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Biomedical subjects

R Nuti

Publications and source records attributed to R Nuti.

At least 55 records · Page 3Linked to original sources

Metabolic effects of rectal administration of unmodified eel calcitonin in humans.

To evaluate the metabolic effects of unmodified eel calcitonin, nine normal subjects and eleven patients with Paget's disease of the bone entered the study. Eel calcitonin was administered via rectal mucosa at the dosage of 100 and 200 MRCU. Plasma calcium, plasma phosphate and plasma cAMP were measured at a baseline and after 10, 20, 30, 60, 90, 120, 180, 240 min. Rectal administration of 100 MRCU of eel calcitonin decreased plasma calcium and phosphate levels in normal subjects; the hypocalcaemic and hypophosphatemic effects were more marked and statistically significant in Paget's disease patients. Using 200 MRCU of eel calcitonin, statistically significant reductions in plasma calcium levels were observed in controls and in Paget's disease patients. Plasma phosphate decreased after rectal administration of the hormone, but not significantly. A slight but not significant increase in plasma cAMP was observed in normal subjects after the administration of 200 MRCU. These data demonstrate that eel calcitonin administered via rectal mucosa can exert some of the known biologic effects of the peptide.

Administration, Rectal↗

[Methods for measuring whole-body adipose tissue: the usefulness of "total body" X-ray densitometry].

"Total body" densitometry, which was first used to determine total-body mineral content, allows, above all in the most recent X-ray (DXA) version, an accurate study to be made of soft tissues in relation to both their adipose and nonadipose components. In addition to being used for overall evaluations, it is possible to use DXA for regional studies of body tissue distribution, thus allowing obesity to be analysed not only in quantitative but also qualitative or more specifically endocrine-metabolic terms. In comparison to other methods DXA is noninvasive, quick to use, low cost and risk free. Given its high accuracy rate it can also be used to monitor patients with demineralizing pathologies, obesity, thinness due to global and/or district edema receiving dietary and/or pharmacological treatment.

Absorptiometry, Photon↗

[An autopsy study of patients who died at the Medical Clinic of the University of Siena from 1986 to 1989].

In the past twenty years autopsies are performed much less frequently in the elderly than in younger patients. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 214 patients who died from 1 January 1986 to 31 December 1989 at our Institute to determine the accuracy of clinical cause of death with respect to the pathologic cause of death. The most common cause of death were bronchopneumonia (25.2%) followed by gastroenteric and lung cancer (20%), cerebrovascular accident (15.8%), myocardial infarction (8%) and pulmonary embolism (7.4%). Pulmonary embolism was correctly classified only in 25% of patients. The most accurately diagnosed condition were neoplastic diseases (88%) and cerebrovascular accident (84.8%) while bronchopneumonia were correctly diagnosed antemortem in 72.2% of the patients studied. Our data suggest that advances in diagnostic technology have not reduced the value of the autopsy and that a goal-directed autopsy remains a vital component in the assurance of good medical care.

Age Factors↗

Comparison of total-body measurements by dual-energy X-ray absorptiometry and dual-photon absorptiometry.

Both dual-photon absorptiometry (DPA) using 153Gd and dual-energy x-ray absorptiometry (DEXA) can be used for measurement of bone mineral content (BMC) and bone mineral density (BMD) of the total skeleton and its seven major regions. The short-term precision (coefficient of variation, CV) of DEXA for total-body BMD using the medium (20 minute) and fast (10 minute) speeds was 0.34 and 0.68% in 5 normal subjects; the corresponding CV in 5 osteoporotic females were 0.70 and 1.04%. The CV for BMD using DPA was 0.82% in 8 normal subjects and 0.70% in 12 osteoporotic patients. The CV for regional BMD using DPA was similar to fast-speed DEXA, without significant differences (p NS); precision with medium-speed DEXA was superior to DPA, and the differences were statistically significant (p less than 0.05) for head, spine, trunk, ribs, and pelvis. Total-body measurements using both DPA and DEXA were done on 99 subjects (84 females and 15 males). Significant correlations (r = 0.98; p less than 0.001) were found between DEXA and DPA measurements of both BMC and BMD. There were also significant correlations (r = 0.94-0.98; p less than 0.001) between DEXA and DPA measurements of anatomic regions (head, trunk, spine, pelvis, ribs, arms, and legs). DPA and DEXA results for BMD of total skeleton, ribs, pelvis, and legs were similar (p NS), and statistically significant differences were found in head, spine, and arm measurements (p less than 0.01, p less than 0.01, and p less than 0.05, respectively); regression equations allowed adjustment of DEXA values in patients already measured with the earlier DPA method.

