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存在HIV感染时的结核病治疗

国际结核病与肺部疾病杂志 1996年第2期 45-51页

作者： J.H.Grosset 李荣德 groupe hospitalier pitie salpetriere ParisFrance

不论结核病病人接受的是用异烟肼(INH)和利福平(RIF)进行的短程化学治疗,结合吡嗪酰胺(PZA)和乙胺丁醇(EMB)或链霉素(SM)与否,还是用INH,SM,和氨硫脲(Tb1)进行的长期化学治疗,HIV阳性和HIV阴性病人痰培养的阴转率都是相似的。为了防止复... 详细信息

不论结核病病人接受的是用异烟肼(INH)和利福平(RIF)进行的短程化学治疗,结合吡嗪酰胺(PZA)和乙胺丁醇(EMB)或链霉素(SM)与否,还是用INH,SM,和氨硫脲(Tb1)进行的长期化学治疗,HIV阳性和HIV阴性病人痰培养的阴转率都是相似的。为了防止复发,曾有人建议至少治疗9个月,并且于痰阴转后至少治疗6个月,或甚至在治疗终了后终生服用异烟肼。但并未观察到HIV阳性和HIV阴性病人之间在复发率上有何差别。在用INH+RIF十PZA+EMB(或SM),或用INH+SM+Tb1治疗的HIV阳性病人中,有20％发生了副作用,表皮坏死溶解是由Tb1造成的,该副作用且导致了一些病例的死亡。染有HIV的结核病病人的平均生存期为作出结核病诊断后10至18个月。其它非结核分支杆菌感染可能是死亡的主要原因。在HIV阳性结核病病人的治疗中,获得性耐药并非常见并发症,但近期在美国已见到数次由医院传染的对多种药物耐药的结核病的流行。 Sparfloxacin是一种新的氟喹诺酮类药物,它的半衰期长,对结核分支杆菌的最低抑菌浓度低(MIC为0.25-0.50mg/l),是一种有前途的抗结核药物。

关键词： tuberculosis HIV感染结核分支杆菌H37Rv 结核病治疗化学治疗药物不良反应最低抑菌浓度 HIV阳性阴性病人利福平

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

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World Journal of Hepatology 2016年第21期8卷 902-914页

作者： Sylvie Lagaye Sonia Brun Jesintha Gaston Hong Shen Ruzena Stranska Claire Camus Clarisse Dubray Géraldine Rousseau Pierre-Philippe Massault Jerome Courcambeck Firas Bassisi Philippe Halfon Stanislas Pol Institut Pasteur INSERM Institut Cochin INSERM U1016CNRS UMR8104Universite Paris Descartes(UMR S1016) Genoscience Pharma KU Leuven Rega Institute Laboratoire Alphabio APHP Groupe Hospitalier La Pitie Salpe-triereService de Chirurgie digestive et Hepato bilio pancreatique APHP Groupe Hospitalier CochinService de Chirurgie digestiveHepato-biliaire et Endocrinienne Universite Paris Descartes APHP Groupe Hospitalier CochinUnite d’Hepatologie Institut Pasteur Departement de Recherche TranslationnelleINSERM

AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

关键词： Host antiviral therapy Hepatitis C virus Tissue culture Autophagy Quinoline derivative

Arrhythmogenic Ventricular Dysplasia/Cardiomyopathy: Insights from the Rationale of Disease Nomenclature and Clinical Perspectives

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World Journal of Cardiovascular Diseases 2015年第8期5卷 218-226页

作者： Aimé Bonny Mohammed A. Talle Guy Fontaine Douala Cardiovascular Research Center University of Douala Douala Cameroon Clinique Paul Picquet Sens France Division of Cardiology Department of Internal Medicine University of Maiduguri Teaching Hospital/University of Maiduguri Maiduguri Nigeria groupe hospitalier pitie salpetriere Unite de Rythmologie Paris France

