替比夫定临床应用专题研讨会纪要

2009年2月7日,我国肝病和感染病领域部分专家在上海召开了"替比夫定临床应用专题研讨会",对替比夫定在临床应用中应注意的问题进行了深入讨论.     

干扰素治疗慢性肝炎的远期疗效评价

目前,干扰素,主要是聚乙二醇干扰素,是治疗慢性丙型肝炎惟一有效的抗病毒药物,同时也是治疗慢性乙型肝炎的首选药物之一.但由于干扰素特别是聚乙二醇干扰素在临床上规范化应用的时间并不太长,加之远期疗效的评价指标较难确定,因此有必要对其治疗慢性肝炎的远期疗效做出正确评价,使其更好地应用于临床.     

干扰素在病毒性肝炎治疗中的联合应用

干扰素是细胞在病毒感染或其他诱导因素作用下产生的具有广谱抗病毒、抗肿瘤、抑制细胞增殖和免疫调节作用的细胞因子[1].自1986年应用于临床以来,因其肯定的疗效已被广泛地用于临床治疗多种疾病,在肝脏疾病中的应用目前主要集中在病毒性肝炎的抗病毒治疗,目前应用最广泛的是乙型病毒性肝炎及丙型病毒性肝炎.     

对免疫反应介导的肝细胞损伤机制的新认识

干扰素是细胞在病毒感染或其他诱导因素作用下产生的具有广谱抗病毒、抗肿瘤、抑制细胞增殖和免疫调节作用的细胞因子[1].自1986年应用于临床以来,因其肯定的疗效已被广泛地用于临床治疗多种疾病,在肝脏疾病中的应用目前主要集中在病毒性肝炎的抗病毒治疗,目前应用最广泛的是乙型病毒性肝炎及丙型病毒性肝炎.     

乙型肝炎病毒共价闭合环状DNA检测的临床应用

HBV共价闭合环状DNA (covalently closed circular DNA,cccDNA)是HBV复制的初始模板.近年来,随着以选择性实时荧光PCR技术为代表的各类cccDNA检测技术日渐成熟,以及临床医生对cccDNA检测临床意义认识的不断提高,cccDNA检测已从基础研究逐渐进入到临床应用.     

乙型肝炎病毒感染的育龄妇女抗病毒药物应用策略

HBV感染的育龄妇女抗病毒问题一直困扰着临床医生.现根据近年来抗病毒药物在妊娠妇女中应用安全性的研究及临床经验,提出了HBV感染的育龄妇女不同时期抗病毒药物治疗的策略,供临床参考.     

恩替卡韦临床应用专家共识：2015年更新

恩替卡韦（entecavir,ETV）是当前慢性乙型肝炎（CHB）患者抗病毒治疗的一线药物之一。2005年美国食品药品监督管理局与中国国家食品药品监督管理局相继批准ETV用于CHB治疗。为了规范与优化ETV的临床应用,《中华实验和临床感染病杂志（电子版）》编辑部、《中国肝脏病杂志（电子版）》编辑部曾于2009年邀请国内部分感染病学与肝病学领域专家召开了ETV临床应用专家研讨会,讨论形成了《2009年恩替卡韦临床应用专家共识》;并于2014年对该共识进行更新。近1年来, ETV治疗CHB患者的大样本长期随访数据不断公布,ETV治疗特殊人群患者的资料进一步积累。为将最新的ETV循证医学证据提供给广大肝病及感染病医务工作者,更好地指导ETV临床应用,《中华实验和临床感染病杂志（电子版）》、《中国肝脏病杂志（电子版）》与《Infection International（electronic version）》杂志编辑部再次组织相关专家,对ETV相关数据进行总结分析,形成了《恩替卡韦临床应用专家共识：2015年更新》。     

肿瘤相关抗原及其自身抗体在肝细胞癌早期诊断中的应用

肝细胞癌(HCC)的早期发现、早期诊断是提高HCC患者生存率的必要手段。研究发现,一种由肿瘤细胞释放的异常蛋白即肿瘤相关抗原刺激产生的自身抗体在HCC患者临床诊断前就已存在,因此可能成为HCC早期诊断的新型潜在标志物。简述了几种新型肿瘤相关抗原抗体在HCC诊断中的应用现状,认为肿瘤相关抗原抗体在HCC诊断中具有较大的前景及临床应用价值。     

索拉非尼在乙型肝炎病毒相关晚期肝细胞癌中的应用价值

中国是乙型肝炎病毒(HBV) 感染的高流行区,HBV 感染是导致原发性肝癌的最常见危险因素,乙肝肝硬化是 肝癌发生的高危因素。在中国近年来原发性肝癌的发病率和病死率呈逐年上升趋势。原发性肝癌起病隐匿,恶性程 度高,病情进展快,大多数发生在肝硬化基础上,确诊时多已进展至中晚期甚至出现远处转移,丧失根治性治疗时机, 治疗手段有限,预后极差。索拉非尼的临床应用使晚期肝癌患者的治疗取得了突破性进展,能有效阻止疾病进展,延 长患者生存时间,开创了晚期肝癌的靶向治疗时代。文章从索拉非尼的作用机制、不良反应处理、HBV 相关原发性 肝癌的内科综合治疗进展,以及笔者近年来应用以索拉非尼为核心的内科综合治疗手段治疗HBV 相关中晚期肝癌 的临床体会等几个方面,对索拉非尼在乙肝相关晚期肝癌患者中的临床应用进行论述。     

亚低温治疗缺血性卒中:从实验向临床转化

作为一种神经保护措施,亚低温在临床实践中的应用与研究已非常广泛.许多疾病,如心脏停搏后脑损伤、新生儿缺血缺氧性脑病等,应用亚低温治疗已取得了肯定的疗效.虽然亚低温在治疗缺血性卒中方面已有大量动物实验和临床研究,而且动物实验已证实其具有确切的神经保护作用,但在临床研究中亚低温治疗缺血性卒中的神经保护作用尚未得出一致的结论,其临床疗效似乎并无预期的乐观.因此,有必要对亚低温治疗缺血性卒中由动物实验向临床转化中存在的问题进行分析,为亚低温治疗缺血性卒中的临床应用提供思路.     

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.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

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.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.