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Biomedical subjects

C Hart

Publications and source records attributed to C Hart.

At least 19 recordsLinked to original sources
PubMed2007

The care home activity project: does introducing an occupational therapy programme reduce depression in care homes?

The primary aim of the study was to test the hypothesis that depression severity in care homes for older people would be reduced by an occupational therapy programme. This was a feasibility study for a cluster randomised controlled trial and involved four intervention and four control homes in northern England. In each intervention home a registered occupational therapist worked full-time for one year delivering an individualised programme to participants. Pre- and post-intervention data for the Geriatric Mental State-Depression Scale (primary outcome measure) were obtained for 143 participants. Secondary outcomes included dependency and quality of life. No significant intervention effects were found in any of the quantitative outcome measures, though qualitative interviews showed the intervention was valued by many participants, staff and relatives. Therapist ratings and qualitative interviews suggested that the intervention was beneficial to some participants but no distinctive characteristics were found that might enable prediction of likely benefit on initial assessment. This exploratory study provides no evidence that this intervention produced benefits in terms of depression, dependency or quality of life. Lack of prior power calculations means these are not definitive findings; but numbers were sufficient to perform the required analyses and data did not suggest effects that would have reached statistical significance with a larger sample. This study highlights issues for consideration in providing such services in care homes.

Aged↗
PubMed2006

Inhibitor treatment in haemophilias A and B: summary statement for the 2006 international consensus conference.

Participants in an international conference on the management of haemophilia patients with inhibitors developed a jointly authored summary of the findings and conclusions of the conference. Current knowledge of the genetic and immunologic mechanisms underlying inhibitor development was briefly summarized. Concerning the purported treatment-related risk factors, conference participants commented on the limitations of the available evidence and the need for more rigorous prospective research in a fully genotyped population. Other clinical considerations discussed included the unproved utility of routine surveillance, the need for assay standardization, the management of acute bleeding and approaches to joint disease prophylaxis and immune tolerance induction (ITI). A number of issues were identified as needing further investigation in larger prospective studies, ideally through international cooperation. Such studies should enroll cohorts that have been scrupulously defined in terms of mutation status and treatment exposure. Finally, conference participants urged their colleagues to participate in the currently ongoing international trials of ITI.

Blood Coagulation Factor Inhibitors↗
PubMed2006

The natural history of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the USA, and it remains one of the few diseases that continues to increase its numbers. The development and progression of COPD can vary dramatically between individuals. A low level of lung function remains the cornerstone of COPD diagnosis and is a key predictor of prognosis. Lung function, however, is not the only factor in determining morbidity and mortality related to COPD, with factors such as body mass index, exercise capability and comorbid disease being important predictors of poor outcomes. Exacerbations of COPD are additional important indicators of both quality of life and outcomes in COPD patients. Definitions of exacerbations can vary, ranging from an increase in symptoms to COPD-related hospitalisations and death. COPD exacerbations are more common in patients with lower levels of lung function and may lead to more rapid declines in lung function. Better understanding of the natural history of COPD may lead to better definitions of specific COPD phenotypes, better interventions and improved outcomes.

Cardiovascular Diseases↗
PubMed2005

Fixation protocols for subcellular imaging by synchrotron-based Fourier transform infrared microspectroscopy.

Synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy is a powerful bioanalytical technique for the simultaneous analysis of lipids, proteins, carbohydrates, and a variety of phosphorylated molecules within intact cells. SR-FTIR microspectroscopy can be used in the imaging mode to generate biospectroscopic maps of the distribution and intensity profiles of subcellular biomolecular domains at diffraction-limited spatial resolution. However, the acquisition of highly spatially resolved IR images of cells is not only a function of instrumental parameters (source brightness, sampling aperture size) but also the cell preparation method employed. Additionally, for the IR data to be biochemically relevant the cells must be preserved in a life-like state without introducing artefacts. In the present study we demonstrate, for the first time, the differences in biomolecular localizations observed in SR-FTIR images of cells fixed by formalin, formalin-critical point drying (CPD), and glutaraldehyde-osmium tetroxide-CPD, using the PC-3 prostate cancer cell line. We compare these SR-FTIR images of fixed cells to unfixed cells. The influence of chemical fixatives on the IR spectrum is discussed in addition to the biological significance of the observed localizations. Our experiments reveal that formalin fixation at low concentration preserves lipid, phosphate, and protein components without significantly influencing the IR spectrum of the cell.

Animals↗
PubMed2005

A participatory approach to the promotion of well-being in the workplace: lessons from empirical research.

