Effects of 1,25(OH)2D3 administration on serum bone GLA protein in predialysis chronic renal failure.
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Adult↗
Biomedical subjects
G Coen
Publications and source records attributed to G Coen.
Treatment of secondary hyperparathyroidism of predialysis chronic renal failure with low doses of 1,25(OH)2D3: humoral and histomorphometric results.
Treatment of secondary hyperparathyroidism and the osteodystrophy of predialysis chronic renal failure (CRF) with 1,25(OH)2D3 has been advocated by several authors, but also opposed by others for alleged renal toxicity. However, current concepts of the pathogenesis of the early occurrence of secondary hyperparathyroidism in predialysis CRF point to deficiency of 1,25(OH)2D3 as a primary factor. The aim of this study was to evaluate if administration of 1,25(OH)2D3 (0.25 microgram daily) in a dose which would not induce hypercalcemia, would improve humoral and bone histomorphometric parameters in predialysis CRF. 15 patients with predialysis CRF (mean age 51.2 +/- 16.9 years, range 13-73 years), serum creatinine 4.93 +/- 1.7 mg/dl, were treated with the vitamin D metabolite for an average of 16.2 +/- 11.3 months, at the end of which a transiliac bone biopsy for histomorphometry was performed. In addition, 23 patients comparable for age, serum creatinine and causes of renal failure, served as controls. Treatment did not induce hypercalcemia nor adversely modify the rate of decline of renal function. Alkaline phosphatase fell significantly while immunoreactive parathyroid hormone (iPTH) and osteocalcin showed a moderate, not significant, decrease. Compared to the control patients, the bone histomorphometric parameters active resorption surface and active osteoblastic surface were significantly lower and almost normalized by treatment. In conclusion, the study provides conclusive evidence of the absence of toxicity of the metabolite at the low doses employed, together with good therapeutic response on bone histology. Treatment at this dosage could be made in the early stages of predialysis CRF without need of close and continuous monitoring of serum biochemical parameters.
Adolescent↗
Digital angiography in evaluation of orthopedic tumors.
Preoperative evaluation of orthopedic tumors using digital subtraction angiography (DSA) proved useful to ascertain the nature of the lesion, its extension to soft tissues and joints, and the presence of arteriovenous (AV) shunts. We report that overall accuracy varied from 89% to 92%, depending on the feature evaluated. The importance of angiographic examination of this entity is discussed as well as the advantages of DSA over conventional angiography.
Angiography↗
Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up.
Serum bone GLA protein (BGP) was measured by radioimmunoassay in 42 patients (age, 47.5 +/- 16.6 years; serum creatinine, 4.32 +/- 1.9 mg/dl) with predialysis chronic renal failure (CRF). Nineteen patients were studied within a short period of time, while 23 were followed with repeated measurements of serum BGP, creatinine, iPTH, and alkaline phosphatase (AP) for a mean period of 17.1 +/- 8.1 months. Eleven of these patients were treated with 1,25(OH)2D3 for a mean of 16.8 +/- 6.4 months. In 23 patients at various stages of CRF, a transiliac bone biopsy was performed for histomorphometric evaluation. In the untreated patients, serum BGP was higher than normal and showed a positive correlation with creatinine levels (P less than 0.001). Serum BGP was also positively correlated with iPTH, AP, serum phosphate, active resorption surface, active osteoblastic surface, osteoid surface, and volume. During treatment with 1,25(OH)2D3, BGP, iPTH, and AP were significantly lower than in the untreated patients. The reduction in iPTH and BGP was proportional, while BGP and AP no longer correlated. Repeated measurements of BGP during the long-term follow-up showed a progressive rise in the untreated patients and a downward course of BGP levels during treatment. In conclusion, serum BGP increases progressively in CRF, rising with advancing renal damage in close correlation with iPTH, AP, and the severity of renal osteodystrophy. Treatment with 1,25(OH)2D3 causes a parallel decline in BGP and iPTH levels and dissociation between BGP and AP can be observed. Compared to AP, BGP seems to be a more reliable index of secondary hyperparathyroidism and potentially more useful in the long-term monitoring of treatment with 1,25(OH)2D3.
