乙醛脱氢酶2基因多态性和饮酒习惯与肝癌的易感性

目的研究乙醛脱氢酶2(ALDH2)基因多态性和饮酒习惯与肝癌的易感性关系.方法在肝癌高发区江苏省泰兴市采用病例对照研究方法,病例为确诊的原发性肝癌(208例)新发病例,对照(208例)按1∶1配对,选取与病例同性别、年龄相差不超过2岁,与病例居住同村或同一街道的非肿瘤居民,调查了研究对象的饮酒习惯等因素,并采用聚合酶链反应-限制性片段长度多态性(PCR-PFLP)方法检测了他们的ALDH2基因型.结果 (1)肝癌组中的ALDH21*1、ALDH21*2、ALDH22*2基因型频率分别为 57.69%、30.77%、11.54% ,与对照组的64.25%、28.50%、7.25%相比,差异无显著性(χ2 =2.64, P=0.267).(2) 携带ALDH2变异基因型(ALDH21*2或ALDH22*2)的饮酒者与携带ALDH2野生(ALDH21*1)基因型的不饮者相比,若开始饮酒年龄＜25岁、每月饮酒量 >3000 g、饮酒年数 >23年和饮酒总量>3千克年时,前者患肝癌的危险性分别是后者的3.62 (95%CI=1.23～10.70)、3.51( 95%CI=1.38～8.95)、3.02 ( 95%CI=1.18～7.71)和3.30 (95%CI= 1.23～8.83)倍.(3)携带ALDH2变异基因型的饮酒者, 患肝癌的OR值与饮酒总量存在显著的剂量效应趋势(P值=0.044).(4)HBsAg阳性并携带ALDH2变异基因型且饮酒>3千克年者, 与HBsAg阴性并携带ALDH2(ALDH21*1)野生基因型且饮酒≤3千克年者相比,发生肝癌的危险性升高52.17倍(95%CI: 5.73～493.39).结论乙醛脱氢酶2基因多态性和大量饮酒与肝癌易感性间存在着明显的协同作用,提示携带ALDH2变异基因型的饮酒者减少酒精消耗量,将有助于降低其发生肝癌的危险性.     

饮酒增加广西乙醛脱氢酶2 基因变异基因型携带者发生肝癌的危险性

 目的 研究乙醛脱氢酶2（ALDH2）基因多态性与饮酒因素交互作用在广西原发性肝癌发生中的作用。方法 对广西壮族自治区300例肝癌患者和292例正常对照人群进行流行病学调查研究，并用PCR-RFLP方法检测ALDH2基因型。结果 肝癌组和对照组中ALDH2变异基因型携带者分别占50．33％和47．95％（P=0．561）。肝癌人群ALDH2基因型不存在区域和民族差异（P〉0．05）。饮酒频度每周≥3次的ALDH₂²携带者发生肝癌的危险性是饮酒频度每周〈3次的ALDH2＊1携带者的3、34倍（95％CI1．75～6．41）。HBsAg阳性者发生肝癌的危险性明显高于HbsAg阴性者（P〈0．001）。结论 ALDH2基因型不构成壮汉族间肝癌发病差异的基础，频繁饮酒可能是ALDH2基因变异基因型携带者发生肝癌的危险因素。     

醇醛脱氢酶基因多态和饮酒习惯与肝癌易感性

目的研究乙醇脱氢酶2（ADH2）和乙醛脱氢酶2（ALDH2）基因多态及饮酒习惯与肝癌的易感性。方法对208例原发性肝癌和208例对照调查饮酒习惯,采用RCT-RFLR方法检测ADH2和ALDH2基因型。结果1）病例与对照ADH2和ALDH2基因型分布频率差异均无统计学意义。2）携带AL-DH2^1＊2或ALDH2^2＊2基因型且饮酒总量〉3kg年者,发生肝癌危险性是携带AL-DH211基因型不饮酒者的3.30倍（95%CI=1.24～8.83）;而携带ADH2^1＊2或ADH2^2＊2基因型者且饮酒总量〉3kg年与携带ADH211基因型不饮酒者相比,患肝癌危险性无显著增加。3）携带AL-DH2^1＊2或ALDH2^2＊2同时携带ADH2^1＊2或ADH2^2＊2基因型且饮酒总量〉3kg年者,与携带ALDH2^1＊1同时携带ADH2^1＊1基因型且饮酒总量≤3kg年者相比,患肝癌OR值虽有增加但未达显著性（OR=4.26,95%CI=0.63～29.08）。4）HBsAg阳性并携带ALDH2^1＊2或ALDH2^2＊2基因型且饮酒〉3kg年者,与HBsAg阴性并携带ALDH2^1＊1基因型且饮酒≤3kg年者相比,患肝癌危险升高49.71倍（95%CI=5.51～448.96）。结论大量饮酒和肝癌的关联与ALDH2基因有关,而与ADH2基因无关。     

