Biomedical subjects
P B Rylance
Publications and source records attributed to P B Rylance.
Anti-platelet therapy in diabetic and non-diabetic progressive renal failure.
Explore the source record for details and available documents.
Haemostatic activation and proteinuria as factors in the progression of chronic renal failure.
Haemostatic activation was measured in patients with either non-diabetic chronic renal failure (CRF) or diabetic nephropathy. We have investigated the relationship between these haemostatic markers and the rate of progression of renal failure. When compared with age- and sex-matched healthy controls, both patient groups showed significantly elevated plasma concentrations of D dimer, von Willebrand factor antigen (vWFAg), and C-reactive protein (CRP) (all P less than 0.001), as well as an increase in spontaneous platelet aggregation (P less than 0.01). Plasma concentration of platelet factor 4 was slightly but not significantly increased. Serum thromboxane was subnormal (P less than 0.01). Multiple regression analysis showed that in non-diabetic CRF proteinuria and serum TxB2 were independently related to the rate of progression of renal failure; in diabetic nephropathy proteinuria and vWFAg were independently related to the rate of progression. In both groups the relationship was stronger with proteinuria (standardised regression coefficients 0.56 and 0.45 respectively) than with serum TxB2 (0.29) or with vWFAg (0.37). We have found haemostatic activation in both non-diabetic and diabetic progressive renal failure. Proteinuria, and also in this study serum TxB2 and vWFAg, appear to be determining factors in the progression of renal failure, and their measurement may have prognostic value.
Blood hyperviscosity and its relationship to progressive renal failure in patients with diabetic nephropathy.
Blood rheology was investigated in patients with diabetic nephropathy and progressive renal insufficiency, and compared with similar non-diabetic patients and healthy control subjects. Plasma viscosity and whole blood viscosity at standardized haematocrit were elevated to a comparable degree in the two patient groups, but erythrocyte deformability was normal. In diabetic patients, the rate of progression of renal failure showed weak, but significant, correlations with plasma viscosity (rs = 0.50, p = 0.005), standardized whole blood viscosity (rs = 0.41, p = 0.021), plasma fibrinogen (rs = 0.46, p = 0.010), C reactive protein (rs = 0.40, p = 0.023), and proteinuria (rs = 0.52, p = 0.003). Both plasma viscosity and plasma fibrinogen correlated significantly with proteinuria (rs = 0.45, p = 0.012 and 0.40, p = 0.027, respectively). Rheological abnormality is probably a manifestation of increased acute phase proteins, but it remains to be determined whether these are the cause or the effect of the renal injury. Abnormal blood rheology may be a risk factor for the progression of renal failure in diabetic nephropathy.
Renal replacement therapy for acute renal failure.
Mortality from acute renal failure (ARF) remains very high and is associated with the development of multisystem failure. Technical developments in haemodialysis machines and dialyser membranes have reduced complications associated with haemodialysis. However, some patients are too unstable to be haemodialysed successfully. Continuous haemofiltration and continuous arterio-venous (or veno-venous) haemodialysis can be performed on Intensive Care Units in hospitals without the availability of a Renal Unit. These techniques provide more effective and controlled removal of fluid and uraemic toxins. There are now few indications for the use of peritoneal dialysis. These new developments have facilitated easier management of the unstable patient with acute renal failure. Whether the prognosis of acute renal failure patients will be improved remains to be determined.
Plasma D dimer: a useful marker of fibrin breakdown in renal failure.
D dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 +/- 31 ng/ml) (mean +/- SEM) and diabetic nephropathy (308 +/- 74 ng/ml), when compared with healthy controls (96 +/- 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 +/- 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.
Carnitine and weakness in haemodialysis patients.
Weakness in haemodialysis patients has been attributed to several factors including carnitine deficiency. Malnutrition, neuropathy, uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced muscle power compared with a normal population, and to be malnourished by dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle, with an excess of esterified carnitine in both plasma and muscle and diminished free plasma carnitine. Muscle biopsy showed no features of carnitine deficiency and electromyography showed a non-specific neuropathy with additional myopathic changes in some. Dietary supplementation with L-carnitine (2 g/day) for 6 weeks in a placebo-controlled trial showed a redistribution of carnitine fractions but no subjective or objective improvement in muscle function. There was no improvement in the plasma lipid profile. The weakness of haemodialysis patients is multifactorial. We have not demonstrated total carnitine depletion in either muscle or plasma, and oral supplementation of L-carnitine has no demonstrable effect in this group.
Platelet function and the bleeding time in progressive renal failure.
Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe renal failure (greater than 600 mumol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p less than 0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.
The effect of induced hypotension and tissue trauma on renal function in scoliosis surgery.
