慢性乙型肝炎治疗中影响HBeAg转阴和定量的有关因素分析

背景：慢性乙型肝炎抗病毒治疗的完全应答包括血清HBVDNA低于检测水平和HBeAg血清学转换,HBeAg是评估乙型肝炎治疗效果和停药的监测指标。目的：探讨替比夫定治疗HBeAg阳性慢性乙型肝炎患者时影响HBeAg转阴的因素。方法：采用替比夫定治疗156例HBeAg阳性慢性乙型肝炎患者48周,观察ALT、HBVDNA、HBeAg治疗前后变化,分析治疗前基线HBVDNA载量、ALT水平、HBVDNA降至检测下限的时间对HBeAg转阴和定量的影响。结果：替比夫定治疗48周后,HBVDNA转阴128例（82．1％）,ALT恢复正常153例（98．1％）,HBeAg转阴52例（33．3％）;HBVDNA载量、HBeAg定量、ALT水平均显著降低（P〈0．01）。治疗前HBVDNA〈10^7 copies／mL、ALT≥200U／L组的HBeAg转阴率分别显著高于HBVDNA≥10^7 copies／mL、ALT〈200U／L组（46．4％对23．0％,P〈0．01;55．2％对16．9％,P〈0．叭）,且HBeAg定量显著降低（P〈0．01）。HBVDNA降至检测下限的不同时间组HBeAg转阴率和定量相比差异均有统计学意义（P〈0．05）。结论：基线HBVDNA〈10^7 copies／mL、ALT水平较高、治疗后HBVDNA降至检测下限的时间对替比夫定治疗48周时HBeAg转阴和定量具有明显的影响。     

影响干扰素治疗慢性乙型肝炎疗效的因素探讨

目的探讨肝组织病理学变化、乙型肝炎病毒DNA（HBVDNA）水平、谷丙转氨酶（ALT）水平对慢性乙型肝炎患者干扰素抗病毒治疗疗效的影响。方法对97例适合抗HBV治疗的慢性乙型肝炎患者应用α-1b干扰素治疗24周，治疗前后对ALT、HBVDNA、HBeAg／HBeAb水平进行检测、分析，其中32例患者在治疗前行肝活检明确肝组织炎症活动情况。结果肝组织炎症活动度较高者抗HBV治疗后HBVDNA转阴率和HBeAg血清转换率较高，而治疗前ALT水平对治疗后HBVDNA转阴率和HBeAg血清转换率影响较小；基线HBVDNA水平在10^5～10^6 copies／ml的患者治疗后HBVDNA转阴率和HBeAg血清转换率较高。结论抗病毒前肝组织炎症活动程度明显者、HBVDNA水平在10^5-10^6copies／ml者干扰素抗HBV疗效较好。     

替比夫定优化治疗HBeAg阳性慢性乙型肝炎的疗效及安全性观察

目的 观察替比夫定(LDT)优化治疗对HBeAg阳性慢性乙型肝炎患者的疗效及安全性.方法 选择基线HBV DNA＜109 copies/ml、ALT＞2 ULN的45例HBeAg阳性慢性乙型肝炎患者,给予LDT600 mg/d治疗.4、12、24、52周时分别检测HBV DNA、HBeAg和肝功能.24周时HBV ...     

乙型肝炎患者血清HBeAg与HBV DNA含量的关系及其临床意义

目的:比较乙型肝炎患者血清中HBeAg含量与HBV DNA含量之间的关系并分析其临床意义。方法:采用微粒子发光分析法检测122例患者血清中HBeAg含量,同时采用荧光定量PCR法检测患者血中HBV DNA含量,并进行比较分析。结果:HBeAg含量>134 PEIU/L组的患者血清HBV DNA平均含量(6.93E±1.03 copies/ml)显著高于HBeAg含量0.28～134 PEIU/L组患者的HBV DNA含量(5.58E±1.84 copies/ml)(t=4.03,P<0.001),在HBeAg阴性组中有52％的患者仍可检出HBV DNA(2.9E±2.44 copies/ml)。122例患者血清HBeAg和HBV DNA的含量高低与ALT(丙氨酸氨基转移酶)无相关关系。结论:血清中HBeAg的含量与HBV DNA含量有一定相关性,与ALT无相关关系,临床应结合两者对病情进行综合判断。     

泛昔洛维加拉米夫丁联合治疗慢性乙型肝炎对HBeAg血清转换的影响

目的观察泛昔洛维加拉米夫丁联合治疗慢性乙型肝炎(CHB)对血清HBeAg血清转换的影响.方法54例慢性乙型肝炎,根据治疗前血清ALT水平,分为A、B、C三组,各组随机分为两种用药模式(1)联合用药(Ⅰ)泛昔洛维(FCV)250mg,t.i.d×6mo加拉米夫丁(LMD)100mg,qd×6mo;(2)单一用药(Ⅱ)LMD 100mg,qd×6mo.结果在A、B、C三组中,各组联合用药的HBeAg血清转换率明显高于单一用药者,(P＜0.05);治疗前血清ALT＞ULN(正常上限)5倍者的HBeAg血清转换率明显高于ALT在ULN 2～5倍或＜ULN 2倍者.结论联合用药可提高HBeAg血清转换率,恢复免疫系统对HBV核衣壳抗原的免疫应答,促进HBV清除.治疗前血清ALT水平也是影响HBeAg血清转换的一个重要因素.     

