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Biomedical subjects

S E Papapoulos

Publications and source records attributed to S E Papapoulos.

At least 127 records · Page 7Linked to original sources
PubMed1986

Effects of decreasing serum calcium on circulating parathyroid hormone and vitamin D metabolites in normocalcaemic and hypercalcaemic patients treated with APD.

The changes of parathyroid hormone (PTH) and of vitamin D metabolites after intravenous administration of the bisphosphonate APD were studied in ten patients with Paget's disease of bone and in ten patients with tumour-induced hypercalcaemia. After APD all patients with Paget's disease became hypocalcaemic and showed an increase in both N-PTH and C-PTH values. Patients with malignancies had a nearly six-fold greater decrease in serum calcium but rises in N-PTH and C-PTH were observed only in those who developed hypocalcaemia. Overall, a clear rise in PTH was found when serum calcium fell below 2.20 mmol/l. Basal 25-hydroxy- and 24,25-dihydroxyvitamin D concentrations were similar in the two groups and showed no change after APD treatment. Circulating 1,25-dihydroxyvitamin D, however, increased in all patients with Paget's disease and in six of the hypercalcaemic patients. It is concluded that the main regulator of PTH secretion is the concentration of calcium per se rather than the magnitude or the rate of its change. The production of 24,25-dihydroxyvitamin D is not affected by wide variations in serum calcium while that of 1,25-dihydroxyvitamin D is sensitive to these changes.

Calcium↗
PubMed1985

Effect of renal function on renal responsiveness to parathyroid hormone in primary hyperparathyroidism and chronic renal failure.

The effect of renal function on the cyclic AMP (cAMP) response to exogenous parathyroid hormone (PTH) was examined in patients with chronic renal failure (n = 22) and primary hyperparathyroidism (n = 19). In the patients with chronic renal failure there was marked resistance to the effect of exogenous PTH. In primary hyperparathyroidism the cAMP responses were variable; most of the patients with an abnormally small response having impaired renal function. After parathyroidectomy, responsiveness improved to varying degrees. In three patients repeatedly tested up to several months after parathyroidectomy, the recovery of responsiveness was a gradual process which began within days but did not, however, return to normal. Thus, there was an irreversible component to the resistance to PTH in these patients. A strong negative correlation between plasma creatinine and the cAMP response to PTH (P less than 0.001) was found in a group of patients, some with treated primary hyperparathyroidism and some with chronic renal failure. Thus, renal impairment is an important, but probably not the sole, contributory factor involved in the irreversible resistance to the action of PTH in hyperparathyroidism.

Adolescent↗
PubMed1985

Characteristics and bisphosphonate treatment of a patient with juvenile osteoporosis.

We studied a 13 1/2-yr-old boy with severe juvenile osteoporosis and multiple metaphyseal and vertebral fractures. Biochemically, there was evidence of non-PTH mediated excessive bone resorption, low intestinal calcium absorption, and a strikingly negative calcium balance. He was treated with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate, a bisphosphonate capable of inhibiting bone resorption rapidly, and had dramatic clinical and biochemical improvement. All indices of resorption were normal within a week after initiation of therapy and his 1,25-dihydroxyvitamin D concentration, which was only 9.6 pg/ml before treatment, rose to 62.4 pg/ml. These changes were associated with an increase in calcium absorption and positive calcium balance. Radiological improvement with healing of metaphyseal and one diaphyseal fractures and signs of sclerosis near the growth plates of the affected metaphyses and at the end plates of the vertebrae also occurred. (3-Amino-1-hydroxypropylidene)-1,1-bisphosphonate, therefore, with its rapid suppression of resorption and the accompanying hormonal changes, is a very effective treatment for juvenile osteoporosis. The primary defect of this obscure syndrome seems to be uncontrolled activity of metaphyseal osteoclasts; disturbances of vitamin D metabolism and of intestinal calcium absorption are secondary events.

Adolescent↗
PubMed1983

Controlled trial of calcitriol in the prevention of bone disease in haemodialysed patients.

