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Biomedical subjects

R M Higgins

Publications and source records attributed to R M Higgins.

At least 55 records · Page 3Linked to original sources

Isolated HLA-DP mismatches between donors and recipients do not influence the function or outcome of renal transplants.

The matching of donors and renal graft recipients for human leukocyte antigens A, B, and DR has been shown to exert beneficial effects on the outcome of transplantation. Until the advent of polymerase chain reaction amplification-based genotyping, the effect of HLA-DP compatibility on graft survival could not be thoroughly investigated. HLA-DP compatibility has been determined in three living-related transplants and 34 cadaveric transplants for donor-recipient pairs matched for HLA-DR and -DQ. The effect of DP mismatching on graft survival and function was assessed. No clear benefit from matching donor and recipient for HLA-DP could be discerned.

Base Sequence↗

Total parathyroidectomy alone or with autograft for renal hyperparathyroidism?

Seventy-six patients underwent parathyroidectomy for renal hyperparathyroidism. There were 10 subtotal parathyroidectomies, 49 total parathyroidectomies with implantation of part of one gland as an autograft, nine total parathyroidectomies with no autograft, and eight patients in whom only three parathyroid glands were found. In 34 dialysis patients who underwent total parathyroidectomy with an autograft there was a high rate of recurrent hyperparathyroidism after 6 years in those remaining on dialysis. Fifty per cent had asymptomatic recurrent hyperparathyroidism and 30 per cent required partial autograft excision for symptomatic hyperparathyroidism. In contrast, recurrent hyperparathyroidism was rare in renal transplant recipients with good renal function. This favourable outcome did not depend upon whether parathyroid surgery was performed before or after transplantation, or on the type of parathyroidectomy. Total parathyroidectomy without an autograft was performed in nine dialysis patients without any short-term adverse effects, and with clinical and pathological improvement in bone disease. In summary, the results of surgery for renal hyperparathyroidism were excellent in patients who received a successful renal transplant. However, there was a high incidence of recurrent hyperparathyroidism in patients who remained on long-term dialysis. Total parathyroidectomy without an autograft may be the treatment of choice in patients unlikely to receive a renal transplant.

Adult↗

Mycobacterial infections after renal transplantation.

Mycobacterial infections occurred in 11 of 633 (1.7 per cent) recipients of successful renal transplants. There were no cases of tuberculosis in patients receiving chemoprophylaxis, but amongst those who did not receive prophylaxis disease occurred in six of the 27 (22 per cent) high-risk patients. The major cause of morbidity during treatment was renal allograft rejection, largely due to reduction in immunosuppressive drug therapy.

Adult↗

Spontaneous rupture of renal allografts: the importance of renal vein thrombosis in the cyclosporin era.

Spontaneous renal allograft rupture occurring within 14 days of transplantation occurred in 15 patients from 791 consecutive transplants. In each of eight patients treated with azathioprine and prednisolone there was pathological evidence of rejection and only two patients had thrombosis of the renal vein. Of the seven cases occurring in patients treated with triple therapy regimen (low dose cyclosporin, prednisolone and azathioprine), histological evidence of rejection was present in only three cases, but renal vein thrombosis was found in all seven. Spontaneous rupture of a transplanted kidney, a relatively uncommon complication, is more likely to be due to renal vein thrombosis than to rejection in the cyclosporin era.

Adult↗

Triple therapy immunosuppression in cadaveric renal transplantation.

One hundred and ninety-two patients received 200 consecutive cadaver renal transplants (158 first and 42 regrafts) and were treated with triple therapy immunosuppression consisting of low-dose cyclosporin, azathioprine and prednisolone. One-year patient and graft survival rates were 95% and 82%, respectively. Against this low rate of graft loss, the proportion of rejection-free patients in the first 3 months was strongly related to matching for HLA-DR (P less than 0.01), although HLA-DR matching was not associated with improved graft survival. More grafts were lost to nonimmunological causes than to rejection, and these losses fell into three main categories, namely, losses in elderly and diabetic patients and losses due to renal vascular thrombosis. Thus, triple therapy immunosuppression appears to offer effective immunosuppression, resulting in good graft and patient survival, especially in highly sensitised patients or patients receiving regrafts. There are relatively few serious adverse effects, although elderly and diabetic patients experienced significant morbidity and mortality after transplantation.

Adult↗

Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy.

Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms.

Azathioprine↗

Skin cancer in renal transplant recipients.