“Arrhythmogenic right ventricular dysplasia” (ARVD), a heart muscle disorder characterized by the presence of fibro-fatty tissue and ventricular electrical vulnerability related to sudden death, was first described in 1977 by a French team. Since then, other terms such as “arrhythmogenic right ventricular cardiomyopathy” (ARVC), “arrhythmogenic cardiomyopathy” (AC), “left-dominant arrhythmogenic cardiomyopathy” (LDAC), and “arrhythmogenic left ventricular dysplasia” (ALVD) have been introduced. These changes in nomenclature of the same disease entity are based on different explanations of pathomorphologic patterns. The dysplasia theory claims cardiac growth “maldevelopment” whereas the cardiomyopathy has been seen as an atrophy from acquired injury (myocyte death) and repair (fibrofatty replacement). The other area of divergent opinion is with regards to involvement of both ventricles rather than being an isolated right ventricular anomaly that may result in increased likelihood of diagnosing the concealed form manifesting with pre-dominant left ventricular arrhythmias. Multiple line of evidences support common disease path-ways: Presence of fibro-fatty and superimposed myocarditis, desmosome mutations and malfunc-tion. These compelling data regarding the heart growth, and pathological, clinical, phenotype/ genotype correlates have advanced our understanding of arrhythmogenic ventricular dysplasia/ cardiomyopathy and increased the diagnostic accuracy as well as providing an avenue for future development of new mechanism-based therapies.

关键词： Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Arrhythmogenic Cardiomyopathy Ventricular Arrhythmia Sudden Cardiac Death

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麻醉恢复室中出现严重手术后疼痛的预测因素

麻醉与镇痛 2009年第3期5卷 76-83页

作者： Frederic Aubrun Nathalie Valade Pierre Coriat Bruno Riou 周全红(译) Departments of Anesthesiology and Critical Care Groupe hospitalier Pitie-Salpetriere Assistance Publique-Hopitaux de Paris(AP-HP) Universite Pierre et Marie Curie-Paris France Departments of Emergency Medicine and Surgery Groupe hospitalier Pitie-Salpetriere Assistance Publique-Hopitaux de Paris(AP-HP) Universite Pierre et Marie Curie-Paris France 不详

背景静脉内吗啡给药（IMT）广泛用于麻醉恢复室内患者镇痛。许多因素影响手术后疼痛程度或吗啡用量。本文前瞻性分析了严重手术后疼痛手术前和手术中的预测因素。严重手术后疼痛的定义是指IMT〉0．15mg／kg或IMT失败。方法我们分析了手... 详细信息

背景静脉内吗啡给药（IMT）广泛用于麻醉恢复室内患者镇痛。许多因素影响手术后疼痛程度或吗啡用量。本文前瞻性分析了严重手术后疼痛手术前和手术中的预测因素。严重手术后疼痛的定义是指IMT〉0．15mg／kg或IMT失败。方法我们分析了手术前疼痛、药物治疗作用以及手术中事件对手术后疼痛的影响。IMT后，患者被分为两组：严重疼痛组（SP）和非严重疼痛组。数据用均数±标准差表示。结果本次研究包括了342例患者，其中非严重手术后疼痛组有200例（58％），严重手术后疼痛组（SP组）有142例（42％）。单因素分析发现两组患者的既往手术史和疾病史没有显著差异，但是SP组手术前治疗更频繁（P〈0．05）。SP组的手术时间和麻醉时间显著长于非SP组（P〈0．001）。SP组的舒芬太尼用量较大，同时IMT结束前和结束时视觉模拟疼痛评分的分值较高（P〈0．001）。多因素分析发现手术中阿片类药物的用量高（舒芬太尼剂量〉0．6μg/kg）（比值比=2．68，P〈0．001）、全身麻醉（比值比=3．96，P=0．03）以及手术前使用镇痛药（比值比=1．91，P〈0．01）是与严重手术后疼痛相关的独立因素。结论严重手术后疼痛与手术中使用大剂量舒芬太尼，全身麻醉以及手术前使用镇痛药有显著关系。

