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Biomedical subjects

S J Carr

Publications and source records attributed to S J Carr.

At least 19 recordsLinked to original sources

Assessing clinical competency in medical senior house officers: how and why should we do it?

Most consultants are involved in the training and assessment of several grades of doctors in training especially senior house officers (SHOs) and specialist registrars. In the medical and other specialties there is an increasing trend towards assessing junior doctors' competency using the record of in-training assessment process for specialist registrars and using the Royal College of Physicians folder to record competences of medical SHOs. It is necessary to consider why there is a need to assess competency, how it may be done practically, and the advantages and disadvantages of this system of assessment. There are considerable hurdles to the implementation of this system in the medical specialties within today's NHS and the organisation may need to undergo fairly radical change to facilitate this system.

Clinical Competence↗

Red cell Na+/Li+ countertransport and Na+/H+ exchanger isoforms in human proximal tubules.

BACKGROUND: Increased activity of the Na+/Li+ countertransporter (SLC) is a well-recognized intermediate phenotype of hypertension and diabetic nephropathy and may indicate a predisposition to hypertension. Previous work has attempted to link this membrane transport marker to altered Na+ reabsorption in the proximal tubule. Since the Na+/H+ exchanger (NHE) isoforms 1 and 3 are expressed in the basolateral and apical membranes of the proximal tubule, respectively, we investigated the relationship between these transport proteins and red cell SLC to examine whether the peripheral blood transport phenotype is associated with altered levels of transport proteins in the proximal tubule. METHODS: Proximal tubules were prepared from human nephrectomy specimens. NHE-1 and NHE-3 were detected on Western blots by specific antibodies. Red cell SLC was also measured. RESULTS: Both NHE-1 and NHE-3 proteins were demonstrated, with molecular weights of 97 and 85 kD, respectively. SLC was very strongly correlated with the level of NHE-3 protein (r = 0.78, P < 0.001) and was negatively related to NHE-1 protein (r = -0.32). In multiple regression analysis, only NHE-3 and NHE-1 protein levels were significant predictors of red cell SLC, accounting for up to about 70% of the variance of this parameter. CONCLUSIONS: We conclude that red cell SLC may be a marker of increased NHE-3 protein expression in the proximal tubule, which may account for the blunted pressure natriuresis and predisposition to hypertension.

Adult↗

A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors.

BACKGROUND: In an attempt to address the shortage of conventional kidney donors, a non-heart-beating donor (NHBD) organ retrieval program has been established. We compared the results of kidney transplants from NHBDs (N = 77) with those from heart-beating cadaveric (HBD; N = 224) and living donors (LD; N = 49), performed in the same eight-year period. METHODS: Patients dying after failed attempts at resuscitation in the accident department or after intracerebral hemorrhage/anoxia were considered as potential NHBDs. After death, in situ kidney perfusion and cooling were achieved using an intra-aortic catheter inserted via a femoral artery cut down. Kidney retrieval and transplant operations were performed using standard techniques. RESULTS: The median (range) warm ischemic time for NHBD kidneys was 25 minutes (5 to 53 min). The initial function rates for NHBD, HBD, and LD transplants were 6.5, 76.3, and 93%, respectively. Primary nonfunction occurred in 5 of 75 evaluable NHBD transplants (7%) compared with only 6 out of 224 (2.7%) HBD and 1 out of 49 (2%) LD transplants (P = NS). Eighty-four percent of NHBD kidney recipients required postoperative dialysis for a median of 19 days. The mean (SD) serum creatinine at 12 months was 179 (73) micromol/L in NHBD kidneys compared with 152 (57) micromol/L for HBD kidneys and 138 (44) micromol/L for LD kidneys. The actuarial five-year graft survival rates for NHBD, HBD, and LD transplants were 79, 75, and 78%, respectively. During the period under study, NHBD organs accounted for 22% of the total renal transplant program. CONCLUSIONS: Despite being associated with poor initial graft function, the long-term allograft survival of NHBD kidneys does not differ significantly from the results of HBD and LD transplants.

Adult↗

Workload generated by a living donor programme for renal transplantation.

