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Biomedical subjects

D N Kerr

Publications and source records attributed to D N Kerr.

At least 19 recordsLinked to original sources

Aluminium intoxication in renal disease.

Aluminium intoxication in renal failure occurred over weeks or months when dialysis fluid or parenteral solutions were heavily contaminated and over many years when the main source was oral administration of aluminium-containing phosphate binders. Encephalopathy was common during subacute intoxication but in slow aluminium poisoning the main brunt was borne by the bones. However, in both tempos of intoxication several organs or systems were involved. Encephalopathy was usually accompanied by bone disease, bone disease by parathyroid suppression and both by anaemia. The heart and the lymphocytes are probably damaged by aluminium overload. Among the many questions left unanswered 15 years after the incrimination of aluminium as the cause of this multi-system illness are: (1) does low level aluminium overload in renal failure cause gradual deterioration in cerebral function? And, if so, (2) does it resemble Alzheimer's disease or a slow-onset version of dialysis encephalopathy? The evidence we review suggests that the answer to (1) is 'yes' and to (2) 'probably the latter'.

Aluminum

Function of the hypothalamo-hypophysial-thyroid axis in chronic renal failure.

Hypothalamo-hypophysial-thyroid function has been studied in twenty-five patients with chronic renal failure. Eight were receiving conservative treatment, nine peritoneal dialysis and eight haemodialysis. All were clinically euthyroid. Total thyroxine (T4) and triiodothyronine (T3) levels were reduced but free T4 levels were normal, while free T3 was reduced in patients with the most severe renal failure. It is suggested that the binding of thyroid hormones by the transport proteins is reduced and that peripheral conversion of T4 to T3 is impaired in renal failure. The thyrotrophin response to thyrotrophin-releasing hormone (TRH) is reduced in renal failure but this reduction is probably independent of alterations in thyroid hormone metabolism. Growth hormone was released by TRH in seven of the patients studied, possibly as a result of protein malnutrition.

Adolescent

Evidence for aluminium accumulation in renal failure.

There is increasing evidence that aluminium accumulation in patients with impaired renal function has pathological consequences. The serum aluminium content of 45 patients with chronic renal failure was found to be significantly elevated when compared with normal subjects. A further rise in serum aluminium concentration was seen in patients with chronic renal failure when they were taking aluminium-containing phosphate binding agents. Patients with stable but moderately impaired renal function who are taking aluminium-containing phosphate binders for several years may be at risk from aluminium accumulation and the development of osteomalacia and encephalopathy as seen in patients on intermittent haemodialysis.

Adolescent

Brain-aluminium concentration in dialysis encephalopathy.

Brain-aluminium concentrations were found to be significantly higher in 7 patients dying with dialysis encephalopathy (mean 15.9 microgram aluminium/g dry weight) than in 11 dialysed controls (4.4 microgram/g) and in 2 uraemic patients who were not dialysed (2.7 microgram/g). The grey matter from the patients with dialysis encephalopathy contained about three times as much aluminium as white matter. The results suggest that dialysis with untreated and/or softened tap-water (aluminium concentration 0.1-1.2 mg/1) makes the major contribution to brain-aluminium levels; dialysis with deionised water (aluminium concentration normally less than 0.02 mg/1) and intake of phosphate-binding AL(OH)3 gel are less important. Brain aluminium levels remain elevated for up to four years after restoration of good renal function by transplantation. The association of dialysis encephalopathy with high levels of aluminium in the brain and in the dialysis water emphasises the potential neurotoxicity of aluminium in man.

Adult

Serum ionised calcium concentration: measurement versus calculation.

Four hundred and eighteen measurements of serum ionised calcium, total calcium, and protein concentrations were made from 47 normal volunteers, 104 patients with chronic renal failure (33 being treated conservatively and 71 with regular haemodialysis), and 83 renal transplant recipients. The serum ionised calcium concentration was measured with an Orion SS-20 meter and calculated from the total serum calcium and protein concentrations by using three formulae and a nomogram. In the normal subjects and patients undergoing regular haemodialysis, whose serum calcium concentrations were in or near the normal range, three of the calculations gave results similar to those obtained by direct measurement. In patients with conservatively treated chronic renal failure and those who had received renal transplants, however, there was poor aggrement between the methods. When patients with hypercalcaemia and hypocalcaemia from all the groups were considered separately there was again poor agreement between calculated and measured concentrations of serum ionised calcium. Of the patients whose measured concentrations of serum ionised calcium were high, 69-76% were classified as normal by the four indirect methods. We conclude that calculation of the serum ionised calcium concentrations is not an adequate substitute for direct measurement.

Blood Proteins

Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium.

In patients maintained on regular haemodialysis in Newcastle upon Tyne the development of osteomalacia is substantially reduced when water used to prepare dialysate is deionised. After 1--4 years of dialysis, osteomalacia was evident in 15% of patients on deionised water in 70% of patients on softened water from the same source. The close association of dialysis encephalopathy and osteomalacia suggests a common aetiology. Both diseases occur in centres with a high tap-water aluminium content. Serum-aluminium concentrations were raised in patients undergoing regular haemodialysis in the Northern Region of England. Those using softened water had higher concentrations than those using deionised water. Patients on softened water who had encephalopathy or dementia had serum-aluminium concentrations similar to those of patients using the same water-supplies without symptoms of these diseases, but they had been treated for longer. The evidence that aluminium absorption from dialysate causes osteomalacia and encephalopathy is strong enough to justify the expense of treating water by deionisation, reverse osmosis, or both in centres where tap-water aluminium is high.

Adolescent

Intellectual impairment in chronic renal failure.

