This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the
prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53
years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was
at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800
mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days
for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of
2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg
of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening,
and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were
−3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to
4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference
between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5%
in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between
groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral
neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between
clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate
in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually
within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose
of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively
reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective,
placebo-controlled trials.
Received: 4 March 2002 / Accepted: 9 July 2002 相似文献
Background: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration.
Methods: An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 106 cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections.
Results: Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 [mu]g/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 [mu]g/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 [mu]g/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 [mu]g/g in lung segments with lung aeration of 50% or more. 相似文献
OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT. 相似文献
Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density (BMD) to evaluate the probability of Colles' fracture. Two-hundred eighty-nine postmenopausal women (62.3 +/- 8.7 yr) with (n = 76) and without (n = 213) Colles' fracture were studied. BMD of lumbar spine and proximal femur was evaluated in all women by dual-energy X-ray absorptiometry (DXA) and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness in the calcaneus were measured by a Sahara ultrasonometer (Hologic). Patients suffering from Colles' fracture had lower values of BMD adjusted by height at the lumbar spine, L2-L4 (0.797 g/cm2 vs 0.860 g/cm2), femoral neck (0.685 g/cm2 vs 0.712 g/cm2 ), SOS (1518 m/sg vs 1525 m/sg), and stiffness (74.6 vs 77.7) (p < 0.05). Nevertheless, BUA values were similar in both groups. After stepwise logistic regression analysis, the area found under receiver operating characteristic (ROC) curves was 0.60 for L2L4 and 0.63 for a formula combining L2L4 and height. Our data suggest that patients suffering from Colles' fracture have lower values of BMD by DXA, SOS, and stiffness. However, the ability of these techniques to discriminate is low because the values for the area under ROC curve are 0.60 for L2-L4 and 0.63 for a formula derived of the combination of L2-L4 and height. 相似文献
Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT. 相似文献
Abstract: In order to evaluate the level of evidence of factors influencing the survival of reconstructions, systematic reviews of the relevant literature were prepared by a group of rapporteurs. The review papers were circulated to the members of the group before the conference and formed the basis for group and panel discussions. Subsequently, modifications were added to the review papers, and suggestions for consensus statements concerning the following topics were prepared and again critically reviewed in the group and in the plenum: Impact of (i) periodontal disease on the survival of tooth-supported reconstructions, (ii) post-surgical factors as supportive therapy on the survival of implant supported reconstructions, (iii) technical and/or biological complications on the survival of different types of reconstructions, (iiii) material choice for reconstructions on the survival of single crowns and fixed dental prostheses. 相似文献