结核性脑膜炎的早期诊断及其发病机制的探讨
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摘要
目的:结核性脑膜炎(Tuberculous meningitis,TBM),简称结脑,是由结核分枝杆菌引起的慢性中枢神经系统感染性疾病。其致死率与致残率高,预后的关键在于早期诊断及时治疗。但是,结脑的早期诊断一直困扰着临床医生,文献报道,早期(一周内)诊断率仅10%[1]。寻找早期快速的诊断方法,成为目前结脑研究中亟待解决的问题。本研究在脑脊液常规生化基础上进行脑脊液细胞学检查、脑脊液单核细胞内结核抗原检测及脑脊液IFN-γ的测定,探讨三种方法在结脑早期诊断中的临床价值,并进一步探讨结脑的发病机制。
方法:将2004年10月～2007年9月住院病人226例按相应的诊断标准分为两组:1.结脑组(病例组):共102例,其中单纯结脑75例,有明确结核病接触史5例,合并有肺结核者16例,结核性腹膜炎者2例,结核性胸膜炎者3例,结核性肾盂肾炎者1例。2.其它疾病组(对照组):共124例,其中化脓性脑膜炎18例,病毒性脑炎46例,隐球菌脑膜炎11例,脑囊虫病9例,血液病8例,吉兰-巴雷综合征6例,脊髓炎3例,多发性硬化4例,蛛网膜下腔出血5例,脑梗塞5例,脑膜癌病5例,脑静脉窦血栓4例。
入院后12～48小时对所有病例进行腰穿送检脑脊液常规、生化、细胞学系列检查(MGG染色、墨汁染色、阿利新兰染色和色氨酸染色)、免疫组织化学法检测脑脊液单核细胞内结核菌素抗原、部分病例用双抗体夹心ABC-ELISA法测定脑脊液IFN-γ含量。
结果:
1脑脊液常规及生化检查结果:病例组异常102例,异常率达100%;对照组异常105例,异常率达84.7%。
2脑脊液细胞学检查结果:病例组脑脊液细胞学主要呈混合细胞学反应,共74例(72.5%);对照组脑脊液细胞学缺乏特异性改变,呈混合细胞学反应33例(26.6%)。若以混合细胞学反应作为诊断结脑的标准,敏感性为72.5%,特异性为73.4%;动态观察结脑组脑脊液细胞学变化发现在抗痨治疗前呈以嗜中性粒细胞为主的混合细胞学反应,在抗痨治疗2~3周后嗜中性粒细胞逐渐减少,免疫活性细胞逐渐增多,但混合细胞学反应仍持续时间较长。
3脑脊液单核细胞内结核菌素抗原检测:诊断敏感性为83.3%,特异性为93.5%。比较病例组发病≤14天、15～30天、>30天抗原检测阳性率,差别无统计学意义,但三组阳性率分别为87.8%、88.8%、68%,提示结核抗原的检测更适用于早期诊断。
4脑脊液IFN-γ含量测定:病例组脑脊液IFN-γ含量的平均值为223.4±141.2pg/ml,对照组脑脊液IFN-γ含量的平均值为31.40±21.5 pg/ml,经统计学处理,两组在IFN-γ含量上差别有统计学意义;以100 pg/ml为诊断结核性脑膜炎的临界值,敏感性为71.4%,特异性为96.9%。以发病≤1个月测定脑脊液IFN-γ的含量>100 pg/ml为标准,则敏感性为92.6%。比较发病≤14天、15～30天、>30天脑脊液IFN-γ的含量,差别有统计学意义。动态观察发现随病情好转,病例组IFN-γ含量逐渐降低,病情恶化,IFN-γ含量升高不明显;对照组在治疗前后变化不大。
5比较脑脊液细胞学、结核菌素抗原检测及脑脊液IFN-γ含量对结脑的诊断价值,经过统计学处理发现三者差异无统计学意义,将三者联合检测,敏感性达96.3%。
结论:
1脑脊液单核细胞内结核抗原检测敏感性最高,IFN-γ含量测定特异性最高;
2发病早期检测(小于1个月)脑脊液IFN-γ含量敏感性、特异性最高;
3将脑脊液细胞学、脑脊液单核细胞内结核菌素抗原检测和IFN-γ含量测定联合会大大提高诊断的敏感性。
Objective:Tuberculous meningitis(TBM),a chronic central nervous system infection disease caused by Mycobacterium tuberculosis, has high rates of case fatality and mutilation. The key point of prognostic resides in the early diagnosis and antituberculosis treatment promptly. Early diagnosis of tuberculous meningitis has been troubled clinicians. It reported the diagnosis rate was only 10% in early stage (within one week). Seeking the early method which is rapid is called the problem urgent to be solved at present. In this study, upon the foundation of CSF routine examination, CSF Cytology、mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal are detected.To evaluate the clinical value of the methods in the early diagnosis and the pathogenesis of tuberculous meningitis.
