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Biomedical subjects

J W Persaud

Publications and source records attributed to J W Persaud.

At least 19 recordsLinked to original sources
PubMed1993

Low-dose simvastatin is safe in hyperlipidaemic renal transplant patients.

Hyperlipidaemia is common after renal transplantation, and because of its association with atherosclerosis, interest has increased in the use of lipid-lowering drugs in transplant patients. Dietary approaches have not been consistently successful, and multiple pharmacotherapy and drug interactions have led to difficulties in establishing lipid-lowering drug regimes. The statins reduce plasma cholesterol by inhibiting the rate-limiting step in cholesterol synthesis, and although some side-effects have been reported in their use after transplantation, the efficacy and safety of low doses has not been formally established. A randomized single-blind placebo crossover study designed to determine the safety and effectiveness of simvastatin in a single daily 5-mg evening dose was therefore conducted in 26 stable renal transplant patients, 14 of whom were receiving cyclosporin A. The results demonstrated no difference between total cholesterol levels in the baseline simvastatin and placebo periods: 7.97 +/- 1.2 and 7.59 +/- 1.5 mmol/l respectively. After 8 weeks of simvastatin, the total cholesterol declined significantly to 6.72 +/- 0.87 mmol/l (P < 0.001). A significant difference was found when the placebo and simvastatin cholesterol levels were compared at 4 and 8 weeks (P < 0.01). LDL cholesterol decreased from 4.74 +/- 0.87 to 3.78 +/- 0.78 mmol/l after 8 weeks on simvastatin (P < 0.001), and apo B fell from 142 +/- 31 to 112 +/- 22 mg/dl (P < 0.001). The difference in LDL cholesterol and apo B after 8 weeks of simvastatin when compared with the corresponding values on placebo was also significant (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Lipoprotein(a) in patients with proteinuria.

Lipoprotein(a) (Lp(a)) has recently been recognized to be a risk factor for coronary heart disease. Lp(a) median values in the absence of renal disease are around 10 mg/dl. Higher levels (greater than or equal to 30 mg/dl) correlate with the occurrence of coronary heart disease, particularly in the presence of elevated cholesterol. We have studied Lp(a) in 76 adults with proteinuria. Fifty had glomerular diseases and 26 non-glomerular diseases, with renal function varying from normal to advanced chronic renal failure. Lp(a) values were shifted to the right, with a median of 21.0 mg/dl, and 25% of patients had values of 30 mg/dl or more. Lp(a) did not correlate with cholesterol, age, lipoprotein subclasses, apoproteins A-I or B-100, albumin, creatinine, or creatinine clearance. Median Lp(a) values did not differ significantly comparing men versus women, or glomerular versus non-glomerular disease. Lp(a) may inhibit fibrinolysis, and is deposited in atherosclerotic lesions. Although the cause of these elevated Lp(a) levels is uncertain, we propose that they contribute to the increased risk of coronary heart disease in the nephrotic syndrome, and may play a role in progressive renal disease.

Adolescent↗
PubMed1991

Effects of dietary fatty acids in an animal model of focal glomerulosclerosis.

The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomerulosclerosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer sclerosed glomeruli in the fish oil group (4.0 +/- 0.8% vs. control 19.4 +/- 4.1%, P less than 0.0005 and vs. beef tallow 10.8 +/- 1.9%, P less than 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1 alpha), PGF2 (PGF2 alpha) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production.

Animals↗
PubMed1991

Partial lecithin:cholesterol acyltransferase (LCAT) deficiency in Balkan endemic nephropathy.