In a dialysis centre with a high tap water aluminium content and a known high incidence of dialysis encephalopathy, 29 patients undertaking regular home dialysis, without clinical evidence of encephalopathy, were studied with a battery of psychological tests that have proved useful in detecting early organic intellectual deterioration in other conditions. Full-scale intelligence quotient, as measured by the Wechsler Adult Intelligence Scale, did not differ significantly from that of the normal population, but the patients showed significant deficiencies in three tests of performance--namely, digit symbol, block design, and picture arrangement. The ability to acquire new information in relation to performance was impaired and the abnormality increased with time on dialysis. Such tests should be useful in early detection of dialysis dementia at a reversible stage.

Adolescent

Choosing the programme for an international congress.

The method of selecting abstracts for an international congress at which only 15% of submitted papers could be accepted entailed a panel of 12 assessors using their specialised knowledge, but presentation of the abstract was also important is selection. There was only a limited agreement between assessors in arranging abstracts in order of merit, so that a single assessor would be unacceptable. Use of the full panel to grade all abstracts was very expensive, but it could be replaced, without unacceptable injustice, by dividing the work randomly among groups of three selectors.

Congresses as Topic

Osteomalacic dialysis osteodystrophy: a trial of phosphate-enriched dialysis fluid.

To assess whether phosphate depletion is an aetiological factor in osteomalacic dialysis osteodystrophy we undertook a prospective trial of phosphate-enriched dialysis fluid, in association with oral 1alpha-hydroxycholecalciferol, for this condition. Thirty patients started the trial; of the 27 who completed more than 6 months' treatment, 14 had iliac crest bone biopsies at the beginning and end of the treatment period. Side effects included pruritus, stiffness, and increase in corneal and vascular calcification. Only one patient showed histological improvement of osteomalacia, and eight deteriorated; in seven the osteitis fibrosa worsened. Myopathy showed some improvement in four patients, but became worse in four. This treatment does not seem to have a place in the routine management of non-hypophosphataemic patients on dialysis.

Adolescent

Determination of serum ionised calcium by ion-exchange electrode in normal subjects.

Serum ionised calcium concentration [Ca2+] was measured with a calcium selective electrode in 65 normal people. A mean value of 1.06 mmol/l (+/- 0.04 S.D.) with an actual range of 0.97 to 1.13 mmol/l was obtained. Serum samples refrigerated at 4 degrees C for 24 h were satisfactory for analysis. Storage of whole blood samples for 6 h at room temperature before separation caused a very small error (+0.04 mmol/l). Mean results and ranges were similar in males and females and there was no significant correlation with age. No significant change in serum [Ca2+] was found following a normal meal. Serum [Ca2+] and total serum calcium showed a very slight correlation (r = 0.35). The method is reproducible and sensitive.

Age Factors

Hemodialysis bone disease: correlation between clinical, histologic, and other findings.

This paper explores in patients with dialysis osteodystrophy the relationship between clinical features and histological, radiological, and biochemical findings. Eighty-five patients treated by hemodialysis for more than 6 months were studied. The following conclusions were drawn: 1) Bone pain in patients on regular hemodialysis is usually a symptom of developing osteomalacia but not of hyperparathyroidism or osteoporosis. 2) Many patients with histological osteomalacia and radiological features of osteomalacia, such as fractures or Looser zones, have no symptoms. 3)In dialysis patients, biochemical and radiological abnormalities are not a reliable means of predicting the presence of osteomalacia, but a raised serum alkaline phosphatase is a good indicator of the presence of osteitis fibrosa. For early detection of osteomalacia, bone biopsy in necessary. 4)A number of our dialysis patients develop an unusual form of osteomalacia characterized by absent or minimal histological osteitis fibrosa, a normal serum alkaline phosphatase, and a high incidence of myopathy and fractures.

Adolescent

Congenital hepatic fibrosis: the long-term prognosis.

The long-term prognosis in congenital hepatic fibrosis has been assessed in 30 patients, 13 treated at Newcastle and 17 from other British centres. Twenty-four patients had been followed-up for more than five years from diagnosis. Shunt operations, performed in 18 patients, were successful in controlling haemorrhage with a low mortality (1/18), low incidence of recurrent haemorrhage (3/18) and portal-systemic encephalopathy (3/18) but with a higher incidence of postoperative jaundice (7/18). About a third of the survivors had some evidence of hepatic dysfunction but none had chronic portal systemic encephalopathy. Intelligence quotient was close to normal but educational achievement and job status were low. Serum albumin fell after shunt surgery and a few patients developed ascites: anaemia and hypersplenism however, were corrected by surgery. Blood ammonia is raised in survivors with congenital hepatic fibrosis and rises further after a normal meal; further observations are needed on cerebral function after several decades of survival.

Adolescent

Effect of 1alpha-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, 3 deoxy-1alpha-hydroxycholecalciferol, 24R, 25-dihydroxycholecalciferol and successful renal transplantation on calcium absorption in haemodialysis patients.

Using a 2-hour 47Ca absorption test, significant depression of active calcium absorption was demonstrated in 48 vitamin D untreated haemodialysis patients. This malabsorption of calcium could be corrected by the daily oral administration of 1--2 microgram of 1alphaOHD3 and 1--1.5 microgram of 1,25(OH)2D3. 5 microgram daily for 2 weeks of 3-deoxy-1alphaOHD3 AND 16 and 64 microgram daily for 1 week of 24R,25(OH)2D3 proved ineffective. In 32 successfully transplanted patients, restoration of normal or near normal renal function (serum creatinine less than 1.9 mg/100 ml) was not always followed by an immediate improvement in active calcium absorption. Calcium absorption, especially in female patients, was adversely affected by the required immunosuppressive prednisone therapy and improvement was slow.

Absorption