急性心肌梗塞后梗塞相关血管再灌注对QTc离散度的影响

目的观察２７例急性心肌梗塞（ＡＭＩ）患者梗塞相关血管（ＩＲＡ）早期再灌注对ＱＴｃ离散度（ＱＴｃｄ）的影响。方法对２７例ＡＭＩ予以静脉溶栓，于溶栓后９０分钟进行选择性冠状动脉造影，在溶栓前后作同步记录１２导联心电图测量ＱＴｃｄ，并与４３例冠状动脉造影正常者进行对照。结果ＡＭＩ组溶栓前与对照组间ＱＴｃｄ差异有极显著性（８６６±１２２ｍｓｖｓ３５．８±１６７ｍｓ，Ｐ＜０００１），前壁与下壁梗塞之间ＱＴ离散度差异无显著性。静脉溶栓后９０分钟冠脉造影显示ＩＲＡ血流达到ＴＩＭＩＩ～ＩＩ者，溶栓后２小时ＱＴｃｄ显著降低（８７２±１２８ｍｓｖｓ５９．５±１３６ｍｓ），而ＩＲＡ未开通者其ＱＴｃｄ在溶栓前后始终保持较高水平，恢复速度显著慢于开通组。６例溶栓前有恶性室性心律失常者其ＱＴｃｄ明显高于无伴心律失常者（９４８±９２ｍｓｖｓ８４．２±１２０ｍｓ，Ｐ＜００５），溶栓后其ＩＲＡ血流均达ＴＩＭＩＩＩ级，ＱＴｃｄ降至６８３±８８ｍｓ，室性心律失常消失。结论成功地溶栓再灌注可使ＱＴｃｄ显著降低，改变其自然演变过程。ＩＲＡ早期再灌注，可减少危险性心律失常的发生。     

急性心肌梗死早期溶栓治疗对QT离散度及恶性室性心律失常的影响

研究急性心肌梗死（ＡＭＩ）后溶栓治疗对ＱＴ离散度（ＱＴｄ）及恶性室性心律失常（ＭＶＡ）事件的影响。回顾性选择分析ＡＭＩ患者７５例（溶栓治疗组４３例、未溶栓组３２例）,通过测量入院时及入院后２４ｈ常规心电图计算ＱＴｄ、校正ＱＴｃ（ＱＴｃｄ）,并在入院后一周内心电监护观察ＭＶＡ事件发生情况。溶栓再通组ＱＴｄ、ＱＴｃｄ较溶栓前显著缩短（４２．６±１４．３ｍｓｖｓ７１．７±１６．９ｍｓ,４５．９±１７．４ｍｓｖｓ７４．８±１８．５ｍｓ,Ｐ均＜０．０１）;溶栓未通组、未溶栓组入院２４ｈ期间ＱＴｄ、ＱＴｃｄ无明显变化（Ｐ＞０．０５）。ＱＴｄ、ＱＴｃｄ≥９０ｍｓ者ＭＶＡ事件明显高于＜９０ｍｓ者（７０．６％ｖｓ１０．２％,Ｐ＜０．０１）,溶栓再通组ＭＶＡ事件与溶栓未通组比较趋于减少（１１％ｖｓ２８％）。结论：ＡＭＩ后成功的溶栓治疗可以缩短心室复极的ＱＴｄ,从而可能减少ＡＭＩ后早期ＭＶＡ的发生;无效的溶栓治疗对ＡＭＩ近期预后无任何影响。     

溶栓治疗老年人急性心肌梗死34例分析

目的观察老年人急性心肌梗死（ＡＭＩ）溶栓治疗的安全性和有效性。方法７１例７０岁以上老年ＡＭＩ患者分成溶栓组（３４例）和对照组（３７例），比较其临床结果。结果（１）梗死相关动脉（ＩＲＡ）的再通率溶栓组显著高于对照组（６１．８％及１３．５％，Ｐ＜０．０１）；（２）溶栓明显改善了老年ＡＭＩ患者的左室射血分数（６３％及５２％，Ｐ＜０．０５）；（３）溶栓显著降低了老年ＡＭＩ患者的住院病死率（３５．１％对１４．７％，Ｐ＜０．０５），降幅为２０．４％；（４）溶栓组发生出血并发症６例（皮肤淤斑４例，上消化道出血２例），无严重出血（无需输血）并发症及脑卒中发生。结论对无禁忌证的老年人ＡＭＩ进行溶栓治疗，可以增加其血管再通率、改善心功能及降低病死率。     

