Bone aluminum and histomorphometric features of renal osteodystrophy.

To evaluate the relationship between aluminum and the characteristics of bone disease in uremia, bone aluminum content and quantitative histomorphometric analysis of bone were evaluated in bone biopsies from 59 uremic patients undergoing maintenance hemodialysis. Biopsies were classified as showing 1) pure osteomalacia (OM) in 23 cases, 2) osteitis fibrosa (OF) in 13, 3) mixed in 7, and 4) mild lesions in 16. There were no significant differences in levels of serum calcium or alkaline phosphatase between the groups, but serum phosphorus levels were slightly higher in those with OF.

Prolactin and calcitonin responses to parathyroid hormone infusion in hypoparathyroid, pseudohypoparathyroid, and normal subjects.

Since parathyroid hormone (PTH) has been reported to release PRL in normal humans, we studied the effects of exogenous PTH infusion (150 U) on the secretion of PRL, TSH, and calcitonin in 10 normal subjects, 5 with hypoparathyroidism, and 10 with pseudohypoparathyroidism, type I (PHP). PTH produced a rise in serum PRL in the normal subjects from 5.1 +/- 0.

Fibroblast defect in pseudohypoparathyroidism, type I: reduced activity of receptor-cyclase coupling protein.

Erythrocytes of many patients with pseudohypoparathyroidism, type I (PHP-I), exhibit reduced activity of the N protein, a guanine nucleotide-binding regulatory component of hormone-sensitive adenylate cyclase. We compared N and adenylate cyclase activities and the accumulation of cAMP in fibroblasts propagated from skin biopsies of six normal subjects and seven PHP-I patients. N activities were reduced by approximately 40% in fibroblasts as well as erythrocytes of five PHP-I patients.

Altered dopaminergic modulation of prolactin and aldosterone secretion in pseudohypoparathyroidism.

It has previously been demonstrated in our laboratory that patients with pseudohypoparathyroidism (PsHP) have impaired PRL responses to TRH and chlorpromazine. We have also observed that these patients have low basal plasma renin activity (PRA) and decreased aldosterone responses to upright posture and isometric handgrip exercise. Since inhibitory dopaminergic modulation of PRL and aldosterone is well established, we have examined whether PsHP is associated with altered dopaminergic inhibition of PRL and aldosterone secretion.

Vitamin-D-resistant osteomalacia in hemodialysis patients lacking secondary hyperparathyroidism.

We describe a sporadic, vitamin-D-resistant osteomalacic syndrome in 19 patients undergoing hemodialysis. The syndrome was found in less than 1.5% of patients from referring dialysis centers.

Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity.

Pseudohypoparathyroidism, type I (PHP-I) is an inherited disorder of primary resistance to multiple hormones that work by stimulating adenylate cyclase. In an attempt to clarify the mode of inheritance of PHP-I, we measured the activity of the N protein, a receptor-cyclase coupling component, in erythrocyte membranes. Erythrocyte N-protein activity was reduced by approximately 50% in erythrocytes of 15 PHP-I patients and was normal in 19 of their clinically normal first degree relatives.

Human mutation affecting hormone-sensitive adenylate cyclase.

Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides. We measured this protein in erythrocyte membranes of ten patients with pseudohypoparathyroidism (PHP), using assays of its biochemical activity and of its susceptibility to radiolabeling in the presence of 32P-NAD and cholera toxin. By both assays, the protein was reduced by 50% in erythrocytes of 4 PHP patients, as compared with normal and hypoparathyroid subjects.

Effects in vivo of vitamin D metabolites and 17 beta-estradiol on parathyroid hormone-dependent formation of adenosine 3',5'-monophosphate in rat bone.

We used an in vivo infusion technique to assess the hypothesis that vitamin D metabolites and estrogens modulate tissue responsiveness to parathyroid hormone via effects on the adenylate cyclase-cAMP system. After treatment with these agents for 3-4 days, rats were thyroparathyroidectomized. Twenty-four hours later, parathyroid extract (PTE) was infused, and cAMP in calvaria was measured.

Defect of receptor-cyclase coupling protein in pseudohypoparathyroidism.

Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. We studied this protein (termed "N") in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein's biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein's activity was reduced by 40 to 50 per cent in erythrocytes of five of 10 patients with Type I pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and one patient with Type II pseudohypoparathyroidism.

Hypertension associated with hyperparathyroidism is not responsive to angiotensin blockade.

Patients with primary hyperparathyroidism are frequently hypertensive. Studies were performed to determine whether the hypertension in this disorder could be corrected by saralasin infusion. Five patients with primary hyperparathyroidism and one patient with secondary hyperparathyroidism were salt depleted before saralasin testing by the administration of 1 mg/kg furosemide at 1700 h on the evening before testing.

Kidney stones.

The prevalence of kidney stones has steadily risen during this century; passage of a calculus and a positive family history increase the probability of recurrence. Findings from recent studies on the cause of renal calculi have stressed crystallization and crystal aggregation of stone minerals from supersaturated urine, rather than excessive organic matrix. Absence of normal urine inhibitors of calcium salts is also stressed.

Unique effects of 24,25-dihydroxyvitamin D3 in uremic patients.

The effects of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), given orally for 7-10 days at doses of 2 and 4 microgram/day, were evaluated in patients with advanced renal failure. There was a significant fall in serum Ca and a rise in alkaline phosphatase; both returned to pretreatment levels 2 weeks after cessation of therapy. There was no change in intestinal absorption of 47Ca.

Bradycardia during stimulation of the septum and somatic afferents in the rabbit.

Experiments were done in paralyzed rabbits anesthetized with either pentobarbital sodium or alpha-chloralose to test the possibility that the septum may alter the cardiovascular responses elicited by stimulation of somatic afferent fibers. Electrical stimulation of the lesser saphenous nerve (LSN), a branch of the sciatic nerve, at certain parameters elicited bradycardia, which could be abolished by bilateral vagotomy or intravenous injection of atropine methylbromide. Distinct and characteristic changes in mean arterial pressure and heart rate were elicited by electrical stimulation of histologically localized sites in five septal areas.

Ankylosing spondylitis and hyperparathyroidism.

An attempt was made to determine whether a relationship exists between ankylosing spondylitis (AS) and hyperparathyroidism (HP). Twenty patients with definite AS, studied for biochemical evidence of HP, did not show consistent abnormalities in serum calcium, phosphorus, alkalinephosphatase, or parathyroid hormone levels or in bone-density measurements. Reviewing roentgenograms of 39 patients with HP showed one patient with sacroiliitis, and one of the 28 hyperparathyroid patients tissue-typed as HLA B27-positive.

Effect of 25-hydroxy-vitamin D3 on intestinal absorption of calcium in normal man and patients with renal failure.

The effects of short-term treatment with 25-hydroxy-vitamin D3 (25(OH)D3) on intestinal absorption of 47Ca were examined in 18 studies of normal subjects and 16 studies of patients with advanced renal failure. Doses of 25(OH)D3 were 20, 100, 500, or 1000 microgram/day given orally for 7--10 days. There was an increase in 47Ca absorption and urinary calcium in normal subjects receiving 20 microgram/day, while doses of 500 or 1000 microgram/day were required to augment 47Ca absorption in renal failure patients.