艾滋病慢性腹泻中医证候特点研究
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摘要
目的
     初步探索艾滋病慢性腹泻的临床特点,并依据导师的学术假说,进一步探索艾滋病慢性腹泻症状、证素、病机等中医证候方面规律及其实验室检查特点。
     方法
     采用回顾性病例调查与横断面研究相结合的方法。
     1回顾性研究用预先制定的调查表对2006.1.1-2008.12.31期间在广州市第八人民医院感染科住院的符合艾滋病慢性腹泻诊断标准的病例进行调查,观测指标包括病例一般信息、症状、合并症、实验室检查、肠镜及病理共5个方面信息,并对数据进行整理分析。
     2横断面调查用预先制定的调查表对2009.4.1-2009.10.31期间在广州市第八人民医院中医科和感染科住院部和门诊部就诊的病例进行调查。研究对象包括艾滋病无症状期(CD4>350 cells/ul.CD4≤350 cells/ul).发病期(腹泻、发热、咳嗽、疮疡)以及非艾滋病慢性腹泻共7组病例。观测指标包括一般信息、症状、证素、实验室检查共4个方面信息,并对数据进行整理分析。
     3统计分析①定量资料:两个组别间对比时若数据呈正态分布则采用两独立样本率的T检验,呈非正态分布时采用两独立样本率的非参数检验(Mann—Whitney U);多个组别间对比时采用单项方差分析(ANOVA):②定性资料:二分类变量数据采用2×2列联表两个独立样本率比较的卡方检验;多分类变量数据分析时若因变量为等级变量则采用多个独立样本率的非参数检验,若因变量为无序变量则采用R×C列联表分析。所有分析均以P<0.05为变量有显著性意义的标准。数据录入采用EpiDate 3.02软件,统计分析采用Spss13.0软件。
     结果
     1回顾性研究共66例病例纳入研究,其中进行大便培养者51例,肠镜检查者34例,病理组织学检查者28例。
     1.1一般资料男性占53例(80.3%),所有病例平均年龄(39.227±10.171)岁,均为汉族,婚姻类别中未婚、已婚、丧偶、离异者分别占27.3%、68.2%、3.0%、1.5%,文化程度中小学、初中、高中/中专分别占13.6%、74.2%、12.1%,感染途径中有偿鲜血、输血、静脉吸毒、性接触、不明原因分别为1.5%、1.5%、39.4%、47.0%、10.6%;
     1.2临床症状出现频次前5位的症状为:口腔豆腐渣样物48例(72.7%),畏寒47例(71.2%),乏力45例(68.2%),发热39例(59.1%)、纳差34例(51.5%),其余尚有咳嗽、气促、腹痛、恶心、呕吐等。
     1.3合并症出现频次在10%以上的合并症为:口腔真菌感染48例(72.7%),肺部感染44例(66.7%),病毒性肝炎34例(51.5%),消瘦综合症28例(42.4%),结核21例(31.8%),深部真菌感染18例(27.3%),电解质紊乱16例(24.2%),疱疹病毒感染12例(18.2%),败血症9例(13.6%);
     1.4实验室检查WBC偏低者26例(39.4%),偏高者9例(13.6%);RBC偏低者37例(56.1%);有贫血表现者50例(75.8%);PLT偏低者12例(18.2%),偏高者(21.2%);LYM偏低者42例(63.6%),ALT偏高者18例(27.3%),AST偏高者41例(62.1%);所有病例CD4在200以下,其中低于50者51例(77.3%);大便培养中致病菌培养阳性10例(19.6%),其中真菌培养阳性7例(13.7%)。
     1.5肠镜及病理检查各部分主要数据为:肠道固有层或黏膜充血水肿者31例(91.2%),病变解剖部位发生在乙状结肠和升结肠各20例(各占58.8%),结肠镜检查提示引起本病的肠道疾病有结肠炎18例(52.9%),肠镜检查提示为单一诊断者21例(61.8%);病理组织学检查中肠道固有层或黏膜组织中淋巴细胞浸润22例(78.6%),粘膜充血水肿16例(57.1%),病变部位在乙状结肠13例(占46.4%),病理诊断为慢性非特异性结肠炎9例(32.1%)。
     1.6学术假说①艾滋病病因病机复杂,涉及较多证素,且不同亚型病例病因病机存在一定差别;②艾滋病腹泻病因以疫毒侵袭为总因,复与湿邪等有关,病机以脾肾阳虚为主,多伴全身气虚,兼夹湿邪和/或淤血;③艾滋病腹泻病例在症状、实验室指标等方面与其他亚型病例存在一定差别。
     2横断面调查共140病例纳入分析,平均分布于无症状期CD4>350组、无症状期CD4≤350组、艾滋病期腹泻组、发热组、咳嗽组、疮疡组以及非艾滋病腹泻对照组共七组,每组各20例病例。
