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Biomedical subjects

J F Moorhead

Publications and source records attributed to J F Moorhead.

At least 73 records · Page 4Linked to original sources
PubMed1989

An in vitro model of nephrocalcinosis using rabbit inner medullary collecting tubular cell culture.

In order to investigate the pathogenesis of medullary nephrocalcinosis, rabbit inner medullary collecting duct cells were grown in media containing different Ca++, PTH and pH levels. It was found that high Ca++ (7.8mM) only reduced growth slightly and that crystalline deposits were found under the cells. This suggests that high Ca++ is not severely toxic to the cells but can lead to deposition of calcium beneath the basement membrane. PTH did not effect cell growth even in the presence of high Ca++ implying that it has an indirect effect on tubular cells in medullary nephrocalcinosis associated with hyperparathyroidism. In renal tubular acidosis these cells are subjected to a persistently high urinary pH and low interstitial pH. Raising the pH reduced the cell growth in normal Ca++ medium whereas lowering the pH increased cell growth in vitro. Our results show that nephrocalcinosis is not due to the direct effect of raised pericellular Ca++ or PTH alone and that persistently alkaline tubular fluid may play a role.

Animals↗
PubMed1989

Logistic regression model for the assessment of microalbuminuria and microproteinuria in insulin-dependent diabetic patients at risk.

Diabetic microalbuminuria, which predisposes to the irreversible macroproteinuria and terminal renal failure, has been shown to be reversible by stringent metabolic control. In this study, using logistic regression, 23 patients with insulin-dependent diabetes mellitus were evaluated. Basing on the reported biochemical changes in patients with diabetes mellitus, the relationship between microalbuminuria and serum biochemistries was assessed. Four biochemical parameters were shown to be significantly related to the amount of microalbuminuria and microproteinuria. The microalbuminuria as assayed by rocket immunoelectrophoresis is closely correlated with the microproteinuria as measured by the Coomassie dye binding method and both have a significant relationship with plasma creatinine, bicarbonate, albumin and globulin as assessed by the Minitab computer program and the Biomedical Data Package--Logistic Regression computer program. The relationship with bicarbonate and creatinine can be due to a decrease in glomerular filtration rate associated with more advanced microproteinuria. The relationship with albumin and globulin is the result of impaired albumin synthesis by the liver in diabetes mellitus. From these data, two simple equations which can provide a relative risk factor with rough quantitative assessment for microproteinuria and microalbuminuria are derived. Thus, from these four parameters available from relatively simple blood biochemistries, assessment can be made of the severity of coexisting diabetic proteinuria. The measurement of the latter is not readily available and is more costly and tedious. This assessment together with the finding of a decrease in albumin, slight increase in creatinine and decrease in bicarbonate associated with the more severe microalbuminuria can be used to alert the diabetologist in implementing tighter metabolic control and other interventional methods before irreversible macroproteinuria develops.

Adult↗
PubMed1989

Low-dose vs high-dose intravenous methylprednisolone therapy for acute renal allograft rejection in patients receiving cyclosporin therapy.

Three mg/kg bodyweight per day of intravenous methylprednisolone for 3 consecutive days is as effective as 15 mg/kg bodyweight per day of methylprednisolone in reversing acute renal allograft rejection (80% vs 68%; 95% confidence intervals of the difference are -8% to 32%). This dose was not associated with an increased incidence of further rejection episodes. It may not be necessary to continue with the common practice of administering high-dose intravenous methylprednisolone for acute renal graft rejection.

Clinical Trials as Topic↗
PubMed1989

In vitro cyclosporine toxicity. The effect of verapamil.