Seventy-six patients receiving regular haemodialysis, without biochemical or radiological evidence of renal osteodystrophy, entered a five-year double-blind placebo-controlled trial of calcitriol (1,25-dihydroxycholecalciferol) in the prevention of bone disease. Significantly more patients on placebo developed bone disease as judged by a sustained elevation of plasma alkaline phosphatase or the development of sub-periosteal erosions on hand radiographs. Serum parathyroid hormone fell significantly in the patients receiving calcitriol and was significantly lower than in patients receiving placebo. It is concluded that calcitriol delays and may prevent the development of metabolic bone disease in patients receiving regular haemodialysis therapy.

Adolescent↗
PubMed1982

Regulation of calcium absorption by 1,25,dihydroxy-vitamin D--studies of the effects of a bisphosphonate treatment.

In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and 1,25-dihydroxy-vitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P less than 0.001) to the serum calcium (r = 0.66), the serum phosphate (r = 0.78), and the serum PTH (r = 0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r = 0.74) and calcium balance (r = 0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis.

Aged↗
PubMed1982

Chronic acidosis with metabolic bone disease. Effect of alkali on bone morphology and vitamin D metabolism.

Chronic metabolic acidosis and osteomalacia developed in two patients following urinary diversion. Good clinical, biochemical, and histologic responses were seen following treatment with alkali alone (vitamin D was not given), despite the presence of markedly impaired glomerular filtration in one of the patients. Plasma 25-hydroxyvitamin D and 1 alpha, 25-dihydroxyvitamin D concentrations were normal before and during treatment in one of the patients and in the other were low before and normal during treatment. The results show that successful treatment of the osteomalacia of chronic acidosis is not necessarily accompanied by changes in the plasma levels of vitamin D metabolites and that even when marked glomerular dysfunction coexists with acidosis and osteomalacia, treatment with alkali may be more appropriate than the administration of vitamin D analogues.

Acidosis↗
PubMed1982

Reversible resistance to the renal action of parathyroid hormone in human vitamin D deficiency.

1. The response to exogenous parathyroid hormone (PTH) was tested in normal subjects and patients with osteomalacia due to vitamin D deficiency; 200 MRC units of bovine PTH were administered intravenously. 2. The rise in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) and the increase in urinary excretion of cyclic AMP were reduced in the patients with vitamin D deficiency. After treatment with vitamin D the responses returned to normal. 3. It is suggested that this reversible resistance is due to the secondary hyperparathyroidism associated with vitamin D deficiency.

25-Hydroxyvitamin D 2↗
PubMed1982

The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose.

1. 1,25- Dihydroxycholecalciferol [1,25-(OH)2D3] was administered orally to four normal subjects and six patients with chronic renal failure not on dialysis. The serum concentration of 1,25-(OH)2D3 was measured by radioimmunoassay in both groups from samples taken before, and at regular intervals up to 48 h after, the oral dose. 2. The plasma half-time for the disappearance of the administered 1,25-(OH)2D3 was estimated by determining the time for a 50% reduction from the peak increment of the sterol. In normal subjects the calculated value ranged from 5 to 8 h compared with 18 to 44 h in uraemic patients. 3. It appears from our studies that in uraemic subjects there is impaired ability to metabolize or excrete 1,25-(OH)2D3.

Adult↗
PubMed1982

Long-term experience of alfacalcidol in renal osteodystrophy.

Thirteen patients receiving regular haemodialysis, with biochemical or radiological evidence of renal osteodystrophy, were treated with alfacalcidol (1 alpha hydroxy vitamin D3) for four years. During the first eighteen months of treatment plasma alkaline phosphatase and serum parathyroid hormone concentrations fell and subperiosteal phalangeal erosions improved. Thereafter plasma alkaline phosphatase and serum parathyroid hormone concentrations rose and after four years' treatment only four patients had a normal plasma alkaline phosphatase, only five a normal serum parathyroid hormone level and in only six had the erosions healed completely. Hypercalcaemia occurred in twelve patients, plasma calcium exceeding 3.0 mmol/l in ten. Plasma calcium rose abruptly close to the time when plasma alkaline phosphatase became normal and often remained raised despite reduction in dosage of alfacalcidol. We have reservations about the ultimate value of long-term treatment with alfacalcidol in haemodialysed patients with renal osteodystrophy and urge caution in its use.

