High‐dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: A prospective randomized trial

Objective

Monthly intravenous (IV) cyclophosphamide for 6 months has been the standard induction regimen for lupus nephritis, followed by a maintenance regimen of quarterly infusions for 2 years. We undertook this study to compare the efficacy and safety of the standard regimen versus a high‐dose IV cyclophosphamide regimen.

Methods

We performed a prospective randomized trial comparing monthly IV cyclophosphamide at 750 mg/m² body surface area for 6 months followed by quarterly IV cyclophosphamide for 2 years (traditional treatment) against high‐dose IV cyclophosphamide (50 mg/kg daily for 4 days) (high‐dose treatment). Entry criteria included renal lupus, neurologic lupus, or other organ system involvement with moderate‐to‐severe activity.

Results

Fifty‐one patients were randomized; 3 withdrew before treatment and 1 committed suicide after 2 months of high‐dose treatment. Twenty‐two had renal lupus, 14 had neurologic lupus, and 11 had other organ involvement. The outcome measure was the Responder Index for Lupus Erythematosus (complete response, partial response, no change, or worsening). At 6 months (the end of induction), 11 of 21 patients (52%) in the high‐dose treatment group had a complete response compared with 9 of 26 patients (35%) in the traditional treatment group (P = 0.13). At the final visit (30 months), 10 of 21 patients (48%) in the high‐dose treatment group had a complete response compared with 13 of 20 patients (65%) who continued with traditional treatment (P = 0.13). Six patients crossed over from traditional treatment to high‐dose treatment because of lack of response, and 3 of those patients became complete responders.

Conclusion

There was not strong evidence that monthly IV cyclophosphamide and high‐dose IV cyclophosphamide differed in complete or in any (complete or partial) response to induction or maintenance therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be rescued with high‐dose IV cyclophosphamide.

     

Ambulatory blood pressure monitoring

Ambulatory blood pressure monitoring (ABPM) in adults is proving to be useful. The aim of this study was to determine if ABPM is accurate in the lower blood pressure range encountered in children and, equally important, whether it is acceptable to children. Thirty one children, between the ages of 6 and 18 years, were assessed using an ambulatory blood pressure monitor that uses an auscultatory method. Blood pressure was measured in the contralateral arm with a mercury sphygmomanometer and an oscillometric device at the beginning and end of the study for comparison. Over a blood pressure range of 90-130 mm Hg systolic and 40-80 mm Hg diastolic, a close agreement was found with the sphygmomanometer; the limits of agreement (+/- 2 SD) were 11.6 mm Hg for systolic blood pressure and 13.6 mm Hg for diastolic blood pressure. The bias was less than 1.0 mm Hg. The ambulatory device was worn by all patients for at least 16 hours with an average of 52 recordings per patient. The majority found the device comfortable to wear and were not woken from sleep.     

Lactobezoar and cows' milk protein intolerance

A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment.     

Duration of migraine is a predictor for response to botulinum toxin type A

OBJECTIVE: To identify the clinical characteristics and/or injection parameters that predict a favorable response to botulinum toxin type A in patients with episodic and chronic migraine. BACKGROUND: There is emerging scientific and clinical evidence to support the utility of botulinum toxin type A (BoNT-A) in the prophylaxis of episodic and chronic migraine headache. However, the patient characteristics and injection strategies that predict a favorable treatment response are unknown. METHODS: We conducted a prospective, open-label study on 74 patients from our clinic receiving BoNT-A for episodic or chronic migraine. For all patients, migraine-related disability (Migraine Disability Assesment [MIDAS]), headache frequency, and average headache intensity were obtained at baseline and at 3 months post-BoNT-A. Information regarding demographic characteristics and injection parameters was also collected. RESULTS: Sixty-one patients met the study criteria and were available for 3-month follow-up. At the 3-month follow-up visit, the mean MIDAS scores of the 61 qualified study patients had decreased from 102 at baseline to 49 (52% decrease, P<.001). The mean number of headache days was reduced from 60 to 39 (P<.001), and the mean headache intensity decreased from 7.6 at baseline to 5.9 (P<.001). Frequency of migraine attacks, presence of analgesic overuse, total BoNT-A dose, and presence of underlying muscle tenderness were not predictive of treatment response. Age and duration of migraine were the only clinical factors significantly predictive of treatment response. Age likely was a predictor only as a consequence of duration of illness as subjects with migraine duration greater than 30 years were significantly less likely to respond to treatment with BoNT-A. CONCLUSION: BoNT-A may be effective in decreasing headache frequency, headache intensity, and headache-related disability in episodic and chronic migraine patients. Duration of illness emerged as a predictor of treatment response. Randomized controlled studies should evaluate headache-related disability as a primary endpoint in patients with episodic and chronic headache.     

