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Biomedical subjects

J F Moorhead

Publications and source records attributed to J F Moorhead.

At least 91 records · Page 5Linked to original sources

Captopril-enhanced 99mTc DTPA scintigraphy in the detection of renal-artery stenosis.

The value of captopril-enhanced 99mTc DTPA scintigraphy as a screening test for renovascular disease was prospectively studied in 44 hypertensive patients suspected to have renal-artery stenosis. Renal impairment (plasma creatinine greater than 130 mumol/l) was present in 29 patients. At angiography 13 patients had unilateral stenosis, two bilateral stenosis, and 29 patients had no renovascular disease. Captopril induced a fall in split renal function in the kidney ipsilateral to the stenosis in all patients with unilateral disease (mean 52 +/- 23% to 44 +/- 21% of total renal function; P less than 0.001). A positive captopril scintigram (defined as a fall of 5% or more in split renal function) had a sensitivity of 85% and a specificity of 72% in the detection of unilateral renal-artery stenosis. Captopril-enhanced 99mTc DTPA scintigraphy is a promising non-invasive screening test for the detection of renal-artery stenosis.

Adult↗

Controlled trial of azathioprine and cyclosporin to prevent anti-HLA antibodies due to third-party transfusion.

The beneficial effect of elective transfusion on renal allograft survival must be weighed against the risks of sensitisation. We report a randomised controlled trial in which patients in end-stage renal failure who were non-parous and not previously transplanted or transfused, were entered in a transfusion protocol during which one group received no drugs (controls), one received azathioprine, and one received cyclosporin. Each group was given three identical transfusions of leucocyte-enriched fresh blood at 2-3 week intervals. The transfused blood was of known HLA type and donor/recipient pairs were completely mismatched. Sensitisation rates were assessed by T and B cell cross-matches between donor and recipients and by the screening of all sera against lymphocytes from 40 random donors. Fifty-one patients have completed the protocol, 20 in the control group, 12 in the azathioprine group, and 19 in the cyclosporin group. The sensitisation rate in the control group was 30%, occasionally of high titre, and persistent. In the azathioprine group, 25% developed anti-HLA antibodies and reactivity was of high titre and was broadly specific. Sensitisation in the cyclosporin group was 10%, was narrowly specific, reacting with only 10% of a panel, and was transient. There was no difference in graft survival between the groups. We conclude that cyclosporin therapy concurrent with third-party transfusion reduces the incidence, titre, and duration of sensitisation.

Antibody Formation↗

Cyclosporin in the treatment of steroid-responsive and steroid-resistant nephrotic syndrome in adults.

The effect of cyclosporin on proteinuria was studied in 11 patients with steroid-responsive nephrotic syndrome (10 minimal change nephropathy, one IgM nephropathy) and in four patients with steroid-resistant nephrotic syndrome from focal segmental glomerulosclerosis. Cyclosporin (mean initial dose 7.7 mg/kg per day) produced a complete remission of proteinuria in 15 nephrotic episodes in the ten patients with minimal-change nephropathy after a mean 14.3 days (range 7-23 days) of therapy. All patients remained in remission while receiving cyclosporin (mean duration of follow-up 147 days; range 40-230 days). However, when cyclosporin was discontinued on nine occasions in five patients, all relapsed after a mean 47.8 days (range 7-180 days). Four of the five patients were subsequently rechallenged with cyclosporin and all responded. Maintenance cyclosporin therapy to prevent relapse was not associated with any adverse effects, and there was no significant difference between the creatinine clearance before and after 30 days of therapy (86.9 +/- 19.3 and 81.7 +/- 23.5 ml/min respectively, P greater than 0.1). The patient with steroid-responsive IgM nephrotic syndrome did not respond to cyclosporin, and there was no significant effect of cyclosporin on proteinuria in the four patients with FSGS. Cyclosporin is an effective agent for the treatment of patients with frequently relapsing minimal-change nephropathy who became steroid dependent when cyclophosphamide is contraindicated. However, unlike cyclophosphamide, long-term remissions which persist after treatment is withdrawn are not obtained, and patients may be said to be cyclosporin dependent.

Adolescent↗

Cyclosporine A enhances platelet aggregation.

In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

Adult↗

Reduction of serum prolactin after salmon calcitonin infusion in patients with impaired renal function.