Adult↗
PubMed1980

Metabolites of vitamin D in human vitamin-D deficiency: effect of vitamin D3 or 1,25-dihydroxycholecalciferol.

Circulating concentrations of hydroxylated metabolites of vitamin D were measured in seven Asian patients with histologically proven osteomalacia before and during treatment with either cholecalciferol (vitamin D3) or 1,25-dihydroxycholecalciferol. All patients showed an excellent clinical and biochemical response to treatment irrespective of type of vitamin D administered. Circulating concentrations of 25-hydroxycholecalciferol and 24,25, 25,26, and 1,25 dihydroxycholecalciferols were abnormally low in the untreated patients. In five patients treated with small doses of cholecalciferol (3000 units, 75 micrograms daily) the concentration of 1,25-dihydroxycholecalciferol rose rapidly to normal and reached supra-normal levels within 72 h. Raised concentrations (up to 200 pg/ml) were sustained for several months and then started falling to normal. Serum 24,25 and 25,26 dihydroxycholecalciferols rose only gradually, after circulating 25-hydroxycholecalciferol concentration had increased to normal. In contrast, in the two patients who received 1,25-dihydroxycholecalciferol (1 microgram daily) serum concentrations of this metabolite rose to normal and only occasionally exceeded the upper limit of normal. The highest concentration observed was 80 pg/ml. Healing of osteomalacia occurred, however, in these two patients in the absence of any measurable increases in 25-hydroxycholecalciferol and 24,25 or 25,26 dihydroxycholecalciferols which all remained abnormally low. Thus, it seems that 1,25-dihydroxycholecalciferol is the most important factor for the healing of vitamin D-deficient osteomalacia and that other hydroxy metabolites are unimportant.

Adolescent↗
PubMed1980

End-organ resistance to 1,25-dihydroxycholecalciferol.

A 13-year-old girl with total alopecia who in infancy had rickets unresponsive to large doses of vitamin D2 is described. She had profound hypocalcaemia which was resistant to treatment with high doses of dihydrotachysterol, 1 alpha-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol. Serum concentrations of 25-hydroxyvitamin D were normal but those of 1,25-dihydroxycholecalciferol were markedly raised (674 and 745 pg/ml). In addition, 24,25-dihydroxyvitamin D was undetectable in serum. Administration of synthetic 24,25-dihydroxycholecalciferol was followed by normocalcaemia which persisted long after treatment was stopped. Her sister, who died at the age of 10 months, also had had total alopecia, rickets, and hypocalcaemia resistant to vitamin-D2 therapy. In this familial syndrome there seems to be end-organ resistance to the action of 1,25-dihydroxycholecalciferol, possibly as a result of changes at the receptor sites.

Adolescent↗
PubMed1980

Determination of circulating 25,26-dihydroxycholecalciferol in man by radioimmunoassay.

1. A radioimmunoassay of 25,26-dihydroxycholecalciferol has been developed with an antiserum raised in a sheep, tritiated 1,25-dihydroxycholecalciferol as tracer and synthetic 25,26-dihydroxycholecalciferol as standard. The metabolite was purified from serum extracts by Sephadex LH 20 and high-pressure liquid chromatography; recovery was monitored with biologically generated, tritiated 25,26-dihydroxycholecalciferol. 2. The mean +/- SEM concentration of 25,26-dihydroxycholecalciferol in serum from 18 healthy subjects was 587 +/- 65 pmol/l. Seven Asian patients with osteomalacia due to vitamin D deficiency had very low or undetectable (< 96--231 pmol/l) circulating 25,26-dihydroxycholecalciferol concentrations. 3. The metabolite was detectable in the sera from seven anephric patients (mean 262 +/- 43 pmol/l), indicating that extrarenal sites for the 26-hydroxylation of 25-hydroxycholecalciferol exist in man. 4. A strong positive correlation between the concentrations of 25-hydroxycholecalciferol and those of 25,26-dihydroxycholecalciferol in serum was obtained. Thus it appears that in man the production of this dihydroxy metabolite of vitamin D depends on the concentration of its precursor, 25-hydroxycholecalciferol.

Adult↗
PubMed1980

Studies of circulating parathyroid hormone in man using a homologous amino-terminal specific immunoradiometric assay.

