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Biomedical subjects

C E Lewis

Publications and source records attributed to C E Lewis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Changing sources of care for HIV infection in California.

A telephone survey was conducted of random samples of primary care physicians in Los Angeles County and in the 26 rural counties of California to assess changes in medical practices that may have occurred with the development of new pharmacological agents and recent changes in the management of infection with the HIV. Seventy-two to seventy-three percent of the physicians selected participated in the survey in both areas. The results indicate a reduction by almost two thirds of the number of primary care physicians who plan to continue to provide care to HIV-infected patients, both in Los Angeles County and the nonmetropolitan counties of California. Although some were no longer caring for HIV patients because of deaths or patient relocation, the overwhelming majority had referred their patients to infectious disease specialists and HIV clinics because of the growing complexity of the management of these patients.

California↗
PubMed1999

The Women's Health Trial Feasibility Study in Minority Populations: changes in dietary intakes.

This randomized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse backgrounds. During 1992-1994, 2,208 women aged 50-79 years, 28% of whom were black and 16% Hispanic, enrolled at clinics in Atlanta, Georgia, Birmingham, Alabama, and Miami, Florida. Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20% of energy and to make other diet modifications. At 6 months postrandomization, the intervention group reduced fat intake from 39.7% of energy at baseline to 26.4%, a reduction of 13.3% of energy, compared with 2.3% among controls. Saturated fatty acid and cholesterol intakes were reduced, but intakes of fruits and vegetables, but not grain products, increased. Similar effects were observed at 12 and 18 months. Black and non-Hispanic white women had similar levels of reduction in fat, but the decrease in Hispanic women was less. Changes did not vary significantly by education. While bias in self-reported intakes may have resulted in somewhat overestimated changes in fat intake, the reported reduction was similar to the approximately 10% of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study populations and in many subgroups.

Aged↗
PubMed1999

Interpreting age, period and cohort effects in plasma lipids and serum insulin using repeated measures regression analysis: the CARDIA Study.

Observed changes in health-related behaviours and disease risk factors may arise from physiological or environmental changes, or from biases due to sampling or measurement errors. We illustrate problems in the interpretation of such changes with longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Mean plasma cholesterol was 14 mg/dl higher in 27- than in 20-year-old black men cross-sectionally, but longitudinally it declined by 4 mg/dl during the 7 years. To sort out these contradictory assessments of the effect of age/passage of time, we estimated age and period effects under the assumptions that age effects are a smooth function of age independent of period, and that period effects are changes common to persons across all ages. Simple estimates the age effect, such as the cross-sectional age slopes, may be confounded by cohort effects, by interactions of time and age after baseline, or by the occurrence of non-linearities in response after baseline. We note examples of each potential type of bias. The data and background literature support the assumption that cohort effects do not seriously compromise interpretation for these variables in the CARDIA study. Strong secular decreases in plasma cholesterol, apparently due to population-wide dietary change, mask increases with ageing. Age increases in triglycerides are largely explained by increases in body fatness. For these data, we cautiously accept the cross-sectional age slope as an estimate of ageing and the age-matched time trend as an estimate of secular trend.

Adolescent↗
PubMed1999

Association of total and central adiposity measures with fasting insulin in a biracial population of young adults with normal glucose tolerance: the CARDIA study.

OBJECTIVE: To determine the association of computed tomography (CT)-measured visceral adipose tissue (AT) and other measures of adiposity with fasting insulin in a biracial (African American and Caucasian) study population of young adults. RESEARCH METHODS AND PROCEDURES: The study population consisted of 251 young adults with normal glucose tolerance (NGT), ages 28-40 years, who were volunteers from the Birmingham, Alabama, and Oakland, California centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study. RESULTS: In regression models with total adiposity measures (body mass index or dual-energy X-ray absorptiometry-measured percent fat), visceral AT (measured as a cross-sectional area in cm2) was generally a stronger predictor of insulin than overall adiposity in all race/gender groups (partial correlation coefficients ranging from 0.31 to 0.47) except for black men, in whom the associations were nonsignificant. Partial correlation coefficients between waist circumference and insulin, controlling for percent fat, were nearly identical to those between visceral AT and insulin in women and in white men. Analyses performed on 2060 NGT CARDIA subjects who were not in this study of visceral AT showed significant correlations of waist circumference with insulin in all race/gender groups, including black men, and that black men in the visceral AT study group were significantly leaner than other black male CARDIA subjects. DISCUSSION: We conclude that visceral AT was associated with fasting insulin in NGT participants in three of the four race/gender groups (black men excepted) and that waist circumference was a good surrogate for visceral AT in examining associations of central adiposity with fasting insulin.