关键词：手术后疼痛麻醉恢复室预测因素视觉模拟疼痛评分阿片类药物术后疼痛程度舒芬太尼全身麻醉

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超声造影对局灶性结节增生大小的研究

国际医学放射学杂志 2014年第6期 609-610页

作者： C.Bertin S.Egels M.Wagner I.Huynh-Charlier V.Vilgrain O.Lucidarme 刘代洪 Service de Radiologie Polyvalente et Oncologique Groupe Hospitalier Pitie-Salpetriere-Charles Foix47-83boulevard de I’ Hopital75651ParisCedexFrance

摘要目的评估在局灶性结节增生(FNH)超声造影(CEUS)检查中与病灶大小相关的离心性强化、轮辐征及中心瘢痕等征象出现的频率。方法回顾性评价94个FNH,评

关键词：超声造影病灶结节离心性 FNH 局灶性

E-Cigarette: A New Tobacco Product for Schoolchildren in Paris

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Open Journal of Respiratory Diseases 2013年第1期3卷 21-24页

作者： Bertrand Dautzenberg Pierre Birkui Maryvonne Noel Johanna Dorsett Monique Osman Marie-Dominique Dautzenberg Paris Sans Tabac(PST) ParisFrance Office Francais de Prevention du Tabagisme(OFT) ParisFrance groupe hospitalier pitie-salpetriere(APHP) ParisFrance UniversitePierre et Marie Curie ParisFrance Rectorat de l’Academie de Paris ParisFrance Hopital Necker Enfants-Malades ParisFrance UniversiteReneDescartes ParisFrance

Objectives: To explore if the dramatic decrease in price of e-cigarette has transformed this new product into a product used for tobacco initiation among a teenage population. Methods: The authors added a question in 2012 on e-cigarette in the yearly survey on tobacco consumption in Paris schoolchildren. The study is conducted on a randomly selected sample from 2% of classes since 1991. Results: 277 (8.1%) of the 3409 schoolchildren studied (including 575 non responders to this question) reported having had an experience with e-cigarette. Experimentation rate is 6.4% among the 12 - 14-year-old, 11.8% among the 15 - 16-year-old and 9% among the 17-year-old schoolchildren. Among the 12 - 14- year-old schoolchildren, 64.4% of e-cigarette experimentation was by non-smokers. Of the 17-year-old teenagers who had used e-cigarettes, 12.4% were non-smokers. For the whole population, 33.2% of those having tried e-cigarette are non-smoker, 22.7% occasional smoker, 3.6% ex-smoker and 40.4% daily smoker. Those who experiment cannabis, shisha or binge-drinking are more frequently users of e-cigarette. In the smoker group, there is an inverse trend of rela- tionship between the readiness to quit tobacco and the rate of use of e-cigarette. Conclusion: For teenager’s, e-cigare- ttes have become not a product to aid quit tobacco but a product for experimentation and initiation of cigarette use. Regulation is urgently needed to control the emergent use of this new tobacco product by children.

关键词： E-Cigarettes Teenagers Tobacco Initiation Epidemiologic Study

Distinct profiles of systemic biomarkers of oxidative stress in chronic human pathologies:Cardiovascular,psychiatric,neurodegenerative,rheumatic,infectious,neoplasmic and endocrinological diseases

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Advances in Bioscience and Biotechnology 2013年第3期4卷 331-339页

作者： Michel Brack Olivier Brack Yves Menezo Dominique Bonnefont Rousselot Gerard Dreyfus MJohn Chapman Anatol Kontush Ge Sante et Retraite ParisFrance Consultant en Statistiques EschesFrance Procrelys Maison Medicale Ambroise PareLyonFrance Laboratoire Clement ParisFrance London Fertlity Associates LondonUK Department of Metabolic Biochemistry La Pitie Salpetriere-Charles Foix(AP-HP)ParisFrance Department of Biochemistry Faculty of PharmacyParis Descartes UniversityParisFrance Ecole Superieure de Physique et de Chimie Industrielles ESPCIParisFrance (CNRS UMR 7084) Laboratoire d’electroniqueParisFrance Universite Pierre et Marie Curie-Paris 6 ParisFrance UMR 939“Dyslipoproteinemia Inflammation and Atherosclerosis”INSERMParisFrance AP-HP Groupe hospitalier Pitie-SalpetriereParisFrance

Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.

