自身免疫性肝炎临床分析——附28例病例报告

目的探讨自身免疫性肝炎(autoimmune hepatitis,AIH)的临床特点,提高诊疗水平。方法对符合国际自身免疫肝炎小组(IAIHG)新修订的描述性诊断标准和积分系统评价标准的28例AIH患者的临床、生化及病理特点进行分析。结果 28例患者中肝功生化检查表现为肝炎样改变;实验室检查主要表现为高免疫球蛋白(Ig G)、高胆红素、高转氨酶(ALP)。自身抗体检测结果显示22例阳性,4例可疑;其中Ⅰ型抗核抗体(ANA)阳性19例(86.4%),Ⅱ型抗平滑肌抗体(SLA)阳性3例(13.6%),合并干燥综合征A抗体(SSA)阳性2例(9.1%),合并抗线粒体抗体(AMA)阳性1例(4.5%)。病理检查发现以界面性肝炎,浆细胞浸润为主。治疗3个月后,患者乏力、黄染明显改善,血清转氨酶、总胆红素、碱性磷酸酶明显下降。结论 AIH患者无典型临床症状,通过自身抗体的检测、病理检查并结合激素试验性治疗可明确诊断,治疗后预后较好。     

自身免疫性肝炎患者临床和肝组织病理学特征

目的 探讨自身免疫性肝炎(AIH)患者临床和肝组织病理学特征。方法 回顾性分析48例AIH患者的临床特点、血生化指标、免疫学检查和肝组织学特征。结果 48例AIH患者男女比例为 1∶5.8,发病年龄最小者为4岁,平均发病年龄为(45.5±4.2)岁;临床表现以反复肝功能异常(46%)、腹痛(37%)、乏力(35%)、黄疸(19%)为主;血生化指标升高,血清IgG水平升高;抗核抗体、抗平滑肌抗体、抗肝肾微粒体抗体、抗肝可溶性抗原抗体、抗中性粒细胞浆抗体和双链DNA抗体阳性率分别为72%、23%、6%、8%、4%和2%;肝组织存在界面炎、浆细胞浸润和小叶炎症,伴有胆管增生者97%、凋亡小体为87%、纤维隔形成为87%、桥接坏死为27%、“玫瑰花环样”改变为18%。结论 AIH患者多见于女性,40岁以上人群高发,临床表现缺乏特异性,需结合血生化学、免疫学特征做出诊断,肝组织病理学检查具有重要的临床诊断价值。     

原发性胆汁性肝硬化44例临床和免疫学及病理学特征分析

目的了解原发性胆汁性肝硬化(PBC)患者的临床、免疫学和病理学特点。方法回顾性分析44例PBC患者的一般资料、临床特点、生化检查、免疫学检查、自身抗体和病理的结果。结果 44例PBC患者男女比例1∶7.8,发病年龄为(57.68±10.71)岁,首次发病诊断分别为肝功能异常(23例,52.27%)、肝硬化(11例,25.00%)、自身免疫性肝炎(2例,4.55%)等;临床表现主要为乏力(25例,56.82%),皮肤瘙痒(17例,38.64%),黄疸(16例,36.36%),口干、眼干(15例,34.09%)等。PBC重叠自身免疫性肝炎(AIH)7例(15.91%),合并其他自身免疫性疾病25例(56.82%),生化检查显示碱性磷酸酶(ALP)、γ-谷氨酰转肽(GGT)水平升高,Ig M升高明显,自身抗体中以ANA、AMA、AMA-M2阳性者为主。肝活检25例,17例可见肝小叶内散在点、片状坏死,20例汇管区碎屑状坏死,21例汇管区淋巴细胞浸润,11例细小胆管增生,16例纤维组织增生,6例假小叶形成,6例胆管上皮变性,7例胆管炎性细胞浸润,3例肝小叶内及汇管区见肉芽肿形成,5例小叶间胆管消失,3例羽毛状变性,2例胆栓形成,6例小叶间胆管炎。结论 PBC女性多见,发病和临床表现无特异性,肝功能检查以肝汁淤积为主,AMA、AMA-M2阳性可诊断。肝组织学改变小叶间胆管炎、胆管数目减少,汇管区淋巴细胞聚集、肉芽肿形成、细小胆管增生,以及肝细胞羽毛状变性是主要病理特点。     

