干扰素a-2b治疗慢性丙型肝炎致白发1例

一、病例资料患者女性,30岁,布依族,农民,体质量50kg.体检结果显示抗-HCV阳性(酶联免疫吸附试验法),无明显肝病症状及体征;进一步检查提示:肝功能指标正常,HCVRNA阳性,为9.50×105拷贝/ml(最低检测限为1000拷贝/ nl),10年前曾因产后大出血接受过500 ml输血治疗;回顾性调查证实献血员为HCV感染者,病毒基因型为1b型;诊断为慢性丙型肝炎.在知情同意的基础上给予干扰素α-2b(购自天津华利达生物有限公司)3 MU,上臂三角肌处皮下注射,隔日1次;同时给予利巴韦林300 mg口服,2次/d;共治疗48周.治疗12周复查,HCV RNA阴性(＜1000拷贝/ml),提示患者获得早期病毒学应答;治疗24、36、48周及停药后24、48周复查,HCV RNA均阴性(最低检测限＜ 15 IU/ml),提示患者获得治疗结束时病毒学应答及持续病毒学应答.     

干扰素治疗慢性丙型肝炎的远期预后

业已证实,干扰素IFN能降低慢性丙型肝炎患者的转氨酶,清除HCV RNA以及减轻肝脏炎症和坏死。研究旨在评估对干扰素治疗持久有效的慢性丙型肝炎患者的预后。 病人和方法:选择1988～1992年间肝穿刺证实的慢性丙型肝炎乃至肝硬化患者426例(16例失访),其中65％为慢性肝炎,35％存在肝硬化,所有患者血清HCV RNA均阳性。给予人淋巴母细胞α-n1 IFN 5MU/m~2或rIFNα-2b 10MU 1周3次肌注,2个月后,α-n1 IFN治疗者减量为3MU/m~2维持4或10个月;rIFNα-2b治疗者减量为5MU维持4个月后,将ALT复查者     

递增剂量α-干扰素联合利巴韦林治疗代偿期丙型肝炎肝硬化患者安全性和有效性研究

目的 探讨应用递增剂量α-干扰素治疗丙型肝炎肝硬化患者的安全性及疗效。方法 给予60 例丙型肝炎肝硬化患者干扰素-α2b 2 MU皮下注射,1次/d,利巴韦林600 ~1000 mg / d ,1~4 w后将干扰素的剂量逐渐提高到 4 MU,1次/d,连续2 w,随后将其改为6 MU,1次/2 d。所有患者治疗120 w,随访24 w。采用基因测序法对 HCV 进行基因分型;应用实时荧光定量RT-PCR法检测血清HCV RNA。结果 60例患者基线血清HCV RNA为（4.3±2.1）lg IU/ml,在治疗24 w和96 w时分别降至（2.1±0.2）lg IU/ml和（1.8±0.3）lg IU/ml（P<0.05）;52例1b型感染者快速病毒学应答、早期病毒学应答、治疗结束时病毒学应答和持续病毒学应答率分别为 30.8%、75.0%、78.8%和73.1%, 而8例2a型感染者则分别为62.5%（P<0.05）、75.0%、87.5%和87.5%。结论 递增剂量α-干扰素联合利巴韦林个体化抗病毒治疗可以使丙型肝炎肝硬化患者获益,但本组非1b型感染者较少,研究结论需进一步证实。     

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.     

干扰素致甲状腺功能异常1例

1.病例资料:患者男性,37岁,汉族,北京籍,教师.因"发现ALT升高5年,间断心悸1年余"就诊.患者5年前劳累后感觉乏力,检查结果显示:ALT 67 U/L、抗-HCV阳性.1年半前HCV RNA水平为2.8×10(5)拷贝/ml,并开始干扰素α-2b 3 MU/d治疗,未服用利巴韦林;治疗3个月时查HCV RNA低于检测限.     