Circulating immunoreactive parathyroid hormone (PTH) was measured by a homologous, amino-terminal, specific, immunoradiometric assay in man. In forty-two healthy subjects the concentrations ranged between < 40 pg/ml and 120 pg/ml. No hormone could be detected in the sera of eleven patients with hypoparathyroidism, but the concentrations were clearly elevated in six patients with pseudohypoparathyroidism (range 190-1120 pg/ml). In thirty-five patients with primary hyperparathyroidism the mean (+/- SEM) concentration was 283.4 +/- 42.4 pg/ml (range 100-1350 pg/ml). A significant positive correlation was demonstrated between immunoassayable hormone and serum calcium concentrations in these patients. In nine patients PTH concentrations were measured before and after parathyroidectomy. In all of them they were elevated pre-operatively but fell to the normal range after parathyroidectomy. The disappearance of exogenously administered synthetic human PTH (1-34) from the circulation of two normal subjects was rapid with an apparent plasma half-disappearance time (t1/2) between 2 and 3 min; the metabolic clearance rate was 12.9 and 9.0 ml. kg-1 . min-1 respectively. Similarly, the disappearance of endogenous, amino-terminal, immunoreactive PTH from the circulation of two patients with primary hyperparathyroidism after parathyroidectomy was rapid; the apparent t1/2 was approximately 3 min. Homologous amino-terminal specific immunoassays for PTH can thus be useful for the study of both the acute, and chronic, changes of circulating hormone in man and represent an improvement over heterologous unselected assay systems.

Female↗
PubMed1980

Parathyroid venous sampling: anatomic considerations and results in 95 patients with primary hyperparathyroidism.

The most successful method of preoperative parathyroid adenoma localization is achieved by assay of venous samples for parathyroid hormone content. Selective sampling of the small veins draining the parathyroid glands increases the accuracy of prediction. Our review of 95 recent cases confirms an efficacy of prediction in 87.5%. The anatomy of the veins draining the parathyroid glands is outlined and we note variations that may occur in the inferior thyroid venous drainage. We consider contralateral venous flow to be of greater significance than has been recognized hitherto. This cross flow occurs through the thyroid plexus, and also via the vertebral venous plexus posteriorly and the anterior jugular veins in the front of the neck. Recent improvements in hormone assay combined with greater knowledge of the parathyroid venous drainage pattern of the individual patient may further improve the prediction rate.

Catheterization↗
PubMed1980

The long-term effect of lowering dialysate magnesium on circulating parathyroid hormone in patients on regular haemodialysis therapy.

Measurement of parathyroid hormone (PTH) in a group of patients on regular dialysis therapy (RDT) showed little acceleration of the development of raised concentrations until the dialysate concentration of magnesium was halved from 0.5 to 0.25 mmol/l. Patients with sustained concentrations of PTH changed less than those who were within the normal range at the outset.

Adult↗
PubMed1980

Development of homologous immunological assays for human parathyroid hormone.

Antisera to a trichloroacetic-acid precipitate of human parathyroid hormone (PTH) were produced in goats. Two of these antisera (G36 and G31) were of high affinity, and the bovine and porcine hormones were less reactive. Synthetic peptides containing the amino-terminal region of human PTH reacted with both antisera; the 1--34 peptide (PTH-(1--34)), with the sequence proposed by Niall, Sauer, Jacobs, Keutmann, Segre, O'Riordan, Aurbach & Potts in 1974, was more reactive than that having the sequence proposed by Brewer, Fairwell, Ronan, Sizemore & Arnaud in 1972. The antisera were further characterized with a number of other native and synthetic fragments of human PTH and reacted poorly with fragments from the carboxy-terminal region of the molecule. Since the amino-terminal fragments did not account for all the immunoreactivity, it is assumed that the antisera had some recognition sites for the central part of the molecule. Highly purified human PTH-(1==84) was labelled with 125I and radioimmunoassays were developed using this tracer and antiserum G36. To avoid the problems associated with labelling human PTH with 125I, a labelled antibody assay was developed with G36 and an immunoadsorbent consisting of human PTH-(1--34) (sequence of Niall et al.) coupled to cellulose. A sensitive homologous amino-terminal specific assay was developed in this way.

Animals↗