自身免疫性肝炎86例临床、病理特点分析

为提高对自身免疫性肝炎(AIH)的诊治水平,采用国际自身免疫性肝炎小组(IAIHG)新修订的描述性诊 断标准和计分系统,对符合诊断的患者进行临床、生化、病理特点分析。86例AIH患者,女75例,男11例,高发年 龄为40～60岁,其中Ⅰ型80例(93．020k),Ⅱ型3例(3．49％);Ⅲ型3例(3．49％);肝功能生化检查表现为肝炎样改 变;实验室检查主要表现为高γ球蛋白血症,高IgG、ALP、γ-GT及甘油三酯增高,81．5％患者抗核抗体阳性:病理改 变以界板性肝炎,浆细胞浸润为主,78％的患者对免疫抑制剂治疗效佳。AIH患者多为中年女性,以血清自身抗体、 高γ球蛋白血症和肝组织活检呈界板性肝炎、浆细胞浸润,对免疫抑制治疗反应良好为特点。     

自身免疫性肝炎的诊断和治疗

自身免疫性肝炎(autoimmune hepatitis,AIH)是一种累及肝脏实质的特发性疾病.临床上,AIH以高血清转氨酶、高γ-球蛋白/Ig、高滴度自身抗体和肝组织学上以界面性肝炎(interface hepatitis)为特点,但需排除其他原因所致慢性肝病的可能.该病一般对糖皮质激素治疗应答良好.基于血清免疫学发现,AIH可分为二型:Ⅰ型AIH是最常见的疾病类型,与抗核抗体(ANA)和/或平滑肌抗体(SMA)、抗肌动蛋白抗体、非典型P-ANCA及抗可溶性肝抗原/肝胰抗体(抗SLA/LP)等有关;Ⅱ型AIH主要发生于儿童,以抗肝/肾微粒抗体1型(抗LKM -1)和抗肝细胞溶质-1抗体(抗LC-1)为主.大约有10％的患者血清自身抗体可呈阴性.按基因型可分为HLADR3( DRBI^0301)、HLA -B8和HLA - DR4CDRBI^0401,0405)等类.在存在相应的组织学改变的基础上,AIH的诊断还需结合临床和生化特点、血清自身抗体和免疫球蛋白水平.     

194例自身免疫性肝炎患者的临床特征分析

目的探讨自身免疫性肝炎(AIH)患者的主要临床特征。方法收集2010年12月-2014年12月于湖北省中医院光谷院区就诊的194例AIH患者资料,另外收集197例健康献血者作为对照组。检测AIH患者的自身抗体、生化指标及肝脏病理学表现,根据自身抗体的检测情况对AIH患者分型,并对全部AIH患者的年龄、性别、生化指标和病理表现进行统计分析。计量资料组间比较采用方差分析,计数资料组间比较采用χ2检验。结果 194例AIH患者中女/男为154/40,40~60岁为AIH的发病高峰,年龄40岁的患者占76.80%(149/194)。依据自身抗体检测情况,194例AIH患者中Ⅰ、Ⅱ、Ⅲ型的人数分别为163、5、26例,女/男分别为:131/32、4/1、19/7,年龄分别为(59.26±10.24)、(16.54±8.21)、(63.38±12.92)岁。AIH中Ⅰ型与Ⅱ、Ⅲ型的ALT、AST、GGT、Ig G检测值差异均有统计学意义(P值均0.05),AIH中Ⅱ型与Ⅰ、Ⅲ型的Ig A检测值差异有统计学意义(P值均0.05)。AIH病理表现主要为界面性肝炎、淋巴细胞及浆细胞浸润和玫瑰花结样改变。结论 AIH以女性且年龄40岁患者为主,40~60岁为发病高峰,Ⅰ、Ⅱ、Ⅲ型AIH的生化指标有不同程度的升高,病理表现主要为界面性肝炎。     

自身抗体阴性自身免疫性肝炎患者临床病理学特点

目的:分析自身抗体阴性自身免疫性肝炎(AIH)患者临床特点,并总结诊疗经验。方法:对167例AIH患者的临床和病理特点进行分析,将自身抗体阴性AIH患者定义为:符合国际自身免疫性肝炎小组(IAIHG)1999年描述性诊断标准且抗核抗体、抗平滑肌抗体、抗肝肾微粒体1型抗体和抗线粒体抗体均为阴性者。结果:167例中17例自身抗体阴性,占10.2%。自身抗体阳性和自身抗体阴性AIH患者在一般情况(诊断时年龄除外)、生化指标方面均无明显差异(P0.05)。自身抗体阴性组血清IgG水平低于自身抗体阳性组,差异有统计学意义(P=0.004)。两组肝组织学炎症分级无明显差异,而自身抗体阴性组中存在更多纤维化进展期患者(P0.001)。采用1999年诊断积分系统评估时,自身抗体阴性组中11例(64.7%)为可能性诊断,其余6例(35.3%)为确定性诊断;采用简化诊断积分系统重新评估后,仅3例(17.6%)达到可能性诊断,且无1例达到确定性诊断标准。与自身抗体阳性组相比,自身抗体阴性AIH患者接受24个月的免疫抑制治疗后累积完全生化缓解率为86%,两组患者无明显差异(P=0.658)。结论:自身抗体阴性AIH在国人中并非罕见,在应用免疫抑制治疗方面与自身抗体阳性AIH患者类似,能取得满意疗效。     

