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Biomedical subjects

M K Ward

Publications and source records attributed to M K Ward.

At least 91 records · Page 5Linked to original sources

A clinical appraisal and comparison of double pump single needle dialysis systems.

Six recently developed double pump tidal flow single needle systems have been assessed clinically and the magnitude of recirculation, efficiency of dialysis determined and compared with the classical system (Bellco BL 760). Results indicate that the problems of designing twin pump systems with instantaneous response, occlusive rollers capable of generating clinically acceptable blood flow rates has been largely overcome and such systems offer a high degree of patient acceptance, flexibility, safety and an efficiency of dialysis comparable with that obtained using two needle access.

Blood Flow Velocity↗

Raised serum nickel concentrations in chronic renal failure.

We have measured serum nickel concentrations using flameless atomic absorption spectrophotometry. In 71 normals the median concentration was 1.0 micrograms/L, range less than 0.6-3.0 micrograms/L. Increased concentrations (p less than 0.05) were found in patients with chronic renal failure (CRF) treated conservatively (median 1.6 micrograms/L, range less than 0.6-3.6 micrograms/L). Significantly increased concentrations (p less than 0.001) were found in patients treated by continuous ambulatory peritoneal dialysis (CAPD) (median 8.6 micrograms/L, range 5.4-11.4 micrograms/L) and haemodialysis. In patients on haemodialysis, post-dialysis concentrations (median 8.8 micrograms/L, range 3.0-21.4 micrograms/L) were significantly higher (p less than 0.001) than pre-dialysis values (median 8.6 micrograms/L, range 0.6-16.6 micrograms/L).

Adult↗

Protein binding of aluminium in normal subjects and in patients with chronic renal failure.

Ultrafiltration of serum through YM10 membranes showed that 46 per cent of the aluminium in normal subjects and 33 per cent of the aluminium in patients with chronic renal failure is ultrafiltrable, suggesting that the majority of the aluminium is bound to some serum component(s) having molecular weight greater than 10,000 daltons. After desferrioxamine infusion, both the ultrafiltrable and protein-bound aluminium increases significantly, probably due to mobilisation of aluminium from body tissues. Gel filtration on Sephacryl S-300 and affinity chromatography have shown that transferrin is the major aluminium binding protein.

Aluminum↗

Ectopic calcification. The role of parathyroid hormone.

In 42 uraemic patients radiological skeletal survey, biochemistry and bone histology were compared before and at 6-12 months (42 patients), 12-24 months (26 patients) or 24-48 months (12 patients) after parathyroidectomy. The presence of small vessel or non-visceral soft tissue calcification was not related to the age, sex, duration of end-stage renal failure treatment, total serum calcium, magnesium, phosphate, Ca x P product, alkaline phosphatase, ionised calcium, serum aluminium, iPTH, severity of radiological and histological osteitis fibrosa or parathyroid gland weight. Twenty-three patients (55%) had small vessel and 20 (48%) soft tissue calcification before parathyroidectomy. Despite a marked improvement in subperiosteal erosions (37 healed, 5 improved) and healing of osteitis fibrosa histologically, seven patients developed new and six developed increased peripheral arterial calcification while in 10 patients non-visceral soft tissue calcification disappeared and in two decreased. Successful parathyroidectomy improves non-visceral calcification but not arterial calcification despite reduction in Ca x P product and iPTH.

Adult↗

Parathyroidectomy in chronic renal failure.

