阿德福韦酯治疗慢性乙型肝炎患者的临床疗效观察

目的观察阿德福韦酯对慢性乙型肝炎患者的临床疗效。方法随机选择慢性乙型肝炎患者39例,其中12例为拉米夫定治疗后出现YMDD变异者。治疗48周,检测血清HBV DNA及HBV血清学标志物和ALT。结果治疗48周时,全组血清HBV DNA水平下降到1.3×103copies/ml,HBV DNA转阴率为56.4%,HBeAg转阴率为35.9%,HBeAg/抗-HBe转换率12.8%,ALT复常率为69.2%;YMDD变异组血清HBV DNA水平下降到7.9×103copies/ml,HBV DNA转阴率为50.0%,HBeAg转阴率为25.0%,HBeAg/抗-HBe转换率8.3%,ALT复常率为58.3%;HBV DNA>108copies/ml组,血清HBV DNA水平下降到6.8×103copies/ml,HBV DNA转阴率为0.0%,无HBeAg转阴和抗-HBe血清转换,ALT复常率为50.0%。结论阿德福韦酯是一有效的抗HBV药物。对HBV DNA野生株、拉米夫定耐药变异株均有抑制作用,HBV DNA基线水平低者疗效好,HBV DNA>108copies/ml者,疗效差。     

拉米夫定治疗慢性乙型肝炎36例临床观察

目的观察拉米夫定治疗慢性乙型肝炎的效果。方法36例患者,采取拉米夫定治疗,分别于12月和24个月时观察ALT复常率,HBV DNA转阴率及HBeAg转阴率,同时检测YMDD变异的情况。结果拉米夫定治疗1年的HBV DNA、HBeAg转阴率为别为54.5%、24.2%,HBeAg/抗HBe血清转换率12.1%,ALT复常率78.8%,YM-DD变异率5.6%。停药半年后血清HBV DNA复阳率为22.2%,YMDD变异率18.2%,ALT再次升高率33.3%,死亡1例。结论拉米夫定能够有效降低HBV DNA水平,随着用药时间的延长,YMDD变异的发生率逐渐升高,部份病例停药后出现病情反复或加重。     

拉米夫定治疗慢性乙肝病毒感染病人的疗效分析

目的：观察拉米夫定（Lamivudine）治疗慢性乙肝病毒（HBV）感染病人的疗效及影响因素。方法：60例慢性HBV感染病人予拉米夫定（100mg qd）治疗12个月。疗效评估包括血清HBV病毒学、血清HBV免疫学、血清生化学应答率。结果：治疗12个月后，HBV DNA PCR荧光定量检测总的血清HBV DNA转阴率为57.89％，HBeAg/抗-HBe血清转换率为6.25％，ALT复常率为68.89％。其中，（1）血清ALT异常、HBeAg阳性组病人的荧光定量检测HBV DNA转阴率为55.56％，HBeAg/抗-HBe血清转换率为8.33％，ALT恢复正常率为63.89％；完全应答率为8.33％，部分应答率为75.00％，无应答率为16.67％。（2）ALT正常、HBeAg阳性组的12例病人中，仅有4例病人的血清HBV DNA转阴，无1例发生HBeAg/抗-HBe血清转换。（3）ALT异常、HBeAb阳性组的9例病人中，8例病人的HBV DNA转阴同时伴ALT复常。结论：本组病例分析结果表明，拉米夫定可以有效地抑制血清HBV的复制，改善肝功能。机体免疫状况对拉米夫定抗病毒治疗有较大影响，治疗前ALT水平是预测疗效的重要指标。对ALT异常的慢性HBV感染病人，HBeAg阴性者似乎比HBeAg阳性者有更好的治疗反应，可能更适合用拉米夫定治疗。病人对拉米夫定普遍耐受性良好。     