在缝合基础上局部应用纤维蛋白胶对周围神经再生的影响

目的:在缝合的基础上局部应用纤维蛋白胶治疗损伤的周围神经,观察纤维蛋白胶对周围神经再生的影响。方法:实验于2005-03/07在大连医科大学中心实验室完成。实验材料:纤维蛋白胶(广州倍绣生物技术有限公司,主要成分:纤维蛋白原50～70mg/支和凝血酶400U/支,从哺乳动物血中提纯,经过灭菌消毒,冻干制成,不含致热源)。实验分组:选择健康SD大鼠48只,按随机数字表法分为两组,每组24只:单纯缝合 纤维蛋白胶组、单纯缝合组。实验方法:大鼠麻醉后,于左大腿后外侧做2cm纵切口,显露坐骨神经。距梨状肌下缘远侧约1.5cm处切断坐骨神经,切除远端1～2mm,采用10-0无创伤线缝合神经外膜,使远近端保留约1～2mm间隙。单纯缝合 纤维蛋白胶组:对称缝合2针,将纤维蛋白胶注入缝合周围在神经对合端生成凝胶环,混合物固化形成再生室。单纯缝合组:单纯外膜缝合。实验评估:①术后连续观察动物行为学:手术侧后肢及足趾的运动情况,有无溃疡形成,足趾、趾甲的溃疡愈合情况,观察展爪反射。②术后8周两组各取4只大鼠行神经电生理检查,检测神经传导速度、潜伏期。③术后2,4,6,8周两组各取2只大鼠行苏木精-伊红染色后光镜下观察神经再生情况。④术后8周两组各取4只大鼠采用LUZEX-F彩色图像分析仪对甲苯胺蓝染色神经组织切片中轴突数目及轴突直径进行分析。⑤术后8周两组各取4只大鼠行醋酸铀枸橼酸铅染色,Phlip-10型透射电镜下观察轴突再生情况。⑥术后8周两组各取4只大鼠行辣根过氧化物酶标记观察脊髓前角运动神经元情况。结果:纳入大鼠48只,均进入结果分析。①术后大鼠行为学观察:术后8周单纯缝合 纤维蛋白胶组大鼠除足趾略见下垂、屈曲现象外,步态基本正常,展爪反射基本正常,下肢活动已接进正常,单纯缝合组下肢活动略差。②神经电生理检查:术后8周单纯缝合 纤维蛋白胶组神经传导速度快于单纯缝合组[分别为(11.13±0.37),(9.26±0.44)m/s],潜伏期短于单纯缝合组[分别为(1.83±0.18),(2.17±0.19)ms],差异有显著性意义(F=27.78,5.53,P<0.05)。③光镜下神经再生情况:单纯缝合 纤维蛋白胶组再生的有髓神经纤维髓鞘较厚、直径较大、数量多、排列规则,再生良好。单纯缝合组再生的有髓神经纤维髓鞘较薄、直径较小、数量少、排列不规则,再生较差。④轴突数目及轴突直径:单纯缝合 纤维蛋白胶组在轴突数目、轴突直径大于单纯缝合组[分别为(2187±107),(1847±96)个/400倍视野;(2.79±0.15),(2.05±0.17)μm],差异有显著性意义(F=80.70,42.92,P<0.05)。⑤透射电镜下轴突再生情况:术后8周单纯缝合 纤维蛋白胶组大鼠再生轴突发育良好,排列有序,轴突直径大小相差小,髓鞘厚薄一致,轴突染色均匀,雪旺细胞核呈卵圆型。单纯缝合组大鼠轴突发育差,排列不规则,髓鞘薄,可见扩张血管,部分区域有出血水肿。⑥辣根过氧化物酶标记观察脊髓前角运动神经元情况:单纯缝合 纤维蛋白胶组在实验侧腰骶段前角可见辣根过氧化物酶标记的大型运动神经元,且数目较多。单纯缝合组标记的数量较少。结论:在修复神经过程中应用纤维蛋白胶,可明显促进损伤的周围神经修复与再生,优于单纯缝合的效果。     

