2009年青海省兴海县儿童大骨节病病情及影响因素调查

目的 调查青海省兴海县大骨节病相对活跃病区儿童大骨节病流行现状,以及当地儿童硒营养水平和家庭主食粮食T-2毒素污染水平.方法 2009年对兴海县唐乃亥乡上、中、下3个村7～ 12岁儿童进行右手X线拍片,根据《大骨节病诊断标准》(GB 16003-1995)进行诊断.同时采集拍片儿童的枕部发样、饮水以及主食粮食(小麦和/或面粉),2,3-二氨基萘荧光法测定其头发、饮水和主食粮食硒含量,酶联免疫吸附试验(ELISA法)检测主食粮食T-2毒素污染水平.结果 儿童大骨节病X线总检出率为12.20％(31/254),其中下村X线检出率达到14.97％(22/147),上村X线检出率为9.52％(6/63),中村X线检出率为6.82％(3/44).病区儿童内外环境硒水平普遍较低,头发、饮水、小麦、面粉硒含量分别为(0.250±0.136)mg/kg、(0.16±0.05)μg/L、(0.0045±0.0030)mg/kg、(0.0067±0.0116)mg/kg.病区儿童家庭主食粮食T-2毒素含量较高,小麦为(78.91±46.17)μg/kg;面粉为(47.47±46.47) μg/kg.结论 青海省兴海县大骨节病相对活跃病区7～ 12岁儿童内外环境硒水平较低,而主食粮食T-2毒素污染水平较高,与当地儿童大骨节病病情分布基本一致.     

克山病发生的原因、条件和相关因素

目的 探索克山病发生的原因、条件与相关因素.方法 采用病例观察、流行病学调查、真菌学与真菌毒素学、分析化学等方法进行现场调查及实验室检测.结果 1973-1975,在克山病严重流行地区凋查了15家病户和1个病情爆发的村庄,发现每个病人在发病前半年至1年都食用过严重发霉的小米、玉米.取病区小米做微生物学检查,发现主要污染真菌是黄绿青霉菌,占20％,毒素是黄绿青霉素(CIT).克山病致病因子进入人体的途径是病区产的粮食而不是饮水,不同种类粮食的传病作用不同,小米、玉米传病,小麦不传.依据全国地方病监测数据,1990年后全国范围已无克山病病例报告,同时克山病病因物质也在减少,但不如病情变化那样快.1983年后实现的农村、农业改革,显著地提高了粮食的卫生学质量,对消除克山病威胁起到了决定性作用.克山病病区分布在寒冷、干燥的西北高原和温暖、潮湿的东南平原交界带,病区在浅山丘陵区而不在平原,平均温度低、湿度适中,适合真菌的生长和产毒.用CIT毒素污染粮食,按体质量4 mg/kg剂量喂养大鼠,4周即可出现心肌坏死,线粒体肿胀、增生和破坏等与克山病相似的改变.结论 克山病的病因物质是CIT;发生条件是西北干旱高原与东南温湿平原交接地带的特殊地理、气候状况和农业生产中粮食保管不良、霉焐;影响因素繁多,主要是促进接触病因物质以及易感的生理因素,包括年龄、性别、职业及接触的机会.     

