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Biomedical subjects

B Newman

Publications and source records attributed to B Newman.

At least 19 recordsLinked to original sources

The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology.

The integration of epidemiology and molecular biology provides a new strategy to identify additional risk factors for breast cancer and to better understand the role played by traditionally recognized risk factors. The Carolina Breast Cancer Study (CBCS) is a population-based, case-control study designed to identify causes of breast cancer among Caucasian and African-American women who are residents of a 24-county area of central and eastern North Carolina. Information on established and potential breast cancer risk factors is obtained by personal interviews. Blood samples are collected from all consenting participants. Medical record documentation and paraffin-embedded tumor specimens are obtained for all breast cancer patients. DNA from tumor tissue is tested for a variety of molecular alterations characteristic of breast cancer. Germline DNA from blood lymphocytes is evaluated for presence of alleles increasing susceptibility to breast cancer. Statistical analyses evaluate gene-environment interaction by exploring the associations between environmental/behavioral factors and breast cancer in relation to specific molecular alterations (germline and tumor). Results will help identify high-risk women, clarify causal pathways, and hopefully contribute to the prevention of breast cancer.

Adult

Rapid reporting of cancer incidence in a population-based study of breast cancer: one constructive use of a central cancer registry.

To support a study of genetic risk factors for breast cancer, the North Carolina Central Cancer Registry has implemented a rapid reporting procedure for hospitals in the study area. This system permits the identification of newly diagnosed breast cancer cases within a very short time period (less than one month). The procedures are straightforward, cost-effective, and greatly benefit the objectives of tissue collection and interviews with the cases. This article describes the rapid reporting procedures and their potential impact for population-based research. For the objective of making generalizable risk statements, the necessity of population-based research is stressed; participation with central cancer registries is endorsed for this and other molecular epidemiologic applications.

Breast Neoplasms

Studying environmental influences and breast cancer risk: suggestions for an integrated population-based approach.

Increased attention has focused in recent years on environmental exposures which may elevate risk of human breast cancer. Following a brief introduction to the topic, we present a summary of recent evidence regarding the role of chlorinated hydrocarbons (e.g. pesticides), occupational exposures (e.g. electromagnetic fields), dietary factors, and other hydrocarbons (e.g. tobacco). Next, we present suggestions for additional measurements which may help to clarify the contribution of environmental factors, including individual and ecologic level exposure histories, polymorphisms in carcinogen-metabolizing enzymes, and interactions among environmental exposures, breast tumor characteristics, and other risk factors for breast cancer. Finally, we discuss how a population-based approach may be used to integrate these sources of information and could provide new clues regarding the role of environmental influences in breast cancer.

Breast Neoplasms

The detection of varicella zoster antibodies by simultaneous competitive EIA and its comparison with radioimmunoassay, latex agglutination and antiglobulin type EIA.

A rapid and simultaneous competitive enzyme immunoassay (EIA) for the detection of human antibodies to varicella zoster virus (VZV) which utilises complement fixing (CF) VZV antigen and peroxidase labelled human antibodies to VZV as reagents is described. The competitive EIA was compared with competitive radioimmunoassay (RIA) in a selection of sera from 501 blood donors and 115 patients. The competitive EIA was comparable in sensitivity and specificity to the RIA, but had the advantage of not requiring radiolabelling or facilities for radioactive handling and disposal, and also had an enhanced stability. The competitive EIA was compared with competitive RIA, a commercially available latex agglutination assay and an antiglobulin type EIA on sera from 100 patients. The competitive EIA and RIA appeared to be the most sensitive tests.

Antibodies, Anti-Idiotypic

Effect of pulse dexamethasone therapy on the incidence and severity of chronic lung disease in the very low birth weight infant.

We conducted a prospective, randomized, double-blind trial to assess the efficacy and safety of pulse doses of dexamethasone on survival without supplemental oxygen in very low birth weight infants at high risk of having chronic lung disease. Seventy-eight infants with birth weights < or = 1500 gm who were ventilator dependent at 7 days of postnatal age were randomly assigned to receive pulse doses of dexamethasone, 0.5 mg/kg per day, divided twice daily (n = 39), or an equivalent volume of saline solution placebo (n = 39), for 3 days at 10-day intervals until they no longer required supplemental oxygen or assisted ventilation, or reached 36 weeks of postmenstrual age. At study entry, the groups did not differ by birth weight, gestational age, or severity of lung disease. At 36 weeks of postmenstrual age, there was both a significant increase in survival rates without oxygen supplementation (p = 0.03) and a significant decrease in the incidence of chronic lung disease (p = 0.047) in the group that received pulse therapy. Supplemental oxygen requirements were less throughout the study period in the group that received repeated pulse doses of dexamethasone (p = 0.013). The total numbers of deaths and the durations of supplemental oxygen, ventilator support, and hospital stay did not differ between groups. Recorded side effects in the pulse therapy group were minimal and included an increase in the use of insulin therapy for hyperglycemia (p < 0.05). We conclude that in this population of very low birth weight infants, treatment with pulse doses of dexamethasone resulted in improvement in pulmonary outcome without clinically significant side effects.

