Reliability of an illness severity measure for headache in a population sample of migraine sufferers

Objectives: To examine the reliability and related measurement properties of an illness severity measure for headache derived from responses to a 16-item self-administered questionnaire, the Headache Impact Questionnaire (HImQ), and to determine if there is support for combining measures of pain and disability into a single scaled measure of severity. Methods: A population-based sample of migraine headache sufferers completed the HImQ twice, an average of 38 days apart. The HImQ included questions about number of headaches in the last 3 months, headache duration, last headache, pain intensity (two questions), need for bedrest (two questions), disability in specific domains of activity (seven questions about interference with ability to work, do household chores, and engage in non-work activity), and symptoms (two questions). Results: Test-retest correlations of individual questions ranged from 0.65 to 0.93. In principal components analysis, a single factor with significant loading emerged. One measure of pain intensity (average pain score from 0 to 10) and items related to disability (i.e., missed days due to headache, and reduced effectiveness because of headache) in defined activity domains (work for pay housework, nonwork activities) had the greatest weights on this single factor, supporting prior work on combining measures of pain and disability into a single scale. The HImQ score was derived as the sum of average pain intensity and total lost time in each of the three domains of activity, expressed as lost days. The latter was derived as the sum of actual missed days in each activity domain and reduced effectiveness day equivalents in each activity with a headache. The test-retest correlation was 0.77 for all eligible subjects and 0.85 when one influential outlier was removed. Cronbach's alpha was 0.83. Conclusions: The HImQ score, based on eight items, is a highly reliable and internally consistent measure of headache severity.     

脐血间充质干细胞与骨髓间充质干细胞对淋巴细胞增殖的抑制效果比较

目的:比较脐血间充质干细胞和骨髓间充质干细胞对植物血凝素诱导的淋巴细胞增殖的抑制作用。方法:实验于2005-07/2006-03在南昌大学第二附属医院血液病研究所及江西省医学分子重点实验室完成。①实验材料:脐带血9份,由南昌大学第二附属医院妇产科提供,产妇及其家属均知情同意。正常骨髓9份,由南昌大学第二附属医院血液科门诊及住院患者提供,均附有捐赠同意书。外周血9份,取自正常自愿者。本实验经医学伦理委员会批准。②实验方法:无菌条件下采集脐血、骨髓和正常人外周血,分离单个核细胞。脐血及骨髓单个核细胞以1×109 L-1接种于培养瓶中,加入含体积分数为0.1的小牛血清、1×10-3mol/L氢化可的松的IMDM培养液,7d后换液,去除悬浮细胞,以后每3～4d换液1次,待细胞90%融合后,胰蛋白酶 乙二胺四乙酸混合消化,传代培养,取第3代细胞用于实验。正常人外周血单个核细胞以1×109 L-1接种于培养瓶中,加入含体积分数为0.1的小牛血清、10mg/L植物血凝素的IMDM液,培养3d后收集细胞用于实验。③实验评估:采用流式细胞术检测脐血间充质干细胞及淋巴细胞表面分子。取第3代的脐血和骨髓间充质干细胞,体外诱导培养后以脂肪染色液鉴定其向脂肪细胞的分化情况。将不同细胞浓度的脐血和骨髓间充质干细胞分别加入到植物血凝素诱导的外周血淋巴细胞增殖体系中,比较两种不同来源的间充质干细胞对淋巴细胞增殖的调控作用。结果:①脐血间充质干细胞和骨髓间充质干细胞的培养及鉴定:第3代脐血间充质干细胞表面分子标记率CD29为85.18%,CD166为72.52%,CD54为33.70%,CD45为6.70%,CD13为1.51%,CD34为0.23%。正常人外周血单个核细胞中的CD3 T细胞为60%～70%,CD20 B细胞为3.5%～4.5%。脐血间充质干细胞诱导培养3周,可见呈桔黄色的脂肪细胞。②脐血间充质干细胞及骨髓间充质干细胞对淋巴细胞增殖的抑制:淋巴细胞:间充质干细胞为1∶1,1∶0.5,1∶0.1,1∶0.05,1∶0.02,1∶0.01时,脐血间充质干细胞对淋巴细胞增殖的抑制率分别为(49.5±4.8)%,(58.4±6.0)%,(38.1±4.0)%,(31.4±3.2)%,(24.3±3.2)%,(12.6±6.7)%,而骨髓间充质干细胞对淋巴细胞增殖的抑制率分别为(52.4±8.4)%,(65.1±9.7)%,(34.7±4.5)%,(13.0±6.4)%,(-10.7±12.6)%,(-43.9±9.4)%。后3种细胞浓度比例脐血间充质干细胞对淋巴细胞的抑制作用明显强于骨髓间充质干细胞(t=7.72,8.14,14.68,P均<0.05)。结论:脐血间充质干细胞与骨髓间充质干细胞一样,也具有抑制植物血凝素诱导淋巴细胞增殖的作用,抑制效果与间充质干细胞数量有关。低浓度的脐血间充质干细胞对淋巴细胞的抑制作用明显强于骨髓间充质干细胞。     

