伊曲康唑治疗中枢神经系统真菌感染的临床开放研究

目的:观察伊曲康唑注射液和口服液序贯治疗中枢神经系统真菌感染的疗效,以及与两性霉素B和(或)氟胞嘧啶联合应用时的安全性。方法:采用开放性临床研究,自2004年6月-2005年9月间共收治17例中枢神经系统真菌感染,均采用伊曲康唑单独或联合两性霉素B和(或)氟胞嘧啶治疗,伊曲康唑注射液治疗至少1 wk以上。伊曲康唑注射液静脉滴注d 1～2为200 mg,q 12 h,d 3～14为200 mg·d-1;继之伊曲康唑口服液200 mg,q 12 h序贯治疗,两性霉素B 20～30 mg·d-1缓慢静脉滴注和(或)氟胞嘧啶6 g·d-1,分4次口服。结果:确诊病例14例,临床诊断病例3例,病原菌包括隐球菌、曲霉菌和小型无绿藻。2例治疗2 d死亡,未纳入疗效评估,临床总有效率为73％(11／15)。其中2例脑曲霉病、1例无绿藻脑膜炎、8例隐球菌脑膜炎(隐脑)均获痊愈;3例隐脑进步,1例侵袭性脑曲霉病无效死亡。治疗过程中,伊曲康唑注射液的不良反应主要为轻度肝功能异常,口服液治疗中部分病人有消化道症状,包括恶心、食欲下降,发生在服药2 mo以后。结论:伊曲康唑注射液和口服液单独或联合其他抗真菌药物治疗中枢神经系统真菌感染具有较好的疗效和安全性。     

Surgical Aspects of Parkinson's Syndrome

Typical psychologic processes come into action as soon as a sick human being consults a physician. These processes are dependent on pre-arranged expectations on the part of both doctor and patient. Scientific expectations, wishes of cure, infantile patterns and unconscious cravings all determine the complicated doctor-patient relationship which influences the therapeutic process.     

Epidemiology of Cryptococcus and cryptococcosis in Western Africa

Cryptococcosis is a serious and sometimes fatal fungal disease caused by Cryptococcus species. Worldwide, it is estimated to kill over 180 000 annually, with 75% of deaths occurring in sub‐Saharan Africa. Though cryptococcal infections are rare in otherwise healthy individuals, there have been reported cases in immunocompetent persons. Most cases occur in individuals who have weakened immune systems, particularly those with advanced HIV/AIDS, thus making West Africa a potential hotspot of the disease. Despite this, there is no recent review article with a focus on published findings on cryptococcosis in Western Africa. Common clinical symptoms include chest pain, dry cough, headache, nausea, confusion, fever, fatigue and stiffness of the neck/neurological impairment. The CNS and the lung remain its preferred target even though rare cases of attack on other parts of the body were reported in this review. Cryptococcal antigen screening and India ink preparation were the most commonly used diagnostic methods. Repeated isolation from environmental samples was observed. Overall, data on the clinical prevalence of Cryptococcus are scarce and variable in the region. The environmental prevalence ranges from 2.3% to 22%. This review covers all published research findings on cryptococcosis in West Africa till date. The epidemiological data will likely be of interest to clinicians within and outside the continent. The nations covered in this review include the following: Benin Republic, Burkina Faso, Cote d'ivoire, Ghana, Guinea, Guinea‐ Bissau, Mali, Nigeria, Senegal and Sierra Leone. More studies are warranted to fill the observed gaps on the epidemiology of Cryptococcus in the region.     

Genotyping and antifungal susceptibility testing of Cryptococcus neoformans isolates from Cameroonian HIV-positive adult patients

Cryptococcus neoformans is the most common cause of meningitis amongst adult Africans with HIV/AIDS. The widespread use of fluconazole may lead to the emergence of isolates with reduced susceptibility. We studied C. neoformans isolates from HIV-infected patients with cryptococcal meningitis. Genotyping and antifungal testing were performed to assess the genetic diversity, occurrence of mixed infections and in vitro activity of antifungal agents. Isolates were recovered from cerebrospinal fluid prior to systemic antifungal treatment. Six isolates were studied for each sample (a total of 114 isolates from 19 patients). Serotyping was performed via LAC 1 and CAP 64 gene amplification and genotyping was performed using phage M13 core, (GACA)₄ and (GTG)₅ primers and restriction polymorphism analysis of the URA5 gene. Susceptibilities for amphotericin B, flucytosine, fluconazole, voriconazole and posaconazole were tested by the Sensititre YeastOne® method. All strains were identified as C. neoformans var. grubii serotype A. We identified nine major genotypes. Up to two genotypes were identified in the same sample. None of the isolates were resistant to the studied drugs. However, 13 of 114 strains exhibited a reduced susceptibility to fluconazole and 13 of 114 strains exhibited a reduced susceptibility to flucytosine. No correlation was found between the genotype and susceptibility. This study confirms the prevalence of C. neoformans serotype A in Cameroon. Two genotypes may be responsible for a single episode of cryptococcosis. The possibility of mixed infection and diminished susceptibility to fluconazole or flucytosine must be considered for the management of cryptococcosis.     

