The Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial II (REACT II): rationale and study design for a clinical trial of physical activity among individuals with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the United States. In addition, persons with COPD are at risk for lower levels of physical activity, leading to further morbidity and mortality. Several studies have demonstrated that long-term exercise therapy confers benefits upon physical functioning among patients with COPD, and some studies indicate that embedding cognitive-behavioral interventions into group-mediated exercise programs is useful in promoting compliance to activity recommendations. However, compliance to long-term activity is low among COPD patients, and the effectiveness of behavioral interventions to enhance long-term activity among these patients has not been extensively explored. Thus, the primary objective of the Reconditioning Exercise and COPD Trial II (REACT II) trial is to determine whether a group-mediated cognitive-behavioral intervention will result in increased physical activity after 12 months, compared to a standard exercise therapy experience among older adults with COPD. The cognitive-behavioral intervention is designed to promote independent physical activity by encouraging participants to self-regulate physical activity with minimal dependence upon staff. The primary study outcome is kcal expended per week in moderate physical activity, and the study is designed to provide 90% power to detect a 400 kcal/week difference in moderate energy expenditure between the two intervention groups. Other outcomes to be compared between the two interventions include physical function, self-reported physical disability, health-related quality of life, exercise capacity, body composition and inflammatory mediators.

Influence of human p16(INK4) and p21(CIP1) on the in vitro activity of recombinant Plasmodium falciparum cyclin-dependent protein kinases.

The regulatory mechanisms of most cyclin dependent protein kinases (CDKs) are well understood and are highly conserved in eukaryotes. CDKs from the malaria parasite, Plasmodium falciparum, appear to be regulated in a similar manner with regard to cyclin binding and phosphorylation. In order to further understand their regulatory mechanisms, we examined two classes of cyclin dependent kinase inhibitors (CDIs) to inhibit a panel of plasmodial CDKs. We find that Pfmrk and PfPK5 are inhibited by heterologous p21(CIP1) with varying degrees of inhibition. In contrast, PfPK6, a kinase with sequence features characteristic of both a CDK and MAP kinase, is unaffected by this CDI. Furthermore, the CDK4/6 specific CDI, p16(INK4), fails to inhibit these plasmodial CDKs. Taken together, these results suggest that plasmodial CDKs may be regulated by the binding of inhibitory proteins in vivo.

Design and synthesis of Pfmrk inhibitors as potential antimalarial agents.

The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar range.

Hazards of powder on surgical and examination gloves: a collective review.

This article reviews information on the hazards associated with dusting powders on latex surgical and examination gloves. Dusting powders were first applied to latex gloves to facilitate donning. After 1980, manufacturers devised innovative techniques to manufacture gloves without dusting powders. It has been well documented that the powders on gloves present a health hazard to patients, as well as to operating-room personnel. First, these powders elicit tissue toxicity in every tissue in the body. Second, these powders serve as carriers of latex allergen and may precipitate a life-threatening allergic reaction in sensitized patients. These well-documented hazards of glove powders have caused a growing number of hospitals in the world to abandon the use of examination and surgical gloves coated with powder, and instead to use only powder-free gloves.

Revolutionary advances in skin stapling: a collective review.

The purpose of this article is to provide a collective review of the literature on skin staplers. On the basis of this review, the Auto Suture Multifire Premium, with its regular and wide metal staples, is recommended for skin closure. The Auto Suture Multifire Graftac-S is ideally suited for skin-graft fixation, because it delivers an absorbable staple that usually does not have to be removed from the healing graft. Dermal skin closure can now be achieved using the Auto Suture SQS-20, which coapts the cut dermal edges with an absorbable straight pin. Dermal wound approximation can be accomplished in significantly less time than dermal suture closure.

Gender moderates the effects of exercise therapy on health-related quality of life among COPD patients.

STUDY OBJECTIVES: To determine whether long-term treatment with exercise therapy results in more favorable, disease-specific, health-related quality of life (HRQL) compared with short-term treatment with exercise therapy; and to determine whether there are gender differences in disease-specific HRQL among individuals randomized into the two treatment groups. DESIGN: Randomized clinical trial. SETTING: Center-based exercise therapy unit at a university. PARTICIPANTS: One hundred forty patients with COPD; 118 completed trial. INTERVENTIONS: Short-term exercise therapy (3 months); long-term exercise therapy (18 months). MEASUREMENTS: Chronic Disease Respiratory Questionnaire (CRQ). RESULTS: After 3 months of treatment, there were significant improvements in all CRQ scores for men and women (p < 0.01), and for the total sample (p < 0.01). At 18 months, individuals randomized into the long-term group had significantly more favorable scores than the short-term group for dyspnea (p = 0.03), fatigue (p < 0.01), emotional function (p = 0.04), and mastery (p = 0.04). However, these effects were moderated by gender. That is, men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea (0.04), fatigue (p < 0.001), emotional function (p = 0.02), and mastery (p = 0.02). At the 18-month assessment, there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ. CONCLUSIONS: Taken collectively, the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy; however, men derive significant benefits from extended training.

