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Biomedical subjects

R Wilkinson

Publications and source records attributed to R Wilkinson.

At least 163 records · Page 9Linked to original sources

Immunoreactive vasopressin in end stage renal failure.

Patients with end stage renal failure have been shown to have higher basal concentrations of plasma arginine vasopressin than subjects with normal renal function. Immunoreactive vasopressin was detected in plasma from patients with severe chronic renal failure and a healthy subject at an elution volume identical to that previously determined with synthetic vasopressin. Assay of all fractions yielded identical chromatograms in the renal failure and healthy control groups. We conclude that the plasma immunoreactive vasopressin in end stage renal failure plasma coelutes with synthetic vasopressin and that the elevated concentrations found in these patients are not due to non-specific depression of binding in the vasopressin radioimmunoassay by circulating substances in renal failure.

Adult↗

Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport.

Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.

Adult↗

Reliability of radionuclide scintigraphy for detection of testicular torsion: an animal study.

Sodium pertechnetate Tc99m scintigraphy is a valuable technique for the evaluation of acute testicular torsion in postpubescent males. However, in neonates and children with small testicles, the method is less reliable. Since the testicles of adult rats and young children are of similar size, the reliability of testicular imaging for detecting torsion was evaluated in this species. The utility of the radionuclide angiogram (RA) and static images were determined in 17 anesthetized animals before, 2 h after and 20 h after ligation of the left spermatic cord. The preligation RA was asymmetric in 27% of animals, while the static images were abnormal in 18%. Postligation flow and static images were abnormal in 57% and 82% of the animals (localized to the correct side, 38% and 36%), respectively. The animals with vascular occlusion failed to show any statistically significant greater incidence of decreased radionuclide accumulation on the ligated side. To determine the influence of relative perfusion and extracellular fluid space of the scrotum and testicles on the images, additional studies were performed with 201Tl (representing perfusion) and 99mTcO4- (representing ECF space). Perfusion was approximately equal in the testis and epididymis but significantly higher in the scrotum. These results suggest that scrotal scintigraphy is unreliable for detecting acute torsion of small testicles.

Animals↗

Biomechanical stability of four-part intertrochanteric fractures in cadaveric femurs fixed with a sliding screw-plate.

Three factors affecting the stability of four-part intertrochanteric fractures were considered; the type of reduction, the quality of bone as assessed by the Singh Index, and the position of the sliding screw within the head fragment. The stability of two different reductions of four-part intertrochanteric fractures created in paired cadaveric femurs was tested after fixation with sliding screw-plates. Cyclic loading over the range 1-6 times body weight was used to simulate physiological forces. The same loading regimen was applied to femurs with deliberately misplaced implants. Bone quality did not affect the incidence of failure. The type of reduction did not affect the incidence of failure, although it affected the mode of failure. Misplacing the implant greatly impaired the stability of the fracture. Thus, to minimize the risk of disruption of the reduced fracture every attempt must be made to ensure that the tip of the nail or plate lies between 5 and 12 mm from the subchondral bone of the femoral head and the shaft of the device in the central third of the neck on both anteroposterior and mediolateral radiographs.

Biomechanical Phenomena↗

Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium.

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.

Adult↗

Relationship between the maximum velocity and sodium affinity of the erythrocyte sodium pump and its rate constant in blood.

1. Young and mature erythrocytes from 15 normal subjects were used to compare the sodium pump rate constant measured in whole blood with the more definitive sodium affinity constant and maximum velocity of the sodium pump measured in artificial media using sodium-loaded cells. 2. Similar values were obtained from both erythrocyte fractions for the sodium affinity constant and maximum velocity and also by using two different plots. The median error in the estimate of individual sodium affinity constants and maximum velocities from regression analysis was about 20% and the precision was not improved by combining the data points for the two erythrocyte fractions. 3. The rate constant in whole blood was closely related to the sodium affinity constant and maximum velocity of the sodium pump (r = 0.75), suggesting that it was a reasonable overall assessment of available sodium pump activity. 4. Differences in the rate constant between subjects were due to differences in both the maximum velocity and sodium affinity constant of the sodium pump so that the rate constant could not be used as a guide to the underlying sodium pump physiology.

Adult↗

A serial study of erythrocyte sodium content and sodium pump kinetics in pregnancy.

1. Normotensive primigravid pregnant women were studied longitudinally during pregnancy and 20 weeks after delivery. 2. Erythrocyte sodium content, ouabain-sensitive sodium flux and sodium pump rate constant were measured in whole blood, and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. 3. Erythrocyte sodium content decreased and the sodium pump rate constant increased up to 26 weeks gestation. The increase in rate constant was due to an increase in the affinity of the sodium pump for sodium up to 20 weeks gestation. After 20 weeks gestation there was an increase in maximum velocity and a decrease in sodium affinity of the sodium pump but no further change in the sodium pump rate constant. 4. At 14 weeks gestation the sodium pump rate constant was correlated with both the maximum velocity and sodium affinity constant. After this time the relationship was much more variable and there was no correlation with the sodium affinity constant. The comparison of measurements of the sodium pump in whole blood and in vitro gave no evidence of sodium pump inhibition. 5. The erythrocyte sodium pump changed throughout gestation with different components to the change, but, overall, available sodium pump activity in blood increased and sodium content decreased.

