Furosemide inhibits regenerative cortical spreading depression in anaesthetized cats

Ionic perturbations occur during cortical spreading depression (SD), a phenomenon implicated in migraine pathophysiology. We studied the effect of 0.2,2 and 20 mg kg⁻¹ iv ( n =4) furosemide on cortical direct current (d.c.) potential, cerebrovascular laser Doppler flux (rCBF_LDF), artery diameter and NO concentration in the parietal cortex of the anaesthetized cat during repetitive SD. In vehicle treated animals ( n =4), SD activity was sustained for 50 1.8 min. However, duration of SD activity was significantly reduced when compared to vehicle to 39 6.6 ( n =4), 3.1 8.3 ( n =4) and 27.3 11.3 min ( n =4), at 0.2, 2 and 20 mg kg⁻¹ iv furosemide respectively. It is hypothesized that the mechanism of inhibition of SD d.c. activity by furosemide may be through alterations in cortica ion buffering capacity or inhibition of cell swelling in neurones or glia. These mechanisms may represent potential novel drug targets in future migraine therapy.     

成都地区50岁以上骨质疏松患者QCT骨密度在不同性别及体质量间的差异

目的:分析成都地区50岁以上骨质疏松患者羟磷灰石定量计算机断层扫描骨密度的变化及部分影响因素。方法:①对象:选择2004-05/2006-02在成都市温江区人民医院内分泌科住院的原发性骨质疏松患者189例。男80例,年龄(69.21±8.87)岁,女109例,年龄(67.14±8.85)岁。②分组:按年龄分为50～59岁,60～69岁,70～79岁,≥80岁4个组,按体质量指数分为<18.5,18.5～23.9,24.0～27.9,≥28.0kg/m2,即消瘦、正常、超重和肥胖4个组。③评估:用国产HK-2000QCT骨矿密度测定校验体模系统测定腰椎L1～3骨密度,分别探讨年龄和体质量指数与QCT骨密度的关系。结果:①男女两组50岁以上骨质疏松患者QCT测定的L1～3骨密度和T值均随年龄增加而逐渐降低,二者与年龄呈直线负相关关系(P<0.01)。②女性患者在60～79岁之间骨密度下降速率与相同年龄男性比较更快。③按体质量指数分组,消瘦组骨密度和T值显著低于正常体质量(P<0.05)和超重组(P<0.01),与肥胖组比较差异无统计学意义(P>0.05)。结论:50岁以上骨质疏松患者骨密度降低随年龄增加而逐渐加重,消瘦患者比正常体质量和超重患者骨密度降低更严重。     

Quantifying the risks and benefits of efavirenz use in HIV‐infected women of childbearing age in the USA

Objectives

The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz‐related teratogenicity) associated with using efavirenz in HIV‐infected women of childbearing age in the USA.

Methods

We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz‐based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor‐based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100 000 women, we incorporated literature‐based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women.

Results

Survival for HIV‐infected women who received an efavirenz‐based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non‐efavirenz‐based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100 000 exposed women, compared with 72.46/100 000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS‐related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz‐exposed women.

Conclusions

Use of non‐efavirenz‐based initial ART in HIV‐infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision‐making regarding efavirenz use presents a trade‐off between these two risks; this study can inform discussions between patients and health care providers.     

Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.     

Platelet kinetics in patients with bone marrow hypoplasia: evidence for a fixed platelet requirement

We have studied 16 normal subjects and 27 patients with stable, untreated thrombocytopenia secondary to bone marrow failure and platelet counts ranging from 12,000 to 70,000/microL. Autologous platelets were labeled with 51Cr for measurement of mean platelet life span in the normal subjects and in 20 patients. Labeled donor cells were used in the remaining subjects. Platelet survival, as determined with both autologous and homologous platelets, correlated directly with platelet count in the thrombocytopenic patients. Platelet life span was only modestly reduced in patients having counts in the range of 50,000 to 100,000/microL (7.0 +/- 1.5 days v 9.6 +/- 0.6; P less than .01) but was markedly reduced when the count fell below 50,000/microL (5.1 +/- 1.9 days, P less than .001). The recovery of donor platelets in severely thrombocytopenic recipients (60% +/- 15%) was equivalent to control values (66% +/- 8%; P greater than .2). The recovery of autologous platelets was normal when the platelet count exceeded 50,000/microL (74% +/- 15%) but was reduced in patients with lower counts (50% +/- 22%; P less than .01). All patient and normal data were well correlated by a model predicting a maximum platelet life span of 10 1/2 days and a fixed requirement for 7,100 platelets per microliter of blood per day, or about 18% of the normal rate of platelet turnover, which averaged 41,200 platelets per microliter per day. We conclude that although relatively few platelets are used to support vascular integrity, this requirement is reflected by a reduced platelet life span in marrow hypoplasia and may contribute to the shortening of platelet survival observed in other thrombocytopenias.     