The role of lipid abnormalities has been also implicated in the progression of renal diseases. The search for lipid abnormalities in Balkan endemic nephropathy (BEN) has roused sporadic interest and has not been fully elucidated. This study was performed in 54 healthy subjects from the families affected with BEN (group A), 18 members from non-affected families living in the same location (group B), and 25 control subjects (group C). Lipid profiles and lecithin:cholesterol acyltransferase (LCAT) were determined in each subject. The most striking distinction between the groups was that of the LCAT activity, which was abnormally low in group A (39 +/- 2), significantly different (P less than 0.0001) from that of the other groups. Thirty individuals from group A were those accounting for the low LCAT activity (A1). This group had a significantly lower total cholesterol and free cholesterol than all of the other subjects. The entire group A subjects had a significantly lower percentage of free cholesterol than the other two groups. There was no significant difference in HDL cholesterol between any of the groups, but group A1 had significantly higher HDL than group C (P less than 0.04). What emerges from our study is that a certain proportion of subjects from BEN families have a peculiar form of lipid abnormalities associated with an abnormal LCAT activity. At present we have no explanation for these findings. We believe that these changes may have an important role in the pathogenesis of BEN.

Adult↗
PubMed1990

Effects of low-density lipoproteins on mesangial cell growth and viability in vitro.

Recent animal studies suggest that abnormal lipid metabolism may play a role in the pathogenesis of glomerulosclerosis. In order to define mechanisms whereby lipoproteins could contribute to glomerular injury, the effect of Low-density lipoprotein (LDL) concentration on the proliferation of rat mesangial cells was studied in vitro. Human LDL was added to culture medium that had been rendered otherwise lipid free and proliferation rate was estimated by measuring incorporation of 3H-thymidine. When compared to standard medium, LDL-enriched medium stimulated cell division when present in protein concentrations of between 10 and 100 micrograms/ml. At greater concentrations (more than 200 micrograms/ml), cell proliferation was inhibited and above 500 micrograms/ml cells sustained visible morphological injury when assessed under phase contrast microscopy. Estimation of 51Cr release from prelabelled cells confirmed that LDL was cytotoxic in these greater concentrations. A similar pattern of proliferation and toxicity has been observed in vascular smooth muscle cell cultures over a corresponding range of LDL concentrations. These results strengthen the analogy between glomerulosclerosis and atherosclerosis and provide further evidence that lipoproteins may contribute directly to glomerular scarring.

Animals↗
PubMed1986

Evaluation of Coomassie dye binding method for microprotein assay in diabetic proteinuria.

A simple and relatively cheap method for quantitating diabetic microproteinuria with Coomassie brilliant blue dye binding method was evaluated. It provides a proportional reactivity to urinary albumin as measured by the more expensive immunoassay. The significant correlation between haemoglobin A1 and microproteinuria shows that the quantity of urinary protein is affected by metabolic control of diabetes.

Adult↗
PubMed1984

Post-heparin hepatic and lipoprotein lipase activities in nephrotic syndrome.

Lipid metabolism was studied in 18 patients with nephrotic syndrome due to various glomerulonephritides. Nephrotic patients had hypercholesterolemia with or without hypertriglyceridemia. The mean serum high-density lipoprotein cholesterol concentration was not significantly reduced in nephrotic patients. Hepatic lipase and lipoprotein lipase activities were measured selectively in post-heparin plasma from all 18 patients using a substrate-specific method. The mean lipoprotein lipase activity in nephrotic patients was markedly reduced while the mean hepatic lipase activity was not significantly different from that of controls. Lipoprotein lipase activities correlated inversely with serum triglyceride concentrations, but positively with in vivo post-heparin fractional clearance rates of Intralipid and with serum high-density lipoprotein concentrations. Nephrotic serum inhibited lipoprotein lipase activity in normal subjects. The percentage inhibition, however, did not correlate with the degree of hypertriglyceridemia. A relatively weak inverse correlation was shown to exist between plasma albumin concentration and hepatic lipase activities.

Adolescent↗
PubMed1983

Digital vascular imaging and selective renin sampling in evaluation of vascular anatomy in renal transplant recipients.

Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation.

Adolescent↗
PubMed1983

Digital vascular imaging and selective renin sampling in post-transplant hypertension. Which kidney is responsible?

