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Biomedical subjects

C E Lewis

Publications and source records attributed to C E Lewis.

At least 109 records · Page 6Linked to original sources

Concentrations of Lp(a) in black and white young adults: relations to risk factors for cardiovascular disease.

The purpose of this report is to compare the distribution of total lipoprotein(a) [Lp(a)] mass in a population-based sample of blacks and whites, and to investigate the association of Lp(a) with other cardiovascular risk factors. A cross-sectional study design was used. Black and white men and women (n = 4125), aged 23-35 from the Coronary Artery Risk Development in Young Adults Study had the following data collected: Lp(a), lipids and lipoproteins, other metabolic parameters, anthropometry, physical activity, dietary intake, cigarette use, and alcohol use. Blacks had concentrations of Lp(a) approximately three-fold higher than whites. Medians were: black men 21.5 mg/dL, black women 23.9 mg/dL, white men 6.1 mg/dL, and white women 6.4 mg/dL. Lp(a) concentrations were higher in women than in men. Lp(a) was not consistently associated with smoking, alcohol consumption, physical activity, dietary fat, or obesity. In stepwise regression analyses in both blacks and whites, Lp(a) was consistently associated with low-density lipoprotein (LDL) cholesterol, fibrinogen, and apoB; regression models explained about 7% of the variance in Lp(a). In whites, Lp(a) tended to be higher in those with a positive family history of myocardial infarction. The large differences in Lp(a) between blacks and whites, and the absence of association with many other variables are consistent with previous suggestions that Lp(a) concentration is in large part genetically determined. The association of Lp(a) with LDL and fibrinogen, two strong risk factors for cardiovascular disease (CVD), could represent part of the mechanism of the CVD risk associated with Lp(a) in other studies. Longitudinal data are needed to determine the extent to which Lp(a) will independently predict disease, especially in diverse ethnic groups.

Adult↗

Expression of tumour necrosis factor alpha and its receptors in carcinoma of the breast.

The expression of tumour necrosis factor alpha (TNF-alpha) and its two distinct receptors, TNF-R p55 and TNF-R p75, was assessed by immunocytochemistry in 28 primary breast cancer and three reduction mammoplasty specimens ('normal' breast tissue). Expression of TNF-alpha or TNF-R p75 was not detectable in normal breast tissue or in non-malignant breast tissue adjacent to the tumours. By contrast, TNF-R p55 was expressed by occasional stromal cells in normal tissue. TNF-alpha was expressed focally in 50% of the tumours studied, being largely localised to macrophage-like cells in the stroma. TNF-R p55 was expressed by a population of stromal cells in all the tumours examined, and a varying proportion of neoplastic cells in 75% of these tissues. TNF-R p75 was detected in about 70% of the tumours, immunoreactivity being confined mainly to cells in the stroma. In this preliminary study there was no association between the above cytokine parameters and such measures of tumour biology as lymph node status, tumour grade, proliferative activity or degree of angiogenesis. However, there was a correlation between the expression of TNF-R p55 by blood vessels and the number of leucocytes present.

Biopsy↗

Comparison of alcohol dependence in subjects from clinical, community, and family studies.

This study contrasts the prevalence of alcohol-related symptoms, ages of onset of alcoholism milestones, and lifetime prevalence of other psychiatric disorders in three samples of alcohol-dependent individuals: alcoholics sampled from a variety of clinical settings (not necessarily alcoholism treatment facilities), relatives of alcoholic probands who participated in a Family Study of alcoholism, and alcoholics identified in the St. Louis Epidemiologic Catchment Area survey. Alcohol dependence (with or without abuse) was assessed using DSM-III diagnostic criteria for all samples. Clinical alcoholics had significantly more lifetime alcohol symptoms than Family Study and Community alcoholics and a significant excess of many alcohol symptoms. Onset information indicated that the three groups were similar in terms of appearance of milestones of alcohol dependence. For females aged 45 or younger, lifetime prevalence of major depression was high in both Clinical and Family Study alcoholics compared with Community alcoholics; male alcoholics from the Community Study had an excess of drug dependence. Findings suggest that, although alcoholics identified in clinical settings may have more severe alcohol dependence, certain types of psychiatric comorbidity are present to a greater degree in other samples of untreated alcoholics.

Adolescent↗

Predictors of mortality in alcoholic women: a 20-year follow-up study.

Very little is known about the factors that predict mortality in female alcoholics. This study investigates these predictors in 103 female alcoholics who were psychiatrically hospitalized between 1967 and 1968 and followed for over 20 years. The findings showed that age, benders, and/or delirium tremens, comorbidity, and 3-year posttreatment drinking status were associated with time to death. That older alcoholics and those with pathological drinking within 3 years after treatment had a significantly shorter time to death was not surprising. However, the association of benders with mortality indicated that women may be very sensitive to short periods of high concentrations of alcohol. Comorbidity also had an intriguing effect in that women with a history of depression were more likely to survive. The predictors of mortality in these female alcoholics differed from those of the male alcoholics in this sample. These differences will be discussed in future publications.

