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Intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) was used to treat 26 patients with Paget's disease. Three daily dosages were studied; 20-30 mg/day in 20 patients, 45 mg/day in three patients and 60 mg/day in three patients, by daily 4-hour infusions for 2-10 days. The fasting urinary hydroxyproline excretion (HypE) declined exponentially, reaching 50% of pretreatment values at 1.92 +/- 0.16 (mean +/- SEM) days. This initial rapid decline was complete by 4 days following treatment to a mean of 28.0 +/- 3.4% of pretreatment values. Thereafter, there was no significant decline in HypE. The initial rate of decline of HypE was unchanged by increasing the daily dose of APD. Transient non-symptomatic hypocalcaemia with secondary hyperparathyroidism occurred in all patients. No adverse changes in the renal handling of calcium or phosphate, as seen with high-dose 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP), were seen in any patient on any daily dose. Fever occurred in 73% of patients in the first 2 days of treatment. Overall, there was a significant fall in the lymphocyte count (P less than 0.005 febrile group, n = 19; P less than 0.02 non-febrile group, n = 7) and a fever-dependent rise in the neutrophil count (P less than 0.005 febrile group only). The occurrence of fever was associated with a more rapid decline in HypE, compared to the non-febrile group, so that HypE was significantly lower in the febrile group by day 5 (P less than 0.025). Seventy-two per cent of patients with bone and/or joint pain reported a reduction in pain.(ABSTRACT TRUNCATED AT 250 WORDS)

White Leghorn cockerels, fed either normal or cholesterol enriched food, were injected with saline, peanut oil, testosterone, oestradiol, progesterone, or oestradiol plus progesterone for 87 days. The ascending aortas, descending aortas and abdominal aortas were examined by light and electron microscopy and both qualitative and quantitative assessments made. The results were subjected to multivariate analysis. Cholesterol feeding increased lipid storage and round cell infiltration in the endothelium and intima, and both the degree of lipid storage and the amount of lumen obstruction was much greater in the abdominal aorta than in the ascending or descending aorta. Treatment with oestrogen plus progesterone, regardless of diet or site of action, caused a highly significant reduction in the percentage of normal cells of the endothelium. Those cockerels treated with oil, androgen and progesterone showed significantly less large foamy eosinophilic endothelial cells than those treated with oestrogen plus progesterone. The degree of round cell infiltration was increased by androgen and oestrogen, but not by oestrogen plus progesterone, when compared with both saline treated and oil treated controls. Cholesterol feeding caused a reduced percentage of normal endothelial cells. This was significantly enhanced by treatment with androgen, progesterone and saline. The effect of cholesterol feeding as a cause of a reduced percentage of normal, and an increased percentage of foamy eosinophilic endothelial cells, was significantly enhanced in the ascending aorta and the descending aorta but not in the abdominal aorta. The same site-dietary interaction was observed in the trend towards an excess of large clear cells over large eosinophilic cells in the intima. In spite of this the extent of plaque likely to cause obstruction as a result of this site-dietary interaction was increased only in the abdominal aorta. An unexpected treatment-site interaction was that progesterone had an enhanced effect, causing disruption of the internal elastic lamina of the ascending aorta but not of the descending or abdominal aortas. There was no evidence that diet or treatment increased the amount of acid esterase in the tissues, even though the chickens showed the expected species deficiency of this enzyme, but there was a significant relationship between the presence of lipid and the amount of acid esterase in the plaques of the abdominal aorta. Male albino Wistar rats were primed with peanut oil, oestrogen and triamcinolone before subcutaneous granulomas were induced by implanting cholesterol, and then treated with these substances for longer periods. Cryostat sections of the granulo