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1、肺隱球菌?。≒C,pulmonarycryptococcosis)-從一個病例談起,病史介紹,患者,女性,47歲主述:因“反復咳嗽伴胸痛1月”入院(B院)現病史:患者于2010.9.5無明顯誘因出現咳嗽,少量白痰,伴右側胸痛,陣發(fā)性鈍痛,深吸氣時明顯,無放射痛,無發(fā)熱,無嘔吐、頭痛,某A院行胸部CT示“右下肺炎”,予以莫西沙星靜滴8天患者咳嗽、胸痛有所緩解,繼續(xù)口服莫西沙星6天,2010.9.27復查CT無吸收。于2010.10.12就診B院。既往:體健。否認性病冶游史。家中曾養(yǎng)寵物(鴿子、狗)。查體:T:37.9,淺表淋巴結不大,右下肺可及濕啰音。輔助檢查:血常規(guī)、肝腎功能、D-二聚體正常;

2、ESR:65mm/h,CRP:48mg/L;血氣分析正常;HIV(-)PPD試驗陰性;LA試驗、G試驗陰性(送至C院檢測),2010.9.6A院CT,2010.9.27A院CT,病史介紹,A院氣管鏡檢查:鏡下:未見明顯異常;右下肺灌洗和刷檢:未見惡性細胞、TB陰性。,2010.10.12B院CT引導下經皮肺穿刺,病理結果確診:肺隱球菌病上皮樣肉芽腫性病變;成堆隱球菌,幾點疑問,真菌病一般都是免疫功能低下的患者隱球菌如何侵襲到肺的LA試驗陰性肺隱球菌病CT表現和肺炎一樣,關于隱球菌,帶厚莢膜的酵母菌(乳膠凝集試驗)腐生菌:土壤、鴿糞、霉爛蔬菜、水果等感染部位:中樞神經系統(tǒng)、皮膚、肺感染途徑:吸入

3、呼吸道經血行播散到其它部位分型:17個種、18個變種(新生隱球菌及變種具有致病性),EpidemiologyI,Amulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2007Totally474casesofpulmonarymycosisfrom16centersin10cities.pulmonaryaspergillosis(180cases,379)pulmonarycandidiasis(162cases,342)pulmonarycryptococcosis(74cases,156)pne

4、umocystiscafiniipneumonia(23cases,4.8)pulmonarymucormycosis(10cases,21)中華結核和呼吸雜志,2011,34(2),EpidemiologyII,Meta-AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69.7%patientshadnounderlyingdiseasesThecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome(AIDS)diabetesmal

5、ignanttumor中國臨床醫(yī)學,2013,20(3):351-354,EpidemiologyIII,Retrospectiveinvestigationof151pulmonarycryptococcosisnon-HIVcasesbetween1977and201244.4%patientshadnoUDs.ThecommonUDswerediabetes(32.1%)hematologicdisease(22.6%)collagendisease(22.6%)JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfect

6、iousDiseases.JInfectChemother.2014Oct29,EpidemiologyIV,219patientswithprovencryptococcosisat20hospitalsinTaiwan,1997-2010210isolateswereC.neoformans(95.9%);9isolateswereC.gattii(4.1%).15.4%didnothaveanyunderlyingcondition.HIVinfectionwasthemostcommonunderlyingcondition(54/219,24.6%).AmongHIV-negativ

7、epatients,liverdiseases(HBVcarrierorcirrhosis)werecommon(30.2%)TaiwanInfectiousDiseasesStudyNetworkforCryptococcosis.PLoSOne.2013Apr17;8(4):e61921.,EpidemiologyV,Clinicalanalysisof76patientspathologicallydiagnosedwithpulmonarycryptococcosis.Of76patients(54malesand22females),41(53.95%)wereimmunocompe

8、tentand35outofthe41wereasymptomatic.ShanghaiPulmonaryHospital.EurRespirJ.2012Nov;40(5):1191-200.,summary,approximatelyhalfofpatientshadnounderlyingdiseasesasignificantnumberofpatientswereasymptomatic,pathogenesis,ThecapsuleisthemostimportantvirulencefactorofthefungalpathogenCryptococcusneoformans.Th

9、estructureProductionOfthecapsuleadhesionofCryptococcusneoformanstoepitheliallungcellsprotectiveimmuneresponsesagainstcryptococcosis,Thestructureofcapsule,Thisstructureconsistsofhighlyhydratedpolysaccharides,includingglucuronoxylomannan(GXM),葡萄糖醛酸木糖甘露聚糖galactoxylomannan(GalXM),半乳糖木糖甘露聚糖mannoproteins(

