Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

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     

Prevention of post-operative infections in urologic surgery. Comparative study of cotrimoxazole and cefazolin

The main point of this study resides in comparing the efficiency and the disadvantages of using cefazoline and cotrimoxazole in the prevention of post-surgery infections of the low urinary tract. 91 patients who were about to undergo urologic surgery were divided in three groups for randomisation. 31 patients received 500 mg of intramuscular cefazoline every eight hours, the day before surgery, the day of surgery and five days following surgery. 30 others received 800 mg of intramuscular sulfametoxazole and 160 mg of trimetoprime every 12 hours during the same lapse of time. The third group of 30 patients did not receive any antibiotics. Age, sex, clinical pathology needing surgery and indwelling catheter were the same in the three groups. The group treated by cefazoline, presented 5 post surgery infections among which 3 transitory fevers and 2 isolated bacteriurias. In the group treated by cotrimoxazole, there were 7 post surgery infections among which 3 fevers and 4 isolated bacteriurias. Tolerance in both cases was similar. In the control group, there were 19 post-surgery infections with 2 cases of sepsis, 14 transitory fevers and 3 isolated bacteriurias. These results show the importance of antibiotic prophylaxy in urologic surgery of the low genital tract whether the patient has a urethral catheter or not and whatever the type of urologic surgery. But, there is no significant difference between cefazoline and cotrimoxazole.     

Delivery of therapeutic doses of doxorubicin to the mouse lung using lung-accumulating liposomes proves unsuccessful

Cancer Chemotherapy and Pharmacology - Addition of solid doxorubicin or solutions to pre-formed liposomes proved to be the optimal method for incorporating the drug into liposomes whilst...     

Current trend in the treatment of Hodgkin's disease

The analysis of three subsequent randomized trials carried out within the frame of the European Organization for Research on Cancer (E.O.R.T.C.) enables to define a strategy for the staging and the treatment of early stages of Hodgkin's disease. Several prognostic factors were identified by multivariate analyses: 1) erythrocyte sedimentation rate, which has a greater impact on relapse-free survival than systemic symptoms but which can be combined with them; the combination of the two is a more powerful prognostic indicator than ESR alone; 2) the number of involved lymphatic areas: patients with one or two lymphatic areas involved (CS I and II2) have a better outcome than stage II patients with 3 or more areas involved (CS II3). Patients with favorable prognostic indicators are submitted to staging laparotomy because for them spleen involvement has a pejorative impact. For patients with unfavorable indicators, the spleen involvement has little prognostic significance and therefore those patients who need, anyway, an aggressive treatment do not undergo staging laparotomy. Patients with favorable prognostic indicators and negative staging laparotomy can be treated by radiotherapy alone, patients with positive laparotomy or patients with unfavorable prognostic indicators are treated by combination of multiple chemotherapy and radiotherapy.     

Motivated behavior and the estrous cycle in rats

(1) The estrous cycle in the rat may be used to study recurrent changes in motor behaviors and motivation which are strongly related to cyclic hormonal and CNS changes. (2) The peak in motivated behaviors occurs during a sharply defined period on the night between proestrus and estrus and is evident in facilitated wheel-running, lordosis, and intracranial self-stimulation. (3) Behaviors without a clearly motivated character do not show an estrous cyclicity. (4) The estrous cyclic variation in intracranial self-stimulation was observed at a specific locus — the pars campacta of the substantia nigra. (5) A neurochemical link between sexually motivated behavior, wheel running and intracranial self-stimulation is suggested. This link is in part dopaminergic but is probably also activated by many other systems.     

Distribution of organic matrix in calcium oxalate renal calculi

Summary The quantity of protein and carbohydrate comprising the matrix of calcium oxalate monohydrate (COM) renal stones was found to decrease with distance from the surface of the stone. The average organic concentration of stones 3 to 30 mm in diameter ranged from 5.7% at the surface to 2.7% at the core. This concentration gradient suggests matrix involvement in a “growth front” on stone surfaces with migration of organic material from the “older” interior. The matrix distribution was not readily correlated with density variations or with the presence of hydroxyapatite or calcium oxalate dihydrate. Surface matrix concentrations were greater than amounts predicted by physical adsorption. Electron microscopy confirmed the presence of the organic-rich surface layer and also suggested that increase in stone size occurs predominantly by crystal growth with microcrystal aggregates as growth centers.     

Sphincter injury after anal dilatation demonstrated by anal endosonography.

Anal dilatation is still used in the treatment of anal fissure and haemorrhoids. Using anorectal physiology and anal endosonography we have studied 12 men presenting with faecal incontinence following anal dilatation. Resting anal pressures were low, pudendal nerve latencies were normal; 11 men had a disrupted internal anal sphincter and in ten this was extensively fragmented. Three also had defects of the external anal sphincter. These findings demonstrate for the first time the nature of the structural injury which may be caused by anal dilatation.