Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin.

A progesterone antagonist (RU 486), combined with oxytocin, was effective in achieving cervical dilation, labor induction, and early delivery in near-term monkeys. Effects of RU 486 included accelerated flow of colostrum and transiently enhanced weight gain in infants. No overt toxicity on fetuses, mothers, or newborns was detected with the use of a single oral dose of 25 mg.

[Recklinghausen's disease with hypophosphoremia and osteomalacia. Apropos of 2 cases]. / Maladie de Recklinghausen avec hypophosphorémie et ostéomalacie. A propos de 2 observations.

The authors report two cases of osteomalacia due to phosphate diabetes in patients with Recklinghausen's disease. In one case abnormalities of vitamin D metabolism were identical with those described in cases of phosphate diabetes associated with mesenchymal tumours. The abnormalities found in the second case were different. The physiopathological mechanism of osteomalacia due to phosphate diabetes in mesenchymal diseases generally and in Recklinghausen's disease in particular is discussed.

Hypercalciuria during experimental vitamin K deficiency in the rat.

Vitamin K promotes the formation of gamma-carboxylated glutamate (GLA) in several protein species. GLA residues have a high affinity for the Ca ion. In the present study, we tested the hypothesis that experimental vitamin K deficiency in rats could induce changes in Ca metabolism. Vitamin K depletion, which was associated with a reduction in urinary GLA excretion, induced within 7 days a significant increase in cumulative urinary Ca excretion that persisted throughout the 21 days of study. The hypercalciuria of vitamin K-deficient rats was corrected on vitamin K supplementation. No concomitant changes were observed in intestinal Ca absorption determined by a balance technic or of skeletal resorption and apposition rates determined by bone histomorphometry. Plasma Ca, but not total protein concentration, of vitamin k-depleted rats showed a transient decrease at day 15 that disappeared at day 21. plasma sodium, phosphate and 1,25(OH)2 vitamin D concentration, and urinary phosphate, sodium, and creatinine excretion remained unchanged. In conclusion, vitamin k deficiency in the rat induced hypercalciuria that could be of renal origin. Its possible relationship to vitamin K-dependent renal GLA protein remains to be clarified.

Renal magnesium and phosphate wastage in a patient with hypercalciuria and nephrocalcinosis: effect of oral phosphorus and magnesium supplements.

We report a 29-year-old man with a mild decrease in glomerular filtration, nephrocalcinosis, hypercalciuria and a renal magnesium leak. He had other features of 'congenital magnesium-losing kidney', such as arthritis and hyperuricemia, short stature and recurrent urinary tract infections, but had no radiological chondrocalcinosis. In addition, pallidal calcification was found. The patient also had a renal phosphate leak. Phosphorus supplements resulted in a decrease in urinary calcium excretion, indicating that hypercalciuria was at least partially a consequence of phosphorus depletion. Plasma and urine magnesium were not affected by phosphorus supplements. Addition of magnesium supplements resulted in a transient and modest decrease in urinary calcium excretion, with no modification in plasma magnesium.

[Incidence of lithiasic recurrence after a diuretic therapy, alone or combined with treatment by a thiazide diuretic or phosphorus]. / Fréquence des récidives lithiasiques après une cure de diurèse simple ou associée à un traitement par un diurétique thiazidique ou le phosphore.

