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Biomedical subjects

J Walls

Publications and source records attributed to J Walls.

At least 181 records · Page 10Linked to original sources

Measurement of renal functional reserve of the single kidney in man.

The renal functional reserve capacity (RFRC) and response of the single kidney to a low protein diet (LPD) were investigated. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured using a single injection of I125 Hippuran and Cr51 EDTA during a dopamine infusion (3 micrograms/kg/min) and after 2 weeks on a LPD (0.6 g/kg/day). Dopamine increased ERPF but the associated rise in GFR was not significant. There was a significant decrease in both ERPF and GFR on LPD. The change in GFR during dopamine infusion, but not during LPD, correlated inversely with baseline GFR. Dopamine and LPD had no effect on heart rate or blood pressure and LPD did not alter urinary sodium excretion. These results suggest that the single kidney lacks functional reserve capacity and that protein restriction may be useful in preserving long term function.

Adult↗

Is chronic renal transplant rejection a non-immunological phenomenon?

Five patients with chronic renal transplant rejection were subjected to dietary protein restriction (0.6 g/kg ideal body weight daily) with no change in immunosuppressive therapy. In all five patients the slope of the curve of reciprocal serum creatinine and time decreased (mean -46.0 +/- 11.8 before diet fell to -11.7 +/- 9.4; p less than 0.01). These findings support the hypothesis that non-immune mechanisms are dominant is chronic renal transplant failure.

Chronic Disease↗

Alterations in lipid and carbohydrate metabolism attributable to cyclosporin A in renal transplant recipients.

Thirteen non-diabetic renal transplant recipients had various aspects of carbohydrate and lipid metabolism studied before and after conversion from cyclosporin A to azathioprine. No patient had a glucose tolerance test result diagnostic of diabetes mellitus before conversion, and there was no change in fasting glucose or immunoreactive insulin values after conversion. There was, however, a fall in the area under the curve of the glucose tolerance test values after conversion. Furthermore, fasting serum cholesterol and triglyceride concentrations fell significantly after conversion. No change in the concentration of high density lipoprotein cholesterol was detected. These findings suggest that cyclosporin A is associated with an inferior lipid profile as compared with azathioprine, which may be important in patients with transplants given the drug long term.

Adult↗

Activation of the adenovirus and BK virus late promoters: effects of the BK virus enhancer and trans-acting viral early proteins.

We have examined the activation of the adenovirus major late promoter (MLP) by the cis-acting enhancer element of the human polyomavirus BK and by the trans-acting simian virus 40 (SV40) T antigen and adenovirus E1A proteins. By using chloramphenicol acetyltransferase expression vectors, we found that the MLP (pLP-CAT) was trans-activated in human and monkey kidney cells expressing the SV40 T antigen. In addition, the MLP could be cis-activated by the BK virus enhancer in both human and monkey kidney cells; approximately 20 times more chloramphenicol acetyltransferase was produced from expression vectors containing a hybrid promoter (BL), in which the BK enhancer was upstream of the MLP, than from expression vectors containing the MLP alone. This same level of enhancement of the MLP by the BK enhancer was observed in cells expressing the T antigen of SV40. However, in the 293 cell line, greater enhancement of MLP activity (70-fold) was observed with the BK enhancer sequence. In contrast, MLP activity in the 293 cell line was unchanged by the SV40 enhancer. In cotransfection experiments, MLP activity, augmented by the BK enhancer, could be further stimulated with a plasmid coding for the E1A gene products. By creating deletion mutants, we determined that the high-level activation of the hybrid BL transcriptional unit by the E1A proteins requires both MLP sequences and an intact BK virus enhancer. On the other hand, activation of the BL transcriptional unit by the T antigen did not require an intact enhancer sequence. Our results suggest that the SV40 T antigen and E1A proteins trans-activate the BL promoter by different mechanisms. We also demonstrate in cotransfection experiments that the BK late promoter is activated 45-fold by the SV40 T antigen.

Adenovirus Early Proteins↗

Influence of atrioventricular synchrony on hemodynamics in patients with normal and low ejection fractions following open heart surgery.

The authors wished to test the hypothesis that atrioventricular synchrony has a relatively greater effect on hemodynamic parameters in postoperative patients with low ejection fractions compared to those with normal ejection fractions. Temporary pacing wires were placed on the right atrium and right ventricle of patients undergoing open heart surgery. Duplicate thermodilution cardiac outputs were determined during atrial pacing and ventricular pacing at 100 beats/min. Mean left atrial and systemic blood pressures were monitored. Thirteen patients with ejection fractions of 45 per cent or less (range 24 to 45%, mean 37.3%) were included in the low ejection fraction group, and 27 patients with ejection fractions of 59 per cent or greater (range 59 to 80%, mean 66.8%) were considered in the normal ejection fraction group. All hemodynamic parameters improved significantly when changing from ventricular pacing to atrial pacing in both the normal ejection fraction group and low ejection fraction group (P less than 0.05). The magnitude of change between the groups showed no significant difference for all parameters except left atrial pressure, which decreased by a greater percentage in the low ejection fraction group with atrial pacing (P less than 0.001). The atrial contribution to hemodynamic enhancement is important in patients with normal and low ejection fraction following open heart surgery. Patients with low ejection fractions do not sustain a relatively greater reduction in cardiac output, stroke volume index, or systemic blood pressure with loss of atrioventricular synchrony when compared to patients with normal ejection fractions.