持续灌流法经皮冠状动脉球囊成形术治疗老年人心肌梗塞的临床价值

对比分析了老年急性心肌梗塞（ＡＭＩ）患者行持续灌流法冠状动脉球囊成形术（ＣＰＰＴＣＡ）２０例（３６支）和常规冠状动脉球囊成形术（ＰＴＣＡ）１８例（２４支）的疗效。两组患者术前冠状动脉狭窄的严重程度及左心室功能相似（Ｐ＞０．０５）。与ＰＴＣＡ组比较，ＣＰＰＴＣＡ对术中阻断血流的心肌有重要保护作用，且术中并发症少（０比３８．９％，Ｐ＜０．０１），残余狭窄轻（１２％±８％比２８％±１８％，Ｐ＜０．０５），再狭窄率（０比２２％，Ｐ＜０．０５），再梗塞率（５％比３３％，Ｐ＜０．０５）及病死率（０比２２％，Ｐ＜０．０５）低。     

急性心肌梗死溶栓治疗肌钙蛋白T动态变化

目的：观察静脉溶栓治疗急性心肌梗死（ＡＭＩ）患者肌钙蛋白Ｔ（ＴｎＴ）的血清浓度动态变化特点，探讨其对溶栓疗效判定价值。方法：采用全自动酶联免疫吸附测定（ＥＬＩＳＡ）法，测定３９例ＡＭＩ患者肌钙蛋白Ｔ血清浓度变化。结果：１４例ＡＭＩ溶栓再通组的肌钙蛋白Ｔ第１高峰时间（１３．４３±４．０３小时）较１３例溶栓未通组（１８．６２±４．０３小时，Ｐ＜０．０１）及１２例非溶栓组（２４．００±１４．８７小时，Ｐ＜０．０５）明显前移；肌钙蛋白Ｔ发病第１２小时／第７２小时比值，在溶栓再通组（２．４４±１．５２）大于溶栓未通组（１．１２±０．８３）及非溶栓组（１．００±１．０３，Ｐ均＜０．０５）；对ＡＭＩ溶栓再通预测的敏感性、特异性及准确性：在以肌钙蛋白Ｔ第１峰时间≤１４小时为界时分别为７１．４％、８４．６％、７８．０％，在肌钙蛋白Ｔ第１２小时／第７２小时比值≥２．０时为６６．７％、８４．６％及７５．７％。结论：肌钙蛋白Ｔ对ＡＭＩ溶栓疗效具有一定的判定价值。     

急性心肌梗死患者溶栓对心率变异性的影响

选取急性心肌梗死（ＡＭＩ）患者３１例，并设正常对照组。采用时域法和频域法研究ＡＭＩ溶栓治疗后心率变异性（ＨＲＶ）的改变。其结果显示:在ＡＭＩ再通组，其ＳＤＮＮ为１０８．１４±２８．４０ｍｓ，高于未通组的６２．６７±２６．１２ｍｓ（Ｐ＜０．０１）但低于对照组的１２８．４７±３５．６１ｍｓ（Ｐ＜０．０５）；其高频面积为２８４．８２±２７６．４５，大于未通组的（１３５．６８±１１７．８２ｂｐｍ２／Ｈｚ，Ｐ＜０．０５）但小于对照组的（６９４．３５±５４０．１１ｂｐｍ２／Ｈｚ，Ｐ＜０．０１）；其低频面积／高频面积为０．９３±０．７１，小于未通组的１．７４±１．０７（Ｐ＜０．０５），但大于对照组的０．５３±０．６１（Ｐ＜０．０１）；其低频面积虽大于未通组和小于对照组，但无统计学意义。本结果表明，ＡＭＩ后ＨＲＶ变小，其迷走神经活性下降，交感神经作用相对增强；溶栓再通后的ＨＲＶ增大，其迷走神经兴奋性增高，交感神经作用减弱。故成功的溶栓治疗对改善ＡＭＩ后自主神经系统功能失衡和减少由此引起的致命性心律失常等事件的发生有积极意义     