Adult

Enhancing patient care: case management and critical pathways.

This paper describes the processes involved in case management and in developing critical pathways as a mechanism to improve customer focused care. Critical pathways can be used to manage the care of patients in settings as varied as acute care hospitals, tertiary care facilities and primary health care areas. Advantages and disadvantages of case management and the critical pathways method of management are outlined from a nursing perspective.

Case Management

Proteus syndrome: emphasis on the pulmonary manifestations.

Published articles on the radiologic aspects of Proteus syndrome are sparse. This report highlights the features of this disease with specific attention to the serious pulmonary manifestations that may occur at an early age. Two cases of Proteus syndrome and severe lung disease are presented, with complete autopsy in one case and correlative surgical pathologic data in the other. Multiple superficial and visceral vascular abnormalities were present in both cases. Both patients developed rapidly progressive diffuse cystic emphysematous pulmonary disease leading to the death of one patient at age 18 years and a heart-lung transplant in the other at age 8 1/2 years. Extensive gross pulmonary cysts were evident pathologically with diffuse panlobar emphysema microscopically. Studies of collagen and cultured fibroblasts in one patient revealed no abnormality. The early presentation, rapid progression and potentially lethal nature of lung involvement has not previously been emphasized.

Adolescent

Recognition of malposition of the liver and spleen: CT, MRI, nuclear scan and fluoroscopic imaging.

Thirteen children initially suspected to have an intrathoracic or intraabdominal mass had malposition of the liver and/or spleen discovered by ultrasound. This group consisted of five children with diaphragmatic eventration or hernia and eight with wandering spleen or liver. Careful ultrasonographic examinations were diagnostic in all patients; seven had surgical confirmation. CT, MRI, nuclear scan and fluoroscopic imaging were useful in select instances. The liver and spleen have a characteristic anatomic configuration and sonographic appearance that should enable them to be recognized, and pathological alterations appreciated, even when these organs are ectopic in location or malformed.

Child

Internalization of Escherichia coli into human kidney epithelial cells: comparison of fecal and pyelonephritis-associated strains.

A gentamicin survival assay, using primary human renal epithelial cells and Escherichia coli strains isolated from the feces of asymptomatic individuals and from the urine or blood of patients with acute pyelonephritis, was used to investigate bacterial internalization as a model for renal parenchymal invasion in pyelonephritis. E. coli strains, regardless of their origin, efficiently entered into human renal epithelial cells, a process inhibited by cytochalasin D. While the percentage of survival of nonhemolytic pyelonephritis isolates did not differ from that of fecal isolates, survival of hemolytic pyelonephritis strains was lower than that of nonhemolytic strains, perhaps as a consequence of the greater cytotoxicity of hemolytic strains. There was no evidence of intracellular multiplication of E. coli. These results demonstrate that human renal epithelial cells are capable of efficient uptake of E. coli regardless of the source of the bacteria.

Cells, Cultured

Iatrogenic tracheobronchial perforation in infants.

We describe the clinical and radiographic features of four premature infants with acute iatrogenic tracheobronchial perforation by endotracheal tube (ETT) placement. One tube penetrated posteriorly into the esophagus, one directly through the carina; one perforated the right main bronchus posteriorly; and one breached the site of a recently repaired tracheoesophageal fistula. In only one infant was the intubation procedure clinically recognized to be traumatic. Radiographs obtained for tube placement demonstrated inferior malposition of the ETT in all four babies, decreased pulmonary aeration in three of four, acute retrocardiac infraazygos pneumomediastinum in three of four, and acute pleural effusion in one of four. Two infants developed progressive air leak and died in spite of drainage with multiple chest tubes; two survived and did well with conservative management. An additional eight cases have been previously reported, with an overall mortality of 58%. Prompt recognition of acute airway perforation can be lifesaving. Unexpected respiratory distress after intubation associated with acute infraazygos pneumomediastinum strongly suggests this entity.

Acute Disease

Multivariate analysis of the insulin resistance syndrome in women.

