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Biomedical subjects

C Gennari

Publications and source records attributed to C Gennari.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

OBJECTIVE: To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN: Retrospective, population based, case-control study by questionnaire. SETTING: 14 centres in six countries in southern Europe. SUBJECTS: 2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES: Number of drugs affecting bone metabolism taken and length taken for. RESULTS: Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS: Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.

Aged↗
PubMed1992

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss.

In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.

Administration, Intranasal↗
PubMed1992

Short-term treatment of Paget's disease of bone with ipriflavone.

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.

Administration, Oral↗
PubMed1992

Treatment of bone metastases with dichloromethylene bisphosphonate.

PURPOSE: The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS: Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS: Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS: We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Evaluation of the hereditary component in patients with essential arterial hypertension].

As is well known, genetic factors play a decisive role in the pathogenesis of essential hypertension (EH), even if they are closely related to environmental factors; it is therefore not possible to quantify with any degree of certainty the role and importance of each in the onset of hypertensive disease. The aim of the present study was to ascertain the presence of hypertensive 1st and 2nd degree ascendant, collaterals and descendants in a group of 355 out-patients with EH (167 males, 188 females; mean age: 52.9 +/- 0.7 years) using an anamnestic analysis. The results of this study confirmed the high prevalence of the hereditary component in EH: familial hypertension was found in 60.6% of the group. From a detailed analysis of the group, with regard to hypertensive ascendant, the hereditary transmission of EH by the mother was significantly higher than that by the father, both the parents and the forefathers, even if it is worth pointing out that the penetration of the genetic character was not always sex-related and was equally distributed between male and female descendents. In addition, it was observed that patients with a familial pattern of hypertension in common with collateral relatives showed significantly enhanced levels of systolic and diastolic pressure in relation to those with another hereditary component. These findings serve to underline the importance of evaluating the effective incidence of EH with regard to an entire family nucleus and not only in individual terms, in order to identify the various means of genetic transmission and possible interactions with environmental factors.

Female↗
PubMed1992

[Metabolic changes in the patient with essential hypertension].

The aim of the present study was to evaluate a number of parameters in a group of patients with essential hypertension and then compare the results with those in a group of healthy normotensive subjects. One hundred and fifty-six patients with essential hypertension (EH) in the non-complicated form (73 males, 83) females; mean age: 54.8 +/- 0.9 years) were selected and compared with 150 normotensive subjects matched for age and sex. After a 2-week period of wash-out during which patients followed a diet with normal sodium and calorie content, body mass index, systolic and diastolic arterial pressure (AP), mean arterial pressure (MAP), heart rate in clino- and orthostatism were measured and blood was collected to assay glycemia, total cholesterolemia, LDL and HDL cholesterolemia and triglycerides. In the group of patients suffering from EH all the above parameters were found to be significantly higher than in normotensive control subjects. In particular, in the hypertensive population the prevalence of obesity was 21.3%, hyperglycemia 26.9%, hypercholesterolemia 65.1% and smoking 36.4%. When the possible relation between one or more risk factors and AP values was assessed, it was found that in hypertensive patients the presence of hyperglycemia alone or in association with other metabolic disorders led to the highest MAP findings. Moreover, having studied the correlation rate of the various parameters, it was seen that in both the hypertensive and normotensive populations systolic AP measured in clinostatism positively correlated with glycemia, total cholesterolemia, and age, whereas correlations were not found between clinostatic diastolic AP and the above parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Use of calcitonin in the treatment of bone pain associated with osteoporosis.

In osteoporosis, calcitonin exerts an analgesic effect that is unrelated to its effect on bone. Although the precise mechanism has yet to be clarified, there is some evidence that the analgesic effect of calcitonin may be mediated through the endogenous opioid system. The intranasal administration of calcitonin seems to be more effective in producing analgesia than parenteral administration.

Bone and Bones↗
PubMed1991

Long-term antihypertensive treatment with lacidipine, a new long-acting calcium antagonist.

Eleven centers in Tuscany, Italy, recruited 96 patients (aged 21-75 years) with mild-to-moderate essential hypertension [diastolic blood pressure (DBP) 95-115 mm Hg; systolic blood pressure (SBP) less than or equal to 200 mm Hg]. After a 4-week, single-blind, placebo run-in period, patients received lacidipine 4 mg once daily. If blood pressure was not controlled after 1 month (control = DBP less than or equal to 90 mm Hg, or less than or equal to 95 mm Hg if reduced by greater than or equal to 15 mm Hg from baseline), the dose was increased to lacidipine 8 mg once daily. Atenolol 50 mg once daily was added after 2 months' monotherapy, if required for blood pressure control. The study continued for 13 months. About 40% of patients were titrated to 8 mg lacidipine; only 7% required addition of atenolol. Lacidipine significantly reduced blood pressure, with 84% of patients showing control of pressure values 24 h after the previous dose on completion of 5 months' monotherapy (63% controlled with lacidipine 4 mg/day; 21% with lacidipine 8 mg/day). There was no clinically relevant difference in the first-dose effect between the two doses of lacidipine (4 mg and 8 mg); both smoothly reduced blood pressure, with maximum effect after 2 h. Lacidipine was well tolerated. Adverse events were those expected with dihydropyridines, were mainly mild and occurred early, disappearing without discontinuation of treatment. Results indicate that 4-8 mg of lacidipine, administered once daily, is effective and well tolerated in mildly to moderately hypertensive patients.

