来那替尼治疗乳腺癌引起肝毒性和胃肠道不良反应风险的Meta分析

目的研究来那替尼治疗乳腺癌引起肝毒性和胃肠道不良反应风险。 方法检索Cochrane、PubMed、Web of Science、中国知网、维普及万方等相关数据库,检索时间为从建库以来至2018年3月1日,收集关于来那替尼治疗乳腺癌且描述了肝毒性[丙氨酸氨基转移酶(ALT)或天门冬氨酸氨基转移酶(AST)升高]和胃肠道不良反应(包括腹泻、呕吐或恶心)等不良事件的随机对照临床研究。不良反应按严重程度分为1～5级,其中所有级别包括1～5级;严重级别包括3级及以上。由2名研究人员独立完成文献筛选、数据提取,运用Cochrane手册推荐的风险评价工具对文献质量进行评价。采用相对危险度(relative risk, RR)和95%置信区间(confidence interval, CI)作为效应量;采用Q检验分析数据的异质性,并根据异质性结果选择固定效应模型或随机效应模型。 结果本研究共纳入4项RCT研究,共3 745例患者。其中2项研究为来那替尼单用,另外2项研究为来那替尼联用紫杉醇。来那替尼组的所有级别ALT与AST升高发生率与对照组比较,差异无统计学意义(ALT：RR＝1.37,95%CI：0.50～3.76,P＝0.54; AST: RR＝1.19,95%CI：0.36～3.92,P＝0.78),但严重级别的ALT升高发生率来那替尼组高于对照组(RR＝3.63,95%CI：1.58～8.36,P<0.01),来那替尼组的严重级别AST升高发生率与对照组比较,差异无统计学意义(RR＝2.08,95%CI：0.80～5.43,P＝0.13)。关于胃肠道不良反应,所有级别与严重级别的腹泻发生率在来那替尼组均高于对照组(所有级别：RR＝2.06,95%CI：1.38～3.08,P<0.01;严重级别：RR＝8.77, 95%CI：2.91～26.40,P<0.01);所有级别与严重级别的呕吐发生率在来那替尼组均高于对照组(所有级别：RR＝2.13,95%CI：1.43～3.18, P<0.01;严重级别：RR＝6.22,95%CI：3.16～12.27, P<0.01)。所有级别和严重级别的恶心发生率,来那替尼组与对照组比较,差异无统计学意义(所有级别：RR＝1.28, 95%CI：0.81～2.04,P＝0.29;严重级别：RR＝3.10, 95%CI: 0.87～11.00,P＝0.08)。 结论来那替尼用于治疗乳腺癌后,严重级别的ALT升高、腹泻和呕吐的发生率增加,AST升高和恶心的发生率没有明显变化,因此,需要密切监测患者的肝功能和胃肠道功能。     

ω⁃3多不饱和脂肪酸应用于放疗患者中疗效meta分析

目的 系统评价ω‐3多不饱和脂肪酸应用于放疗患者中的疗效。方法 检索PubMed、Medline、Embase、Cochrane图书 馆、中国期刊全文数据库、万方数据等数据库，检索时限至2020年5月，收集在常规饮食或标准肠内营养制剂（对照组）的基础上 加用ω‐3多不饱和脂肪酸（试验组）改善放疗患者营养状况和预防并发症的随机对照试验。提取符合本研究纳入标准的临床对 照试验相关数据，采用Cochrane系统评价员手册5.1标准进行文献质量评价，应用Stata14.0统计软件对两组放疗前后体重丢失情 况与总体并发症发生率进行meta分析。结果 共纳入10项随机对照试验，合计486例患者。结果显示，两组患者放疗前后体重变 化值（SMD＝-0.02，95%CI：-0.26～0.21，P＝0.838）、BMI变化值（SMD＝0.06，95%CI：-0.23～0.34，P=0.696）、总体不良反应发生 率（RR=0.97，95%CI：0.84～1.12，P＝0.678）和厌食不良反应发生率（RR＝0.79，95%CI：0.49～1.28，P=0.345）比较差异均无统计学 意义。结论 在普通膳食或常规营养制剂的基础上加用ω‐3多不饱和脂肪酸并不能改善放疗患者的体重丢失和预防并发症。     