CYP2E1基因多态性与肝癌易感性的关系

目的 :研究细胞色素P45 0 2E1(CYP2E1)基因多态性与肝癌易感性的关系。方法 :在肝癌高发区泰兴市进行病例对照研究 ,调查研究对象的饮酒习惯 ,以PCR RFLP方法分析CYP2E1基因型。结果 :肝癌病例组与对照组中CYP2E1变异基因型 (C1/C2 C2 /C2 )的分布频率分别为 41 0 6%和 3 7 0 2 % ,两者差异无统计学意义 ;从饮酒习惯等方面分析 ,携带CYP2E1变异基因型的饮酒者与携带野生基因型的不饮酒者间患肝癌危险性差异无统计学意义。结论 :CYP2E1基因多态性与泰兴市肝癌的发生无关     

江苏汉族人乙醛脱氢酶2基因型分布及其与饮酒习惯的关系

目的:研究乙醛脱氢酶2(ALDH2)基因多态性在江苏汉族人中的分布频率及其与饮酒习惯的关系.方法:在江苏泰兴市选择273例正常人进行流行病学调查研究,并应用聚合酶链反应-限制性片段长度的多态性(PCR-RFLP)方法检测研究对象的ALDH2基因型.结果:ALDH2变异型等位基因在中国人中的分布频率为47.25 %.ALDH2变异型等位基因携带者与ALDH2正常等位基因携带者之间饮酒频度和每次饮酒量间差异均无显著性.结论:中国人ALDH2酶的活性普遍缺乏.人们的饮酒习惯与ALDH2基因型分布无明显的相关关系.     

乙醛脱氢酶2基因多态性和饮酒习惯与肝癌、胃癌、食管癌的易感性

目的：研究乙醛脱氢酶2（ALDH2）基因多态性和饮酒习惯与肝癌、胃癌和食管癌的易感性。方法：88例肝癌以性别、年龄和居住地与对照按1：1配对；104例胃癌和98例食管癌选择同一组（235例）非肿瘤居民为对照，用PCR－RFLP方法检测研究对象的ALDH2基因型。结果：肝癌、胃癌、食管癌病例与对照组中ALDH2变异基因型携带者分别占36．36％和35．23％、47．12％和45．36％、32．65％和45．36％，差异无显著性。在携带ALDH2变异基因型的饮酒人中，每月饮酒总量＞3kg者发生肝癌的危险性是≤3kg者的7．2倍，并存在显著的剂量效应关系。在携带ALDH2谷氨酸纯合型的男性中，饮酒者发生癌的危险性是不饮酒者的2．69倍。结论：该研究揭示了携带ALDH2变异基因型者大量饮酒将显著增加患肝癌的危险性。     

GSTM1、GSTT1基因多态性和饮酒习惯与原发性肝癌发生的危险性

目的　研究GSTM 1和GSTT 1基因的多态性和饮酒习惯与原发性肝癌发生的危险性。方法　在肝癌高发区江苏省泰兴市进行了以人群为基础的病例对照研究 ,并应用多重PCR法检测了 2 0 7例原发性肝癌及其 1∶1配对的正常对照的GSTM 1和GSTT 1基因型。结果　GSTM 1空白基因型的频率 ,病例组为 5 8.94% ,对照组为 5 7.0 0 % ;GSTT 1空白基因型的频率 ,病例组和对照组分别为 5 2 .17%和 46.86% ,2组间无显著性差异。但GSTT 1的空白基因型与非空白基因型相比 ,当其长期饮用高度白酒达2 3年以上或月饮酒量大于 3 0 0 0 g时 ,患肝癌的危险性显著增高 (OR =2 .5 6,95 %CI为 1.0 8～ 6.0 5或OR =3 .48,95 %CI为 3 1.47～ 8.2 2 ) ;此外分析饮酒总量 (kg·年 )也得到同样的结果 (OR =3 .71,95 %为 1.5 1～ 9.12 )。结论　携带GSTT 1空白基因型且有长期大量饮酒习惯者 ,其患肝癌的危险性显著增高     

