原发性高血压患者左室舒张功能与血清瘦素浓度的关系

目的 探讨原发性高血压(EH)患者左室舒张功能与血清瘦素(Leptin)浓度关系的临床研究。方法 采用放免法测定30例正常人和54例EH患者的血清瘦素浓度。用多普勒组织成像(DTI)技术检测正常人及EH患者二尖瓣环舒张早期运动速度(Ea)、舒张晚期运动速度(Aa)及Ea/Aa,比较其测定值与血清瘦素浓度的相关性。结果 患者组二尖瓣环DTI参数明显低于正常对照组(P<0.01);患者组血清瘦素浓度与Ea、Ea/Aa呈负相关(r=-0.41 P<0.01,r=-0.43 P<0.01)。结论 检测血清瘦素浓度有利于EH患者左室舒张功能受损程度的判断。     

Performance of colposcopy in five sub-Saharan African countries

Objective  The performance of colposcopy provided in a screening study in five African countries was evaluated.
Design  Cross-sectional study.
Setting  Burkina Faso, Congo Brazzaville, Guinea Conakry, Mali and Niger.
Population  Women aged 25–59 years.
Methods  A total of 29 294 women participated in a cervical screening study in the five study sites, and newly trained local doctors performed colposcopy and directed biopsies as indicated. Using meta-analytical tools, four measures of colposcopy performance at different thresholds of colposcopic abnormalities were assessed. Sources of heterogeneity were also assessed.
Main outcome measures  Proportions of women receiving biopsies, adequate biopsies and women diagnosed with cervical intraepithelial neoplasia (CIN).
Results  Among 28 553 women with satisfactory colposcopy, 3101 had a colposcopic diagnosis of probable low-grade or worse lesions and 1128 probable high-grade or worse lesions. Overall, the measures that reached the set standards were proportion of biopsy taken at colposcopy threshold of probable high-grade or worse lesions (95%, 95% CI 90–100%) and proportion of adequate biopsy samples. The set standards were not met for the proportions of women diagnosed with CIN at different colposcopic abnormality thresholds. Detection of CIN2 or worse lesions increased with increasing colposcopic abnormality.
Conclusions  The performance of colposcopy in some of the African sites studied was comparable to that previously observed in other studies. With appropriate training, monitoring, continuing practice and quality assurance, adequate standards of colposcopy can be attained in sub-Saharan Africa.     

鱼腥草药材挥发油的指纹对照法研究

目的：建立鱼腥草药材中挥发油成分的指纹图谱,对各产地药材实现定性定量地评价,并对挥发油中主要成分进行鉴别。方法：采用气相色谱-氢离子火焰检测（GC-FID）技术测定不同产地的13批鱼腥草药材挥发油成分GC指纹图谱。以甲基正壬酮为对照品,以内标法估算各产地药材中各成分的相对含量,以夹角余弦和相对欧氏距离为参考指标进行评价;利用气相色谱-质谱-计算机检索技术（GC-MS-DS）对各色谱峰进行鉴别。结果：建立的鱼腥草药材挥发油成分指纹图谱确立23个共有峰,方法学考查显示各特征指纹峰保留相对稳定,经考察甲基正壬酮在6．6-660μg／ml内线性关系良好,经空白回收率校正后加样回收率为93．46％（n=6）。经鉴定识别其中24种主要成分。结论：建立的鱼腥草药材挥发油成分指纹图谱重复性好,综合了指纹对照法、定性和定量相似度,能更好地评价鱼腥草药材的质量。     

Integrating children's services in England: national evaluation of children's trusts

