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Biomedical subjects

R D Stevenson

Publications and source records attributed to R D Stevenson.

At least 19 recordsLinked to original sources

Exercise responses following heart transplantation: 5 year follow-up.

Heart transplantation is an established treatment for end stage heart failure. In addition to increased life expectancy, heart transplant recipients report a remarkable improvement in symptoms and functional capacity. Exercise performance following heart transplantation, however, remains impaired even in the absence of exertional symptoms. We have assessed the response to exercise in 47 patients with cardiac failure prior to and then at yearly intervals to five years post transplantation. All patients performed incremental symptom limited exercise tests during which minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) and heart rate (HR) were measured. Ventilatory response (V'E/V'CO2), anaerobic threshold (V'O2 AT %predicted) and heart rate response (HR/VO2) were calculated. The dead space to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (A-aO2) were computed from transcutaneous monitoring. Despite substantial improvement in subjective functional capacity, heart transplant recipients continue to have limited exercise performance [Maximal V'O2% predicted pre-transplant 41.3 (2.2); 1 year 48.6 (1.7), p <0.001: V'O2 AT% 31.5 (1.1); 1 year 35.6 (1.0); respectively p<0.05]. The maximal oxygen uptake continued to improve at two years post-transplant but, thereafter, there was no further significant change at up to 5 years post transplant [50.9 (1.5)]. At one year post-transplantation peak HR [65.2 (0.9) vs 79.1(1.4)] and the HR/VO2 response [24.0(1.8) vs 79.6(4.2)] were significantly reduced compared to pre-transplant values. The heart rate response remained lower compared to predicted at 5 years post-transplant although there was a significant increase compared to one year post-transplant (32.9 vs 24.0mls/bt). There was a weak but significant relationship between maximal VO2 and peak HR (0.39, p<0.05) and HR/VO2 (r= 0.37, p<0.05) at one year post-transplant. Prior to transplantation the ventilatory response to exercise was elevated [V'E/V'CO2 45.6 (2.5)] and decreased significantly following transplantation [1 yr 34.1 (1.3), respectively p<0.001]. In addition, despite significant improvement in VD/VT after transplantation, it remained higher than normal [Pre VD/VT at maximum exercise 0.35 (0.02); 1 yr 0.31 (0.02); p<0.05]. There was a further fall in the VE/VCO2 and VD/VT at two years post-transplantation with no further change at up to 5 years post transplantation [VE/VCO2 32.0 (1.0); VD/VT 0.29 (0.01)]. Although cardiac output is markedly improved after transplantation, due to chronotropic incompetence associated with denervation, its response remains subnormal and this may explain the residual abnormalities of ventilatory and gas exchange responses to exercise following transplantation.

Adult↗

Use of reactance to estimate transpulmonary resistance.

This study examines the relationship of respiratory system resistance (R(rs)) and reactance (X(rs)) measured by forced oscillometry with transpulmonary resistance (R(L)) measured by oesophageal manometry. Simultaneous forced oscillometry using a single frequency of 5 Hz and oesophageal manometry were performed on five asthmatics during bronchoprovocation. The data obtained were used to derive prediction equations for R(L) from oscillometric parameters, which were tested on a further six asthmatics and 35 nonasthmatic subjects. In the first five asthmatic subjects, R(L) correlated more strongly with X(rs) than with R(rs). In the second set of asthmatics, R(L) ranged 0.0005-4.57 kPa.s.L(-1), with a median of 0.21 kPa.s.L(-1). The R(L) values predicted from X(rs) showed a mean+/-sd difference of -0.067+/-0.25 kPa.s.L(-1) compared with the values measured in this set of patients. X(rs) in subjects with other respiratory conditions appeared to follow the same relationship with R(L) as in asthmatics. Lumped element modelling suggested that the linear relationship between X(rs) and R(L) was a consequence of the increasing contribution of central and upper airway wall shunts as peripheral airway resistance rose, and that this effect was much larger than that due to changes in static elastance. In conclusion, the reactance of the respiratory system can predict transpulmonary resistance more accurately than can the resistance of the respiratory system.

Adult↗

Health status of children with moderate to severe cerebral palsy.