The surgical correction of scoliosis in adolescents involves considerable trauma to bone and muscle which, together with hypotensive anaesthesia, might be expected to compromise renal function. Our recent observation of acute renal failure in two such patients prompted a prospective study of renal function following 52 operations in 43 patients. Despite hypotension, blood loss, muscle damage and evidence of fat embolism, renal function was unaltered in all patients, and there was no impairment of spinal cord function. Careful attention was paid to the maintenance of circulating volume which is essential to protect renal perfusion.
Abnormal blood rheology in progressive renal failure: a factor in non-immune glomerular injury?
Chronic renal insufficiency progresses by a final common pathway of glomerular damage characterised by microvascular injury and glomerulosclerosis. In order to investigate the possible role of blood rheology in this process, rheological indices were compared between healthy controls and a group of patients with progressive renal failure due to renal diseases that were not considered to be immunologically mediated. Plasma viscosity was significantly increased in the renal insufficiency group (P less than 0.005), and correlated with raised plasma concentrations of fibrinogen (r = 0.63; P less than 0.005). Whole-blood viscosity corrected to a standard haematocrit of 0.45 was also raised. A weak but significant correlation was seen between plasma viscosity and 24-h urinary protein excretion (r = 0.50; P less than 0.005). Our data show that in chronic renal insufficiency, rheology is abnormal. Proteinuria correlates with plasma viscosity, which is consistent with the hypothesis that raised plasma viscosity leads to an increase in glomerular capillary pressure and thence glomerular permeability. Correction of rheological abnormalities might help to preserve kidney function and reduce proteinuria in these patients.
Fish oil modifies lipids and reduces platelet aggregability in haemodialysis patients.
Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.
Natural progesterone and antihypertensive action.
In a placebo controlled, double blind crossover study natural progesterone was given by mouth, in increasing doses, to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. When compared with values recorded before treatment and during administration of placebo progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. This possible protective effect of progesterone should be investigated further.
Haemodialysis with prostacyclin (Epoprostenol) alone.
Dialysis with prostacyclin (Epoprostenol, PGI2) alone prevents platelet activation and endothelial cell stimulation but not the elevation of fibrinopeptide A (FPA), a sensitive marker of fibrin generation. The generation of FPA may explain why some patients develop clot in the dialysis circuit during PGI2-only dialysis. In combination with heparin, PGI2 augments the anticoagulant effect of the heparin as well as providing platelet protection.
Correction of citrate concentration is necessary in platelet aggregometry studies in uremia.
Explore the source record for details and available documents.
Generalised epileptic fits in renal transplant recipients given cyclosporin A.
Explore the source record for details and available documents.
An assessment of whole blood impedance aggregometry using blood from normal subjects and haemodialysis patients.
Impedance aggregometry allows the measurement of platelet responses in whole blood as well as in PRP. The variability of haematocrit values encountered when applying this technique to haemodialysis patients prompted an investigation of the effects of red cells on platelet aggregation in whole blood. Collagen induced aggregation was measured in both PRP and whole blood from haemodialysis patients and healthy controls. Platelets from haemodialysis patients were less aggregable than those from the controls when tested in PRP, but more aggregable when tested in whole blood. Blood samples with a range of haematocrit values were prepared by mixing PRP and autologous red cells, and used to study the effect of haematocrit on platelet aggregation. In blood from control subjects aggregation rate was reduced by rising haematocrit but no reduction of maximum aggregation occurred until haematocrit exceeded 40%. In contrast uraemic platelets showed increased responses in the presence of red cells. In a limited cross over study no significant difference was found in the effect on platelet aggregation of washed erythrocytes from uraemic and non-uraemic donors. It is concluded that red cell presence influences platelet aggregation by complex mechanisms during impedance aggregometry and that this effect must be considered when interpreting results.
Epoprostenol during haemodialysis.
Explore the source record for details and available documents.
Relationship between vitamin A and bone disease in chronic renal failure.
A study has been made of possible interrelationships between circulating vitamin A concentration and indicators of altered calcium homeostasis in 31 patients with stable chronic renal failure. Plasma retinol concentrations were high, possibly as a result of increased retinol-binding-protein concentrations secondary to renal failure. There was no correlation between retinol concentration and any other measurement, including vitamin A intake. However, there were significant correlations between plasma parathyroid hormone and calcium, phosphate, alkaline phosphatase, urea, and creatinine concentrations; and those patients with radiological sub-periosteal erosions tended to have the highest concentrations of circulating parathyroid hormone. Our data give no support to the contention that vitamin A status has any bearing on the progression and severity of the hyperparathyroid bone disease of renal failure.