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Biomedical subjects

K Allen

Publications and source records attributed to K Allen.

At least 37 records · Page 2Linked to original sources

Passive smoking and the risk of coronary heart disease--a meta-analysis of epidemiologic studies.

BACKGROUND: The effect of passive smoking on the risk of coronary heart disease is controversial. We conducted a meta-analysis of the risk of coronary heart disease associated with passive smoking among nonsmokers. METHODS: We searched the Medline and Dissertation Abstracts Online data bases and reviewed citations in relevant articles to identify 18 epidemiologic (10 cohort and 8 case-control) studies that met prestated inclusion criteria. Information on the designs of the studies, the characteristics of the study subjects, exposure and outcome measures, control for potential confounding factors, and risk estimates was abstracted independently by three investigators using a standardized protocol. RESULTS: Overall, nonsmokers exposed to environmental smoke had a relative risk of coronary heart disease of 1.25 (95 percent confidence interval, 1.17 to 1.32) as compared with nonsmokers not exposed to smoke. Passive smoking was consistently associated with an increased relative risk of coronary heart disease in cohort studies (relative risk, 1.21; 95 percent confidence interval, 1.14 to 1.30), in case-control studies (relative risk, 1.51; 95 percent confidence interval, 1.26 to 1.81), in men (relative risk, 1.22; 95 percent confidence interval, 1.10 to 1.35), in women (relative risk, 1.24; 95 percent confidence interval, 1.15 to 1.34), and in those exposed to smoking at home (relative risk, 1.17; 95 percent confidence interval, 1.11 to 1.24) or in the workplace (relative risk, 1.11; 95 percent confidence interval, 1.00 to 1.23). A significant dose-response relation was identified, with respective relative risks of 1.23 and 1.31 for nonsmokers who were exposed to the smoke of 1 to 19 cigarettes per day and those who were exposed to the smoke of 20 or more cigarettes per day, as compared with nonsmokers not exposed to smoke (P=0.006 for linear trend). CONCLUSIONS: Passive smoking is associated with a small increase in the risk of coronary heart disease. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease may be important.

Coronary Disease↗

Tidal breathing parameters in young children: comparison of measurement by respiratory inductance plethysmography to a facemask pneumotachograph system.

The ratio of expiratory time at tidal peak flow to total expiratory time (t(ptef)/t(e)) correlates with conventional measures of airway obstruction. It is usually assessed using a facemask and pneumotachograph system which may be poorly tolerated in young children and hence limits the usefulness of this technique. We therefore determined in young asthmatic children the accuracy of t(ptef)/t(e), using an uncalibrated respiratory inductance plethysmograph (RIP), and compared the results with those from a facemask-pneumotachograph system. We also assessed whether age influenced the agreement between measurements using the two devices. Forty-seven children aged between 1 month and 12 years were recruited: 39 were inpatients recovering from an acute wheezy episode, and 8 were recruited from the asthma clinic. All were receiving bronchodilators. Tidal breathing parameters t(ptef)/t(e), the duty cycle (t(i)/t(tot)), and respiratory rate were initially measured using the Respitrace alone and then simultaneously with both the Respitrace and the facemask-pneumotachograph system. Eight children did not tolerate the facemask, and in two others it was impossible to analyze the Respitrace trace due to artefacts. In the remaining 37 children, the reliability coefficients and coefficients of variation of the two techniques were similar. Similar values of t(i)/t(tot) and respiratory rate were obtained using the two devices. The mean t(ptef)/t(e) obtained using the Respitrace was lower than with the facemask-pneumotachograph system (P < 0.01), although this was age group-dependent (P < 0.05), as the difference was less apparent in the 1 to 2-year-old children than in other age groups. Application of the facemask-pneumotachograph system did not significantly influence the results obtained using the Respitrace. We conclude that uncalibrated respiratory inductance plethysmography can measure tidal breathing parameters as reliably as a facemask-pneumotachograph system in young asthmatic children, and is better tolerated than the pneumotachograph system. The results obtained using the two devices are not interchangeable.

Age Factors↗

Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation.

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases.

Amino Acid Sequence↗

Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion.

Propagation of the yeast protein-based non-Mendelian element [PSI], a prion-like form of the release factor Sup35, was shown to be regulated by the interplay between chaperone proteins Hsp104 and Hsp70. While overproduction of Hsp104 protein cures cells of [PSI], overproduction of the Ssa1 protein of the Hsp70 family protects [PSI] from the curing effect of Hsp104. Here we demonstrate that another protein of the Hsp70 family, Ssb, previously implicated in nascent polypeptide folding and protein turnover, exhibits effects on [PSI] which are opposite those of Ssa. Ssb overproduction increases, while Ssb depletion decreases, [PSI] curing by the overproduced Hsp104. Both spontaneous [PSI] formation and [PSI] induction by overproduction of the homologous or heterologous Sup35 protein are increased significantly in the strain lacking Ssb. This is the first example when inactivation of an unrelated cellular protein facilitates prion formation. Ssb is therefore playing a role in protein-based inheritance, which is analogous to the role played by the products of mutator genes in nucleic acid-based inheritance. Ssb depletion also decreases toxicity of the overproduced Sup35 and causes extreme sensitivity to the [PSI]-curing chemical agent guanidine hydrochloride. Our data demonstrate that various members of the yeast Hsp70 family have diverged from each other in regard to their roles in prion propagation and suggest that Ssb could serve as a proofreading component of the enzymatic system, which prevents formation of prion aggregates.