吡咯替尼新辅助治疗人表皮生长因子受体2阳性乳腺癌疗效及安全性的Meta分析

目的评估吡咯替尼联合新辅助化疗治疗HER-2阳性早期或局部晚期乳腺癌的疗效及安全性。 方法检索中国知网、万方、维普、中国生物医学文献服务系统(SinoMed)及PubMed、Embase、Cochrane Library等数据库中吡咯替尼治疗HER-2阳性早期或局部晚期乳腺癌的随机对照研究,检索年限为建库以来至2022年2月9日,文献质量按照Cochrane Review Handbook 5.1.0进行评分,提取指标包括客观反应率、总病理完全缓解率、腹泻等不良事件发生率。对符合质量评价标准的研究使用RevMan 5.4.1软件进行数据提取及定量合成,并根据其异质性大小分别采用固定效应模型或随机效应模型的方法进行分析。 结果最终纳入4项研究,共554例患者,其中吡咯替尼联合化疗组278例,单用化疗组276例。Meta分析结果显示,吡咯替尼联合化疗较单用化疗能明显提高患者的客观反应率(RR＝1.15,95%CI：1.07~1.24,P<0.001)和总病理完全缓解率(RR＝1.90,95%CI：1.45~2.50,P<0.001)。不良反应方面,吡咯替尼联合化疗组≥3级腹泻发生率及任何级别腹泻事件发生率均明显升高(RR＝7.67,95%CI：4.38~13.45,P<0.001;RR＝5.62,95%CI：3.95~8.00,P<0.001);而2组患者白细胞减少、血小板减少、恶心/呕吐以及手足综合征发生率的差异均无统计学意义(RR＝1.02,95%CI：0.87~1.21,P＝0.790;RR＝1.00,95%CI：0.70~1.43,P＝0.990;RR＝1.30,95%CI：1.00~1.68,P＝0.050;RR＝1.46,95%CI：0.75~2.86,P＝0.270)。 结论针对早期或局部晚期HER-2阳性乳腺癌患者,吡咯替尼联合化疗的新辅助治疗方案能够明显提高其客观反应率及总病理完全缓解率,但同时也增加患者≥3级腹泻的发生风险。在临床实践中需重视对腹泻等不良事件的管理,以保证患者治疗的顺利进行及提高其生活质量。     

T-DM1治疗Her-2阳性晚期或转移性乳腺癌有效性及安全性的Meta分析

摘 要：［目的］ 系统评价T-DM1治疗Her-2阳性晚期或转移性乳腺癌的有效性和安全性。［方法］ 检索PubMed、Web of Science、EMBASE、the Cochrane Libarary、CNKI、万方数据库,搜集国内外公开发表的有关T-DM1治疗Her-2阳性晚期或转移性乳腺癌的随机对照研究（RCT）,检索时限从建库到2017年12月。由2名评价员按纳入、排除标准独立进行文献筛选、提取资料,并评价纳入文献的偏倚风险,采用Stata12.0软件进行Meta分析。［结果］ 共纳入4项随机对照试验,共计2812例患者。Meta分析结果显示：与传统的治疗相比,T-DM1治疗Her-2阳性晚期或转移性乳腺癌,疗效方面,两组完全缓解率（RR=0.88,95%CI：0.57～1.36,P=0.574 ）和部分缓解率（RR=1.05,95%CI：0.85～1.29,P=0.667）差异均无统计学意义;安全性方面,两组总不良反应发生率无显著差异（RR=0.99,95%CI：0.98～1.01,P=0.319）;但T-DM1组3级及以上不良反应发生率低于对照组（RR=0.77,95%CI：0.65～0.92,P=0.004）。［结论］ 与传统治疗相比,T-DM1治疗晚期或转移性乳腺癌对完全缓解率、部分缓解率及总不良反应事件发生率无明显改善,但可减少3级以上不良反应发生率。     