Evaluating and understanding performance testing in COPD patients.

PURPOSE: There is increasing interest in the use of performance tests to assess physical function among patients with debilitating diseases. The purpose of this study was to describe the measurement properties of a performance test battery used in the Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial and to explore how well-selected physiologic and psychosocial measures explained test performance. METHODS: To assess test-retest reliability of the performance tests, older patients with chronic obstructive pulmonary disease (n = 30) completed, on two different occasions, a 6-minute walk for distance, a timed stair climb, and a timed elevated-arm task. In addition, stepwise regression analyses were conducted on a larger sample (n = 209) to examine how effective conceptually relevant physiologic and psychosocial variables were at explaining variation in task performance. RESULTS: Results showed that all three performance tasks had good test-retest reliability (all coefficients > 0.80) and shared variance in expected directions with VO2peak, forced expiratory volume in 1 second (FEV1), and self-reported disability. Regression analyses suggest that VO2peak, FEV1, self-efficacy, and self-reported disability are important variables to consider in attempts to understand performance-related disability in patients with chronic obstructive pulmonary disease (COPD). CONCLUSIONS: The physical performance test battery appears to be a reliable means of assessing physical functioning in older patients with COPD. Furthermore, findings support the important role that VO2peak plays in task performance and suggest that patients' perceptions should be given careful consideration when attempting to understand physical decline in clinical settings.

quick-to-court, a Drosophila mutant with elevated levels of sexual behavior, is defective in a predicted coiled-coil protein.

Remarkably little is known about the molecular mechanisms that drive sexual behavior. We have identified a new gene, quick-to-court (qtc), whose mutations cause males to show high levels of male-male courtship. qtc males also show a novel phenotype: when placed in the presence of a virgin female, they begin courtship abnormally quickly. qtc mutations are striking in their specificity, in that many aspects of male sexual behavior are normal. We have cloned the qtc gene and found that it encodes a predicted coiled-coil protein and is expressed in the olfactory organs, central nervous system, and male reproductive tract.

Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum.

The eukaryotic cell cycle is regulated by a group of highly conserved cyclin dependent protein kinases (CDKs). Several CDKs have been identified in Plasmodium falciparum, however, their regulatory mechanisms as well as their role in parasite growth and differentiation are not understood fully. To further our understanding of Plasmodium CDK regulation, we have characterized Pfmrk kinase activity. Pfmrk was expressed and purified as a 6xHis tagged recombinant protein from Escherichia coli and assayed for histone H1 kinase activity. Pfmrk has significant histone H1 kinase activity and is autophosphorylated in vitro. Human cyclin H forms a stable complex with Pfmrk and stimulates kinase activity. This is the first indication that Plasmodial CDKs are partially regulated by cyclin subunits, as are human CDKs. CDKs are attractive drug targets due to their role in cellular proliferation. Specific CDK inhibitors were selected to evaluate Pfmrk as a potential drug target. Olomoucine and roscovitine failed to inhibit Pfmrk kinase activity which places Pfmrk with a class of CDKs that are insensitive to these compounds. A molecular model of Pfmrk provides a structural explanation for the failure of these compounds to inhibit Pfmrk.

An enhancer trap line identifies the Drosophila homolog of the L37a ribosomal protein.

A gene identified from an enhancer trap screen is shown to encode the Drosophila melanogaster homolog of the L37a ribosomal protein. The predicted 92 amino-acid sequence of this protein is 78% identical to mammalian L37a proteins, and contains a conserved Cys-X2 Cys-X14-Cys-X2-Cys zinc finger motif that may be involved in interactions with ribosomal RNA. The Drosophila L37a homolog is a single copy gene comprised of four exons and is ubiquitously expressed throughout the animal. Cytological localization reveals that Drosophila L37a maps to position 25C1-3, very near the previously described Minute mutation M(2)25C.

Tobacco, alcohol and drug use in eight- to sixteen-year-old twins: the Virginia Twin Study of Adolescent Behavioral Development.

OBJECTIVE: This study reports prevalences of lifetime and current alcohol, tobacco and drug use in adolescents; examines associations between substance use and a number of putative risk factors; and estimates the contribution of genetic, shared and unique environmental influences on substance use. METHOD: Substance use data were collected using the Child and Adolescent Psychiatric Assessment on a population sample of 1,412 male and female monozygotic and dizygotic twin pairs, aged 8 through 16, from the Virginia Twin Study of Adolescent Behavioral Development. RESULTS: Heritabilities were estimated to be 84% and 82% for liability to lifetime and current tobacco use, respectively. For alcohol use the role of genes and environment varied according to the context of reporting. Liability to lifetime alcohol use was estimated to be under environmental control, with 71% of the variation shared by members of a twin pair and 29% unique to individual twins. Lifetime alcohol use without the permission of a parent or guardian and current use of alcohol were predominantly explained by genetic factors (h2 = 72% and 74%). The role of genetic factors increased and that of unique environmental factors decreased with increasing severity of alcohol use. Lifetime use of any drug showed a heritability of 45%, with the shared environment accounting for 47% of the variation. Shared environmental factors explained most of the variation in marijuana use. CONCLUSIONS: Genetic factors explained a significant proportion of the variation in the use of tobacco, alcohol and other drugs. Shared environmental factors contributed significantly to lifetime alcohol use and other drug use.