2008年四川省阿坝州大骨节病相对活跃病区硒及T-2毒素水平调查

目的 调查2008年四川省阿坝州大骨节病相对活跃病区儿童内、外环境含硒量及主食粮T-2毒素污染水平.方法 对阿坝州11个县48个监测点进行7～13岁儿童右手X线拍片,根据X线检出结果以及历史病情选择大骨节病相对活跃病区作为调查现场.对大骨节病相对活跃病区中7～13岁儿童进行调查采样,测定尿硒、发硒、水硒、粮硒及主食粮中T-2毒素水平.结果 共拍X线片2145张,其中阳性66张,儿童大骨节病X线检出率为3.08%(66/2145).选择马尔康县、金川县[X线检出率分别为10.98%(29/264)、8.52%(19/223)]和壤塘县[历史重病区,X线检出率为0.75%(3/400)]3个大骨节病相对活跃病区为调查现场.3个县7～13岁儿童尿硒水平[(10.41±4.67)、(10.11±3.65)、(8.42±2.68)μg/g Cr]比较,差异无统计学意义(F=0.901,P>0.05).马尔康县儿童发硒[(0.18±0.04)mg/kg]低于金川县[(0.21±0.04)mg/kg,P<0.05],金川县水硒[(0.225±0.124)μg/L}低于马尔康县和壤塘县[(0.320±0.092)、(0.339±0.105)μg/L,P均<0.05],金川县粮硒(0.0033 mg/kg)低于马尔康县和壤塘县(0.0258、0.0137 mg/kg,Z值分别为-6.146、-3.042,P均<0.017).3个县粮食粉末中T-2毒素水平(19.60、17.95、26.25 ng/g)比较,差异无统计学意义(X2=5.623,P>0.05):马尔康县粮食颗粒中T-2毒素水平(10.72 ng/g)高于金川县和壤塘县(3.74、3.30 ng/g,Z值分别为-6.315、-4.407,P均<0.017);粮食粉末中T-2毒素水平均高于粮食颗粒(Z值分别为-6.690、-5.493、-3.676.P均<0.05).结论 阿坝州3个大骨节病相对活跃病区7～13岁儿童内、外环境硒营养状态以及家庭主食粮T-2毒素水平与当地大骨节病病情分布基本一致.     

山西省2007～2008年克山病病情调查结果分析

目的了解山西省克山病病情,为防治工作提供科学依据。方法在历史重病区永和、石楼每县选择1个病区乡,吉县选择2个病区乡,每乡选择1个病区村;每村选择600人左右,开展临床查体和心电图描记,同时采集部分居民发样和主食粮样检测内外环境硒含量水平。结果共检查3 285人,检出克山病病人142例,总检出率型4.32%。其中慢型克山病病人5例,检出率0.15%;潜在型克山病病人137例,检出率4.17%。检出异常心电图369例,异常率11.23%。克山病人心电图异常改变以完全性右束枝传导阻滞和ST-T改变为主,分别占到总异常项次的43.6%和24.8%。克山病病例男女性别比为1∶1.09。小麦、玉米、小米、豆面、头发样品硒含量水平分别为(0.020±0.006)、(0.014±0.009)、(0.017±0.012)、(0.051±0.024)和(0.051±0.024)mg/kg。结论本次调查山西省克山病检出率高于2007年全国平均水平,代表了山西省病情最严重的情况。但从总体上来说,全省病情基本稳定。研究结果再次证明,克山病病区内外环境处于低硒水平。克山病仍是严重的公共卫生问题之一,应该充分认识到防治监测工作的长期性、重要性和艰巨性。     

汉源县影响大骨节病病情下降的主要因素调查

目的研究大骨节病病情与自然、经济、生产、生活等相关因素的关系.方法按照大骨节病监测方案要求,连续进行13年的病情监测,调查病区居民的膳食结构及生产、生活、经济收入情况,将收集的资料进行分析.结果病区居民年人均主食自产面粉50 kg时,儿童发硒<0.10 μg,大骨节病X线阳性检出率高达50%.自产面粉减少到10 kg,儿童发硒含量>0.16 μg,X线阳性检出率下降到4.5%.结论大骨节病流行的必备因素是病区自产面粉,同时也受自然、经济、生产、生活等因素的制约与影响.     

嫩江县石头沟村大骨节病病情调查报告

目的通过病村(嫩江县石头沟村)典型调查，了解黑龙江省大骨节病病情现况。方法对94名儿童和89名成年志愿者进行右手X线拍片检查；采集农户自产粮食进行T-2毒素检测。结果儿童和成人大骨节病患病率分别为2．13％和67.42％；农户自产面粉中T-2毒素水平为4．4～22．8ng／g。结论初级预防已取得成功．病区粮食中T-2毒素水平降至很低，儿童大骨节病病情已经基本控制；成人大骨节病问题严重，成为中老年人群疾病的重要部分．亟待解决。     

