大剂量聚乙二醇干扰素α-2a治疗基因1型丙型肝炎患者1例

1.病例资料:患者女性,48岁,汉族,辽宁籍.因"发现ALT升高2年余,间断乏力1年"就诊.患者2年前体检时发现ALT升高至70 U/L,无特殊不适主诉,1年前劳累后感觉乏力明显,检查结果显示ALT 150 U/L,血清抗-HCV阳性,HCV RNA 2.3 × 106拷贝/ml,并开始接受干扰素α-2b 3 MU 3次/周联合利巴韦林治疗,抗病毒治疗12周后血清HCV RNA 1.3×103拷贝/ml,ALT仍未复常,于2008年12月来我院就诊.患者20年前曾输血,既往无高血压和糖尿病史,排除其他肝脏疾病,无家族遗传病史和传染病史,无烟酒嗜好.     

大剂量干扰素治疗原发性无应答慢性丙型肝炎1例

1.病例资料:患者男性,22岁,汉族,职员.主因"反复肝功能异常4年"入院.患者4年前体检发现肝功能异常,ALT 126 U/L,无明显不适.在本院门诊检查抗-HCV阳性、HCV RNA阳性,诊断为慢性内型肝炎.因患者拒绝抗病毒治疗,故仅给予普通保肝、降酶治疗,1个月后ALT恢复正常.此后定期复查,ALT在正常～100 U/L之间波动.2年前检查结果显示:ALT 511 U/L、AST 226 U/L、总胆红素(TBil)28 μmol/L,住院治疗.     

抗病毒治疗肾移植后丙型肝炎复发患者1例

患者男性,36岁,汉族.因"反复肝功能异常1年"入院.2008年1月诊断"尿毒症",一直进行"血液透析"治疗维持肾功能;6月发现抗HCV阳性,HCV RNA 1.1×106 IU/ml;于6～12月采用聚乙二醇干扰素α-2a 180μg,每周1次皮下注射,联合利巴韦林900 mg/d抗病毒治疗,12月复查HCV RNA阴性,遂停止治疗.     

丙型肝炎患者治疗期间HCVRNA含量变化及其与血清ALT、前白蛋白、总胆红素的相关性研究

目的探讨丙型肝炎患者治疗期间HCV RNA含量的变化及其与血清ALT、前白蛋白(PA)、总胆红素(TBil)的相关性。方法选取我院收治的62例丙型肝炎患者作为研究对象,治疗前后采集外周静脉血进行HCV RNA含量、抗HCV、ALT、PA、TBil检测,对比治疗前后的HCV RNA阳性检出率及ALT、PA、TBil水平变化,分析HCV RNA含量与ALT、PA、TBil的相关性。结果治疗前,HCV RNA+抗HCV联合检测的阳性率为91.94%,明显比HCV RNA和抗HCV单独检测的阳性率更高(P0.05)。治疗后的HCV RNA、抗HCV、HCV RNA+抗HCV阳性率均明显低于治疗前,且HCV RNA阳性率明显低于抗HCV和HCV RNA+抗HCV阳性率(P0.05)。不同HCV RNA含量患者治疗前的抗HCV、TBil水平比较差异无统计学意义(P0.05),ALT、PA水平比较差异有统计学意义(P0.05)。与治疗前相比,4组不同HCV RNA含量(1.0×10~3、1.0×10~4、1.0×10~5、≥1.0×10~6)患者的ALT水平均明显降低、PA水平明显升高(P0.05)。相关性分析显示,丙型肝炎患者治疗前后的HCV RNA含量与ALT异常率、PA异常率均呈正相关(P0.05)。结论丙型肝炎患者治疗期间的HCV RNA含量与ALT、PA水平变化密切相关,同时进行HCV RNA含量、ALT、PA监测有助于更好地评估丙型肝炎治疗效果。     