慢性乙型肝炎患者替比夫定治疗达完全应答后序贯普通干扰素巩固治疗的疗效观察

目的 对接受替比夫定(LDT)治疗的HBeAg阳性慢性乙型肝炎患者获完全应答后,比较序贯干扰素(IFN)巩固治疗或单一LDT巩固治疗的疗效;并探索治疗期间血清HBsAg水平对停药后持续应答的预测价值. 方法 对20例接受LDT治疗的HBeAg阳性慢性乙性肝炎患者获完全应答后,继续LDT治疗6个月,然后分为序贯IFN巩固组或单一LDT巩固组.序贯IFN巩固组给予IFN α-1b治疗6个月;单一LDT巩固组继续给予LDT治疗6个月.分别在停药后1、2、3、6、9、12个月及之后每半年随访1次,肝功能采用全自动生物化学分析仪检测;血清HBV DNA定量采用实时荧光定量PCR法检测;HBsAg定量采用化学发光法检测.率的比较采用Fisher精确概率法、组间均数比较采用t检验;血清HBsAg水平对停药后复发的预测价值用受试者工作特征曲线分析. 结果 序贯IFN组与单一LDT组的复发率分别为30％、40％,差异无统计学意义(P＞0.05).LDT治疗24周时血清HBsAg水平下降幅度的受试者工作特征曲线下面积为0.689,大于治疗12周的0.652、48周的0.545.24周时血清HBsAg水平下降幅度对停药后持续应答有一定的预测价值,差异有统计学意义(P＜0.05);治疗24周时血清HBsAg水平下降幅度≥1000 IU/ml的患者其持续应答率较下降幅度＜ 1000 IU/ml的患者高[90.9％(10/11)与33.3％(3/9),P＜0.05].治疗结束时血清HBsAg水平＜200 IU/ml的患者持续应答率高于≥200 IU/ml的患者[100％与53.3％,P＜ 0.05].结论 序贯普通IFN α-1b巩固治疗并不能降低停药后复发率.LDT治疗24周时血清HBsAg水平下降幅度≥1000 IU/ml的患者其持续应答率高于下降幅度＜1000 IU/ml的患者.     

干扰素γ对丙型肝炎病毒复制子的抑制作用

目的研究干扰素（IFN）γ直接抑制丙型肝炎病毒（HCV）复制子的作用及其与IFN α联合用药的疗效，并对可能介导IFN γ抗HCV作用的干扰素刺激基因（ISG）的表达水平进行探讨。方法建立HCV复制子细胞模型，用IFN γ或IFN γ联合IFN α处理HCV复制子细胞，通过半定量逆转录聚合酶链反应（RT-PCR）及实时定量PCR检测细胞中HCV RNA水平；western blot检测细胞中HCV非结构蛋白5A（NS5A）。结果IFN γ对HCV RNA的复制及NS5A的表达有明显抑制作用，10U／ml IFN γ可使HCV RNA较对照组减少36％，25U／ml减少80％；IFN γ对HCV RNA及NS5A蛋白的抑制作用与其剂量及作用时间呈正相关。用IFN γ预处理的细胞对IFN α抗HCV的作用更敏感，且细胞内干扰素调节因子-1（IRF-1）、干扰素刺激基因因子3 γ（ISGF3 γ）和2’5’-寡腺苷酸合成酶（2’5’-OAS）呈明显的诱导性表达。结论IFN γ能有效抑制HCV RNA的复制，并与IFN α有协同抗HCV的作用。IRF-1、ISGF3 γ和2’5’-OAS可能参与介导IFN γ抗HCV的作用。     

聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者疗效比较和影响疗效的预测因素分析

目的 比较聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者的疗效,并对影响抗病毒疗效的因素进行分析。方法 2010年5月~2014年8月我院收治的慢性丙型肝炎患者116例,随机将患者分为研究组和对照组,每组58例。给予对照组患者普通干扰素α-2b 联合利巴韦林治疗,给予研究组患者聚乙二醇α-2a干扰素联合利巴韦林治疗。采用实时荧光定量PCR法检测血清HCV RNA定量,对两组病毒学应答率以及性别、年龄、体质指数和病毒载量对治疗效果的影响进行比较分析。结果 在治疗12周、24周、48周以及停药后12周和24周,研究组患者血清HCV RNA转阴率分别为51.72%、60.34%、72.41%、68.97%和65.52%,显著高于对照组患者的31.03%、48.27%、55.17%、48.27%和41.38% （P<0.05）;研究组患者快速病毒学应答率、早期病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为75.86%、84.48%、86.20%和74.14%,显著高于对照组的51.72%、60.34%、63.79%和55.17%（P<0.05）;在治疗4周、12周、24周和48周,研究组患者血清HCV RNA水平分别为（4.72±1.30） IU/ml、（4.09±1.21） IU/ml、（3.79±1.18） IU/ml和（3.26±1.08） IU/ml,显著低于对照组患者的（5.27±1.52） IU/ml、（4.68±1.41） IU/ml、（4.15±1.37） IU/ml和（3.99±1.16） IU/ml（P<0.05）;两组患者在治疗过程中,均出现发热、失眠、肌肉酸痛、乏力和白细胞下降等不良反应,但差异均不具有统计学意义（P>0.05）;研究组获得SVR患者治疗前血清HCV RNA水平为（3.57±0.45） IU/ml,显著低于未获得SVR患者的（4.92±0.09） IU/ml（P<0.05）。讨论 聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者有效且安全,治疗前患者病毒载量低将预示疗效好。     