Background Poor co‐ordination of services can have severe consequences for disadvantaged children with complex needs. Since 2003 national and local governments in England embarked on sweeping reforms aimed at improving and integrating local health, education and social services for children. These were to be organized locally by children's trusts and piloted by 35 children's trust pathfinders. Methods This study described and compared the experience of integrating children's services in all 35 children's trust pathfinders, covering 20% of children in England. It had a prospective mixed‐methods design. Over 3 years we interviewed 147 managers and professionals working in the children's trusts, including 172 semi‐structured interviews, carried out two questionnaire surveys of the 35 children's trusts and analysed official documents. Results In most areas different agencies jointly commissioned children's services, especially for mental health, disabilities and multi‐purpose children's centres, and increasingly pooled finances. Provision of multi‐agency and multi‐professional services was increasing. Professionals generally supported these changes but found them stressful. All children's trusts appointed directors of children's services and established boards representing multiple agencies. Systems for sharing information about individual children were mostly in place but were still underused. Health services were generally less involved in joint work than were local authorities' education and social care services, with notable exceptions. Areas where local authorities and health authorities shared geographical boundaries made most progress. Some children's trusts made few changes beyond their statutory obligations. Conclusion Children's trusts enabled major changes to services in areas where local actors and organizations were motivated and empowered. In other areas the remit of children's trusts was often too broad and vague to overcome entrenched organizational and professional divisions and interests. Policymakers need to balance facilitation of change in areas with dynamic change agents with methods for ensuring that dormant areas and agencies are not left behind.     

HMBA对粘液表皮样癌P53蛋白表达和细胞增殖周期的影响

目的：研究六亚甲基二乙酰胺（ＨＭＢＡ）诱导人粘液表皮样癌（ＭＥＣ－１）细胞分化与细胞Ｐ５３蛋白表达和细胞增殖周期的关系。方法：ＭＴＴ比色法测定ＨＭＢＡ对ＭＥＣ－１细胞体外生长的作用;Ｆｅｕｌｇｅｎ染色测定细胞ＤＮＡ含量;ＡＢＣ免疫酶染色检测Ｐ５３蛋白;ＦＣＭ法测定细胞增殖周期。结果：ＨＭＢＡ对ＭＥＣ－１细胞的生长抑制作用呈剂量依赖性和时间依赖性;ＨＭＢＡ诱导的细胞与对照细胞比较,ＤＮＡ含量减少,Ｐ５３蛋白水平降低,Ｇ１期细胞数增加和Ｓ期细胞数减少。结论：ＨＭＢＡ对ＭＥＣ－１细胞的诱导分化作用与其调节Ｐ５３基因蛋白表达和细胞增殖周期有关。     

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients

Introduction

Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.

Methods

Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.

Results

365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.

Conclusions

Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.     

Twelve-month safety of entacapone in patients with Parkinson's disease

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.     

Parkinson's disease dementia can be easily detected in routine clinical practice

Parkinson's disease (PD) is mainly characterized by its motor manifestations, but it is also frequently associated with dementia. Early diagnosis of PD dementia (PDD) is particularly important because effective cholinesterase inhibitor treatments are available. This study aimed at validating a short procedure for screening for PDD in routine clinical practice and which adopts recently published diagnostic criteria. One hundred eighty‐eight patients with PD participated in the study. The examination procedure comprised three steps: standard clinical examination, a short cognitive function assessment fulfilling the requirements of the Movement Disorders Society (Mini Mental State Examination, five‐word test, word generation task, and impact on daily life, including a questionnaire on compliance with medication) and an extensive evaluation of cognitive functions and behavior. After each step, the suspected presence or absence of dementia was recorded. After the short cognitive function assessment, PDD was suspected in 18.62% of the patients [95% confidence interval (CI): 13.32‐24.93%]. After the extensive assessment, 21.81% (95% CI: 16.13‐28.40%) met the criteria for probable PDD. The short battery's sensitivity and specificity were 65.85% (95% CI = 49.41‐79.92%) and 94.56% (95% CI = 89.56‐97.62%), respectively. A stepwise logistic regression analysis showed that use of a specific cut‐off considerably enhanced the short battery's sensitivity (85.37%, 95% CI = 70.83‐94.43%) without decreasing its specificity (83.67%, 95% CI = 76.69‐89.25%). With an easy‐to‐use, short battery of tests that are commonly used in routine clinical practice, it is possible to diagnose PDD in accordance with reference criteria and with the same sensitivity and specificity as in a more extensive evaluation. © 2010 Movement Disorder Society     

