NXY-059治疗急性缺血性卒中

Background: NXY-059 is a free-radical-trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke. Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke. The primary outcome was disability at 90 days, as measured according to scores on the modified Rankin scale for disability (range, 0 to 5, with 0 indicating no residual symptoms and 5 indicating bedbound, requiring constant care). Results: Among the 1699 subjects included in the efficacy analysis, NXY-059 significantly improved the overall distribution of scores on the modified Rankin scale, as compared with placebo (P = 0.038 by the Cochran-Mantel-Haenszel test). The common odds ratio for improvement across all categories of the scale was 1.20 (95 percent confidence interval, 1.01 to 1.42). Mortality and rates of serious and nonserious adverse events were each similar in the two groups. NXY-059 did not improve neurologic functioning as measured according to the National Institutes of Health Stroke Scale (NIHSS): the difference between the two groups in the change from baseline scores was 0.1 point (95 percent confidence interval, -1.4 to 1.1; P = 0.86). Likewise, no improvement was observed according to the Barthel index (P = 0.14). In a post hoc analysis of patients who also received alteplase, NXY-059 was associated with a lower incidence of any hemorrhagic transformation (P = 0.001)and symptomatic intracranial hemorrhage (P = 0.036). Conclusions: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke.

Thrapeutic equivalence in the treatment of hypertension:Can lercanidipine and nifedipine GITS be considered to be interchangeable?

AIM: To undertake a review of the evidence that nifedipine GITS and lercanidipine are therapeutically equivalent in the management of essential hypertension.METHODS: A systematic review of the published literature was prompted by the findings of two meta-analyses which indicated that there was a lower incidence of peripheral(ankle) oedema with lercanidipine. However,neither meta-analysis gave detailed attention to comparative antihypertensive efficacy or cardiovascular protection. Accordingly,a systematic,detailed and critical review was undertaken of individual published papers. The review started with those studies incorporated into the 2 meta-analyses and then all other salient and directly relevant papers identified through the following search criteria: all randomized controlled trials in which the therapeutic profile and antihypertensive effects of lercanidipine were directly compared with those of nifedipine GITS(in hypertensive patients). The searchstrategy was focused on the reports of clinical trials of lercanidipine vs nifedipine GITS,which were identified through a systematic search of PubMed(from 1966 to October 2012),Embase(from 1980 to October 2012) and the Cochrane library(from 1 October 2008 to end October 2013). The search combined terms related to lercanidipine vs nifedipine GITS(including MeSH search using calcium antagonists,calcium channel blockers and dihydropyridines).RESULTS: With regard to blood pressure(BP) control and the consistency of BP control throughout 24-h,there is limited published evidence. However,two studies using 24 h ambulatory blood pressure monitoring clearly identified the dose-dependency of BP lowering with lercanidipine and its variably sustained 24-h efficacy. In contrast,there is evidence of a consistent antihypertensive effect throughout 24 h with nifedipine GITS. The incidence of the most common "side effect",i.e.,peripheral(ankle) oedema can be estimated as follows. For every 100 patients treated with lercanidipine,2.5 will report oedema compared to 6 patients treated with nifedipine GITS. However,98 or 99 patients will continue treatment with nifedipine GITS,compared with 99.5 patients on lercanidipine. Finally,with regard to outcome studies of cardiovascular(CV) morbidity and mortality,there is definitive outcome evidence for nifedipine GITS but there is no evidence that treatment with lercanidipine leads to reductions in CV morbidity and mortality.CONCLUSION: There is no evidence in terms of longterm BP control and CV protection to justify the contention that lercanidipine is therapeutically equivalent to nifedipine GITS.

关于房颤患病率、发病率、初级保健负荷和治疗的苏格兰全民调查

目的：调查房颤（AF）的流行病学、初级保健负荷和治疗。设计：纳入2001年4月至2002年3月间参与苏格兰连续患病记录计划的初级保健机构，获取横断面资料。地点：55个初级保健机构（362155例患者）。参与者：3135例AF患者。结果：在苏格兰，AF的患病率在男性中为9．4／1000，女性中为7．9／1000（P〈0．001），且随着年龄的增长而增加（年龄〉85岁的个体中为71／1000）。AF患病率随着社会经济匮乏的增高而减少（最小匮乏人群为9．2／1000，最大匮乏人群为7．5／1000，趋势P=0．02）。71％的AF患者接受了心率控制治疗：28％采用β阻断剂，42％为控制心率的钙通道阻断剂，43％为地高辛。

心力衰竭患者的临床特征及预后的性别差异:来自CHARM(坎地沙坦治疗心力衰竭降低死亡率和发病率的评估)研究的结果

背景:作者拟通过比较左室射血分数(LVEF)水平分布广泛的男性和女性心力衰竭患者发生致死性和非致死性预后的情况。

Is There a Crisis in Heart Transplantation? Reflection over 10 Years

Heart transplantation is without doubt a very effective treatment for patients’ whose lives and well-being are threatened by their failing heart. We previously categorized our concerns into four areas or Ds: Donor availability, Disorganization, Disillusionment (of clinicians) and Disaffection (of tomorrow’s clinicians). After a decade, this is a timely reflection on this crisis of cardiac transplantation. It is also appropriate to set this in the context of a fifth D, the Demand for heart transplantation. In this reflective analysis, we use the 5 Ds to explore the current climate in heart transplantation, with particular reference to the situation in the UK.