促性腺激素释放激素激动剂对绝经前乳腺癌患者化疗期间月经复潮影响的Meta分析

目的研究绝经前乳腺癌患者促性腺激素释放激素激动剂(GnRHa)联合化疗能否提高月经复潮,保护卵巢功能。 方法检索Embase、PubMed、MEDLINE、中国知网、维普、万方网数据库,收集截至2016年12月关于GnRHa对绝经前乳腺癌患者化疗期间卵巢功能影响的随机对照临床试验。由2名研究人员独立完成文献筛选、数据提取,运用Jadad评价量表进行文献质量评价。采用比值比(OR)和95%可信区间(CI)作为效应量,选择相应效应模型并使用RevMan 5.0软件进行Meta分析。 结果共纳入6项随机对照研究,纳入患者714例。接受GnRHa联合化疗的患者自然月经复潮率高于单纯化疗(OR＝2.42,95%CI：1.16～5.05,P＝0.02)。敏感性分析结果稳定(OR＝1.76,95%CI：1.21～2.56,P<0.01)。年龄与月经复潮率无关(<40岁组：OR＝1.71,95%CI：0.70～4.15;P＝0.24;≥40岁组：OR＝1.27,95%CI：0.48～3.34;P＝0.63)。与他莫昔芬联合GnRHa组相比,未使用他莫昔芬组患者的月经复潮率差异有统计学意义(OR＝3.39,95%CI：1.73～6.65,P<0.01)。以蒽环类为基础的化疗方案联合GnRHa对月经复潮有影响(OR＝2.49,95%CI：1.06～5.89,P＝0.04)。联合化疗组与单纯化疗组患者的潮热、阴道干涩、情绪改变及性欲下降等不良反应发生率比较,差异均无统计学意义(OR＝1.87,95%CI：1.00～3.51,P＝0.05;OR＝1.20,95%CI：0.66～2.20,P＝0.55;OR＝1.51,95%CI：0.56～4.07,P＝0.41;OR＝1.21,95%CI：0.64～2.32,P＝0.56)。 结论GnRHa联合化疗可以提高绝经前乳腺癌患者化疗期间的月经复潮率。     

TACE联合SBRT治疗原发性肝癌的Meta分析

目的：系统评价经导管肝动脉化疗栓塞术（ TACE ）单用与联合应用体部立体定向放疗（ SBRT）治疗原发性肝癌的疗效和不良反应,为临床实践提供参考。方法检索PubMed、Cochrane Library、EMBase、Ovid、MEDLINE、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊全文数据库、医学期刊全文数据库,查找关于TACE和SBRT治疗原发性肝癌的临床对照试验研究。按照Cochrane协作网的RevMan 5.2软件进行Meta分析。分析TACE单用与联合应用SBRT两组间的近期疗效,肿瘤局部控制率,1、2、3、5年生存率的差异。结果共有10篇文献,1143例患者满足纳入标准。Meta分析结果显示, TACE联合SBRT组比单纯TACE组近期疗效,肿瘤局部控制率,1、2、3、5生存率均高（RR＝1.43,95%CI为1.32~1.56,P﹤0.00001;RR＝2.09,95%CI为1.63~2.69,P﹤0.00001;RR＝1.31,95%CI 为1.21~1.42,P﹤0.00001;RR＝1.46,95%CI为1.23~1.72,P﹤0.00001;RR＝1.76,95%CI为1.14~2.71,P＝0.01;RR＝2.29,95%CI为1.22~4.32,P＝0.01）。白细胞减少（ RR＝0.97,P＝0.61）、血小板减少（ RR＝0.99,P＝0.85）、血红蛋白减少（RR＝0.95,P＝0.63）、恶心呕吐（RR＝1.00,P＝0.98）、肝功能损害（RR＝0.98,P＝0.87）的发生率两组之间差异无统计学意义。结论与TACE相比,TACE联合SBRT能明显提高患者近期疗效,提高肿瘤局部控制率和1、2、3、5生存率,同时不增加不良反应发生率,但其长期疗效和安全性尚需开展更多大样本、高质量的临床对照试验加以验证。     