107例自身免疫性肝炎及其重叠综合征患者的临床分析

目的 分析自身免疫性肝炎(AIH)77例及其重叠综合征患者30例的临床表现、免疫学及生物化学特点及其治疗方案.方法 164例自身免疫性肝病患者中,AIH患者77例和AIH胆汁性肝硬化(PBC)重叠综合征患者30例,分析患者的临床特点、生物化学及组织学变化和治疗应答反应等. 结果 AIH患者的发病年龄高峰在50岁左右,肝功能生物化学检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常.74%的患者抗核抗体阳性,32%的患者抗平滑肌抗体阳性,52%的患者伴发了肝外自身免疫性疾病.肝组织病理变化以界面性肝炎为主(65%),在中、重度患者则出现小叶性肝炎、玫瑰花结样改变、桥接样坏死等.AIH-PBC重叠综合征患者血清ALT、AST、γ谷氨酰转移酶、碱性磷酸酶和抗核抗体、抗线粒体抗体(AMA)/AMA-M2阳性率较高,组织学检查往往还伴有胆管的病变.60例AIH患者接受免疫抑制剂强的松龙联合硫唑嘌呤治疗第1年时,AIH治疗患者达完全缓解者42例(70%),其中26例持续缓解,16例复发(激素减量至≤10 mg/d或停药后),10例部分缓解,8例无应答.持续缓解者的AST、ALT、免疫球蛋白G、丙种球蛋白及血总胆红素水平均显著低于非持续缓解者(34例,JD值均＜0.05),此类患者撤除了硫唑嘌呤,单用激素的剂量均可维持在5～10 mg/d.AIH-PBC重叠综合征组经联合熊去氧胆酸治疗后除碱性磷酸酶和γ谷氨酰转移酶外,其余肝功能指标(ALT、AST、总胆红素)亦明显改善(P值均＜0.01).结论 AIH及AIH-PBC重叠综合征在临床上并不少见,诊断需综合临床、生物化学、免疫学和病理学等检测结果.AIH患者联合应用糖皮质激素、硫唑嘌呤达持续缓解者,可改为单用小剂量激素治疗.AIH-PBC患者加用熊去氧胆酸治疗,亦可获得较好的疗效.     

自身免疫性肝病临床及免疫学特征

目的 分析自身免疫性肝病的临床特征和免疫学特点,以提高对该类疾病的认识和诊断水平.方法 对164例自身免疫性肝病患者的临床症状、体征及免疫学检查资料进行回顾性分析.结果 原发性硬化性胆管炎(PSC)多发于青年男性,自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(AIH-PBC)多发于中年女性;临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84%、78%、90%和67%,皮肤瘙痒的发生率分别为43%、56%、81%和60%.但AIH、PBC和PBC-AIH患者之间的年龄、性别、黄疸、皮肤瘙痒等症状无显著性差异(P均＞0.05).AIH首诊正确诊断率为8%(6/77),PSC为9%(1/11),PBC为13%(6/46).从发病到确诊PBC平均为38月,AIH为46月,PSC为31月,PBC-AIH重叠综合征确诊最难,平均需51月,常误诊为可能的AIH或单纯PBC.AIH、PBC、PSC和PBC-AIH肝外自身免疫性疾病的发生率分别为47%、11%、27%和24%,各自身免疫性肝病患者均有较高的自身抗体发生率.结论 自身免疫性肝病在临床上并不少见,患者常伴发肝外自身免疫性疾病及较高的自身抗体发生率;诊断需综合临床、生化、自身抗体和病理组织学等指标.     

自身免疫性肝炎的免疫学致病机制和免疫干预研究进展

自身免疫性肝炎(AIH)是以肝脏为主要免疫损伤器官的自身免疫性疾病,以波动性黄疸、氨基转移酶持续升高等肝功能损害为主要临床表现;具有高丙球蛋白血症和高血清自身抗体等免疫学特征;组织学见大量淋巴细胞与浆细胞浸润、汇管区形成界面性肝炎.根据自身抗体的不同可分为Ⅰ、Ⅱ、Ⅲ三型.AIH对糖皮质激素和硫唑嘌呤表现出良好的反应性,但需长期用药,治疗预后差异较大且易复发,多数患者最终发展为肝硬化,甚至肝癌[1].AIH病因目前尚不明确,多数学者认为病原微生物、化学物质以及药物等环境因素可诱发遗传易感个体而致病.     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.