肾上腺髓质素抑制内皮素的促血管平滑肌细胞增殖作用

目的观察肾上腺髓质素ａｄｒｅｎｏｍｏｄｕｌｉｎ，ＡＭ）对血管平滑肌细胞（ＶＳＭＣ）内丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎ－ａｃｔｉｖａｔｅｄｐｒｏ－ｔｅｉｎｋｉｎａｓｅ，ＭＡＰＫ）活性和ＶＳＭＣ增殖的作用。方法测定培养的ＶＳＭＣ内ＭＡＰＫ活性和３Ｈ－ＴｄＲ参入。结果１０－８ＥＴ－１可明显增加培养的ＶＳＭＣｓ内３Ｈ－ＴｄＲ参入（增加６７％，Ｐ＜０．０１）和ＡＰＫ激活（活性增高１１倍，Ｐ＜０．０１），而１０－１０～１０－７ｍｏｌ／Ｌ肾上腺髓质素（１３－５２）［ＡＭ（１３－５２）］与ＥＴ－１（１０－８ｍｏｌ／Ｌ）同时孵育，则可显著抑制ＥＴ－１的上述作用，与１０－８ｍｏｌ／ＬＥＴ－１单独应用时相比，３Ｈ－ＴｄＲ参入和ＭＡＰＫ活性分别减低２２％～５２％（Ｐ值均＜０．０１）和８．１～２９．４％（Ｐ值分别＜０．０５或０．０１）。而单用ＡＭ（１３－５２）对培养的ＶＳＭＣ３Ｈ－ＴｄＲ参入和ＭＡＰＫ活性无明显影响（Ｐ值＞０．０５）。结论ＡＭ（１３－５２）具有抑制ＥＴ所致的ＭＡＰＫ激活和ＶＳＭＣ增殖的作用。ＡＭ与ＥＴ相互作用，参与内皮源的细胞旁分泌调节体系的构成，共同维持循环系统功能的稳态     

低氧对肺血管周细胞增殖及分化的影响

目的研究低氧对肺血管周细胞增殖及分化的影响,探讨低氧性肺动脉高压时无肌型肺动脉肌化的细胞来源。方法实验分为４组：直接低氧组（Ｈ组）,常氧组（Ｎ组）,低氧内皮细胞条件培养液组（ＨＥＣＣＭ组）,常氧内皮细胞条件培养液组（ＮＥＣＣＭ组）。应用细胞培养、３Ｈ胸腺嘧啶核苷（３ＨＴｄＲ）、免疫细胞化学、图像分析等技术,研究低氧对肺血管周细胞３ＨＴｄＲ的掺入量、增殖细胞核抗原（ＰＣＮＡ）、α平滑肌肌动蛋白（αＳＭＡｃｔｉｎ）表达的影响。结果Ｈ组周细胞３ＨＴｄＲ的掺入量、ＰＣＮＡ及αＳＭＡｃｔｉｎ的表达量分别是Ｎ组的２．１６倍（Ｐ＜０．０１）、１．１６倍（Ｐ＜０．０１）及１．１１倍（Ｐ＜０．０５）,ＨＥＣＣＭ组周细胞３ＨＴｄＲ的掺入量、ＰＣＮＡ及αＳＭＡｃｔｉｎ的表达量分别是ＮＥＣＣＭ组的１．８倍（Ｐ＜０．０１）、１．１５倍（Ｐ＜０．０１）及１．１２倍（Ｐ＜０．０５）。结论低氧可直接或刺激内皮细胞分泌某些细胞因子促进肺血管周细胞增殖、并向平滑肌样细胞分化。肺血管周细胞的增殖、向平滑肌样细胞分化是低氧性肺动脉高压无肌细动脉肌化的重要细胞来源     

急性脑梗塞患者血浆cAMP和cGMP的含量变化及其临床意义

用放射免疫分析法对８４例急性脑梗塞患者（脑梗塞组）及６０例同龄健康者（对照组）的血浆环磷酸腺苷（ｃＡＭＰ）和环磷酸鸟苷（ｃＧＭＰ）含量进行了测定。结果显示，脑梗塞组血浆ｃＡＭＰ和ｃＧＭＰ含量及其比值均低于对照组，ｃＡＭＰ降低明显（Ｐ〈０．０１），ｃＧＭＰ降低轻微（Ｐ〉０．０５），其ｃＡＭＰ含量降低及ｃＡＭＰ／ｃＧＭＰ比值减小与病情呈正相关，提示检测血浆ｃＡＭＰ和ｃＡＭＰ含量有助于判断脑梗塞病情，指     

