Effect of clodronate treatment on risk of fracture: a systematic review and meta-analysis.

A systematic review and a meta-analysis of data of literature were performed to evaluate the efficacy of clodronate in the reduction of risk of fractures in patients with osteoporosis or tumour diseases. A systematic review was conducted to identify original articles, reviews, and any other literature report suitable for the purposes of the meta-analysis, limited to prospective randomized trials that included a placebo or an untreated control arm. The search has identified 18 trials, 13 of which in patients with cancer diseases (breast cancer and multiple myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in elderly women living in community. A placebo control arm was used in 13 trials. Treatment and follow-up duration ranged from 3 months to 5 years. The meta-analysis showed that treatment with clodronate was associated with a reduction of the probability of new fractures compared with controls (OR = 0.572, 95% CI 0.465-0.704 for new vertebral fractures; OR = 0.668, 95% CI 0.494-0.905 for new non-vertebral fractures; and OR = 0.744, 95% CI 0.635-0.873 for new overall fractures in those articles where vertebral and non-vertebral new fractures were not considered separately). Similar findings were observed in the separate analysis in patients with cancer forms or osteoporosis. The results of the meta-analysis have demonstrated that clodronate is effective in reducing the risk of vertebral, non-vertebral, and overall fractures in patients with skeletal fragility.

Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.

This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP < or =90 mm Hg) and responder (sitting DBP reduction of 10 mm Hg or DBP < or =90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.

Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects.

Aim of the study was to investigate activin A serum concentration in healthy adult males and post-menopausal females over a wide age-range and its correlation to gonadotropins, inhibin B and testosterone concentrations. The study included 73 males (aged 30-101 years) and 42 postmenopausal females (aged 50-104 years). Blood samples were collected after an overnight fast to measure serum activin A, inhibin B, LH, FSH, and gonadal steroid levels. A significant increase in serum activin A levels over age in both genders, especially in the oldest age-groups, was observed. Serum inhibin B and testosterone concentrations showed a sharp decrease in male subjects, reflecting the age-related decrease of testicular function and by consequence serum FSH and LH significantly increased. In female subjects LH and FSH levels were very high in subjects in their 50s and showed a continuous decline due to pituitary aging. Simple and multivariable regression analyses demonstrated the lack of correlation between activin A and FSH in both males and females. In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified.

Corticosteroids administered by nebulization to children with bronchial asthma.

Inhaled corticosteroids are recommended for long-term control of asthma in children, and nebulization simplifies administration to patients who lack hand-to-lung coordination. Information on the efficacy and safety of nebulized corticosteroids in children with mild to moderate asthma is limited, however, and comparison between corticosteroids is lacking. One hundred thirty-three patients 6 to 14 years of age with bronchial asthma were randomly assigned to receive flunisolide 500 microg or budesonide 500 microg, both administered twice daily by nebulizer for 4 weeks. Morning peak expiratory flow rate (primary efficacy endpoint) increased significantly from baseline (P<.001) with both medications (P = NS between treatments). Use of salbutamol as rescue medication decreased by 82.6% with flunisolide and by 82.7% with budesonide; respective decreases in asthma score were 78.8% and 82.3% (P<.001 vs baseline, P = NS between treatments). Only flunisolide reduced the number of nocturnal awakenings (P<.001). Ten patients in the flunisolide group and 12 in the budesonide group reported adverse events, none of which required discontinuation of treatment. In children with asthma, nebulized corticosteroids are effective and have good safety and tolerability profiles. Flunisolide and budesonide seem to produce equivalent clinical responses.

Beclomethasone dipropionate versus budesonide inhalation suspension in children with mild to moderate persistent asthma.

Inhaled steroids are the most effective long-term treatment of persistent asthma but many children are unable to use correctly the available inhalers. Administration of nebulized corticosteroids has some advantages over the administration with pressurised metered-dose inhalers (pMDls). The objective of this multicenter randomised study was to compare the efficacy and tolerability of nebulized corticosteroids in paediatric patients with asthma. 127 patients aged > or = 6 and < or = 14 years with a diagnosis of mild to moderate persistent asthma (PEFR % predicted > 50% and < 85%) and positive response to the reversibility test were randomized. The patients were assigned by randomisation to one of the two treatment groups (4 weeks): beclomethasone dipropionate (BDP) 800 microg/daily b.i.d. (n = 66) or budesonide (BUD) 1000 microg/daily b.i.d. (n = 61) both administered by nebulizer. The primary efficacy end point was the final mean of PEFR measured at clinical visit (clinic PEFR). In the BDP group clinic PEFR increased from 177.5 +/- 80 L/min to 246.6 +/- 84.2 L/min (p < 0.001 vs baseline), while in the BUD group the increase was from 180.4 +/- 77.8/min to 260.9 +/- 84.1 L/min (p < 0.001 vs baseline) (NS between treatments). FEV1 (% predicted) increased from 77.8% to 92.7% (p < 0.001 vs baseline) and from 74.1% to 95.9% (p < 0.001 vs baseline) in BDP and BUD group respectively (NS between treatments). Patients reduced the use of salbutamol rescue medication by 76% and 81% in BDP and BUD group respectively (p < 0.001 vs baseline, NS between treatments). 4 patients in the BDP group and 2 in the BUD group reported adverse events (AEs). AEs were mild to moderate and never there was the need to discontinue the treatments. In conclusion the results of this study demonstrate that both BDP (800 microg/daily) and BUD (1000 microg/daily) administered by nebulization are effective and with a acceptable safety and tolerability profile.

Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis.

Forty postmenopausal women with bone mineral density (BMD) > 2 standard deviations below the mean value for healthy age matched controls were enrolled into an open controlled study to evaluate the metabolic and bone effects of ipriflavone (IP) versus salmon calcitonin (sCT) over a 12 month period. Both treatments significantly increased BMD after 6 and 12 months. A 4.3% increase of BMD was obtained in the IP treated group and a 1.9% in the sCT treated group after 12 months (p < 0.001 between treatments). Bone metabolism markers (serum osteocalcin, alkaline phosphatase, urinary calcium and hydroxyproline/creatinine ratio) were significantly reduced in both groups (p < 0.001). The reduction of urinary hydroxyproline/creatinine ratio was significantly greater (p < 0.05) in the IP group after 12 months. Both treatments were well tolerated. Four patients in the IP group reported gastralgia while two patients in the sCT group reported pruritus and one patient epistaxis.

Comparison of cefatrizine and erythromycin for pediatric ear, nose, and throat infections.

A comparison was made of cefatrizine in dosages of 75 mg/kg/day administered once daily or twice daily and erythromycin in a mean daily dosage of 50 mg/kg given in three divided doses for the treatment of acute infections of the ear, nose, and throat in children. Temperature was recorded twice a day during therapy. At the end of treatment, a clinical evaluation of cure, improvement, or failure was made, based on defervescence and abatement of symptoms. All ten children given cefatrizine once daily were cured (P less than or equal to 0.05), as were eight of ten given cefatrizine twice daily and four of ten given erythromycin. The remaining eight patients were improved. One patient given cefatrizine had diarrhea, which appeared on the fifth day of treatment. No other side effects were observed. Cefatrizine appeared to be similarly effective whether given once a day or twice a day; further trials are warranted to confirm the efficacy of once-daily treatment with this cephalosporin.

Chemiluminescence, phagocytosis, chemotaxis and killing activity of human leukocytes exposed to Clindamycin.

We measured the chemiluminescence (CL) of human leukocytes (PMNs) exposed to different concentrations of Clindamycin (1; 5; 1 mcg/ml) using a standardized luminolamplified reagent-instrument methodology (Auto Picolite 6500 Luminometer and ZAP/Picolite Kits, Packard Instruments Co. Drowners Grove, IL. USA). Cells obtained from healthy donors were also tested for chemotaxis with Boyden chambers, for phagocytosis and for killing activity against Staphylococcus aureus by the agar-medium culture plate technique. Clindamycin does not induce significant variations of the CL response in whole blood, or changes in phagocytosis and killing activity. On the contrary, concentrations of drug corresponding to therapeutically obtainable levels significantly increase light emission by isolated cells. A concentration effect was seen on leukotaxis, that was increased, but not significantly, at 1 and 5 mcg/ml and decreased (P less than 0.01) at 10 mcg/ml. CL assay is a simple, sensitive, reproducible technique to assess the PMNs functions during antibiotic therapy.

Evaluation of systolic time intervals in patients with angina pectoris.

We have explored the systolic time intervals of 52 patients with angina pectoris at the time of their hospitalization in our wards. Our results are in close agreement with published data, essentially indicating prolongation of the preejection time and shortening of the ejection time. These alterations of systolic times can be interpreted pathophysiologically as as expressing reduced myocardial contractility. The long PEP-short LVET polygraph picture, occurring in the course of chronic ischemic heart disease, reveals the deficit of myocardial contractility at a stage of the disease at which clinical evidence of left ventricular failure is usually not yet detectable.

[5 years' experience with spectinomycin in treating gonorrhea]. / Cinque anni di esperienza con la spectinomicina nel trattamento della gonorrea.

Incidence of gonorrhoea in over 50,000 outpatients of the University of Bologna Department of Dermatology reduces to 50% in the five-year period 1976-1980. At the same time effectiveness of spectinomycin in the treatment of gonorrhoea remains unchanged.

A polygraph study of ischemic heart disease: short-term prognosis of acute myocardial infarction based on early modifications of isometric contraction time.

The authors have explored the early modifications of systolic time intervals in 90 patients hospitalized as emergency cases for acute myocardial infarction. From analysis and interpretation of the collected data they conclude that such modifications have considerable prognostic value. All patients fitting the specifications of NYHA classes I and II, but at the same time showing a shortening of the isometric contraction time to less than 39 +/- 1.4 ms turned out to constitute a high-risk group for the development of major mechanical and electrical complications in the next 2 weeks.

[Sclerodermic heart. Report of a case with malignant evolution (author's transl)]. / Il cuore sclerodermico. A proposito di un caso ad evoluzione maligna.

In progressive systemic sclerosis, cardiac involvement, evidenced by histology, is rather unusual and even more rarely it gives clinical manifestations. In our patient cardiac symptoms, characterized by recurrent pulmonary edema as well as by serious conduction defects and arrhythmias, are prevailing and have a rapid and fatal course, whereas the involvement of the skin and of other internal organs is not important. The post-mortem examination gives an evident explanation of the clinical course of the disease, which we can consider as a typical manifestation of sclerodermic heart.