The aim of the study was to evaluate the health of children with cerebral palsy (CP) using a global assessment of quality of life, condition-specific measures, and assessments of health care use. A multicenter population-based cross-sectional survey of 235 children, aged 2 to 18 years, with moderate to severe impairment, was carried out using Gross Motor Function Classification System (GMFCS) levels III (n = 56), IV (n = 55), and V (n = 122). This study group scored significantly below the mean on the Child Health Questionnaire (CHQ) for Pain, General Health, Physical Functioning, and Impact on Parents. These children used more medications than children without CP from a national sample. Fifty-nine children used feeding tubes. Children in GMFCS level V who used a feeding tube had the lowest estimate of mental age, required the most health care resources, used the most medications, had the most respiratory problems, and had the lowest Global Health scores. Children with the most severe motor disability who have feeding tubes are an especially frail group who require numerous health-related resources and treatments. Also, there is a relationship among measures of health status such as the CHQ, functional abilities, use of resources, and mental age, but each appears to measure different aspects of health and well-being and should be used in combination to reflect children's overall health status.

Activities of Daily Living↗

Dual X-ray absorptiometry assessment of body composition in children with altered body posture.

Many children have contractures and/or deformities that preclude positioning in a fully supine position. The purpose of this study was to evaluate the effects of "poor" positioning on the assessment of body composition with dual X-ray absorptiometry (DXA) in thirty-seven normal child volunteers ages 3-16 yr. Multiple whole-body DXA scans of each child were performed: duplicate scans in the correct fully supine position, two scans while simulating different positions typical of children with contractures, and a scan while positioned in the full lateral position as a "worst-case" scenario. Also evaluated were the precision of duplicate measures in the altered positions, the effect of knee flexion contractures, and the impact of metallic orthopedic fixation devices. Errors in body composition assessment did occur from "poor" positioning. In those positions simulating children with contractures, the mean errors were 4-6% for measures of bone mineral content, 1-3% for lean body mass, and 5-11% for fat mass. Measures in the correct fully supine position and the contracted positions were highly correlated. The errors obtained by altering position were small. If errors of this magnitude are of significance, then corrective equations could be utilized to improve accuracy. Precise and reasonably accurate measures of body composition can be obtained with DXA in children with disabilities and deformities that preclude fully supine positioning.

Absorptiometry, Photon↗

Hospital at home services for acute exacerbation of chronic obstructive pulmonary disease: a survey of British practice.

OBJECTIVES: To identify the prevalence of and attitudes towards hospital at home services for acute exacerbation of chronic obstructive pulmonary disease (COPD) in Great Britain. To identify the models of service in existence, in particular staff numbers and the workload experienced. DESIGN: A postal survey was used to locate existing schemes. Telephone interviews were conducted with each of the hospital at home services identified. SUBJECTS & SETTING: A questionnaire was sent to one consultant in each of 223 respiratory departments in Great Britain. Thirty six departments were subsequently contacted by telephone. OUTCOME MEASURES: Awareness and prevalence of hospital at home services. Perceived problems with starting a service. Details of organisation of existing services. RESULTS: We received 186 replies to the postal questionnaire. Of these respiratory departments, 179 (96%) were aware of hospital at home services for acute exacerbation of COPD and, in November 1999, 30 (16%) were running such a service. Difficulty in obtaining funding was the main reason for not setting up a service rather than lack of evidence of benefit or unsuitability of local circumstances. Median staffing level was two nurses (range one to six) looking after a median number of new patients of five per week (range 0.5 to 12). There was wide variation in the organisation of services. CONCLUSIONS: Despite lack of objective evidence of effectiveness, there was a high level of awareness of and interest in starting hospital at home services for acute exacerbation of COPD in British respiratory departments when assessed in November 1999.

Acute Disease↗

Mechanisms of pulmonary transfer factor decline following heart transplantation.

OBJECTIVE: Although the decline in the pulmonary transfer factor (TL(CO)) following heart transplantation is well documented, the causes and mechanisms of this decline remain unknown. The aim of this study was to determine the relative contribution of each of TL(CO) components (the diffusing capacity of the alveolar-capillary membrane (D(M)), the pulmonary capillary blood volume (V(C)) and haemoglobin concentration) to TL(CO) reduction in heart transplant recipients. METHODS: TL(CO) and its components were measured in 75 heart transplant recipients (mean age 48 years, range 19-61) between 6 weeks and 36 months after transplantation using the Roughton and Forster method and the single-breath technique. Results were compared with data from 38 heart transplant candidates (mean age 51 years, range 34-61) and 26 normal subjects (mean age 47 years, range 27-62). RESULTS: The mean percentage predicted TL(CO) was reduced in recipients compared to candidates (56.9 and 69.9%, respectively, P<0. 001) and both were lower than normal controls (97.7%, P<0.001). The mean percent predicted V(C) was also reduced in recipients compared to candidates (52.8% vs. 80.2 (4.2)%, P<0.001) which was also lower than normal subjects (102%, P<0.001). D(M) was equally reduced in recipients and candidates (77.7 and 81.4%, respectively, P=0.48) compared to normal subjects (100.0%, P<0.001). Correction for haemoglobin concentration increased TL(CO) in recipients to 63.5% (P<0.001), but it remained lower than haemoglobin-corrected TL(CO) in candidates (71.1%, P<0.001). In recipients, the intra-capillary resistance (1/thetaV(C)) formed 60% of the total resistance to CO transfer (1/TL(CO)) compared to 50% in candidates and normal subjects. CONCLUSIONS: TL(CO) decline following heart transplantation is due to an increase in the intra-capillary resistance, and this appears to be due to a combination of anaemia and reduced pulmonary capillary blood volume, with the diffusing capacity of the alveolar-capillary membrane remaining unchanged.

