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     

Image technique optimization in MR imaging of a titanium alloy joint prosthesis

The purpose of this study was to explore systematically the effect of the imaging parameters changeable by the user in spin-echo (SE) imaging sequences to minimize image distortion when imaging joint prostheses. A titanium alloy hip joint prosthesis was studied at 1.0 T. The SE imaging parameters were bandwidth/pixel (BW/p), TE, strength of encoding gradients (matrix size), echo train length (ETL), and direction of phase and frequency encoding. The effect of ETL in rapid acquisition relaxation enhanced (RARE) sequences was also evaluated with a turbo-SE sequence using a different ETL with the same TR and an effective TE. It is concluded that an optimized image quality can be achieved in SE imaging by using a high bandwidth/pixel value (at least 130 Hz/pixel), a high resolution matrix (256–512), sequences with multiple refocusing, and a frequency-encoding axis parallel to the long axis of the prosthesis. The degree of distortion is reduced with this optimized technique.     

Effect of totally absorbable implant volume on wound infection rate: Study of 2500 operated fractures, osteotomies, and ligament injuries

Between November 1984 and January 1994 in our department, a total of 2500 patients were treated with totally absorbable internal fixation devices. We studied these patients and analyzed results with regard to the volume of the absorbable implants and the development of wound infection. Of the 2500 patients 2044 were trauma patients and 456 were operated on for orthopedic disease. In 1466 patients treated with implants made of self-reinforced polyglycolic acid (SR-PGA) only, the patients who developed wound infection had a higher implant volume (P=0.07) than those who did not; this difference was close to statistical significance. In the 446 patients who received only implants made of self-reinforced poly-l-lactic acid (SR-PLLA), the 5 who developed wound infection had a mean implant volume more than three times that of the non-infected patients (P=0.01). We found that in the patients treated with the earlier SR-PGA implants, which contained a green staining material, there was no correlation between implant volume and incidence of wound infections. On the other hand, both the non-stained SR-PGA implants, which have been in clinical use since 1989, and the SR-PLLA implants, seem to be more predictable in terms of wound infections. We believe that this difference, is largely due to the lower level of tissue reactions with these newer implants.     

Misuse of zopiclone and convulsions during withdrawal.

It has been documented that benzodiazepines have the potential to cause dependence and withdrawal reactions, including convulsions. However, the available data concerning zopiclone, a nonbenzodiazepine hypnotic, are insufficient. The present study describes the case of a 36-year-old man who repeatedly misused zopiclone, in daily doses of 60-90 mg. Furthermore, the patient suffered from convulsion on two occasions following abrupt withdrawal of zopiclone. The concomitant use of alcohol, trimipramine, and promazine may have contributed to the development of convulsions. It is concluded that zopiclone may cause problems associated with misuse and withdrawal reactions similar to those of benzodiazepines.     

Role of pulmonary diseases and physical condition in the regulation of vasoactive hormones

Lungs have many non-respiratory metabolic functions, of which some take place in the capillary endothelium, while others are in parenchymal lung tissue. We have studied the role of the lungs in the metabolism of vasoactive and some other hormones by comparing patients who have undergone lung resection to those having various obstructive or fibrotic lung diseases. We have also compared these groups with persons in good physical health. The data suggested that lung resection patients had low angiotensin II levels in plasma but the response of angiotensin II to exercise was normal. Also adrenalin concentration was low in the lung resection group while dopamine did not show any significant difference between the groups. When hormone levels were correlated to the exercise data, renin levels were especially related to physical condition. Serum post-exercise renin values were inversely related to the uneven distribution of lung perfusion, possibly thus reflecting the diminished pulmonary vascularization. A negative association was found between angiotensin II and diffusion capacity. Thus, the angiotensin II levels may preferably be controlled by the non-circulatory functions of the lungs.     

Traumatic deaths in the emergency room: A retrospective analysis of 115 consecutive cases

Objective:   

The aim of the present study was to characterise traumatic deaths occurring in the emergency room (ER) and to assess retrospectively the quality of given emergency care by evaluating whether any of the deaths could be identified as potentially preventable.     

Screening of urinary tract abnormalities among day and nightwetting children

In order to detect possible urinary tract abnormalities among wetters, assessments of previous history completed by ultrasonography of the urinary tract and uroflowmetry were obtained for 145 wetting children and a random sample of 156 sex-matched non-wetting children drawn from a population of 3,375 seven-year-olds. Ultrasonography revealed abnormalities, including both morphological ones and cases with incomplete bladder emptying, in 5 out of 73 nightwetters (6.8%, 95% confidence limit, CL, 1.1-12.6), 10 out of 72 day and day and nightwetters (hereafter daywetters) (13.9%, CL 5.9-21.9) and 4 controls (2.6%, CL 0.1-5.0), the figure for the daywetters differing significantly from that for the controls (p less than 0.01). A fractioned voiding curve was recognized in 1 nightwetter (1.4%, CL -1.3-4.0), 7 daywetters (9.7%, CL 2.9-16.6) and 7 controls (4.5%, CL 1.2-7.7) the difference between the nightwetters and daywetters being significant (p less than 0.05). Depending on the previous history and abnormal findings in ultrasonography or uroflowmetry, examinations were continued with intravenous pyelography, voiding cystography, cystoscopy and/or by cystometry. Finally, marked structural or functional disorders of the urinary tract were detected in 11 out of 72 daywetters (15.3%, CL 7.0-23.6), 1 out of 73 pure nightwetters and 1 out of 156 control children. It is concluded that imaging of the urinary tract is not necessary for pure nightwetters, while ultrasonography or uroflowmetry and more sophisticated radiological or urological methods should be focused on those children with daytime wetting and clinical symptoms of voiding disturbances.     

Percutaneous aspiration and ethanol sclerotherapy of symptomatic hepatic cysts

Nineteen patients with 49 symptomatic non-neoplastic non-parasitic simple hepatic cysts were subjected to ultrasonographically guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. Small cysts were treated twice, the large ones three times at the same sitting. The volume of alcohol per injection varied from 20 to 100 ml, depending on the size of the cyst. A cure was usually achieved with one ethanol sclerotherapy treatment. Only minor side effects such as transient pain and temperature elevation occurred. Forty-seven of the 49 cysts could be treated adequately, and did not recur during a follow-up period af 12–40 months. The results indicate that aspiration an and ethanol sclerotherapy is the treatment of choice in patients with symptomatic non-neoplastic simple hepatic cysts or polycystic liver disease. Correspondence to: A. Leinonen