Adenosine Triphosphatases↗

Should we genetically test everyone for haemochromatosis?

The increasing availability of DNA-based diagnostic tests has raised issues about whether these should be applied to the population at large in order to identify, treat or prevent a range of diseases. DNA tests raise concerns in the community for several reasons. There is the possibility of stigmatisation and discrimination between those who test positive and those who don't. High-risk individuals may be identified for whom no proven effective intervention is possible, or conversely may test "positive" for a disease that does not eventuate. Controversy concerning prenatal diagnosis and termination of affected pregnancies may arise. Haemochromatosis, however, is a disease that is not only treatable but also preventable if those at high risk are identified presymptomatically. This paper will identify and discuss key issues regarding DNA-based population screening for haemochromatosis, and argue that population-based genetic screening for haemochromatosis should be supported when a number of contentious issues are addressed. In the context of a health system with limited resources haemochromatosis is the paradigm of a disorder where there is an ethical and clinical imperative to encourage presymptomatic DNA testing for all in ethnically relevant communities.

Adolescent↗

Nutritional Management of Patients With Esophageal and Esophagogastric Junction Cancer.

BACKGROUND: Malnutrition is common in patients with esophageal and esophagogastric cancer. Compared to patients with other digestive and extradigestive neoplasia, the highest incidence (78.9%) was found in those with esophageal cancer. Malnutrition is associated with postoperative complications, increased morbidity, and prolonged hospital stays. METHODS: The authors review the impact and causes of malnutrition in esophageal cancer patients and present strategies that can be used to preserve or restore the nutritional status in this patient population throughout treatment. RESULTS: Patients usually are unable to sustain weight on oral intake alone and require additional means of nutritional support. Several methods can be used to provide nutritional care to the esophageal cancer patient, such as diet modification, oral supplementation, and enteral or parenteral nutrition. The enteral route is preferred due to preservation of gut integrity, reduced risk of complications, and less expense. In terminally ill patients, minimal nutritional intervention may be all that is needed to achieve patient comfort. CONCLUSIONS: In order to improve clinical outcomes and the quality of life for patients with esophageal and esophagogastric cancers, the extent of malnutrition must be identified and treated.

Journal Article↗

North Staffordshire Community Beds Study: longitudinal evaluation of psychiatric in-patient units attached to community mental health centres. I: Methods, outcome and patient satisfaction.

BACKGROUND: This study evaluates two in-patient units attached to community mental health centres (CMHCs) that were designed to supplement acute in-patient care and to integrate with community-based after-care services. AIM: To examine the comparative outcome of patients with severe mental illness (SMI) admitted to the two units. METHOD: All patients with SMI admitted to the acute psychiatric wards serving the two CMHCs, those transferred to the community in-patient units and those admitted directly to these units (n = 110) were compared with patients (n = 67) admitted to acute wards serving two similar catchment areas without associated community beds. Baseline clinical and social measures were made and repeated at six and 12 months. Satisfaction with services was assessed at 12 months. RESULTS: The experimental group showed significantly better outcomes, significant reduction in unmet need and better satisfaction with services. CONCLUSIONS: The use of the community beds appears to have significant benefits for patients with SMI.

Adult↗

North Staffordshire Community Beds Study: longitudinal evaluation of psychiatric in-patient units attached to community mental health centres. 2: Impact upon costs and resource use.

BACKGROUND: Innovative approaches to the provision of psychiatric care must justify their ability to improve the quality of life within the resource constraints imposed on psychiatry. AIMS: To examine the average costs per patient of the experimental and control group services. METHOD: An individual patient costing methodology that identified, measured and valued all public and private resources. RESULTS: The experimental group was more likely to remain in contact with services over a 12-month period, had fewer acute readmissions and spent less time in acute in-patient units. There were significantly different levels and patterns of resource consumption between the groups and between the two separate catchment areas. CONCLUSION: The cost analysis should be assessed in the context of the previous outcome analysis. It is likely, but not inevitable, that such units will increase the overall costs of care provision; this largely depends on the effectiveness with which such units are integrated into existing care provision.

Community Mental Health Services↗

Modifications to standard guidelines and changes in blood pressure readings: use of an automatic blood pressure device.

The purpose of the study was to determine what effect modifications to American Heart Association (AHA) guidelines produce when taking blood pressures with an automatic device. Eight blood pressure measurements were taken at least 2 minutes apart; two with standard AHA guidelines and six with modifications. Findings of this study suggest that elevation of the arm can have a significant effect on both the systolic and diastolic blood pressure. Two modifications, talking and placing the arm beside the trunk, raised the diastolic pressure. However, some modifications did not have a statistically significant effect. Techniques used to take blood pressures with an automatic device can have a significant effect on the readings.