Adult↗

Identification of malnutrition in children with cerebral palsy: poor performance of weight-for-height centiles.

This study aims to evaluate the use of the United States National Center for Health Statistics (NCHS) weight-for-height centiles (WHC) in screening children with cerebral palsy (CP) for depleted body fat and to identify an alternate screening method. Growth data from 276 children aged from 3 to 12 years with CP were analyzed retrospectively. Height or a proxy for height, mid-upper arm circumference, weight, and skinfold thicknesses were recorded. Mid-upper arm fat area was calculated for each participant. The sensitivities and specificities of WHC and a number of alternative anthropometric screening methods for identifying participants with severely depleted fat stores were determined. WHC <10th centile failed to identify 45% of children with severely depleted fat stores. Triceps skinfold thickness <10th centile identified 96% of malnourished children. WHC standards lack adequate sensitivity for identification of severely depleted fat stores in children with CP. Use of triceps skinfold thickness, using cut-off value of <10th centile for age and sex, is recommended to screen for suboptimal fat stores in children with CP.

Anthropometry↗

The alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume in heart transplant candidates.

OBJECTIVES: To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TL(CO)) in heart transplant candidates, as this is the most common lung function abnormality. SETTING: Regional cardiopulmonary transplant centre. METHODS: TL(CO) and its components (the diffusing capacity of the alveolar-capillary membrane (D(M)) and the pulmonary capillary blood volume (V(C))) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS: Mean per cent predicted TL(CO), D(M), and V(C) were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p < 0.001). The relative contribution of the two components of TL(CO) in patients was similar to that of normal subjects, with each component accounting for approximately 50% of the total resistance to diffusion (1/TL(CO)). CONCLUSIONS: TL(CO) impairment in patients with severe chronic heart failure awaiting heart transplantation results from a proportionate reduction in both D(M) and V(C), suggesting a significant disturbance of the pulmonary vascular bed.

Adult↗

Early discharge for patients with exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: We have previously reported the use of a hospital based respiratory nurse service (Acute Respiratory Assessment Service, ARAS) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD. METHODS: Patients with COPD admitted as emergencies were identified the next working day. They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD, but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management. Of 360 patients reviewed, 209 were being assessed for other active medical problems and were excluded, 33 potential participants were already involved in research studies and so were ineligible, and 37 did not wish to participate in the study. Eighty one patients were randomised to receive conventional inpatient care (n=40) or to planned early discharge the next working day (n=41). Those discharged early continued treatment at home under the supervision of specialist respiratory nurses. Outcome measures were readmission, additional hospital days, and deaths within 60 days of initial admission. Process measures included number of visits, duration of follow up by the respiratory nurse, and additional treatment provided to support early discharge. RESULTS: On an intention to treat basis, a policy of early discharge reduced inpatient stay from a mean of 6.1 (range 1-13) days with conventional management to 3.2 (1-16) days with an early discharge policy. Twelve patients (30% conventional management, 29.3% early discharge) were readmitted in each group giving a mean difference in readmission of 0.7% (95% CI of the difference -19.2 to 20.6). In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group, giving a mean difference of 0.92 days (95% CI of the difference -6.5 to 8.3). There were two deaths (5%) in the conventional management group and one (2.4%) in the early discharge group, a mean difference of 2.6% (95% CI of the difference -5.7 to 10.8). CONCLUSIONS: Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses. No difference was found in the subsequent need for readmission.

Aged↗

Exercise intolerance following heart transplantation: the role of pulmonary diffusing capacity impairment.