单剂量巴利昔单抗对肾移植受者外周血Foxp3mRNA、CD4+CD25+调节性T细胞、白细胞介素2及其受体的影响

目的观察单剂量巴利昔单抗对肾移植受者外周血Foxp3mRNA、CD4+CD25+调节性T细胞、白细胞介素2及可溶性白细胞介素2受体的影响,分析其预防移植肾急性排斥反应的作用途径.方法选择2005-10,2006-12在上海解放军第四五五医院行同种异体肾移植的患者66例,移植前均行维持性血液透析治疗.按随机数字表法分为2组,常规组接受常规免疫抑制剂治疗,巴利昔单抗组在常规免疫抑制剂治疗的基础上加用巴利昔单抗(商品名舒莱,诺华制药公司,批号S20040059,20 mg/瓶),每组33例.另外选择年龄性别相配的健康体检者30例作为对照组.以上所有观察对象均知情同意,且得到医院伦理道德委员会批准.两组肾移植患者分别于移植前(手术当天)和移植后1,2,4,8周清晨采静脉血肝素抗凝,以流式细胞仪检测外周血中CD4+CD25+调节性T细胞含量,应用荧光定量PCR检测Foxp3mRNA的表达,应用双抗体夹心酶联免疫吸附法检测血浆中自细胞介素2及其受体,采用生化仪检测血肌酐及尿素氮水平,必要时行移植肾多普勒超声检查和病理活检,观察其急性排斥反应发生情况.结果66患者全部进入结果分析,无脱落.①常规组患者急性排斥反应的发生率21.12%(7/33)显著高于巴利昔单抗组6.1%(2/33)(p＜0.05).②移植后第1,2,4和8周巴利昔单抗组Foxp3、CD4+CD25+调节性T细胞和白细胞介素2水平均高于常规组(P＜0.05～0.01),可溶性白细胞介素2受体水平均低于常规组[(306.31±98.43,327.60±109.74,316.71±104.54,388.33±13242;410.14+112.04,442.82±118.94,450.80±123.63,445.61±115.24)U/mL(p＜0.05～0.01)].③两组肾移植患者无论移植前还是移植后,其血浆CD4+CD25+调节性T细胞百分率与Foxp3mRNA表达水平均呈明显正相关(r=0.892～0.932,P＜0.01).结论单剂量巴利昔单抗可以有效地减少移植肾急性排斥反应的发生率,作用途径可能与其增加外周血中Foxp3mRNA、CD4+CD25+调节性T细胞和白细胞介素2表达,减少血浆可溶性白细胞介素2受体水平有关.     

Nasal hyperreactivity in rhinitis: A diagnostic and therapeutic challenge

Although nasal hyperreactivity (NHR) is a common feature in patients suffering from allergic and nonallergic rhinitis, it is widely neglected during history taking, underdiagnosed in the majority of patients with rhinitis and rhinosinusitis, not considered as an outcome parameter in clinical trials on novel treatments for rhinitis and rhinosinusitis, and no target for routine treatment. In contrast to the simple nature of diagnosing NHR by a history of nasal symptoms induced by nonspecific exogenous and/or endogenous triggers, quantification is hardly performed in routine clinic given the lack of a simple tool for its diagnosis. So far, limited efforts have been invested into gaining better insight in the underlying pathophysiology of NHR, helping us to explain why some patients with inflammation develop NHR and others not. Of note, environmental and microbial factors have been reported to influence NHR, contributing to the complex nature of understanding the development of NHR. As a consequence of the neglect of NHR as a key clinical feature of rhinitis and chronic rhinosinusitis (CRS), patients with NHR might be suboptimally controlled and/or dissatisfied with current treatment. We here aim to provide a comprehensive overview of current knowledge on the pathophysiology, and the available tools to diagnose and treat NHR.     