The preventive affects on recurrent renal calcium stones of water diuresis alone or combined with drugs aimed at lowering urinary calcium were evaluated prospectively in 51 patients with calcium nephrolithiasis. Following clinical and metabolic examination, the patients were allocated at random to 3 treatment groups: water diuresis alone (group I, n = 19) or associated with hydrochlorothiazide 50 mg/day (group II, n = 19) or with a neutral phosphate preparation 1500 mg/day (group III, n = 13). Results were assessed on the number of recurrences; 24-h urinary calcium was measured at regular intervals. The mean follow-up (2 years; range 1-4 years) was the same in all 3 groups. A significant fall in recurrence rate as compared with pre-treatment values was observed in groups I and II. The recurrence rate was the same in both groups during treatment. However, less patients had recurrences in group I (1/19) than in group II (5/19). No significant fall in recurrence rate was observed in group III, owing to some patients in this group having frequent recurrences. The recurrence rate was unrelated to clinical findings and biochemical values ( oxaluria , calciuria) measured before treatment and to the urinary Ca/Cr ratio calculated during treatment. This study confirms that water diuresis is effective in preventing recurrent renal calcium stones and that diuretics of the thiazide group reduce the number of patients with recurrences.

Total parathyroidectomy and delayed parathyroid autotransplantation using a simplified cryopreservation technique: human and animal studies.

Following earlier studies using a simplified cryopreservation method in rats, we report the successful use of this technique in a hemodialysis patient who had previously undergone total parathyroidectomy. In additional studies, parathyroid glands from rats were conserved by this rapid freezing procedure after total parathyroidectomy. Six weeks after parathyroid autotransplantation the animals were submitted to a low-calcium diet and their parathyroid gland function compared to that of rats that had previously undergone sham operation, immediate autotransplantation, or delayed autotransplantation using the classical cryopreservation method. With both cryopreservation techniques, plasma calcium, phosphorus, and 1,25 (OH)2 vitamin D concentrations after low-calcium diet were similar although results were less satisfactory than with immediate autotransplantation or after sham operation. We suggest that this simplified cryopreservation technique, developed in rats, yields functioning parathyroid gland tissue and can be successfully used in the human.

[1,25-(OH)2-D3 treatment of hypophosphoremic osteomalacia associated with villonodular synovitis]. / Traitement par le 1,25 (OH)2 D3 d'une ostéomalacie hypophosphorémique associée à une synovite villonodulaire.

The authors report a case of hypophosphoremic osteomalacia due to a soft tissue tumor. This case confirm 1,25 (OH)2 cholecalciferol deficiency. Treatment with phosphorus and 1,25 (OH)2 cholecalciferol cured osteomalacia. Accountable tumor (villonodular synovitis) had never been described previously.

[Predictive value of lithogenic risk in hypercalciuria: should 24-hour urine calcium be measured?]. / Valeur prédictive du risque lithogéne de l'hypercalciurie: faut-il mesurer la calciurie des 24 heures?

Three studies have been undertaken to evaluate the predictive value for new stone formation of urinary calcium excretion. In study 1, 24-hr calciuria was similar in 52 patients with benign stone disease (less than 3 new stones or 1 staghorn calculus in the 5 preceeding years) and in 46 patients with severe lithiasis (more than 3 stones or 1 staghorn calculus), based on a retrospective assessment of stone disease evolution. In study 2, urinary fasting Ca/Creat was identical in 43 non-hyperparathyroid stone formers (including 31 with severe lithiasis) and in 35 patients with proven or suspected primary hyperparathyroidism (including 19 with benign lithiasis, 8 with severe lithiasis and 8 with no stone). In study 3, stone recurrence, assessed prospectively, felt significantly in patients given a high fluid intake alone or associated with 50 mg/d of hydrochlorothiazide, independently of urinary calcium excretion. Urinary calcium determination therefore appears useless for stone recurrence prediction.

[Medical treatment of calcium nephrolithiasis (author's transl)]. / Le traitement médical de la lithiase calcique.

Calcium calculi are by far the most frequent of urinary stones. In many cases their formation is enhanced by lithogenetic abnormalities, including idiopathic calciuria. The basis of the treatment is to promote diuresis by absorbing for an indefinite period a mineral water containing less than 100 mg/l of calcium. There is no evidence that drugs reducing calciuria (thiazides, phosphorus) or uraturia (allopurinol) are effective, and they should be reserved to cases of rapidly progressive lithiasis. A long-term strategy for the prevention of lithiasis is discussed.