     2.1一般资料男性89例,男女比例为1.75:1,感染途径中血液途径11例(9.2%),性接触90例(75%),吸毒11例(9.2%),男性、汉族、已婚或同居、初中文化程度、工人和农民是本研究组病例的主要特点。
     2.2症状特点无症状期组腹部不适、发热、神疲、身体困重、咳嗽、咳痰、咽喉不适、食少纳呆、口渴、口味异常、恶心呕吐、肢体倦怠、消瘦、面色少华、唇甲色淡、情绪低沉、出血17个症状频数低于发病期组,头痛、发脱2个症状高于发病期组。在腹泻组症状与其他各组的比较中,腹泻组腹部不适、发热、神疲、身体困重、食少纳呆、口渴、口味异常、肢体倦怠、消瘦、唇甲色淡、情绪低沉、畏寒肢冷12个症状频数高于CD4>350组,恶风寒、头痛2症状低于CD4>350组;腹泻组腹部不适、发热、神疲、身体困重、食少纳呆、口渴、口味异常、恶心呕吐、肢体倦怠、消瘦10个症状频数高于CD4≤350组,头痛频数低于CD4≤350组;腹泻组腹部不适、大便异常高于发热组,发热频数低于发热组;腹泻组腹部不适、耳鸣2症状频数高于疮疡组,皮肤瘙痒频数低于疮疡组;腹泻组腹部不适症状频数高于咳嗽组,咳嗽、咳痰2症状频数低于咳嗽组。腹泻组汗出异常、咳嗽、气短、口渴、肢体倦怠、消瘦、唇甲色淡、情绪低沉、耳鸣9个症状频数高于非艾滋病腹泻组。
     2.3证素特点艾滋病腹泻组有脾、胃、湿、阳虚4证素高于无症状期CD4>350组;脾、湿2证素高于CD4≤350组,气虚证素低于CD4≤350组;脾、胃2证素高于发热组,胸隔证素低于发热组;脾、胃、阳虚3证素高于艾滋病咳嗽组,肝、肌肤、血虚3证素频数低于艾滋病咳嗽组;肾、胃、湿3证素高于疮疡组,肺证素低于疮疡组;肺、脾、肾、气虚、阳虚5证素高于非艾滋病腹泻组,小肠、大肠2个证素低于非艾滋病腹泻组,所有P<0.05。
     2.4实验室检查特点发病期病例外周血Hb、RBC、LYM、CD4、CD8、CD4/CD8指标均低于无症状期组(P<0.01),艾滋病期病例Hb在腹泻组、发热组、咳嗽组均偏低(P<0.01),WBC在组间差异无显著意义,RBC在咳嗽组RBC含量偏低(P<0.01),PLT的各组间差异具有明显统计学意义(P<0.01),CD4、CD8和CD4/CD8在发病期4组均偏低,各组间差异具有明显统计学意义(P<0.01);在腹泻组实验室指标与其他各组的多重比较中,Hb、PLT、CD8与各组间的差异无显著意义,RBC在CD4≤350组计数较高,CD4和CD4/CD8在CD4>350组计数较高。
     结论
     1艾滋病慢性腹泻病例证素和病因病机特点
     1.1证素特点
     病位证素主要在脾、肾、胃,病性证素以湿、气虚和阳虚为著。
     1.2病因病机特点病因总因病毒入侵,复与房劳、精神、医过等有关;病机以脾肾阳虚为主,多伴气虚,并可兼夹湿邪阻滞和/或胃失和降。
     1.3不同艾滋病亚型病例病因病机存在一定差别。
     2艾滋病慢性腹泻病例症状特点
     2.1常见症状
     脘腹症状、水样便、烂便、身体困重、口腔豆腐渣样物、纳差(食少纳呆)、恶心呕吐、口味异常、口渴、畏寒肢冷、腰膝酸软、乏力(神疲、肢体倦怠)、唇甲色淡、面色少华、气促(气短)、情绪低落、畏寒、发热、汗出异常、咳嗽、咽喉不适、健忘等。
     2.2艾滋病腹泻组病例临床表现比无症状期和非艾滋病腹泻病例更为严重。
     2.3不同艾滋病亚型病例临床症状存在一定差别。
     3艾滋病慢性腹泻病例实验室检查特点
     3.1艾滋病腹泻病例实验室指标特点
     多有RBC、Hb下降和AST升高及CD4明显下降;肠镜和病理检查多见肠道形态学改变以黏膜充血水肿为主,肠黏膜组织大量淋巴细胞浸润,病变部位以回盲瓣、乙状结肠、升结肠、回肠、横结肠较多。
     3.2不同艾滋病亚型病例实验室指标存在一定差别。
     4艾滋病慢性腹泻病例一般特征
     具备下列特征的人群有较高的患病率和发病率:男性、中年、汉族、已婚、初中文化程度、性接触和静脉吸毒及血液传播、职业为无业或商业人员或农民或工人。
     5艾滋病慢性腹泻病因病机研究方法
     回顾性研究和横断面研究相结合是一种较好的研究方法,可以避免结论真实性的偏倚和研究资源的浪费。
Objectives:
     To explore the clinical characters of Acquired Immunodeficiency syndrome (AIDS)-Associated chronic Diarrhea (AACD) and make further study of it's regularities on symptoms, symptom factors, mechanism of disease etc. in TCM theory and laboratory findings based on the hypothesis of advisor.
