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Biomedical subjects

R S Rodger

Publications and source records attributed to R S Rodger.

At least 37 records · Page 2Linked to original sources

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.

Adult↗

Anti-CD45 monoclonal antibody perfusion of human renal allografts prior to transplantation. A safety and immunohistological study. CD45 Study Group.

The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.

Adult↗

Colour Doppler ultrasound in renal transplant artery stenosis: which Doppler index?

A prospective study comparing colour Doppler ultrasound (US) with the 'gold standard' of intra-arterial digital subtraction angiography in the evaluation of renal transplant artery stenosis was performed. Both the intrarenal vessels and the transplant renal artery were examined by Doppler US. Diagnostic arteriography was performed only if, on Doppler, the peak systolic velocity in the transplant renal artery exceeded 1.5 ms-1. Of 109 patients, the transplant artery could not be visualized using colour Doppler US in three, and these were omitted from statistical analysis. Of the remaining 106 patients, 31 had a peak systolic velocity greater than 1.5 ms-1 in the transplant renal artery and were referred for DSA. Of the multiple renal Doppler indices recorded, the peak systolic velocity in the transplant artery was the best discriminating measurement for the detection of renal artery stenosis. A peak systolic velocity of > or = 2.5 ms-1 in the transplant renal artery had a sensitivity of 100% and a specificity of 95% for the detection of renal artery stenosis ( > 50% diameter reduction). Although a significant difference in Pulsatility Index, Resistive Index, Acceleration Index and Acceleration Time was recorded from the intrarenal vessels in the angiographically normal and stenosed groups with Doppler, these measurements were less useful as discriminating diagnostic tests. In conclusion, the peak systolic velocity in the transplant renal artery is the most sensitive Doppler criterion for renal artery stenosis and is sensitive and specific enough to be used as a screening test. The intrarenal acceleration time and index should not be used in isolation.

Angiography, Digital Subtraction↗

Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection.

OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.

Acute Disease↗

IgA anticardiolipin antibodies associated with Henoch-Schönlein purpura.

Henoch-Schönlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-Schönlein purpura. A potential role for IgA autoantibodies in Henoch-Schönlein purpura needs to be further explored.

Antibodies, Anticardiolipin↗

Hypothalamo-pituitary-adrenal axis in uraemia: evidence for primary adrenal dysfunction?

To study hypothalamo-pituitary-adrenal axis disturbances in chronic renal failure, we administered corticotrophin-releasing hormone to patients undergoing haemodialysis and CAPD and to normal controls. Cortisol, ACTH, and ACTH precursors were measured before and after corticotrophin-releasing hormone using sensitive and specific two-site assays. Baseline ACTH and cortisol were similar in all groups. Peak values occurred at 30 min (ACTH) and between 30 and 60 min (cortisol). The cortisol (but not the ACTH) responses were significantly reduced in patients with renal failure (P < 0.05). ACTH precursors did not change from baseline following corticotrophin-releasing hormone but were significantly elevated in patients with renal failure compared to controls (P < 0.01). The reduced cortisol response to corticotrophin-releasing hormone may reflect a primary defect of adrenal function in renal failure.

Adolescent↗

Dialysis at home in the west of Scotland: a comparison of hemodialysis and continuous ambulatory peritoneal dialysis in age- and sex-matched controls.

OBJECTIVE: To audit the outcome of patients treated at home by hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective comparison of nondiabetic hemodialysis patients with age- and sex-matched nondiabetic patients treated by CAPD. SETTING: Renal Units, Stobhill General Hospital and Western Infirmary, Glasgow, providing the home dialysis service for the West of Scotland. PATIENTS: Between 1982 and 1988, 139 hemodialysis patients starting treatment at home, compared with 139 matched patients starting CAPD over the same time period. MAIN OUTCOME MEASURES: Patient characteristics and cardiovascular risk factors at the start of home treatment. Patient and technique survival with both forms of dialysis. RESULTS: Patients selected for home hemodialysis were less likely to be smokers (p < 0.02) and to have electrocardiographic evidence of ischemia or left ventricular hypertrophy (p < 0.05) than patients treated by CAPD. Patient survival and technique survival (excluding death and renal transplantation) at 3 years were 93.8% versus 86.2% (p < 0.05) and 94.2% versus 80.8% (p < 0.04) for hemodialysis and CAPD, respectively. Cardiovascular events were responsible for the majority of deaths in both groups, but there was a greater proportion of deaths from other causes in patients treated by CAPD. There was no significant difference in the transplantation rate between the two treatment groups. CONCLUSIONS: Home dialysis is an effective method of renal replacement treatment for patients with end-stage renal disease. The results of hemodialysis are superior to CAPD, but this may be partly due to selection bias.