Adolescent↗
Successful treatment of long-lasting severe hypertension with captopril during a twin pregnancy.
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Adult↗
[Acebutolol as monotherapy of essential arterial hypertension].
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Acebutolol↗
Circannual versus seasonal variations of longitudinally sampled 25-hydroxycholecalciferol serum levels.
Seasonal variations in human serum levels of 25-hydroxycholecalciferol (25OHD) have been largely documented in transverse studies of population. But seasonality is not per se a demonstration that 25OHD serum levels fluctuate along the course of year according to a waveform profile with a periodic rhythm. Because of this, we attempted to investigate the possible occurrence of a circannual rhythm for 25OHD serum levels in a longitudinal design, by fitting a 365.25-day cosine curve to temporal biodata recorded in 10 clinically healthy subjects, monthly sampled for RIA determinations of 25OHD. Cosinor procedure statistically validated the occurrence of a circannual rhythm for 25OHD serum concentrations at a highly significant level of probability (P = 0.0015) for null hypothesis amplitude = 0. With 95% of probability, amplitude ranges from 5.0 to 16.5 ng/ml (mean value of oscillation = 10 ng/ml), while acrophase is temporally located from September 14 to December 3 (mean timing = October 21). Yearly, mean values for 25OHD serum concentrations is of 40.3 +/- 5.4 ng/ml as quantified by the line which transversely divides the cosine curve interpolating original biodata. By calculating the band of a complete 12 months variability which includes 90% of the distribution with 90% confidence limits, the circannual chronodesm of 25OHD serum levels has been obtained. Such a chronodesmic sinusoid has been compared to the circannual chronogram. By this comparison, a dissociation between the crest (October) and the peak (August) has been detected. The finding suggests that seasonal variations are superimposed to the circannual rhythm. Seasonal but also circannual changes, thus, characterize the yearly variability of 25OHD serum levels in man.
Adult↗
1-alpha-OH-cholecalciferol (1-alpha-OHD3) and low phosphate diet in predialysis chronic renal failure: effects on renal function and on secondary hyperparathyroidism.
The effect of 1-alpha-OHD3 on the rate of decline of renal function was studied in 18 patients with predialytic chronic renal failure. 9 patients with serum creatinine 4.19 +/- 1.63 mg/dl, were treated with 1-alpha-OHD3 0.4 +/- 0.11 micrograms/day and a low phosphate diet and 9 patients, with serum creatinine 3.69 +/- 1.24 mg/dl, received the low phosphate diet alone. In the first group retrospectively in 8 patients up to 3-44 months and prospectively in all patients reciprocal values of serum creatinine levels fell linearly with time. Comparison of the slopes of the regression lines before and following the start of treatment did not show statistical differences in 6 cases, in 1 case the decline of renal function improved significantly and in 1 case it became positive. Serum calcium increased significantly (p less than 0.025), alkaline phosphatase decreased (p less than 0.005) and serum iPTH decreased in 6 of 8 cases. In the low phosphate diet group, serum calcium, alkaline phosphatase did not change while iPTH increased in 8 of 9 cases. The rate of decline of renal function before treatment in 3 cases did not improve after the institution of the diet. In conclusion improvement or prevention of secondary hyperparathyroidism in predialytic chronic renal failure can be achieved with daily doses of less than or equal to 0.5 micrograms 1-alpha OHD and a low phosphate diet. The small increment in serum calcium levels induced by the treatment did not accelerate the deterioration of renal function while showing a better control of alkaline phosphatase and serum iPTH than the low phosphate diet alone.
Adult↗
Diabetic neuroarthropathy of the foot.
The authors describe 5 cases of diabetic neuroarthropathy of the foot that came under their observation. They report the clinical radiological and histological findings and discuss the most widely accepted pathogenetic theories, including their own, based on their histological data. They also outline a programme of treatment and prophylactis measures to be adopted in these cases.
Adult↗
[Calcium-phosphorus changes in chronic anticonvulsant therapy: effects of the administration of 25-hydroxyvitamin D3 on secondary hyperparathyroidism].