     Methods:
     The integration of retrospective study and cross-sectional study was adopted.
     1 Retrospective study:With pre-formed questionnaire, medical data from patients with ARCBD and hospitalized at the Infection Department of The 8th Hospital of Guangzhou City from Jan 1,2006 to Dec 31,2008, contains demographics, symptoms, complications, laboratory findings, enteroscopy and histopathologic examination were retrospective analyzed.
     2 Cross-sectional study:With pre-formed questionnaire, medical data from patients received intervention at either In-department or Out-department of Infection Department and TCM Department to The 8th Hospital of Guangzhou City from Apr 1,2009 to Oct 31,2009, contains demographics, symptoms, symptom factors, and laboratory findings were analyzed. The eligable participants includes 3 groups divided into 7 subgroups, which contain CD4>350 cells/ul (High Concentration in the Asymptomatic Stage, HCAS), CD4≤350 cells/ul (Low Concentration in the Asymptomatic Stage, LCAS) in the stage I, CAAD, AIDS-Associated Fever (AAF), AIDS-Associated Cough (AAC), AIDS-Associated Maculopapular Rash (AAMR) in the stageⅡ-Ⅳ, and No AIDS-Associated Diarrhea (NAAD).
     3 Statistical Analysis:Using the Two-Independent-Samples T Test for data with normal distribution and Two-Independent-Samples Nonparametric Test (Mann-Whitney U) for data with nonnormal distribution between two groups, ANOVA for the comparison among different groups, chi-square statistics by 2X2 contingency tables for dichotomous variables, and RXC contingency tables for the disordered dependent variables. Variable with statistically results at a p-level<0.05 were considered as significantly. With EpiDate 3.02 and Spss13.0 software, the data entry and analysis were performed respectively.
     Results
     1 Retrospective study:A total of 66 patients were enrolled in the outcome analysis. Of these,51,34,28 patients with feces culture, enteroscopy and histopathologic examination, respectively.
