Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

New stand magnifiers do not meet rated levels of performance

A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'_v) rather than equivalent dioptric power (F_m) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use.     

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     

183例老年人骨密度检测分析

目的 :研究老年人不同疾病时骨密度 (BMD)的分布情况。方法 :用DXADAS 6 0 0EX型骨密度仪对183例老年患者进行左侧远程桡骨加尺骨BMD检测。结果 :内分泌疾病组、消化道疾病组和其它疾病组的患病率分别为 72 7% ,2 0 6 %和 31 4 %。T值比较 :三组差异明显 (P <0 0 0 1)。累积骨丢失率 (ABLR)比较 :前一组明显高于后两组病人 (P <0 0 1)。BMD比较中 ,内分泌和其它疾病组明显低于消化道疾病组 (P <0 0 0 1)。相关分析显示 ,内分泌和消化道疾病组的年龄变化与BMD呈正相关 (r =0 5 19P <0 0 0 1和r =0 5 89P <0 0 0 1) ,内分泌疾病组和其它疾病组的体重变化与BMD呈正相关 (r=0 918P <0 0 0 1和r =0 338P <0 0 0 1)。结论 :老年人骨质疏松 (OP)患病率以内分泌疾病组最高 ,消化道疾病组较低 ;随年龄和体重增加 ,BMD降低加重。     

The Treatment of Low Grade Cerebral Astrocytomas by Radiotherapy in Queensland

The records of 108 adult patients with supratentorial low grade astrocytoma presenting between 1/1/80 and 31/12/87 were examined for the following factors which might affect survival: patient age, extent of surgical resection, site of tumour, tumour grade, radiation field size and radiation dose. Univariate analysis showed that patient age, field size and radiation dose were significant prognostic factors, but with multivariate analysis only patient age and radiation field size were significant independent variables. It is possible that field size is a proxy variable for tumour size.     

State and output feedback design for robust tracking of linear systems with rate limited actuators

A design technique (Control of Uncertain Systems with Bounded Inputs, Tarbouriech S, Garcia G, (Eds), Lecture Notes in Control and Information Sciences, vol. 227 , Springer: Berlin, 1997; 173–186) recently proposed for stabilization of a linear system with rate‐limited actuators is utilized to design feedback laws that cause the system output to track a desired command signal. This design technique combines two design techniques recently developed for linear systems with position limited actuators, piecewise‐linear LQ control (Automatica, 1994; 30 : 403–416) and low‐and‐high gain feedback (IEEE Trans. Automat. Control, 1996; 41 : 368–378), and hence takes advantage of both design techniques, while avoiding their disadvantages. In the case that only the output is available for feedback, the performance of the state feedback law is preserved by the use of a fast observer. An open‐loop exponentially unstable fighter aircraft is used to demonstrate the effectiveness of the proposed control design method. Copyright © 2002 John Wiley & Sons, Ltd.     

河南食管癌高、低发区无症状人群食管固有膜血管乳头的变化

目的：探讨食管癌高、低发区无症状居民食管上皮固有膜血管乳头（简称乳头）增生特征（乳头密度和高度）及其与病变分布的关系，加深对食管癌变早期形态学变化特征的了解。方法：2480例无症状人群食管粘膜活检组织，采用食管癌高低发区食管纤维内镜检查，粘膜活检，组织病理学检查和形态学测量技术对食管乳头的分布特征及其与病变的关系进行分析。结果：食管癌高低发区居民食管中、下段乳头升高（≥上皮厚度的1／2）发生率之间差异并不明显（P＞0．05），但是，高发区居民食管中段乳头密度（乳头数目／mm)明显高于下段，并高于低发区居民食管中段的乳头密度（P＜0．05）；高发区居民食管上皮乳头升高伴基底细胞过度增生患者明显高于正常人（P＜0．05），而低发区未观察到类似情况。结论：乳头增生表现为乳头数目增多和乳头升高是食管癌高发区人群食管上皮特征性形态学变化，高分区居民上皮乳头升高伴明显基底细胞过度增生，提示乳头增生可能是食管癌变极早期阶段的重要形态学变化，反映了上皮细胞的增生状态。     

单能量X线测定骨密度的初步分析

目的：了解温州地区人群不同年龄组骨质疏松患病率及同年龄组男女骨质疏松患病的差异，强调早期预防治疗老年人及绝经期妇女骨质疏松的重要性，方法：应用单能量X线（SXA）骨密度仪测量246例正常人的右跟骨骨密度，结果：男性大于60岁组较小于60岁组骨密度（BMD）降低明显（P＜0．05）；女性50岁以上组与小于50岁组相比，BMD下降差异有极显性（P＜0．01）；各年龄组男女相比，男性BMD明显高于女性（P＜0．05）。结论：女性骨质疏松症的发病大多以绝经后为主，雌激素在维持骨量方面具有重要的作用。SXA检测的跟骨含95％小梁骨，能较好地确定骨质疏松的风险水平，且其具有价廉、简便，快捷，较准确等特点，故不失为一种较好的临床筛查手段。