BACKGROUND: The ethical and medical implications of live kidney donation result in a comprehensive work-up process. The aim of this study was to determine the magnitude of the workload and the yield of renal transplants generated by a live donor programme. METHODS: Referrals to the Leicester live donor programme over the five-year period 1994-1998 were retrospectively assessed. These were initiated by nephrology referral and subsequently investigated in a stepwise manner. Patients were counselled and baseline tests performed prior to consultant surgeon review and assessment of donor renal function/anatomy. RESULTS: One hundred and fifty referrals consisting of 150 recipients with 269 potential donors were originally made. This resulted in 32/120 (27%) related and 3/30 (10%) unrelated recipients (P=0.06) and 32/220 (15%) related and 3/49 (6%) unrelated donors proceeding to live donor transplantation, with a mean work-up time (+/-SD) of 9 (+/-7) months. One hundred and fifteen recipients (77%) and 234 (87%) donors failed to proceed at various stages of assessment, for a variety of immunological, medical and social reasons. A large number of expensive immunological investigations were required for potential donors, the majority of which did not proceed to transplantation. However as a result of performing these in the early stages of assessment the number of more invasive tests is kept to a minimum. CONCLUSIONS: There is a relatively low yield of transplants from live donor referrals, particularly those between unrelated individuals. The vast majority of referrals fail to proceed for legitimate reasons, but as a result, create a significant workload with notable staffing and financial implications.

Health Care Costs↗

Raised affinity for extracellular sodium of the sodium-lithium countertransporter is associated with a family history of hypertension and uraemia in patients with renal disease.

1. Increased affinity for sodium (Km) at an external site of the sodium-lithium countertransporter and altered membrane microviscosity in the surface regions of the lipid bilayer identifies a group of essential hypertensive patients with a genetic predisposition to hypertension. The present study investigated the kinetic properties of the sodium-lithium countertransporter and membrane microviscosity in patients with hypertension, renal disease and impaired renal function. 2. Sixty patients with renal disease (28 chronic renal failure, 30 hypertensive, 23 family history of hypertension) were investigated. Standard erythrocyte sodium-lithium countertransport activity, sodium affinity constant (Km), maximum reaction velocity (Vmax) and membrane microviscosity were measured. 3. Patients with renal disease and a family history of hypertension had significantly lower Km (P < 0.05) values and raised membrane microviscosity measured by 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy (P < 0.05) compared with patients without a family history of hypertension. 4. Uraemic subjects had low K(m) values compared with patients with renal disease and normal renal function (P < 0.05). However, there was no significant difference in membrane microviscosity between uraemic and non-uraemic subjects. 5. In patients with a family history of hypertension, sodium-lithium countertransport activity and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy are important markers of cellular changes in essential hypertension, independent of renal disease. Uraemia, independently of hypertension, produces an alteration in the function of the sodium-lithium countertransporter which has previously been associated with a genetic predisposition to hypertension and cardiovascular disease.

Antiporters↗

Altered membrane microviscosity in essential hypertension: relationship with family history of hypertension and sodium-lithium countertransport activity.

OBJECTIVE: To investigate the alterations in erythrocyte ghost membrane microviscosity in essential hypertensive patients and to determine the relationship between these changes and the sodium-lithium countertransport activity as a sensitive marker of membrane function. SUBJECTS: Forty-three normolipidaemic essential hypertensive patients (23 treated, 20 untreated) and 27 normotensive controls were studied. Patients were attending the hospital hypertension clinic or a local general practitioner's surgery. METHODS: Erythrocyte sodium-lithium countertransport activity was measured. The Michaelis constant (Km) for extracellular sodium and maximal reaction velocity for sodium-lithium countertransport were measured in a subgroup consisting of 22 essential hypertensive patients and 11 normotensive controls. Erythrocyte membrane microviscosity was measured using fluorescence polarization anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). RESULTS: There was no significant difference in the fluorescence polarization anisotropy of DPH or TMA-DPH between normotensive and essential hypertensive patients. However, the fluorescence polarization anisotropy of TMA-DPH was increased significantly (reflecting increased membrane microviscosity) in hypertensive patients with a family history of hypertension compared with in patients without a family history of hypertension. The standard sodium-lithium countertransport activity was elevated in essential hypertensive patients compared with normotensive controls, and the Km for sodium was significantly lower in patients with a family history of hypertension than in patients without a family history of hypertension. Patients with a family history of hypertension were clustered, with significantly lower Km for sodium and higher TMA-DPH anisotropies than either hypertensive patients without a family history of hypertension or normotensive controls. CONCLUSIONS: These findings suggest that a high membrane microviscosity affecting the outer region of the lipid bilayer is associated with altered sodium-lithium countertransport kinetics in a subgroup of essential hypertensive patients consisting of those with a family history of hypertension.

Antiporters↗

Plasma amino acid profile in the elderly with increasing uraemia.

Abnormalities in plasma amino acid profiles have been reported in severe uraemia and dialysis patients and may be a consequence of altered protein metabolism in the presence of metabolic acidosis. We studied plasma amino acid profiles in 7 control subjects [GFR 92.7 +/- (SEM) 14.5 ml/min/1.73 m2] and 7 elderly patients with renal failure (GFR 16.5 +/- 1.3 ml/min/1.73 m2). Uraemic patients had significantly reduced plasma levels of valine, tyrosine, phenylalanine, tryptophan and elevated histidine compared to controls. There was no correlation between arterial pH or bicarbonate and plasma amino acid levels.