拉米夫定联合α-干扰素治疗慢性乙型肝炎对HBV YMDD变异的影响

目的探讨α-干扰素联合拉米夫定治疗慢性乙型肝炎对HBV YMDD变异的影响。方法40例患者被随机分为治疗组20例，给予口服拉米夫定100mg／d，同时予以αlb-干扰素5MU／d，肌肉注射，两周后改为隔日一次，疗程1年；对照组20例，单用拉米夫定100mg／d，疗程1年。结果疗程结束时，两组患者HBV YMDD变异率分别为15．0％和30．0％（P〈0．05），HBeAg血清转换率分别为40．0％和35．0%（P〉0．05）。治疗组发生YMDD变异率明显低于对照组。结论拉米夫定联合干扰素治疗慢性乙型肝炎，不能提高HBeAg血清转换率，但可降低YMDD变异率。     

拉米夫定与α干扰素联合治疗慢性乙型肝炎

目的 观察拉米夫定(LAM)联合干扰素α1b(IFNα1b)治疗慢性乙型肝炎的近期疗效和安全性。方法 HBV DNA和HBeAg均阳性的90例慢性乙型肝炎患者，按1：1：1的比例进入三个不同的治疗组。联合治疗组：用IFNα1b 5MU，隔日肌肉注射，及口服LAM 100mg／d，共6个月，随后单用口服LAM 100mg／d6个月；LAM组：口服LAM 100mg／d共12月：IFN组：IFN α1b 5MU，隔日肌肉注射，共6个月。结果 治疗结束时，HBV DNA转阴率，联合治疗组为90．0％，LAM组为80％，IFN组为46．7％。丙氨酸氨基转移酶(ALT)复常率，联合治疗组为90．0％，LAM组为80．0％，IFN组为53．3％。HBeAg／抗HBe血清转换率，联合治疗组为46．7％，LAM组为13．3％，IFN组为33．3％。联合治疗组患者治疗结束时无一例检测到YMDD变异。结论 联合治疗组对HBV DNA抑制作用及ALT复常率高于单用干扰素组，与单用拉米夫定组接近。HBeAg／抗HBe血清转换率高于拉米夫定组，与单用干扰素组相近。初步显示联合治疗组发生YMDD变异较少。     

拉米夫定联合胸腺肽治疗慢性乙型肝炎的疗效观察

目的 评价拉米夫定联合胸腺肽治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性，探讨两者联合治疗的协同作用。方法 将207例HBV DNA及HBeAg阳性的CHB患者随机分为甲乙两组，甲组采用拉米夫定和胸腺肽联合治疗，乙组单用拉米夫定治疗。胸腺肽15mg口服，每日1次，疗程6个月。两组拉米夫定治疗均为100mg，每日1次，口服，其中甲组92例(92／124)、乙组70例(70／83)用药超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，治疗结束后继续随访12个月。结果 治疗6个月时，甲乙两组ALT复常率分别为87．1％和74．7％，甲组显著高于乙组(P＜0．05)，但两组HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均无显著性差异(P＞0．05)。治疗12个月时，甲乙两组ALT复常率和HBV DNA阴转率无显著性差异(P＞0．05)，甲组HBeAg阴转率及HBeAg／抗-HBe血清转换率均显著高于乙组(P＜0．05)。随访结束时，甲组从量复常率、HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均显著高于乙组(P＜0．05)。结论 拉米夫定与胸腺肽联合治疗CHB，疗效明显优于单用拉米夫定，是CHB患者安全有效的治疗方法。     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者7年结果总结