The Drosophila beta FTZ-F1 orphan nuclear receptor provides competence for stage-specific responses to the steroid hormone ecdysone.

The acquisition of competence is a key mechanism for refining global signals to distinct spatial and temporal responses. The molecular basis of competence, however, remains poorly understood. Here, we show that the beta FTZ-F1 orphan nuclear receptor functions as a competence factor for stage-specific responses to the steroid hormone ecdysone during Drosophila metamorphosis. beta FTZ-F1 mutants pupariate normally in response to the late larval pulse of ecdysone but display defects in stage-specific responses to the subsequent ecdysone pulse in prepupae. The ecdysone-triggered genetic hierarchy that directs these developmental responses is severely attenuated in beta FTZ-F1 mutants, although ecdysone receptor expression is unaffected. This study define beta FTZ-F1 as an essential competence factor for stage-specific responses to a steroid signal and implicates interplay among nuclear receptors as a mechanism for achieving hormonal competence.

Are endothelial cell patterns of astrocytomas indicative of grade?

BACKGROUND: The most common primary brain tumors in children and adults are of astrocytic origin. Classic histologic grading schemes for astrocytomas have included evaluating the presence or absence of nuclear abnormalities, mitoses, vascular endothelial proliferation, and tumor necrosis. MATERIALS AND METHODS: We evaluated the vascular pattern of 17 astrocytoma surgical specimens (seven from children and 10 from adults), and four normal brains obtained at autopsy, utilizing antibody to glial fibrillary acidic protein (GFAP) and von Willebrand factor (vWF) utilizing confocal microscopy. A modified WHO classification was used. RESULTS: All tumor cases showed cells positive for GFAP. Control tissues showed a few, widely separated vessels. Pilocytic astrocytomas (four cases) showed lacy clusters of small-to-medium sized vessels, with intact vessel wall integrity. Diffuse, low grade astrocytoma (three cases) showed a staining pattern similar to control tissue; intermediate grade (one case), anaplastic astrocytoma (three cases) and gliobastoma multiforme (six cases) showed an increased vessel density with multiple small vessels (glomeruloid clusters), some with prominent intimal hyperplasia, loss of vessel wall integrity, and with numerous vWF-positive single cells/microvessels within the tumor substance. CONCLUSIONS: Evaluation of astrocytomas utilizing antibody to vWF and confocal microscopy aids in the grading of these neoplasms.

Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha 2-adrenergic receptors.

Several Gi-protein-coupled receptors normally expressed in islet beta-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting beta-cells, we stably transfected cDNA encoding the mouse alpha 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the alpha 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin (PTX) treatment of cells was able to reverse partially the reduced insulin secretory response. Our results suggest that overexpression of a Gi-protein-coupled receptor in beta-cells causes tonic inhibition of both insulin synthesis and secretion. Abnormalities in expression or function of such receptors could be a contributory factor in the impaired insulin secretion present in type II diabetes.

Perceived smokeless tobacco addiction among adolescents.

Although the prevalence and associated factors of smokeless tobacco (SLT) use are well-documented, there are no data on the prevalence and associated factors of SLT dependence-addiction. From a survey of 11,057 adolescents in the nonurban Southeastern United States, 3,726 reported having tried SLT, and 17% of those who had tried SLT perceived that they were addicted to it. Years of SLT use, frequency of use per day, and hours of exposure per day were strongly related to perceived addiction. Those using SLT for 1 year or longer had perceived addiction rates of 37% and were over 12 times more likely to report being addicted than were those using for less than 1 year. After controlling for level of SLT use, other factors including parental SLT use, perceived control over health, and racial-ethnic group also contributed minimally but significantly to reported SLT addiction.

Surveyed use of fetal and uterine monitoring during maternal surgery.

The goal of this study was to determine the frequency and methods of intraoperative fetal and uterine monitoring during maternal surgery in the United States. Maternal surgery was defined as nonobstetric surgery during pregnancy that required general or regional anesthesia. We mailed a 21-item questionnaire to the perioperative nurse managers of US hospitals at which more than 2,000 babies are delivered annually (n = 579). Nearly 60% of responding hospitals routinely used some form of fetal monitoring during maternal surgery; more than 40% of responding hospitals did not use intraoperative fetal and uterine monitoring routinely during maternal surgery.