Methods:CSF samples were collected from 206 patients with definite diagnosis. All these patients were from the Second Hospital of Hebei Medical University during the period of 2004 October~2007 September. These patients were divided into two groups.⑴TBM group(Case group): Totally 102 patients. Among them 75 patients were pure TBM,5 patients have a history of exposure to tuberculosis,16 patients combined Pulmonary tuberculosis,2 patients combined Tuberculous peritonitis,3 patients combined Tuberculous pleurisy and 1 patient combined TB pyelonephritis. (2)Other diseases(Control group): Of the 124 patients,18 had pyogenic meningitis,46 had meningoencephalitis of viral,11 had cryptococcal meningitis, 9 had brain cysticercosis,8 had blood disease,6 had Guillain-Barre syndrome (GBS),3 had myelitis,4 had Multiple Sclerosis,5 had subarachnoid hemorrhage(SAH),5 had cerebral thrombosis,5 had meningeal carcinomatosis and 4 had Cerebral venous sinus thrombosis.
CSF was collected by lumbar puncture in all patients, and analyzed within 12 hours~48 hours, biochemical, cytology (MGG dye, Indian ink and aricine blue staining), demonstration of mycobacterial antigen in monocytes (macrophages) are carried out at the same time.Some of the CSF was detected by ABC-ELISA method in order to evaluate the value of IFN-gamma.
Results:
1 CSF routine test: The case group was 102 of abnormal, and the rate of abnormality was 100%; the control group was 105 of abnormal and the rate of abnormality was 84.7%.
2 CSF Cytology: A total of 112 cases in TBM group show a mixed-cell response in CSF(72.5%);but Control group, lack of specificity of change,33 cases show a mixed -cell response in CSF(26.6%).If take a mixed-cell response in CSF as the diagnostic criteria, the sensitivity was 72.5%, and specificity was 73.4%. At the dynamic observation, patients in TBM group show polymorphonuclear dominant mixed-cell response before anti-tuberculosis treatment, while neutrophil gradually reduced after 2~3weeks treatment. The monocyte and lymphoid cells increased at the same time,but a mixed-cell response would last a long time .
3 The demostration of antigens in monocytes: The sensitivity was 83.3%, and specificity was 93.5%.Compared the positive rate of≤14 days(87.8%)、15～30days(88.8%)、>30days(68%), it didn’t have significant difference.So the demostration of antigens in monocytes is suitable for the early diagnosis.
4 The levels of IFN-gamma:Compare the IFN-γlevels in cerebrospinal fluid in case group (223.4±141.2 pg/ml) and control group(31.40±21.5 pg/ml),there was a statistical significance. Take 100 pg/ml as the diagnostic criteria, the sensitivity and the specificity was 71.4% and 96.9%. Compare the IFN-γlevels of≤14 days、15～30days、>30days, there was a statistical significance. At the dynamic observation, the IFN-γlevel gradually delined with the condition improves in case group, but the levels didn’t increase with the aggravation of disease.And the control group didn’t change too much around the treatment.