     1.1 Subject Characteristics Of those 66 patients (Ages:39.227±10.171, Male: 80.3%), singlehood, married, loss of spouse, and dissociation were 27.3%, 68.2%,3.0%and 1.5%respectively, elementary school, primary school and high school education were 13.6%,74.2%and 12.1%, sell blood, blood transfusion, drug abuse through intravenous injection, sex and in nubibus reasons were 1.5%, 1.5%,39.4%,47.0%and 10.6%respectively in the routes of infection.
     1.2 Symptoms:According to the frequency, the former 5 symptoms were tofukasu analog in oral cavity (72.7%), chilly (71.2%), debilitation (68.2%), fever (59.1%), and anorexy (51.5%), which may accompany with cough, gasping, bellyache, nausea, vomiting etc..
     1.3 Complications:Complications with the frequency percentage≥10%contained oral thrush (72.7%), pneumonia infection (66.7%), virus hepatitis (51.5%), cachexia (42.4%), tuberculosis (31.8%), fungal infections (27.3%), electrolyte disturbances (24.2%), cytomegalovirus (18.2%), and septicemia (13.6%).
     1.4 Laboratory findings:26 (39.4%),37 (56.1%),50 (75.8%),12 (18.2%),42 (63.6%),0 (0), and 0(0) patients had lower WBC, RBC, HGB, PLT, LYM, AST, and ALT concentration than normal range respectively, contrarily,9 (13.6%),0 (0),0(0),14 (21.2%),0(0),18 (27.3%), and 41 (62.1%) patients had higher concentration respectively. CD4≤200 cells/ul for all patients, of these, 51 (77.3%) patients were≤50 cells/ul. And 10 (19.6%) patients had positive results in the feces culture, of these,7 (13.7%) were positively in the eumycete culture.
     1.5 enteroscopy and histopathologic examination:31 patients (91.2%) had hyperemia and edema in the lamina propria or mucosa of intestinal tract, which had occurred in the sigmoid colon and ascending colon (58.8%), and 18 patients (52.9%) were diagnosed as colonitis. In the histopathologic examination,22 patients (78.6%) had lymphocyte infiltration in the lamina propria or mucosa of intestinal tract, and 9 patients (32. 1%)were diagnosed as non-specificity colonitis.
     1.6 Hypothesis:(1) Because many symptom factors were involved, the reasons and mechanism of AIDS were complicated, and were variably among different subtypes of AIDS; (2) The reasons of CAAD was the invasion of Ai poison, and the mechanism of CAAD was the spleen-kidney yang deficiency mainly, which maybe accompany with qi deficiency, dampness obstruction and/or congestion; (3) Patients with CAAD has own characters on symptoms and laboratory findings, which maybe different with other subtypes of AIDS.
     2 cross-sectional study:A total of 140 patients were enrolled in the outcome analysis. Of these,20 patients were divided in HCAS, LCAS, CAAD, AAF, AAC, AAMR and NAAD subgroup in average, respectively.
     2.1 Subject Characteristics:Of these 140 patients (Male:63.6%), male, HAN people, married or cohabitation, primary school education, farmer or laborer were the main characters. In addition, blood transfusion, sex and drug abuse through intravenous injection were 9.2%,75%, and 9.2%respectively in the routes of infection.
     2.2 Symptoms:17 symptoms which include abdominal discomfort, fever, tired, weary and heavy body, cough, expectoration, throat indisposition, anorexy, thirsty, abnormal taste, nausea and vomiting, lassitude, emaciation, light on face, light color on lip and nail, depression and bleeding in the asymptomatic stage had higher present percentage than patients in the stageⅡ-Ⅳ, but the headache and alopecie were lower. In the comparison between CAAD and other subtypes,12 symptoms which include abdominal discomfort, fever, tired, weary and heavy body, anorexy, thirsty, abnormal taste, debilitation, emaciation, light color on lip and nail, depression, chill and limb cold had higher present percentage than patients in the HCAS subgroup, but the aversion to wind and cold and headache were lower;
     10 symptoms which include abdominal discomfort, fever, tired, weary and heavy body, anorexy, thirsty, abnormal taste, nausea and vomiting, debilitation and emaciation had higher present percentage than patients in the LCAS subgroup, but the headache were lower; abdominal discomfort and abnormal stool had higher present percentage than patients in the AAF subgroup, but the fever was lower; abdominal discomfort and tinnitus had higher present percentage than patients in the AAMR subgroup, but the itch of skin was lower; abdominal discomfort was higher than patients in the AAC subgroup, but cough and expectoration was lower; 9 symptoms which include abnormal perspiration, cough, gasping, thirsty, tired, emaciation, light color on lip and nail, depression and tinnitus had higher present percentage than patients in the NAAD subgroup.
