Biomedical subjects
J Moorhouse
Publications and source records attributed to J Moorhouse.
Role of an improvement in acid-base status and nutrition in CAPD patients.
Short-term correction of metabolic acidosis in normal and uremic subjects has been shown to decrease protein degradation, but the long-term effects of better correction of acidosis on nutrition in ESRF are unknown. The aim of this study was to assess the possible benefits, in the nutritional state and morbidity, of improved correction of acidosis in the first year of treatment with continuous ambulatory peritoneal dialysis (CAPD). Two hundred consecutive new CAPD patients were randomized, in a single-blind fashion, to receive a high (HA; lactate 40 mmol/liter) or low (LA; lactate 35 mmol/liter) alkali dialysate for one year. Calcium carbonate and sodium bicarbonate were also used to correct acidosis in the HA group. At one year, the venous serum bicarbonate and arterial pH were 7.44 +/- 0.004 and 27.2 +/- 0.3 mmol/liter in the HA group, and 23.0 +/- 0.3 mmol/liter and 7.4 +/- 0.004 in the LA group (P < 0.001). Dialysis dose, at one year or at the point of leaving the study (HA 8.0 +/- 0.1 liters/day vs. LA 8.5 +/- 0.3 liters/day) was not significantly different (P = 0.18). At one year, the increase in body weight in the HA group (6.1 +/- 0.66 kg) was higher than in the LA group (3.71 +/- 0.56 kg, P < 0.05). The increase in midarm circumference in the HA patients (1.26 +/- 0.16 cm) was significantly higher than the increase in the LA patients (0.61 +/- 0.16 cm, P < 0.05). The increase in triceps skinfold thickness were not significantly different (HA 2.5 +/- 0.41 mm vs. LA 1.24 +/- 0.38 mm, P = 0.1). Serum albumin was 37.8 +/- 0.4 g/dl at one year in the HA group, and 38.2 +/- 0.5 g/dl in the LA group (NS). Dietary protein intake at one year (HA 0.9 +/- 0.2 g/kg/day vs. LA 1.0 +/- 0.1 g/kg/day) was not significantly different. There were fewer hospital admissions in the HA group (1.13 +/- 0.16 per patient per year) compared to the LA group (1.71 +/- 0.22 per patient per year, P < 0.05). The HA patients spent less days in hospital per year than the LA patients (16.4 +/- 1.4 days/year vs. 21.2 +/- 1.9 days/year; P < 0.05). It is concluded that better correction of metabolic acidosis leads to greater increases in body weight and midarm circumference, but not triceps skinfold thickness, in the first year of CAPD. The improvement in morbidity, in terms of number of admissions and days in hospital per year, may be associated with the improvement in nutritional state.
The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.
The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.
Peritonitis rate: traditional versus low calcium dialysate.
The results of nonrandomized retrospective studies have suggested that low calcium dialysate (LCD; ionized calcium concentration 1.25 mmol/L) is associated with a higher peritonitis rate than traditional dialysate (TD; ionized calcium concentration 1.75 mmol/L). For this reason, 86 consecutive new continuous ambulatory peritoneal dialysis patients were randomized, in a single-blind fashion, to TD or LCD for 1 year. The results were analyzed on an intention-to-treat basis, no matter what fluid or what modality of treatment was being used at the end of the year. The two groups were well matched at baseline. At 1 year, 28 of 43 TD patients were still on continuous ambulatory peritoneal dialysis (one had a catheter changed due to peritonitis), four had a working transplant, one had recovered renal function, nine had died, and one had been transferred to hemodialysis because of peritonitis. Twenty-seven of 43 LCD patients were on continuous ambulatory peritoneal dialysis (one catheter change), nine had a working transplant, six had died, and one was on hemodialysis. There were 17 proven (33 possible) peritonitis episodes in 417 patient-months in the TD group. In the LCD group, there were 17 (35 possible) episodes in 432 patient-months. The proven peritonitis rate was 0.49 episodes/patient/yr in the TD group versus 0.48 episodes/patient/yr in the LCD group (P = NS). In conclusion, there is no controlled evidence that LCD is associated with a higher incidence of peritonitis than TD.
Influence of nifedipine on interstitial fibrosis in renal transplant allografts treated with cyclosporin A.