Actuarial Analysis↗

A closer look at the Autism Behavior Checklist: discriminant validity and factor structure.

The psychometric properties of the Autism Behavior Checklist (ABC; Krug, Arick, & Almond, 1980a, 1980b), a 57-item screening checklist for autism was investigated. Professional Informants completed the ABC on 67 autistic and 56 mentally retarded and learning-disabled children. The autistic children were the total population of autistic children aged 6-15 in two circumscribed suburban and rural regions. Using the total score, the ABC accurately discriminated 91% of the children, with 87% of the autistic and 96% of the nonautistic group correctly classified. Moreover, the accuracy of classification was virtually identical when only the more heavily weighted checklist items were used. A 3-factor model accounted for 32% of the total variance in the checklist. Seventeen items loaded .4 or more on Factor 1, 12 items loaded on Factor 2, and 10 items loaded on Factor 3. The present results fail to provide empirical support for a single unidimensional scale for autism. Also, there is little support for subdividing the checklist into five subscales based on symptom areas.

Adolescent↗

Ranitidine suppresses aluminium absorption in man.

1. Intragastric pH monitoring was performed before and after the single-blind administration of ranitidine or placebo (saline) in eight healthy subjects and four patients with end-stage renal disease who were on regular haemodialysis. 2. The subjects were studied on two occasions and were given aluminum hydroxide (1185 mg) orally 90 min after the administration of ranitidine or saline. 3. Plasma aluminum concentrations and, in normal men, urinary excretion of aluminum were monitored before and after the oral aluminum load. 4. Intragastric pH increased significantly with ranitidine but not with placebo (P less than 0.001). Urinary aluminum excretion increased significantly after the administration of aluminum hydroxide during the placebo phase (P less than 0.001) but not during the ranitidine phase. Plasma aluminium concentrations were higher in the patients with renal failure than in the normal subjects (P less than 0.05), but were unchanged in both groups after the oral aluminium load. 5. This study shows that gastric pH is an important factor in the modulation of aluminum absorption in man, and indicates that reducing gastric acid secretion with ranitidine may reduce the toxicity of orally administered aluminium compounds.

Adult↗

The effect of renal impairment on the pharmacokinetics and metabolism of bopindolol.

The pharmacokinetics of the non-selective beta-adrenoceptor antagonist, bopindolol, have been studied in 18 hypertensive patients with varying degrees of renal impairment following single and multiple oral dosing. Bopindolol, which undergoes extensive hepatic metabolism, was found to accumulate in patients with chronic renal failure but the disposition in patients on regular haemodialysis did not differ significantly from patients with normal renal function. The mechanism underlying these changes in pharmacokinetics is not clear but suggests the presence of metabolic inhibitors in uraemic plasma which are removed by regular haemodialysis.

Adrenergic beta-Antagonists↗

Inhibitory effect of uraemia on the hepatic clearance and metabolism of nicardipine.

1. The principal aim of this study was to investigate the effect of renal impairment on the pharmacokinetics of nicardipine following intravenous and oral dosing. 2. The plasma clearance of nicardipine was significantly lower at 6.5 ml min-1 kg-1 in patients with impaired renal function, compared with a mean value of 10.4 in patients with normal renal function and with 12.5 ml min-1 kg-1 in patients on regular haemodialysis treatment. 3. In comparison to the patients with normal renal function, there were significant increases in AUC and Cmax in the patients with renal impairment. These increases were particularly marked during chronic dosing - AUC was increased by 163%, Cmax by 127% and apparent oral bioavailability by 90%. There were no such increases in the dialysis group whose values were similar to those for normal renal function. 4. There were no significant differences in volume of distribution or protein binding, nor in the measured indices of hepatic function to account for the reduction in drug clearance in the patients with renal impairment. 5. The results of this study indicate that renal impairment may have a significant and potentially important impact on the disposition of a drug which, under normal circumstances, is highly extracted by the liver. Accumulation of a metabolic 'inhibitor' substance is a possible explanation.

Administration, Oral↗