Adult↗

Continuing medical education about AIDS--a needs assessment.

The incidence of the acquired immunodeficiency syndrome (AIDS) among Latinos and African Americans nationally and in Los Angeles has risen substantially. No data exist to indicate which physicians (or groups of physicians) provide care to these groups, however. To better plan AIDS educational programs, efforts were made to identify those physicians whose offices were located in areas with high proportions of nonwhites. Many physicians in these areas--30% of all office-based primary care physicians in Los Angeles--were found to be graduates of international medical schools. A survey of a stratified random sample of international medical graduates revealed that compared with a random sample of United States medical graduates, they had a greater proportion of nonwhite patients, often of an ethnicity similar to theirs; practiced in areas with a greater proportion of Asians and lower family incomes; had fewer patients infected with the immunodeficiency virus (HIV) in their practices; and were more avoidant of such patients. As the incidence of HIV infection increases among minority groups, means need to be developed to ensure their access to counseling and screening, as well as treatment with the latest available agents. Options include imaginative and engaging approaches to continuing medical education for all physicians and the creation of separate public sector infrastructures to meet the HIV-related needs of these communities.

Acquired Immunodeficiency Syndrome↗

Inconsistent associations of caffeine-containing beverages with blood pressure and with lipoproteins. The CARDIA Study. Coronary Artery Risk Development in Young Adults.

The authors examined associations of caffeine and caffeinated beverage intakes with blood pressure and with lipoproteins in 5,115 black and white men and women aged 18-30 years during 1985-1986. Caffeine and beverage intakes were not consistently associated with blood pressure in analyses controlling for race, sex, Keys score, sucrose intake, physical activity, oral contraceptive use, body mass index, alcohol use, age, and smoking. Associations of caffeine and beverage intakes with cholesterol, triglycerides, high-density lipoprotein cholesterol, and high-density lipoprotein2 cholesterol were also inconsistent. There is little or no association of caffeine with lipoproteins or with blood pressure in this cohort of healthy young adults.

Adolescent↗

Secretion of epidermal growth factor by macrophages associated with breast carcinoma.

By means of a cytokine release assay we have shown that in cell populations derived from primary breast carcinoma, epidermal growth factor (EGF) is secreted by cells with the characteristic morphological and immunophenotypic profile of activated macrophages (positive for CD68, CD16, CD25). EGF secretion was observed in 11 (31%) of 35 primary tumours. Secretion of EGF by normal or malignant epithelial cells was not observed. We found no association between EGF secretion by the primary tumour and recognised clinical indices of prognosis.

Adult↗

Growth factors: regulation of normal and neoplastic growth.

This paper presents an overview of current trends in growth factor research. The first part of the review considers the current classification of growth factors and their receptors. A model of cell proliferation regulation by growth factors is then presented. The final section reviews the latest concepts of the involvement of growth factors in the development of neoplasia.

Cell Division↗

Epidermal growth factor, insulin-like growth factor-1 and basic fibroblast growth factor modulate the cytostatic effect of tumour necrosis factor-alpha on the breast cancer cell line, T47D.

The effect of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) on the cytostatic activity of tumour necrosis factor-alpha (TNF-alpha) was studied on the breast cancer cell line, T47D. TNF-alpha completely blocked the potent growth-promoting activity of all three factors on T47D cells. EGF, bFGF and IGF-1 partially antagonized the inhibition of cell growth and thymidine incorporation induced by TNF-alpha. These data suggest that the growth of these breast cancer cells is regulated, in part, by the antagonistic interaction between the cytostatic effect of TNF-alpha and the growth-promoting activity of factors such as EGF, IGF-1 and bFGF.

Breast Neoplasms↗

Growth arrest of the breast cancer cell line, T47D, by TNF alpha; cell cycle specificity and signal transduction.

