25例原发性胆汁性肝硬化患者临床和病理特征分析

目的通过分析原发性胆汁性肝硬化患者的临床资料,旨在提高对该病的诊治水平。方法对25例原发性胆汁性肝硬化患者的临床和病理资料进行回顾性分析,总结患者的临床特征、各项生化指标、免疫学与病理学特点。结果在25例PBC患者,ALP均明显升高(524.9±214.4U/L),17例γ-GT升高(431.1±248.9U/L),8例总胆红素升高(274.1±161.6μmol/L),均以直接胆红素升高为主,21例抗核抗体(ANA)阳性;12例行肝穿刺病理检查,其中11例符合PBC;8例影像学检查显示肝内胆管扩张,走行僵直。结论PBC主要累及中老年女性,血清ALP、γ-GT水平升高,AMA阳性以及病理学与影像学检查有助于诊断本病。     

肝叶切除加“T”管引流术与胆总管空肠Roux-en-Y吻合术治疗肝内胆管结石临床对比研究

目的探讨肝叶切除加"T"管引流术与胆总管空肠Roux-en-Y吻合术治疗肝内胆管结石的临床效果,评价手术的优越性。方法选择我院2011年1月至2015年1月收治的80例肝内胆管结石患者,采用随机数字表法分为肝叶切除加"T"管引流术组和胆总管空肠Roux-en-Y吻合术组,比较两组患者近期并发症、远期并发症和肝功能指标。结果 39例肝叶切除患者术后早期出现残留结石7例(18.0%)、切口感染4例(10.3%)、腹腔感染6例(15.4%)、胆漏4例(10.3%),而41例空肠Roux-en-Y吻合患者则分别为8例(19.5%,P0.05)、5例(12.2%,P0.05)、6例(14.6%,P0.05)、4例(9.8%,P0.05);肝叶切除患者术后出现残胆管炎(8.3%)、结石复发(4.2%)、结石合并胆管炎(4.2%)、吻合口狭窄(4.2%)的比较明显低于空肠Roux-en-Y吻合患者(分别为24.4%、19.5%、7.3%、22.0%,P0.05);治疗后,肝叶切除患者血清TBIL为(10.87±2.36)μmol/L、ALT为(38.96±10.28)U/L、AST为(34.76±5.47)U/L、ALP为(108.04±23.40)U/L,而空肠Roux-en-Y吻合患者则分别为(18.96±2.01)μmol/L、(76.83±15.67)U/L、(45.54±4.58)U/L、(176.42±34.58)U/L(P0.05)。结论肝叶切除加"T"管引流术治疗肝内胆管结石患者疗效显著,远期并发症发生率较低。     

胆管乳头状黏液瘤致急性胰腺炎一例

患者女,79岁.因"腹痛伴恶心呕吐,皮肤、巩膜黄染13天"于2009年6月27日入院.患者40年前曾行胆囊切除术,后因胆总管结石先后行4次手术.13日前无明显诱因出现持续性腹痛,向腰背部放射,伴恶心、呕吐胃内容物多次,无发热、黄疸和腹泻.CT平扫考虑急性胰腺炎(AP).给予禁食及对症治疗后病情缓解.7 d前患者突然出现黄疸,查WBC 22.4×10~9/L,中性0.87,血淀粉酶1320 U/L,谷丙转氨酶(ALT)56U/L,谷草转氨酶125 U/L,总胆红素104 pmol/L,直接胆红素70μmol/L,碱性磷酸酶167 U/L.外院上腹部MRCP示胆总管及肝内胆管明显扩张,胆总管下端狭窄,肝左叶萎缩,慢性胆管炎,胆囊缺如,十二指肠降部与胆总管侧壁相通,胰管扩张及AP表现(图1).胃碘水造影示十二指肠胆总管瘘.     

原发性硬化性胆管炎13例临床分析

目的　探讨原发性硬化性胆管炎 (PSC)的临床表现。方法　回顾性分析 13例PSC患者的临床表现 ,并检测其血清自身抗体。结果　 13例PSC患者中 ,男性 8例 ,女性 5例。平均年龄5 5 .73岁。以重度黄疸、轻度乏力为主要表现 ,伴有瘙痒、上腹钝痛、白陶土样便。硷性磷酸酶(ALP) 2 74U/L ,谷氨酰氨基转肽酶 ( 2 98± 77.78)U/L。血清抗中性粒细胞胞浆抗体周围型 (pANCA)阳性 7例 ,抗核抗体 (ANA)阳性 2例 ,平滑肌抗体 (SMA)、抗线粒体抗体 (AMA)分别有 1例阳性 ,抗肝肾微粒体抗体 1(LKM 1)及抗可溶性肝抗原抗体 (SLA)均阴性。B超检查主要表现为胆管壁增厚、回声增强及胆管内径变细。内镜逆行胰胆管造影 (ERCP) 13例全部阳性 ,肝外型 9例 ,混合型 4例。纤维结肠镜检查提示溃疡性结肠炎 6例。结论　原发性硬化性胆管炎好发于中年男性 ,临床表现为梗阻性黄疸 ,硷性磷酸酶 (ALT)、γ 谷氨酰胺转移酶 (GGT)明显升高为其显著特点 ,pANCA阳性率较高 ,往往伴有溃疡性结肠炎。B超对本病诊断具有提示和辅助作用     