STUDY OBJECTIVES: Although impairment of the diffusing capacity of the lung for carbon monoxide (DLCO) in heart transplant recipients is well-documented, there are limited data on its impact on exercise capacity in these patients. The aim of this study was to determine the effect of DLCO reduction on exercise capacity in heart transplant recipients. DESIGN: Descriptive cohort study. SETTING: A regional cardiopulmonary transplant center. PARTICIPANTS: Twenty-six heart transplant recipients who were studied before and after transplantation compared with 26 healthy volunteers. MEASUREMENTS: Spirometry and static lung volumes were measured using body plethysmography, DLCO was measured using the single-breath technique, and progressive cardiopulmonary exercise was performed using a bicycle ergometer, continuous transcutaneous blood gas monitoring, and on-line analysis of minute ventilation, oxygen uptake (VO(2)), and carbon dioxide production. RESULTS: Before transplantation, the mean percent predicted for hemoglobin-corrected DLCO was reduced in patients (73.2%) compared to healthy control subjects (98.8%; p < 0.001) and declined significantly after transplantation (60.1%; p < 0.05). Although the mean maximal symptom-limited VO(2) (VO(2)max) increased after transplantation (increase, 41.3 to 48.6% of predicted; p < 0.05), it remained substantially lower than normal (92.9%; p < 0.001). There was a significant correlation between DLCO and VO(2)max after transplantation (r = 0.61; p = 0.001), but not before transplantation (r = 0.09; p = 0.66). DLCO was also inversely correlated with other respiratory responses to exercise, including the following: the ventilatory response to exercise (r = -0.44; p < 0.05); dead space to tidal volume ratio (r = -43; p < 0.05); and the alveolar-arterial oxygen gradient (r = -0. 45; p < 0.05), but there was no correlation between any of these variables and DLCO before transplantation. CONCLUSION: DLCO reduction after heart transplantation appears to represent persistent gas exchange impairment and contributes to exercise limitation in heart transplant recipients.

Adult↗

Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids.

The possibility that glucocorticoids upregulate the expression of anti-inflammatory mediators is an exciting prospect for therapy in inflammatory diseases, because these molecules could give the therapeutic benefits of steroids without toxic side effects. Supernatants from monocytes and macrophages cultured in the presence of glucocorticoids increase the dispersion of neutrophils from a cell pellet in the capillary tube migration assay. This supernatant factor, unlike other neutrophil agonists, promotes dispersive locomotion of neutrophils at uniform concentration, lowers their adhesion to endothelial cells, inhibits their chemotactic response to fMLP and induces distinctive morphological changes. Here we show that thymosin beta4 sulfoxide is generated by monocytes in the presence of glucocorticoids and acts as a signal to inhibit an inflammatory response. In vitro, thymosin beta4 sulfoxide inhibited neutrophil chemotaxis, and in vivo, the oxidized peptide, but not the native form, was a potent inhibitor of carrageenin-induced edema in the mouse paw. Thymosin beta4 is unique, because oxidation attenuates its intracellular G-actin sequestering activity, but greatly enhances its extracellular signaling properties. This description of methionine oxidation conferring extracellular function on a cytosolic protein may have far-reaching implications for future strategies of anti-inflammatory therapy.

Amino Acid Sequence↗

Home treatment of exacerbations of chronic obstructive pulmonary disease by an acute respiratory assessment service.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease are a major cause of hospital admissions, but do not require intensive investigation or complex therapy. We investigated the suitability of home care for severe uncomplicated exacerbations. METHODS: Over 3.5 years we assessed 962 patients with exacerbations of chronic obstructive pulmonary disease after referral to a hospital respiratory department by their family physicians. All patients had chest radiographs, oxygen-saturation or arterial-gas analysis, spirometry, and physical assessment. Unless admission was thought to be essential, patients were allowed home with a customised treatment package. Each patient was visited daily by a respiratory nurse who monitored progress and treatment compliance and provided education and reassurance. FINDINGS: 145 (15%) of 962 required admission at initial referral and 115 (12%) were admitted later. 653 (68%) patients were managed entirely at home and 49 (5%) were referred inappropriately. One patient died at home. All patients had severe disease with a mean forced expiratory volume in 1 s of 1.02 L and 395 (41%) had required hospital admission in the previous year. INTERPRETATION: After formal assessment in a hospital respiratory unit, many patients with exacerbations of chronic obstructive pulmonary disease can be treated at home by respiratory nurses.

Acute Disease↗

The measurement of the single-breath transfer factor for carbon monoxide and its components using the Morgan Transflow system.

In contrast to the standard single-breath transfer factor for carbon monoxide (TLCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume (VC) and membrane component (DM), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24-55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23-54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of TLCO were used to derive a mean value for DM and VC for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean TLCO (mmol min-1 kPa-1) (standard first 5.13 +/- 1.15, high-oxygen first 5.14 +/- 1.12; limits of agreement -0.57 to 0.59 for DM or for VC. The long or short protocol produced no significant differences between the means of TLCO (mmol min-1 kPa-1) (long 8.0 +/- 1.9, short 8.0 +/- 1.9; limits of agreement -0.5 to 0.5), DM or VC. This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.