The present study represents a contribution to the knowledge of secondary hyperparathyroidism (SHP) in patients treated with anticonvulsant drugs (AC). In these subjects alterations of the calcium: phosphorus metabolism as rickets and osteomalacia are frequent; however literature data on SHP are scarce. Our research carried out on 29 adult patients under treatment with one or more AC for periods ranging from 9 months to 12 years confirmed that 25-OHD levels in the serum are low, especially in patients treated for longer times. The iPTH levels in the serum are increased with respect to normal controls, while blood calcium and phosphate levels are normal as are urine calcium and phosphate. The 25-OHD levels in serum present the same seasonal variations as the normal controls. The administration of 25-OHD3 (20 micrograms/day for 3 months) to 12 of these patients who had the lowest 25-OHD spring levels rendered the 25-OHD levels attain normal values. Cyclic AMP was normalized; serum and urine calcium and phosphorus and urinary hydroxyproline were not modified significantly. On the basis of the present data it is recommended that chronic AC treatment should be accompanied by long term administration of 25-OHD3 for prophylaxis and/or for treatment of SHP.
Adolescent↗
[Bone histomorphometry: methodological criteria in the study of metabolic skeletal diseases].
The present study deals with the appropriate statistical approach to the histomorphometric technique carried out on bone tissue with the Merz and Schenk integrating eyepiece. Statistical analysis of the results obtained from ten bone biopsies of renal osteodystrophic patients enabled to calculate the values of standard errors for each histomorphometric parameter as a function of measured histological fields. The examination of 42 fields chosen at random on histological sections from different sites of the bone biopsy guarantees sufficiently low standard error values. This technique is of invaluable help in the study of metabolic bone diseases, and extremely useful in the evaluation of treatment trials in renal osteodystrophy.
Biopsy↗
[Assay of serum 24,25-dihydroxycholecalciferol by a competitive protein binding method].
24-25(OH)2 D3 is a vitamin D metabolite due to renal 24-hydroxylation of 25OHD3. The metabolite has some important biological functions on the bone and intestine. Its affinity to the D serum binding protein allows a competitive binding protein assay to be carried out as for 25OHD3, following a chromatographic purification step on Sephadex LH 20. Serum levels of the metabolite in 18 control subjects were found to be 2,69 +/- 1,34 ng/ml while 25OHD3 was 17,41 +/- 7,39 ng/ml and the ratio 24-25(OH)2D3 /25OHD3 in the serum was 0,15. The assay of 24-25(OH)2D3 is useful for physiological studies and for identification of vitamin D depletion states.
24,25-Dihydroxyvitamin D 3↗
[Circannual rhythm of plasma 25-hydroxycholecalciferol in normal man].
Circannual rhythm of serum 25OH-cholecalciferol has been evaluated in 11 normal adult subjects. Blood samples were collected monthly. The pattern of serum levels of the metabolite was biphasic with the lower average values between January and June and maximal mean levels between July and October. Mean values were higher than in North-European countries. The estimated dietary intake of cholecalciferol was in the normal range. Therefore diet does not seem to account for the relatively elevated serum levels of the metabolite. On the contrary sunlight exposure appeared to have marked influence both on mean 250HD levels and on the seasonal rhythm. In spite of seasonal wide variation of serum 250HD levels, blood calcium and phosphate values were stable. The results of serum PTH assay favour the hypothesis that the maintenance of steady blood calcium levels may be due to seasonal variation of parathyroid secretion.
Adult↗
Albright's hereditary osteodystrophy.
The authors observed different clinical forms of Albright's hereditary osteodystrophy in 4 members of a family (two sisters, their mother and the maternal grandfather). The sisters were affected by pseudohypoparathyroidism type I, the older manifested the hypocalcemic variety, the younger the normocalcemic variety; the mother and the grandfather presented only with short stature and subcutaneous calcifications. The variety of clinical and biochemical alterations observed in these 3 generations supports evidence that Albright's hereditary osteodystrophy has a broad spectrum and that distinctions between the various forms of pseudohypoparathyroidsim should not be rigidly considered.
Adult↗
[Physiopathological and therapeutic aspects of vitamin D (author's transl)].