Forty-four hypertensive transplant patients were investigated by digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity to attempt to identify those patients whose hypertension may be amenable to surgical treatment. Localization of renin hypersecretion was possible in 12 patients. In ten of these, hypersecretion originated from the native kidney and in two from the graft. Localization was possible in a significantly higher proportion of patients with severe hypertension (8 of 17), and all of these had native kidney hypersecretion. Bilateral nephrectomy may be indicated in these patients. No cases of functionally significant renal artery stenosis were identified. The other major types of abnormal vascular pattern found on digital vascular imaging, diffuse intra-renal arterial attenuation and lower pole hypoperfusion may be secondary to hypertension. This combined technique may be useful in the evaluation of post-transplant hypertension, especially when hypertension is severe.

Adult↗
PubMed1982

Plasma LCAT activities in renal allograft recipients.

Plasma LCAT activities were measured in 51 renal allograft recipients as well in 18 patients before and after successful renal transplantation. The mean plasma LCAT activity of the 51 patients did not differ significantly from that of 27 normal subjects. When the patients were separated into two groups according to whether they had normal or impaired renal function, there was no significant difference in their mean LCAT activities. Plasma LCAT activities correlated significantly with total cholesterol and total triglyceride concentrations. The sequential study demonstrates that the low plasma LCAT activities in uraemic patients rose towards normal after successful transplantation. At the same time, total cholesterol and HDL-cholesterol concentrations also increased. The increase in LCAT activity after renal transplantation is due to increased concentrations of the enzyme and probably reflects increased turnover of triglyceride-rich lipoproteins.

Adult↗
PubMed1982

Plasma lecithin-cholesterol acyltransferase activities in uraemic patients.

Plasma lecithin-cholesterol acyltransferase (LCAT) activity was measured in 43 haemodialysis and 15 peritoneal dialysis (CAPD) patients. LCAT activities in both groups of patients were significantly lower than those of normal subjects and did not correlate with any of the other biochemical parameters studied. The effect of intravenous administration of 100 U/kg of heparin on LCAT activity was examined in 21 haemodialysis patients and 19 normal subjects. Heparin inhibited LCAT activity by increasing plasma free fatty acid concentrations. LCAT remained inhibited throughout a dialysis session and returned towards pre-dialysis levels an hour after haemodialysis was discontinued. The cause of the low LCAT activities in the patients was not certain, but did not appear to be due to the presence of inhibitors in the uraemic plasma. The significance of these findings is discussed.

Adult↗
PubMed1982

Response patterns to DL-carnitine in patients on maintenance haemodialysis.

10 hypertriglyceridaemic hemodialysis patients were given dl-carnitine, 600 mg daily, for 8 weeks and then 1.2 g daily for 12 weeks. Serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol and plasma free fatty acid (FFA), glucose, and immunoreactive insulin concentrations were measured at regular intervals during the treatment. Intravenous fat tolerance tests were performed in 9 patients. Plasma FFA concentrations fell and the post-heparin fractional clearance rate of Intralipid increased significantly after all-carnitine administration. While overall no clear-cut effect of dl-carnitine on serum lipids was found, two patterns of response to dl-carnitine could be distinguished: the 'paradoxic' response with a rise in serum triglyceride concentrations and the dual response to two different dosages of dl-carnitine.

Adult↗
PubMed1982

Hyperlipidemia in patients on maintenance hemo- and peritoneal dialysis: the relative pathogenetic roles of triglyceride production and triglyceride removal.