拉米夫定治疗慢性乙型肝炎的疗效及其预测因素分析

目的评价拉米夫定治疗慢性乙型肝炎的疗效及影响疗效的预测因素。方法应用拉米夫定治疗90例慢性乙型肝炎患者,观察48周的疗效。结果在90例患者中,完全应答21例(21.3%)、部分应答64例(71.1%)、无应答5例(5.6%);在基线ALT≥2×ULN和HBeAg阴性患者,完全应答率及病毒学应答率较高(P0.05);治疗4周时HBVDNA下降≥2lg copies/ml者,完全应答率为25.5%,病毒学应答率为91.5%;在71例HBeAg阳性患者中,HBeAg转阴21例(29.6%),出现HbeAg/抗HBe血清学转换7例(9.9%);年龄、性别和乙型肝炎家族史对疗效无预测价值。结论拉米夫定治疗慢性乙型肝炎患者疗效显著,基线ALT水平高、HBVDNA水平低、HBeAg阴性和治疗4周HBVDNA下降超过2lg copies/ml者,疗效较好。     

慢性乙型肝炎HBV前C区基因突变与sIL—2R的关系

目的探讨细胞因子sIL-2R在慢性乙型肝炎HBV前C区突变致病机理中的意义.方法采用PCR-单链构象多态性分析银染技术检测52例HBVDNA阳性患者的HBV前C区基因突变,ELISA法测定血清中sIL-2R.结果52例HBVDNA阳性患者,检出HBV前C区突变32例,突变率为61.5%;突变组sIL-2R水平为699.98±138.17U/ml,非突变组sIL-2R为458.71±114.92U/ml,两组比较P＜0.01;突变组的ALT、AST分别为152.19±53.87U/L、219.23±64.59U/L,显著高于非突变组,P＜0.01.结论细胞因子sIL-2R参与了突变株感染所引起的肝损伤.     

乙型肝炎病毒表面抗原定量与肝癌的关系探讨

目的结合HBVDNA载量、HBeAg阳性与HBeAg阴性,评价HBsAg在原发性肝癌(HCC)发生、发展中的意义。方法采用化学发光法检测306例HBV感染所致肝硬化及肝硬化合并HCC的两组患者血清乙型肝炎病毒标志物(HBVM)滴度,采用荧光定量PCR技术检测患者血清HBVDNA载量。结果肝硬化组:血清HBsAg滴度≥250IU/ml者占67.5%;HBeAg阳性者占23.8%;HBeAg阴性者占76.2%;HBVDNA≥104copies/ml者占79.5%。肝硬化合并HCC组:血清HBsAg滴度≥250IU/ml者占81.9%;HBeAg阳性者占38.1%;HBeAg阴性者占61.9%;HBVDNA≥104copies/ml者占61.3%。两组中HBsAg≥250IU/ml与HBVDNA≥104copies/ml病例比较差异有统计学意义(P<0.05)。结论在HBV感染所致肝硬化患者中,长期高滴度状态的HBsAg在评价肝硬化发展为HCC中同样起到预警信号的作用。     

抗HBV特异性主动免疫疗法联合干扰素抗乙型肝炎病毒的临床研究

目的探讨抗 HBV 特异性主动免疫疗法(主动免疫)和干扰素(IFN)联合使用,观察其抗乙型肝炎病毒的效果。方法应用前瞻性随机分组的方法,对180例未经治疗的慢性乙型肝炎患者分3组进行观察,每组60例,A 组:(主动免疫联合IFN),主动免疫每月1次,α-1b-IFN 5MU,每周3次;B组:α-1b-IFN 5MU,每周3次;C 组:对照组。总疗程为12个月。分别于治疗后第3、6、9、10、11、12个月和随访半年时抽血检查,并观察各组 HBV DNA 复制水平、HBeAg、肝功能变化。结果 A 组有显著的抗病毒效果,显著高于 B 组和 C 组,直至治疗结束后6个月,均显示出极好的抑制 HBV 复制和持续的丙氨酸氨基转移酶复常效果(34.0±1 1.4)U/L 对(86.4±31.4)U/L,P<0.01。A 组与 B 组比较,治疗结束6个月,病毒负荷量(11.02±1.52)×10~5copies/ml 对(77.98±3.12)×10~5 copies/ml,P<0.01,差异有显著性。结论抗 HBV 特异性主动免疫疗法联合α-1b 干扰素的应用,具有显著增加抗病毒效果,特别是停药后持续抗病毒及肝功能持续正常的疗效更为显著。     

拉米夫定联合中药治疗HBeAg阳性患者60例

拉米夫定(商品名贺普丁)是治疗慢性乙型肝炎临床常用的疗效相对较好的一种抗病毒药物,但在疗程、复发、变异、联合用药等问题上仍未得到很好解决。我们采用拉米夫定联合中药治疗该病患者60例,经与未联用中药的60例患者对比,观察到联用中药能增强疗效。 1 资料与方法 1.1病例 120例均为我院住院或门诊的慢性乙型肝炎患者,丙氨酸氨基转移酶(ALT)升高(120±55)U/L,HBeAg阳性。HBV DNA>4.0×10~2拷贝/ml。诊断符合2000年第十次全国病毒性肝炎与肝病学术会议制定的诊断标准,且除外合     

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.