UVA1光疗法治疗脂质渐进性坏死

The primary c ause of collagen degeneration in necrobiosis lipoidica (NL) is proposed to be immunologically mediated vascular disease. Ultraviolet (UV)A1 has been used successfully to treat scleroderma in which both vascular damage and collagen dysregulation also occur. We treated six patients with NL [(five women; mean age of 32 years (range 22-70) and mean disease duration of 2.9 years (range 6 months to 5 years)] with a high-output ultraviolet (UV)A1 2-kW filtered metal halide source (Dr; Dermalight ultrA 1) having an emission spectrum of 340-440 nm. All patients had NL on the shins, which had been unresponsive to potent topical corticosteroid therapy (n = 6) and had responded minimally or not at all to TL-01UVB (n = 2), topical psoralen plus UVA(PUVA) soaking (n = 2) or oral PUVA(n = 1) therapy. Patients received a variable number of total exposures (15-51), given 3-5 times weekly. NL resolved completely in one patient; this patient had minimal improvement after the first course of 16 exposures, but after a further 13 exposures, resolution occurred 6 months later. Two subjects obtained moderate improvement in their overall disease severity after 15 and 24 exposures, while two had only minimal improvement after 15 and 51 exposures. The remaining patient had no improvement after 16 treatments. Patients with the shortest disease duration had the greatest response. UVA1 therapy may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids or as a second-line alternative to other phototherapies, and may have a superior outcome in a proportion of patients.

UVA1光疗法治疗生殖器萎缩性硬化苔藓

Background. Lichen sclerosus (LS) is characterized histologically by an inflammatory T-cell infiltrate, sclerosis and thickening of the dermis, and epidermal atrophy. Ultraviolet (UV) A1 therapy has been shown to be effective in the management of morphea and scleroderma, diseases that have some histological and clinical similarities with LS, and more recently in extragenital LS. Aim. To determine the effectiveness of UVA1 therapy for genital LS. Methods. Seven women with severe genital LS uncontrolled by ultrapotent topical corticosteroids, with a median age of 62 years (range 48-78) and disease duration of 6-47 years, were treated with UVA1 therapy from a high output source. After completion of UVA1 therapy, a clinician and the patient graded the overall response of symptoms and physical signs. Results. Five patients improved with therapy. Three obtained moderate improvement in overall disease severity and two had minimal improvement. Of these five, one relapsed within 3 months and another after a year. Both had a further course of UVA1 therapy, resulting in minimal improvement in one and moderate improvement in the other. In the remaining three, disease severity had improved to a point where intermittent use of topical corticosteroids resulted in acceptable control. Discussion. UVA1 therapy may be of benefit in the management of vulval LS, a disease that is often poorly responsive to standard therapies. The therapy is well tolerated and could provide an acceptable therapeutic option for patients with severe disease.

每日与每周局部应用5%氟尿嘧啶(Efudix~霜)治疗光化性角化病的随机试验

Background: Topical 5-fluorouracil (5-FU) cream is widely used in the treatment of actinic keratoses (AKs) but the optimumtreatment regimen that provides efficacywhileminimizing side-effects remains unclear. Objectives A randomized trial to compare the efficacy and side-effects of daily vs. weekly application of 5%5-FU in the treatment of AKs of the scalp and face. Patients/methods Twenty patients were recruited and randomized to two groups. Group 1 (13 patients) appl ied 5%5-FU twice daily for 3 weeks, group 2 (seven patients) applied 5%5-FU twice daily for 1 day per week for 12 weeks. Patients were reviewed at weeks 3, 12, 24 and 52. At each review a lesion count and lesion map were completed and p atients were asked to score efficacy and inflammation. Results At week 0 the med ian lesion count was the same in both groups, 17.5 lesions. At 12 weeks the medi an lesion count in group 1 had fallen to 0 where it remained for the duration of follow-up. In group 2 the median lesion count fell to 6 at 12 weeks, 5.5 at 24 weeks and was 3 at 52 weeks. The difference in the lesion count was significant at all time points after week 0: P < 0.05 at weeks 12 and 52, and P < 0.01 at w eek 24. The mean inflammation score was higher in patients clear of AKs at 12 we eks compared with those who had not cleared, 3.8 compared with 1.9. This differe nce was statistically significant (P < 0.05) suggesting that inflammation is nec essary for efficacy. Conclusions We conclude that daily application of 5%5-FU cream is more effective than weekly application at clearing AKs from the scalp a nd face. Our results also suggest that inflammation is likely to be required to achieve a therapeutic effect.

