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Biomedical subjects

N A Hamdy

Publications and source records attributed to N A Hamdy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Serum type I procollagen peptide: a non-invasive index of bone formation in patients on haemodialysis?

The value of serum procollagen peptide (PICP) as a non-invasive index of bone formation was studied in 18 patients established on haemodialysis. There was a significant correlation between PICP and serum alkaline phosphatase activity (ALP; r = 0.55, P < 0.05), and between PICP and osteocalcin (r = 0.53, P < 0.05). PICP also correlated significantly with histomorphometric indices of bone formation, particularly bone formation rates (BFR) as estimated by the tetracycline double-labelled technique (r = 0.74, P < 0.01), but not with those of bone resorption. There was a similar relationship between BFR and ALP. From the regression analyses, a normal BFR was associated with normal PICP values despite the absence of renal function, suggesting that the impact of renal function on serum concentrations of PICP may not be large. Seven patients had histochemical evidence for significant aluminum overload. In these patients the expected suppression in biochemical and histological indices of bone formation was associated with inappropriately raised PICP concentrations. The mechanism of this discrepancy is not clear, but caution is advocated in the interpretation of PICP in the presence of significant aluminium overload. Our findings otherwise suggest that PICP may be a useful non-invasive index of bone formation in patients on haemodialysis.

Adolescent↗
PubMed1994

Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN: Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS: Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-cAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid malignancies and hypercalcaemia and bone scans were performed. RESULTS: In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)2D concentrations were not appropriately suppressed (> 92 pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1.6 pmol/l) had lower serum 1,25-(OH)2D concentrations than those with elevated levels (> 1.6 pmol/l) (47 +/- 6 vs 70 +/- 7 pmol/l, respectively; P < 0.04). Serum 1,25-(OH)2D concentrations were higher in patients with negative bone scans than in those with metastatic bone disease (80 +/- 9 vs 50 +/- 5 pmol/l; P < 0.01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25-(OH)2D (r = 0.51; P < 0.03) whereas there was no such correlation in those with a positive scan. CONCLUSION: Contrary to current belief, serum 1,25-(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.

Aged↗
PubMed1993

Urinary collagen crosslink excretion: a better index of bone resorption than hydroxyproline in Paget's disease of bone?

The 24 h urinary excretion of the collagen degradation products pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been proposed as specific and quantitative indices of bone resorption. We compared the value of the urinary excretion of Pyr and Dpyr to that of hydroxyproline (OHP) in 11 patients with Paget's disease of bone before and during treatment with inhibitors of bone resorption, during admission to a metabolic ward and maintenance on a gelatin-free diet. Pyr and Dpyr excretion rates were significantly correlated with those of OHP (r = 0.81 and 0.77, respectively, P < 0.001; n = 106). The rate and degree of suppression of bone resorption were monitored in 6 of the patients similarly treated with intravenous dimethyl-APD at a dose of 4 mg/day for 10 days, by daily measurements of the 24 h urinary excretion of Pyr, Dpyr and OHP. Treatment with dimethyl-APD resulted in a decrease in the three indices of bone resorption. The percentage change from baseline values was similar for the three indices, although changes in Dpyr appeared to follow more closely those of OHP. Our findings suggest that Pyr and Dpyr are useful and specific indices of bone resorption in Paget's disease of bone. They appear to confer no advantage, however, over the traditional determination of the urinary excretion of OHP, in the monitoring of response to treatment of such patients with inhibitors of bone resorption. Further studies are required to establish the value of these new biochemical indices of bone resorption, possibly in more subtle disorders of bone metabolism such as osteoporosis.

Amino Acids↗
PubMed1991

Scintigraphy in the clinical evaluation of disorders of mineral and skeletal metabolism in renal failure.

In patients with renal bone disease skeletal and extra-skeletal abnormalities can be visualised using conventional bone scintigraphy. Some of these abnormalities are associated with characteristic scintigraphic appearances, which are reviewed in detail, and the possible mechanisms involved are discussed. Specific imaging with iodine 123 serum amyloid P component and iodine 131 beta 2-microglobulin is also discussed in the diagnosis of beta 2-microglobulin amyloidosis specific to patients on dialysis. In the light of available evidence, it appears that bone scintigraphy plays, so far, a limited role in the clinical evaluation of skeletal and extra-skeletal abnormalities in chronic renal failure. The potential role of bone scintigraphy in identifying patients with aluminium-related bone disease needs to be investigated further, and in this respect special attention must be given to the problem of high soft-tissue activity associated with impaired renal function. Timing haemodialysis sessions before scintigraphic imaging deserves wider recognition as it reduces high soft-tissue activity, thereby allowing bone uptake to be assessed more accurately. Specific imaging of amyloidosis resulting from beta 2-microglobulin deposition is a promising technique, but the relative value of the two proposed radiopharmaceuticals needs further clarification.

