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Biomedical subjects

C A Walker

Publications and source records attributed to C A Walker.

At least 19 recordsLinked to original sources

Sick notes, general practitioners, emergency departments and fracture clinics.

BACKGROUND: General practitioner waiting times are increasing. The two national surveys regarding general practice showed that the number of patients waiting for >or=2 days for an appointment rose from 63% to 72% between 1998 and 2002, with 25% waiting for >or=4 days. The Department of Health recognised that many patients discharged from hospitals and outpatient clinics required to visit their general practitioner for the sole purpose of obtaining a sick note. The report entitled Making a difference: reducing general practitioner paperwork estimated that 518 000 appointments (and 42 000 GP h) could be saved by ensuring that these patients were issued with a sick note directly from hospital rather than being referred to their general practitioner. This practice was to be adopted from July 2001 and included patients discharged from wards as well as those seen in outpatient departments. METHOD: 50 emergency departments and fracture clinics in Scotland and England were contacted to assess whether these guidelines had been adopted. Only hospitals with both accident and emergency and fracture clinics were included; nurse-led and paediatric departments were excluded. RESULTS: Of the 25 Scottish emergency hospitals contacted, 4 (16%) accident and emergency departments and 8 (32%) fracture clinics issued sick notes. This was compared with 5 of 25 (20%) accident and emergency departments and 12 of 25 (48%) fracture clinics in England. Four Scottish and five English accident and emergency departments stated that it was policy to give sick notes, three Scottish and four English departments said that it was policy not to give them and the rest (72% in Scotland and 64% in England) stated that they had no clear policy but "just don't give them". CONCLUSION: The 2001 guidance from the joint Cabinet Office/Department of Health has not been fully incorporated into standard practice in Scotland and England. If all emergency departments and fracture clinics were to issue sick notes to patients requiring >7 days absence from work, this could reduce general practitioner consultations and improve waiting times.

Emergency Service, Hospital↗

Walking at work: a pedometer study assessing the activity levels of doctors.

BACKGROUND: The World Health Organisation cites a sedentary lifestyle as one of the top ten causes of morbidity and mortality worldwide.4 A recent, large-scale clinical study showed that brisk walking and vigorous exercise are associated with substantial (and similar) reductions in the incidence of coronary heart disease. Current guidelines suggest 10,000 steps per day as an appropriate activity target for healthy adults. AIMS: This study aims to assess whether doctors are meeting this daily walking target during working-hours, and whether additional out-of-hours exercise is required. METHODS: 16 doctors from St. John's Hospital in Livingston (comprising 4 Medical Consultants, 4 Surgical Consultants, 4 Medical PRHOs and 4 Surgical PRHOs) each used a belt-worn pedometer to record all steps made during 5 consecutive day shifts. Stride length and total daily steps were recorded. Steps made out-with working hours were not counted. Total steps and hours worked were recorded at the end of each day. RESULTS: Average daily steps recorded were 7907 (Medical PRHOs), 5068 (Surgical PRHOs), 4822 (Surgical Consultants) and 4647 (Medical Consultants). P values of < 0.1 were obtained for the variation in steps between the Medical PRHOs and both the Consultant Surgeons and Consultant Physicians. Distance walked per shift varied from 3.84 (Consultant Physicians) to 6.85 kilometres (Medical PRHOs). CONCLUSION: Walking at work does provide a substantial proportion of a doctor's recommended daily activity quota. However, it is still necessary to engage in additional, out-of-hours exercise in order to consistently meet the current recommendations for physical exercise.

Adult↗

beta-Adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium.

BACKGROUND: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in beta-adrenergic receptor (beta-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on beta-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. METHODS AND RESULTS: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10(-6) to 0(-9) mol/L) as well as after (-)isoproterenol (10(-6) to 10(-2) mol/L) or forskolin (0.05 to 30.0 micromol/L) stimulation. beta-AR and ET receptor profiles were determined by radiolabeled ligand assays. ET-1 inhibited basal cAMP production in all preparations in a concentration-dependent manner. However, beta-AR-stimulated cAMP production by either isoproterenol or forskolin was not significantly affected by ET-1. beta-AR receptor density was reduced, and a selective reduction of the ET(B) receptor occurred in both forms of DCM. CONCLUSIONS: Under basal conditions, ET receptor stimulation reduced cAMP levels, which may influence contractility, particularly with DCM.