肝炎与肝外梗阻性黄疸的B超鉴别

1992～1994年,我们对76例黄疸病人进行B超检查,其中22例诊为肝外梗阻性黄疸,均经CT、磁共振及病理检查确诊,现报道如下。 临床资料:本组年龄45～81岁,平均55岁,确诊为病毒性肝炎43例,肝炎后肝硬化11例,胰腺癌8例,肝癌6例,胆总管结石4例,胆管癌3例,急性化脓性梗阻性胆管炎1例。临床症状以食少、恶心、乏力、腹胀最多见,半数以上有肝区或上腹部疼痛。病人均出现胆红素及转氨酶(ALT)升高,胆红素>171μmol/L27例;ALT200～600U/L36例,800U/L以上7例;HBsAg(+)48例。B超检查示肝、胆、胰、脾大致正常18例,肝缩小11例,肝大14例,肝内外胆管扩张24例,肝内及肝门区团块状回声6例,脾大18例,胰腺肿大6例。腹部CT、磁共振检查26例,病理检查11例,全部确诊。     

三镜联合分期手术与腹腔镜手术治疗老年胆总管结石合并胆囊结石患者疗效对比研究

目的 探讨采用三镜联合分期手术与全腹腔镜同期手术治疗老年结石性胆道梗阻并发不同程度急性胆管炎患者的效果。方法 回顾性分析青岛市第三人民医院收治的老年胆总管结石伴急性胆管炎合并胆囊结石患者75例,其中35例观察组患者在入院后急诊行ERCP术,取出胆总管结石或留置胆管支架引流,择期再次入院行腹腔镜胆囊切除术(LC)或LC联合腹腔镜下胆总管取石术(LCBDE),40例对照组患者入院后急诊行LC联合LCBDE术。结果 观察组两次手术时间显著长于对照组(P<0.05),但术中出血量显著少于对照组(P<0.05);手术后观察组WBC计数、NEUT百分比、血清CRP和PCT水平均显著低于对照组(P<0.05);术后,观察组血清脑钠肽(BNP)和CK水平分别为(427.0±327.0)pg/ml和(95.0±30.0)U/L,显著低于对照组【分别为(944.0±648.0)pg/ml和(149.0±67.0)U/L,P<0.05】,而血清肌钙蛋白(TNT)和乳酸脱氢酶(LDH)水平分别为(62.8±54.5)pg/ml和(272.0±48.0)U/L,显著高于对照组【分别为(3...     

阿苯达唑致广州管圆线虫病患者肝损害的临床分析

目的 分析口服阿苯达唑治疗广州管圆线虫病致急性肝损害作用. 方法 对41例广州管圆线虫病患者接受阿苯达唑治疗后出现的急性肝损害(肝功能变化)、基础疾病及转归进行分析. 结果 1)用阿苯达唑治疗广州管圆线虫病疗程结束后,26例患者丙氨酸氨基转移酶(ALT)升高,范围为42.00～252.00 U/L,平均(97.66±56.66)U/L;9例患者天门冬氨酸氨基转移酶(AST)增高,范围为41.00～131.00 U/L,平均(60.66±29.34)U/L;13例患者γ-谷氨酰转移酶(GGT)升高,范围为56.90～213.00 U/L,平均(99.52±46.65) U/L;碱性磷酸酶(ALP)、蛋白质及胆红素水平未见显著变化;2)阿苯达唑治疗过程中,同时加用保肝药物(甘利欣、肝泰乐)组68.42%(13/19)氨基转移酶升高,未使用保肝药物组59.09%(13/22)氨基转移酶升高,差异无统计学意义(P＞0.05);3)肝功异常者停用阿苯达唑后开始出现好转,出院2个月后血清氨基转移酶大多恢复至正常水平. 结论 口服阿苯达唑可导致急性肝损害,其剂量须根据患者具体情况进行调整,临床应用时注意监测肝功能,并合理使用保肝药物.     