A study was undertaken in 76 patients on maintenance hemodialysis and 26 patients on maintenance peritoneal dialysis to elucidate the pathogenesis of hyperlipidemia in these patients. A high prevalence of hypertriglyceridemia and low concentrations of high density lipoprotein cholesterol was found. Hemodialysis patients had low or normal total cholesterol concentrations which were significantly lower than those on peritoneal dialysis. The length of treatment did not affect the prevalence of the lipid abnormalities. Both pre- and post-heparin fractional clearance rates of Intralipid were markedly reduced in both groups of dialysis patients and were correlated inversely with serum triglyceride concentrations. However, when compared with normal subjects with similar fractional clearance rates of Intralipid, both groups of dialysis patients had higher serum triglyceride concentrations, probably reflecting increased triglyceride production. Serum triglyceride concentrations in both groups of dialysis patients were positively correlated with plasma immunoreactive insulin levels. Furthermore, a significant inverse correlation was observed between plasma immunoreactive insulin levels and post-heparin fractional clearance rates of intralipid. It was concluded that insulin resistance probably caused the defective triglyceride removal, and that both decreased removal and increased production of triglycerides contributed to the hyperlipidemia in dialysis patients.

Adult↗
PubMed1981

Hyperlipidaemia in untreated nephrotic syndrome, increased production or decreased removal?

The relative importance of increased lipoprotein synthesis and decreased lipoprotein catabolism is examined in 13 patients with untreated nephrotic syndrome by the use of intravenous fat tolerance tests analysed in relation to other parameters of lipid metabolism. Increased lipoprotein synthesis in nephrotic patients was indicated by the fact that at a given fractional clearance rate of Intralipid (K2), nephrotic patients had higher serum TG concentrations than did control subjects. A defect in lipoprotein catabolism was also suggested by the frequent finding of intermediate density lipoproteins on electrophoresis and the marginally low (p = 0.05) mean K2 in nephrotic patients. A highly significant (p less than 0.001) positive correlation between HDL-cholesterol concentrations and postheparin fractional clearance rates (K'2) of Intralipid led to the speculation that in the severe nephrotic state (albumin less than 20 g/l) the loss of high density lipoproteins may contribute to the hyperlipidaemia.

Adolescent↗
PubMed1981

Fat clearances and hyperlipidaemia in renal allograft recipients--the role of insulin resistance.

The mechanism of hyperlipidaemia in renal allograft recipients was investigated in 19 patients randomly selected from a cohort of 54 patients with functioning renal allografts. Serum cholesterol, triglyceride and high-density lipoprotein cholesterol concentrations as well as plasma immunoreactive insulin levels were measured in fasting blood samples. Intravenous fat tolerance tests were performed before and 15 min after heparin administration. Renal allograft recipients had reduced fractional clearance rates of Intralipid and a positive correlation was demonstrated between plasma immunoreactive insulin levels and serum triglyceride concentrations. Plasma immunoreactive insulins also correlated inversely with fractional clearance rates of Intralipid. It was concluded that both increased production and decreased removal of lipoproteins contribute to the hyperlipidaemia and that insulin resistance due to corticosteroids was the centre of the problem.

Adult↗
PubMed1981

The role of multiple pharmaco-therapy in the pathogenesis of hyperlipidemia after renal transplantation.

A study was undertaken in 54 renal allograft recipients to evaluate the multiple factors contributing to the pathogenesis of hyperlipidemia after renal transplantation. Serum triglyceride concentrations were found to correlate positively with the cummulative prednisolone dose, and with abdominal skin fold thickness. Serum cholesterol concentrations correlated significantly with serum creatinine concentrations. Patients on beta adrenergic blocking agents had lower plasma free fatty acid concentrations and patients on diuretics had higher serum triglyceride concentrations. The implication of these findings are discussed.

Adolescent↗
PubMed1981

The effects of vitamin A toxicity on calcium and lipid metabolism in chronic renal failure.

Serum vitamin A levels were high in haemodialysis patients, and were found to correlate with plasma calcium, triglyceride, cholesterol and insulin levels. Vitamin A containing multivitamin supplements were found to contribute to increased serum vitamin A levels, and their withdrawal in seven patients caused a significant decrease in serum vitamin A and calcium levels, with no effect on lipid levels. Vitamin A containing preparations should therefore be prescribed with caution in these patients.

Adult↗