乙醇脱氢酶2和乙醛脱氢酶2基因多态性及饮酒习惯与直肠癌易感性的研究

目的:研究乙醇脱氢酶2(ADH2)、乙醛脱氢酶2(ALDH2)基因多态性与直肠癌易感性的关系。方法:采用病例-对照研究方法,以PCR-DH-PLC检测研究对象的ADH2/ALDH2基因型,比较不同的基因型及生活习惯与直肠癌的关系。结果:1)与不饮酒者相比较,饮酒者患直肠癌的危险性显著增高(OR=2.20,95%CI:1.47～3.28,P=0.000);2)多因素分析结果未发现ADH2、ALDH2各基因型与直肠癌的危险性有关。3)对ADH2、ALDH2基因多态相互作用的分层分析发现,同时携带ADH2A/A和ALDH2G/G基因型者,发生直肠癌的危险性显著增高(性别、年龄和吸烟调整OR=1.82,95%CI:1.07～3.09)。4)在饮酒者中,ADH2A/A、A/G G/G基因型者患直肠癌的调整OR分别为2.56(95%CI:1.38～4.73)和2.10(95%CI:1.15～3.84);ALDH2G/G基因型者发生直肠癌的调整OR为1.82(95%CI:1.07～3.09)。结论:饮酒是直肠癌的危险因素;ADH2A/A与ALDH2G/G基因型在增加直肠癌易感性上有协同作用;ALDH2G/A A/A基因型可减弱饮酒患直肠癌的危险性。     

乙醛脱氢酶2基因多态性与食管癌易感性的关系

目的 研究乙醛脱氢酶2（ALDH2）基因多态性和饮酒习惯与食管癌易感性间的相互关系。方法 在江苏泰兴市选择食管癌新发病例98例和正常对照273例进行流行病学调查研究。并用PCR－RFLP方法检测研究对象的ALDH2基因型。应用EpiInfo统计软件包,分析了男性食管癌组和男性对照组间不同饮酒习惯,ALDH2基因多态性与食管癌易感性的关系。结果 食管癌组和对照组ALDH2变异基因型携带者分别占43．88％和47．25％,两者间的差异无显著性。饮酒频度每周＜3次的男性ALDH2基因型携带者与每周≥3次男性ALDH2^1*2/ALDH2^2基因型携带者间,经统计学分析病例组与对照组间存在显著性的差异。结论 饮酒频度可能影响ALDH2基因多态性与食管癌易感性的关系。     

乙醇和乙醛脱氢酶基因多态与男性结直肠癌的易感性

目的研究乙醇脱氢酶2(ADH2)和乙醛脱氢酶2(ALDH2)基因多态及饮酒习惯与男性结直肠癌易感性的关系。方法在江苏省进行了一项病例-对照研究(结直肠癌患者190例,人群对照222名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用聚合酶链反应(PCR)和变性高效液相色谱法(DHPLC)检测研究对象的ADH2Arg47His(G-A)和ALDH2Glu487Lys(G-A)的基因型。结果①ADH2A/A和ALDH2G/G基因型显著增加结直肠癌的易感性。在调整了年龄和吸烟状况后,ADH2A/A基因型者与携带G等位基因者相比,发生结直肠癌的危险性上升到1.61(95%CI:1.09~2.38);ALDH2G/G基因型者与携带A等位基因者相比,发生结直肠癌的危险性上升到1.79(95%CI:1.19~2.69)。②与ADH2G和ALDH2A等位基因携带者相比,同时携带ADH2A/A和ALDH2G/G基因型者发生结直肠癌的OR值上升到3.05(95%CI:1.67~5.57);与不饮酒的ADH2G等位基因携带者相比,拥有ADH2A/A基因型的饮酒者的OR值上升到3.44(95%CI:1.84~6.42);与不饮酒的ALDH2A等位基因携带者相比,拥有AL-DH2G/G基因型的饮酒者的OR值上升到2.70(95%CI:1.57~4.66)。结论ADH2和ALDH2基因多态性与男性结直肠癌的易感性相关。ADH2,ALDH2基因多态之间以及基因多态与饮酒习惯之间,在结直肠癌发生中存在显著的协同作用。     

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.     

裘法祖教授生平

Prof.Fazu Qiu,member of the Chinese Communist Party,surgery professor of Tongji Hospital,departed in Tongji Hospital,Wuhan,China,at fourteen to nine a.m,June 14,2008,after a disease.He turns 94 this year.He was the senior academician of the Academia Sinica,the illustrious medical scientist of China,and the Honorary Director of Tongji Medical College,as well as Huazhong University of Science & Technology.     

Dermatomycosis in Dogs

During the routine examination of dogs for cutaneous lesions, 205 dogs were screened for fungi other than dermatophytes. Twenty-two dogs (10.8%) revealed the presence of non-dermatophytic fungi suspicious for representing the etiologic agents of the skin lesions. The fungi isolated were Alternaria sp. (2.9%), Penicillium sp. (2.4%), Aspergillus fumigatus (2.0%), Mucor sp. (1.5%), Cladosporium sp. (1.5%) and Fusarium sp. (0.5%). No dermatophyte was isolated in association with these fungi. The incidence of these infections was found to be greater in warm and humid climate.     

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.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

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.