陕西省大骨节病病情现状与相关因素调查

目的 进一步掌握陕西省大骨节病病情消长态势和相关环境因素对大骨节病发生、发展的影响,为今后大骨节病的防治决策提供依据.方法 在陕西省大骨节病病区范围内分别选择了6个项目调查点和20个省级自设监测点.临床检查7～12岁儿童2568例,右手X线拍片1788例.采集项目点粮样600份和发样300份,测定粮硒、发硒及食粮(180份)T-2毒素水平,调查相关因素与病情的关系.结果 全省23个病区县(区)26个调查点中,大骨节病临床Ⅰ度以上患者无检出,X线总检出率为1.29%;儿童发硒为(0.37±0.07)mg/kg,粮食硒(0.049±0.016)mg/kg,粮食T-2毒素(3.82±4.38)μg/kg.结论 陕西省儿童大骨节病病情处于基本控制后的平稳低发态势,病区内外环境硒水平的明显升高、饮食结构的明显改善、粮食卫生学质量的提高及经济收入的增加是病情得到控制的主要因素,应进一步深化防治措施落实和加强病区群众健康教育.     

山西省儿童大骨节病控制和消除评价

目的评价山西省儿童大骨节病病情及防治效果,为实现大骨节病消除目标提供依据。方法 2012—2015年对全省35个大骨节病区县开展2次病情调查,每个县随机抽取5个病区乡(镇,不足5个则全部抽取),每个乡(镇)随机抽取3个病区村(不足3个则全部抽取),所调查病区村的7~12岁儿童全部进行临床及X线检查,并了解调查村防治措施落实情况;按照《重点地方病控制和消除评价办法》,评价大骨节病防治技术和管理指标。结果第一次共调查了318个病区村、10 872名7~12周岁儿童,X线检出5例干骺端阳性、阳性检出率0.046%;第二次共调查了293个病区村、10 510名7~12周岁儿童,X线未检出阳性病例;X线检出率差异无统计学意义(χ2=3.067,P0.05);所有调查的病区村7~12周岁儿童未检出大骨节病临床病例,以村为单位的X线阳性检出率在3%以下,且绝大多数村为零检出,无手部骨端改变病例;大骨节病防治工作组织管理得分均在85分及以上。结论山西省35个大骨节病病区县均达到消除标准;应继续加强大骨节病病情监测和健康教育工作,持续巩固防治成果。     

2006年青海省兴海县大骨节病调查报告

目的 通过对青海省兴海县大骨节病新发病区调查,了解大骨节病病区分布范围,流行强度和流行趋势,为大骨节病防治研究提供依据.方法 按全国大骨节病监测方案要求,对兴海县唐乃亥乡,子科滩镇,桑当乡及曲什安乡共6个村的7～13岁儿童进行流行病学调查,临床检查及X线拍片,并采集发样,粮样,土样,水样.用2,3-二氨基萘荧光法进行含硒量测定.结果 在4个调查点的6个村共临床检查7～13岁少年儿童373人,检出大骨节病45例,检出率为12.06%.X线拍片347人,X线阳性75例,阳性检出率为21.61%.子科滩镇泉曲村含硒量最低,发硒为(77.70±42.04)μg/kg,粮硒为(7.44±6.93)μg/kg,曲什安乡才乃亥村含硒量最高,发硒为(103.88±58.57)μg/kg,粮硒为(29.58±24.11)μg/kg.结论 兴海县4个调查点为大骨节病新病区.调查点大骨节病病情严重,致病因子活跃.     

克山病的病因与流行机制

目的报告关于克山病病因的研究结果。方法病因流行病学方法；病理学和实验病理方法；文献学方法。结果克山病病因流行病学研究所见：克山病的病因是特定自然、社会、生活条件下形成的黄绿青霉毒素(citreoviridin，CIT)中毒；传播途径是病区产的粮食与饮水无关；玉米、小米等粮食传病，小麦不传或少传；粮食在湿冷环境中被青霉菌污染并产生CIT毒素。克山病的病理、病理化学、实验病理研究所见：从亚急型克山病以及解剖可见，心肌的早期病理改变是线粒体功能与结构的破坏。ATPases同琥珀酸脱氢酶等系列心肌酶的活性被明显抑制、改变、比例失衡，同时线粒体的结构也出现了相应的改变。心肌线粒体肿胀，嵴膜破坏，线粒体膜融合、消失。CIT毒素对心肌线粒体的作用机制：CIT是ArrP的类似物，可与AIPases相作用而降低其活性。由此开始，逐步发展、变化，最终导致克山病特异的心肌坏死。结论上述的3个方面基本是相互独立的各自发现，但可紧密的相互认证，相互支持，支持克山病的致病因子可能是青霉菌污染粮食产生的黄绿青霉毒素。     