Skin cancer was found in 31 of 598 patients transplanted in Oxford. No cases occurred during the first 3 years after transplantation but the prevalence rose after 12 years to 18.2 per cent. The main risk factors predisposing to skin cancer were the time after transplantation and male sex. Comparison with data from other centres suggests that exposure to ultraviolet light is a major aetiological factor in the speed of development of skin cancer. As the incidence of new cases rose progressively with time in our patients, it would seem that skin cancer is likely to become a major clinical problem as more patients enjoy prolonged survival after renal transplantation. Preventative and screening measures should be taken by transplant units both in the UK and in other countries with similar temperate climates.

Adolescent↗

Antithymocyte globulin for steroid resistant rejection in renal transplant recipients immunosuppressed with triple therapy.

Steroid resistant rejection, confirmed histologically, occurred in 35 of 187 consecutive cadaveric renal transplants treated with triple therapy (cyclosporin, azathioprine and prednisolone) in the Oxford Transplant Unit. Twenty-seven of these were treated with a rabbit antithymocyte globulin (ATG) and 19 showed recovery of function. The level of serum creatinine, the renal biopsy appearance and the requirement for dialysis at the start of ATG treatment did not predict which patients would respond to the therapy. One year after transplantation there was no significant difference between the mean plasma creatinine levels of those patients with steroid resistant rejection who had been given ATG and responded (151.6 mumol/l) and those who had responded to steroids alone (165.0 mumol/l). Adverse effects of ATG treatment included a mean fall in white cell count of 62.2% and a mean fall in platelet count of 45.1%. Two of the 27 patients who received ATG died (7.4% mortality). ATG would appear to be an effective treatment of steroid resistant rejection in patients receiving triple therapy immunosuppression, and graft function may subsequently be excellent in those patients who respond to treatment.

Adult↗

HLA-DQ mismatches between donor and recipient in the presence of HLA-DR compatibility do not influence the function or outcome of renal transplants.

Although matching of kidney donors and recipients for antigens of the HLA-DR series is considered to have a significant influence on graft outcome, the independent effects of incompatibilities for the closely linked HLA-DQ series of antigens are unknown largely because serological compatibility for HLA-DR usually ensures a corresponding compatibility for HLA-DQ. In a retrospective study using restriction fragment analysis we have identified clear HLA-DQ mismatches in 25 out of 62 recipients of HLA-DR-compatible kidney grafts. Though these incompatibilities correspond to differences at the cell surface and hence potential alloantigenic stimuli, none of the eight clinical parameters examined indicate that HLA-DQ mismatches in the presence of compatibility for HLA-DR have any significant effect on either graft function or outcome.

Adolescent↗

Infections in a renal unit.

Five hundred and thirty-three patients in the Oxford renal unit were reviewed to determine the incidence of infection in one calendar year. There were 310 patients who received dialysis, 53 with acute renal failure and 211 with chronic renal disease. Renal transplant patients were not included in the study. Apart from infections related to dialysis access, patients on maintenance haemodialysis or continuous ambulatory peritoneal dialysis developed few serious infections unless they had another disease causing suppression of immune function. A total of 97 urinary tract infections were seen; in patients with chronic renal disease not receiving dialysis the incidence of urinary tract infection was significantly associated with increasing uraemia, with diabetes, and with treatment with azathioprine or cyclophosphamide. In patients with acute renal failure, Gram-negative septicaemia and fungal infections were important causes of morbidity and mortality, but cardiovascular disease caused 42 per cent of the deaths unlike results from other series where sepsis has been by far the commonest cause of death.

Acute Kidney Injury↗

Empyema and mesangiocapillary glomerulonephritis with nephrotic syndrome.

Two cases of empyema with nephrotic syndrome are described, a previously unreported association. In one case the nephrotic syndrome resolved with treatment of the empyema. Renal biopsy in both patients showed mesangiocapillary glomerulonephritis and in one case there was evidence of activation of the alternative complement pathway, which is often associated with this histological type of glomerulonephritis. The association between glomerulonephritis and empyema is important because it represents a potentially reversible form of renal disease.

Adult↗

Should ipratropium bromide be added to beta-agonists in treatment of acute severe asthma?

In a double-blind randomized trial, 40 patients with acute severe asthma were given either nebulized salbutamol, 5 mg, or salbutamol, 5 mg mixed with ipratropium bromide 500 micrograms, on admission to hospital and again two hours later. There was no significant difference between the mean peak flows of the two treatment groups at any time. However, two hours after each treatment, there were fewer subjects in the ipratropium and salbutamol group whose peak flow rates had fallen back toward baseline levels than in the salbutamol only treatment group. Thus, although ipratropium did not improve the overall maximal bronchodilator response, it may have prolonged the duration of the response, which would be a clinically useful effect.

Acute Disease↗