两种剂量重组干扰素α2a治疗慢性丙型肝炎的随机对照研究

本研究的是按照临床试验管理规范(GCP)的原则，比较两种剂量的重组干扰素α2a(罗扰素)对慢性丙型肝炎的疗效；63例有血清学和肝组织学证实的慢性丙型肝炎病人，随机分成两组。甲组30例，用IFNα2a注射，6MU 1周3次，3个月，继之为3MU 1周3次3个月。乙组33例，IFNα2a 3MU 1周3次，共6个月。在治疗结束时，甲组的ALT复常率为60．0%，HCV RNA阴转率为53．3%。乙组的ALT复常率和HCV RNA阴转率分别为72．7%和61．3％。停药6个月后，甲组的ALT复常率和HCV RNA阴转率分别为56．7％和63．3%；乙组则分别为69．7%和54．8%。两组的疗效比较无显著差异(P>0．05)：HCV基因型与疗效关系不大，肝组织学病变较轻者疗效较好。6例病人在治疗过程中出现干扰素中和抗体，4例显效，2例无效。IFN α2a的不良反应与文献报告相同，但绝大多数病人能耐受。本组中，1例因出现病情加重，1例白细胞明显降低而中止治疗。     

聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者疗效比较和影响疗效的预测因素分析

目的比较聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者的疗效,并对影响抗病毒疗效的因素进行分析。方法 2010年5月~2014年8月我院收治的慢性丙型肝炎患者116例,随机将患者分为研究组和对照组,每组58例。给予对照组患者普通干扰素α-2b联合利巴韦林治疗,给予研究组患者聚乙二醇α-2a干扰素联合利巴韦林治疗。采用实时荧光定量PCR法检测血清HCV RNA定量,对两组病毒学应答率以及性别、年龄、体质指数和病毒载量对治疗效果的影响进行比较分析。结果在治疗12周、24周、48周以及停药后12周和24周,研究组患者血清HCV RNA转阴率分别为51.72%、60.34%、72.41%、68.97%和65.52%,显著高于对照组患者的31.03%、48.27%、55.17%、48.27%和41.38%(P0.05);研究组患者快速病毒学应答率、早期病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为75.86%、84.48%、86.20%和74.14%,显著高于对照组的51.72%、60.34%、63.79%和55.17%(P0.05);在治疗4周、12周、24周和48周,研究组患者血清HCV RNA水平分别为(4.72±1.30)IU/ml、(4.09±1.21)IU/ml、(3.79±1.18)IU/ml和(3.26±1.08)IU/ml,显著低于对照组患者的(5.27±1.52)IU/ml、(4.68±1.41)IU/ml、(4.15±1.37)IU/ml和(3.99±1.16)IU/ml(P0.05);两组患者在治疗过程中,均出现发热、失眠、肌肉酸痛、乏力和白细胞下降等不良反应,但差异均不具有统计学意义(P0.05);研究组获得SVR患者治疗前血清HCV RNA水平为(3.57±0.45)IU/ml,显著低于未获得SVR患者的(4.92±0.09)IU/ml(P0.05)。讨论聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者有效且安全,治疗前患者病毒载量低将预示疗效好。     

What a difference a day makes

With the availability of group A beta-hemolytic streptococcal (GABHS) antigen detection tests, the management of adult pharyngitis is being reassessed. A decision analytic model was developed which considered four strategies: immediate treatment, no treatment, performing a rapid antigen test, or obtaining a bacterial culture. Patient outcomes were expressed in “well” days, which were reduced by the “sick” days associated with adverse reactions to treatment or complications of GABHS infection. When immediate test results are available, testing is the optimal strategy for probabilities of GABHS between 1 and 49 per cent. This range includes almost all patients, using probability estimates based on clinical criteria. The absolute benefit of testing was 0.1 days. The major advantage of a rapid test is the avoidance of penicillin reactions. Variations in the symptomatic benefits of treatment had minimal effects on the analysis. The analysis supports the use of an antigen test for adult patients with pharyngitis. Received from the Division of General Medicine and Primary Care. Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond. Virginia. A preliminary version of this work was presented at the seventh annual meeting of the Society for Medical Decision Making, October 21, 1985.     