[Compared metabolic effects of phosphorus or hydrochlorothiazide therapy in hypercalciuric stone-formers (author's transl)]. / Efficacité métabolique comparée d'un traitement par le phosphore ou par l'hydrochlorothiazide chez des lithiasiques hypercalciuriques.

The hypocalciuric effect of phosphorus or hydrochlorothiazide therapy was evaluated in 26 hypercalciuric stone-formers after 2 to 4 months and 8 to 12 months treatment. After 2 to 4 months, a significant decrease of the urinary calcium to creatinine ratio was noted only in a group of 7 patients receiving phosphorus supplementation (1500 mg/day). The decrease was transient however, since in 5 of these patients, the calcium to creatinine ratio was found to be at pretreatment levels when the patients were reinvestigated after 8 to 12 months on phosphorus. In contrast, in 8 patients receiving hydrochlorothiazide (50 mg/day) during 8 to 12 months, this ratio was significantly lower (P less than 0.01) than before treatment. A group of patients maintained on high water intake alone for 8 to 12 months served as a control and no modification in calcium excretion was observed. This study indicates that long-term treatment with hydrochlorothiazide is more efficient in lowering urinary calcium excretion than phosphorus therapy.

Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type).

Sporadic hypophosphataemic osteomalacia (adult-onset type) was demonstrated in a 40-year-old man on the basis of severe osteomalacia, hypophosphataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9.3 ng prot./ml (normal range: 4-8 ng prot./ml). Plasma 25-hydroxy-vitamin D and 24,25-dihydroxy-vitamin D concentrations were 11 and 2.4 ng/ml respectively. Basal 1 alpha,25-dihydroxy-vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low-phosphorus diet. The patient was put on oral treatment with 25-hydroxycholecalciferol (100 microgram per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH)D was 44 ng/ml, plasma 1,25(OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/l). These facts suggest in our patient the existence of a vitamin D-independent renal phosphorus leak.

Plasma 1,25(OH)2D3 and iPTH in transplanted adults with persisting hypophosphataemia.

Hypophosphataemia is a common finding among kidney transplanted patients [1,2]. In a previous study in kidney transplanted children with plasma creatinine below 1.1mg/dl, we demonstrated [3] a negative correlation between plasma phosphorus and 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), the renal hormonal form of vitamin D. No such correlation was apparent in children with minimal increase in plasma creatinine. The aim of the present investigation carried out in hypophosphataemic transplanted adults was two-fold: 1) to determine whether hypophosphataemia results from persisting hyperparathyroidism or from a renal phosphorus leak, or both, and 2) to study the relation between plasma phosphorus, iPTH and 1,25(OH)2D3 in these patients.

[Hypophosphoremic osteomalacia secondary to benign connective tissue tumors: a report on three unusual cases with vitamin D metabolites measurements (author's transl)]. / Ostéomalacies hypophosphorémiques guéries par l'ablation de tumeurs bénignes du tissue conjonctif: étude de trois observations avec dosages pré- et post-opérations des métabolites de la vitamine D.

Three cases of benign connective tissue tumors (intracranial frontal hemangiopericytoma, rectosigmoid hemangioma, intraspinal neurinoma) associated with hypophosphoremic osteomalacia and reduction in plasma 1-25 (OH)2D levels are described. Rapid reversal of biological anomalies and subsequent recovery from clinical manifestations were observed after tumor ablation. Twenty-two identical cases have been reported in the published literature. The sharp- fall in 1-25 (OH)2D levels without secondary hypocalcemia or hyperparathyroidism suggests that intestinal absorption of calcium is not entirely dependent on this metabolite. Increased phosphoremia without a parallel rise in 1-25 (OH)2D levels was noted in one case. The possibility of an existing connective tissue tumor should be explored in all cases of hypophosphoremic osteomalacia.