5 Compare the clinical value of CSF Cytology、mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal, it didn’t have significant difference. If joint the three methods the sensitivity may reach 96.3%
Conclusions:
1 The sensitivity of antigens demonstration is the highest,while the specificity of determination of IFN-gamma is the highdest.
2 Determination of IFN-gamma has the highest sensitivity and specificity at the early stage of disease(less than a month).
3 Joint the three method will be helpful to elevate the diagnosis rate.
方法:将2004年10月～2007年9月住院病人226例按相应的诊断标准分为两组:1.结脑组(病例组):共102例,其中单纯结脑75例,有明确结核病接触史5例,合并有肺结核者16例,结核性腹膜炎者2例,结核性胸膜炎者3例,结核性肾盂肾炎者1例。2.其它疾病组(对照组):共124例,其中化脓性脑膜炎18例,病毒性脑炎46例,隐球菌脑膜炎11例,脑囊虫病9例,血液病8例,吉兰-巴雷综合征6例,脊髓炎3例,多发性硬化4例,蛛网膜下腔出血5例,脑梗塞5例,脑膜癌病5例,脑静脉窦血栓4例。
入院后12～48小时对所有病例进行腰穿送检脑脊液常规、生化、细胞学系列检查(MGG染色、墨汁染色、阿利新兰染色和色氨酸染色)、免疫组织化学法检测脑脊液单核细胞内结核菌素抗原、部分病例用双抗体夹心ABC-ELISA法测定脑脊液IFN-γ含量。
结果:
1脑脊液常规及生化检查结果:病例组异常102例,异常率达100%;对照组异常105例,异常率达84.7%。
2脑脊液细胞学检查结果:病例组脑脊液细胞学主要呈混合细胞学反应,共74例(72.5%);对照组脑脊液细胞学缺乏特异性改变,呈混合细胞学反应33例(26.6%)。若以混合细胞学反应作为诊断结脑的标准,敏感性为72.5%,特异性为73.4%;动态观察结脑组脑脊液细胞学变化发现在抗痨治疗前呈以嗜中性粒细胞为主的混合细胞学反应,在抗痨治疗2~3周后嗜中性粒细胞逐渐减少,免疫活性细胞逐渐增多,但混合细胞学反应仍持续时间较长。
3脑脊液单核细胞内结核菌素抗原检测:诊断敏感性为83.3%,特异性为93.5%。比较病例组发病≤14天、15～30天、>30天抗原检测阳性率,差别无统计学意义,但三组阳性率分别为87.8%、88.8%、68%,提示结核抗原的检测更适用于早期诊断。
4脑脊液IFN-γ含量测定:病例组脑脊液IFN-γ含量的平均值为223.4±141.2pg/ml,对照组脑脊液IFN-γ含量的平均值为31.40±21.5 pg/ml,经统计学处理,两组在IFN-γ含量上差别有统计学意义;以100 pg/ml为诊断结核性脑膜炎的临界值,敏感性为71.4%,特异性为96.9%。以发病≤1个月测定脑脊液IFN-γ的含量>100 pg/ml为标准,则敏感性为92.6%。比较发病≤14天、15～30天、>30天脑脊液IFN-γ的含量,差别有统计学意义。动态观察发现随病情好转,病例组IFN-γ含量逐渐降低,病情恶化,IFN-γ含量升高不明显;对照组在治疗前后变化不大。
5比较脑脊液细胞学、结核菌素抗原检测及脑脊液IFN-γ含量对结脑的诊断价值,经过统计学处理发现三者差异无统计学意义,将三者联合检测,敏感性达96.3%。
结论:
1脑脊液单核细胞内结核抗原检测敏感性最高,IFN-γ含量测定特异性最高;
2发病早期检测(小于1个月)脑脊液IFN-γ含量敏感性、特异性最高;
3将脑脊液细胞学、脑脊液单核细胞内结核菌素抗原检测和IFN-γ含量测定联合会大大提高诊断的敏感性。
Objective:Tuberculous meningitis(TBM),a chronic central nervous system infection disease caused by Mycobacterium tuberculosis, has high rates of case fatality and mutilation. The key point of prognostic resides in the early diagnosis and antituberculosis treatment promptly. Early diagnosis of tuberculous meningitis has been troubled clinicians. It reported the diagnosis rate was only 10% in early stage (within one week). Seeking the early method which is rapid is called the problem urgent to be solved at present. In this study, upon the foundation of CSF routine examination, CSF Cytology、mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal are detected.To evaluate the clinical value of the methods in the early diagnosis and the pathogenesis of tuberculous meningitis.