聚乙二醇干扰素α-2a联合利巴韦林治疗普通干扰素应答不佳的慢性丙型肝炎1例

1.患者资料:男性,53岁,体质量83kg.6年前,出现肝区不适、食欲不振、肝功能异常,HCV RNA为5×106IU/ml,确诊为慢性丙型肝炎.曾接受干扰素(IFN)α-2b联合利巴韦林(RBV)1000 mg/d治疗,IFN α-2b初始剂量为3 MU,隔天肌注,治疗至12周时HCV RNA降至6×104 IU/ml,期间出现皮肤、黏膜干燥的轻微症状.由于病毒学应答情况不佳,当时采取IFN o-2b强化治疗方案(6 MU)继续治疗4周后,HCV RNA降至5×103IU/ml,但同时出现较严重的皮肤炎症反应,注射部位出现明显的泡状红疹,脸部、头颈部、肢端、手背、躯干部、臀部出现瘙痒性丘疹样红疹.随后,IFN α-2b剂量恢复至3 MU,给予皮质激素对症治疗.48周治疗结束时,HCV RNA阴转,皮肤炎症恢复正常,但随访6周后复发.     

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎对肝纤维化的影响

目的 研究聚乙二醇干扰素(pegylated interferon,Peg-IFN)α-2a联合利巴韦林(ribavirin,RBV)治疗慢性丙型肝炎(chronic hepatitis C,CHC)对肝脏硬度测定(liver stiffness measurement,LSM)值的影响.方法 选择我院2010年10月-2012年9月接受Peg-IFN α-2a(180 μg/周)联合RBV[10.6～15.0 mg/(kg·d)]治疗48周的基因1b和非1b/2a型CHC患者91例,观察基线水平、治疗第12、24、48周以及停药后第24、48周的LSM值、HCV RNA和ALT水平的变化,分析抗病毒治疗对上述指标的影响.结果 治疗后,LSM值、HCV RNA和ALT水平明显降低,与治疗前相比,差异有统计学意义(P＜0.05).持续病毒学应答(sustained virological response,SVR)率为79％,获得SVR的患者中有4例复发,复发患者具有高龄、高LSM值且均为基因1b型等特征.结论 Peg-IFN α-2a联合RBV治疗有效降低CHC患者体内HCV RNA和ALT水平,可改善肝纤维化.     

荧光定量PCR与微粒子酶免分析法同步检测HCV对比分析

目的　对荧光定量PCR与微粒子酶免分析法 (MEIA法 )同步检测HCV进行比较。方法　收集北京协和医院 2 0 0 3- 0 1～ 12门诊及住院 5 0例ALT正常 ,无恶心、呕吐、乏力、黄疸临床表现 ,行胃镜和肠镜检查的门诊病人。检查前用MEIA法检测HCV 3抗体弱阳性 (1～ 2 0S/CO) ,对其进行荧光定量PCR检测HCV RNA ;5 0例用荧光定量PCR检测HCV RNA阳性血清 (HCV RNA≥ 5 0× 10 5copies/L) ,再进行HCV 3抗体检测。 结果　MEIA法检测HCV 3抗体阳性在 1～ 2 0S/CO且ALT正常病人 ,用荧光定量PCR检测HCV RNA含量 ,3例(6 % )高于最低检测限 (5 0× 10 5copies/L)。对 5 0例用荧光定量PCR检测HCV RNA阳性血清 (HCV RNA≥ 5 0× 10 5copies/L) ,且ALT正常病人 ,进行HCV抗体检测 ,2例 (4 % )丙肝抗体阴性 ,余丙肝抗体数值在 80～ 15 0S/CO。结论　MEIA法在AXSYM机器上检测HCV 3抗体弱阳性时 ,不能轻易得出丙肝的诊断 ,应检测HCV RNA并结合临床表现。定量PCR不适宜检测含量较低的HCV RNA ,MEIA法在AXSYM机器上检测HCV抗体作为献血员筛查不失为一种好方法。     