Absorptiometry, Photon↗
PubMed1999

Macrophage responses to hypoxia: relevance to disease mechanisms.

Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.

Animals↗
PubMed1999

Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast.

Necrosis is a common feature of invasive carcinoma of the breast and is caused by chronic ischaemia leading to infarction. Although necrosis was previously assumed to be due to a generally poor blood supply in the tumour, in this study we show that it is present in tumours with focal areas of high vascular density situated away from the actual sites of necrosis. This may account, in part, for the previous observation that necrosis is linked to poor prognosis in this disease. Highly angiogenic tumours often display blood vessel shunting from one tumour area to another, which further exacerbates ischaemia and the formation of tumour necrosis. We have recently demonstrated that high focal microphage infiltration into breast tumours is significantly associated with increased tumour angiogenesis and poor prognosis and that the macrophages accumulate in poorly vascularized, hypoxic areas within breast tumours. In order to investigate the interactions of macrophages with chronic ischaemia (as reflected by the presence of necrosis) and angiogenesis in breast tumours, we quantified the levels of these three biological parameters in a series of 109 consecutive invasive breast carcinomas. We found that the degree of tumour necrosis was correlated with both microphage infiltration (Mann-Whitney U, P-value = 0.0009; chi-square, P-value = 0.01) and angiogenesis (Mann-Whitney U P-value = 0.0008, chi square P-value = 0.03). It was also observed that necrosis was a feature of tumours possessing an aggressive phenotype, i.e. high tumour grade (chi-square, P-value < 0.001), larger size (Mann-Whitney U, P-value = 0.003) and low oestrogen receptor status (Mann-Whitney U, P-value = 0.008; chi-square, P-value < 0.008). We suggest, therefore, that aggressive tumours rapidly outgrow their vascular supply in certain areas, leading to areas of prolonged hypoxia within the tumour and, subsequently, to necrosis. This, in turn, may attract macrophages into the tumour, which then contribute to the angiogenic process, giving rise to an association between high levels of angiogenesis and extensive necrosis.

Adult↗
PubMed1999

The effect of needle gauge and local anaesthetic on the diagnostic accuracy of breast fine-needle aspiration cytology.

AIMS: The value of breast fine needle aspiration cytology (FNAC) is well established. This prospective study evaluates the effects of local anaesthetic (LA) and different gauge needles on the diagnostic accuracy of breast FNAC. METHODS: Aspirates were obtained from 59 consecutive excised breast tumours (51 malignant, eight benign) using green (21-G) and blue-hub (23-G) needles, both before and after infiltration of LA at the aspiration site. RESULTS: There was good agreement for the cytological diagnosis of each tumour when compared by needle size (kappa = 0.85) and the presence of LA (kappa = 0.77). Diagnostic sensitivity ranged from 88 to 92%. None of the differences were statistically significant. In addition LA appeared to have no effect upon the cytological grading of breast carcinomas (chi2 = 1.98, (df 3, P = 0.58). DISCUSSION: The use of the smaller gauge blue-hub needle or LA does not appear to affect adversely the diagnostic accuracy of breast FNAC. Whether using LA or the blue needle routinely in the breast clinic will have an effect upon the discomfort experienced during FNAC remains to be proven.

Anesthetics, Local↗
PubMed1999

Racial differences in amounts of visceral adipose tissue in young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study.