Absorptiometry, Photon↗

Long-term treatment with calcitriol in postmenopausal osteoporosis.

In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.

Aged↗

Total body and regional bone mineral analysis by dual-photon absorptiometry in Paget's disease of bone.

Total body density (TBD), total body bone mineral (TBBM) and bone mineral content of major anatomical skeletal areas were measured in 66 patients with Paget's disease of bone (54 polyostotic; 12 monostotic; 38 males; 28 females; 38-88 years), by dual-photon absorptiometry (153 Gd). TBD was elevated in 23 males and three females with Paget's disease; a statistically significant correlation was found between elevated values of TBD and a widespread extent of the disease. The mean value of TBBM was higher in pagetic males, while in pagetic females it was similar to normal subjects. The separate analysis of anatomical areas allowed us to appreciate increased values of bone mineral content in head, trunk, spine, pelvis, arms. Moreover in 28 patients with easily detectable pagetic lesions of long bones, 38 specific regions of interest (ROI) were evaluated: pagetic areas showed significantly higher values of bone density and bone mineral content in comparison with contralateral uninvolved areas.

Adult↗

Main endocrine modulators of vitamin D hydroxylases in human pathophysiology.

Vitamin D is considered to be devoid of direct biological activity. It must be first hydroxylated in the liver by a 25-hydroxylase (25OHase), then in the kidney by a 1 alpha-hydroxylase (1 alpha OHase) which is responsible for the synthesis of the active metabolite, 1,25-dihydroxyvitamin D (1,25(OH)2D). The activity of 1 alpha OHase is known to be under the control of a series of endocrine modulators, particularly parathyroid hormone (PTH) and estrogens. We report here our studies in humans concerning the behaviour of vitamin D hydroxylases in some pathological conditions. In chronic liver disease no severe impairment of vitamin D-25-hydroxylation has been observed, except in the latest stages: this is probably due to the great functional reserve of the liver, so that normal levels of serum 25OHD can be maintained on condition that the vitamin D supply is adequate. 1 alpha OHase is impaired in chronic renal failure due to the decrease in the number of functioning nephrons. It has been demonstrated that kidney transplantation restores normal 1,25(OH)2D levels. A decrease in 1,25(OH)2D production due to reduced PTH stimulation has been observed in hypoparathyroidism: in these patients a subcutaneous substitution therapy with synthetic human parathyroid hormone resulted in restoration of normal 1,25(OH)2D levels. A reduced activity of 1 alpha OHase due to reduced estrogen stimulation plays a key role in postmenopausal osteoporosis. In these patients estrogens increase 1,25(OH)2D levels, as it has been demonstrated directly and indirectly. In the aforementioned pathological conditions an impairment of calcium absorption has been observed; it was directly related to the reduced production of 1,25(OH)2D. Treatment with 1,25(OH)2D3 was effective in restoring normal calcium absorption. In postmenopausal osteoporosis the reduced levels of 1,25(OH)2D were accompanied by serum levels of 25-hydroxyvitamin D (25OHD) higher than in age-matched control women. In these cases long-term treatment with physiological doses of 1,25(OH)2D3 resulted in a progressive decrease in 25OHD serum levels which approached to the normal range. These findings are likely to be related one to another: the low 1,25(OH)2D levels are responsible for reduced product-inhibition of 25OHase, so that the synthesis of 25OHD increases. A similar mechanism occurs in renal failure and in hypoparathyroidism.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Carbocalcitonin treatment in Sudeck's atrophy.

The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

Adult↗

Pathophysiological aspects of calcium metabolism in spasmophilia.

In order to clarify the pathophysiological mechanisms of spasmophilia, 34 subjects (31 females and 3 males) with spasmophilia were studied. The diagnosis of spasmophilia was based on a specific clinical protocol and electromyographic criteria. In the study, markedly reduced plasma ionized calcium and serum magnesium concentrations were observed together with slightly and non-significantly reduced plasma calcium and phosphate levels. An impairment of intestinal radiocalcium absorption was also noticed. Parathyroid secretion did not show any significant disturbance, but circulating calcitonin levels were found to be significantly lower than in normal subjects. The mean value of serum 25OHD was within the normal range, while a slight reduction in bone Gla protein, an index of osteoblastic activity, was detected. No difference between patients with spasmophilia and normal subjects was observed concerning 47Ca kinetics in red blood cells. The studies indicated that an impaired intestinal calcium transport together with low levels of circulating calcitonin represent the most important pathophysiological determinants of spasmophilia.