Adult↗

Nursing challenges in cancer pain assessment and management: setting an agenda for the CANO Pain Initiative.

The purpose of this inventory was to determine what oncology nurses perceived to be the challenges and priorities in pain assessment and management in Canada. It was recognised that there are a variety of practices in Canada, and if we are to establish an educational framework, there is a need to know what some of the issues are and what assessment tools are being used. Sixty-six survey questionnaires were sent to centres with an oncology or palliative care focus. Thirty-one surveys were returned with a great deal of information. The findings of this descriptive inventory of cancer pain assessment and management hold several key implications for future directions of the CANO Pain Initiative. The findings provide further support for ongoing efforts to educate and inform health professionals about the nature of cancer pain and associated assessment and management issues. A number of other issues have been identified with this survey which continues to support the efforts of the CANO Pain Initiative in developing educational modules, comprehensive care plans and practical ways to document pain interventions.

Canada↗

Structural and functional changes in proteins induced by free radical-mediated oxidative stress and protective action of the antioxidants N-tert-butyl-alpha-phenylnitrone and vitamin E.

The free radical theory of aging proposes that reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject. It is the cumulative and potentially increasing amount of accumulated damage that accounts for the dysfunctions and pathologies seen in normal aging. We have previously demonstrated that both normal rodent brain aging and normal human brain aging are associated with an increase in oxidative modification of proteins and in changes in plasma membrane lipids. Several lines of investigation indicate that one of the likely sources of ROS is the mitochondria. There is an increase in oxidative damage to the mitochondrial genome in aging and a decreased expression of mitochondrial mRNA in aging. We have used a multidisciplinary approach to the characterization of the changes that occur in aging and in the modeling of brain aging, both in vitro and in vivo. Exposure of rodents to acute normobaric hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins and loss of activity for the oxidation-sensitive enzymes glutamine synthetase and creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal membrane protein oxidation following hyperoxia. These changes are similar to the changes seen in senescent brains, compared to young adult controls. The antioxidant spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) was effective in preventing all of these changes. In a related study, we characterized the changes in brain protein spin labeling and cytosolic enzyme activity in a series of phenotypically selected senescence-accelerated mice (SAMP), compared to a resistant line (SAMR1) that was derived from the same original parents. In general, the SAM mice demonstrated greater oxidative changes in brain proteins. In a sequel study, a group of mice from the SAMP8-sensitive line were compared to the SAMR1-resistant mice following 14 days of daily PBN treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the cytoskeletal protein labeling toward that of the normal control line (SAMR1). The results of these and related studies indicate that the changes in brain function seen in several different studies may be related to the progressive oxidation of critical brain proteins and lipids. These components may be critical targets for the beneficial effects of gerontotherapeutics both in normal aging and in disease of aging.

Adult↗

Biosynthesis of endotubin: an apical early endosomal glycoprotein from developing rat intestinal epithelial cells.

Endosomes are the site of sorting of internalized receptors and ligands in all cell types and, in polarized cells, the apical endosomal compartment is involved in the selective transepithelial transport of immunoglobulins and growth factors. The biochemical composition of this specialized compartment remains largely unresolved. We have characterized a glycoprotein, called endotubin, that is located in the apical endosomal tubules of developing rat intestinal epithelial cells. A monoclonal antibody against endotubin recognizes a broad band of 55-60kDa, which upon isoelectric focusing can be resolved into two bands, and a faint band of 140kDa. Metabolic labelling followed by immunoprecipitation indicates that endotubin is synthesized as a 140kDa precursor that is cleaved to the 55-60kDa forms. High pH washing of endosomal membranes removes the 55-60kDa forms from the membrane, whereas the high-molecular-mass form remains membrane associated and appears to be an integral membrane protein. Immunoblotting with a polyclonal antibody against the putative cytoplasmic tail of the protein identifies a 140kDa band and a band of 74kDa, presumably the cleavage product. Immunoprecipitation with antibodies against the 55-60kDa form results in coprecipitation of a 74kDa protein, and immunoprecipitation with antibody against the 74kDa protein results in coprecipitation of the 55-60kDa form. Epitope mapping of the monoclonal antibody binding site supports a proposed type I membrane protein orientation. We propose that endotubin is proteolytically processed into a heterodimer with the 55-60kDa fragment remaining membrane-associated through a non-covalent association with the membrane-bound 74kDa portion of the molecule.

Animals↗

Conceptualizing sexual health in cancer care.

This qualitative study was designed to describe women's experiences with changes in sexual function related to physical comfort, sexual satisfaction, and feelings of intimacy post-treatment for gynecological cancer. The 17 women who participated in this study described sexuality as a much broader construct. Contrary to existing literature, sexual functioning was found to be one aspect that contributed to the view of the self as a sexual being, but the women's perceptions were not limited to this single dimension. The identification of multidimensional components to be considered in developing a conceptual model to describe sexual health are presented. This study indicates that sexuality should be viewed as a health issue that has an impact on quality of life.

Adult↗