苏格兰心力衰竭的流行、发病率、基础护理负担及治疗状况的国内调查

Objective: To examine the epidemiology, primary care burden, and treatment of heart failure in Scotland, UK. Design: Cross sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 1999 and 31 March 2000. Setting: 53 primary care practices(307 741 patients). Subjects: 2186 adult patients with heart failure. Results: The prevalence of heart failure in Scotland was 7.1 in 1000, increasing with age to 90.1 in 1000 among patients ≥85 years. The incidence of heart failure was 2.0 in 1000, increasing with age to 22.4 in 1000 among patients ≥85 years. For older patients, consultation rates for heart failure equalled or exceeded those for angina and hypertension. Respiratory tract infection was the most common comorbidity leading to consultation. Among men, 23%were prescribed a βblocker, 11 %spironolactone, and 46%an angiotensin converting enzyme inhibitor. The corresponding figures for women were 20%(p=0.29 versus men), 7%(p=0.02), and 34%(p< 0.001). Among patients< 75 years 26%were prescribed a βblocker, 11%spironolactone, and 50%an angiotensin converting enzyme inhibitor. The corresponding figures for patients ≥75 years were 19%(p=0.04 versus patients< 75), 7%(p=0.04), and 33%(p < 0.001). Conclusions: Heart failure is a common condition, especially with advancing age. In the elderly, the community burden of heart failure is at least as great as that of angina or hypertension. The high rate of concomitant respiratory tract infection emphasises the need for strategies to immunise patients with heart failure against influenza and pneumococcal infection. Drugs proven to improve survival in heart failure are used less frequently for elderly patients and women.

Barrett食管在胃酸反流时硝酸盐与亚硝基的化学作用

Background and aims: When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide. In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia. We have studied the location of this luminal chemistry in Barrett’s patients during acid reflux. Methods: Ten Barrett’s patients were studied before and after administration of 2 mmol nitrate. Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barrett’s segment, hiatal sac, proximal stomach, and distal stomach. In a subgroup, real time nitric oxide concentrations were also measured. Results: During acid reflux, Barrett’s segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate. Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites. On entering the acidic Barrett’s segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site. Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 μM within the Barrett’s segment. Conclusion: The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barrett’s oesophagus.

老年患者应用经导管房间隔缺损封堵器的技术因素和短期效果

Background: Device closure of an atrial septal defect(ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients > 60 years. Methods: Retrospective study of Amplatzer Septal OccluderTM device closures from a single institution(May 1999- August 2002). Results: Fifty subjects aged > 60 years(range 60-85 years) had ASD device closure(27% of the total cohort). Defect size and shunt size were similar for both younger and older groups(2.2: 1 in both groups, p=0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular(RV) systolic pressure((younger vs. older) 39 vs. 49 mmHg, p< 0.001) and right ventricular size(45 vs. 51 mm, p< 0.001) were greater in the older group. Following closure RV systolic pressure(49 vs. 45 mmHg, p< 0.01) and RV size(51 vs. 44 mm, p=0.01) decreased in the older group. Conclusion: Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.

对子宫内胎儿双眼发育性白内障的诊断的临床病理研究

Background: We report a case of unusual, bilateral developmental cataracts in a fetus with a supernumerary chromosome. Methods: A 42- year-old woman presented during her 6th pregnancy for assessment of fetal karyotype. This showed a supernumerary chromosome derived from chromosome 21. Subsequently fetal ultrasound suggested the presence of bilateral cataracts and the pregnancy was terminated at 19 weeks and 3 days’ gestation. Both eyes were submitted for histopathological and electron microscopical examination. Results: Histopathological examination revealed unusual bilateral developmental cataracts with abnormal bladder-type cells lining the posterior aspect of the lens vesicle, a poorly formed nuclear bow and a central mass of fibrillar material associated with macrophages lying within an area of liquefaction. Transmission electron microscopy revealed the presence of peg and socket joints in both central and posterior regions and degenerate crystallins in the posterior region. Conclusions: We described an unusual case of developmental cataract diagnosed in utero by ultrasound. The morphological appearances suggest that the defect occurred during or after formation of the secondary lens fibres. Detailed descriptions of cases such as this one may contribute to our understanding of lens development and cataract formation.