The insulin resistance syndrome (IRS) is characterized by a constellation of interrelated coronary heart disease (CHD) risk factors, including dyslipidemia, obesity, central obesity, elevated systolic blood pressure, and hyperinsulinemia. Factor analysis was used to investigate the clustering of these risk factors in individuals by examining the correlational structure among these variables. Data from 281 genetically unrelated nondiabetic women who participated in exam 2 (1979 to 1980) of the Kaiser Permanente Women Twins Study were used. Factor analysis reduced 10 correlated risk factors to 3 uncorrelated factors, each reflecting a different aspect of the IRS: factor 1 (increased body weight, waist circumference, fasting insulin, and glucose), factor 2 (increased postload and fasting glucose and insulin and systolic blood pressure), and factor 3 (larger low-density lipoprotein particles, decreased plasma triglycerides, and increased high-density lipoprotein). Together, the factors explained nearly 66% of the total variance in the data. Thus, factor analysis defined three distinct aspects of the IRS in this sample of nondiabetic women. These factors may reflect separate underlying mechanisms of the syndrome, each of which may also be involved in CHD risk.

Blood Glucose

LDL subclass phenotypes and the insulin resistance syndrome in women.

BACKGROUND: Low-density lipoprotein (LDL) subclass phenotype B, characterized by predominance of small, dense LDL particles, is associated with elevated plasma triglycerides and apolipoprotein B and with lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Because these abnormalities resemble the dyslipidemia of insulin resistance, we examined associations of LDL subclass phenotype with plasma insulin levels and with other aspects of the insulin resistance syndrome. METHODS AND RESULTS: LDL subclass phenotypes were determined by gradient gel electrophoresis in 682 female twins aged 30 to 91 years who participated in the second examination of the Kaiser Permanente Women Twins Study. Prevalence of phenotype B and the intermediate phenotype (I) increased strongly with age, obesity, and non-insulin-dependent diabetes. In multivariate analysis of nondiabetic women, phenotype B or I was independently associated with each aspect of the insulin resistance syndrome, including higher plasma triglycerides, waist-hip ratio, fasting and postload insulin levels, and systolic blood pressure and lower HDL cholesterol levels after adjustment for age and body mass index. The prevalence of phenotype B or I rose progressively from 5.6% in women with no manifestations of the insulin resistance syndrome to 100% in women with four syndrome components. In 25 nondiabetic, monozygotic twin pairs discordant for subclass phenotype, the twins with phenotype B (or I) had significantly higher levels of body mass index, waist-hip ratio, and systolic blood pressure than their twins with phenotype A. Thus, nongenetic variation in these risk factors is important in explaining their associations with LDL subclass phenotype. CONCLUSIONS: Small, dense LDL is an integral feature of the insulin resistance syndrome. Nongenetic (ie, behavioral or environmental) factors are important for the expression of the phenotype and for its association with other heart disease risk factors.

Adult

Alcohol consumption and insulin concentrations. Role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides.

BACKGROUND: The relation between alcohol intake and insulin levels may explain, in part, the reported associations of alcohol with cardiovascular disease risk factors, including high-density lipoprotein (HDL) cholesterol, triglycerides, blood pressure, and glucose levels, each of which has been recognized as a component of the insulin resistance syndrome. METHODS AND RESULTS: Subjects included nondiabetic participants of the Kaiser Permanente Women Twins Study (1989 through 1990). Usual alcohol intake was assessed as part of a food frequency questionnaire. For women from twin pairs in which both twins drank (n = 338), an increment of 12 g of alcohol per day (about one drink) was associated with an 8% lower 2-hour post-glucose-load insulin (P < .01) in a multiple regression analysis for twin data, adjusted for age, body mass index, waist-to-hip ratio, total caloric intake, and family history of diabetes. With genetic influences removed by matched analysis of the subset of 98 monozygotic twin pairs, an intrapair difference of 12 g of alcohol per day was associated with a 12.4% intrapair decrement in postload insulin (P < .01). Inverse associations were also seen for fasting insulin. Alcohol consumption was inversely associated with postload glucose but not with fasting glucose in unmatched (P = .05) and matched (P = .005) analyses. A significant positive association of alcohol intake with high-density lipoprotein cholesterol and an inverse relation of alcohol intake with triglycerides were each independent of insulin levels (P < or = .02 in the matched models). Neither systolic nor diastolic blood pressures were related to alcohol consumption in this sample, perhaps because of the rather low level of alcohol intake in the study population (median, 4 g/d). CONCLUSIONS: Within the range of light to moderate drinking habits, alcohol consumption was inversely related to fasting and postload insulin levels. This relation did not explain associations of alcohol intake with lipid levels and may instead reflect an additional mechanism by which moderate alcohol consumption impacts cardiovascular disease risk.

Adult