     2.3 symptom factors:In the comparison between CAAD and other subtypes,4 symptom factors include spleen, stomach, dampness and yang deficiency had higher present frequency than HCAS; spleen and dampness were higher than LCAS; spleen and stomach were higher but the septum pectorale was lower than AAF; spleen, stomach and yang deficiency had higher present frequency but the liver, skin and blood deficiency were lower than AAC; kidney, stomach and dampness were higher but the pneumonia was lower than AAMR; 5 symptom factors include pneumonia, spleen, kidney, qi deficiency and yang deficiency had higher present frequency but the small intestine and large intestine were lower than NAAD, and all the values of P<0.05.
     2.4 Laboratory findings:Concentration of HGB, RBC, LYM, CD4, CD8 and CD4/CD8 in the stageⅡ-Ⅳwere higher than patients in the asymptomatic stage. In the comparison between CAAD and other subtypes, HGB, RBC, PLT, CD4, CD8 and CD4/CD8 had significant difference in the analysis between subgroups, and in the multiple comparisons, RBC concentration in the LCAS was higher, and CD4 concentration and CD4/CD8 in the HCAS were higher than CAAD, but the HGB, PLT and CD8 concentration were nonsignificance.
     Conclusion
     1 The characters of symptom factors and mechanism of AACD
     1.1 The characters of symptom factors:The location of disease were main focused on spleen, kidney and stomach, and the nature of disease main focused on dampness, qi deficiency and yang deficiency mainly.
     1.2 The characters of reasons and mechanism The reasons of disease was the invasion of Ai poison, which effected by sex, mental health and iatrogenic lapsus etc.. The mechanism of disease was spleen-kidney yang deficiency mainly, which maybe accompany with qi deficiency, dampness obstruction and/or stomach disharmony.
     1.3 The characters of reasons and mechanism were variably among different subtypes of AIDS.
     2 The symptoms characters of AACD
     2.1 Normal clinical symptoms:abdominal discomfort, watery stool, rotten stool, weary and heavy body, tofukasu analog in oral cavity, anorexy, nausea and vomiting, abnormal taste, thirsty, chill and limb cold, feeble on waist and knee, debilitation, light color on lip and nail, light on face, gasping, depression, chill, fever, abnormal perspiration, cough, throat indisposition, forgetful etc..
     2.2 The clinical symptoms of patients with CAAD were more severe than patients in the asymptomatic stage or with NAAD.
     2.3 The characters of symptoms were variably among different subtypes of AIDS.
     3 The characters of laboratory findings of AACD
     3.1 The characters of laboratory findings:Usually accompany with descent of RBC, HGB and CD4 especially, and heighten of AST. In the enteroscopy and histopathologic examination, morphology change of intestinal tract were the hyperemia and edema mainly, and usually had lymphocyte infiltration, which often occurred in the ileal valve, sigmoid colon, ascending colon, ileum and transverse colon.
     3.2 The characters of laboratory findings were variably among different subtypes of AIDS.
     4 The common demographics characters of AACD
     People with the following demographics characters may have high risks on the morbidity of AIDS or CAAD:male, middle aged, HAN people, married, primary school education, sex or drug abuse through intravenous injection or blood transfusion, and the occupation was farmer, or laborer, or commerce personnel, or unemployment.
     5 Approaches of reasons and mechanism of AACD study
     The integration of retrospective study and cross-sectional study was a suitable method for the reasons and mechanism of CAAD study, which may avoid the biases of the validity and the waste of research resources.
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