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免疫低下状态特异性感染的影像学研究
The Radiological Study of Specific Infections in Immunocompromised Host
【作者】 陈友三;
【作者基本信息】 第二军医大学 , 影像医学与核医学, 2008, 硕士
【摘要】 【背景】免疫力低下患者伴发的真菌或结核感染为临床所常见,隐球菌病是新生隐球菌感染所致的全身感染性疾病,好发于细胞免疫功能低下患者。肺隐球菌病在肺部真菌病发病率中占第2位,其致病机制不明,影像学表现不典型;隐球菌性脑膜脑炎是最常见的中枢系统真菌病,临床表现不典型,诊断不易;免疫损害患者的增多是近年来我国肺结核发病率增高的原因之一。本课题针对隐球菌病和肺结核两种特异性感染分别进行动物实验研究和临床病例回顾性研究。第一部分兔的新生隐球菌肺炎的动物实验研究—CT表现及病理对照【目的】构建新西兰大白兔的肺部新生隐球菌感染模型,并观察CT表现。【材料和方法】新西兰白兔24只,雌雄不限,体重1.5~2.5kg,随机分为实验组20只与对照组4只,实验第1~5天,实验组每日耳缘静脉注射阿糖胞苷440mg/m~2,6天后隔日注射维持低免疫状态。于实验第1、6天分别做血常规比较。第4日起应用万古霉素15mg/kg、头孢他定150mg/kg静脉注射,每日1次;庆大霉素5mg/kg静脉注射,隔日1次。实验菌株为新生隐球菌H99A标准株,制备新生隐球菌菌悬液浓度为1.25×10~8~2.5×10~8cfu/ml。第6日采用经皮气管穿刺法接种,将麻醉后的动物固定于生物安全柜操作台上,固定气管,试验组20只兔、对照组随机选取一只共21只兔气管内分别注入上述隐球菌菌液0.4ml-0.8ml。对照组剩余3只气管注入生理盐水0.4ml。接种后隔日行CT检察,观察并记录兔的自然死亡时间。第12天处死所有试验动物都。死亡后取肺组织病理学检查及真菌培养。【结果】:试验组20只新西兰大白兔中19只隐球菌培养阳性。组织病理检查可见肺泡壁增厚,间质细胞增生,炎细胞浸润(18只);肺泡大量渗出,间质充血渗出(12只);出血性坏死,坏死区机构不清(6只);还可见玻璃样变(1只);3例见肉芽肿形成,5例病灶间质、细支气管和肺泡腔内可见隐球菌。14只CT扫描有异常改变,其中实变型13只,多为多发,分布于左右肺各叶,以肺野外周分布常见;混合型1只,为右肺上中下叶的多发斑片及结节影。14只中有11只病变随时间而进展,其余3只的肺内病变没有明显进展或吸收。【结论】:采用阿糖胞苷抑制兔的免疫力,然后经皮气管穿刺接种隐球菌的方法可以成功建立隐球菌肺部感染模型;兔的肺部CT改变大多出现于接种后两天;14例兔的肺隐球菌病中13例CT表现以实变为主,病变多分布于肺野外周带,病变与支气管关系紧密。第二部分隐球菌性脑膜脑炎的CT和MRI表现【目的】:提高对新生隐球菌性脑膜脑炎的影像学认识,探讨CT和MRI在新生隐球菌性脑膜脑炎诊断中的应用。【材料和方法】:回顾性分析自2001—2007年间通过脑脊液墨汁染色或培养证实的新生隐球菌性脑膜脑炎21例,其中男性13例,女性8例,年龄范围8~53岁,主要症状有头痛、恶心、呕吐、发热。21例患者中1例为慢性粒细胞白血病患者,1例为系统性红斑狼疮患者,长期使用糖皮质激素,其余患者无明显导致免疫功能低下的基础疾病。21例患者中6例同时行头颅CT和MRI检查,6例仅行MRI检查,9例仅行CT检查。【结果】:21例病患20例为阳性,主要表现有软脑膜异常强化(13例),脑内斑片样损害灶(4例),基底节区、半卵圆区多发点片状异常信号或密度(5例),脑积水(5例)。【结论】:CM临床误诊率高,临床表现无特异性,确诊需依靠病原菌检查如脑脊液墨汁染色或隐球菌培养。CT及MRI在一定程度上能够反映其病理学特征,MRI显示颅内病变、观察病灶细节更敏感,软脑膜异常强化及伴发的神经核团的信号改变是隐脑的特征性征象。第三部分综合性医院对肺结核的CT诊断分析—免疫低下及糖尿病患者肺结核的CT特征【目的】:探讨综合医院肺结核病的CT表现,分析免疫低下及糖尿病患者肺结核的影像学特征。【材料和方法】:对我院2001年~2007年间出院诊断为肺结核的患者病历进行逐项分析,共202例资料完整,严格符合结核病诊断标准,并均行胸部CT检查。按照病变分布、形态特点对这202例肺结核病CT表现进行回顾性分析。从202例结核病中筛选出45例免疫异常组,包括免疫抑制剂使用者21例,糖尿病伴发肺结核24例,并与普通组进行对比研究,相关统计分析采用SPSS16.0软件。【结果】:一、202例综合医院肺结核包含Ⅲ型最多148例(73.3%),Ⅳ型肺结核次之49例(24.3%),Ⅱ型较少4例(2.0%),Ⅰ型1例(0.4);CT影像表现以肺内浸润或实变灶最为多见132例(65.3%),胸腔积液49例(24.3%),其中球形结核21例(10.3%),空洞出现17例(8.4%)。二、免疫抑制剂应用组并发肺结核时,表现血行播散相对较多(2例),肺内实变阴影大小疏密不一,散在分布,肺内播散多;糖尿病并发肺结核表现为程度较重的实变,分布广泛,容易伴有胸腔积液。两者合并为免疫低下及糖尿病患者肺结核组,共45例,CT表现以中重度浸润性实变灶为主,可以发生在非肺结核好发部位,与非免疫低下发生肺结核组对比,空洞征和支气管播散征更为多见,有统计学意义(P<0.05)。【结论】:CT检查在综合性医院住院患者结核病的诊断中具有重要的地位,更多见的空洞和支气管播散征是免疫低下及糖尿病患者肺结核的特征性的CT表现。
【Abstract】 【Background】The pulmonary infections in immunocompromised host is popular.Cryptococcosis is a systemic disease caused by Cryptococcus neoformans.In recent years,there has been a dramatic rise in the incidence of cryptococcosis,especially in immunocompromised patients,such as AIDS people,or those who received organ or marrow transplantation (BMT).The incidence of pulmonary cryptococcosis is next to pulmonary aspergillomycosis among all pulmonary mycosis.The patients with pulmonary tuberculosis admitted to general hospital are often under low immunity condition.The increase of immunocompromised host is an important reason for buildup of pulmonary tuberculosis these years in China.This study includes animal experimentation and retrospective clinical analyses,to respectively aim at the three specific infections: pulmonary mycosis,pulmonary tuberculosis,and cryptococcus meningoencephalitis.PartⅠThe Animal Experimentation on Pulmonary Cryptococcosis in Rabbits—CT Appearances and Pathology Control Study【Objective】To establish the animal model on pulmonary cryptococcosis in New Zealand Rabbits, and to analyze the manifestations of chest computed tomography.