多基因遗传风险评分指导肺癌个体化筛查的前瞻性队列研究

目的探索如何利用遗传风险评分,制订个体化的肺癌筛查方案。方法利用中国慢性病前瞻性研究(CKB)队列10个地区100615例具有全基因组基因分型信息的样本,根据前期课题组发表的19个遗传变异构建肺癌多基因遗传风险评分PRS-19。以55岁且吸烟剂量30包/年人群的5年绝对发病风险为参考届值,在吸烟者和非吸烟者中分别计算不同遗传风险人群5年肺癌绝对发病风险随年龄和吸烟剂量的变化趋势,并绘制5年绝对发病风险分布图,从而判断不同遗传风险人群达到参考界值时的理论年龄或吸烟剂量。根据上述结果给出不同遗传风险人群参加肺癌筛查起始年龄的具体建议。结果CKB队列中55岁吸烟者,当吸烟量为30包/年时,5年内发生肺癌的绝对风险为0.67%。在吸烟者中,随着遗传风险增加,其5年绝对发病风险呈不断上升趋势,对于高遗传风险人群应降低筛查起始年龄,遗传风险最高的1%人群建议从50岁开始进行筛查;若保持筛查起始年龄55岁不变,则应在高遗传风险人群中降低吸烟剂量标准;不管累积吸烟剂量为多少,遗传风险最高的1%人群都应纳入肺癌筛查。在非吸烟者中,高遗传风险人群同样具备筛查价值,建议遗传风险最高的1%人群从62岁起进行肺癌筛查,而对于遗传风险最低的5%人群,当年龄达到74岁时才可达到参考届值。结论对于不同遗传风险的个体,可采用个体化的肺癌筛查方案,对于高遗传风险的吸烟者可减小肺癌筛查起始年龄或吸烟剂量,而我国高遗传风险的非吸烟者同样具备筛查价值。     

非酒精性脂肪肝患者血清Leptin、TNF-α与胰岛素抵抗关系的探讨

目的检测 NAFL 患者血清 Leptin、TNF-α水平,分析与 IR 等指标的相关性并探讨其在脂肪肝形成中的作用。方法 2型糖尿病患者根据 B 超检查结果诊断为糖尿病合并非酒精脂肪肝者48例(DFL 组)、糖尿病无脂肪肝者45例(DM 组)、非糖尿病非酒精性脂肪肝患者30例(FL 组)和正常健康对照组32例(NC 组)。测定四组患者血清 Leptin、TNF-α、FFA 水平,血脂全套、血糖和胰岛素(空腹、餐后2h);采用稳态模式 HOMA 和胰岛素敏感指数(ISI)评价胰岛素抵抗。结果①糖尿病合并脂肪肝的发病率为51.6%,Loglistic 逐步回归分析显示:BMI、FBG、TG 为脂肪肝形成的主要影响因素;②DFL 组和 FL组 FINS、HOMA-IR、Leptin、TNF-α均显著高于 DM 组和 NC 组,ISI 均显著低于 DM 组和 NC 组;③相关分析显示 Leptin 与HOMA-IR、TG、VLDL、BMI、Sex、Age 呈显著正相关,与 ISI 呈显著负相关;TNF-α与 Leptin、BMI 呈显著正相关。结论①肥胖、高血糖、糖尿病、及高脂血症与 NAFL 密切相关,是其形成的主要危险因素;②NAFL 患者存在 IR,且 IR 可能是其形成的始发因素;③NAFL 患者血清 Leptin、TNF-α水平升高,且与肥胖、IR 密切相关,在脂肪肝的发生、发展中有着重要作用。