Search PubMed⌕ Search

Biomedical subjects

J Walls

Publications and source records attributed to J Walls.

At least 91 records · Page 5Linked to original sources

Plasma amino acid profile in the elderly with increasing uraemia.

Abnormalities in plasma amino acid profiles have been reported in severe uraemia and dialysis patients and may be a consequence of altered protein metabolism in the presence of metabolic acidosis. We studied plasma amino acid profiles in 7 control subjects [GFR 92.7 +/- (SEM) 14.5 ml/min/1.73 m2] and 7 elderly patients with renal failure (GFR 16.5 +/- 1.3 ml/min/1.73 m2). Uraemic patients had significantly reduced plasma levels of valine, tyrosine, phenylalanine, tryptophan and elevated histidine compared to controls. There was no correlation between arterial pH or bicarbonate and plasma amino acid levels.

Aged↗

Glomerular disease as a cause of isolated microscopic haematuria.

Microscopic haematuria is a common clinical finding, with reported prevalences of up to 22%. The role of renal biopsy in the investigation of this condition is still debated. Currently urological investigation including cystourethroscopy is often regarded as adequate. We investigated 165 patients (94 male, 71 female; mean age 37.5 years, range 10-71) referred with isolated microscopic haematuria, using renal biopsy and cystourethroscopy. All patients were normotensive with normal serum creatinine, no proteinuria, sterile urine and a normal IVU. Renal biopsy abnormalities were found in 77/165 (46.6%): IgA nephropathy (49), global or segmental mesangial proliferative glomerulonephritis without IgA deposits (16), thin membrane nephropathy (7), vascular changes suggestive of hypertension (3), interstitial nephritis (1), and membranous nephropathy (1). Only five abnormalities were found on cystourethroscopy (cystitis 3, urethral stricture 1, bladder stone 1). Two patients with cystitis also had IgA nephropathy. Biopsy abnormalities were commonest under the age of 20 (69.2%), but 40% of biopsies were abnormal even in the seventh decade of life. Because renal biopsy abnormalities are very frequent in patients with isolated haematuria, renal biopsy is indicated in patients over 45 years of age if renal imaging and cystoscopy are normal. In those under 45 years, renal biopsy should replace cystoscopy as the investigation to follow normal renal imaging.

Adolescent↗

Treatment of the axilla in patients with screen-detected breast cancer.

Management of the axillary lymph nodes in patients with screen-detected breast cancer is controversial. Optimal treatment should combine accurate determination of node status and avoidance of unnecessary morbidity. This study attempted to determine whether axillary node status could be accurately predicted using selected criteria in women with screen-detected breast cancer. Of 223 breast cancers excised in the Greater Manchester breast screening programme, 180 were invasive and 40 of these had associated lymph node metastases. The presence of involved nodes was associated with large tumour size, high tumour grade and the absence of mammographic microcalcification. Multiple logistic regression analysis revealed that each of these three factors was independently significant. Women with a screen-detected breast cancer < 1 cm in diameter or those with grade I tumours < 3 cm (35 per cent of the total) could be spared axillary surgery with an expected reduction in morbidity and operating time.

Axilla↗

Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria.

Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were "definitely" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.

Adolescent↗

Early increase in glomerular leucocyte number after a reduction in renal mass: implications for the pathogenesis of glomerulosclerosis.

1. Adult female Wistar rats underwent uninephrectomy (n = 8) through a flank incision, or a sham operation (n = 7). One to two weeks later the kidney was perfused in situ and glomeruli were isolated from cortical tissue by sequential sieving, and partially digested. Glomerular leucocytes were labelled with a mouse monoclonal antibody against leucocyte common antigen followed by a fluorescein-labelled anti-mouse immunoglobulin to allow counting. 2. In a further group of animals 24 h albumin excretion and glomerular size were measured 2 weeks after either uninephrectomy (n = 6) or sham operation (n = 6). 3. Glomerular leucocyte number was significantly increased in uninephrectomized animals (15.7 +/- 0.9 versus 8.9 +/- 0.4, P < 0.001), with some glomeruli having leucocyte numbers comparable with those seen in glomerulonephritis. 4. Albuminuria was not increased 2 weeks after uninephrectomy (233 +/- 35 versus 170 +/- 42 micrograms/24 h, not significant), and glomerular size was unchanged. Light microscopical appearance was normal. 5. An increase in glomerular leucocyte number is an early response in what was previously considered a non-immunological lesion. It precedes the development of renal scarring and may be important in the pathogenesis of this process.