【Materials and Methods】Twenty four New Zealand rabbits,male or female,weight 1.5kg-2.5kg,were divided into experimental group and control group.Experimental group included 20 rabbits,and control group included 4 rabbits.To maintain low immune state,experimental group rabbits were treated with Cytarabine,440mg/m2,intravenous injection every day from first day and every other day from sixth day.Blood routine examination was perform on first and sixth day.In prevention from bacterium infections,experimental group and control group were all treated with Vancomycin,15mg/kg,ceftazidime,150mg/kg every day,and Gentamicin,5mg/kg every other day from forth day.The experimental Cryptococcus strain was Cryptococcus neoformans type strain H99A.After resuscitation and activation,the density of suspension was 1.25×108~2.5×108 cfu/ml.All experimental group rabbits and one control group rabbit were treated as percutaneous trache puncture innoculation.After paralysed,the rabbits were fixed on bacteria safety cabinet,held trache,injected with 0.4-0.8ml suspension,then reversed trendelenburg position.The remained rabbits were injected with normal sodium 0.4ml.Chest CT scans were performed every other day after inoculation.After rabbits died, pathology inspection and fungus cultivation were performed.【Results】:Cryptococcus neoformans for cultivation were positive in 19 rabbits of experimental group.Histopathology findings included alveolar wall thickening,interstitial cell hyperplasia,inflammatory cell infiltration(18),lung alveolus exudation,interstitial substance congestion(12),hemorrhagic necrosis(6),hyalinization(1),granuloma formation(5).And Cryptococcus spore were found in interstitial substance and lung alveolus in 5 rabbits.In HE stain,spore was small round vesiculose.In PAS stain cell wall became red.Lung lesions on thoracic CT scan were displayed in fourteen rabbits.Thirteen of them were the type of consolidation.Lesions were multiple and peripheral distributed on each lobe.The rest rabbit’s imaging was the mixed type.There were multiple nodules and consolidation on every lobe of right lung.The lesions aggravated in 11 of 14 rabbits when followed up.They became dense and scattered in larger area.The rest 3 rabbits kept invariably.【Conclusion】:Intravenous injection with Cytarabine and percutaneous trache puncture Cryptococcus neoformans spore suspension inoculation are feasible in establishment of the pulmonary cryptococcosis model.Abnormal CT findings often display the type of consolidation,and the lesion distributed in peripheral lung field has close relationship with bronchus,and often occur at the second day after inoculation,which supports that earlier radiological examination is advantageous for diagnosis.PartⅡCT and MRI Findings of Cryptococcus Meningoencephalitis【Objective】:To evaluate imaging appearances of cryptococcus meningoencephlitis,and to study the value of CT and MRI scan in the diagnosis of cryptococcus meningoencephalitis. 【Materials and Methods】:In retrospective study on medical record of all inpatients with CM from 2001 to 2007, 21 patients with complete data,including radiology examinations were collected.9 of them received CT,6 of them received MRI,6 cases received both CT and MRI.21cases included male 13 and female 8,from 8~53 ages.The main clinical manifestations included headache,nauseated,disgorging,and fever.2 cases had underlying diseases,as chronic granulocytic leukemia and systemic lupus erythematosus.