Gastro-oesophageal reflux disease and respiratory disease

Abstract An epidemiological survey showed that respiratory symptoms with gastro-oesophageal reflux (GER) were twice as high as those without GER symptoms. In 46 cases of unknown chronic cough or asthma, 67% had positive oesophageal pH monitoring. Of 34 patients with snoring and reflux symptoms, 16 (47.1%) were confirmed as positive for obstructive sleep apnoea (OSA) and GER. Anti-reflux therapy significantly improved both GER and OSA.     

Report: Association of coronary artery disease and valvular heart disease in chile

This study analyzes the prevalence of coronary artery disease (CAD) among patients with rheumatic valvular heart disease (VHD) in Chile. Coronary angiography was performed in all patients referred to cardiac catheterization with VHD who were over age 50 years and who had angina or ECG signs of ischemia. A total of 100 patients entered the study. Significant CAD (greater than 50% obstruction) was found in 14% of the cases: 7% in patients with mitral valve disease (MVD), 18% in aortic valve disease (AVD), and 21% in combined mitral and aortic valve disease (MAVD). Angina was present in 14% of the patients with MVD, 63% with AVD, and 53% with MAVD. Only 57% of patients with CAD had angina pectoris; 20% with angina had CAD. Hemodynamic parameters and left ventricular ejection fraction were not correlated with the presence or absence of CAD. We conclude that in patients with valvular heart disease, the incidence of CAD is lower in Chile than previously reported in the English literature. We confirmed the fact that angina is often not associated with CAD, and that CAD is often present in the absence of angina.     

Therapeutic and management challenges in Wilson's disease

Abstract   Wilson's disease, an inborn error of copper metabolism, is an important cause of liver disease in India. A high index of suspicion is necessary for diagnosis as it can have a varied clinical presentation (e.g. all forms of acute and chronic liver disease, minimal to severe neurological disease, bony deformities, hemolytic anemia). Hepatic copper estimation is the most reliable diagnostic test, but is not easily available in India. In the absence of hepatic copper, a low ceruloplasmin, high 24 h urinary copper and presence of KF rings aid in making the diagnosis (at least two of these). Life-long therapy is necessary with D-Penicillamine, Trientine or zinc. Though response to therapy may be unpredictable, acute and early presentations such as fulminant hepatic failure have a poor outcome without liver transplantation. The siblings of all cases must be screened, as early diagnosis and treatment results in a good outcome. The identification of the Wilson's disease gene on chromosome 13 has led to the possible use of molecular genetics (haplotype and mutational analyses) in the diagnosis of the disease.     

Risk of cardiovascular disease in inflammatory bowel disease

Abundant scientific evidence supporting an association between inflammatory bowel disease(IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.     

Caroli's disease in congenital hepatic fibrosis and infantile polycystic disease

ABSTRACT— Two of three patients with infantile polycystic disease and all three patients with congenital hepatic fibrosis revealed multiple gross cystic dilatation of the intrahepatic biliary tree, referred to as Caroli's disease. All three patients with congenital hepatic fibrosis showed recurrent cholangitis related to coexisting Caroli's disease, and two of them died of sepsis following cholangitis. There were several common morphologic findings in the intrahepatic biliary tree of macroscopic and microscopic levels in infantile polycystic disease and congenital hepatic fibrosis with Caroli's disease: 1. irregular, non-obstructive dilatation of the duct lumen; 2. bulbar protrusion of the duct wall into the lumen; and 3. bridge formation of the duct wall across the lumen. These ductal changes might be caused by a combination of uneven and disproportionate overgrowth of biliary epithelia and their supporting connective tissue. This pathogenetic mechanism might be operative along the entire intrahepatic biliary system in this disease group, and involvement of the smaller levels in early life might result in infantile polycystic disease and congenital hepatic fibrosis and simultaneous or possibly later involvement of the larger levels in Caroli's disease.     