Adolescent↗

Endothelin-1 during and after cardiopulmonary bypass: association to graft sensitivity and postoperative recovery.

OBJECTIVE: Our objectives are 2-fold: (1) to serially measure the release of endothelin and graft-conduit endothelin sensitivity during and after coronary artery bypass grafting and (2) to define potential relationships of changes in endothelin levels to perioperative parameters. METHODS: Endothelin plasma content was measured in patients (n = 105) undergoing bypass grafting from select vascular compartments before operations and at specific intervals up to 24 hours postoperatively. Endothelin sensitivity was determined in isolated internal thoracic artery segments. RESULTS: Systemic arterial and pulmonary arterial endothelin levels were increased by approximately 50% immediately after bypass grafting and increased by another 85% during the first 24 hours postoperatively. Endothelin levels were highest in patients with prolonged ventilatory requirements and extended stays in the intensive care unit (10.2 +/- 0.8 vs 13.2 +/- 1.1 fmol/mL, P =.02, and 9.8 +/- 0.7 vs 13.9 +/- 1.2 fmol/mL, P =.01, respectively. Endothelin sensitivity of the internal thoracic artery was increased in patients requiring prolonged vasodilator support with nitroglycerin. CONCLUSIONS: Systemic and pulmonary arterial endothelin levels remained increased for at least 24 hours postoperatively. Prolonged pharmacologic management and increased intensive care unit stay were associated with increased systemic endothelin release and heightened graft-conduit sensitivity to endothelin.

Analysis of Variance↗

Endothelin receptor subtype A blockade selectively reduces pulmonary pressure after cardiopulmonary bypass.

BACKGROUND: The bioactive peptide endothelin-1 is elevated during and after cardiopulmonary bypass and exerts cardiovascular effects through its 2 receptor subtypes, endothelin-1A and endothelin-1B. Increased endothelin-1A receptor stimulation after cardiopulmonary bypass can cause increased pulmonary vascular resistance and modulate myocardial contractility. However, whether and to what degree selective endothelin-1A blockade influences these parameters in the postbypass setting is not completely understood. OBJECTIVES: Our objective was to measure left ventricular function and hemodynamics in a porcine model of cardiopulmonary bypass after selective blockade of endothelin-1A. METHODS: Adult pigs (n = 23) underwent 90 minutes of cardiopulmonary bypass and were randomized 30 minutes after bypass to receive a selective endothelin-1A antagonist (TBC 11251, 10 mg/kg; n = 13) or saline vehicle (n = 10). RESULTS: After bypass and before randomization, pulmonary vascular resistance rose nearly 4-fold, and left ventricular preload recruitable stroke work fell to one third of baseline values (both P <.05). In the vehicle group pulmonary vascular resistance continued to rise, and preload recruitable stroke work remained reduced. However, after endothelin-1A blockade, the rise in pulmonary vascular resistance was significantly blunted compared with that in the vehicle group. Moreover, the reduction in pulmonary vascular resistance with endothelin-1A blockade was achieved without a significant change in systemic perfusion pressures. CONCLUSIONS: The present study demonstrated that increased activity of the endothelin-1A receptor likely contributes to alterations in pulmonary vascular resistance in the postbypass setting. Selective endothelin-1A blockade may provide a means to selectively decrease pulmonary vascular resistance without significant effects on systemic hemodynamics.

Analysis of Variance↗

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery.

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.

Adult↗

Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass.