BACKGROUND: In several white populations, visceral adipose tissue (VAT) is a risk factor for development of type 2 diabetes and dyslipidemia. VAT can be accurately assessed by computed topography or magnetic resonance imaging, but is also estimated from anthropometric variables, such as waist-to-hip ratio, waist circumference, or sagittal diameter. To date, anthropometric variables have been used largely in whites and inadequate data are available to evaluate the validity of these variables in other groups. OBJECTIVES: The objectives of this study were to 1) determine whether amount of VAT in relation to total body fatness differs in different race and sex groups and 2) determine which anthropometric variables predict amount of VAT in different race and sex groups. DESIGN: We determined the amount and location of body fat, including assessment of VAT by computed tomography, in young adult white and black men and women participating in the 10-y follow-up of the CARDIA (Coronary Artery Risk Development in Young Adults) Study. RESULTS: Black men had less visceral fat (73.1+/-35.9 cm2) than white men (99.3+/-40 cm2), even when VAT was corrected for total body fatness. Black women were more obese than white women and thus had more visceral fat (75.1+/-37.5 compared with 58.6+/-35.9 cm2, respectively). This difference disappeared when corrected for total body fatness. CONCLUSIONS: Both waist circumference and sagittal diameter were good predictors of VAT in all groups. However, the nature of this relation differed such that race- and sex-specific equations will likely be required to estimate VAT from waist circumference or sagittal diameter.

Adipose Tissue↗
PubMed1998

Expression of estrogen receptor alpha and beta transcripts in female monkey hippocampus and hypothalamus.

Understanding mechanisms of estrogen effects on cognition is critical for designing therapies for post-menopausal women and others with dementia. Hippocampus, an area important to cognitive function, responds robustly on estrogen. ERbeta and ERalpha transcripts were detected in the hippocampus and hypothalamus of an ovariectomized female monkey at a relatively high ERbeta/ERalpha ratio. These results suggest that ERbeta may play a role in mediating estrogen effects in the primate hippocampus and hypothalamus.

Animals↗
PubMed1998

Validation of anti-vascular endothelial growth factor (anti-VEGF) antibodies for immunohistochemical localization of VEGF in tissue sections: expression of VEGF in the human endometrium.

Transient transfection of COS-1 cells followed by fixation, embedding in paraffin, and immunohistochemistry has identified anti-vascular endothelial growth factor (anti-VEGF) mouse monoclonal antibodies that efficiently immunostain VEGF in paraffin-embedded tissue sections. Immunohistochemical localization of VEGF in 34 specimens of normal human endometrium that had been collected at different stages of the menstrual cycle was then performed. VEGF was present at all stages of the cycle, but both the pattern and the intensity of staining varied. Thus, VEGF expression occurred predominantly in the endometrial epithelium and while weak in the proliferative phase, was strong in the secretory phase. VEGF expression in the stroma was weaker than in the proliferative phase glands and did not change throughout the cycle. These findings are in agreement with reports of VEGF mRNA expression in the endometrium, but disagree with previous immunohistochemical studies that employed an immunohistochemically unvalidated antiserum. This study has shown that the commercially available anti-VEGF monoclonal antibody M293 is excellent for the immunohistochemical localization of VEGF in paraffin sections.

Adenocarcinoma↗
PubMed1998

Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults.

This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated.

Adolescent↗
PubMed1998

Recruitment strategies in the women's health trial: feasibility study in minority populations. WHT:FSMP Investigators Group. Women's Health Trial:Feasibility Study in Minority Populations.

The Women's Health Trial:Feasibility Study in Minority Populations (WHT:FSMP) examined the feasibility of recruiting postmenopausal women from a broad range of racial and socioeconomic backgrounds into a primary prevention trial requiring marked reductions in dietary fat. Postmenopausal women aged 50-79 yr who had no history of cardiovascular disease or cancer and who consumed 36% or more total energy from fat qualified to participate. We randomized the women into dietary intervention (60%) or control (40%) groups; we aimed to randomize 750 women in 18 months in each of the three clinical centers. All centers achieved goals for randomization based on ethnicity, and two centers exceeded overall recruitment goals. The greatest source of randomized participants was mass mailing, followed by items in the media, referrals, and community outreach. Recruitment yields were generally similar for the ethnic groups but lower for less-educated participants. The experience of WHT:FSMP indicates that postmenopausal women from the African-American, Hispanic, and non-Hispanic white communities can be recruited into dietary intervention studies for the prevention of disease.

