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Biomedical subjects

D N Kerr

Publications and source records attributed to D N Kerr.

At least 55 records · Page 3Linked to original sources

Methods for studying the binding of aluminum by serum protein.

We describe methods for studying the binding of Al by protein in serum: ultrafiltration, gel filtration, and immuno-affinity chromatography. For ultrafiltration we used an Amicon YM10 cellophane membrane with a nominal cutoff of 10 000 Da to separate ultrafiltrable and non-ultrafiltrable Al. For gel filtration we used Sephacryl S-300, and for immuno-affinity chromatography we used anti-transferrin coupled to CNBr-activated Sepharose to identify the Al-binding protein. For 30 normal subjects 54% of the total Al in serum was non-ultrafiltrable; for 30 patients with chronic renal failure being treated by hemodialysis 67% was non-ultrafiltrable. In both groups transferrin was identified as the major Al-binding protein in the serum. Results of gel-filtration studies should be interpreted with caution: some gel media adsorb "free" Al, which can be subsequently taken up by transferrin or desferrioxamine passing through the column. We find affinity chromatography to be a specific and reliable method, suitable for use in quantitative studies.

Adult↗

Factors affecting development of peritonitis in continuous ambulatory peritoneal dialysis.

A questionnaire based survey in patients receiving continuous ambulatory peritoneal dialysis showed that there was an increased incidence of upper respiratory tract symptoms (suggestive of viral illness) in the 14 days before the development of peritonitis. No other factors were identified that might distinguish patients who develop peritonitis. The possibility that viral infections predispose to peritonitis by altering host defence mechanisms in patients receiving this form of renal replacement therapy warrants further study.

Humans↗

Surgical aspects of continuous ambulatory peritoneal dialysis--3 years experience.

Since January 1979, 122 patients (mean age 38.5 years, range 5-72 years) with chronic renal failure have been treated with continuous ambulatory peritoneal dialysis (CAPD). Peritoneal access was achieved by inserting silicone rubber Tenckhoff peritoneal dialysis catheters (Quinton, Seattle, Washington) by an open (76 per cent) or closed technique. Actuarial analysis showed a patient survival of 98 and 94 per cent and a success rate of 88 and 64 per cent at 1 and 2 years, respectively. Currently, 74 patients are using CAPD and 8 have been treated for 30-36 months. Thirty-five patients (29 per cent) required two or more peritoneal catheters and 69 per cent of these patients are still on CAPD. Catheter-related peritonitis was the most frequent complication (233 separate episodes in 94 patients) and necessitated catheter removal in 16 per cent of episodes, although 37 per cent of patients from whom catheters were removed because of peritonitis later resumed CAPD. Extravasation of dialysate from the peritoneal cavity (31 episodes) and catheter obstruction (31 episodes) required surgical replacement of catheters in 8 and 23 cases, respectively. Twenty patients (16 per cent) developed 24 abdominal hernias, only one of which caused failure of CAPD. Infective and mechanical complications of CAPD frequently require surgical intervention but only occasionally result in failure of the technique, and even multiple catheter replacements are compatible with successful long term CAPD.

Abdomen↗

Short-term studies on the use of glycerol as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD).

The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l) in peritoneal dialysis fluid was investigated over 3 days in six patients on continuous ambulatory peritoneal dialysis and compared with two concentrations of glucose (76 mmol/l and 215 mmol/l) in the same patients. The calorific value of the absorbed osmotic agent was lower, by 19% with isotonic and 22% with hypertonic solutions, when glycerol was used in place of glucose. However, glycerol provided significantly lower total ultrafiltration than glucose at each concentration, despite a higher initial osmotic pressure of the glycerol-based solutions. Thus, the higher concentration of glycerol required to provide equal ultrafiltration may offset any calorific advantage. Equilibration of creatinine and urea was slower and creatinine clearance lower with glycerol. Solutions containing glycerol were initially less acid (pH 6.5) than those containing glucose (pH 5.1). Blood glycerol levels, which were in the physiological range with glucose as the osmotic agent, reached a peak 80-fold greater at 4.3 +/- 0.8 mmol/l during dialysis with fluid containing glycerol at 272 mmol/l and eightfold higher at 0.42 +/- 0.09 mmol/l with glycerol at 92 mmol/l. There was no evidence of haemolysis or other toxic effect despite these levels. The rise in blood glucose and insulin noted during the use of glucose-based solutions was not found with glycerol. Circulating levels of lactate, pyruvate, alanine, non-esterified fatty acids and the ketone bodies were similar with the two agents. Although these short-term studies have shown no conclusive advantage of glycerol over glucose, long-term effects of glycerol, particularly on circulating lipid levels, will determine its future role as an osmotic agent in continuous ambulatory peritoneal dialysis.

Adult↗

Idiopathic hypergammaglobulinaemia associated with nephrogenic diabetes insipidus and distal renal tubular acidosis.

Renal tubular dysfunction may be recognized in patients suffering from urinary light chain disease or non-myelomatous hypergammaglobulinaemia. We report a patient who has the combination of distal renal tubular acidosis and nephrogenic diabetes insipidus in association with hypergammaglobulinaemia due solely to increased IgG. We postulate that the abnormalities of distal nephron function resulted from cell-mediated immune damage.

Acidosis, Renal Tubular↗

Bone disease in long-term hemodialysis patients with low dialysate aluminium.

