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Biomedical subjects

P Sweny

Publications and source records attributed to P Sweny.

At least 19 recordsLinked to original sources
PubMed1992

Double-blind, placebo-controlled trial of human lymphoblastoid interferon prophylaxis of cytomegalovirus infection in renal transplant recipients.

We have conducted a double-blind, placebo-controlled trial of human lymphoblastoid interferon prophylaxis of cytomegalovirus (CMV) infection in 74 renal transplant recipients. Interferon (3 x 10(6) units was given thrice weekly for the first 6 weeks, then twice weekly for a further 8 weeks. During the period of interferon therapy, the incidence of CMV excretion was lower in the interferon group (28% versus 50%, P = 0.065), mainly due to a significant reduction of CMV reactivation (9% versus 56%, P = 0.02). However, for the whole study period (including the follow-up period after interferon therapy), there was no difference in the incidence of CMV excretion (44% versus 53%). The onset of CMV excretion was delayed (8.2 +/- 0.8 to 20.9 +/- 5.5 weeks, P = 0.04). The duration of CMV excretion was also reduced (11.1 +/- 3.1 to 29.4 +/- 5.7 weeks, P = 0.008). The number of positive CMV isolates from urine and saliva was significantly less in the interferon group. There was no difference in the site of CMV excretion. Of the patients in the treatment group who excreted CMV, 43% developed disease as compared to 63% in the control group (difference not significant). There was also no significant difference in the severity of the CMV infection between the two groups. Benefit appears to be restricted to seropositive recipients of seronegative kidneys. The interferon regime used in this study was well tolerated, with mild fever being the only reported side-effect. No patient had to stop therapy because of toxicity. The incidence of rejection and graft loss was not different between the two groups.

Adult↗
PubMed1992

Screening for renovascular disease with captopril-enhanced renography.

Changes in renal function caused by angiotensin-converting-enzyme (ACE) inhibitors can be detected on 99mTc-DTPA renography so that DTPA scanning before and after a single dose of captopril can be used to screen for renovascular disease. We have performed captopril-DTPA scans with renal arteriography on 104 patients, of whom 27 had renal artery stenosis, all due to atheroma. Using a 5% fall in divided function or a delay of greater than 15 min in time to peak activity on one side after captopril, or the finding of greater than 90% divided function on one side before captopril as criteria for a positive scan, a sensitivity of 93% and specificity of 70% was achieved. The negative predictive value of the test in our population was 93%. Bilateral improvement in renographic function after captopril was seen in patients with accelerated phase hypertension. The presence of bilateral renal artery disease did not reduce the sensitivity of the test, but sensitivity was reduced (75%) in patients with renal impairment. Clinical characteristics in our patients most strongly associated with renal artery stenosis were abdominal bruit, recurrent left ventricular failure, and peripheral vascular disease. In view of the well-publicized risks of ACE inhibitor therapy, care should be exercised in the use of these agents in such patients.

Adult↗
PubMed1992

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

1. Perindopril, an orally active angiotensin converting enzyme inhibitor, was given to 23 hypertensive patients with stable chronic renal failure for 15 days. The dose of perindopril was 2 or 4 mg once a day according to the degree of renal failure. The creatinine clearance of the patients ranged from 6 to 67 ml min-1 1.73 m-2. The pharmacokinetics of perindopril and perindoprilat, its active metabolite, were studied after acute and chronic administration of perindopril. 2. The drug was well tolerated and creatinine clearance was unaltered by treatment. 3. In both groups, steady-state was reached within 3 days of chronic treatment. 4. After both acute and chronic drug administration renal impairment had no effect on perindopril pharmacokinetics but the pharmacokinetics of perindoprilat were altered significantly. After chronic administration the serum accumulation ratio was 1.81 in patients with mild renal failure and 5.35 in patients with severe renal failure. Chronic administration did not modify the renal clearance of perindoprilat nor its elimination half-life. 5. A significant correlation between the renal clearance of perindoprilat and creatinine clearance was observed (r = 0.87 first dose, r = 0.83 last chronic dose). 6. A non-linear relationship between serum perindoprilat concentration and inhibition of angiotensin converting enzyme was described by a modified Hill equation. Values of IC50 were 1.11 +/- 0.07 micrograms I-1 (mean +/- s.d.) in patients with severe renal failure and 1.81 +/- 0.20 micrograms l-1 in patients with moderate renal failure. Chronic administration increased maximal inhibition and decreased the time to maximal inhibition only in patients with severe renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Phenytoin-induced pseudolymphoma. A report of a case and review of the literature.

We report a patient with phenytoin-induced pseudolymphoma mimicking cutaneous T-cell lymphoma (CTCL). Despite withdrawal of phenytoin, there was persistence of the cutaneous eruption and lymphadenopathy. Southern blot analysis of immunoglobulin and T-cell receptor genes was therefore used to assess whether there was a clonal lymphoid expansion. However, no rearrangement of the beta T-cell receptor gene or immunoglobulin heavy-chain gene was detected in tissue DNA from skin and lymph nodes. One year later the patient became asymptomatic, although he is still at risk of developing a true malignant lymphoma in the future, a condition known as pseudo-pseudolymphoma. It is suggested that genotypic studies may help in the initial diagnosis and the subsequent management of such patients.