Black or African American↗
PubMed1998

Competencies for population-based clinical managers. A survey of managed care medical directors.

BACKGROUND: The evolution of American health care into integrated systems of delivery and finance requires a specialized set of population-based skills for physicians. The field of preventive medicine represents one source of this expertise. Specific competencies for the emerging area of managerial medicine have not been well delineated. METHODS: Using concept documents from the Residency Review Committee for Preventive Medicine and the American Board of Preventive Medicine, a list of proposed competencies for managerial medicine was identified. Surveys were mailed to medical directors of all members of the American Association of Health Plans and to a random sample of diplomates of the American Board of Preventive Medicine. Respondents were asked to rate the importance of these competencies for a population-oriented clinician manager. RESULTS: Areas rated highly by medical directors included health services research (including outcome research), quality assurance and improvement, health risk assessment and reduction, programmatic skills, and clinical preventive skills. Responses from preventive medicine specialists were similar, but placed lower emphasis on these skills. CONCLUSION: Despite its limited response rate, this survey may be useful in the implementation of specialty training in managerial medicine. Residency training programs may choose to emphasize specific content area that reflect the priorities expressed by physicians actively involved in management.

Attitude of Health Personnel↗
PubMed1998

Differences in cardiovascular disease risk factors in black and white young adults: comparisons among five communities of the CARDIA and the Bogalusa heart studies. Coronary Artery Risk Development In Young Adults.

PURPOSE: To examine community differences in cardiovascular disease (CVD) risk factors among black and white young adults by combining data from two large epidemiologic studies. METHODS: Data are from participants aged 20-31 years in the Coronary Artery Risk Development In Young Adults (CARDIA) study (1987-1988; N = 4129) and the Bogalusa Heart study (1988-1991; N = 1884), adjusting for data collection differences prior to analysis. CARDIA includes four urban sites: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. Bogalusa is a semi-rural town in Southeastern Louisiana. CVD risk factors examined were smoking status, body habitus, and blood pressure. RESULTS: In Birmingham and Bogalusa, more white than black women were current smokers; no ethnic differences were observed among men. In Chicago, Minneapolis, and Oakland, more blacks were current smokers than were whites. For all sites, educational level was strongly inversely related to current smoking status; ethnic differences were more apparent among those with up to a high school education. Among white men and women, prevalence of obesity (body mass index > 31.1 kg/m2 in men and 32.3 kg/m2 in women) was greater in Birmingham and Bogalusa than in Chicago. Minneapolis, and Oakland. Mean systolic blood pressures were highest in Bogalusa, and the proportion of black men with elevated blood pressure (> or = 130/85 mmHg) was higher in Bogalusa and Birmingham. CONCLUSIONS: Community and ethnic differences in CVD risk factors were observed among young adults in two large epidemiologic studies. Further studies may enhance our understanding of the relationship of geographic differences in CVD risk to subsequent disease.