松栀丸治疗湿热蕴结兼气滞血瘀证慢性丙型肝炎临床研究

目的:评价松栀丸治疗湿热蕴结兼血瘀证慢性丙型肝炎(CHC)的临床疗效。方法:采用随机、盲法、阳性药物平行对照方法,将409例湿热蕴结兼血瘀证CHC患者按3:1的比例随机分为治疗组305例和对照组104例。治疗组患者给予松栀丸(5g/次,2次/d,口服),对照组患者给予利肝f片(3片/次,2次/d,口服),疗程为6个月,停药后各随访6个月。观察两组患者治疗前后的临床症状体征、中医证候积分、肝功能(ALT、AST、ALP、GGT、TBil、DBil)、HCV RNA、肝组织病理的变化。结果:治疗后,治疗组和对照组的临床总有效率分别为70.00%和34.15%,两组比较差异有显著性意义(P0.00);两组患者中医证候积分较治疗前均有显著性下降(P0.01),且治疗组较对照组下降更为显著(P0.01);两组患者ALT、AST、GGT、TBil、DBil水平较治疗前均有显著性下降(P0.01),且治疗组患者ALT、AST、GGT的水平较对照组下降更为显著(P0.01);治疗后两组患者HCV RNA阴转率分别为36.55%、2.43%,两组比较差异有显著性意义(P0.01),治疗组患者HCV RNA水平下降幅度较对照组明显(P0.01);治疗结束后随访6个月,治疗组与对照组HCV RNA阴转率分别为48.15%、1.75%(P0.01);治疗结束后两组患者肝功能正常者随访6个月ALT、AST的反跳率分别为11.7%、11.46%和26.67%、20.00%(P0.05);治疗结束后两组患者肝功能异常者随访6个月ALT、AST的复常率分别为54.74%、49.46%和7.14%、19.15%(P0.05)。治疗组治疗后肝脏炎症活动度、肝脏纤维化程度与治疗前比较均有一定程度的改善(P0.05);治疗组患者主要症状除身目发黄与蜘蛛痣外,其他症状改善情况与对照组比较差异有显著性意义(P0.01)。治疗中未观察到与试验药物有关的不良反应。结论:松栀丸可显著改善湿热蕴结兼血瘀证CHC患者的临床症状和体征,抑制HCV RNA病毒复制,改善肝功能,在临床上具有一定的推广作用。     

HCV RNA病毒载量和肝功能及白蛋白的相关性研究

目的:研究血液中丙型肝炎病毒核糖核酸(HCV RNA)载量与肝功能及白蛋白(ALB)等指标间的相关性,探讨病毒含量和肝组织损伤之间的关系。方法:选取193例大连地区汉族人群HCV感染患者为研究对象,检测血液中HCV RNA病毒载量,同时测定谷丙转氨酶(ALT)、谷草转氨酶(AST)、AST/ALT及ALB等指标。用豆形图展示HCV RNA病毒载量数据,分析HCV RNA载量与各指标间的相关性。结果:不同性别组HCV RNA载量分布差异无统计学意义(P0.05);HCV RNA载量与年龄不存在显著的相关性(P0.05)。HCV RNA载量与ALT、AST、AST/ALT及ALB均不相关(P0.05)。根据受试者HCV RNA载量数量级将其分为4组,ALT、AST、AST/ALT及ALB在各组间差异无统计学意义(P0.05)。结论:大连地区汉族人群HCV患者血液中HCV RNA载量与ALT、AST、AST/ALT及ALB等指标不相关,HCV RNA病毒载量不能反映肝脏损伤程度。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎过程中出现听力障碍2例

一、病例资料病例l:女性患者,53岁,因发现抗-HCV阳性3年,间断乏力伴恶心、食欲减退3个月,于2009年4月16日入我院治疗.20年前行"左乳腺癌根治术",术中输血(具体量不详),否认耳部、甲状腺、自身免疫、血液系统及精神神经系统疾史.体格检查:血压120/80mm Hg(1 mm Hg=0.133kPa),皮肤、巩膜无黄染,可见肝掌,无蜘蛛痣,心、肺查体未见异常,腹平软,无压痛,肝脏、脾脏未触及.实验室检查:抗-HCV阳性,HCV RNA l.438x 106 IU/ml,HCV基因型Ib型;外周血白细胞计数(WBC) 5.2x 109/L,血小板计数139×109/L;血清ALT 42 U/L,AST 34 U/L.肝组织病理学检查:慢性丙型病毒性肝炎,G(1 -2) Sl,诊断为慢性丙型肝炎.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.