Workplace stress and burnout are recognized phenomena which impact negatively on the delivery of care by health and social work organizations. In an attempt to address the negative consequences of stress in the workplace, a collaborative Participatory Action Research project (PAR), involving two large organizations, namely a Healthcare Trust and a Social Services Organization in the United Kingdom (England) was conducted. The project involved a team of professionals from Anglia Polytechnic University working with senior managers and employees of a health care organization and latterly with managers of a Social Services Organization (SSD) to develop a mental well-being strategy in each of these workplaces. This involved organizing and running of a series of five workshops in each of the two organizations and additionally surveys to determine the extent of the problem on staff and effects on their working and personal lives. An overview of the processes and reflective critique of the strengths and weaknesses of participatory action research methodology is provided. The short, medium and long-term strategies formulated by the active engagement of staff in the workshops, and the challenges in delivering and responding to these issues are carefully detailed. Recommendations are made for future collaborative work within hierarchical organizations and more importantly, the implications of delayed response to governmental policies.

Data Collection↗
PubMed2003

Intravenous versus intrastriatal cord blood administration in a rodent model of stroke.

Human umbilical cord blood (hUCB) is a rich source of hematopoietic stem cells that have been used to reconstitute immune cells and blood lineages. Cells from another hematopoietic source, bone marrow, have been found to differentiate into neural cells and are effective in the treatment of stroke. In this study, we administered hUCB cells intravenously into the femoral vein or directly into the striatum and assessed which route of cell administration produced the greatest behavioral recovery in rats with permanent middle cerebral artery occlusion (MCAO). All animals were immunosuppressed with cyclosporine (CSA). When spontaneous activity was measured using the Digiscan automated system, it was found to be significantly less when hUCB was transplanted 24 hr after stroke compared with nontransplanted, stroked animals (P < 0.01). Furthermore, behavioral recovery was similar with both striatal and femoral hUCB delivery. This is in contrast to the step test, in which significant improvements were found only after femoral delivery of the hUCB cells. In the passive avoidance test, transplanted animals learned the task faster than nontransplanted animals (P < 0.05). Together, these results suggest that hUCB transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders. In addition, intravenous delivery may be more effective than striatal delivery in producing long-term functional benefits to the stroked animal.

Animals↗
PubMed2003

Orthodontic preparation for orthognathic surgery: how long does it take and why? A retrospective study.

We investigated the duration of pre-operative orthodontic treatment of patients who had combined orthodontic and orthognathic treatment and examined the variables that influenced this. Records of patients who had undergone such treatment in the past 5 years were collected (n=65) from three consultant orthodontists and one Senior Specialist Registrar/Fixed Term Training Appointment (FTTA). The number of days from placement of the first active orthodontic component to the day that final planning impressions were taken was used to calculate the duration of treatment before the patient was ready for operation. The variables investigated were: sex, age, malocclusion, extractions (excluding third molars), and the clinician. The median duration of pre-operative treatment was 17 months (range 7-47). Only the orthodontist appeared to affect this duration, but this requires further investigation as it may merely reflect variation in other factors such as compliance. We conclude that patients should be informed that the pre-operative phase may last 12-24 months.

Adolescent↗
PubMed2003

Consensus perspectives on prophylactic therapy for haemophilia: summary statement.

Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Consensus Statements as Topic↗
PubMed2001

The socioeconomic position of employed women, risk factors and mortality.

Many studies have demonstrated the graded association between socioeconomic position and health. Few of these studies have examined the cumulative effect of socioeconomic position throughout the lifecourse, and even fewer have included women. Those that have explored gender differences affirm the importance of studying the factors that predict women and men's health separately. This study addresses the associations between cross-sectional and longitudinal socioeconomic position, risk factors for cardiovascular disease and mortality from various causes. Analyses are based on data from a cohort of working Scottish women recruited between 1970 and 1973. Five socioeconomic measures were explored in relation to diastolic blood pressure, plasma cholesterol concentration, body mass index, forced expiratory volume in 1 s (FEV1). amount of recreational exercise taken, cigarette smoking and alcohol consumption. In general, for each of the five measures of socioeconomic position, there were significant differences in at least one of the age-adjusted physiological risk factors for cardiovascular disease (diastolic blood pressure, plasma cholesterol concentration, body mass index, FEV1). There were also significant differences in the percentage of current cigarette smokers according to different measures of socioeconomic position, although this was not the case for the other behavioural risk factors for cardiovascular disease (amount of recreational exercise taken, and alcohol consumption). Measures of socioeconomic position were also examined in relation to cause of death for the women who died before 1 January 1999. After adjusting for age and risk factors, a composite measure of lifetime socioeconomic experience was a more potent predictor of all cause mortality and mortality from cardiovascular disease than other measures of socioeconomic position. It therefore seems that conventional measurcs of socioeconomic position, estimated at one point in time, do not adequately capture the effects of socioeconomic circumstances on the risk of mortality among employed women. Thus, a broader range of explanatory factors for mortality differentials than currently exists must be considered, and must include consideration of factors operating throughout the lifecourse.