Biological Transport, Active↗

Potassium supplementation in the treatment of idiopathic postural hypotension.

We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.

Aged↗

Sodium content and transport of white and red blood cells in undialysed uraemic and continuous ambulatory peritoneal dialysis patients.

Leukocyte cation content and sodium pump transport were measured in 14 undialysed uraemic and 15 CAPD patients and compared with results from healthy controls. Sodium content was elevated in the undialysed group compared with the CAPD group (P = 0.05) or the healthy controls (P less than 0.001), but this abnormality could not be clearly attributed to increased sodium influx or reduced sodium pumping. Sodium content correlated with plasma urea (rs = 0.69, P = 0.005) and creatinine (rs = 0.56, P = 0.031) concentrations in the CAPD group only. In subgroups of 12 undialysed and ten CAPD patients, erythrocyte sodium content and pump transport were measured at the same time as the leukocyte studies. Erythrocyte sodium was less in the undialysed group (P less than 0.01) and again there was no evidence of significant sodium-pump inhibition. The abnormalities in sodium content in undialysed patients were therefore in opposite directions in the two cell types, and were significantly less in both cell types in CAPD patients. These results emphasise the dangers of assuming that abnormalities of sodium transport seen in a single cell type can be taken as evidence of a generalised abnormality.

Adolescent↗

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↗

Survival associated with renovascular disease in Glasgow and Newcastle: a collaborative study.

Data from 121 consecutive patients with hypertension and renovascular disease, first diagnosed between 1975 and 1982 in Glasgow and Newcastle, were analysed retrospectively to determine the factors which influenced their outcome. Thirty-six patients died between the data of arteriography and 1st January 1987, giving five and ten year survival rates of 83% and 67%. Survival was greatly reduced in comparison with that of age-sex-matched controls in the general population of the West of Scotland, and was also less than that of essential hypertensives matched for age, sex, initial diastolic blood pressure and smoking habit who had attended the Glasgow Blood Pressure Clinic during the same period. Multivariate analysis showed that age, cigarette smoking and presence of atheromatous disease were significantly and independently related to outcome among the patients with renovascular disease, whereas male sex, centre of origin, severity of hypertension when first seen, initial renal function and presence of bilateral disease were not. Despite a trend towards benefit from surgical intervention (ten year survival in medical group 62%, in surgical group 71%; p = 0.19) our data do not prove that intervention is better than medical treatment, largely because the decision on intervention was not randomised. A prospective trial would be required to answer this important question.

Adult↗

A dose finding study of the combination of atenolol and nifedipine in hypertension.

A randomized, double-blind, crossover study was carried out to compare the antihypertensive efficacy and tolerability of two doses of a fixed combination of 50 mg atenolol and 20 mg nifedipine slow release (1 capsule or 2 capsules once daily) in 16 hypertensive patients, treated for 4 weeks with each dose. The results suggest that the combination exerted a greater antihypertensive effect at 3 hours compared with 24 to 28-hours post-dose. Demonstrable differences in resting blood pressure between the low and high dose of the combination occurred at the 3-hour but not at the 24 to 28-hour post-dose time point. This apparent difference was also evident under exercise conditions, although no significance between dose differences were demonstrable at either time point. Thus, it appears that any additional benefit in efficacy obtained with the higher dose is not sustained over a 24-hours period. Side-effects were relatively uncommon with the combination, occurring least commonly with the lower dose.

Adolescent↗

Upper airway obstruction due to goitre: detection, prevalence and results of surgical management.

A group of 132 women and 12 men with goitre were studied to determine the prevalence of upper airway obstruction caused by the goitre. Inspection of flow-volume loops was used to detect upper airway obstruction and this suggested that 44 subjects (31 per cent) had the condition. Of these 44 subjects 19 per cent were men, which was a greater proportion than could be accounted for by chance. Flow-volume loops after surgery were recorded on 43 patients of whom 29 were from the group thought to have had upper airway obstruction. Comparison of measurements before and after surgery showed no important change in the 14 without, and improvement in 27 of those with, upper airway obstruction. Analysis indicated two failures of treatment and four probable false-positives among the group with upper airway obstruction. Inspection of the flow-volume loop had a 78 per cent specificity and 100 per cent sensitivity in detecting upper airway obstruction whereas an FEV:PEF ratio above 8 had a specificity of 94 per cent and a sensitivity of 64 per cent in this respect. Ultrasonography and plain radiography of the upper airway accurately predicted retrosternal extension of the goitre but did not predict upper airway obstruction. It is recommended that all patients with symptomatic goitre should have a flow volume loop recorded.

Adult↗