Adult↗
PubMed1991

Plethysmographic evaluation of the vascular effects of human calcitonin gene-related peptide in man.

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 micrograms human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP provoked a transient but significant decrease in systolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial O2 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and metabolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropeptide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels.

Calcitonin Gene-Related Peptide↗
PubMed1991

Dose-response bioactivity and bioavailability of salmon calcitonin in premenopausal and postmenopausal women.

We investigated the acute, dose-response to three intranasal doses of salmon calcitonin (sCT) (50 IU, 100 IU, and 200 IU) and one im dose (50 IU) in eight premenopausal and eight early postmenopausal women. Total serum calcium and serum beta-endorphin revealed significant changes after all four administrations (P less than 0.05). After the two highest intranasal and the im doses cAMP increased 10% and 35%, respectively (P less than 0.05). All administrations except the 50 IU intranasal dose produced significant increases in plasma sCT (P less than 0.05). The areas under the concentration-time curves, calculated for the period with the maximal changes (i.e. 120-240 min), illustrated a significant dose-related response in total serum calcium, beta-endorphin, and sCT (P less than 0.01-0.001). cAMP showed a dose-related tendency, the response to the im injection being significantly higher than that to the two lowest doses of intranasal sCT (P less than 0.05). We conclude that the doses administered produce a dose-related biological response and bioavailability. In women with normal and high bone turnover, sCT 100 IU intranasally seems as optimal as 50 IU im. The response to sCT should, furthermore, be assessed on bioactivity rather than on bioavailability.

Administration, Intranasal↗
PubMed1991

Abnormalities in calcium metabolism in sarcoidosis.

In sarcoidosis the excess of calcitriol of extrarenal origin induces changes in calcium metabolism (CM), specifically hypercalciuria and less often hypercalcemia. We report the results of the study of CM in 44 sarcoidosis patients (mean age 43.7 +/- 11 years, M +/- SD, 21 males). 25% were on steroid therapy at the time of the tests. 34% of the patients had hypercalciuria, this figure rose to 39% if only untreated patients were considered. Hypercalcemia was found in only 2.2%. Chronic forms and extrathoracic involvement (mostly skin) were more frequent in the hypercalciuric patients than in the normocalciuric.

Adult↗
PubMed1990

Calcitonin, estrogens and the bone.

Estrogen deficiency following natural or surgical menopause, is thought to be the main factor leading to postmenopausal bone loss. Furthermore, after estrogen failure a significant reduction of intestinal calcium absorption and a negativization of calcium balance has been observed. The mechanism of estrogen effect on skeletal tissue is not yet fully elucidated. Recently, specific receptors for estrogens in osteoblastic cells have been described; however their low density does not give a full explanation about their functional role. Therefore estrogens act, at least in part, indirectly through calciotropic hormones. In order to further elucidate this issue, we performed some studies in postmenopausal osteoporotic patients and in fertile oophorectomized women. In the first double blind placebo controlled study, after a 1-year estrogen treatment period we observed an increase in bone mineral content in the hormone-treated patients. Furthermore, in all treated patients an improvement of intestinal calcium absorption was detected, while 1,25-dihydroxy-vitamin D serum levels did not show significant changes. To further analyse the relationship between estrogens (E) and calcitonin (CT) in postmenopausal osteoporosis, we performed a double blind placebo controlled study to evaluate the effects of 1-yr estro-progestative treatment on CT secretory reserve, evaluated by calcium infusion test. Blood levels of CT showed a progressive increase during the study period in the hormone-treated group, with a significant increase in the CT response to calcium stimulation test, suggesting a modulation of CT secretion by E. Recently, we performed two studies in fertile oophorectomized women. In the first, we followed longitudinally 24 fertile women for 1 yr. In these patients we measured, before and after oophorectomy, biochemical indexes of bone metabolism and bone mass. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. In the second study, performed on 14 women before and 6 months after oophorectomy, a treatment with conjugated estrogens allowed the correction of the primary intestinal defect responsible for the reduced calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