared to normal astrocytes suggested that the mechanism of HDL-induced inhibition may be important for tumor growth in vivo. One possible mechanism under investigation is the possibility of HDL modulation of a membrane-associated, tumor-specific phosphatase.

Apolipoprotein A-I↗

Stress stimuli-induced lymphocyte activation.

Oxidants, heavy metals, and heat shock, collectively known as stress stimuli, induce the synthesis of a variety of proteins, termed stress proteins, and enhance glucose uptake. In this study, we have demonstrated that stress stimuli enhance protein tyrosine phosphorylation (PTyr-P), modulate protein tyrosine phosphatase (PTPase) activity, activate the src family protein tyrosine kinase (PTK), p56lck, and enhance glucose uptake in human peripheral blood mononuclear cells. The heavy metal Hg2+ and heat shock stimulated PTPase activity at an optimal dose, whereas the oxidant phenylarsine oxide (PAO) was only marginally stimulatory. Treatment of lymphocytes with stress stimuli at a dose which activated PTPase did not produce discernable PTyr-P using Western blotting techniques. PTyr-P was only seen at doses of stress stimuli which were associated with an inhibition of PTPase activity. We could demonstrate a correlation between the dose of stress stimuli effective in increasing PTPase activity and p56lck activation using heat shock and Hg2+ as stress stimuli. On the other hand, much lower concentrations of PAO were effective in activating PTPase than those effective in eliciting p56lck activation. We could not demonstrate a correlation between an effective dose inducing PTyr-P and glucose uptake. Our data do not permit us to draw a simple correlation between enhancement of PTPase activity, activation of p56lck, induction of PTyr-P, and induction of the biological response. It is possible that both stimulation and inhibition of PTPase could regulate PTyr-P by either activating the src family PTKs or preventing dephosphorylation of target proteins which are involved in the biological response. Our data may also provide the biochemical basis for the previously reported mitogenic effects of Hg2+ on lymphocytes.

Cells, Cultured↗

Evaluation of a model curriculum on substance abuse at The Johns Hopkins University School of Medicine.

Beginning in 1985, The Johns Hopkins University School of Medicine developed a model curriculum on alcohol abuse to enhance the education of medical students in issues related to the abuse of alcohol and other drugs. By 1987, preclinical courses (given in years one and two) reflected the goals of the curriculum; however, integration of the curriculum into the clinical courses (given in years three and four) was only partially successful. This paper reports on nine annual surveys of students (the classes of 1989-1992) that were conducted from 1987 to 1990 to measure the effects of the curriculum, using previously validated instruments to record the students' knowledge, attitudes, beliefs in role responsibility, and confidence in clinical skills. Significant improvements occurred in the students' attitudes, beliefs in role responsibility, and confidence in skills during their preclinical years. These positive changes were stronger, and better sustained during the clinical years, in students who participated in special programs or elective courses focusing on substance abuse; the positive changes were not always sustained in other students. The authors suggest that enhanced experiential sessions, elective programs, and greater emphasis during the clinical years on issues relating to substance abuse are necessary for maintaining the desirable educational outcomes of a substance abuse management curriculum, and that an intensive program against a backdrop of curriculum reform is a useful model.

Baltimore↗

Physician estimates of substance abuse in Baltimore and Cumberland: 1991.

By identifying and counseling substance abusers within their own practices, primary care physicians can play a major role in reducing levels of substance abuse. How proficient area physicians are in identifying substance abuse is examined by comparing physician estimates of substance abuse in their patient populations with local and national statistics.

Baltimore↗

A partnership with minority populations: a community model of effectiveness research.

This paper describes a community-based approach, including a partnership of an academic medical institution and a high-risk, urban, African-American population, directed at decreasing premature morbidity and mortality and enhancing health and functional status. The intervention approach is based on a model of community-based leadership and "ownership" of interventions and programs to enhance sustainability of effective approaches, and it follows specific stages to assure appropriate assessment and evaluation. Initial efforts were directed at the control of hypertension and were coordinated through decentralized mayor's stations in Baltimore, Maryland. This approach was successful in significantly enhancing control of hypertension and reducing related morbidity and mortality. Over time, an enhanced partnership has been coordinated through churches in the community and organized around a program entitled "Heart, Body, and Soul." Current efforts are directed at the major risk factors and preventable and/or controllable problems in the population, such as hypertension, smoking, obesity, diabetes, hyperlipidemia, and cervical and breast cancer. Key components include the training of neighborhood health workers to provide screening, counseling, monitoring, support, and follow-up; enhanced access to care; training of high school students as health counselors; and use of media to promote healthier life-styles.