可切除食管鳞癌新辅助放化疗的Meta分析

目的:评价术前放化疗联合手术治疗(neoadjuvant chemoradiotherapy and surgery,CRT+S)与单纯手术治疗(surgery,S)对可切除食管鳞癌患者生存及手术的影响。方法:检索PubMed系统中所有CRT+S与S治疗可切除食管鳞癌的随机对照研究(randomized controlled trial,RCT),应用RevMan 5.2软件进行Meta分析。结果:共纳入10篇文献。CRT+S与S组比较:1)患者1年生存率差异无统计学意义,RR=1.03,95%CI为0.96～1.10,P=0.37。2)CRT+S组提高了3、5年生存率,3年RR=1.32,95%CI为1.17～1.50,P<0.001;5年RR=1.24,95%CI为1.03～1.49,P=0.02。3)相比于S组,CRT+S组的手术率较低,RR=0.84,95%CI为0.72～0.99,P=0.04;术后并发症的发生率较高,RR=1.25,95%CI为1.02～1.53,P=0.03;死亡率也较高,RR=2.34,95%CI为1.37～3.99,P=0.002;但提高了R0切除率,RR=1.18,95%CI为1.06～1.32,P=0.002。4)术后局部复发率差异无统计学意义,RR=0.82,95%CI为0.31～2.16,P=0.68;术后远处转移率差异无统计学意义,RR=0.86,95%CI为0.60～1.22,P=0.39。结论:CRT+S治疗明显提高了可切除食管鳞癌患者的长期生存率及R0切除率。     

真空辅助旋切活检和金属丝定位活检对不能触及乳腺病灶的诊断价值

目的 评价真空辅助旋切活检和金属丝定位活检对不能触及的乳腺病灶(NPBL)诊断的准确性和有效性.方法 将97例NPBL患者随机分为两组,分别行金属丝定位切除活检(48例)和真空辅助旋切活检(49例),活检标本均经钼靶确认.记录真空辅助活检组对不典型增生和导管原位癌的低估率以及切缘.对术后的乳房美容效果及术后第1天疼痛强度进行评分.结果 两组患者均成功活检,真空辅助旋切活检组的标本大小为2.3 cm3,显著小于金属丝定位切除活检组(18.4cm3,P=0.03).真空辅助活检组对不典型增生和导管原位癌的低估率分别为16.7%和11.1%.真空辅助旋切活检组的诊断符合率为97.9%,假阴性率为2.1%,无假阳性病例.真空辅助旋切活检组手术后第1天疼痛评分为1.7,低于金属丝定位切除活检组(2.5,P=0.02).真空辅助旋切活检组术后美容评分优良40例,良好8例;金属丝定位切除活检组优良25例,良好24例,两组差异有统计学意义(P<0.05).结论 真空辅助旋切活检结果 可靠,可使大部分良性病变患者免于开放手术,但由于组织学诊断的低估以及较高的切缘阳性率,真空辅助旋切活检尚不能完全替代金属丝定位活检.     