Work-related disability: results from the American migraine study

Migraine headache is a highly prevalent, often severely painful and frequently disabling disorder. The indirect costs related to disability greatly exceed the direct cost of medical care. The objective of this paper is to describe work-related disability associated with migraine headache and predictors of disability. In a two-stage survey of the US population, we estimate missed workdays and impairment at work in a sample of 1663 migraine sufferers, age 18 years and older. Lost workday equivalents (LWDE) was derived as the sum of actual missed workdays and the product of percentage effectiveness at work and days at work with the most severe headache. Overall, reported actual lost workdays and reduced effectiveness at work contributed approximately equally to total LWDE. A total of 51.1% of females and 38.1% of male migraineurs experienced six or more LWDE per year. This subgroup of migraine sufferers accounted for about 90% of the total LWDE experienced by all respondents. Among women, headache duration was the strongest predictor of LWDE followed by less significant associations with number of symptoms and pain level. Among men, only pain level was significantly associated with LWDE. Among sociodemographic factors, disability was more likely among older (40+) subjects and less likely among individuals with higher education and higher income (females only), even after adjusting for headache features. Health-care interventions may yield the greatest individual benefit (by reducing pain and disability) and the greatest societal benefit (by reducing indirect costs) if they are directed to those who account for the greatest proportion of disability.     

Prospective validation of a point score system for predicting blood transfusion following hip or knee replacement

BACKGROUND: The purpose of this study was to validate a previously published point score system for predicting the likelihood of a postoperative blood transfusion following hip or knee replacement. STUDY DESIGN AND METHODS: Data were collected prospectively on 460 sequential patients undergoing elective hip and knee replacement at two academic hospitals. Blood transfusion frequency was determined for patients in each of the four risk strata, as defined by the point score system. The accuracy of the system was validated by calculating the area under the receiver operating characteristic (ROC) curve for each site. Data were then combined and inappropriate blood transfusions were eliminated, by using the American College of Physicians guidelines. The frequencies of blood transfusion within each strata were recalculated along with an ROC curve. RESULTS: The point score system accurately predicted the likelihood of blood transfusion at both hospitals, despite marked differences in overall transfusion frequencies. The calculated areas under the ROC curves were 0.78 and 0.79 for the two sites. The point score system also proved valid when only appropriate blood transfusions were considered, with a calculated area under the ROC curve of 0.74. CONCLUSION: The point score system can accurately predict the likelihood of postoperative blood transfusion following hip or knee replacement. Such a system can be used to target high-risk patients for preoperative autologous blood donation.     

Chromosomal assignment of the human thrombin receptor gene: localization to region q13 of chromosome 5

A functional thrombin receptor (TR) structurally related to other members of the seven-transmembrane receptor family has been isolated from diverse cellular types intimately involved in the regulation of the thrombotic response. This receptor recapitulates many of the previously identified sequelae of thrombin-mediated cell activation phenomenon, and requires proteolytic cleavage for downstream effector- response coupling events. Using two complementary approaches, we have now completed the chromosomal assignment of the human thrombin receptor gene. Discordancy analysis of polymerase chain reaction products from a human-rodent hybrid cell mapping panel assigned the sequence to human chromosome 5 with no observed discordancies. Cytogenetic localization using fluorescence in situ hybridization on human metaphase chromosomes specifically localized the human TR gene to region q13 of chromosome 5, confirming its presence as a single-locus gene in the human genome. The chromosomal localization of the human TR gene is at or contiguous with the proximal breakpoint site identified in the majority of patients with the 5q- syndrome (dysmegakaryocytopoiesis and refractory anemia).