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Biomedical subjects

A M Pierides

Publications and source records attributed to A M Pierides.

At least 19 recordsLinked to original sources

Serum alkaline phosphatase in azotemic and hemodialysis osteodystrophy: a study of isoenzyme patterns, their correlation with bone histology, and their changes in response to treatment with 1alphaOHD3 and 1,25(OH)2D3.

One hundren seventy-eight azotemic patients, 114 on hemodialysis, had measurements of total serum ALP, and definition of isoenzyme patterns on acrylamide gel electrophoresis. In addition, bone histomorphometry was defined in all of the patients by means of transiliac bone biopsies. Serial estimations over 2 years were carried out on several patients, including some being treated with vitamin D2, 1alphaOHD3, and 1,25(OH)2D3. (1) In both nondialyzed and dialyzed patients, serum ALP showed a significant positive correlation with osteitis fibrosa due to secondary hyperparathyroidism irrespective of the presence or absence of concurrent osteomalacia. Increases in the bone isoenzyme were largely responsible for the rise in total ALP. (2) A higher incidence of osteomalacia (p less than 0.001) was observed in patients on hemodialysis in Newcastle Upon Tyne. In hemodialyzed patients where osteomalacia was accompanied by either no secondary hyperparathyroidism (21 patients) or minimal secondary hyperparathyroidism (14 patients), serum ALP remained within normal limits, giving no indication of the existing osteomalacic bone disease. Isoenzyme studies revealed a high prevalence of the intestinal type and also varied combinations of hepatic, intestinal, and bone types. (3) Good response to vitamin D depended on the presence of significant amounts of the bone isoenzyme. Azotemic osteodystrophy characterized by a raised serum ALP and a prominent bone isoenzyme predicted a good response to vitamin D, and the decrease in serum ALP following vitamin D was the result of a reduction in the bone isoenzyme. Patients with symptomatic dialysis osteomalacic bone disease, accompanied by normal total serum ALP and no elevation of the bone isoenzyme, responded less well.

Alkaline Phosphatase

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

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

Ultrafiltration followed by haemodialysis. A longterm trial and acute studies.

Separate ultrafiltration followed by haemodialysis (U.F.-H.D.) using Gambro Major or Cordis-Dow hollow-fiber dialyzers were evaluated in 10 dialysis patients over a mean period of 4 1/2 months and 455 U.F.-H.D. procedures. Fluid control was facilitated in oedematous patients but the number of hypotensive episodes during the combined procedure requiring intravenous 5% saline did not significantly decrease. No significant improvement in hypertension was noted. Ultrafiltration (U.F.) alone for acutely water overloaded, azotaemic patients proved very useful. Two to five liters of oedema fluid could be removed asymptomatically in one to three hours using transmembrane pressures of 250 to 500 mmHg and U.F. rates of 10 to 42 ml/min. Two patients became acutely and symptomatically hypotensive. One was an insulin dependent diabetic in whom 3800 ml were removed in 75 minutes and the other a hypertensive patient undergoing treatment with Minoxidil and propranolol.

Diabetes Mellitus, Type 1

Serum ferritin concentration: a reliable guide to iron overload in uremic and hemodialyzed patients.

The inter-relationships between serum ferritin, hemoglobin, serum iron and total body iron stores were studied in 20 patients with chronic renal failure treated conservatively and in 20 patients on regular hemodialysis. There was no relationship between serum iron or transferrin and bone marrow iron deposits, but serum ferritin concentration was a good indicator of increased marrow iron stores. All patients with serum ferritin levels above 300 microgram/l had increased iron stores. Serum ferritin assay is a useful non-invasive technique for detecting iron overload in uremic and hemodialyzed patients.

Adolescent

Serum gamma-glutamyl transferase activity in chronic renal failure during regular hemodialysis and after successful renal transplantation.

Serum gamma-glutamyl transferase activity (gamma-GT) was measured in 108 uraemic patients, 110 patients on regular haemodialysis and 71 sucessfully transplanted patients. The incidence of abnormal results was 11, 14 and 28%, respectively. The results in the non-dialyzed and dialyzed patients indicate that in uraemia serum gamma-GT activity remains normal and as such, significant hepatic microsomal enzyme induction does not appear to occur. Raised serum gamma-GT in uraemic patients and after renal transplantation should suggest concurrent, added, pathology such as hepatobiliary disease or the administration of hepatic microsomal enzyme inducing drugs.

Creatinine

Seasonal variation of serum 25-hydroxyvitamin D in patients with chronic renal failure treated by regular haemodialysis.