延边地区汉族和朝鲜族居民脂肪分布与代谢异常的关系

目的:了解延边地区朝鲜族和汉族居民的脂肪分布特征及其与血压、血脂及血糖的关系。方法:于2006-08-8/17在延边地区九龙和翁声社区随机选择40～60岁朝鲜族和汉族常住居民2378名进行内脏脂肪率和体脂肪率以及血压、血脂、血糖等生化指标的检测。调查以健康体检形式进行,①内脏脂肪和体脂肪率测定采用日本TANITA株式会社生产的BC-600型体成分计测定,并且按其判定标准确定超过标准者[内脏脂肪率≥15%(男)、≥10%(女),体脂肪率(40～59岁)≥23%(男)、≥36%(女),体脂肪率(≥60岁)≥25%(男)、≥37%(女)]。②取清晨空腹(禁食12h)静脉血,采用日立-7600-010全自动生化分析仪测量血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、空腹血糖等指标。③高血压的诊断标准:收缩压≥140mmHg(1mmHg=0.133kPa)及或舒张压≥90mmHg。④血脂异常的诊断标准:总胆固醇≥5.72mmol/L,三酰甘油≥1.7mmol/L,高密度脂蛋白胆固醇<0.90mmol/L(男)、<1.0mmol/L(女)。⑤高血糖的诊断标准:空腹血糖≥6.1mmol/L。结果:①汉族男性的内脏脂肪率和体脂肪率均值分别为(10.51±3.66)%和(22.70±4.85)%,朝鲜族男性分别为(9.16±3.81)%和(20.28±5.02)%,汉族均高于朝鲜族(P<0.01);汉族女性的内脏脂肪率和体脂肪率分别为(6.22±2.27)%和(35.31±5.65)%,朝鲜族女性分别为(5.88±2.19)%和(34.00±5.72)%,汉族均高于朝鲜族(P<0.01)。②汉族男性的内脏脂肪率和体脂肪率超标率分别为12.1%和45.8%,朝鲜族男性分别为7.8%和28.6%,汉族均高于朝鲜族(P<0.05);汉族女性的内脏脂肪率和体脂肪率超标率分别为6.7%和47.9%,朝鲜族女性分别为3.8%和37.3%,汉族均高于朝鲜族(P<0.05)。③Logistic逐步回归分析结果表明,内脏脂肪率与民族、性别、年龄、高血压、高三酰甘油血症和高血糖有密切关系;体脂肪率与民族、性别、高血压、高三酰甘油血症、低高密度脂蛋白血症和高血糖有密切的关系。结论:①延边地区汉族居民内脏脂肪率和体脂肪率平均水平及其超标率明显高于朝鲜族。②内脏脂肪率和体脂肪率均与民族、性别、年龄(体脂肪率除外)、高血压、高三酰甘油血症和高血糖相关。     

非亲缘外周血造血干细胞移植治疗重型β-地中海贫血1例

患儿,女,4岁,体质量19kg。生后4个月开始进行性面色苍白伴巩膜黄染,血红蛋白65g/L,白细胞和血小板均正常,血红蛋白电泳血红蛋白A48.1%、血红蛋白A24.2%、抗碱血红蛋白47.7%,基因型为β地贫纯合子,诊断为重型β地中海贫血,以间断大量输血维持生命。于2005-12-09在厦门大学附属中山医院血液科接受非亲缘性外周血干细胞移植。预处理方案采用常规氟达拉滨、白消胺、环磷酰胺三药联合方案,以环孢菌素A、霉酚酸酯、抗胸腺淋巴细胞免疫球蛋白联合预防移植物抗宿主病,供受者人类白细胞抗原高分辨全相合,ABO血型次要不合(O-A),输入CD34 干细胞11.4×106/kg。植入成功,移植后12d中性粒细胞>0.5×109L-1,移植后37d血小板>50×109L-1,移植后35d患者血型检测转变为供者血型,患儿血红蛋白达到100g/L的时间是28d,移植后患儿未再输血,血红蛋白维持130g/L以上,整个移植过程顺利,未出现严重感染和移植物抗宿主反应,随访18个月,患儿生活正常,发育良好。