Adult↗
PubMed2001

P-glycoprotein and bilirubin disposition.

P-glycoprotein (Pgp), an ATP-dependent plasma membrane efflux pump, is expressed in abundance on the luminal aspect of brain capillary endothelial cells and astrocytes of the blood-brain barrier where it limits the passage of a variety of lipophilic substrates into the central nervous system. This review summarizes current evidence characterizing (1) unconjugated bilirubin as a potential substrate for Pgp and (2) the ontogeny of Pgp expression at the blood-brain barrier and apical brush border epithelium of the gastrointestinal tract, findings that may provide insights regarding the disposition of bilirubin in immature subjects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Are the effects of psychosocial exposures attributable to confounding? Evidence from a prospective observational study on psychological stress and mortality.

STUDY OBJECTIVES: To examine the association between perceived psychological stress and cause specific mortality in a population where perceived stress was not associated with material disadvantage. DESIGN: Prospective observational study with follow up of 21 years and repeat screening of half the cohort five years from baseline. Measures included perceived psychological stress, coronary risk factors, and indices of lifecourse socioeconomic position. SETTING: 27 workplaces in Scotland. PARTICIPANTS: 5388 men (mean age 48 years) at first screening and 2595 men at second screening who had complete data on all measures. MAIN OUTCOME MEASURES: Hazard ratios for all cause mortality and mortality from cardiovascular disease (ICD9 390-459), coronary heart disease (ICD9 410-414), smoking related cancers (ICD9 140, 141, 143-9, 150, 157, 160-163, 188 and 189), other cancers (ICD9 140-208 other than smoking related), stroke (ICD9 430-438), respiratory diseases (ICD9 460-519) and alcohol related causes (ICD9 141, 143-6, 148-9, 150, 155, 161, 291, 303, 571 and 800-998). RESULTS: At first screening behavioural risk (higher smoking and alcohol consumption, lower exercise) was positively associated with stress. This relation was less apparent at second screening. Higher stress at first screening showed an apparent protective relation with all cause mortality and with most categories of cause specific mortality. In general, these estimates were attenuated on adjustment for social position. This pattern was also seen in relation to cumulative stress at first and second screening and with stress that increased between first and second screening. The pattern was most striking with regard to smoking related cancers: relative risk high compared with low stress at first screening, age adjusted 0.64 (95% CI 0.42, 0.96), p for trend 0.016, fully adjusted 0.69 (95% CI 0.45, 1.06), p for trend 0.10; high compared with low cumulative stress, age adjusted 0.69 (95% CI 0.44, 1.09), p for trend 0.12, fully adjusted 0.76 (95% CI 0.48, 1.21), p for trend 0.25; increased compared with decreased stress, age adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.09, fully adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.08. CONCLUSIONS: This implausible protective relation between higher levels of stress, which were associated with increased smoking, and mortality from smoking related cancers, was probably a product of confounding. Plausible reported associations between psychosocial exposures and disease, in populations where such exposures are associated with material disadvantage, may be similarly produced by confounding, and of no causal significance.

Adult↗
PubMed2001

Milk, coronary heart disease and mortality.

STUDY OBJECTIVE: To study the association between reported milk consumption and cardiovascular and all cause mortality. DESIGN: A prospective study of 5765 men aged 35-64 at the time of examination. SETTING: Workplaces in the west of Scotland between 1970 and 1973. PARTICIPANTS: Men who completed a health and lifestyle questionnaire, which asked about daily milk consumption, and who attended for a medical examination. MAIN RESULTS: 150 (2.6%) men reported drinking more than one and a third pints a day, Some 2977 (51.6%) reported drinking between a third and one and a third pints a day and 2638 (45.8%) reported drinking less than a third of a pint a day. There were a total of 2350 deaths over the 25 year follow up period, of which 892 deaths were attributed to coronary heart disease. The relative risk, adjusted for socioeconomic position, health behaviours and health status for deaths from all causes for men who drank one third to one and a third pints a day versus those who drank less than a third of a pint was 0.90 (95% CI 0.83, 0.97). The adjusted relative risk for deaths attributed to coronary heart disease for men who drank one third to one and a third pints a day versus those who drank less than one third of a pint was 0.92 (95% CI 0.81, 1.06). CONCLUSIONS: No evidence was found that men who consumed milk each day, at a time when most milk consumed was full fat milk, were at increased risk of death from all causes or death from coronary heart disease.