The effects of tumour necrosis factor-alpha (TNF alpha) on the growth and DNA synthesis of the human breast cell line, T47D, were studied. A dose-dependent, reversible inhibition of thymidine incorporation and cell growth was observed in the range of 0.1 ng ml-1 to 100 ng ml-1 of TNF alpha. Cell viability was not impaired in any of the experiments. Flow-cytometric DNA analysis demonstrated that after 24 h exposure to TNF alpha, T47D cells accumulated in the G1 phase of the cell cycle, and were depleted in the G2/M and S phases, suggesting a block in the progression of the G1/S transition. The involvement of protein kinases (PK) and protein phosphatases in TNF alpha-induced signal transduction was also investigated. A transient and rapid 2-fold increase in total cellular protein kinase C (PKC) activity was detected after 10 min exposure to TNF alpha. To study the role of the observed PKC activation in the cytostatic effect of TNF alpha, T47D cells were exposed to the cytokine in the presence of the potent PKC inhibitor, H7. The inhibitory effect of TNF alpha on thymidine incorporation was not affected by exposure to H7 at concentrations sufficient to block the stimulation of thymidine up-take induced by the PKC agonist, phorbol-12-myristate-13-acetate (PMA). The involvement of other signalling pathways was addressed using the cyclic nucleotide-dependent PK inhibitor, H8; the calmodulin-dependent PK inhibitor, W7; and the inhibitor of protein phosphatases PP1 and PP2B, okadaic acid. Exposure of T47D cells to these enzyme inhibitors failed to antagonise the inhibition of thymidine incorporation by TNF alpha. Taken together, these results indicate that the cytostatic effect of TNF alpha on T47D cells occurs at the G1/S transition of the cell cycle, and is mediated by an intracellular pathway which does not involve the activity of protein kinases C and A, nor protein phosphatases PP1, PP2B.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Lipoprotein[a] concentrations and apolipoprotein[a] phenotypes in Caucasians and African Americans. The CARDIA study.

Little is known about racial differences in lipoprotein[a] (Lp[a]) concentrations and apolipoprotein[a] (apo[a]) phenotypes. Lp[a] protein concentrations were determined by a double monoclonal antibody enzyme-linked immunosorbent assay method in 4165 Caucasian and African American men and women from four US communities. Apo[a] phenotypes were determined by polyacrylamide gel electrophoresis and immunoblotting on a random subset of these participants (n = 690). The distribution of Lp[a] protein levels in Caucasians was highly skewed (mean, 6.9 mg/dL; median, 3.7 mg/dL). In contrast, the distribution in African Americans was less skewed (mean, 13.0 mg/dL; median, 11.6 mg/dL), and Lp[a] protein levels were approximately double those in Caucasians within most apo[a] phenotypes. The previously described inverse relationship between apo[a] size and Lp[a] concentration was generally confirmed in Caucasians, but the B phenotype had lower Lp[a] levels than the S1 or S2 phenotype. In African Americans, both the B and S1 phenotypes had lower Lp[a] levels than the S2 phenotype. The frequencies of the apo[a] phenotypes in African Americans differed from those in Caucasians (P < .001) and also differed from the frequencies reported in a Sudanese population (P < .002). African Americans had a lower frequency of the S2 phenotype than Caucasians (8% vs 18%; P < .01) and a higher frequency of S3 (36% vs 25%; P < .01). As compared with the data reported in Sudanese, African Americans also had a higher frequency of the S3 phenotype (36% vs 14%; P < .001) and a lower frequency of S4 (29% vs 44%; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Physical activity of public housing residents in Birmingham, Alabama.

OBJECTIVES: Because few data are available concerning physical activity among minority and low-income persons, we characterized physical activity patterns among public housing residents. METHODS: Two separate cross-sectional surveys were conducted 1 year apart of randomly selected residents of eight rental communities administered by the housing authority of Birmingham, Ala. Indigenous interviewers completed 687 interviews in survey 1 and 599 in survey 2. RESULTS: In both surveys, respondents were most frequently young adult African-American women, reflecting the predominance of women in these communities. Participants were generally poorly educated and either unemployed or working in service occupations. Thirty percent of the respondents in both surveys reported no participation in any of 13 physical activities in the previous year; approximately half reported activity levels equivalent to or less than walking 4 hours per week for 8 months of the year. Respondents who were younger and male were significantly more likely to have higher activity levels. CONCLUSIONS: A sedentary life-style is common among this low-income minority group, and, thus, interventions to promote exercise in these communities are needed.

Adolescent↗

Continuing medical education for AIDS: an organizational response.

The Management of the Southern California Kaiser-Permanente Medical Group mandated a day-long program of continuing medical education on AIDS for all staff physicians at one facility. Presentations dealt with cognitive (transmission/diagnosis), skills (risk factors, history taking), and affective (discomfort/attitudes) domains. All physicians participated in 2 small-group workshops on sexual history taking and ethical issues. An evaluation compared primary care physicians' attitudes and practices before and after the program at the experimental site (Medical Center), a comparison site (written materials only), and a "no-treatment" facility. A sample of new patients (N = 2,689) seen by study physicians (N = 253) before and after the educational intervention were telephoned to determine if sexual history questions were asked by their physicians. There was a significant increase in the frequency of sexual history questions asked by internists at the experimental site. Over 95% of all patients were accepting of sexual history questions. This program has since been repeated at 11 medical centers involving over 3,500 Kaiser-Permanente physicians throughout Southern California.

Acquired Immunodeficiency Syndrome↗

Promoting physical activity in low-income African-American communities: the PARR project.

