Biomedical subjects
Publications and source records attributed to A M Brownjohn.
Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis.
Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.
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Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.
Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim was to evaluate plasma proteins during continuous ambulatory peritoneal dialysis (CAPD) in relation to dialysis losses, membrane permeability, renal insufficiency, and time on CAPD. Ten male patients, established on CAPD for at least 14 months, were studied every 8 weeks for 56 weeks. Blood and dialysate from the morning exchange were analysed for urea, creatinine, and 7 proteins, and used to calculate dialysate to plasma concentration ratios (D/P). These ratios were not significantly changed suggesting that permeability remained constant. However, there was a trend for beta 2-microglobulin, creatinine, and urea to increase progressively. After 56 weeks, beta 2-microglobulin had increased from 27.9 to 31.3 mg/L (p less than 0.05) and creatinine 1006 to 1099 mumoL/L (p less than 0.05) and both correlated with time on CAPD (p less than 0.001). Plasma alpha 1-acid glycoprotein, albumin, transferrin, IgG, IgA, and complement C3 were not significantly changed, although IgA and complement C3 were each negatively correlated with time on CAPD (r = -0.70 and -0.67, respectively), creatinine (r = 0.51 and -0.54), and urea (r = -0.61 and -0.61) (p less than 0.001 for all). It is concluded that increases in beta 2-microglobulin, creatinine, and urea are not due to loss of membrane permeability but reflect a slight increase in uraemia. Long-term decreases in immunological proteins may be caused by uraemia or progressive depletion.
A total of 1347 patients with severe acute renal failure, treated at a single centre between 1956 and 1988, are reviewed. Only patients with an acute uraemic episode requiring dialysis and/or with serum creatinine levels above 600 mumols/l were included. The age of patients increased from median 41.25 years in the 1950s to 60.5 years in the period 1980 to 1988. The case-mix also altered with a decline in obstetric and traumatic disease, both of which carried an excellent prognosis, and an increase in the number of elderly patients with complicated medical and surgical conditions. Survival significantly decreased with increasing age and in the presence of complicating factors such as sepsis or malignancy. Despite these changes, there has been a progressive improvement in survival from 48.8 per cent in 1956-1959 to 57.9 per cent in 1985-1988. Survival for medical and surgical cases has improved from 38.5 per cent in 1956-1959 to 57.9 per cent in 1985-1988 (overall survival for non-obstetric cases was 44.2 per cent), due to improved prognosis for acute renal failure in general and acute renal failure due to intrinsic renal disease in particular.
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The effect of nisoldipine on renal function after 6 weeks treatment was investigated in hypertensive patients with and without renal impairment. Nisoldipine was well tolerated and an effective antihypertensive agent when administered over a period of 6 weeks. There were no significant changes in glomerular filtration, cardiac output, plasma renin activity or serum biochemistry during nisoldipine administration. Effective renal plasma flow was unaffected by treatment in the patients with normal renal function, but in the patients with renal insufficiency, the value decreased by a mean of 12%. Nisoldipine had no major untoward effects on renal function after 6 weeks administration, but minor changes in renal haemodynamics in the patients with renal insufficiency would suggest that careful monitoring of renal function is indicated in such patients.
During the evaluation of 1% amino acid solution as an alternative osmotic agent to glucose, we measured amino acids and proteins in dialysate, urine and plasma to evaluate the uptake of amino acids and their effects on membrane permeability. Eight patients (plasma albumin less than 35 g/l) were on 21 exchanges of glucose fluid for 4 weeks before and after 12 weeks, during which a solution of 15 amino acids (Baxter '151') was used for the morning exchange. The absorption of amino acids from the single daily '151' exchange increased during the study: 16.4 g at 4 weeks and 17.1 g after 12 weeks (P less than 0.01) with increases in eight amino acids. Amino acid uptake was related to the permeability characteristics of the patients. Following each '151' exchange, 1% of the amino acids absorbed were dialysed into subsequent glucose exchanges. Consequently the net daily gain was 15.0 g increasing to 15.6 g, whereas daily depletion during glucose exchanges was 1.8 g both before and after '151'. Clearance of five proteins increased both at the start and after 12 weeks of '151'. Total protein and prealbumin loss into dialysate increased by about 20%, and when glucose was restored loss of transferrin, albumin and immunoglobulin G decreased. Urinary concentrations were similar throughout. Amino acid uptake from '151' greatly exceeded all losses although our results suggest small reversible increases in macromolecular permeability of the peritoneum.
Eight patients with end-stage renal failure (plasma albumin less than 35 g/l) who were established on glucose CAPD exchanges, were studied for 4-week periods before, and after 12 weeks when 1% amino-acid solution had been used for the morning exchange. Anthropometric, biochemical, clinical and dietary assessments were made every 4 weeks. Dietary intakes of protein and calories were maintained. Studies with amino-acid solutions showed a mean of 13% and 8% amino acids remaining in the dialysate after 6 and 8 h respectively. Plasma amino acids increased to a maximum after 2 h of dialysis; however, fasting concentrations were constant over the 5 months. Osmolality of amino acids decreased comparably with 1.36% glucose during 8-h exchanges although the recovery of fluid was marginally less. Plasma transferrin increased significantly after 8 weeks of amino acids but subsequently decreased in one patient due to infection. No significant changes occurred in albumin, apolipoprotein A, IgG, IgA or prealbumin. Cholesterol and apolipoprotein B decreased in seven patients but increased in one due to rising calorie intake. Increases in urea and decreases in bicarbonate were not clinically significant. Amino-acid-based fluid was well tolerated with modest nutritional benefit and reduction in hyperlipidaemia. Optimal effects of amino acids are likely at higher concentrations using two or more exchanges in patients eating less than 0.9 g protein/kg per day.
The clinical features, treatment and survival of 36 patients with microscopic polyarteritis diagnosed between 1957-1988 have been reviewed. All had a focal segmental necrotizing glomerulonephritis on renal biopsy with evidence of a small vessel vasculitis. Most had a prodromal illness of less than 1 month. Severity of renal disease varied from microscopic haematuria which has a good prognosis to acute oliguric renal failure which carries a high mortality. The prognosis of microscopic polyarteritis can be improved if the condition is recognized early and treated with steroids and cyclophosphamide.
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Total protein and 12 specific proteins were measured in dialysates from 8 patients on continuous ambulatory peritoneal dialysis during training. Mean daily loss of total protein was 10.5 g and this included 5.2 g albumin, 805 mg of the immunoglobulins G, A and M, 323 mg transferrin and 530 mg of the remaining 7 proteins measured. The plasma to dialysate ratio of protein concentrations correlated with the natural logarithm of molecular weight, suggesting that proteins in dialysate are an ultrafiltrate of plasma. A greater loss of proteins overnight was due to longer dwell time as the mean rate of loss was similar for all exchanges. Losses were similar with 1.36% and 3.86% dextrose fluids, suggesting that the initial effects of hypertonicity are diminished or reversed by dilution and absorption of dextrose. Daily outflow volumes for 4 patients correlated inversely with the quantities of several proteins removed, probably due to effects of osmolality. It is concluded that protein losses are related to plasma concentration, molecular weight and osmolality of the dialysis solution and to the physiology of the patient.