Amyloidosis↗
PubMed1991

Effects of amino-butylidene diphosphonate in hypercalcemia due to malignancy.

We studied the effect of a single 5 mg intravenous infusion of amino-butylidene diphosphonate (ABDP) in nine patients with hypercalcemia of malignancy, in whom serum calcium values were stable or rising after intravascular volume expansion. Serum calcium fell progressively in all patients and in seven reached the normal reference range by day 6 (p less than 0.001). The decrease in serum calcium was associated with a decrease in the fasting urinary calcium/creatinine ratio (p less than 0.05). Hypercalcemia recurred in seven of the patients by day 12, but two patients remained normocalcemic for 21 days. We conclude that ABDP is a highly potent diphosphonate and that a single intravenous infusion is capable of inhibiting tumour-mediated bone resorption for several days.

Adult↗
PubMed1990

Treatment of Paget's disease of bone with aminohydroxybutylidene bisphosphonate.

This study examined the effects of aminohydroxybutylidene bisphosphonate in 30 patients with Paget's disease of bone, administered as an intravenous infusion for 5 consecutive days. Treatment (5 mg IV daily) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 50% of pretreatment values within 2 weeks and was followed by a similar, but later, decline in the serum activity of alkaline phosphatase. Disease activity remained suppressed throughout the 6 months of observation, and only 1 patients showed biochemical signs of an early relapse. Symptomatic improvement was noted in 27 of the 30 patients. Bone biopsies, undertaken in 10 patients, indicated no adverse effects on mineralization. Transient falls were noted in the total white cell count, particularly the lymphocyte and neutrophil fractions, and were associated with short-lived fever in 3 patients. We conclude that short courses of intravenous AHButBP provide a promising treatment for active Paget's disease of bone.

Aged↗
PubMed1990

A comparison of the acute effects of subcutaneous and intranasal calcitonin.

1. We studied the acute effects of intranasal and subcutaneous calcitonin in 40 patients with active Paget's disease of bone. Patients received a single dose of either 400 units of calcitonin delivered as a nasal spray, or 1, 10 or 100 units of subcutaneous calcitonin, or placebo. 2. Subcutaneous salmon calcitonin, administered at doses of 1, 10 and 100 units to nine patients with Paget's disease of bone, induced a dose-dependent fall in the serum calcium. This calcium-lowering effect was not seen with a second group of nine patients receiving placebo. 3. The lower doses of calcitonin had significant effects, and these were more pronounced in patients with lower rates of bone turnover. 4. Four hundred units of calcitonin administered as a nasal spray induced effects qualitatively similar to those seen with subcutaneous calcitonin, with an efficacy equivalent to approximately 30 units of subcutaneous calcitonin. 5. We conclude that the bioequivalence of calcitonin given by intranasal insufflation is low compared with its parenteral administration. The intranasal route may be more appropriate for managing patients with disorders associated with low bone turnover.

Administration, Intranasal↗
PubMed1990

Broadband ultrasound attenuation in the os calcis: relationship to bone mineral at other skeletal sites.

1. We have examined the relationship between broadband ultrasound attenuation in the os calcis and measurements of bone mineral in the distal forearm and lumbar spine of normal and postmenopausal osteoporotic women. 2. Values of broadband ultrasound attenuation in postmenopausal women with vertebral osteoporotic fractures were significantly lower (35%) than in normal pre- and peri-menopausal women (55.4 +/- 3.8 and 79.6 +/- 0.8 dB/MHz, respectively). 3. Broadband ultrasound attenuation correlated significantly with bone mineral content measured in the distal forearm by single-photon absorptiometry (r = 0.77, P less than 0.0001) and with bone mineral content (r = 0.66, P less than 0.0001) and bone mineral density (r = 0.72, P less than 0.0001) measured in the lumbar spine by dual-photon absorptiometry. 4. Although significant, these correlations are not sufficiently close to be predictive. However, the accuracy of broadband ultrasound attenuation in discriminating between normal subjects and patients with vertebral fracture compared very favourably with direct measurements in the spine by dual-photon absorptiometry. 5. Broadband ultrasound attenuation, but not the other measurements, correlated significantly with age in the osteoporotic patients (r = 0.50, P less than 0.05). 6. These findings may reflect the partial dependence of broadband ultrasound attenuation on the intrinsic trabecular architecture of cancellous bone, the disruption of which contributes to an increase in fracture risk.

Absorptiometry, Photon↗
PubMed1990

Effects of clodronate in severe hyperparathyroid bone disease in chronic renal failure.