The epithelial cell line LLC-PK1, which expresses many proximal tubular characteristics, was used to investigate the relationship between calcium, the calcium channel blocker verapamil, and cyclosporine toxicity. The LLC-PK1 cells took up cyclosporine when this was added in a concentration of 2 micrograms/ml, and this uptake was maximal at 30 min (112 +/- 3 ng cyclosporine/mg cell protein). At 12 micrograms/ml it inhibited the sodium glucose cotransporter, as assessed by phlorizin-inhibitable 14C-alpha-methyl glucopyranoside (alpha-MG) uptake (control 37.2 +/- 6.3, 12 micrograms/ml 21.2 +/- 1.1 mumol/hr/mg protein). Cyclosporine at 2 micrograms/ml did not affect cell growth after 5 days (control 945 +/- 60 micrograms cell protein per 25 cm2 flask, 2 micrograms/ml cyclosporine/ml 1046 +/- 32 micrograms protein/flask), even in the presence of 7.6 mM ionized calcium (862 +/- 37 micrograms protein/flask). Cyclosporine at 12 micrograms/ml inhibited cell growth (286 +/- 27 micrograms protein/flask), and raising the ambient ionized calcium concentration to 7.6 mM reduced cell growth further (91 +/- 6 micrograms protein/flask). Cyclosporine at concentrations of 2 and 12 micrograms/ml produced increasing cell vacuolation, as seen in vivo. Short-term uptake of 2 micrograms/ml cyclosporine could be inhibited by 1.0 mM and 0.5 mM verapamil (49 +/- 9.5 and 71 +/- 6.4 ng cyclosporine/mg cell protein, respectively, at 30 min). However, in the presence of 2 micrograms/ml cyclosporine 0.1 mM verapamil was toxic to the cells grown over five days (44 +/- 5 micrograms protein/flask). At 0.01 mM verapamil was not toxic to cell growth (921 +/- 29 micrograms protein/flask), but raising the medium calcium to 7.6 mM reduced cell growth (652 +/- 96 micrograms/ml). Inhibition of cyclosporine uptake did not occur with 0.01 mm verapamil (control 145.6 +/- 12.3 vs. 0.01 mM verapamil 150.4 +/- 3.8 ng cyclosporine/mg cell protein). The LLC-PK1 cell line represents a good in vitro model for cyclosporine renal tubular toxicity, as the in vivo observation of glycosuria and proximal tubular cell vacuolation in cyclosporine nephrotoxicity can be reproduced. In vitro this is shown to be associated with inhibition of sodium-dependent glucose cotransport. Verapamil inhibited cyclosporine uptake, but only at concentrations that were toxic to the cells. Verapamil potentiated rather than reduced the increased cyclosporine toxicity produced by increasing the medium calcium concentration. The suggested protective effect of verapamil against cyclosporine nephrotoxicity is therefore unlikely to be due to inhibition of cyclosporine uptake or of calcium entry into proximal tubular cells.

Calcium Channels↗
PubMed1989

Glomerular structures and lipids in progressive renal disease.

In the last few years, remarkable advances have been made in the understanding of lipoprotein metabolism in the pathogenesis of renal disease in animal models and in vitro cell culture. Central to this work is the problem of the progression of renal disease in humans. This review recapitulates the theory (Lancet 1982; II: 1309-1312) that the progression of disease depends in part on the damage inflicted on the glomerulus by lipoproteins. The glomerular environment of high or low pressure, basement membrane damage, and destruction or damage of the mesangial and epithelial cells permits the filtration of protein, the consequence of which is hyperlipidemia. Whatever the therapeutic measures employed, if proteinuria persists, hyperlipidemia will follow. This suggest that lipoprotein toxicity may contribute to the final common path of renal damage in progressive renal disease. "Lipoprotein toxicity" in arteries is called atherosclerosis, but this term ignores the complexity of the glomerulus and the possible tubular damage that might be caused by filtered lipoprotein. It is clear there is insufficient knowledge of the metabolism of the damaged kidney to confidently attribute the pathology of progression of disease to any single process.

Animals↗
PubMed1989

Dietary fish oil supplements preserve renal function in renal transplant recipients with chronic vascular rejection.

The effect of dietary fish oil supplements on renal failure and lipid abnormalities was studied in 14 adult renal transplant recipients with chronic vascular rejection. The rate of decline of renal function (assessed by studying the slope of reciprocal plasma creatinine plots) slowed significantly during a 6-month period on fish oil supplements compared with the preceding 6-month control period (slope 1/cr during supplementation -3.6 X 10(-5) mumols/l per month compared with -13.5 X 10(-5) before, the difference in slope being -9.8 X 10(-5), 95% confidence interval (CI) -16.2 X 10(-5), -3.5 X 10(-5), P less than 0.05). Total plasma triglyceride concentrations decreased during supplementation (mean change -1.15 mmol/l, 95% CI -1.84, -0.47, P less than 0.003), but there was no change in total plasma cholesterol concentration or urinary protein excretion. Platelet function was studied in nine patients. Platelet aggregation induced by adrenaline and collagen was reduced by fish oils (median change in per cent aggregation), adrenaline 2 mumols/l, -36% (95% CI -68%, -8%, P less than 0.05), collagen 1 mg/1, -13% (95% CI -44%, -2%, P less than 0.05). Platelet thromboxane A2 release in response to these agents was also significantly reduced. These results demonstrate that fish oils preserve residual function in renal graft failure due to chronic vascular rejection.

Adult↗
PubMed1989

Atherosclerotic renovascular disease causing renal impairment--a case for treatment.

Renovascular disease is a potentially curable cause of renal failure. In a prospective survey over an eighteen month period atherosclerotic renal artery disease was the cause of renal failure in 14% of patients over the age of fifty years accepted for renal replacement therapy at this hospital. Ten patients were found to be suffering from atherosclerotic renovascular disease causing renal failure but in only one was treatment able to reverse renal failure. The major problem with this group of patients is the widespread nature of their disease affecting many other organs. Significant morbidity is associated with their investigation. Although potentially curable, atherosclerotic renovascular disease is a frequent cause of renal failure in patients over the age of fifty years but is also difficult to treat.