苏格兰地区心绞痛的患病率、发病率、初级医疗负担和药物治疗:一项关于年龄、性别和社会经济学差异的人群研究

Objective: To examine the epidemiology, primary care burden and treatment of angina in Scotland. Design: Cross-sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 2001 and 31 March 2002. Setting: 55 primary care practices(362 155 patients). Participants: 9508 patients with angina. Results: The prevalence of angina in Scotland was 28/1000 in men and 25/1000 in women(p< 0.05) and increased with age. The prevalence of angina also increased with increasing socioeconomic deprivation from 18/1000 in the least de-prived category to 31/1000 in the most deprived group(p< 0.001 for trend). The incidence of angina was higher in men(1.8/1000) than in women(1.4/1000)(p=0.004) and increased with increasing age and socioeconomic deprivation. Socioeconomically deprived patients(0.48 contacts/patient among the most deprived) were less likely than affluent patients(0.58 contacts/patient among the least deprived) to see their general practitioner on an ongoing basis (p=0.006 for trend). Among men, 52%were prescribed βblockers, 44%calcium channel blockers, 72%aspirin, 54%statins and 36%angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The corresponding prescription rates for women were 46%(p< 0.001), 41%(p=0.02), 69%(p< 0.001), 45%(p< 0.001) and 30%(p< 0.001). Among patients< 75 years old 52%were prescribed a βblocker and 58%a statin. The corresponding figures for patients ≥75 years were 42%(p< 0.001) and 31%(p< 0.001). Conclusions: Angina is a common condition, more so in men than in women. Socioeconomically deprived patients are more likely to have angina but are less likely to consult their general practitioner. Guideline-recommended treatments for angina are underused in women and older patients. These suboptimal practice patterns, which are worst in older women, are of particular concern, as in Scotland more women(and particularly older women) than men have angina.

缺血性脑卒中的急性期后治疗和二级预防

这篇综述（BMJ2011；342：d1938）两部分的第一部分讨论了脑血管病事件急性期诊断和治疗。目前很多研究、公共卫生法案和健康政策都集中在卒中急性期、超急性期的治疗。然而，卒中治疗的主要目标是最大限度的恢复功能并预防复发。

Effect of oral administration of vitamin C on human aqueous humor ascorbate concentration

AIM:To study oral administration of vitamin C on human aqueous humour ascorbate concentration.METHODS:High performance liquid chromatography(HPLC)coupled with electrochemical detector(BCD)was used.The effect of oral administration of various doses of ascorbic acid,0(control),1.0,1.5,2.0,3.0,and 5.0 g,on its concentration in aqueous humour,obtained from volunteer cataract patients was studied.RESULTS:The concentration of ascorbic acid in aqueous humour of control group without administration of vitamin-C tablet or drug containing ascorbic acid was(254±119)mg·L^(-1).This study revealed that the administration of 2.0 g of.ascorbic acid saturate the aqueous humour and further increase in the dose(3.0 g and 5.0 g)did not increase its concentration in aqueous humour,although its concentration was increased in plasma.CONCLUSION:Oral administration of 2.0 g of Vc is sufficient to saturate the aqueous humour where it may be helpful in controlling the intra-ocular pressure.

2004英国高血压学会高血压治疗指南(BHS-IV):概要

在高血压领域，不断出现的新证据已日益受到关注。例如：血压可作为心血管疾病的一个危险因素；改进生活方式对于预防和治疗高血压的重要意义；不同类型药物的有效性和安全性；高危高血压患者包括糖尿病患者的治疗；心血管疾病总体危险性评估的重要性以及使用他汀类药物所获得的额外益处。

在临床实践中如何测定肾功能

本文要点构成慢性肾脏病分期的基础是估计肾小球滤过率(eGFR)当 eGFR 在60～89ml/min/1.73m^2之间,但缺乏其他肾脏疾病证据时,并不代表有慢性肾脏疾病,也不需要进一步检查慢性肾病患者罹患心血管疾病的风险升高基于"4-vMDBD"公式的 eGFR 和血肌酐一样,已经成为生化实验室常规报告的指标(除了那些未经验证的患者人群)eGFR 或血肌酐水平可以用于监测患者个体肾功能的变化正规的 GFR 检测主要用于对潜在的肾移植供者的肾功能进行准确评价和研究放射性同位素或碘造影剂需要多份血标本,如果肾功能下降。

腹股沟疝

对于没有症状的腹股沟疝，如果患者适于手术，应该进行手术修补网片修补是复发率最低的疝修补方式建议对复发和双侧的腹股沟疝采用腹腔镜修补，初发疝修补也可以采用该方法疝修补术后患者不上班的中位时间是7天，对于那些高强度劳动者可能为14天早期并发症包括淤血。