The dialysis unit in Sunderland uses softener water treatment with low Al concentration (dialysate mean Al 22 micrograms/L) but employs continuous oral Al (OH)3 to control serum phosphate. Thirty-one patients, 22 males and 9 females, with a mean age of 45 years, maintained on hemodialysis for a mean of 48 months were studied. Patients had higher Al concentrations than normal controls (p less than 0.001) and the postdialysis serum Al levels were also significantly higher than the predialysis levels. Twenty-four of 31 patients had evidence of hyperparathyroidism on radiology but only 4 of 31 had fractures. From a histopathological point of view, the patients were found to have no lesions (4 patients), osteitis fibrosa alone (17 patients), and osteitis fibrosa combined with osteomalacia (5 patients). The effect of 1-alpha(OH)D3 treatment was checked by repeated bone biopsies. One case of the last group showed no improvement of osteitis fibrosa, while osteomalacia progressed to severe. We conclude that both antacids and dialysate contribute to the serum and tissue Al accumulation in Sunderland Renal Unit, where over a period of ten years only one patient developed Al-related osteomalacia.

Adult↗

Isolated C3 deposition in patients without systemic disease.

Deposition of C3 without immunoglobulins ("isolated C3") was found in 9.8% of 540 renal biopsies performed between 1976 and 1982. Thirty-two of these samples were from patients with systemic diseases (16), well defined forms of glomerulonephritis (9), other renal diseases (4) or renal allografts (4). The remaining 22 patients are described. Five had nephrotic syndrome, three of them with minimal changes on light microscopy and good response to corticosteroids. We were left with a group of 17 patients who presented with gross (4) or microscopic (12) hematuria or asymptomatic proteinuria (1) whose biopsies showed mesangial proliferation or/and hyperplasia and who followed a benign course over the mean 3 years of follow-up, with the exception of one whose renal function is declining. This clinicopathological picture is similar to that described in two previous publications suggesting that "Isolated C3 mesangial proliferative nephritis" is a recognizable sub-group within the spectrum of glomerulonephritis.

Adolescent↗

The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults.

Sixty-four patients (47 male, 17 females) aged between 20 and 70 years with idiopathic membranous glomerulonephritis, never having received steroid or immunosuppressive drugs prior to and subsequent to biopsy, have been followed to terminal renal failure or for a minimum of two up to fifteen years. Presentation was with asymptomatic proteinuria in 12 and nephrotic syndrome in 52. The serum creatinine at time of biopsy was less than or equal to 99 mumoles/l in 25, 100-119 mumoles/l in 18 and greater than or equal to 120 mumoles/l in 21. During the follow up there was no deterioration in renal function in 30 patients (48%). In 27 patients (43.5%) there was a steady deterioration in renal function, on the average 30 months (range 5-60) for the serum creatinine to double and 32 months (range 5-49) for the serum creatinine to reach 400 mumoles/l. In five patients there was a slow deterioration. A plot of the reciprocal of the sequential serum creatinine values with time indicates that the rate of deterioration is essentially constant in any patient but that there is a wide variation between patients. The reciprocal of the serum creatinine is a useful means of following the evolution of the disease. In two patients there was a change in the rate of deterioration and a cause could be identified (one with renal vein thrombosis, one with interstitial nephritis). Poor prognostic indicators were: nephrotic syndrome at presentation, impaired function at time of diagnosis, male patients and older age.

Adult↗

The associations of HLA and other genetic markers with glomerulonephritis.

One hundred and seventy-nine patients with various forms of glomerulonephritis confirmed histologically were tested for HLA A and B antigens: Thirty-four with membranous glomerulonephritis were also typed for DR antigens. One hundred and forty-one of these patients were further tested for blood group, red cell enzyme, and plasma protein systems. The minimal-change and the mesangio-capillary glomerulonephritis showed a significant association with B8 and Bw44 antigens respectively, whereas the membranous nephritis in addition to B8 was also found to be associated with DR3 antigen. Previously described associations with Henoch-Schönlein and Berger's nephritis were not proved. A large group with nonspecific proliferative glomerulonephritis did not show any association with HLA. Among the other single-gene characters studied, a significant association was found with Bf (Factor B or C3 proactivator) and adenosine deaminase, both markers thought to be involved in the immune response. The close association of the markers located on chromosome 6 and glomerulonephritis indicates that there may be an immunological component in the aetiology of the disease. The significance of the various associations found is discussed.

Blood Group Antigens↗

Engineering design of haemodialysers.

Haemodialysis is a widely used treatment for chronic and acute renal failure and relies on the diffusion of solutes and water in a mass exchanger or haemodialyser. The design concepts of haemodialysers are discussed together with limitations of existing design solutions and work on the optimization of design reviewed.

Equipment Design↗

Carbohydrate and lipid metabolism during continuous ambulatory peritoneal dialysis (CAPD): the effect of a single dialysis cycle.

The effect on hormonal status and intermediary metabolism of a single 6 h dialysis cycle at two different concentrations of dialysate glucose was investigated in six patients on continuous ambulatory peritoneal dialysis. The basal blood glucose level was elevated by 0.5 mmol/l, associated with a threefold increase in basal serum insulin compared with seven normal controls. Blood glucose and serum insulin rose further during dialysis, particularly with hypertonic (215 mmol of glucose/l) dialysis fluid and levels remained high for 6 h after the onset. Plasma glucagon concentrations were 2.7-fold increased and did not decrease to normal during dialysis. Concentrations of the gluconeogenic precursors lactate and alanine were consistently raised, and levels of circulating non-esterified fatty acids and ketone bodies were lowered, particularly with hypertonic dialysis fluid. The long-term effects of sustained hyperinsulinaemia, including suppression of lipolysis and ketogenesis, require further investigation.

Adult↗