Academic Medical Centers↗

Social integration and black intraracial variation in blood pressure.

An evaluation is made of the inverse role social integration plays in explaining variation in blood pressure among a sample of 1420 black Americans. This sample is part of a larger representative sample of 6717 adults (18 years and older) who were interviewed in the 1981-82 Maryland Statewide Hypertension Control Program. Social integration is operationalized in terms of five submeasures: employment, marriage, church affiliation, group affiliation, and having someone to talk to when needed. Separate multiple regression analyses were conducted for males (n = 587) and females (n = 833), and selected covariates (eg, age, education, body mass index, physical exercise, current use of antihypertension medication, cigarette smoking) were entered to assess more adequately the hypothesized inverse relationship between social integration and systolic and diastolic blood pressure. Only church affiliation appears inversely associated with systolic (males: b = -4.898; 95% CI = -10.385 to 0.589; females: b = -4.005; 95% CI = -8.341 to 0.331) and diastolic (males: b = -6.511; 95% CI = -10.038 to -2.985; females: b = -5.318; 95% CI = -8.329 to -2.307) blood pressure. These results indicate that several pathways can influence how social integration, especially affiliation with a church, contributes to lower levels of blood pressure. The possibility that biological as well as psychosocial pathways operate is discussed. Given the dominant and independent inverse association of church affiliation to blood pressure, health education is discussed as a public health strategy to disseminate information regarding the possible health importance of social integration for black Americans. The adherence to sound preventive health practices (eg, exercising, lower weight-to-height body ratio) should also be part of the health education strategy to reduce elevated blood pressure in black Americans.

Adolescent↗

Control of variance in experimental studies of hyperlipidemia using the WHHL rabbit.

Between-animal variability has frustrated many experimental studies in outbred animal models of human disease. Variability that arises from genetic heterozygosity can be minimized by use of experimental designs that match littermates (polyzygotic twins) across control and treatment groups. Poor breeding vigor has prevented use of this experimental design in the WHHL rabbit model of hyperlipidemia and atherosclerosis. A comparison of reproduction in WHHL and normal rabbits demonstrated that litter size is limited by functional deficits at ovulation, implantation, and gestation in WHHL females. Superovulation of females reliably produced expanded litters of WHHL rabbits. Plasma lipids were measured in expanded litters of Japanese White WHHL (JW-WW) and English Half-lop WHHL (EHL-WW) rabbits. The variance of plasma cholesterol within sibships was two- to three-fold less than that between-litters. Intraclass correlation of total cholesterol within litters of EHL-WW was 0.72 and within litters of JW-WW was 0.67. These data provide evidence of genetic modulation of hypercholesterolemia in WHHL rabbits and demonstrate that experimental designs in which littermates are paired across groups can decrease the number of animals needed or increase the sensitivity of hypothesis tests by two- to threefold.

Animals↗

Tolerance for ambiguity among medical students: implications for their selection, training and practice.

The practice of medicine has always been characterized by uncertainty. Yet, attempts to study tolerance for uncertainty in medicine have been few, and limited to its influence on specialty preferences and test-ordering behavior. In particular, studies have not investigated how the process of socialization into the medical profession affects tolerance for uncertainty. Based on the assumption that uncertainty and ambiguity are related concepts, a modified version of a tolerance for ambiguity scale was used to study Johns Hopkins medical students' (N = 386) tolerance for ambiguity (TFA) through 4 yr of medical school. In addition, using alcoholism as an example of a clinically ambiguous condition, the association between students' tolerance for ambiguity and their perceived role in diagnosing and treating alcoholism was also investigated. Results indicate that tolerance for ambiguity (1) does not change throughout medical school, (2) is lower among men, whites and students who are younger when they begin medical school, (3) is higher among prospective psychiatrists than surgeons, and (4) is lower among students who do not feel responsible for diagnosing and treating alcoholism. These findings suggest that tolerance for ambiguity may, indeed, affect practitioners' career choices and performance and that selection of medical students may be more important than medical training per se in influencing students' tolerance for ambiguity. If medical schools admitted students who possess a high tolerance for ambiguity, quality of care for ambiguous conditions might improve, imbalances in physician supply and practice patterns might be reduced, and the increasing ambiguity in medical practice might be better acknowledge and accepted.

Alcoholism↗