AIMS: To compare the degree of interstitial fibrosis in renal transplant biopsy specimens from immunosuppressed patients using conventional doses of cyclosporin with and without calcium channel blockade with a combination of low dose cyclosporin and azathioprine; to correlate the degree of interstitial fibrosis with the glomerular filtration rate. METHODS: A single blind histomorphometric assessment was done of cortical interstitial volume fraction from biopsy specimens taken intraoperatively and at one, six, and 12 months after transplantation from three prospectively randomised groups of patients: (A) conventional dose cyclosporin; (B) conventional dose cyclosporin plus nifedipine; (C) low dose cyclosporin plus azathioprine. RESULTS: Interstitial volume increased with time in all groups. No differences in interstitial volume were present at operation or at one month, but at six months interstitial volume was significantly less in group B than group A (p < 0.001) or group C (p < 0.05). More grafts failed in group A than group B leaving only small numbers for comparison at 12 months. At 12 months the differences persisted but did not reach significance. These results strongly reflected the clinical findings, where glomerular filtration rate was significantly lower in group A than groups B or C at six and 12 months; no differences in glomerular filtration rate were found at one month. In a direct comparison glomerular filtration rate showed a significant negative correlation with interstitial volume fraction. CONCLUSIONS: These findings suggest that calcium channel blockade with nifedipine slows the development of interstitial fibrosis in renal transplant recipients treated with cyclosporin. When clinical data are considered, it is suggested that calcium channel blockade may have a mitigating effect on the long term nephrotoxic effects of cyclosporin and should be considered as adjunctive treatment in patients requiring this immunosuppressant following renal transplantation.
Evidence for a multi-allelic heterokaryon incompatibility (het) locus detected by hybridization among three heterokaryon-compatibility (h-c) groups of Aspergillus nidulans.
A strain of heterokaryon-compatibility (h-c) group A was crossed sexually to strains of h-cB and h-cGL of Aspergillus nidulans. A back-crossing programme established that there were seven hetero-allelic heterokaryon compatibility (het) genes controlling somatic incompatibility between strains of h-cA and h-cB. A similar back-crossing programme between strains of h-cA and h-cGL confirmed that these two groups differ at six het loci. Previous work has shown that h-cB differs from h-cGL at two het loci, hetA on linkage group V and hetB on linkage group VI. As an allelic difference at a single het locus is enough to cause two strains to be heterokaryon incompatible, 15 alleles spread over seven het loci are necessary to explain the h-cA, h-cB, h-cGL triangular compatibility relationship. One het locus is multi-allelic and this locus must be either hetA or hetB.
Renal transplantation: nifedipine for the nonstarters? A prospective randomised study.
Explore the source record for details and available documents.
Nifedipine improves immediate, and 6- and 12-month graft function in cyclosporin A (CyA) treated renal allograft recipients.
To investigate the effect of oral nifedipine, a calcium channel blocker known not to modify cyclosporin A (CyA) pharmacokinetics, on immediate transplant function and CyA nephrotoxicity, 68 adult renal transplant recipients were pre-operatively randomized to one of three regimes: A (high-dose CyA, initial dose 17 mg/kg per day, maintenance dose 7 mg/kg per day); B (regime A plus oral nifedipine); C low-dose CyA, initial dose 10 mg/kg per day, maintenance 4 mg/kg per day plus azathioprine 1 mg/kg per day). All three groups received identical steroid regimes. Calcium channel blockers of all types were avoided in groups A and C. Delayed graft function (dialysis dependence by day 4) was seen least frequently in group B (P < 0.02). Group B had improved graft function at 6 months compared with group A, identified by differences in serum creatinine (P < 0.05), GFR (P < 0.01) and ERPF (P < 0.05). Similar differences in serum creatinine (P < 0.05) and GFR (P < 0.05) were also identified at 12 months. Group C also had better 6- and 12-month GFR values than group A (P < 0.05 each). The three groups did not differ in donor or recipient age, HLA matching, ischaemic or anastomosis times, frequency of early rejection or whole-blood CyA levels. These results indicate that nifedipine significantly improves immediate and medium-term graft function.
Improved immediate graft function with nifedipine in cyclosporine-treated renal allograft recipients--a randomized prospective study.
Explore the source record for details and available documents.
The location and analysis of two heterokaryon incompatibility (het) loci in strains of Aspergillus nidulans.
The heterokaryon incompatibility system in Aspergillus nidulans has been investigated by parasexual methods. The use of complementary auxotrophs with a repeated serial transfer method or with a protoplast fusion technique has enabled heterokaryons and diploid strains to be recovered from heterokaryon incompatible combinations of strains. The effects of allelic interaction at heterokaryon incompatibility (het) loci on the morphologies of the heterokaryon and diploid colonies isolated are described. Parasexual analyses conducted among strains belonging to the heterokaryon compatibility groups, h-cGl and h-cB, and the two recombinant compatibility classes, have located the hetA and hetB genes to linkage groups V and VI respectively.