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Biomedical subjects

D N Kerr

Publications and source records attributed to D N Kerr.

At least 37 records · Page 2Linked to original sources

Affinity of the aluminium binding protein.

The affinity for aluminium of the binding protein (transferrin) in serum was studied by in vitro ultrafiltration and equilibrium dialysis. It was found that the binding of aluminium to transferrin is very tight and cannot be dissociated by prolonged dialysis or desferrioxamine (DFO). The tight binding of aluminium to transferrin may play a role in the development of microcytic hypochromic anaemia in aluminium intoxicated patients despite the presence of adequate iron.

Aluminum↗

Complement activation in haemodialysis: a comparison of new and re-used dialysers.

The magnitude of leucopenia and complement activation when reusing cellulose based (Cuprophan) and synthetic (polyacrylonitrile AN-69S) haemodialysis membranes as well as their modifications by the priming of the dialysers with fresh frozen plasma and by the introduction of a period of stagnation during haemodialysis were studied using radioimmunoassay (C3a), centrifugal analysis (C3d), immunochemical (C3, Factor B) and functional (CH50 and alternate pathway) assays. Our findings demonstrate that complement activation and leucopenia induced by Cuprophan are linked and are modified when the membrane is reused, or primed with plasma protein. However, chemical exposure during reuse to sodium hypochlorite modifies these observations. Reuse of the AN-69S membrane resulted in no modification of either leucopenia or complement activity, but this membrane consistently demonstrated lower levels of C3a than observed with either first use or reused Cuprophan membranes.

Acrylic Resins↗

Loss of pulsatile luteinising hormone secretion in men with chronic renal failure.

In an attempt to determine the nature of hypothalamic and pituitary dysfunction in renal failure the secretory patterns of luteinising hormone were measured in men with end stage renal disease and compared with those in healthy controls and renal transplant recipients of similar age distribution. Mean luteinising hormone and oestradiol concentrations were significantly higher and the number of luteinising hormone secretory pulses was significantly lower in uraemic men compared with controls. Plasma testosterone and oestradiol concentrations were significantly lower in renal transplant recipients than normal men, but there were no significant differences in mean gonadotropin concentrations or the number of pulses of luteinising hormone between the two groups. As pulses of luteinising hormone are thought to reflect episodic gonadotropin releasing hormone from the hypothalamus these data suggest that uraemia interferes with central mechanisms controlling synchronised release of gonadotropin releasing hormone. This defect appears to be reversible after successful transplantation.

Adult↗

Urographic findings in adults with chronic pyelonephritis.

The radiological findings in a cohort of 138 adults with chronic pyelonephritis are presented and the following conclusions made. Scarring is commoner in the right kidney than the left and is found in the upper, middle and lower poles with decreasing frequency from above down. Agreement between observers in the grading of scarring in urograms taken without standardisation or routine tomography, is sufficiently high to justify the continued use of the intravenous urogram as a screening test but is not high enough to detect any progression of scars in the group over a 6.5-year period. Repetition of urograms seldom reveals the development of calculi or other new abnormalities and is not justified as a clinical routine. The combination of extensive bilateral renal scarring and proteinuria is associated with the worst renal function.

Adult↗

Compensatory renal hypertrophy after donor nephrectomy.

Renal length was measured radiographically in 65 living kidney donors, aged 27-69 years, who had undergone unilateral nephrectomy during the past 20 years. In 34 of these subjects, pre- and post-operative kidney length, glomerular filtration rate (GFR) and blood pressure were available for analysis. Male donors developed greater compensatory hypertrophy than female donors. The extent of renal enlargement correlated negatively with the age of the subject at the time of nephrectomy and with the current mean arterial blood pressure. However, no correlation was found between the percentage change in renal length and either GFR or time since nephrectomy.

Adult↗

Twenty-four hour hormonal and metabolic profiles in uraemic patients before and during treatment with continuous ambulatory peritoneal dialysis.

Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (+/- SEM) levels fell from 6.63 +/- 0.40 to 6.00 +/- 0.26 mmol/l (P less than 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 +/- 0.42 mmol/l before dialysis to 2.02 +/- 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose.

Adult↗

Hyperchloraemia: a non-specific finding in chronic renal failure.

To determine the prevalence of hyperchloraemia (plasma chloride concentration of 107 mmol/l or above) in chronic renal failure (CRF), we retrospectively analysed the acid-base and electrolyte status of 102 Italian and 53 English patients with impaired renal function. Hyperchloraemia was a frequent finding at all stages of CRF with a prevalence ranging from 30 to 50%. It was common both in tubulointerstitial nephropathies (45%) and chronic glomerulonephritis (39%). Hyperchloraemic patients were more acidotic than the normochloraemic.

Acid-Base Equilibrium↗

Renal function and blood pressure after donor nephrectomy.

Pre- and post-nephrectomy renal function and blood pressure were compared in 75 subjects who had donated a kidney for transplantation during the past 20 years. The function of the remaining kidney was not adversely affected by prolonged compensatory hyperfiltration. However, an increased prevalence of hypertension was found in 'long-term' kidney donors.

Blood Pressure↗

Aluminum in the dialysis fluid.

The major source of aluminum in patients with chronic renal failure treated by hemodialysis is the hemodialysis fluid. The aluminum is derived from both the water and the chemical concentrate used in the preparation of the hemodialysis fluid. Due to the complex physico-chemistry of aluminum in water and dialysis fluid, both the total aluminum concentration and the proportion of aluminum species able to cross the hemodialysis membrane may vary from water supply to water supply and from day to day within a supply. A "safe" level of aluminum in dialysis fluid, which will prevent aluminum transfer from dialysis fluid to blood, and promotes aluminum removal from blood, has yet to be determined.

Aluminum↗

Factors influencing normal reference intervals for creatinine, urea, and electrolytes in plasma, as measured with a Beckman Astra 8 Analyzer.

In a study of 514 healthy adults, we used a Beckman Astra 8 Analyzer to establish normal reference intervals for plasma creatinine, urea, and electrolytes. For potassium and chloride these were considerably lower and higher, respectively, than previously reported ranges. All of these analytes showed significant sex-related differences; all except chloride showed age-related changes. The relationship of these biochemical indices to fasting, cigarette smoking, alcohol intake, regular exercise, and the contraceptive pill--independent of these age- and sex-related differences--was assessed by multiple linear regression. The effect was significant in each case. Our results underline the importance of regular review of reference values.

Adolescent↗

Renal osteodystrophy and metastatic calcification in long-term continuous ambulatory peritoneal dialysis.

The biochemical data and drug histories related to bone disease were extracted from the case records of 47 patients who had been treated by continuous ambulatory peritoneal dialysis (CAPD) for more than two years. These data were reviewed in conjunction with the skeletal surveys done over the same period in all patients, with particular reference to secondary hyperparathyroidism, osteomalacia and non-visceral metastatic calcification. Paired bone biopsies were available in 20 of these patients and the histology was quantitated. In the majority of our patients secondary hyperparathyroidism was controlled or improved on CAPD. Osteomalacia also improved in two of the three patients in whom it was initially present and did not develop in any patient whilst on CAPD. We did, however, note a high incidence of non-visceral metastatic calcification. Small vessel calcification developed in 19.6 per cent of patients, large vessel calcification developed in 23.9 per cent and soft tissue calcification developed in 21.7 per cent of patients. We conclude that CAPD, as a form of treatment for end-stage renal disease, satisfactorily controls the osteodystrophy associated with renal failure in the majority of patients. The significance of the high incidence of non-visceral metastatic calcification remains to be established.

Adult↗

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↗