双丁酰环腺苷酸对体外HT29细胞增殖的调节

采用酸性磷酸酶细胞原位计数及流式细胞仪（ＦＣＭ）技术，观察了双丁酰环腺苷酸（ｄｂ－ｃＡＭＰ）对体外人结肠腺癌细胞系（ＨＴ２９）增殖的影响。结果：ｄｂ－ｃＡＭＰ在１０－４～１０－９Ｍ范围内可促进细胞增殖，尤其在１０－６～１０－８Ｍ时，ｄｂ－ｃＡＭＰ组ＯＤ值分别为１．５０±０．１１，１．５８±０．０７，１．５７±０．１２，分别为对照组的１０．３０％，１６．１８％和１１．７６％，差异显著（Ｐ＜０．０５或０．０１）。ｄｂ－ｃＡＭＰ浓度为１０－３Ｍ时，则抑制细胞增殖，至培养第５天，ｄｂ－ｃＡＭＰ组ＯＤ为１．０５±０．１３，对照组为１．２３±０．１７，有显著差异（Ｐ＜０．０５）。ＦＣＭ结果提示，ｄｂ－ｃＡＭＰ对细胞的抑制作用，与延长细胞Ｇ１／Ｓ期有关。结果表明，ｄｂ－ｃＡＭＰ对ＨＴ２９细胞增殖有双向调节作用。作者还对其作用机制进行了探讨。     

血管利钠肽减弱去甲肾上腺素对心肌生长的刺激作用

本实验目的在于研究血管利钠肽（ Ｖ Ｎ Ｐ）对去甲肾上腺素（ Ｎ Ｅ）促心肌生长作用的影响,并对其机制进行探讨。分离、培养乳鼠心肌细胞,完全随机分为三组:对照组、 Ｎ Ｅ组和 Ｖ Ｎ Ｐ＋ Ｎ Ｅ组。以 Ｍ Ｔ Ｔ法和总蛋白含量测定法观察各组细胞的生长情况。进而采用放射免疫方法研究了 Ｖ Ｎ Ｐ对细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平的影响。结果发现: Ｎ Ｅ（１０－ ７ ｍ ｏｌ／ Ｌ～１０－ ５ ｍ ｏｌ／ Ｌ）可以使培养的乳鼠心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值显著升高（ Ｐ＜ ０．０５ ｖｓ 对照组）,并且具有剂量依赖性。 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）可以显著降低 Ｎ Ｅ（１０－ ６ ｍ ｏｌ／ Ｌ） 刺激的心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值和细胞内总蛋白含量（ Ｐ＜０．０５ ｖｓ Ｎ Ｅ组）。对照组和 Ｎ Ｅ组细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平无显著差异,而 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）能升高细胞内ｃ Ｇ Ｍ Ｐ水平,降低ｃ Ａ Ｍ Ｐ水平（ Ｐ＜ ０．０５ ｖｓ对照组、 Ｎ Ｅ组）。提示 Ｖ Ｎ Ｐ能减弱 Ｎ Ｅ对心肌生长的刺激作用,其机制可能与ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ等信号转导分子有关。     

高血压病患者细胞环核苷酸与循环血管活性物质的关系

目的：探讨环核苷酸与血管活性物质与高血压病的关系。方法：观察１０７例高血压病患者和３０ 例正常人淋巴细胞环核苷酸和血浆多种血管活性物质变化,其中３１ 例高血压病患者服依那普利２４ 周后复查各项指标。结果：高血压病患者淋巴细胞环磷酸腺苷（ｃＡＭＰ）和环磷酸鸟苷（ｃＧＭＰ）高于对照组（Ｐ＜ ０．０１）;血浆内皮素（ＥＴ）、血管紧张素Ⅱ（ＡｎｇⅡ）、去甲肾上腺素（ＮＥ）、内源性洋地黄物质（ＥＤＬＳ）和心钠素（ＡＮＰ）增高并与ｃＡＭＰ呈正相关,ＡＮＰ与ｃＧＭＰ呈正相关（Ｐ＜ ０．０５～Ｐ＜ ０．０１）;依那普利干预后,上述指标均低于治疗前（Ｐ＜ ０．０５～Ｐ＜ ０．０１））。结论：细胞环核苷酸含量升高可能部分与循环多种血管活性物质水平增高有关,其相互作用改变可能参与高血压病的发病过程     