[Evidence for a glucose-dependent renal phosphorus leak in normo- and hypercalciuric stone-formers (author's transl)]. / Mise en évidence d'un trouble de la conservation rénale du phosphore dépendant du glucose chez des lithiasiques normo-ow hypercalciuriques.

Changes in phosphatemia and in maximum renal threshold phosphate concentration (TmP/GFR) have been measured before and 45 and 75 min after oral ingestion of 75 g of glucose in 10 hypercalciuric lithiasic patients (HCI), 8 normocalciuric lithiasic patients (NCI) and 7 control subjects. After glucose ingestion, whereas plasma phosphorus decreased in all 3 groups, TmP/GFR decreased significantly in HCI and NCI but not in controls. A slight increase in calcium excretion was noted in the subjects with HCI and NCI after glucose load. Plasma concentration of 1,25(OH)2D was measured in 8 HCI and 7 controls before and after glucose: there was a significant increase in HCI 45 min after glucose and no modification in control subjects. These results show that a glucose load causes a decrease in TmP/GFR in lithiasic subjects. The results demonstrate the existence in lithiasic patients of perturbations of renal handling of phosphates which could, at least in part, be related to glucose metabolism. This trouble could contribute to the elevation of the serum 1,25(OH)2D observed in these patients.

[Idiopathic hypercalciuria: effects of acute phosphorus deficiency (author's transl)]. / Hypercalciurie idiopathique: effet d'une carence aiguë en phosphore.

Eleven patients with kidney stone disease and idiopathic hypercalciuria (urinary calcium above 4 mg/kg/j), without phosphorus renal leak and 6 control subjects have been put for 3 days on a diet containing 1 g calcium and 1 phosphorus daily (period A), and then for 4 days on a diet containing 1 g calcium, 450 mg phosphorus and 3 g aluminium hydroxyde daily (period B). During period A, no significant difference in blood calcium, phosphorus and magnesium, not in phosphaturia, rate of phosphorus reabsorption (RPR) and ratio maximum RPR/creatinine clearance was found between the two groups. After 2 days on a low phosphate diet (period B) the blood phosphorus decreased significantly in the hypercalciuric patients but not in the control subjects, thus revealing among the forme a latent abnormality in the retention of phosphates. This abnormality could play an important role in the pathogenesis of hypercalciuria.

Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors.

Whether the mineralocorticoid effect of glycyrrhetinic acid is mediated by the adrenal glands or is due to a direct action on the renal tubule remains controversial. The affinity of glycyrrhetinic acid for mineralocorticoid receptors has been studied by several types of competition experiments. When rat kidney slices were incubated with 2 times 10- minus 9 M [3H]aldosterone, glycyrrhetinic acid (2 times 10- minus 5 M) was able to compete with aldosterone for the cytosolic receptor and to decrease the formation of a chromatin-[3Hi1 aldosterone-receptor complex. In cytosol, in vitro, 6 times 10- minus 4 M glycyrrhetinic acid was able to inhibit aldosterone binding by 70 percent, whereas the same dose produced only a 20 percent inhibition of dexamethasone binding. The apparent KDiss of glycyrrhetinic acid for the mineralocorticoid receptor was 2 times 10- minus 6 M. That glycyrrhetinic acid appeared to compete mainly with mineralocorticoid receptors was confirmed by sedimentation in the sucrose gradients: [3H]Aldosterone specifically bound to an 8 S peak was displaced by 5 times 10- minus 5 M glycyrrhetinic acid, whereas the [3H]dexamethasone peak was not affected by this compound. Glycyrrhizic acid showed no significant affinity for mineralocorticoid or glucocorticoid kidney receptor sites. Glycyrrhetinic acid and glycyrrhizic acid had no affinity for rat cortisol binding globulin. Glycyrrhetinic acid has a low but definite affinity for mineralocorticoid receptors and thus appears to have a direct mineralocorticoid action. The low affinity of this compound for mineralocorticoid receptors is in good agreement with the very high doses required to exhibit its biological activity.