【Results】:CT and MRI scans showed as follows:diffues cerebral edema(1 case),multiple patching lesions(4 cases),multiple small abnormally density or signal intensity in basal ganglia or oval area(5 cases),meningeal enhancement(13 cases) and hydrocephalu(5 cases).【Conclusion】:CT an d MRI can provide useful information which are the basis for localization of lesion,ascertaining the extent and type and development stage of lesion,give help to choosing of treatment planning an d estimating prognosis of CM.PartⅢCT Features of Pulmonary Tuberculosis in General Hospital—CT findings of pulmonary Tuberculosis in Immunocompromised and Diabetic Patients【Objective】:To analyze radiological characteristics of pulmonary tuberculosis in general hospital, and to analyze CT features of pulmonary tuberculosis in immunocompromised and diabetic patients,and to assess the value of CT in diagnosis of pulmonary tuberculosis in immmunocompromised host.【Materials and Methods】:In retrospective study on medical record of all inpatients with pulmonary tuberculosis from 2001 to 2007,202 patients with complete data,including chest CT scanning,and laboratory results were collected.All patients were examined with spiral CT.The imaging of 202 patients were analyzed according to distribution and morphous,et al.The radiological features of 45 immunocompromised and diabetic patients of 202 cases (prescribed immunosuppressant 21 cases and patients with diabetes 24 cases) were compared with those of immunocopetent patients.Statistical analysis applied software SPSS16.0.【Results】:202 cases with tuberculosis divided into four types.TypeⅢof 148 cases(73.3%),the most,typeⅣof 49 cases(24.3%),typeⅡof 4 cases and typeⅠof 1 case.CT appearances included consolidation,132(65.2%),pleural effusion,49(24.3%),Spheral Tuberculosis,21(10.3%),cavitation,17(8.4%).Hematogenous dissemination,multiply consolidation and diffused distribution were CT characteristic appearances in 21 patients prescribed immunosuppressant with pulmonary tuberculosis.CT findings of pulmonary tuberculosis in 24 patients with diabetes often included serious consolidation,general distribution,and more chances to combine pleural effusion.The CT appearances in 45 cases of immunocompromised and diabetic patient were serious consolidation,which might not just locate on predilection site. The characteristic appearances of pulmonary tuberculosis under immunocompromised condition were more chances of cavitates formation and bronchus dissemination(P<0.05).【Conclusion】:The CT scan is of great use in the diagnostic work-up of patients with pulmonary tuberculosis in general hospital and it is helpful in diagnosis and identification of pulmonary tuberculosis in immunocompromised and diabetic patients.The characteristic appearances of pulmonary tuberculosis in immunocompromised and diabetic host are cavitation and bronchus dissemination.
【Key words】 Cryptococcus neoformans; Pulmonary cryptococcosis; Animal model; Tomography, X-ray computed; Immunocompromised host; Cryptococcus meningoencephalitis; Meningitis; Cryptococcus neoformans; Magnetic resonance imaging; General hospital; Pulmonary tuberculosis; Tomography, X-ray Computed; Diabetes mellitus;