Adult↗
PubMed2001

Perceived stress and coronary heart disease risk factors: the contribution of socio-economic position.

OBJECTIVES: The aim of this study was to explore the relationship between risk factors for coronary heart disease (CHD) and perceived stress, adjusted for socio-economic position. DESIGN: Cross-sectional analysis of CHD risk factors, perceived stress and socio-economic position. METHOD: A cohort of employed Scottish men (N = 5848) and women (N = 984) completed a questionnaire and attended a physical examination. RESULTS: Higher socio-economic groups registered higher perceived stress scores. Perceived stress was associated with the following CHD risk factors in the expected direction: high plasma cholesterol, little recreational exercise, cigarette smoking, and high alcohol consumption. Contrary to expectations, stress was related negatively to high diastolic blood pressure, body mass index (BMI) and low forced expiratory volume. Correction for socio-economic position tended to abolish the associations between stress and physiological risk factors; the associations between stress and behavioural risk factors withstood such correction. The residual patterns of associations between perceived stress and CHD risk were broadly similar for men and women. A lower BMI, a greater number of cigarettes smoked, and greater alcohol consumption were associated with higher levels of perceived stress for both sexes. Lower levels of recreational exercise were associated with higher levels of stress for men only. CONCLUSIONS: Self-reported stress is related to health-related behaviours and to physiological CHD risk factors. The direction of the association with physiological risk was often contrary to expectation and appeared to be largely due to confounding by socio-economic position. In contrast, the association with health-related behaviours was in the expected direction and was largely independent of such confounding.

Journal Article↗
PubMed2001

Ontogeny of P-glycoprotein in mouse intestine, liver, and kidney.

BACKGROUND: P-glycoprotein (Pgp) is an ATP-dependent, integral plasma-membrane efflux pump that is constitutively expressed on (i) adult apical brush-border epithelial cells of the intestine, (ii) the bile canalicular face of hepatocytes, and (iii) the brush border epithelium of renal proximal tubules. This Pgp tissue distribution and localization affects the absorption, distribution, metabolism, and excretion of Pgp substrates. Little is known regarding the ontogeny of Pgp expression in these tissues. METHODS: Postnatal expression of Pgp on brush border membranes of small intestine, liver, and kidney as a function of maturity from birth through adulthood was determined using Western immunoblotting and immunohistochemical techniques. Tissue was isolated from FVB mice at four different ages: day of life 0 (D0), day of life 7 (D7), day of life 21 (D21), and adult (Ad). The relative expression of Pgp protein on Western immunoblots was assessed by scanning densitometry and indexed as a percentage (mean+/-SEM) of the adult levels. RESULTS: On Western immunoblots, Pgp expression was limited at birth (19+/-6% of Ad) and increased significantly with maturation in intestine (ANOVA, P<0.005). In contrast, hepatic (113+/-12% of Ad) and renal (96+/-15% of Ad) Pgp expression were at adult levels at birth. The tissue-specific developmental pattern of Pgp expression was confirmed by immunohistochemistry. CONCLUSIONS: We conclude that Pgp is expressed in a tissue-specific and developmentally regulated fashion and speculate that developmental modulation of intestine-Pgp expression may affect the oral bioavailability of Pgp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Searching for kinesin's mechanical amplifier.

Kinesin, a microtubule-based motor, and myosin, an actin-based motor, share a similar core structure, indicating that they arose from a common ancestor. However, kinesin lacks the long lever-arm domain that is believed to drive the myosin power stroke. Here, we present evidence that a much smaller region of ca. 10-40 amino acids serves as a mechanical element for kinesin motor proteins. These 'neck regions' are class conserved and have distinct structures in plus-end and minus-end-directed kinesin motors. Mutagenesis studies also indicate that the neck regions are involved in coupling ATP hydrolysis and energy into directional motion along the microtubule. We suggest that the kinesin necks drive motion by undergoing a conformational change in which they detach and re-dock onto the catalytic core during the ATPase cycle. Thus, kinesin and myosin have evolved unique mechanical elements that amplify small, nucleotide-dependent conformational changes that occur in their similar catalytic cores.

Animals↗