Methods:CSF samples were collected from 206 patients with definite diagnosis. All these patients were from the Second Hospital of Hebei Medical University during the period of 2004 October~2007 September. These patients were divided into two groups.⑴TBM group(Case group): Totally 102 patients. Among them 75 patients were pure TBM,5 patients have a history of exposure to tuberculosis,16 patients combined Pulmonary tuberculosis,2 patients combined Tuberculous peritonitis,3 patients combined Tuberculous pleurisy and 1 patient combined TB pyelonephritis. (2)Other diseases(Control group): Of the 124 patients,18 had pyogenic meningitis,46 had meningoencephalitis of viral,11 had cryptococcal meningitis, 9 had brain cysticercosis,8 had blood disease,6 had Guillain-Barre syndrome (GBS),3 had myelitis,4 had Multiple Sclerosis,5 had subarachnoid hemorrhage(SAH),5 had cerebral thrombosis,5 had meningeal carcinomatosis and 4 had Cerebral venous sinus thrombosis.
CSF was collected by lumbar puncture in all patients, and analyzed within 12 hours~48 hours, biochemical, cytology (MGG dye, Indian ink and aricine blue staining), demonstration of mycobacterial antigen in monocytes (macrophages) are carried out at the same time.Some of the CSF was detected by ABC-ELISA method in order to evaluate the value of IFN-gamma.
Results:
1 CSF routine test: The case group was 102 of abnormal, and the rate of abnormality was 100%; the control group was 105 of abnormal and the rate of abnormality was 84.7%.
2 CSF Cytology: A total of 112 cases in TBM group show a mixed-cell response in CSF(72.5%);but Control group, lack of specificity of change,33 cases show a mixed -cell response in CSF(26.6%).If take a mixed-cell response in CSF as the diagnostic criteria, the sensitivity was 72.5%, and specificity was 73.4%. At the dynamic observation, patients in TBM group show polymorphonuclear dominant mixed-cell response before anti-tuberculosis treatment, while neutrophil gradually reduced after 2~3weeks treatment. The monocyte and lymphoid cells increased at the same time,but a mixed-cell response would last a long time .
3 The demostration of antigens in monocytes: The sensitivity was 83.3%, and specificity was 93.5%.Compared the positive rate of≤14 days(87.8%)、15～30days(88.8%)、>30days(68%), it didn’t have significant difference.So the demostration of antigens in monocytes is suitable for the early diagnosis.
4 The levels of IFN-gamma:Compare the IFN-γlevels in cerebrospinal fluid in case group (223.4±141.2 pg/ml) and control group(31.40±21.5 pg/ml),there was a statistical significance. Take 100 pg/ml as the diagnostic criteria, the sensitivity and the specificity was 71.4% and 96.9%. Compare the IFN-γlevels of≤14 days、15～30days、>30days, there was a statistical significance. At the dynamic observation, the IFN-γlevel gradually delined with the condition improves in case group, but the levels didn’t increase with the aggravation of disease.And the control group didn’t change too much around the treatment.