非免疫缺陷者肺隐球菌病110例临床分析

目的探讨非免疫缺陷患者肺隐球菌病的临床特征、影像学表现、诊断和治疗,提高对本病的认识。方法对1995年1月至2012年6月本所确诊的110例非免疫缺陷肺隐球菌病患者进行回顾性研究,分析其临床特点。结果肺部隐球菌病以中青年（62例．56．4％）男性（82例,72．7％）多见。临床表现主要为咳嗽（67例,60．9％）、咳痰（43例。39．1％）、发热（21例．19．1％）、胸痛（21例,19．1％）、气促（21例,19．1％）、消瘦（11例,10．0％）,亦可无症状（28例．25．5％）。胸部影像学表现为孤立性肿块影（26例,23．6％）、多发结节影（20例,18．204）、斑片实变影（33例,30．0％）、结节影与斑片影共存（31例,28．2％）。病变分布晕下肺多于中上肺（60．0％vs18．2％）、右肺多于左肺（39．1％vs32．7％）的特点．31例（28．2％）双肺均有病变。45例行血清隐球菌抗原乳胶凝集试验,阳性29例（64．4％）,弱阳性2例（4．4％）,阴性14例（31．1％）。全部病例均经病理确诊。手术切除病灶或足疗程抗真菌治疗可取得理想的疗效。结论肺隐球菌病多发生于无基础肺疾患的男性中青年．临床症状无特异性,影像学改变多样性,易被漏诊、误诊。疑似病例应行血清乳胶凝集试验、经纤维支气管镜或经皮肺穿刺活检确诊,手术切除及足疗程的抗真菌治疗可取得较好疗效。     

肺真菌病59例病原学和影像学分析

目的：探讨肺真菌病的病原学分布和影像学特征。方法收集肺真菌病59例,均经支气管镜、经皮肺穿刺活检或手术切除送病理学确诊,分析其病原学分布和影像学特征。结果59例病理学确诊肺真菌病患者中,肺曲霉病24例（40．7％）,肺隐球菌病24例（40．7％）,肺毛霉病5例（8．5％）,肺念珠菌病4例（6．8％）,组织胞浆菌病2例（3．4％）,合并放线菌肺炎1例（1．7％）。胸部影像学改变包括肺部肿块23例（39．0％）,渗出性病变23例（39．0％）,结节8例（13．6％）,支气管肿物3例（5．1％）,空洞病变1例（1．7％）,弥漫性病变1例（1．7％）。误诊为肺炎12例（20．3％）,肺结核7例（11．9％）,肺癌4例（6．8％）。结论病理学确诊的肺真菌病以肺曲霉病和肺隐球菌病为多见,影像学表现主要以肺部肿块影和渗出性病变为主。肺真菌病影像学表现多种多样、缺乏特征性,诊断应尽早取得病理学依据。     

29例不同免疫状态肺隐球菌病临床分析

目的分析不同免疫状态肺隐球菌病的临床表现、治疗。方法回顾性分析2004年1月至2011年5月我院确诊为肺隐球菌病患者的临床资料。结果确诊肺隐球菌病共29例,免疫低下组9例,免疫正常组20例。免疫低下组仅3例(33.3%)无症状,而免疫正常组有12例(60%)无症状。免疫低下组有6例(66.7%)累及双肺,而免疫正常组仅6例(30%)累及双肺。两组病例共随诊22例,均未发生隐球菌全身播散。结论肺隐球菌病起病隐匿,临床及影像学不特异,诊断主要依赖病原学及病理检查。治疗应根据不同患者的免疫状态采取合理的方法,免疫功能正常的患者预后较好。     

Oral, Topical and Parenteral Antifungal Treatment with Itraconazole in Normal and in Immunocompromised Animals

Summary: Itraconazole was dissolved in polyethylene glycol for oral and topical treatment and in hydroxypropyl-β-cyclo-dextrin for oral, topical or parenteral treatment.
Topical and oral treatment was successful in microsporosis, trichophytosis, skin-and vaginal candidosis, pityrosporosis and eye mycosis by Candida, Fusarium and Aspergillus . Vaginal candidosis could be cured with a one-day topical or oral treatment.
The same results could not be obtained with any of the reference compounds (griseofulvin, terbinafine, ketoconazole or fluconazole) on amg per kg body weight base, nor on a% concentration base. Antifungal levels were determined by bioassay: biologically active antifungal levels were present in plasma and vaginal fluid of rats, after one oral dose of 10mg.kg^-1, for at least 72 and 96 hours respectively. This was in good correlation with findings on prophylaxis of vaginal candidosis. Itraconazole was also successfully used, in normal animals and animals immunodepressed with various agents, in disseminated and systemic diseases: trichophytosis, sporotrichosis, histoplasmosis, candidosis, aspergillosis and cryptococcosis. Oral and parenteral treatment with itraconazole was compared in various models to oral and parenteral fluconazole and to parenteral amphotericin B. The outcome with itraconazole was better than with the other antifungals. Meningeal cryptococcosis responded very well to itraconazole. Combination therapy of itraconazole and fluconazole was not superior to treatment with itraconazole alone. No side-effects were observed in relation to itraconazole treatment.b