Adult↗

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis.

Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 microgram/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3). Basal serum BGP was significantly lower in osteoporotic women (3.8 +/- 1.4 ng/ml) than in age-matched controls (6.8 +/- 2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8 +/- 1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25(OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation.

Aged↗

[Effects of nandrolone decanoate on bone mineral content and intestinal absorption of calcium].

To evaluate the effects of a long-term treatment with nandrolone decanoate on metabolism of the skeleton, a double-blind randomized study was carried out in women with joint diseases without metabolic bone derangement. Ten patients were treated with 50 mg of nandrolone decanoate every three weeks for two years; in six subjects a treatment with placebo was performed. As it concerns plasma calcium and phosphate, serum alkaline phosphatase, urinary excretion of calcium, phosphate, hydroxyproline and cAMP, as parathyroid index, it was not observed significant differences in the two examined groups. While in placebo group at the end of the study the intestinal radiocalcium remained unchanged and bone mineral content showed a slight decrease, on the contrary nandrolone decanoate treatment promoted a significant improvement in intestinal calcium absorption and an increase in bone mineral content.

Adenosine Monophosphate↗

25-Hydroxycholecalciferol as an antagonist of adverse corticosteroid effects on phosphate and calcium metabolism in man.

The present study was performed in 30 patients who needed steroid therapy: courses of triamcinolone or DTM 8-15 given orally lasted 30 days. In 15 of these patients glucoactive corticosteroids were administered in combination with 5 micrograms/day of 25OH-vitamin D3 (25OHD3). 47Calcium oral test and 99mTc-MDP kinetics, as an index of bone turnover, were performed at the beginning of the therapy and after 30 days. At the end of treatment a significant improvement of intestinal radiocalcium transport together with a decrease in bone turnover in the group of patients treated with 25OHD3 was observed. As it concerns plasma calcium level, inorganic phosphate, the urinary excretion of calcium, phosphate and hydroxyproline no significant difference between the two groups examined were noticed. These results indicate that the adverse effects of glucoactive corticosteroids on intestinal calcium transport and bone turnover may be counteracted by the combined administration of physiological doses of 25OHD3.

Adolescent↗

The hormonal form of vitamin D in the pathophysiology and therapy of postmenopausal osteoporosis.

Sixty-two women with symptomatic postmenopausal osteoporosis underwent long-term treatment with 1,25-dihydroxyvitamin D3. The following results were obtained: i) a dramatic improvement of the intestinal transport of radioactive calcium, which was impaired prior to the treatment; ii) non significant increases in fasting serum calcium; iii) significant increases in the 24 h urinary excretion of calcium and phosphate, resulting from the improvement of intestinal calcium absorption, and a decrease in the urinary cAMP/Cr ratio; iv) non significant changes in serum phosphate, serum alkaline phosphatase, urinary hydroxyproline; v) non significant increases in bone mineral content; vi) relief from pain and improvement of motility in all the patients; vii) no side effect was noticed. In conclusion the treatment with 1,25-dihydroxyvitamin D3 was shown to be useful in postmenopausal osteoporosis.

Aged↗

Clinical, biochemical and histological results of a double-blind trial with 1,25-dihydroxyvitamin D3, estradiol and placebo in post-menopausal osteoporosis.

Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aimed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), estradiol valerate (E2) and placebo. Patients were divided into 4 groups: group 1 was given 1,25(OH)2D3 alone, group 2 was given E2 alone, group 3 was given 1,25(OH)2D3 + E2, group 4 received a placebo. The evaluation of the effects of the treatments included clinical examination of patients, the measurement of a number of biochemical parameters, such as plasma and urinary calcium and phosphate, urinary hydroxyproline, serum alkaline phosphatase, the measurement of intestinal calcium absorption and bone mineral content (BMC) and a histomorphometric study of bone biopsies from the iliac crest. The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3, while patients in the placebo group worsened. BMC decreased in the placebo group and increased, although non significantly, in the patients treated with 1,25(OH)2D3 or E2 or both. The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2. Changes in the volume density of trabecular bone paralleled those in BMC. The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis.

Aged↗