5 Compare the clinical value of CSF Cytology、mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal, it didn’t have significant difference. If joint the three methods the sensitivity may reach 96.3%
Conclusions:
1 The sensitivity of antigens demonstration is the highest,while the specificity of determination of IFN-gamma is the highdest.
2 Determination of IFN-gamma has the highest sensitivity and specificity at the early stage of disease(less than a month).
3 Joint the three method will be helpful to elevate the diagnosis rate.
引文
1 武俊平,吴琦.结核性脑膜炎诊断与治疗研究进展.国外医学呼吸系统分册,2005,25(1):49-51
2 Ahuja GK,Mohan KK,Kprasad,et al.Diagnostic criteria for tuberculous meningitis and their validation[J].Tuber Lung Dis,1994,75:149-152
3 王维治,罗祖明主编.神经病学[M].第四版.北京:人民卫生出版社, 2002:164-190
4 巫顺秀,陈显光,李森美,等.脑脊液 γ-干扰素检测对结核性脑膜炎诊断价值的探讨.华中医学杂志,2006,30(1):41-4
5 全国结核病流行病学抽样调查技术指导组.第四次全国结核 病 流 行 病 学 抽 样 调 查 报 告 . 中 华 结 核 和 呼 吸 杂志,2002,25(1):3-7
6 World Health Organization.Antrtuberculosis drug resistance in the world.Report No.2.Prevalence and trends,Geneva:WHO,2000
7 World Health Organization.Global tuberculosis control.WHO report 2000.Geneva:WHO,2000
8 何俊瑛,孔繁元,郭力.临床脑脊液细胞学诊断.石家庄:河北科学技术出版社,2007
9 王宁山,侯熙德.结核性脑膜炎脑脊液实验室指标的检测分析.中华结核和呼吸杂志,1994,1:54
10 范超平,陈琼,王蕾.结核性脑膜炎 30 例脑脊液细胞学动 分析.中国实用神经疾病杂志,2007,2(10)
11 OEHMICHEN M,DOMASCH D,WIETHOLTER H.Origin,proliferation and fate of cerebrospinal cells[J].J Neuro,1982,227(3):145-150
12 THWAITES G,CHAU T T,MAI N T,et al.Tuberculous meningitis[J].J Neurol Neurosurg Psychiatry,2000,68(3):289-299
13 Mathai A, Radhakrishnan VV, Sarada C,et al. Detection of heat stable mycobacterial antigen in cerebrospinal fluid by Dot-Immunobinding assay[J].Neurol India, 2003,51:52-54
14 Bera Swati, Shende Niraj,Kumar Satish,etal. Detection of antigen and antibody in childhood tuberculous meningitis. The Indian Journal of Pediatrics. 2006 Aug;73(8):675-679
15 Samuel AM. A sensitive and specific method for diagnosisof tubercular meningitis[J].Indian J Med Res ,1983 ;77 :752～753
16 Cambiaso CL.J Immun Meth.1990;129:9
17 Alamelu Raja Immunology of tuberculosis[J].Indian Med Res,2006,120:213-232
18 何俊瑛,黄庆生,卜晖.脑脊液单核细胞内结核抗原检测对结 脑 早 期 诊 断 的 意 义 . 脑 与 神 经 疾 病 杂志,2005,13(3):204-205
19 Douglas AD, Pieter JML, Ronald A.Greenfield Invasion of the Central Nervous System by Intracellular Bacteria.Clin Microbiol Rev,2004,17(2): 323- 347