Data suggest that low-income and minority individuals are less physically active than the general population. We conducted a constituency-based physical activity promotion program, the Physical Activity for Risk Reduction (PARR) project, from 1988 to 1991, with residents of rental communities administered by the Housing Authority of the Birmingham District in Birmingham, Alabama. Data collected through focus groups and by survey of randomly selected residents' exercise practices, beliefs, barriers to and facilitators of physical activity were used to develop specific intervention programs that were implemented and evaluated in six intervention and two control communities through surveys and process evaluations. Trained community residents conducted data collection and interventions. Ninety-nine percent of respondents in the baseline survey were African Americans. Thirty-one percent reported no participation in any of 13 physical activities in the previous year. Significant differences (P < .05) in average attendance by community at group exercise sessions indicated substantial variability in effectiveness of the intervention, due at least in part to factors related to both the communities and the leaders. This variability appeared to explain patterns of change in preintervention and postintervention physical activity scores in intervention communities. Data and experiences from PARR will be applicable to the delivery of similar types of health-related programs in undeserved communities.

Adolescent↗

Effect of major surgery on the release of interferon gamma by peripheral blood mononuclear cells: an investigation at the single cell level using the reverse haemolytic plaque assay.

The release of interferon gamma (IFN-gamma) by peripheral blood mononuclear cells from patients undergoing abdominal aortic aneurysm repair was measured using the reverse haemolytic plaque assay. The plasma of these patients was also assayed for interferon gamma using enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells from the surgical patients released significantly more IFN-gamma by 9 hours after incision than that released prior to surgery (P less than 0.001). This change persisted up to 9 days after surgery. Plasma IFN-gamma was not detectable using either of two different ELISA techniques. The increased secretion of IFN-gamma by peripheral blood mononuclear cells following major surgery may be a beneficial component of the host's immune response to injury.

Aged↗

Primary care physicians' refusal to care for patients infected with the human immunodeficiency virus.

We conducted a telephone survey of a random sample of office-based primary care physicians in Los Angeles County to determine their practice experiences with patients infected with the human immunodeficiency virus (HIV). Telephone interviews included questions related to the physicians' experiences evaluating patients for HIV infection during the past 6 months and the presence of HIV-infected patients in their practices. Those without HIV-infected patients were asked if this was because they had not encountered such patients, because those patients had died, or because the physicians had chosen to refer these patients elsewhere or the patients had gone elsewhere for care. Of physicians who participated in the survey, 78% had evaluated a patient for HIV infection in the past 6 months; 34% were currently providing primary care for infected patients; and 36% had elected to refer HIV-infected patients elsewhere, or their patients had elected to find other physicians. In all, 48% of physicians in the sample had elected not to care for, or said they would not provide care for, patients with HIV infection. Among Los Angeles County primary care physicians, 36% have refused to provide continuing care for HIV-infected patients and another 12% indicated their unwillingness to do so should such patients present themselves for care. As of 1991, the reservoir of primary care physicians in Los Angeles not yet involved with but willing to care for HIV-infected patients is relatively small (15%).

Attitude of Health Personnel↗

How satisfying is the practice of internal medicine? A national survey.

OBJECTIVE: To survey members of the American College of Physicians about their level of satisfaction and sources of dissatisfaction with practice, the extent to which their satisfaction is reflected in their counseling of students about careers in internal medicine, the prevalence of their concerns about patients' access to care, and their attitudes toward changes in the health care system. DESIGN: A questionnaire survey of a random sample of members of the College. PARTICIPANTS: Members (2254) of the College were surveyed; 1446 (64%) responded and 1290 (57%) of the responses were usable. MEASUREMENTS AND MAIN RESULTS: More than 80% of respondents were satisfied with their relationships with patients, professional challenges, and opportunities to interact with colleagues. Only about half were satisfied with their potential income, and most were dissatisfied with their autonomy or loss of control over clinical decision making. Major sources of concern were administrative burdens, the threat of malpractice litigation, loss of income, and loss of clinical autonomy. Forty percent of internists say that they discourage students from careers in internal medicine, and only 39% would once again pursue such a career. "Pain in the practice" seems generalized among internists: logistic regression analysis failed to show any specific groups who were most dissatisfied or concerned. With regard to access, 18% of internists had many patients without health care insurance; 69% had some patients without coverage; and the majority (61%) had some patients who lost their insurance because of changing jobs or location. Assuring universal access to care received the highest priority rating of a set of criteria for health care reform. CONCLUSIONS: There is growing dissatisfaction with the practice of internal medicine, primarily related to concerns over loss of clinical autonomy, the increase in administrative burdens, the potential loss of income, and the threat of malpractice litigation. Although physicians are concerned about patients' access to care, proposals to improve access should be examined for their effects on the major sources of physicians' dissatisfaction with practice.

Attitude of Health Personnel↗