We have examined the effects of the diphosphonate, clodronate, in 9 haemodialysis patients with severe hyperparathyroid bone disease. Clodronate (300-600 mg infused after dialysis on 5 consecutive occasions) significantly decreased mean serum calcium, phosphate and hydroxyproline. This was associated with an increase in serum immunoassayable parathyroid hormone and activity of alkaline phosphatase. These changes reversed 2-4 weeks after stopping treatment but were sustained when treatment with oral clodronate (1.6 g daily) was supplemented for 2 weeks. Our findings suggest that intravenous clodronate is capable of inhibiting osteoclast-mediated bone resorption in chronic renal failure. The therapeutic potential of clodronate alone or with vitamin D derivatives merits further evaluation, particularly in patients with severe hyperparathyroidism, when the use of D metabolites alone is precluded by the presence of hypercalcaemia.

Administration, Oral↗
PubMed1989

Intravenous calcitriol lowers serum calcium concentrations in uraemic patients with severe hyperparathyroidism and hypercalcaemia.

We studied the effects of intravenous calcitriol in four persistently hypercalcaemic patients established on haemodialysis. All had marked hyperparathyroidism and had been previously shown to be intolerant to vitamin D by mouth. Calcitriol was administered at the end of each dialysis session in doses of 0.5-2.5 micrograms for 2 months and continued for 7 and 8 months in two patients. A significant decrease in serum calcium was observed after 2 weeks, which was maintained throughout treatment despite increasing the dose of calcitriol. This was associated with a decrease in serum concentrations of iPTH (28% of the initial value at 4 weeks), suggesting a shift in the set-point for PTH secretion. During longer-term treatment, serum calcium values increased, but lower concentrations of iPTH were maintained. We conclude that an increment in serum calcium is not a prerequisite for the suppressive action of calcitriol on parathyroid secretion and that the presence of hypercalcaemia does not preclude its use. Longer-term studies on a larger number of patients are required to assess the therapeutic potential of intravenous calcitriol in hypercalcaemic patients.

Adult↗
PubMed1989

Phosphate binding efficiency of a polyuronic acid in normal subjects.

We evaluated the phosphate-binding efficiency of Sorbiphos, a non-toxic aluminium-free natural polymer, in five volunteers aged 28-34 years with normal renal function. After an overnight fast, a placebo, 2 g of Sorbiphos or a therapeutic dose of Alu-Cap (950 mg) were given, 30 min before a dietary load of phosphorus. Serum and urinary phosphate were measured on hourly samples. A similar increment in serum and urine phosphate was noted after the ingestion of placebo or Sorbiphos, but both serum and urine phosphate increased less after Alu-Cap. Since the recommended dose of Sorbiphos is half that of Alu-Cap, we conclude that Sorbiphos has little phosphate-binding efficiency in normal subjects given moderate phosphate loads.

Adult↗
PubMed1988

Renal osteodystrophy.

Over the past decade important advances in our understanding of the pathophysiology and treatment of renal osteodystrophy have been made. In particular, the role of calcitriol deficiency in the genesis of hyperparathyroidism in early renal failure is now better understood. So too are the effects of aluminium on bone, and whereas the more florid aluminium related disease is now unusual the more subtle effects of aluminium are now being appreciated. There is still a major problem in the long-term treatment of hyperparathyroid bone disease. The reasons why parathyroid gland proliferation continues to occur on dialysis therapy require a better understanding of cellular events regulating hormone production and parathyroid cell replication. The case for early intervention with vitamin D is now strong but whether such an approach materially influences the long-term outcome is not yet established. Changes in the approach to treatment and in the modalities used for renal replacement therapy will continue to modify the nature of the bone disease.

Aluminum↗
PubMed1988

Diphosphonates and phosphate homoeostasis in man.

1. The effects of three intravenous diphosphonates (etidronate, clodronate and aminohexane diphosphonate) on phosphate homoeostasis were studied in 30 patients with Paget's disease of bone and in three patients with hypoparathyroidism. 2. In Paget's disease, all three diphosphonates induced significant increases in serum phosphate and renal tubular reabsorption of phosphate. This effect was most marked and persistent after etidronate, whereas in the clodronate- and aminohexane diphosphonate-treated patients the increases were less, of shorter duration and followed thereafter by significant decreases in serum phosphate and renal tubular reabsorption of phosphate. Unlike etidronate, both clodronate and aminohexane diphosphonate caused a significant reduction in serum and urinary calcium, with appropriate homoeostatic increases in immunoassayable parathyroid hormone. 3. Phosphaturic responses to infused parathyroid hormone were observed in two patients with etidronate-induced hyperphosphataemia. 4. In three hypoparathyroid patients, clodronate induced a more marked increase in serum phosphate and renal tubular reabsorption of phosphate than in Paget's disease, which was of comparable degree but of shorter duration than that after etidronate in Paget's disease. 5. These findings suggest that all three diphosphonates increase renal tubular reabsorption of phosphate, but that this effect is attenuated with those diphosphonates which induce secondary hyperparathyroidism.

Diphosphonates↗