20 Sumi MG, Mathai A, Reuben S,et al. Immunocytochemical Method for Early Laboratory Diagnosis of Tuberculous Meningitis[J].Clin Diagn Lab Immunol,2002,9(2):344-347
21 Mazurek GH,LoBue PA,Daley CL,et al.Comparison of a whole-blood interferon assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection.JAMA,2001,286:1740-1747
22 马志明,肖芃,唐林国,等. γ-干扰素基因多态性与肺结核易感性的研究.中华结核和呼吸杂志.2007,30(10):777-778
23 Aoe K,Hiraki A, Murakami T, et al Diagnostic significance of interferon-γin tuberculous pleual effusion [J]. Chest,2003,123(3):740-744
24 冯经华,尹凤鸣,严振球.目前结核分枝杆菌感染中重要免疫 细 胞 和 细 胞 因 子 作 用 的 研 究 进 展 . 临 床 军 医 杂志,2007(35)4:291-295
1 Feng CG, Britton WJ, Palendira U, et al. Up-regulation of VCAM-1 and differential expansion of β integrin-expressing T lymphocytes are associated with immunity to pulmonary Mycobacteriym tuberculosis infection[J]. J Immunol, 2000, 164(9):4853-4896
2 刘举祥,王翠兰,孙颖.中枢神经系统感染患者血清中sICAM-1 和TNF-α 的水平及临床意义[J].神经疾病与精神卫生,2005,5(2):99-101
3 梁艳,董德琼,杨渝浩.可溶性血管细胞黏附分子 1 在肺结核发病机制中的作用和临床意义[J].中华结核和呼吸杂志,2006,29(4):266-269
4 张庆华,邵祥稳.结核性脑膜炎患者脑脊液中转铁蛋白测定及临床意义[J].现代医药卫生,2004,20(9):772-773
5 王秀霞,檀国军,罗克娴.检测脑膜炎患儿脑脊液肿瘤坏死因子-α 的临床意义[J].临床荟萃,2002,17(6):347
6 Saunders BM, Briscoe H, Britton WJ, et al. T cell-derived tumour necrosis factor is essential, but not sufficient, for protection against Mycobacterium tuberculosis infection[J].Clin Exp Immurol,2004, 137(2):279-287
7 柏雪莲,傅斌,刘克义.结核分枝杆菌感染中一些重要免疫细 胞 和 细 胞 因 子 作 用 的 进 展 研 究 [J]. 中 国 防 痨 杂志,2006,28(3):178-181
8 宋方禹,陈翠玲.中枢神经系统感染脑脊液研究进展[J].脑与神经疾病杂志,2005,13(2):157-159
9 刘怀深,吕喜英,兰桂云.结核性脑膜炎患者血清 sIL-2R 的检测分析[J].临床荟萃,2002,17(22):1343-1344
10 Lee KY, Kim EH, Yang WS, etal. Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis[J].J Neurol Sci, 2004, 220(1-2):73-78
11 冯勋刚,牛瑞云,李宪章.动态测定结核性脑膜炎脑脊液S100B 蛋 白 的 临 床 意 义 [J]. 济 宁 医 学 院 学报,2003,26(4):30-31
12 林存智,朱新红,华裕忠,等.干扰素-γ 含量和腺苷脱氨酶活性对结核性和肿瘤性胸腔积液的鉴别诊断价值[J].中国全科医学,2007,6(10)
13 罗英琳.多指标检测对结核性和癌性胸腔积液的诊断价值[J].广西医学,2005,8(27):1170-1171
14 Poyraz B, Kaya A, et al. Diagnostic significance of gammar interferon in tuberculous pleurisy [J]. Tuberk Toraks, 2004,52(3):211-217
15 Aoe K,Hiraki A, Murakami T, et al Diagnostic significance of interferon-γin tuberculous pleual effusion [J]. Chest,2003,123(3):740-744
16 Feng CG, Jankovic D, Kullberg M, et al. Maintenance of Pulmonary Th1 Effector Function in Chronic Tuberculosis Requires Persistent IL-12 Production [J]. J Immurol.,2005,174(7):4185-4192