OBJECTIVE: Increased systemic levels of the bioactive peptide endothelin 1 during and after cardioplegic arrest and cardiopulmonary bypass have been well documented. However, endothelin 1 is synthesized locally, and therefore myocardial endothelin 1 production during and after cardiopulmonary bypass remains unknown. METHODS: Pigs (n = 11) were instrumented for cardiopulmonary bypass, and cardioplegic arrest was initiated. Myocardial interstitial and systemic arterial levels of endothelin 1 were measured before cardiopulmonary bypass, throughout bypass and cardioplegic arrest (90 minutes), and up to 90 minutes after separation from bypass. Myocardial interstitial endothelin 1 was determined by microdialysis and radioimmunoassay. RESULTS: Baseline myocardial endothelin 1 levels were higher than systemic endothelin 1 levels (25.6 +/- 6.7 vs 8.3 +/- 1.1 fmol/mL, P <.05). With the onset of bypass, myocardial endothelin 1 increased by 327% +/- 92% from baseline (P <.05), which preceded the increase in systemic endothelin 1 levels. CONCLUSION: Myocardial compartmentalization of endothelin 1 exists in vivo. Cardiopulmonary bypass and cardioplegic arrest induce temporal differences in endothelin 1 levels within the myocardial interstitium and systemic circulation, which, in turn, may influence left ventricular function in the postbypass period.

Analysis of Variance↗

ET-1 in the myocardial interstitium: relation to myocyte ECE activity and expression.

Increased plasma levels of endothelin-1 (ET-1) have been identified in congestive heart failure (CHF), but local myocardial interstitial ET-1 levels and the relation to determinants of ET-1 synthesis remain to be defined. Accordingly, myocardial interstitial ET-1 levels and myocyte endothelin-converting enzyme (ECE)-1 activity and expression with the development of CHF were examined. Pigs were instrumented with a microdialysis system to measure myocardial interstitial ET-1 levels with pacing CHF (240 beats/min, 3 wk; n = 9) and in controls (n = 14). Plasma ET-1 was increased with CHF (15 +/- 1 vs. 9 +/- 1 fmol/ml, P < 0.05) as was total myocardial ET-1 content (90 +/- 15 vs. 35 +/- 5 fmol/g, P < 0.05). Paradoxically, myocardial interstitial ET-1 was decreased in CHF (32 +/- 4 vs. 21 +/- 2 fmol/ml, P < 0.05), which indicated increased ET-1 uptake by the left ventricular (LV) myocardium with CHF. In isolated LV myocyte preparations, ECE-1 activity was increased by twofold with CHF (P < 0.05). In LV myocytes, both ECE-1a and ECE-1c mRNAs were detected, and ECE-1a expression was upregulated fivefold in CHF myocytes (P < 0.05). In conclusion, this study demonstrated compartmentalization of ET-1 in the myocardial interstitium and enhanced ET-1 uptake with CHF. Thus a local ET-1 system exists at the level of the myocyte, and determinants of ET-1 biosynthesis are selectively regulated within this myocardial compartment in CHF.

Animals↗

Mapping of quantitative trait loci on porcine chromosome 4.

A F2 population derived from a cross between European Large White and Chinese Meishan pigs was established in order to study the genetic basis of breed differences for growth and fat traits. Chromosome 4 was chosen for initial study as previous work had revealed quantitative trait loci (QTLs) on this chromosome affected growth and fat traits in a Wild Boar x Large White cross. Individuals in the F2 population were typed for nine markers spanning a region of approximately 124 CM. We found evidence for QTLs affecting growth between weaning and the end of test (additive effect: 43.4 g/day) and fat depth measured in the mid-back position (additive effect: 1.82 mm). There was no evidence of interactions between the QTLs and sex, grandparents or F1 sires, suggesting that the detected QTLs were fixed for alternative alleles in the Meishan and Large White breeds. Comparison of locations suggests that these QTLs could be the same as those found in the Wild Boar x Large White cross.

Animals↗

Taoism: the way.

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Female↗

No association between p53 status and alpha-particle-induced chromosomal instability in human lymphoblastoid cells.

