Showing papers by "Wake Forest University published in 1994"

c-erbB-2 Expression and Response to Adjuvant Therapy in Women with Node-Positive Early Breast Cancer

Abstract: Background The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy. Methods Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation. Results Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if thei...

A Randomized Trial Comparing Fluconazole with Amphotericin B for the Treatment of Candidemia in Patients without Neutropenia

Abstract: Background Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. Methods To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count ≥ 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. Results Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. T...

Health-related quality of life measures for women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program in Women (CPW) Research Group.

Abstract: Urinary incontinence (UI) is a relatively common condition in middle-aged and older women Traditional measures of symptoms do not adequately capture the impact that UI has on individuals' lives Further, severe morbidity and mortality are not associated with this condition Rather, Ul's impact is primarily on the health status and health-related quality of life (HRQOL) of women Generic measures of HRQOL inadequately address the impact of the condition on the day-to-day lives of women with UI The current paper presents data on two new condition-specific instruments designed to assess the HRQOL of UI in women: the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionaire (IIQ) Used in conjunction with one another, these two measures provide detailed information on how UI affects the lives of women The measures provide data on the more traditional view of HRQOL by assessing the impact of UI on various activities, roles and emotional states (IIQ), as well as data on the less traditional but critical issue of the degree to which symptoms associated with UI are troubling to women (UDI) Data on the reliability, validity and sensitivity to change of these measures demonstrate that they are psychometrically strong Further, they have been developed for simple, self-administration

Self-presentation: Impression Management And Interpersonal Behavior

Abstract: Provides an up-to-date analysis of the effects of self-presentation on behaviour. This text integrates the latest research from personality, social, organisational and health psychology.

Wound treatment employing reduced pressure

Abstract: A method of treating tissue damage comprises applying a negative pressure to a wound sufficient in time and magnitude to promote tissue migration and thus facilitate closure of the wound. The method is applicable to wounds, burns, infected wounds, and live tissue attachments. A wound treatment apparatus is provided in which a fluid impermeable wound cover is sealed over a wound site. A screen in the form of an open-cell foam screen or a rigid porous screen is placed beneath the wound cover over the wound. A vacuum pump supplies suction within the wound cover over the treatment site.

Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.

Abstract: BACKGROUND HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease. METHODS AND RESULTS Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02). CONCLUSIONS In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.

Racial Differences in Survival From Breast Cancer: Results of the National Cancer Institute Black/White Cancer Survival Study

Abstract: Objective. —To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. Design and Participants. —Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. Main Outcome Measure. —Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. Results. —After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio=1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer—specific mortality. Conclusions. —Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women. ( JAMA . 1994;272:947-954)

A Clinical Grading Scale to Predict Malignant Hyperthermia Susceptibility

Abstract: Background:The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of

Internists' Attitudes about Clinical Practice Guidelines

Abstract: Objective: To assess internists' familiarity with, confidence in, and attitudes about practice guidelines issued by various organizations. Design: Cross-sectional, self-administered survey. Partici...

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

Abstract: An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Self-presentation can be hazardous to your health: impression management and health risk.

Abstract: People's concerns with how others perceive and evaluate them can lead to behaviors that increase the risk of illness and injury. This article reviews evidence that self-presentation motives play a role in several health problems, including HIV infection; skin cancer; malnutrition and eating disorders; alcohol, tobacco, and drug use; injuries and accidental death; failure to exercise; and acne. The implications of a self-presentational perspective for research in health psychology, the promotion of healthful behaviors, and health care delivery are discussed. Language: en

Costs and benefits of plant responses to disease: resistance and tolerance

Abstract: A major assumption of models of the evolution of plant resistance to disease is that plant resistance involves fitness costs. To test this assumption, a field experiment was performed so that a quantitative-genetic analysis could be used to detect fitness costs to Ipomoea purpurea of resistance to different fungal isolates of Colletotrichum dematium, a pathogenic fungus causing the disease anthracnose. This experiment yielded no evidence that resistance to anthracnose involves direct fitness costs. Nevertheless, trade-offs in plant fitness that were unrelated to resistance were detected between different disease environments. Tolerance, defined as the ability to compensate in part for fitness decrements caused by disease, was found to involve fitness costs. Halfsib families that were more tolerant of disease had lower fitness in the absence of disease. The possibility that the cost of tolerance could obscure fitness costs of resistance is explored.

Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure.

Abstract: BACKGROUNDThe mechanism of the alterations in the pattern of left ventricular (LV) filling during the development of congestive heart failure (CHF) is not fully understood.METHODS AND RESULTSWe studied six conscious dogs instrumented to measure LV and left atrial (LA) pressures and LV volume as CHF was induced by rapid pacing. Diastolic filling dynamics were serially measured over 4 weeks during normal sinus rhythm. Four days after we initiated pacing, the peak early diastolic filing rate decreased from 108 +/- 24 to 88 +/- 27 mL/s (P < .05) as the maximal early diastolic LA-LV pressure gradient decreased associated with a slowing of the rate of LV relaxation. Subsequently, the peak early filling rate progressively increased, returning to control at 1 week, and by the fourth week, it had increased to 168 +/- 39 mL/s (P < .05). These changes in early filling rates occurred as the maximal early diastolic LA-LV pressure gradient increased in association with a progressive increase in LV pressure despite furt...

Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial

Abstract: In order to evaluate further the efficacy of local intramuscular injections of botulinum-A toxin (BAT-A) in the management of dynamic equinus deformity associated with cerebral palsy, a randomized, double-blind, placebo-controlled study was undertaken. When evaluated using our Physician Rating Scale, 83% (five of six) of patients receiving toxin showed improvement, versus 33% (two of six) receiving placebo. There were no major complications. BAT-A injections appear to be safe and effective in children, and merit further prospective study.

Self‐Reported Causes of Physical Disability in Older People: The Cardiovascular Health Study

Abstract: OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people ≥ 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.

Prevalence of Subclinical Atherosclerosis and Cardiovascular Disease and Association with Risk Factors in the Cardiovascular Health Study

Abstract: The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.

Remodeling of Coronary Arteries in Human and Nonhuman Primates

Abstract: Objective. —To compare coronary artery remodeling (compensatory enlargement) in human and nonhuman primates. Design. —Coronary artery data were analyzed retrospectively for 416 nonhuman primates and 100 men and women. Setting. —The monkeys had been in experiments involving diet-induced coronary artery atherosclerosis. The human hearts were obtained from the North Carolina Baptist Hospital, Winston-Salem, and age greater than 25 years was the only criterion. Patients and Other Participants. —The left anterior descending coronary arteries from 100 humans, 328 cynomolgus monkeys, and 88 male rhesus monkeys were used. Interventions. —None; this was a cross-sectional observational study. Main Outcome Measures. —Coronary artery size, lumen area, and plaque size. In the humans, we also examined demographic characteristics (ethnicity, sex, and history of hypertension) and pathologic criteria (eccentricity or concentricity of plaque area). Results. —On average, lumen size remained unaffected by plaque size. Lumen size was variable and could not be predicted by traditional risk factors for coronary heart disease. However, lack of compensation (decreased lumen size as plaques enlarged) and history of coronary heart disease were significantly correlated. Conclusions. —The similarity of remodeling in human and nonhuman primates suggests that the process has general biologic significance. Lack of remodeling may be a major determinant of whether a person with coronary artery atherosclerosis develops its complications. ( JAMA . 1994;271:289-294)

Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse.