Adult↗
PubMed1991

Can urinary thyroid hormone loss cause hypothyroidism?

Four patients presented with nephrotic syndrome associated with hypothyroidism; none had thyroid antibodies. Hypothyroidism resolved on remission of nephrotic syndrome in two patients; thyroxine (T4) replacement was ineffective during periods of gross proteinuria in another, and the fourth had had normal thyroid function a year before presentation. Urinary T4 excretion was measured in ten further patients with proteinuria. It was detectable in the urine in five, who had significantly lower serum free T4 (8.5 [95% confidence interval 5.8-11.2] vs 13.9 [11.1-16.7] pmol/l; p less than 0.01) and free triiodothyronine (3.1 [2.2-4.0] vs 4.9 [3.8-6.0] pmol/l; p less than 0.01) concentrations than the five patients without detectable urinary T4.

Aged↗
PubMed1991

The use of captopril-DTPA scanning in the diagnosis of atherosclerotic renal artery stenosis in patients with impaired renal function.

We have analyzed our use of captopril-diethylene-triaminepentaacetic acid (DTPA) scanning in patients presenting to the Royal Free Hospital predominantly with renal impairment. The sensitivity was found to be as good in patients with bilateral disease or disease of a single kidney as in patients with unilateral disease. On a number of occasions, though, the scan suggested unilateral disease when bilateral disease existed. There were, however, a large number of patients for whom captopril-DTPA scanning was not performed because of severe renal impairment or the possibility of renal artery stenosis in a single functioning kidney.

Aged↗
PubMed1990

Conversion of stable renal allografts at one year from cyclosporin A to azathioprine: a randomized controlled study.

Seventy-seven stable, nondiabetic, cadaveric renal transplants were randomized at 1 year to convert from cyclosporin A to azathioprine or to continue on cyclosporin A. Prednisolone was increased twofold during the period of conversion, and there was a 3-week overlap period during which azathioprine and cyclosporin A were given. No grafts were lost due to rejection related to conversion, but 9 of the 33 patients who were randomized to convert experienced rejection episodes and 6 were returned to cyclosporin A. Conversion to azathioprine resulted in a drop in creatinine and improvement in blood pressure control. In the group randomized to stay on cyclosporin A, 6 patients had to be subsequently converted to azathioprine because of cyclosporin A toxicity in spite of well-controlled plasma levels. The creatinine levels after successful conversion remained stable whereas those of the patients continuing on cyclosporin A showed a progressive decline. We conclude that conversion from cyclosporin A to azathioprine can be achieved safely. Progressive deterioration in graft function with continuing cyclosporin A therapy does occur and should be taken as an indication for conversion.

Adult↗
PubMed1990

Effects of low-density lipoproteins on mesangial cell growth and viability in vitro.

Recent animal studies suggest that abnormal lipid metabolism may play a role in the pathogenesis of glomerulosclerosis. In order to define mechanisms whereby lipoproteins could contribute to glomerular injury, the effect of Low-density lipoprotein (LDL) concentration on the proliferation of rat mesangial cells was studied in vitro. Human LDL was added to culture medium that had been rendered otherwise lipid free and proliferation rate was estimated by measuring incorporation of 3H-thymidine. When compared to standard medium, LDL-enriched medium stimulated cell division when present in protein concentrations of between 10 and 100 micrograms/ml. At greater concentrations (more than 200 micrograms/ml), cell proliferation was inhibited and above 500 micrograms/ml cells sustained visible morphological injury when assessed under phase contrast microscopy. Estimation of 51Cr release from prelabelled cells confirmed that LDL was cytotoxic in these greater concentrations. A similar pattern of proliferation and toxicity has been observed in vascular smooth muscle cell cultures over a corresponding range of LDL concentrations. These results strengthen the analogy between glomerulosclerosis and atherosclerosis and provide further evidence that lipoproteins may contribute directly to glomerular scarring.

Animals↗
PubMed1990

Cyclosporin-induced renal magnesium leak in renal transplant patients.

Renal transplant patients (n = 116) attending an outpatients clinic were screened for hypomagnesaemia. No azathioprine-treated patients (n = 46) but 24% (17 of 70) of the cyclosporin treated patients were hypomagnesaemic. The hypomagnesaemia in all cases was associated with a renal magnesium leak. This leak did not correlate with plasma bicarbonate, urate, calcium, cyclosporin or creatinine concentrations, nor did it correlate with the use of loop diuretics or duration of the transplant. A renal magnesium leak is common in renal transplant patients treated with cyclosporin and it is independent of other markers of nephrotoxicity.

Adult↗
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

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↗