原发性硬化性胆管炎28例临床特征及疗效回顾分析

目的分析原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)的临床特征及诊治经验,以提高对该病的认识。方法对我院2000年1月-2010年12月收治确诊的28例PSC患者的临床特征、生化、免疫学、组织学及治疗等资料进行回顾性分析。结果 28例PSC患者中男21例(75%),女性7(25%),中位诊断年龄52岁(4～69岁);临床表现主要为黄疸(89.3%,25/28)、纳差(32.1%,9/28)、皮肤瘙痒(25.0%,7/28)、肝区疼痛(25.0%,7/28);实验室检查表现为总胆红素水平升高(89.3%,25/28);均以结合胆红素升高为主,肝酶升高(89.3%,25/28),包括谷丙转氨酶、谷草转氨酶、碱性磷酸酶及γ-谷氨酰转肽酶,但均以轻度升高为主;20例(90.9%,20/22)患者经胆管造影检查得到确诊,主要表现为肝内外胆管变细、粗细不均和/或走行僵直,其中经内镜逆行胰胆管造影(ERCP)确诊11例(100%,11/11)、经磁共振胰胆管造影(MRCP)确诊6例(85.7%,6/7)、经皮肝穿刺胆管造影(PTC)确诊2例(66.7%,2/3),经T管造影确诊1例(100%,1/1);其余8例(100%,8/8)患者经肝穿刺活检病理组织学检查确诊,主要表现为汇管区胆管周围炎症及纤维组织增生;25例患者经药物治疗后,13例(52%,13/25)生化指标有不同程度好转,3例经手术治疗的患者1例(33.3%,1/3)好转。结论 PSC发病机制未明,好发于男性,黄疸为主要症状,主要表现为肝酶和胆红素轻度升高,确诊应首选胆道造影检查,目前尚无特效治疗药物。     

原发性硬化性胆管炎27例临床病理特点分析

目的 总结原发性硬化性胆管炎(PSC)的临床病理特点,提高临床医师对该病的认识.方法 回顾性分析27例PSC患者的临床资料并随访患者当前情况.临床资料主要包括各项肝功能指标、自身抗体及免疫球蛋白,影像学及病理学检查结果将PSC患者分为大胆管型或小胆管型;治疗措施包括药物、内镜及手术治疗,治疗3～6个月后,ALT≤1.5倍、Tbil≤2倍、ALP≤2.5倍正常上限为有效.大胆管型PSC与小胆管型PSC的疗效比较采用非参数检验CMH法,P＜0.05为差异有统计学意义.结果 27例PSC患者中,男性7例,女性20例,平均年龄47.6岁.大胆管型PSC 18例,小胆管型PSC 9例.主要临床表现为黄疸(85.2%)、瘙痒(48.1%)、乏力(68.4%)、腹痛(40.7%)及发热(14.8%);常见体征包括:肝大(44.4%)、脾大(48.1%)、腹水(14.8%)等;胆红素升高10倍以上者占30.8%,IgG异常率81.8%、抗核抗体阳性率69.6%、抗中性粒细胞胞浆抗体阳性率52.9%;合并溃疡性结肠炎者占22.2%,干燥综合征患者占22.2%.经药物、内镜或手术治疗后,部分病例病情缓解,3例死亡;小胆管型PSC的疗效优于大胆管型PSC(66.7%比33.3%,x2=4.173,P=0.041).结论 本组少数PSC患者合并溃疡性结肠炎.小胆管型PSC治疗效果优于大胆管型PSC,提示早期诊治的必要性.     

血清CA199与胆管结石及胆管炎的关系

目的 研究胆管结石合并胆管炎患者血清糖类抗原CA199水平与胆红素及肝酶谱之间的关系,探讨胆管结石并胆管炎患者血清CA199升高的原因及临床意义.方法 以350例胆管结石合并胆管炎患者为病例组,350例健康体检者为对照组,回顾性分析患者的血清CA199水平,用SPSS统计软件分析血清CA199水平与血清胆红素及肝酶谱水平之间的关系.结果 病例组患者血清CA199水平明显高于健康对照组;病例组血清CA199与血清总胆红素、直接胆红素、碱性磷酸酶、γ-谷氨酰转移酶之间呈正相关,与谷丙转氨酶、谷草转氨酶之间无相关;病例组中胆管梗阻解除及炎症控制后CA199水平明显下降.结论 胆管结石、胆管炎是造成血清CA199水平升高的原因之一,治疗前后动态观察CA199水平变化有助于良恶性疾病鉴别.     

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.