Acquired von Willebrand disease and storage pool disease in chronic myelocytic leukemia

Platelet function was evaluated in 20 patients with chronic myelocytic leukemia (CML), all Ph positive. Seven showed abnormal epinephrine-induced aggregation, while four had impaired both ADP- and collagen-induced aggregation. The platelets of all patients aggregated with arachidonic acid, thus ruling out cyclooxygenase or lipoxygenase deficiency. The intracellular concentrations of ATP and ADP were significantly below normal, and the ratio of ATP/ADP was greater than normal in all 12 patients. ATP released from platelets by Lumi-aggregometer was reduced. In four patients with abnormal ristocetin-induced aggregation, vWF:Ag, RCoF, and FVIII:C were all reduced. No significant inactivation of factor VIII was induced in normal plasma by incubation with patient's plasma. The crossed immunoelectrophoretic analysis revealed that vWF:Ag in these patients was mainly composed of more anodic component as compared with that of normal plasma. The ratio of vWF:Ag/RCoF was significantly greater than normal. A marked increase of factor VIII and a rapid return of vWF:Ag and RCoF to the baseline after the 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. Transient increase in vWF:Ag after the infusion of DDAVP appeared with less anodic forms and in the same relative proportion as that in normal plasma. The present study shows that in some patients with CML storage pool disease occurs with acquired von Willebrand disease.     

High one year mortality in adults with sickle cell disease and end-stage renal disease

Adequate pre-dialysis care reduces mortality among end-stage renal disease (ESRD) patients. We tested the hypothesis that individuals with ESRD due to sickle cell disease (SCD–ESRD) receiving pre-ESRD care have lower mortality compared to individuals without pre-ESRD care. We examined the association between mortality and pre-ESRD care in incident SCD–ESRD patients who started haemodialysis between 1 June, 2005 and 31 May, 2009 using data provided by the Centers for Medicare and Medicaid Services (CMS). SCD–ESRD was reported for 410 (0·1%) of 442 017 patients. One year after starting dialysis, 108 (26·3%) patients with incident ESRD attributed to SCD died; the hazard ratio (HR) for mortality among patients with SCD–ESRD compared to those without SCD as the primary cause of renal failure was 2·80 (95% confidence interval [CI] 2·31–3·38). Patients with SCD–ESRD receiving pre-dialysis nephrology care had a lower death rate than those with SCD–ESRD who did not receive pre-dialysis nephrology care (HR = 0·67, 95% CI 0·45–0·99). The one-year mortality rate following an ESRD diagnosis was almost three times higher in individuals with SCD when compared to those without SCD but with ESRD and could be attenuated by pre-dialysis nephrology care.     