17 熊力凡,金大鸣.脑脊液生化与免疫学检测[J].中华检验医学杂志,2004,11(27):815-816
18 王北宁,韩玲霞,靳淑玲,等.结核性脑膜炎脑脊液中性粒细胞集落刺激因子的测定.中国防痨杂志,1997,19(1):29-30
19 Ladel CH, Blum C, Dreher A, et al. Lethal tuberculosis in interleukin-6-deficient mutant mice [J]. Infect Immun. 1997,65(11):4843-4849
2 Ahuja GK,Mohan KK,Kprasad,et al.Diagnostic criteria for tuberculous meningitis and their validation[J].Tuber Lung Dis,1994,75:149-152
3 王维治,罗祖明主编.神经病学[M].第四版.北京:人民卫生出版社, 2002:164-190
4 巫顺秀,陈显光,李森美,等.脑脊液 γ-干扰素检测对结核性脑膜炎诊断价值的探讨.华中医学杂志,2006,30(1):41-4
5 全国结核病流行病学抽样调查技术指导组.第四次全国结核 病 流 行 病 学 抽 样 调 查 报 告 . 中 华 结 核 和 呼 吸 杂志,2002,25(1):3-7
6 World Health Organization.Antrtuberculosis drug resistance in the world.Report No.2.Prevalence and trends,Geneva:WHO,2000
7 World Health Organization.Global tuberculosis control.WHO report 2000.Geneva:WHO,2000
8 何俊瑛,孔繁元,郭力.临床脑脊液细胞学诊断.石家庄:河北科学技术出版社,2007
9 王宁山,侯熙德.结核性脑膜炎脑脊液实验室指标的检测分析.中华结核和呼吸杂志,1994,1:54
10 范超平,陈琼,王蕾.结核性脑膜炎 30 例脑脊液细胞学动 分析.中国实用神经疾病杂志,2007,2(10)
11 OEHMICHEN M,DOMASCH D,WIETHOLTER H.Origin,proliferation and fate of cerebrospinal cells[J].J Neuro,1982,227(3):145-150
12 THWAITES G,CHAU T T,MAI N T,et al.Tuberculous meningitis[J].J Neurol Neurosurg Psychiatry,2000,68(3):289-299
13 Mathai A, Radhakrishnan VV, Sarada C,et al. Detection of heat stable mycobacterial antigen in cerebrospinal fluid by Dot-Immunobinding assay[J].Neurol India, 2003,51:52-54
14 Bera Swati, Shende Niraj,Kumar Satish,etal. Detection of antigen and antibody in childhood tuberculous meningitis. The Indian Journal of Pediatrics. 2006 Aug;73(8):675-679
15 Samuel AM. A sensitive and specific method for diagnosisof tubercular meningitis[J].Indian J Med Res ,1983 ;77 :752～753
16 Cambiaso CL.J Immun Meth.1990;129:9
17 Alamelu Raja Immunology of tuberculosis[J].Indian Med Res,2006,120:213-232
18 何俊瑛,黄庆生,卜晖.脑脊液单核细胞内结核抗原检测对结 脑 早 期 诊 断 的 意 义 . 脑 与 神 经 疾 病 杂志,2005,13(3):204-205
19 Douglas AD, Pieter JML, Ronald A.Greenfield Invasion of the Central Nervous System by Intracellular Bacteria.Clin Microbiol Rev,2004,17(2): 323- 347
20 Sumi MG, Mathai A, Reuben S,et al. Immunocytochemical Method for Early Laboratory Diagnosis of Tuberculous Meningitis[J].Clin Diagn Lab Immunol,2002,9(2):344-347
21 Mazurek GH,LoBue PA,Daley CL,et al.Comparison of a whole-blood interferon assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection.JAMA,2001,286:1740-1747