In the last decade our knowledge on vitamin D has grown considerably due to the identification of numerous steps of the vitamin D metabolism and to the isolation and synthesis of active metabolites. Therefore a lot of progress had been made in the understanding of the physiological mechanism of regulating blood calcium homeostasis and of the pathogenesis of many related diseases. The diseases connected to the calcium-phosphate metabolism requiring treatment with vitamin D and its metabolites are numerous. The basis for a rational therapeutic approach is provided by the new concepts on the pathogensis of the various diseases and on the pharmacology of vitamin D metabolites. Pure vitamin D depletion may be controlled with physiological doses of vitamin D. Administration of 25-OHD3 is advisable in chronic hepatitis or cirrhosis accompanied by a defect of 25-hydroxylation and/or intestinal loss of the metabolite. A defect in the synthesis of 1,25-(OH)2D3, the metabolite of renal origin, is present in an interesting and wide group of diseases. These are: chronic renal insufficiency, hypoparathyroidism, hypocalcemic D-resistant rickets and senile or post-menopausal osteoporosis. In the treatment of this group of diseases, which sometimes is of a preventive nature, it is preferable to administer the dihydroxylated metabolites of vitamin D. The results of treatments and prevention in a few selected conditions are reported.
Chronic Kidney Disease-Mineral and Bone Disorder↗
[Behavior of serum 25-hydroxycholecalciferol in humans after administration of vitamin D and 25-OHD3].
Serum levels of 25 hydroxycholecalciferol were evaluated following i.m. and p.o. vit. D2 and D3 and p.o. 25OHD3 administration. While no increment in 25OHD3 serum levels were observed after i. m. administration of non-hydroxylated calciferols, a marked increment of the metabolite was found following the oral administration. However the peak values were largely impredictable. Acute and chronic p.o. administration of 25OHD3 determines a rapid and dose-dependent increase of the serum levels of the metabolite. In addition considering that a lower dosage is required of 25OHD3 compared to vit. D, this metabolite is preferable in the therapeutic use.
Cholecalciferol↗
25-hydroxycholecalciferol in the treatment of renal osteodystrophy in haemodialysed patients.
The effects of 25-OHD3 on renal osteodystrophy have been studied in 6 patients on maintenance haemodialysis. Administration of 25-OHD3, 50 microgram/day, did not improve biochemical data and intestinal absorption of calcium. With a dose of 100 microgram/day in all patients an increase in blood calcium levels eventually reaching hypercalcemic values was observed. In two cases a fall in alkaline phosphatase toward normal values was noted. In the same cases the treatment-induced hyperphosphatemia, uncontrolled by AI(OH)3 supplementation and similarly high iPTH levels were observed. In two cases repeated bone biopsy following 8 months treatment and not show substantial improvement of bone lesions. In one case addition of 1,25-(OH)2D3 to the treatment with 25-OHD3 led to a more rapid improvement in biochemical parameters and iPTH serum levels. Doses of 25-OHD3 capable to correct blood calcium levels and intestinal absorption of calcium, may have minimal benefit on the osteitis fibrosa component of the bone lesion.
Adolescent↗
[Importance of the thyroid gland in calcemic homeostasis during intestinal calcium absorption in man].
The importance of calcitonin (CT) in calcaemic homeostasis has been studied in control subjects and in thyroidectomized patients. After administration per os of a calcium load together with a radioactive tracer, calcaemia increases more markedly in thyroidectomized cases while the radioactivity curve shows no difference between the two groups. Unlike the controls, in patients the absorption-induced calcaemic increment curve coincided with the cumulative intestinal calcium absorption curve evaluated by the biradioisotopic method. Thus absorption-induced hypercalcaemia in athyroid subjects would not seem to be controlled by homeostatic factors. Through CT, the thyroid exerts an evident, though limited, braking action on calcaemic increase due to absorption. Considering that absorption of calcium is prolonged for a number of hours, CT secretion will last at least as long as will its action on the skeleton. The saving of skeletal mineral that follows may be considered to be physiologically more important than the effect of the hormone on calcaemic homeostasis.
Adolescent↗