慢性阻塞性肺疾病合并心血管疾病的危险因素及预后

目的 探讨慢性阻塞性肺疾病(COPD)合并心血管疾病(CVD)的危险凶素及预后.方法选取2004年至2009年我院因COPD急性加重住院的患者为研究对象,按是否合并CVD进行分组,所有患者均详细记录病史、体格榆查结果,记录血常规、血脂、血糖、心肌酶等化验及肺功能、心电图、超声心动网等检查.对结果采用SPSS 16.0软件进行分析.结果两组患者在年龄、性别、吸烟史方面差异无统计学意义,COPD+CVD组患者体质量指数(BMI)均值(24.29±4.07)kg/m2,高于COPD组(P=0.011);COPD+CVD组合并高血压、高脂血症、糖尿病的比例与COPD组相比[(64.70%vs 58.24%)、(17.65%vs 9.89%)、(26.47%vs 8.79%)],只有合并糖尿病的比例差异具有统计学意义(P=0.023);COPD+CVD组FEV1/FVC、FEV1%pred(吸入支气管扩张剂后)均值低于COPD组[(46.64±8.10)%vs(50.79±10.94)%、(44.62±9.80)%vs(50.21±13.76)%],差异有统计学意义(P值均<0.05),且COPD+CVD组肺功能Ⅲ～Ⅳ级的比例高于COPD组(76.47%vs 49.50%)(P=0.016);COPD+CVD组患者PaO2低于C()PD组[(67.67±10.31)mm Hg vs(73.74±13.67)mm Hg](P=0.038);COPD+CVD组在与炎症相关的指标如白细胞、中性粒细胞比例、C反应蛋白(CRP)、超敏CRP及纤维蛋白原水平上均高于COPD组(P值均<0.05),而在血脂,血糖水平上的差异无统计学意义(P值均>0.05);COPD+CVD组患者平均住院大数、平均再住院次数、死亡患者比例高于COPD组[(21.12±9.83)d vs(17.75±7.37)d、(1.59±1.67)次vs(O.90±1.17)次、20.59%vs 7.69%],且差异有统计学意义(P值均<0.05).Logistic回归分析表明,BMI、是否合并糖尿病、肺功能、血氧水平及与炎症相关的指标都和COPD合并CVD存在一定相关性,但经多因素Logistic回归分析,只有CRP水平与COPD合并CVD 独立相关(P=O.026).结论传统的CVD危险冈素及肺功能的下降都在COPD合并CVD中起一定的作用,这些作用的机制可能与全身炎症和缺氧等因素有关.合并CVD的COPD患者预后差.

Abstract：

Objective To discussion the risk factors and prognosis of chronic obstructive pulmonary disease (COPD) with cardiovascular disease (CVD). Methods We choose the hospitalized patients diagnosis of AECOPD ( n = 125) during 2004-2009 and group them according to the combination of CVD or not. The history, physical examination, laboratory tests, lung function, ECG and echocardiography were recorded. All data were analysis by SPSS 16.0. Results Of the two groups, there are no significant difference in age, sex and smoking history. The BMI of the group COPD+ CVD is (24. 29± 4.07) kg/m2,higher than the group of COPD( P =0. 011). About combined disease, the percentage of hypertension of the COPD+CVD group, hypcrlipidemia, and diabetes, which are higher than the COPD group[ (64.70 %vs 58.24%),(17.65% vs 9.89%),(26.47% vs 8.79%)], but only the differences in the percentage of diabetes is significant statistically( P =0. 023). There are significant differences in lung function and the percentage of GOLD Ⅲ-Ⅳ between the two groups. The PaO2 level of the group COPD+CVD is lower than the COPD group [(67.67±10.31) mm Hg vs (73.74±13.76) mg Hg](P =0.038). About laboratory tests, there are significant differences in the inflammation-related indicators such as the count of white blood cell, the proportion of neutrophils, CRP, high sensitivity CRP and Fib( P<0.05) but no significant differences in blood glucose and lipids. The average length of stay, re-hospitalization and the proportion of patients died of COPD+ CVD group are higher than group COPD[( 21.12±9.83) days vs (17.75±7.3) days, (1.59 ± 1.67) times vs (0.90±0.17) times, 20.59~ vs 7.69%]. Logisticregression analysis showed that BMI, combined with diabetes or not, lung function, blood oxygen levels and inflammation-related indicators are all related with the increase of CVD in COPD. Multivariate Logistic regression analysis show that only CRP level is associated with the increase of CVD in COPD independently( P = 0. 026). Conclusions Traditional cardiovascular risk factors and the decline of lung function are both play a role in the increase risk of CVD in COPD. The mechanisms of these effects may be related to systemic inflammation and hypoxia etc. The prognosis is poor in COPD patients when they combined with CVD.     

Celiac disease and pulmonary hemosiderosis in a patient with chronic granulomatous disease

We report on a patient with the hitherto undescribed combination of chronic granulomatous disease, pulmonary hemosiderosis, and celiac disease. The hemosiderosis resolved with a gluten-free diet and glucocorticosteroid pulse therapy, but the restrictive lung function pattern remained unchanged. Lung function improved markedly by immunosuppression with daily glucocorticosteroid and azathioprine treatment.