Adult↗

Linear growth velocity in children with cerebral palsy.

Retrospective analysis of an anthropometric database collected prospectively in children with cerebral palsy (CP) was carried out to evaluate linear growth velocity and identify risk factors for poor linear growth. Growth velocity measures were compared with published norms for prepubertal growth velocity and z scores were calculated. Mean growth velocity z score (Gvz) was -0.97+/-1.9. Boys grew more slowly than girls (mean Gvz = -1.5+/-1.9 versus -0.3+/-1.7 P = 0.003). Gvz did not correlate with type of CP or presence/absence of microcephaly. Young age was a risk factor for poor linear growth (mean Gvz = -2.40+/-2.6 for children under 2 years of age versus -0.76+/-1.9 ages 2 to 6 and -0.77+/-1.6 ages 6 to 10, P = 0.04). Children at nutritional risk (triceps skinfold thickness < or =55%) grew poorly (mean Gvz = -1.46+/-1.5 versus -0.30+/-1.8, P = 0.01). For children over 2 years, those with cognitive impairments grew more slowly than those with normal cognition (mean Gvz = -1.25+/-1.9 versus -0.12+/-1.8, P = 0.02) and non-ambulatory children grew more slowly than ambulatory children (mean Gvz = -1.20+/-1.5 versus -0.35+/-1.9, P = 0.03). Prepubertal children with CP grow more slowly than expected compared with age- and sex-based standards. Sex, age, cognitive impairment, ambulatory status, and nutritional state are factors which may contribute to slow growth. These results add to the growing data that children with CP have unique growth patterns. Further study is needed to clarify the factors which contribute to poor linear growth in this population.

Cerebral Palsy↗

The time course of pulmonary transfer factor changes following heart transplantation.

OBJECTIVE: The pulmonary transfer factor for carbon monoxide (TLCO) has been reported to decline following heart transplantation, but the time course of this decline is not well documented. The aim of this study was to define the longitudinal changes in TLCO after heart transplantation. METHODS: Single breath TLCO, lung volumes and expiratory flow rates were prospectively measured in 57 patients (mean age 49 years, range 19-61) before and at least once after heart transplantation. Thirty seven of the 57 patients had four post-transplant assessment which were performed at 6 weeks, 3, 6 and 12 months in 26 patients and at 12, 18, 24 and 36 months in 11 patients. Results were compared with data from 28 normal subjects (mean age 40 years, range 19-61). RESULTS: Before transplantation there was a mild impairment of lung volumes and expiratory flow rates. At 6 weeks after transplantation, there was a further reduction in the forced expiratory volume in one second, forced vital capacity, residual volume and total lung capacity, but all of these increased in the subsequent measurements to exceed their pre-transplant values at about 1 year after transplantation. Haemoglobin-corrected TLCO was also reduced before transplantation compared to normal controls (74.3% and 98.6% of predicted respectively, P < 0.001). Although TLCO per unit alveolar volume (KCO) was relatively preserved in heart transplant candidates, it was still significantly lower than that of normal controls (92.6% and 105.3% of predicted respectively, P < 0.05). After transplantation, mean haemoglobin-corrected TLCO and KCO declined by 12% and 20% of predicted respectively) with the majority of patients having reductions greater than 10% of predicted. The decline in TLCO and KCO was evident at 6 weeks after transplantation with no further changes in the subsequent measurements. CONCLUSIONS: TLCO is reduced in heart transplant candidates and declines further after heart transplantation despite improvement in lung volumes and airway function. The early and non-progressive nature of TLCO decline suggests an aetiology exerting its effect on TLCO within the first 6 weeks after transplantation.

Adult↗

Audit of oxygen therapy.

We audited the use of oxygen in our hospital. Over three days we found 119 patients using oxygen, 21 wearing their mask incorrectly or not at all. The commonest indication was chronic obstructive pulmonary disease. Forty patients had no record of arterial gas analysis. Of those who had, 29 did not require oxygen and the average time from last arterial gas analysis was 5.7 days and only eight patients were being monitored with an oximeter. Taking into account the risk of exacerbating carbon dioxide retention and the problems that arise when discharging a patient who has been receiving oxygen therapy for the duration of their admission, we fee oxygen therapy should only be administered with the knowledge of the arterial gases and with frequent reassessment during therapy.

Adult↗