充血性心衰患者血浆内皮素和一氧化氮变化的临床意义及培哚普利的干预作用

为了解充血性心衰（ＣＨＦ）时心钠素（ＡＮＦ），内皮素（ＥＴ）和一氧化氮（ＮＯ）变化的临床意义及培哚普利的于预作用，我们选择４０例临床确诊为ＣＨＦ的患者，并随机分为培哚普利治疗组和常规治疗组，放免法测定血浆ＡＮＦ，ＥＴ含量，比色法测定血浆ＮＯ含量，与正常对照组比较，并观察治疗前后上述指标的变化情况。结果ＣＨＦ患者的血浆ＡＮＦ，ＥＴ水平均显著高于对照组（Ｐ＜０．０１），ＮＯ明显低于对照组（Ｐ＜０．０５）。常规治疗组治疗前后上述指标无明显改变（Ｐ＞０．０５），培哚普利平均治疗８周后ＡＮＦ，ＥＴ显著下降（Ｐ＜０．００１）而ＮＯ显著上升（Ｐ＜０．０５），提示ＡＮＦ，ＥＴ和ＮＯ参与了ＣＨＦ的病理生理过程。培哚普利可以降低ＣＨＦ的治疗有益。     

病毒性肝炎患者血清TGF－β1活性及其与肝纤维化关系的研究

采用改良的ＭＶ１ＬＵ细胞生长抑制ＭＴＴ法，检测了１０８例病毒性肝炎患者血清ＴＧＦ－β活性和血清ＰＣⅢ、ＨＡ、ＬＮ的含量，结果表明各型肝炎患者血清ＴＧＦ－β活性较正常对照都明显增高（Ｐ＜０．０１）。随病情的发展，ＴＧＦ－β１活性逐渐增高，ＰＣⅢ、ＨＡ、ＬＮ含量也明显增加，慢迁肝、慢活肝、肝硬化各组间ＴＧＦ－β１活性和ＰＣⅢ、ＨＡ、ＬＮ含量均有显著性差异（Ｐ＜０．０１），并呈正相关。肝硬化合并肝癌患者血清ＴＧＦ－β活性较正常对照增加１０倍以上。作者认为ＴＧＦ－β１活性可较好地反映肝纤维化进展状况，是调控肝纤维化的重要因子；肝硬化合并肝癌时，ＴＧＦ－β１活性显著增高，提示其可作为肝癌诊断、预后判断的另一指标。     

充血性心力衰竭患者血浆内在素与脂质过氧化的关系

为研究充血性心力衰竭（ＣＨＦ）时血浆内皮素与脂质过氧化的关系，我们观察了４０例ＣＨＦ患者治疗前后及不同心功能状态下血浆内皮素（ＥＴ）和丙二醛（ＭＤＡ）的变化。结果显示：ＣＨＦ患者的血浆ＥＴ及ＭＤＡ均较对照组明显增高（Ｐ＜０．０００１），且其含量均随心功能恶化而增加，治疗后血浆ＥＴ和ＭＤＡ均明显下降，其血浆ＥＴ与ＭＤＡ间呈正相关（Ｐ＜０．０５）。     

~(131)I抗AFP抗体-MMC双弹头导向治疗肝癌31例

目的观察化疗兼内照射的新型双弹头免疫导向治疗肝癌的疗效．方法以马抗人ＡＦＰ多克隆抗体（抗ＡＦＰＡｂ）和大鼠抗人ＡＦＰ单克隆抗体（抗ＡＦＰＭｃＡｂ）为载体，核素１３１Ｉ和丝裂霉素（ＭＭＣ）为双弹头，采用改良氯胺Ｔ法制备１３１Ｉ抗ＡＦＰＭｃＡｂＭＭＣ（双弹头１）和１３１Ｉ抗ＡＦＰＡｂＭＭＣ（双弹头２），静脉滴注，每月１次，治疗不能切除中晚肝癌３１例（治疗组）．治疗１，２，３次分别占４，１７和１０例，放射剂量（ＭＢｑ／例）均值依次为１９３５１±３７７４，６５１９±２３２４和９９２０±２３０５．结果治后肿瘤缩小率、血清ＡＦＰ下降率和１，２年生存率分别高于同期经动脉插管灌注（ＴＡＩ）或化疗栓塞（ＴＡＣＥ）的对照组（５００％，１５／３０比３００％，９／３０Ｐ＜００５；６６７％，１８／２７比２８０％，７／２５Ｐ＜００１和５００％比３３０％，３４０％比３３％Ｐ＜００１），治疗组病例的进展率（１００％）明显低于对照组（４００％，Ｐ＜００１）．结论双弹头疗效提高，由于抗体、核素１３１Ｉ和抗癌药的协同作用而增强了对癌细胞的杀伤力所致．     

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.