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Biomedical subjects

Z Varghese

Publications and source records attributed to Z Varghese.

At least 73 records · Page 4Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

Detection of cytomegalovirus by ELISA in urine samples is inhibited by beta 2 microglobulin.

During development of an enzyme immunoassay for the detection of cytomegalovirus (CMV) we previously discovered that virus found naturally in urine specimens could not be captured onto the solid phase by CMV-specific monoclonal antibodies, whereas these same antibodies could capture CMV from cell culture supernatants. We now report that urine from normal CMV-seronegative individuals contains a substance of molecular weight 11-12,000 daltons that inhibits the ELISA detection of cell culture-grown CMV. The addition of a known urinary protein of this molecular weight, beta 2 microglobulin (beta 2m; 11,700 daltons), inhibited the detection of cell culture-grown CMV in the ELISA over the concentration range found in clinical urine samples. In contrast, another low molecular weight urinary protein, lysozyme, had no inhibitory effect. beta 2m caused inhibition only when added to the virus preparation and not to the antibody-capture stage. We conclude that beta 2m in urine prevents the detection of CMV by ELISA by binding to the virus and masking its antigenic determinants and we calculate that of the order of 10(5) molecules of beta 2m bind to each particle of cell culture-grown CMV. We postulate that CMV in fresh urine specimens is similarly coated with beta 2m, accounting for the failure to detect it by ELISA.

Antigens, Viral↗
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

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↗