Abstract: We have examined the ability of different neurotrophic and growth factors to prevent axotomy-induced motoneuron cell death in the developing mouse spinal cord. After postnatal unilateral section of the mouse sciatic nerve, most motoneuron (MN) loss occurs in the lateral motor column of the fourth lumbar segment (L4). Significant axotomy-induced cell death occurred after surgery performed on or before postnatal day (PN) 5. In contrast, no significant cell loss was found when axotomy was performed after PN10. Axotomy on PN2 or PN5 resulted in a 44% loss of L4 motoneurons by 7 days, and a 66% loss of motoneurons by 10 days postsurgery. Implantation of gelfoam presoaked in various neurotrophic factors at the lesion site rescued axotomized motoneurons. Nerve growth factor (NGF), neurotrophin-4/5 (NT-4/5) and ciliary neurotrophic factor (CNTF) rescued 20%-30% of motoneurons, whereas brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and insulin-like growth factor 1 (IGF-1) rescued virtually all motoneurons from axotomy-induced death. By contrast, platelet-derived growth factor (PDGF)-AA, PDGF-AB, basic fibroblast growth factor (bFGF), and interleukin (IL-6) were ineffective on motoneuron survival following axotomy. NGF, BDNF, NT-3, IGF-1, and CNTF also prevented axotomy-induced atrophy of surviving motoneurons. These data show that mouse lumbar motoneurons continue to be vulnerable to axotomy up to about 1 week after birth and that a number of trophic agents, including the neurotrophins, CNTF, and IGF-1, can prevent the death of these neurons following axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Expandable, intraluminal stents

Abstract: An expandable, intraluminal stent is provided which can be inserted into a body passage, and is capable of supporting an intact vascular graft. The stent is a thin-walled, generally tubular member having a plurality of rigid support tabs spaced uniformly around the perimeter of the two ends of the stent. A plurality of spacer bars span longitudinally between the rigid support tabs at one end of the stent and corresponding rigid support tabs at the other end. The spacer bars serve as struts to prevent longitudinal expansion or contraction of the stent so that the length of the stent is maintained. Plastically deformable connecting links interconnect adjacent rigid support tabs around each end of the stent to enable the stent to be expanded to an enlarged diameter. The stent can be expanded with a delivery system which applies a radially, outwardly extending force from the exterior of the stent. Alternatively, the stent can be expanded using an angioplasty balloon.

Testing the Generalizability of Intervening Mechanism Theories: Understanding the Effects of Adolescent Drug Use Prevention Interventions

Abstract: Outcome research has shown that drug prevention programs based on theories of social influence often prevent the onset of adolescent drug use. However, little is known empirically about the processes through which they have their effects. The purpose of the present study was to evaluate intervening mechanism theories of two program models for preventing the onset of adolescent drug use. Analyses based on a total of 3077 fifth graders participating in the Adolescent Alcohol Prevention Trial revealed that both normative education and resistance training activated the causal processes they targeted. While beliefs about prevalence and acceptability significantly mediated the effects of normative education on subsequent adolescent drug use, resistance skills did not significantly predict subsequent drug use. More impressively, this pattern of results was virtually the same across sex, ethnicity, context (public versus private school students), drugs (alcohol, cigarettes, and marijuana) and levels of risk and was durable across time. These findings strongly suggest that successful social influence-based prevention programs may be driven primarily by their ability to foster social norms that reduce an adolescent's social motivation to begin using alcohol, cigarettes, and marijuana.

Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague‐Dawley and Fischer 344 rats

Abstract: The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague-Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague-Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of days in estrus or under the influence of exposure to estrogen, (3) earlier onset of galactocele formation, and (4) earlier onset of mammary and pituitary tumor formation but not an increased incidence of mammary and pituitary tumors when compared to concurrent control rats. Fischer 344 female rats fed atrazine at an MTD exhibited slightly lengthened estrous cycles, but no effects were observed on estradiol or progesterone levels, or on the onset or incidence of mammary tumors. These results support a hypothesis that high-dose atrazine administration in Sprague-Dawley females is related to an acceleration of age-related endocrine changes leading to an earlier onset and/or increased incidence of mammary tumors. This endocrine-mediated response, which appears to be unique to the Sprague-Dawley female rat, occurs only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, promoting prolonged exposure to endogenous estrogen.