22 马志明,肖芃,唐林国,等. γ-干扰素基因多态性与肺结核易感性的研究.中华结核和呼吸杂志.2007,30(10):777-778
23 Aoe K,Hiraki A, Murakami T, et al Diagnostic significance of interferon-γin tuberculous pleual effusion [J]. Chest,2003,123(3):740-744
24 冯经华,尹凤鸣,严振球.目前结核分枝杆菌感染中重要免疫 细 胞 和 细 胞 因 子 作 用 的 研 究 进 展 . 临 床 军 医 杂志,2007(35)4:291-295
1 Feng CG, Britton WJ, Palendira U, et al. Up-regulation of VCAM-1 and differential expansion of β integrin-expressing T lymphocytes are associated with immunity to pulmonary Mycobacteriym tuberculosis infection[J]. J Immunol, 2000, 164(9):4853-4896
2 刘举祥,王翠兰,孙颖.中枢神经系统感染患者血清中sICAM-1 和TNF-α 的水平及临床意义[J].神经疾病与精神卫生,2005,5(2):99-101
3 梁艳,董德琼,杨渝浩.可溶性血管细胞黏附分子 1 在肺结核发病机制中的作用和临床意义[J].中华结核和呼吸杂志,2006,29(4):266-269
4 张庆华,邵祥稳.结核性脑膜炎患者脑脊液中转铁蛋白测定及临床意义[J].现代医药卫生,2004,20(9):772-773
5 王秀霞,檀国军,罗克娴.检测脑膜炎患儿脑脊液肿瘤坏死因子-α 的临床意义[J].临床荟萃,2002,17(6):347
6 Saunders BM, Briscoe H, Britton WJ, et al. T cell-derived tumour necrosis factor is essential, but not sufficient, for protection against Mycobacterium tuberculosis infection[J].Clin Exp Immurol,2004, 137(2):279-287
7 柏雪莲,傅斌,刘克义.结核分枝杆菌感染中一些重要免疫细 胞 和 细 胞 因 子 作 用 的 进 展 研 究 [J]. 中 国 防 痨 杂志,2006,28(3):178-181
8 宋方禹,陈翠玲.中枢神经系统感染脑脊液研究进展[J].脑与神经疾病杂志,2005,13(2):157-159
9 刘怀深,吕喜英,兰桂云.结核性脑膜炎患者血清 sIL-2R 的检测分析[J].临床荟萃,2002,17(22):1343-1344
10 Lee KY, Kim EH, Yang WS, etal. Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis[J].J Neurol Sci, 2004, 220(1-2):73-78
11 冯勋刚,牛瑞云,李宪章.动态测定结核性脑膜炎脑脊液S100B 蛋 白 的 临 床 意 义 [J]. 济 宁 医 学 院 学报,2003,26(4):30-31
12 林存智,朱新红,华裕忠,等.干扰素-γ 含量和腺苷脱氨酶活性对结核性和肿瘤性胸腔积液的鉴别诊断价值[J].中国全科医学,2007,6(10)
13 罗英琳.多指标检测对结核性和癌性胸腔积液的诊断价值[J].广西医学,2005,8(27):1170-1171
14 Poyraz B, Kaya A, et al. Diagnostic significance of gammar interferon in tuberculous pleurisy [J]. Tuberk Toraks, 2004,52(3):211-217
15 Aoe K,Hiraki A, Murakami T, et al Diagnostic significance of interferon-γin tuberculous pleual effusion [J]. Chest,2003,123(3):740-744
16 Feng CG, Jankovic D, Kullberg M, et al. Maintenance of Pulmonary Th1 Effector Function in Chronic Tuberculosis Requires Persistent IL-12 Production [J]. J Immurol.,2005,174(7):4185-4192
17 熊力凡,金大鸣.脑脊液生化与免疫学检测[J].中华检验医学杂志,2004,11(27):815-816
18 王北宁,韩玲霞,靳淑玲,等.结核性脑膜炎脑脊液中性粒细胞集落刺激因子的测定.中国防痨杂志,1997,19(1):29-30
19 Ladel CH, Blum C, Dreher A, et al. Lethal tuberculosis in interleukin-6-deficient mutant mice [J]. Infect Immun. 1997,65(11):4843-4849