300万U尿激酶溶栓治疗急性心肌梗塞231例的临床初步总结

目的为观察３００万Ｕ尿激酶（ＵＫ,由广州天普洛欣生物制品厂生产）静脉溶栓治疗急性心肌梗塞（ＡＭＩ）的临床疗效和安全性。方法对６１１例ＡＭＩ患者进行ＵＫ静脉溶栓治疗,Ｂｏｌｕｓ法给药。随机分为Ａ组（３００万Ｕ）、Ｂ组（２５０万Ｕ）和Ｃ组（１５～２００万Ｕ）。对比观察三组患者临床疗效、副作用、５周病死率、左室射血分数（ＥＦ）、再通时间、各种严重并发症发生率和心肌断层显像（ＳＰＥＣＴ）及心肌缺血面积（ＩＭＡ）定量分析。结果按临床判定标准,Ａ组和Ｂ组梗塞相关血管（ＩＲＡ）再通率各为８１．８％和７４．１％,均显著高于Ｃ组（６９．０％,Ｐ＜０．０１,０．０５）。三组５周病死率分别为３．０３％、４．１５％和８．５６％,Ａ组显著降低（Ｐ＜０．０５）。Ａ组和Ｂ组比Ｃ组轻度出血和中重度出血发生率略有增高,但差异无显著性（Ｐ＞０．０５）,三组均未发生脑出血。Ａ组和Ｂ组ＥＦ≥５０％者所占比率显著增高Ｃ组。Ａ组各种严重并发症发生率均显著降低（Ｐ＜０．０５或０．０１）。Ａ组和Ｂ组再通时间均显著缩短［（９９．６３±９．２４）ｍｉｎ对（１５２．６１±１０．９２）ｍｉｎ,Ｐ＜０．００１;（１１２．２１±７．２２）ｍｉｎ对（１５２．６１±１０     

早期静脉溶栓治疗对老年人急性心肌梗塞近期预后的影响

为探讨静脉溶栓治疗对老年（６０岁以上）急性心肌梗塞（ＡＭＩ）患者近期预后的影响。方法对比分析２０例尿激酶静脉溶栓治疗与３８例非溶栓治疗的老年人ＡＭＩ患者住院期间临床疗效。结果显示溶栓组住院期间４周内病死率明显低于非溶栓组（Ｐ＜０．０５）,且心绞痛、心力衰竭及严重心律失常、泵衰竭的发生率明显低于非溶栓组（Ｐ＜０．０５）。临床判断梗塞相关血管（ＩＲＡ）再通率为７５．０％（１５／２０）,０～６小时ＩＲＡ再通率为８３．３％（１０／１２）,６～１２小时为６２．５％（５／８）,溶栓组无一例发生颅内出血及过敏反应。结论　提示用尿激酶静脉溶栓治疗老年ＡＭＩ为一种安全有效的方法,ＡＭＩ后梗塞相关血管及时有效再灌注有利于改善心肌梗塞的近期预后。     

溶栓治疗老年急性心肌梗塞患者的利弊分析

将１０６例急性心肌梗塞（ＡＭＩ）患者分为两组,≥７０岁组３１例,＜７０岁组７５例,均在发病６小时内接受尿激酶静脉溶栓治疗。结果：≥７０岁组与＜７０岁组比较,血管再通率分别为６７．７％及７０．６％（Ｐ＞０．０５）,４周病死率分别为６．５％及５．３％（Ｐ＞０．０５）,左室射血分数（ＬＶＥＦ）分别为０．４９±０．１２及０．５１±０．１４（Ｐ＞０．０５）,出血并发症分别为４５．１％及２０％（Ｐ＜０．０１）。血管再通者与血管未通者比较,病死率分别为２．７％及１２．５％（Ｐ＜０．０５）,ＬＶＥＦ分别为０．５６±０．１４及０．４４±０．１１（Ｐ＜０．０１）。因此认为,溶栓治疗ＡＭＩ的疗效与年龄无关,而与血管是否再通密切相关。老年ＡＭＩ患者行溶栓治疗虽出血等并发症高,但其利大于弊。     

溶栓及PTCA治疗急性心肌梗塞92例临床分析

本文总结１９９１年８月至１９９６年４月应用溶栓及ＰＴＣＡ治疗ＡＭＩ９２例，男７６例，女１６例，年龄４６～７０岁之间，平均年龄６０．２±１０．５岁。治疗分为：①冠状动脉内输注尿激酶（ＩＣＵＫ）组３２例；②静脉输注尿激酶（ＩＶＵＫ）组４１例；③经皮冠状动脉腔内成形（ＰＴＣＡ）组１９例。全组再通６９例，总再通率为７５．０％，ＩＣＵＫ组、ＩＶＵＫ组、ＰＴＣＡ组再通率分别为７５．０％、６５．７％和９４．７％三组再通率比较有显著差异。三组患者近期预后比较：全组９２例，死亡９例，死亡率９．７８％，８例发生于梗塞血管未通者，１例发生于血管再通者。ＩＣＵＫ组３２例，死亡３例（９．３７％），发生心功能不全８例（２５．０％）；ＩＶＵＫ组４１例，死亡５例（１２．０％），发生心功能不全１１例（２６．８３％）；ＰＴＣＡ组１９例，死亡１例，死亡率为５．２６％，ＰＴＣＡ组无心功能不全者。     

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.