真空辅助旋切活检和金属丝定位活检对不能触及乳腺病灶的诊断价值

目的 评价真空辅助旋切活检和金属丝定位活检对不能触及的乳腺病灶(NPBL)诊断的准确性和有效性.方法 将97例NPBL患者随机分为两组,分别行金属丝定位切除活检(48例)和真空辅助旋切活检(49例),活检标本均经钼靶确认.记录真空辅助活检组对不典型增生和导管原位癌的低估率以及切缘.对术后的乳房美容效果及术后第1天疼痛强度进行评分.结果 两组患者均成功活检,真空辅助旋切活检组的标本大小为2.3 cm3,显著小于金属丝定位切除活检组(18.4cm3,P=0.03).真空辅助活检组对不典型增生和导管原位癌的低估率分别为16.7%和11.1%.真空辅助旋切活检组的诊断符合率为97.9%,假阴性率为2.1%,无假阳性病例.真空辅助旋切活检组手术后第1天疼痛评分为1.7,低于金属丝定位切除活检组(2.5,P=0.02).真空辅助旋切活检组术后美容评分优良40例,良好8例;金属丝定位切除活检组优良25例,良好24例,两组差异有统计学意义(P<0.05).结论 真空辅助旋切活检结果 可靠,可使大部分良性病变患者免于开放手术,但由于组织学诊断的低估以及较高的切缘阳性率,真空辅助旋切活检尚不能完全替代金属丝定位活检.     

真空辅助旋切活检和金属丝定位活检对不能触及乳腺病灶的诊断价值

目的 评价真空辅助旋切活检和金属丝定位活检对不能触及的乳腺病灶(NPBL)诊断的准确性和有效性.方法 将97例NPBL患者随机分为两组,分别行金属丝定位切除活检(48例)和真空辅助旋切活检(49例),活检标本均经钼靶确认.记录真空辅助活检组对不典型增生和导管原位癌的低估率以及切缘.对术后的乳房美容效果及术后第1天疼痛强度进行评分.结果 两组患者均成功活检,真空辅助旋切活检组的标本大小为2.3 cm3,显著小于金属丝定位切除活检组(18.4cm3,P=0.03).真空辅助活检组对不典型增生和导管原位癌的低估率分别为16.7%和11.1%.真空辅助旋切活检组的诊断符合率为97.9%,假阴性率为2.1%,无假阳性病例.真空辅助旋切活检组手术后第1天疼痛评分为1.7,低于金属丝定位切除活检组(2.5,P=0.02).真空辅助旋切活检组术后美容评分优良40例,良好8例;金属丝定位切除活检组优良25例,良好24例,两组差异有统计学意义(P<0.05).结论 真空辅助旋切活检结果 可靠,可使大部分良性病变患者免于开放手术,但由于组织学诊断的低估以及较高的切缘阳性率,真空辅助旋切活检尚不能完全替代金属丝定位活检.     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases

Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA.     

Isoconazole nitrate in the treatment of tropical dermatomycoses

Summary. A total of 54 patients with culturally proven tropical dermatomycoses, comprising 23 with various types of dermatophytoses, one with foot infection due to Trichosporon beigelii and one with foot infection due to Geotrichum candidum , two with candidoses of the groin and 27 with pityriasis versicolor, were included in a clinical trial of efficacy of 1% isoconazole cream (Travogen^R, Schering, Berlin, Germany). Five patients were not evaluable. A clinical and mycological cure was achieved in 29 cases in 3–4 weeks. In 15 (31%) of the remaining patients treatment was required for 5–6 weeks, while another three patients required treatment for 8 weeks. In two patients the disease proved to be resistant to treatment with the drug.
Zusammenfassung. Insgesamt 54 Patienten mit kulturell gesicherter Dermatomykose, (23 unterschiedliche Dermatophytosen, eine Trichosporon beigelii - und eine Geotrichum candidum -Fußinfektion, 2 Candidosen der Leistengegend und 27 Pityriasis versicolor) wurden in einer klinischen Wirksamkeits-studie mit 1% iger Isoconazol-Creme (Travogen^R, Schering, Berlin, Deutschland) behandelt. Fünf Patienten waren nicht auswertbar. Eine klinische und mykologische Heilung wurde bei 47 von 49 Patienten (96%) erreicht. Bei 29 patienten (59%) wurde die Heilung bereits nach 3–4 Wochen Behandlung erreicht. Weitere 15 Patienten (31%) benötigten 5–6 Wochen und drei Patienten 8 Wochen Behandlungsdauer. Zwei Mykosesituationen erwiesen sich als therapieresistent.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma''s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.