In order to establish whether parathyroidectomy altered the natural history of ectopic calcification in patients with renal failure we undertook a detailed analysis of 62 patients with hyperparathyroidism secondary to chronic renal failure who were submitted to parathyroidectomy. Biochemical data (61 patients) and radiological skeletal surveys (42 patients) were studied before and after parathyroidectomy. Transiliac bone biopsies were obtained at (or some time in the previous six months before) parathyroidectomy in 30 and in 36 patients after surgery. Paired bone biopsies were available from 17 of these patients. In the majority of patients secondary hyperparathyroidism was controlled after parathyroidectomy although in seven patients (11 per cent), who underwent subtotal parathyroidectomy, it relapsed after initial improvement. Non-visceral soft tissue calcification disappeared or decreased in 60 per cent of the patients after parathyroidectomy. However, despite marked improvement in subperiosteal erosions and histological osteitis fibrosa, with significant reductions in iPTH and Ca X P product after parathyroidectomy, small peripheral arterial calcification developed or progressed in 56 per cent of the patients. Histological osteomalacia after parathyroidectomy developed after operation in two patients. Both had positive aluminium stains for excess aluminium in their bone. Numbers of osteoclasts and the amount of marrow fibrosis declined in parallel following parathyroidectomy, but woven bone persisted for months or years.

Adult↗

Dual lumen subclavian catheters for haemodialysis.

The dual lumen catheter has recently been developed as a subclavian vascular access device for haemodialysis. This paper describes our preliminary experience with two currently available catheters of this design: the Shiley Dual Lumen Catheter, and the Quinton-Mahurkar Dual Lumen Catheter. The performance of both catheters, characterised by high blood flow rate capabilities, low venous resistances and minimal recirculation, is superior to that of other types of subclavian haemodialysis cannula.

Aged↗

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↗

Cardiac abnormalities and exercise tolerance in patients receiving renal replacement therapy.

The exercise tolerance of the survivors of a consecutive group of 100 patients in a renal dialysis and transplant programme was compared with the prevalence of cardiac abnormalities detected by exercise testing, echocardiography, and radionuclide angiography. Fifty four patients attended for investigation 27 (SD 7) months after starting renal replacement therapy. Forty three of them (80%) were receiving antihypertensive treatment. Their performance on a bicycle ergometer exercise test was compared with that of 62 normal subjects and the patients divided into five groups of decreasing ability. The exercise tolerance of the patients was very poor, only 17 performing within the normal range. Impairment in exercise capacity was not explained by the type or quality of renal replacement therapy. Fourteen patients developed ischaemic electrocardiographic changes on exercise. Left ventricular ejection fraction was assessed by gated blood pool scanning in 37 patients; all nine of the patients with an abnormally low radionuclide ejection fraction also had abnormal exercise tolerance. Satisfactory M mode echocardiograms were obtained from 45 of the patients, and only two were normal. Left ventricular hypertrophy was detected in 25 (56%) of the echocardiograms, and abnormalities indicating impaired left ventricular function were common and widespread. Grouping all the abnormal cardiac features together for the patients in each exercise group showed a striking linear trend of increasing proportion of cardiac abnormalities with worsening exercise tolerance among the five exercise groups (p less than 0.001). The proportion of patients becoming unemployed within one year of starting renal replacement therapy similarly increased, from nil to 60% from the best exercise group to the most incapacitated. Twenty nine of the original cohort of 100 patients subsequently died, cardiovascular disease accounting for 12 (41%) of these deaths. Diminished exercise tolerance in patients receiving renal replacement therapy is strongly associated with cardiac abnormalities and reduced employment prospects.

Adolescent↗

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↗

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↗

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↗

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↗

Sequential changes in serum lipids and their subfractions in patients receiving continuous ambulatory peritoneal dialysis.

Serum cholesterol, triglycerides and their fractions in high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins were measured sequentially in fasting patients on continuous ambulatory peritoneal dialysis (CAPD) who entered a prospective study. Of the 30 who entered, all have been followed to 3 months, 24 to 6 months and decreasing numbers to 18 months. Serum total cholesterol, VLDL cholesterol, total triglycerides and VLDL triglycerides all rose significantly during the first 6 months and VLDL cholesterol has remained elevated to 18 months. Changes in other fractions have been insignificant or inconsistent. 1 patient has developed angina. No associations were found between use of high dextrose fluid, weight gain and hyperlipidemia, probably because of consistent practice between patients. Our results confirm the adverse effect of CAPD on serum lipids and the need for dietary modification but are broadly similar to the changes that have been observed during regular hemodialysis.

Adolescent↗