目的 评估拉米夫定治疗乙型肝炎5年的长期疗效和安全性,以及对病毒变异发生率的影响.方法 429例HBsAg,HBeAg阳性的慢性乙型肝炎患者,先按3:1随机双盲分成拉米夫定组和安慰剂组,治疗共12周,以后所有患者均服拉米夫定100 mg/d,共5年.结果 服药治疗5年后,血清HBV DNA仍持续降低,在YMDD变异患者中则增高,中位值为107.5 Meq/nd.HBeAg阴转率和HBeAg/抗Hbe血清转换率分别为28.6%和27.5%.与治疗前ALT水平有显著关系.治疗前ALT基础值＞2×ULN(正常值上限)和＞5×ULN者,5年时HBeAg阴转率和血清转换率均为50%和67%.治疗前ALT增高的患者,5年治疗后,ALT的复常率为58%,治疗前ALT正常的患者,67.0%仍正常.1,2,3,4和5年的YMDD变异率分别为12.1%,49.7%,70.5%,67.0%和70.8%.发生变异后,HBV DNA大多仍可有一定程度抑制,在基线以下少部分可回升.在YMDD变异患者,继续有HBeAg阴转和血清转换,分别为18.4%和17.8%,低于非变异组患者.疗程中ALT增高＞5×ULN有22例,其中变异者16例,非变异者6例,经处理后均缓解.在5年治疗期间,不良反应24.8%.结论 长期应用拉米夫定可持久抑制HBV复制和促进血清转换,耐受性和安全性好,选择适合的患者,可取得最佳疗效.     

拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床

目的:探讨拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床的关系。方法:对应用拉米夫定治疗的19例慢性乙型肝炎患者进行肝功能、乙肝病毒血清学标志物、HBV YMDD变异检测,个别病例进行肝组织病理学检查。结果:ALT异常率为47％,HBeAg血清转换率为15.8％,HBV YMDD变异发生率为25％,肝组织中HBsAg和HBcAg依然阳性。结论:运用拉米夫定治疗慢性乙型肝炎6个月后可出现HBV YMDD变异,随着治疗时间延长,其变异发生率越高;该药远期降酶作用不够理想;HBeAg血清转换率不高;肝组织内仍处于炎症状态。     

拉米夫定联合苦参素治疗HBeAg阳性慢性乙型肝炎70例

[目的]观察拉米夫定联合苦参素治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效。[方法]将140例CHB患者随机分为2组,治疗组70例给予拉米夫定联合苦参素治疗;对照组70例单服拉米夫定疗程均1 a。比较2组治疗后血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)复常率,HBeAg/抗-HBe转换率,HBeAg、HBV DNA转阴率,YMDD突变率。[结果]治疗组治疗后12个月血清HBeAg/抗-HBe转换率、HBeAg转阴率、YMDD突变率分别为35.7%、47.1%、12.9%;对照组分别为17.1%、27.1%2、8.6%,2组差异有统计学意义(P0.05),2组ALT、AST的复常率比较均P0.05,HBV DNA转阴率P0.05。[结论]拉米夫定联合苦参素治疗HBeAg阳性CHB疗效优于单用拉米夫定治疗。     

阿德福韦酯初始治疗慢性乙型肝炎疗效观察

目的观察阿德福韦酯治疗慢性乙型肝炎患者的临床疗效及不良反应。方法选择慢性乙型肝炎患者433例,分为HBeAg（＋）组270例,HBeAg（-）组163例,口服阿德福韦酯10mg,1／d,连续服用。检测肝功能指标ALT、AST、TBIL及HBV血清学标志物HBV DNA、HBVM。结果随治疗时间的延长,2组患者血清ALT复常率、HBV DNA阴转率或HBeAg血清转换率均逐渐升高,HBV DNA下降幅度逐渐增大。在12个月时2组ALT复常率分别为77．4％和74．7％,HBV DNA阴转率为56．5％和54．2％,HBV DNA下降幅度3．79log10和2．96log10,HBeAg（＋）组HBeAg血清转换率为25．6％;在24个月时2组ALT复常率分别为92．9％和85．7％,HBV DNA阴转率分别为72．6％和66．7％,HBV DNA下降幅度分别为3．90log10和3．14log10,HBeAg（＋）组HBeAg血清转换率为33．3％。2组临床疗效相似,各指标未见统计学差异。所有病例均未见严重不良反应。结论阿德福韦酯是一种有效的抗HBV药物,对HBeAg（＋）和HBeAg（-）慢性乙型肝炎均能有效控制病毒复制,改善肝功能,促使HBeAg血清学转换。长期用药安全性及耐受性良好。     

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.     

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.     

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.