Serum 25-hydroxyvitamin D was measured by a competitive protein-binding assay in 44 normal subjects, 60 uraemic patients on regular haemodialysis at different times of the year and in 13 non-dialyzed uraemic patients. The results obtained indicate that uraemic patients on regular haemodialysis have a mean serum 25-hydroxyvitamin D concentration comparable to controls and that they also exhibit a seasonal variation with a significant reduction during the winter months. However, serum 25-hydroxyvitamin D concentration remained essentially within the normal range and did not reflect the increased incidence of osteomalacia in these patients. In the 13 non-dialyzed uraemic patients, serum 25-hydroxyvitamin D concentrations were lower than in the dialyzed patients, but the explanation is not yet clear. This reduction in serum 25-hydroxyvitamin D was not accompanied by any osteomalacia. The results indicate that deficiency of 25-hydroxyvitamin D in our patients on regular haemodialysis is uncommon and clearly not the explanation of dialysis osteomalacia.

Carrier Proteins

The need and use of a phosphate-enriched dialysate during regular hemodialysis.

A disabling osteomalacic syndrome seen only during regular hemodialysis is described. Its features include skeletal fractures, pain, suppression of pre-existing hyperparathyroidism, and failure to improve with any of the vitamin-D metabolites. Phosphate depletion may be an important etiological factor but this could not explain all cases. A trial with phosphate-enriched dialysate and 1alphaOHD3 resulted in sustained clinical improvement in 54% of the patients and healing of fractures in 33%. Other etiological factors independent of 1,25(OH)2D3 deficiency and phosphate depletion must be considered. Current, indirect evidence suggests that accumulation of water toxins including aluminium may be important.

Adolescent

Histopathology of renal osteodystrophy with particular reference to the effects of 1alpha-hydroxyvitamin D3 in patients treated by long-term haemodialysis.

(1) The bone histology of 233 non-dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non-dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non-dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty-six haemodialysed patients with 1alpha-hydroxyvitamin D3 (1alpha-OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25-dihydroxyvitamin D3 deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, 1alpha-OHD3 therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred alone (Group IIb).

Adolescent

The effect of 1alpha-hydroxyvitamin D3 in pre-dialysis renal bone disease.

Assessment of 18 azotaemic patients treated with long-term 1alpha-hydroxyvitamin D3 (1alpha-OHD3) confirms the generally favourable effect of this analogue of 1,25-dihydroxyvitamin D3 in azotaemic osteodystrophy. Growing children with radiological rickets respond very well as do adults showing mild hyperparathyroidism with or without osteomalacia. However, patients with severe 'pure' hyperparathyroidism and features of autonomy do not respond well and in such patients 1alpha-OHD3 alone should be avoided. Phosphate restriction and occasionally a sub-total parathyroidectomy may be indicated in these patients.

Adolescent

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy.

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.

Adolescent

Effect of renal transplantation on marrow mast cell hyperplasia of chronic renal failure.

Marrow mast cells have been counted in iliac bone from patients with chronic renal failure treated by renal transplantation. Mast cell numbers were initially increased but returned to the normal range in many patients after renal transplantation. Improvement in osteitis fibrosa and osteomalacia after transplant was not clearly related to this diminution in the number of mast cells. The use of prednisone in renal transplant patients may have some effect in reducing the numbers of mast cells. There is no fully acceptable explanation for the increase in marrow mast cells which occurs in chronic renal failure.

Bone Marrow

Photon absorptiometry of bone after successful renal transplantation.

Photon absorptiometric measurements of the right lower femur were carried out at regular intervals of one to three months in 58 recipients of renal transplant. (1) During the first six months after transplant 57% showed a significant and abnormal rate of loss of bone mineral (mean 11.7% per year. +/- 1.1% S.E.M.) while 30 months' after transplantation only 17% showed such a significant loss (p=0.025). (2) Eighteen months after transplantation both male and female recipients of transplants had a significantly lower mean bone mineral index than controls (p less than 0.001). (3) Male patients who developed new post-transplant fractures had a lower mean bone mineral content compared with age and sex-matched controls taken from transplant recipients without such fractures (p less than 0.01). Similarly male patients with post-transplant fractures had a significantly longer mean period on regular haemodialysis (p less than 0.05) compared with patients without such fractures. Regular photon absorptiometric measurements provide an accurate, informative and non-invasive technique for following changes of bone mineral content after successful renal transplantation.

Bone Diseases