The physiological role of calcitonin is still uncertain. Recently human calcitonin gene-related peptide, produced by alternative RNA processing from the calcitonin gene, was shown to have structural homology to salmon calcitonin and probably have a modulator function in the hypothalamus. In this study, salmon calcitonin was infused at a low dose (10 MRC units over 30 min) in seven patients with impaired renal function (51-Cr-EDTA clearance = 34.8 +/- 4.8 ml/min) in order to elucidate its effects on PRL secretion. The results show that salmon calcitonin at a subhypocalcaemic dose significantly suppresses PRL secretion by over 40% (P less than 0.01) and may be of therapeutic use in the treatment of gonadal dysfunction in chronic renal failure.

Adult↗

Successful renal transplantation with cadaveric donor kidneys of extremely prolonged cold ischaemic time.

At 3, 6 and 12 months, there was no difference in renal function and survival between a group of renal transplant recipients who received cadaveric donor kidneys of extremely prolonged cold ischaemic time (group median 60 h; range 35-82 h), compared to a group who received cadaveric donor kidneys of shorter cold ischaemic time (group median 20 h; range 6-44 h). The prolonged cold ischaemic time group had a higher incidence of primary non-function, but the duration of primary non-function was not different between the two groups. The prolonged cold ischaemic time group had significantly fewer episodes of rejection. Despite the increased incidence of primary non-function, this study shows that it is safe to use low-dose cyclosporin A in kidney grafts with an extremely prolonged cold ischaemic time.

Adolescent↗

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↗

Cefuroxime pharmacokinetics in continuous and intermittent peritoneal dialysis.

Pharmacokinetics of cefuroxime was studied in patients on continuous ambulatory or intermittent peritoneal dialysis. A single intravenous bolus (15 mg/kg) of cefuroxime provided a mean serum concentration of 86 mg/litre 5 min, 40 mg/litre 1 h, 163 mg/litre 24 h after the injection. The peritoneal clearance of cefuroxime varied widely among different individuals, ranging from 1.45 to 6.17 ml/min with a mean of 3.59 ml/min during 4-hour exchanges, and from 0,52 to 11.3 ml/min during 2-hour exchanges. A single injection (15 mg/kg) of the antibiotic could not provide satisfactory antibiotic concentrations in peritoneal effluent during peritoneal lavage. When cefuroxime had been added to peritoneal dialysis solution before the solution was instilled into the peritoneal cavity, a significant decrease in cefuroxime concentration occurred in the peritoneal effluent even after a short equilibration time. Furthermore, cefuroxime concentrations measured in residual dialysis solutions in the plastic bags ranged from 44.3 to 1,351% of the concentration of cefuroxime calculated from the added doses, indicating that despite great care, mixing of the antibiotic with dialysis solutions in plastic bags was far from uniform.

Adult↗

Selective effect of low protein diets in chronic renal diseases.

It has recently been established that the rate of progression of chronic renal failure in man can be slowed by restricting dietary protein. Consequently, the short term and long term effects of a low protein diet on the course of different chronic nephropathies were studied in an attempt to delineate the factors that determine the response to such a diet. When a low protein diet was given for six months renal function improved significantly in nine patients with chronic tubulointerstitial nephritis (p less than 0.025); the diet had a marginally beneficial effect in 12 patients with chronic glomerulonephritis (p less than 0.05) and no effect in nine with hypertensive nephrosclerosis. The heterogeneous functional response in the patients with chronic glomerulonephritis correlated closely with the effect of the diet on these patients' proteinuria (r = 0.76, p less than 0.01). In a short term study (four weeks) of 12 patients with chronic renal failure changes in renal plasma flow were proportional to dietary protein intake. Renal vascular resistance fell during a high protein diet and increased when dietary protein was restricted. The changes in renal plasma flow during the low protein diet correlated well with the patients' long term functional response to the diet (r = 0.76, p less than 0.01). It is concluded that the response to a low protein diet in chronic renal failure is determined, firstly, by the nature of the underlying nephropathy, with maximal benefit being observed in non-glomerular disorders; secondly, by the effect of the diet on the proteinuria in chronic glomerulonephritis; and, thirdly, by the haemodynamic response to the diet, with patients with a reactive renal vascular bed improving with a low protein diet.

Adolescent↗