Previous work has demonstrated that alpha-particle irradiation of primary human bone marrow cells leads to the transmission of chromosomal instability in the descendants of the irradiated cell, although there is some interindividual variation. We have extended these studies to human EBV-transformed lymphoblastoid cell lines in order to establish an in vitro model system. The five cell lines analyzed, including one from a Fanconi anaemia patient, exhibited high levels of persistent chromatid aberrations up to approximately 40 cell generations after alpha-irradiation. The p53 status of the cell lines was defined according to whether cellular p53 levels were induced by irradiation, translocated to the nucleus and were able to bind a p53 DNA consensus recognition sequence in vitro. Together with the primary bone marrow cell studies, we conclude that alpha-particle induced chromosomal instability is independent of the p53 status of the cell as defined in these studies.

Alpha Particles↗

Coalescing the theories of two nurse visionaries: Parse and Watson.

The theories of two nurse visionaries, Rosemarie Rizzo Parse and Jean Watson, are examined for areas of agreement and notable differences. Watson and Parse reject (or hold seriously suspect) traditional, positivistic methods of studying human behaviour and posit their theories as alternatives to the totality paradigm. Since both of these theories, Parse's theory of human becoming and Watson's theory of transpersonal care, borrow heavily from existential phenomenology, major tenets of this philosophic perspective are outlined. Each theory is then described with emphasis on anchoring motifs, concepts, and principles. Next both theories are analysed and critiqued simultaneously. Finally, the theories are applied to a case study with the intent of maximizing their mutual strengths and diminishing their limitations. Coalescence of compatible theories is recommended as a way of enhancing the application of nursing knowledge in practice.

Adult↗

FIRO-B: the power of love and the love of power.

Factor analysis of FIRO-B data obtained from new software product teams had led to a reformulation of Schutz's ideas on team compatibility. The concept of Group-Warmth as a derivative of the FIRO-B Inclusion and Affection scales was developed and shown to be related to the commercial effectiveness of teams. In a like manner, the FIRO-B constructs of Control-Expressed and Control-Wanted were explored through concurrent factor analysis of 16 PF data. A new interpretation has been given to both FIRO-B Control scales, namely, Assertive-Impulsive.

Adult↗

Hepato-biliary and renal excretion in mice of charged and neutral gadolinium complexes of cyclic tetra-aza-phosphinic and carboxylic acids.

Tissue distribution of 21 new 157/153Gd complexes was measured at 5 min and 24 hr after an intravenous injection into mice. A complex was judged to be stable in vivo when the percentage of 153Gd retained in the liver and skeleton at 24 hr was comparable with that of 153Gd(DOTA)-. Complexes varied in net charge and lipophilicity and 20 were phosphinic or carboxylic acid derivatives of tetra-aza-cyclo-dodecane. Three anionic, lipophilic complexes were cleared predominantly by the hepato-biliary pathway and were stable in vivo. The remaining 18 complexes were cleared mainly by the kidneys. Of these 18, 1 anionic, 8 neutral, and 3 cationic complexes were stable in vivo. These findings augur well for the future of hepato-biliary and general purpose Gd contrast enhancing agents for MRI.

Animals↗

67Ga-9N3 uptake by xenografts of human melanotic melanoma in mice.

Tumour uptake of the inert, neutral complex 67Ga-9N3 and the tumour:blood concentration ratio (1,4,7,triazacyclononane-1,4,7, triacetic acid) were measured in mice bearing xenografts of the human melanotic melanoma HX118. Between 1 and 4 h after the injection the tumour:blood ratio increased from 3.5 to 21 and the concentration of 67Ga-9N3 in the tumour decreased from 0.43 to 0.13% g-1. During the first 24 h the concentration of 67Ga-9N3 in the tumour exceeded that in all other tissues except the liver and kidneys. The tumour:blood ratio and tissue distribution of 67Ga-9N3 at 4 h were compared with those of four other complexes. The results indicated that of the five complexes 67Ga-9N3 would be the most suitable for tumour imaging at early times after administration. Imaging would not be restricted to gamma emitting 67Ga as there is also the possibility of using the 9N3 ligand to bind 111In for single photon emission computed tomography (SPECT), 68Ga for positron emission tomography (PET) or even stable Ga for direct in vivo nuclear magnetic resonance (NMR) detection.

Animals↗