Albuminuria↗

Effects of acid loading on serum amino acid profiles and muscle composition in normal fed rats.

1. Impaired body growth, loss of lean body mass and negative nitrogen balance are common findings in chronic renal failure. Enhanced endogenous protein catabolism in skeletal muscle induced by co-existent metabolic acidosis seems to be an important aetiological factor. 2. In uraemic patients abnormalities in blood amino acid profiles are present after a protein meal, suggesting impaired metabolism of ingested proteins. 3. This study demonstrates that acidosis induces changes in arterial amino acid profiles in fed non-uraemic rats. These included increased levels of threonine, histidine, proline, serine and glycine, and decreased levels of tryptophan. These changes are similar to those found in uraemic patients after a protein meal, suggesting a pathogenic role of acidosis in the impairment of exogenous protein metabolism. 4. Intracellular amino acid levels in the muscle tissue partly reflect the changes in the extracellular level. 5. Acidotic animals had a decreased body weight gain and a reduced alkali-soluble protein/DNA ratio in muscle cells compared with controls. 6. In conclusion, the results show that acidosis per se modifies the circulating amino acid profile in fed rats, resulting in a pattern similar to the post-prandial amino acid changes described in uraemic patients. These abnormalities occur together with impaired growth of skeletal muscle cells.

Acidosis↗

Hemodialysis and iopamidol clearance after subclavian venography.

RATIONALE AND OBJECTIVES: The dialyzability of iopamidol is unknown and was investigated in patients undergoing long-term hemodialysis for chronic renal failure. METHODS: Ten patients received 30 ml Niopam 300 (Bracco SpA, Milan, Italy) (identical to 18372 mg iopamidol) intravenously into a forearm vein to investigate for occult subclavian stenosis. RESULTS: The elimination half-life of iopamidol before hemodialysis was 69.6 hours and during 4 hours of hemodialysis was 3.5 hours. A single 4-hour hemodialysis cleared 55.7% (95% Ci 51-5-59.8) of the administered dose, while second and third dialyses cleared 25.3% (95% Ci 21.4-29.1) and 10.1% (95% Ci 7.7-12.6) of the administered dose, respectively. Two patients with significant residual urine excretion excreted more than 10% of the administered dose in the urine. For anuric patients, extrarenal clearance provided total body clearance of up to 0.266 L/hr. CONCLUSIONS: Hemodialysis is a rapid and efficient means of clearing iopamidol provided it is performed soon after the contrast study.

Adult↗

Effect of cholesterol on the position of segmental lesions in unilaterally nephrectomized rats.

Different positions of segmental lesions within glomeruli may correspond to different pathogenetic mechanisms. The effect of a high cholesterol diet on the position of lesions had not previously been investigated. This was studied in rats following unilateral nephrectomy, as a change in position would suggest a different mechanism of damage. Thirty-two female WAG/ola rats had unilateral nephrectomy. Half the rats were given a diet supplemented with 4 per cent cholesterol and 1 per cent cholic acid. At death, six at 10 weeks after nephrectomy and the rest at 24 weeks, kidney sections were examined microscopically. There were significantly more segmental lesions in the cholesterol-fed rats than in the controls, and these lesions were almost entirely at the glomerular hilum in both groups. Significantly more glomeruli contained foamy cells in the cholesterol-fed group, both within lesions and away from them. These findings confirmed that in reduced renal mass, segmental lesions are mainly hilar. The diet increases the number of glomeruli affected by lesions, but these are still mainly hilar. Therefore one possibility is that hypercholesterolaemia worsens the hyperfiltration effect on glomeruli. The diet also produces foamy cells scattered throughout the glomeruli but these do not appear to develop into segmental lesions.

Animals↗

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.

Adult↗