Aged↗

A middle ear teratoma causing acute airway obstruction.

A rare benign teratoma of the middle ear, eustachian tube and nasopharynx presenting in an 8-month-old infant, is reported. The true nature of the tumour was not appreciated until after partial surgical resection from the middle ear. This procedure was complicated 3 days later by life-threatening airway obstruction, caused by the tumour slipping from the eustachian tube and obstructing the larynx. This unusual presentation and the pathology of the teratoma are discussed. The case demonstrates the importance of nasopharyngeal examination where middle ear lesions distort the eustachian tube.

Airway Obstruction↗

Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type 1 diabetes.

1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension. 2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients. 3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax) was increased. 4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal. 5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes.

Adult↗

Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy.

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.

Antiporters↗

Three psychological treatments for bulimia nervosa. A comparative trial.

The specificity and magnitude of the effects of cognitive behavior therapy in the treatment of bulimia nervosa were evaluated. Seventy-five patients who met strict diagnostic criteria were treated with either cognitive behavior therapy, a simplified behavioral version of this treatment, or interpersonal psychotherapy. Assessment was by interview and self-report questionnaire, and many aspects of functioning were evaluated. All three treatments resulted in an improvement in the measures of the psychopathology. Cognitive behavior therapy was more effective than interpersonal psychotherapy in modifying the disturbed attitudes to shape and weight, extreme attempts to diet, and self-induced vomiting. Cognitive behavior therapy was more effective than behavior therapy in modifying the disturbed attitudes to shape and weight and extreme dieting, but it was equivalent in other respects. The findings suggest that cognitive behavior therapy, when applied to patients with bulimia nervosa, operates through mechanisms specific to this treatment and is more effective than both interpersonal psychotherapy and a simplified behavioral version of cognitive behavior therapy.

Adolescent↗

Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.

Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.

Adult↗

Effects of induced elated and depressed mood on self-focused attention.

Recent accounts of depression propose a central role for increased self-focus in the onset and maintenance of depression. The present study investigated whether there might also be a converse effect of depressed mood increasing self-focus. A state measure of self-focused attention was administered to normal subjects before and after induction of depressed or happy mood. Compared to happy subjects, depressed subjects showed more negative and less positive self-focus. Positive and negative external focus were unaffected by mood. A reciprocally reinforcing relationship between depressed mood and negative self-focus may be important in onset and maintenance of depression.

Adult↗

Role of air sampling in investigation of an outbreak of legionnaires' disease associated with exposure to aerosols from an evaporative condenser.

Epidemiologic studies have suggested that legionnaires' disease can be transmitted to susceptible hosts by contaminated aerosolized water from cooling towers and evaporative condensers; however, epidemic strains of Legionella have not been isolated by air sampling at such sites during epidemiologic investigations. An outbreak of legionnaires' disease occurred at a retirement hotel; Legionella pneumophila serogroup 1 was isolated from an evaporative condenser and from potable water. A case-control study showed that the only significant exposure risk was in area A. L. pneumophila serogroup 1 was isolated during air sampling near the evaporative condenser exhaust site, the air conditioning intake vent, and an air vent in area A, but not in shower stalls. Monoclonal antibody subtype patterns of L. pneumophila serogroup 1 isolates from patients matched those from the evaporative condenser but not from shower water. Air sampling and monoclonal antibody subtyping results support epidemiologic evidence that the evaporative condenser was the source of this outbreak.

Aerosols↗

Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension?

Erythrocyte sodium-lithium countertransport was measured in normolipidaemic and hyperlipidaemic hypertensive patients, hyperlipidaemic normotensive patients and normal controls. Hypertension and hyperlipidaemia were each independently associated with raised sodium-lithium countertransport (by analysis of variance, P less than 0.01 and P less than 0.01). The effects were additive so that hyperlipidaemia could not explain raised sodium-lithium countertransport in hypertension. In hyperlipidaemic hypertensive patients, levels of plasma cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were increased, and high-density lipoprotein (HDL) cholesterol was reduced. Of these patients, 73.3% had a known family history of hypertension. Their normotensive first degree relatives were studied, and 48% of these also had raised sodium-lithium countertransport and abnormal plasma lipids (raised cholesterol, triglycerides and LDL cholesterol, and reduced HDL cholesterol). Relatives with normal sodium-lithium countertransport had normal lipids. Therefore, raised sodium-lithium countertransport was associated with the inheritance of both hypertension and hyperlipidaemia, and this could explain why raised sodium-lithium countertransport has been associated with a family history of both hypertension and associated cardiovascular disease.

Antiporters↗