10、MPs),甘露糖蛋白,lessthan1%ofthecapsularweight,ProductionOfthecapsuleI,CA/CO2-sensingpathways.1RegulationofcapsulesynthesisbycarbondioxideJClinInvest,1985,76(2):508-5162ComparativetranscriptomeanalysisoftheCO2sensingpathwayviadifferentialexpressionofcarbonicanhydraseinCryptococcusneoformans.Genetics.2010A

11、ug;185(4):1207-19.,ProductionOfthecapsuleII,cryptococcalpolysaccharidesynthesisisincreasedbylimitationofferricironavailabilitytothecellandbydissolvedCO2,andthetwoeffectsareadditive.Regulationofcryptococcalcapsularpolysaccharidebyiron.JInfectDis.1993Jan;167(1):186-90.,ProductionOfthecapsuleIII,capsul

12、eenlargementinlivingC.neoformanscellswasinfluencedbyCa(2+)intheculturemedium.EukaryotCell.2007Aug;6(8):1400-10.,ProductionOfthecapsuleIV,basedontheaxiallengtheningofPSmolecules.CapsuleofCryptococcusneoformansgrowsbyenlargementofpolysaccharidemolecules.ProcNatlAcadSciUSA.2009Jan27;106(4):1228-33.PS,e

13、tccapsule?,alveolarmicroenvironment,adhesiontoepitheliallungcells,anadhesion-likeinteractionbetweenMPonthefungalsurfaceandthecomplementaryreceptormoleculesontheepithelialcells.FrontCellInfectMicrobiol.2014Aug19;4:106.,Phagocytosisdefence,SizeofCryptococcusneoformans.DynamicchangesinthemorphologyofCr

14、yptococcusneoformansduringmurinepulmonaryinfection.GXMagainstalveolarmacrophages(AM).Mechanismsofimmuneevasioninfungalpathogens.1Microbiology.2001Aug;147(Pt8):2355-65.2CurrOpinMicrobiol.2011Dec;14(6):668-75.,immuneresponse,SP-DincreasessusceptibilitytoC.neoformansinfectionbypromotingC.neoformans-dri

15、venpulmonaryIL-5andeosinophilinfiltration.Th1/Th2cytokineimbalance.BcellsprovideafirstlineofdefenseduringpulmonaryC.neoformansinfectioninmice1GenetMolRes.2013Nov18;12(4):5733-422InfectImmun.2014Feb;82(2):683-933JImmunol.2012Dec15;189(12):5820-30,Myopinioni,ChangealveolarmicroenvironmentAbrogationofI

16、L-4receptor-dependentalternativelyactivatedmacrophagesissufficienttoconferresistanceagainstpulmonarycryptococcosisdespiteanongoingT(h)2response.IntImmunol.2013Aug;25(8):459-70.,RadiologyI,Peripherallydistributedpulmonarynodules/massesweremostcommonlyseen.JapaneseSocietyofChemotherapyandTheJapaneseAs

17、sociationforInfectiousDiseases.JInfectChemother.2014Oct29Radiological(computedtomography)findingsshowedpredominantlyperipheralfindings(85.53%)includingnodularmasses(55.26%),pneumonicinfiltrates(23.68%)andmixedtype(21.05%).ShanghaiPulmonaryHospital.EurRespirJ.2012Nov;40(5):1191-200.71.8%patientswerec

18、haracterizedbynodularlumpshadows;23.8%byflake-likeinfiltratedshadows,and7.4%haddiffusemixedlesionsZhongshanHospital.ChineseJournalofClinicalMedicine,2013,RadiologyII,CTscanfindingsof29immunocompetentand43immunocompromisedpatientsPulmonarynodules/masses,eithersolitaryormultiple,werethemostcommonCTfin

19、ding,presentin65(90.3%)ofthe72patientsCavitationswithinnodules/massesweremorecommonlyseeninimmunocompromisedpatients,especiallyAIDSpatientsairbronchogramsweremorecommonlyseeninimmunocompetentpatientsPulmonarycryptococcosis:comparisonofCTfindingsinimmunocompetentandimmunocompromisedpatients.ActaRadiol.2014Apr22.,Myopinionii,Molecular/functionalradiology,currentsituationindiagnosis,43.42%(33/76)wereinitiallymisdiagnosed,oftenascancerbyfalse-positive(18)FDG-PETFailureofthecryptococcalserumanti

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