Charge of a quasiparticle in a superconductor

Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias V_SD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eV_SD and Δ the superconducting order parameter. Exceptionally, just above the gap eV_SD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1–4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eV_SD ～ 2Δ, we found a reproducible and clear dip in the extracted charge to q? ～ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure.Excitations in superconductors (Bogoliubov quasiparticles) can be described according to the Bardeen–Cooper–Schrieffer (BCS) theory (1) as an energy-dependent superposition of an electron with amplitude u(ε), and a hole with amplitude v(ε), where the energy ε is measured relative to the Fermi energy (2). Evidently, the expectation value of the charge operator (applied to the quasiparticle wave function), which we address as the quasiparticle charge e* = q(ε)e, is smaller than the charge of an electron, q(ε) = |u(ε)|² ? |ν(ε)|² (3). Solving the Bogoliubov–de Gennes equations, one finds that |u(ε)|2=1/2[1+(ε2−Δ2/ε)] and |v(ε)|2=1/2[1−(ε2−Δ2/ε)], with the expected charge evolving with energy according to q(ε)=ε2−Δ2/ε––vanishing altogether at the superconductor gap edges (3). Note, however, that the quasiparticle wave function is not an eigenfunction of the charge operator (3, 4). Properties of quasiparticles, such as the excitation spectra (5), lifetime (6–10), trapping (11), and capturing by Andreev bound states (12, 13), had already been studied extensively; however, studies of their charge are lagging. In the following we present sensitive shot-noise measurements in a Josephson junction, resulting in a clear observation of the quasiparticle charge being smaller than e, q(eV_SD∼2Δ) < 1, and evolving with energy, as expected from the BCS theory.To observe the BCS quasiparticles in transport we study a superconductor–insulator–superconductor (SIS) Josephson junction in the nonlinear regime. The overlap between the wave functions of the quasiparticles in the source and in the drain is expected to result in a tunneling current of their effective charge. This is in contrast with systems which are incoherent (14, 15) or with an isolated superconducting island, where charge conservation leads to traversal of multiples of e – Coulomb charge (16). As current transport in the nonlinear regime results from “multiple Andreev reflections” (MAR), it is prudent to make our measurements credible by first measuring the charge in this familiar regime.In short, the MAR process, described schematically in Fig. 1, carries a signature of the shuttled charge between the two superconductors (SCs), being a consequence of n traversals through the junction (as electron-like and hole-like quasiparticles), with n an integer larger than 2Δ/eV_SD. A low transmission probability t (via tunneling through a barrier) in the bias range 2Δ/n < eV_SD < 2Δ/(n ? 1) assures dominance of the lowest order MAR process (higher orders are suppressed as tⁿ), with the charge evolving in nearly integer multiples of the electron charge. Although there is already a substantial body of theoretical (3, 17–23) and experimental (24–29) studies of the MAR process, charge determination without adjustable parameters is still missing. An important work by Cron et al. (27) indeed showed a staircase-like behavior of the charge using “metallic break junctions;” however, limited sensitivity and the presence of numerous conductance channels some of which with relatively high transmission probabilities did not allow exact charge quantization. Our shot-noise measurements, performed on a quasi-1D Josephson junction (single-mode nanowire) allowed clear observation of charge quantization without adjustable parameters. To count a few advantages: (i) the transmission of the SIS junction could be accurately controlled using a back-gate; (ii) this, along with our high sensitivity in noise measurements, enabled us to pinch the junction strongly (thus suppressing higher MAR orders); and (iii) with the Fermi level located near the 1D channel van Hove singularity, a rather monoenergetic distribution could be injected (SI Appendix, section S7).Open in a separate windowFig. 1.MAR. Illustrations of the leading processes contributing to the current as function of bias. In general, for 2Δ/(n ? 1) > eV_SD > 2Δ/n the leading charge contribution to the current is ne. An electron-like quasiparticle is denoted by a full circle, whereas a hole-like quasiparticle is denoted by an empty circle. (A) When the bias is larger than the energy gap, eV_SD > 2Δ, the leading process is a single-path tunneling of single quasiparticles from the full states (Left) to the empty states (Right). This current is proportional to the transmission coefficient t. Higher-order MAR process (dashed box), being responsible for tunneling of Cooper pairs, is suppressed as t². (B) For 2Δ > eV_SD > Δ, the main charge contributing to the current is 2e with probability t². (C) For Δ > eV_SD > 2Δ/3, the main charge contributing to the current is 3e with probability t³.