Aged↗
PubMed1989

Prognosis of critically-ill patients with acute renal failure: APACHE II score and other predictive factors.

The survival from acute renal failure requiring renal replacement therapy was studied in 90 critically-ill patients admitted to an intensive care unit. Mean age (+/- SD) was 51 +/- 14.6 (range 17 to 81) years. Mechanical ventilation was required in 88 patients and 71 patients received total parenteral nutrition. Thirty-three per cent of patients left the intensive care unit alive and 24 per cent survived to leave hospital. Final survival was 20 per cent in medical patients (n = 49), 29 per cent in surgical patients (n = 38) and 100 per cent in obstetric patients (n = 3). Hypotension, requirement for inotropic support, oliguria and sepsis were all associated with a poorer prognosis. The mode of renal replacement therapy did not affect survival, but additional haemodialysis was required in 33 of 65 patients treated by continuous arteriovenous haemofiltration but none of 22 treated with continuous arteriovenous haemodialysis (p less than 0.001). APACHE II score was calculated for 87 patients. Mean APACHE II score was 26.1 +/- 6.9 (range 14 to 44). APACHE II score on admission predicted the likelihood of survival well. No patients with a score of more than 40 survived, compared to 40 per cent of those with scores of 10 to 19. Pre-existing organ insufficiency or immunosuppression meriting a CHE score of 5 was associated with a very poor survival (1 of 30 patients). APACHE II score is a reliable indicator of severity of illness and likelihood of survival in critically-ill patients with acute renal failure. The widespread adoption of APACHE II scoring for patients with acute renal failure requiring intensive care would facilitate medical audit and comparison of studies from various centres.

Acute Kidney Injury↗
PubMed1989

Apolipoprotein B turnover in dialysis patients: its relationship to pathogenesis of hyperlipidemia.

Exogenously labelled Iodine-125-VLDL (very low density lipoprotein) was given intravenously to twelve dialysis patients and four normal controls. Specific activities of I-125-VLDL apoB (apolipoprotein B) and I-125-IDLapoB (intermediate density lipoprotein apolipoprotein B) were measured for forty-eight hours. Synthesis rates (flux) and fractional catabolic rates (FCRs) of VLDLapoB and IDLapoB for hyperlipidemic (n = 8), normolipidemic (n = 4) dialysis patients and controls (n = 4) were calculated. Dialysis patients had lower VLDLapoB FCRs than controls (p less than 0.05); hyperlipidemic dialysis patients had marginally raised VLDLapoB flux over normolipidemics (p = 0.0508), suggesting apoB production might play a greater role in the pathogenesis of hyperlipidemia. Hyperlipidemics had lower IDLapoB FCRs than controls (p = 0.01). IDLapoB flux was similar in all three groups. The discrepancy in VLDLapoB fluxes between hyperlipidemics and normolipidemics with similar IDLapoB fluxes suggested that VLDLapoB could be directly catabolized in hyperlipidemics. ApoB concentration was increased in VLDL, IDL of hyperlipidemics when compared with normolipidemics (p less than 0.05) and controls (p = 0.01). Hyperlipidemic VLDL plasma levels were relatively enriched with cholesterol when compared with controls, p less than 0.01, and normolipidemics, p less than 0.05. These factors might all contribute towards accelerated atherogenesis in hyperlipidemic dialysis patients.

Adult↗
PubMed1988

ACE inhibitors.

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Effects of diets with high carbohydrate content on diabetic hyperlipidaemia and microalbuminuria.

Recent dietary recommendations for patients with diabetes mellitus have focussed on the liberalisation of carbohydrate intake to at least 50% of total calories. However, there are reports that this diet may cause adverse metabolic effects as a result of high intake of carbohydrate. Whether this high-carbohydrate diet will exacerbate hypertriglyceridaemia, which increases the risk of atherosclerosis, and diabetic microalbuminuria, which predisposes to progressive renal failure, is unknown. The dietary intake of 28 patients with insulin-dependent diabetes mellitus was assessed by diet histories with both questionnaire surveys and 3-day recall methods. The dietary contents of different constituents were graded according to the type and amount of food typically eaten, and the frequency of their consumption in the past 6 months. Twelve patients were found to have a high dietary intake of carbohydrate and this was confirmed by detailed assessment of food intake records over a 3-day period. The carbohydrate intake of these 12 patients amounted to at least 55% of total calories. Total calorie intake, body weight, mean blood pressure, glycaemic control, and glomerular filtration rate were similar between the 12 patients with high intake of carbohydrate and the other 16 patients with low intake. Urinary protein and albumin appearance as measured by dye binding and immunoassay, fasting cholesterol, triglyceride and high-density lipoprotein cholesterol were also comparable between the two groups. This study provides evidence that a high-carbohydrate diet in the treatment of diabetes mellitus is not associated with significant alterations in the amount of microalbuminuria or in hypertriglyceridaemia.

Adult↗