Adult↗
PubMed1998

Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

Angiogenesis is an essential requirement for tumour growth and metastasis and is regulated by a complex network of factors produced by both stromal cells and neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to promote tumour angiogenesis. We have demonstrated recently that high numbers of tumour-associated macrophages (TAMs) are significantly associated with increased tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We have also shown that TAMs are a major source of TNF-alpha in invasive breast carcinomas, and that macrophage-like stromal cells as well as tumour cells synthesize TP in such tumours. However, little is known of the factors that regulate the production or activity of these factors in the tumour microenvironment. As TNF-alpha has been shown to up-regulate TP expression in tumour cells in vitro we performed an immunohistochemical study to investigate the possibility that TNF-alpha may be involved in the regulation of TP expression by malignant breast epithelial cells in vivo. To do this, we used a cocktail of non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha-expressing macrophages and TNF-alpha bound to its receptors on tumour cells and endothelial cells in a series of 93 invasive carcinomas of the breast. A semiquantitative grading system was then used to compare these staining patterns with that for TP in the same biopsies. TNF-alpha immunoreactivity was also compared with various important tumour variables known to relate to outcome in this disease (microvessel density, node status, grade, stage, receptor status and macrophage infiltration), as well as relapse-free and overall survival data for these patients. Our data show significant positive correlations between TNF-alpha bound to its receptors on tumour cells and: (1) TP protein production by tumour cells, and (2) axillary lymph node status (i.e. metastasis). These results suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring TAMs may play a part in the regulation of TP expression by tumour cells as well as their metastatic behaviour. This may explain, in part, the relationship between increased macrophage infiltration and angiogenesis in breast cancer, and further supports the contention that TAMs may represent an important target for future anti-angiogenic therapies.

Adult↗
PubMed1998

Is fasting insulin concentration inversely associated with rate of weight gain? Contrasting findings from the CARDIA and ARIC study cohorts.

OBJECTIVE: To test whether a higher fasting insulin concentration is associated with a lower rate of weight gain over six to seven years. DESIGN: Two longitudinal epidemiologic cohorts including blacks and whites. SUBJECTS: The Coronary Artery Risk Development in Young Adults (CARDIA) Study examined subjects aged 18-30 y in 1985-86 and 1992-93 (n = 3636), and the Atherosclerosis Risk in Communities (ARIC) Study examined subjects aged 45-64 y in 1987-89 and 1993-95 (n = 11179). MEASUREMENTS: In each study, fasting insulin at baseline and weight change during follow-up were measured in participants without diabetes. RESULTS: In whites and black men in CARDIA, there was a positive age-adjusted association between baseline insulin and weight change, although weight change was not entirely monotonic across the insulin quartiles. In these race-gender groups, the linear regression coefficients indicated that each 50 pmol/L increment of baseline insulin was associated (P < 0.05) with approximately 0.10 kg/y greater rate of weight gain (95% confidence intervals (CI) for this estimate in kg/y were 0.023-0.187 for white women, 0.015-0.150 for black men, and 0.011-0.158 for white men). The association was eliminated entirely with adjustment for baseline weight. In contrast, among whites and black women in ARIC, the association was negative, with the linear regression coefficients suggesting that each 50 pmol/L higher fasting insulin concentration was associated (P < 0.05) with a 0.03-0.10 kg/y lower rate of weight gain (95% CI for this estimate in kg/y were -0.133 to -0.061 for black women, -0.106 to -0.054 for white women, and -0.055 to -0.009 for white men). This finding was generally strengthened by adjustment for baseline body mass index (BMI). CONCLUSIONS: A higher fasting insulin concentration is associated modestly with a lower rate of weight gain in ARIC, but not in CARDIA.

Adult↗
PubMed1998

Response of tumour cells to hypoxia: role of p53 and NFkB.

Hypoxia is present in several areas of malignant tumours and is thought to result from an inadequate rate of tumour angiogenesis, vascular collapse, or both. The presence and extent of these hypoxic tumour microenvironments have recently been shown to influence tumour progression by regulating both tumour cell survival and the expression of key angiogenic molecules. Recent studies have suggested that mutations in the tumour suppressor gene, p53, may play an important role in regulating the adaptive response of tumour cells to hypoxia by enhancing their survival and release of proangiogenic factors such as vascular endothelial growth factor. It has even been suggested that hypoxia may select for the survival of the more malignant clones harbouring such genetic defects as mutations in p53. Recently, the transcription factor, NFkB, has also been implicated as a novel mediator of the effects of hypoxia and reoxygenation in tumour cells. This article reviews some of the molecular mechanisms subserving the responses of tumour cells to hypoxic stress, particularly the role and relation of NFkB and p53 in regulating this phenomenon.

Genes, p53↗