FasL^＋组织工程化猪软骨细胞的同种异体移植

目的:探讨表达FasL的猪组织工程化软骨细胞在同种异体内的生长状况和免疫排斥反应。方法:实验于2002-09/2004-03在上海交通大学医学院,上海市免疫学研究所进行。①分离制备猪软骨细胞。②制备FasL 软骨细胞,构建重组pGCEN-FasL反转录病毒载体,转染PA317细胞。经G418筛选获得分泌pGCEN-FasL病毒颗粒的PA317细胞克隆,选择高滴度的病毒液,感染猪软骨细胞。再经过G418筛选获得FasL 的软骨细胞克隆,扩增培养。③FACS检测FasL的表达,应用JAM试验测定FasL 的软骨细胞诱导Fas 的Jurkat细胞及活化的T细胞的凋亡率。同时制备转染pGCEN反转录病毒空载体的软骨细胞为对照。④取FasL 的软骨细胞与可注射性生物材料PluronicF127混合,注射于同种异体猪的腹壁皮下。在第4,5周取材,通过组织病理和免疫组织化学等方法,检测软骨细胞生长和免疫排斥反应。结果:①经转染的软骨细胞表面FasL的表达率为57%。②FasL 的软骨细胞具有明显诱导Fas 细胞和活化的同种异体T细胞的凋亡,最大的凋亡率分别为53.41%,30.38%(效/靶=10∶1),对照组分别为32.27%,13.16%(效/靶=10∶1)。③组织工程化猪软骨结节的结构与正常软骨组织基本一致,可见清晰的软骨凹陷和软骨膜,仅细胞排列较正常软骨略显混乱、不均匀现象。④免疫组织化学染色显示FasL 的组织工程化猪软骨结节的Ⅱ型胶原蛋白分布均匀,形状清楚,与正常软骨比较基本一致。⑤第5周的软骨细胞表面的FasL分子表达明显,周围的炎性细胞浸润相对较少。而对照组的软骨细胞周围可见到大量浸润的炎性细胞。结论:成功构建FasL 软骨细胞并有效表达,抑制免疫排斥反应,为建立同种异体软骨细胞移植的免疫耐受提供了实验依据。     

手术及经皮自体骨髓移植治疗骨延迟愈合和骨不连

观察手术及经皮自体骨髓移植治疗四肢骨折骨不连、骨延迟愈合的临床效果。选择1997-11/2004-02山东省聊城市第二人民医院应用经皮自体骨髓移植法治疗骨不连、骨延迟愈合的患者23例,患者均了解相关治疗目的、方法并同意治疗方案。①17例骨不连患者采用手术治疗。15例存在骨质缺损者在骨折端间隙及周围自体髂骨植骨10例,收集术中骨屑及骨髓原位植骨4例,异体植骨1例;2例单纯外固定架重新固定未植骨并行自体骨髓移植。术后2周抽取自体骨髓注入骨折部位,注射10～20mL/次,每2周1次,需注射2～4次。②6例骨延迟愈合患者仅行自体骨髓移植,未改变固定方式。术后定期随访,观察患者骨折愈合情况。骨折愈合标准:X射线片显示连续骨痂通过折线,骨折处无疼痛及压痛,能够全部负重。23例骨不连、骨延迟愈合患者全部进入结果分析,无脱落。23例患者术后平均随访12.5个月,其中随访7～9个月11例,10～12个月6例,13～15个月5例,16个月1例。23例患者均达到骨性愈合,愈合率100%,平均愈合时间为5.6个月。坚强固定加必要的植骨修复骨缺损是治疗骨折术后骨不连的基础和关键,自体骨髓具有成骨作用,可进一步促进骨折愈合。     

全膝关节置换术前模板测量预测术中假体型号：92例资料回顾

目的：人工关节置换术前应用模板测量预测术中所用假体型号,是完善术前设计的重要方面,但其准确性和可靠性尚无定论,文章对初次全膝关节置换术前模板测量的准确性进行回顾性分析。方法：选择在北京积水潭医院矫形骨科2004-01/2007-01进行人工全膝关节置换患者92例107膝,男15例17膝,女77例90膝。其中55膝采用了GenesisⅡ假体（Smith＆nephew人工关节公司提供）,52膝采用了ΣPFC假体（美国Depuy人工关节公司提供）,术前X射线片分别使用上述两套全膝关节假体系统模板进行测量。比较模板测量的膝关节假体型号与手术实际使用的膝关节假体型号的一致性,以κ系数加以评估（0～1,0表示完全不一致,1表示完全一致）;依据术中实际所用的假体型号,以百分数表示测量者术前模板测量的准确率,2组患者的测量准确率应用SPSS11.5统计学软件以配对χ^2检验进行比较。结果：对于GenesisⅡ假体,术前测量的股骨假体和胫骨假体型号的准确率分别为50.9%和56.3%;对于ΣPFC假体,准确率分别为51.9%和55.8%。κ系数结果提示,术前应用模板测量结果与实际植入假体的大小具有适中的一致性。配对χ^2检验的结果提示2组患者的测量准确率之间无显著性差异。结论：全膝关节置换术前模板测量对于预测实际所用假体型号可以起到一定的指导作用,但其准确性并不十分理想。要正确认识模板测量在全膝关节置换中的地位,并且要综合考虑会影响到假体型号选择的各种因素。     

Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of [35S] sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate [35S] proteoglycans. When "MMC-like" cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1- W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these "second generation PMC" formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.