关键词： Vitamin C Vitamin E β-Carotene Glutathione Thiols Urate 8-Hydroxy-2’-Deoxyguanosine

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阿斯匹林预防心血管疾病的剂量系统综述

美国医学会杂志（中文版） 2007年第5期26卷 292-298页

作者： Charles L. Campbell Susan Smyth Gilles Montalescot Steven R. Steinhubl 李呈亿（译） Gill He＇art Institute University of Kentucky Lexington Gill Heart Instiute and Institut de Cardiologie-Centre hospitalier Universitaire pitie-salpetriere Paris France

背景：为了长期预防心血管疾病，目前美国有5千万以上的成年人定期服用阿斯匹林，所用剂量通常为81mg／d或325mg／d。关于长期服用阿斯匹林的最佳剂量目前仍有争议。目的：复习阿斯匹林的作用机制，对论述阿斯匹林剂量、效果和安全性相... 详细信息

背景：为了长期预防心血管疾病，目前美国有5千万以上的成年人定期服用阿斯匹林，所用剂量通常为81mg／d或325mg／d。关于长期服用阿斯匹林的最佳剂量目前仍有争议。目的：复习阿斯匹林的作用机制，对论述阿斯匹林剂量、效果和安全性相互关系的临床文献进行系统回顾。证据获取：使用MEDLINE和EMBASE（至2007年2月）对相关英文文献进行系统回顾。所用检索词为：阿斯匹林或乙酰水杨酸和剂量。检索限于临床试验，通过审查相关原始资料报告和综述文章的参考文献进一步扩展检索范围。已发表的关于心血管患者使用不同剂量阿斯匹林的前瞻性研究亦纳入分析。证据综合：尽管药理学数据证实长期服用30mg／d阿斯匹林足以充分抑制血小板血栓烷生成，但是目前批准使用的剂量高达1300mg／d。在美国，最常采用的剂量为81mg／d（60％），其次为325mg／d（35％）。现有证据（主要来自二级预防观察研究）支持下述观点：阿斯匹林剂量大于75至80mg／d并不提高疗效，更大剂量反而增加出血事件发生率，后者主要与胃肠道毒性有关。结论：对于心血管疾病的预防，现有临床数据并不支持常规、长期使用大于75～81mg／d剂量阿斯匹林。较高剂量的阿斯匹林虽然常用，但是并不能更好地预防心血管事件，而且发生胃肠道出血的危险增加。

关键词：心血管疾病阿斯匹林最佳剂量预防观系统综述 MEDLINE 长期服用系统回顾

PCR是1995年结核病诊断的有用手段吗?

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国际结核病与肺部疾病杂志 1995年第3期 92-93页

作者： J.Grosset Y.Mouton 屠德华 Laboratoire Central de bactériologie-Virologie Groupe Hospitalier Pitie SalptrièreParis Service Régional Universitaire des Maladies Infectieuses et du Voyageur Centre Hospitalier de TourcoingTourcoing France

广泛应用于微生物学研究的聚合酶链反应(PCR)DNA扩增技术在用于结核病临床诊断作为重要的进展已有若干研究系列的报告。应用根据PCR的技术可能:1.迅速确定临床标本中镜检鉴定的抗酸菌是结核分支杆菌还是非典型分支杆菌。2.在流行病学相... 详细信息

广泛应用于微生物学研究的聚合酶链反应(PCR)DNA扩增技术在用于结核病临床诊断作为重要的进展已有若干研究系列的报告。应用根据PCR的技术可能:1.迅速确定临床标本中镜检鉴定的抗酸菌是结核分支杆菌还是非典型分支杆菌。2.在流行病学相互关系的研究中确定来自不同病人所分离的结核分支杆菌是否属于共同来源。3.鉴定已知的与某些抗分支杆菌药物耐药性有关的遗传变异的存在。4.对镜检阴性的临床标本通过鉴定结核分支杆菌DNA以快速地诊断结核病。

关键词：结核病诊断 tuberculosis 结核分支杆菌 Mycobacterium 临床实验室敏感性和特异性临床标本药物耐药性 1995年遗传变异