Cardiac Output↗

High risk acute renal failure.

Acute renal failure carries a high mortality and little change in survival rate over the last three decades has been seen. Patients requiring intensive care, most of whom have developed acute renal failure following trauma or surgery, have a worse prognosis. The survival in this series of 100 consecutive patients admitted to one intensive care unit between 1976 and 1985 was 35 per cent. The only factors which differed significantly between the surviving and non-surviving patients were age, requirement for mechanical ventilation and maximum serum creatinine level before the first dialysis. It is difficult to predict outcome for an individual patient at the start of treatment and an aggressive approach to management is advocated.

Acute Kidney Injury↗

Vitamin A and bone formation. Effect of an excess of retinol on bone collagen synthesis in vitro.

The influence of an excess of retinol on bone formation was studied by using cultures of embryonic-chick calvaria. Retinol decreased collagen synthesis in a dose-dependent manner, non-collagenous protein synthesis being relatively unaffected. Collagen synthesis was significantly inhibited after 24 h of culture with retinol and was progressively decreased, compared with control cultures containing no retinol, as the period of culture was increased. The effect of retinol on collagen synthesis could be reversed by incubation of calvaria for further periods in retinol-free medium. Incorporation of [3H]thymidine and [3H]uridine into DNA and RNA respectively was not altered by culturing calvaria with retinol for 22 h. These latter findings, and the selectivity for collagen synthesis, all suggested that the effect observed was not a cell-toxicity phenomenon. The effect of retinol on collagen synthesis by chick calvarial osteoblasts was probably direct and not mediated by osteoclasts, since a negligible number of the latter cells is present in chick calvaria. In cultures of neonatal murine calvaria, which contain many osteoclasts, retinol similarly inhibited synthesis of collagen, but not of non-collagenous protein; the concentrations of retinol necessary to produce the response were similar to those required to stimulate bone resorption in vitro.

Animals↗

The effect of bezafibrate on hyperlipidaemia in experimental nephrotic syndrome in rats.

The effects of bezafibrate on hyperlipidaemia in experimental nephrotic syndrome in rats has been investigated. The treated group received bezafibrate 10 mg kg-1 p.o. daily. No significant differences in total serum cholesterol occurred, but a significant reduction in serum triglyceride (P less than 0.005) and elevation in HDL cholesterol (P less than 0.005) occurred. These findings may have implications for therapeutic intervention in severe hyperlipidaemia of the nephrotic syndrome in man.

Animals↗

High incidence of minimal change nephrotic syndrome in Asians.

Between 1973 and 1982 there was a significantly higher incidence of minimal change nephrotic syndrome among Asian compared with non-Asian children in Leicestershire. Most Asians in Leicestershire are Gujarati-speaking Hindus, but Sikhs and Muslims are also represented; no group of Asians (defined by religion, language, or birthplace) was at special risk of developing nephrotic syndrome. Nephrotic syndrome was more preponderant in Asian children living within the city of Leicester, and there was an unusually low incidence in non-Asian children within the city. Both racial and environmental factors may be important in the increased susceptibility to minimal change nephrotic syndrome in Asian children.

Adolescent↗

Metabolic effects of conversion from cyclosporine to azathioprine in renal transplant recipients.

The metabolic effects of conversion from cyclosporine (Cys) to azathioprine were studied in 10 non-diabetic renal transplant recipients. Following conversion there was a significant improvement in renal function. There was no evidence of glucose intolerance pre-conversion, and no change in glucose metabolism following conversion. However, fasting cholesterol and triglyceride levels were significantly improved following conversion. The mechanism of this change and its significance needs further investigation.

Adult↗

Alteration of the course of chronic renal failure by dietary protein restriction.

The role of dietary protein restriction in the progression of chronic renal failure has been investigated in 47 patients suffering with moderate and severe renal impairment. Prescription of a diet containing 0.6g/kg body weight protein resulted in 87 per cent of the patients exhibiting a diminution in the decline of renal function, as assessed by a reciprocal creatinine plot. Those patients with the most rapidly declining renal function showed the greatest response, but no correlation with initial renal function, age, sex or drug therapy could be found. No adverse nutritional effects, within the parameters examined, was found.

Adolescent↗