拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化84例10年临床分析

目的:对拉米夫定联合阿德福韦酯治疗10年的乙型肝炎肝硬化患者的疗效和安全性进行分析。方法:对84例乙型肝炎肝硬化患者应用拉米夫定100 mg/d联合阿德福韦酯10 mg/d口服治疗10年,分析比较患者在治疗前后的临床表现、生化学指标、病毒学改变、Child-Pugh分级情况。结果:62例(73.8%)患者经治疗后病情缓解并稳定,肝功能明显好转或恢复正常,Child-Pugh积分下降,HBV DNA水平明显下降,部分出现HBeAg/抗-HBe血清学转换。12人死亡,6人因中途停药,出现慢性肝衰竭死亡,2人因肠道肿瘤死亡;出现肝癌8例,4例带瘤生存,4例死亡。10例(11.9%)因病毒学耐药,调整治疗方案。结论:应用拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化可长期抑制HBV DNA的复制,促进肝功能的恢复,使Child-Pugh积分下降,缓解病情发展,治疗10年药物安全性好,耐药发生率低。     

拉米夫定治疗失代偿期乙型肝炎肝硬化患者的临床分析

目的探讨拉米夫定治疗失代偿期乙型肝炎肝硬化的疗效和安全性。方法将60例HBeAg/HBV DNA阳性的失代偿期乙型肝炎肝硬化患者随机分为两组,对照组30例只接受一般保肝、利尿及对症支持治疗,治疗组30例患者加用拉米夫定治疗104周。结果在治疗104周结束时,治疗组患者肝功能明显改善,ALT从135.6±22.5U/L下降到30.9±10.7U/L,TBIL从58.6±16.2μmol/l下降到28.2±18.4μmol/l,HBV DNA转阴率为86.7%,以上指标均优于对照组。结论拉米夫定治疗失代偿期乙型肝炎肝硬化能够快速抑制HBV复制,显著改善肝功能。     

阿德福韦酯、拉米夫定联合乳果糖治疗乙型肝炎肝硬化的疗效及肝纤维化保护作用

目的探讨阿德福韦酯、拉米夫定联合乳果糖治疗乙型肝炎肝硬化的临床疗效及其对肝纤维化的保护作用。方法将98例乙型肝炎肝硬化患者按照随机数字表法分为2组:研究组49例应用阿德福韦酯、拉米夫定联合乳果糖治疗,对照组49例应用阿德福韦酯、拉米夫定治疗。比较2组的病毒复制情况、肝功能指标、肝脏Child-Pugh评分、肝纤维化指标变化。结果 (1)肝功能生化指标:治疗后2组的ALT、AST、A/G、TBil均较治疗前显著改善,且研究组的改善程度优于对照组(P0.05);(2)肝脏Child-Pugh评分:治疗后2组的Child-Pugh评分均显著降低,且研究组显著低于对照组(P0.05);(3)肝纤维化指标:治疗后2组的HA、LN、Ⅳ-C、PC-Ⅲ均显著降低,且研究组的下降幅度较对照组更为明显(P0.05);(4)病毒学指标:HBV DNA转阴率、HBeAg转阴率与HBeAg/抗-HBe转换率依次为77.55%、24.49%、18.37%,均较对照组的61.22%、12.24%、6.12%提高(P0.05)。结论阿德福韦酯、拉米夫定联合乳果糖治疗乙型肝炎肝硬化能够加速肝功能的恢复,抑制肝纤维化进程。     

拉米夫定联合安络化纤丸治疗乙型肝炎肝硬化30例临床观察

目的 探讨乙型肝炎肝硬化患者通过拉米夫定和安络化纤丸联合治疗的效果.方法 随机选择45例乙型肝炎肝硬化患者,分别给予拉米夫定联合安络化纤丸和拉米夫定治疗1年6个月.结果 治疗结束时,联合组的血清谷丙酶和透明质酸水平下降比单用拉米夫定组优;治疗组30例中17例(56.7%)HBV DNA阴转,17例HBeAg阴转,7例出现抗-HBc(+);对照组15例中8例HBV DNA阴转(53.3%),8例HBeAg阴转,2例出现抗-HBc(+).结论 拉米夫定联合安络化纤丸治疗慢性乙型肝炎肝硬化疗效确切,安络化纤丸有较好抗肝纤维化及改善肝功能,缓解临床症状作用.但抗乙型肝炎毒复制作用不突出.     

替比夫定治疗活动性乙型肝炎肝硬化疗效观察

目的观察和比较替比夫定与拉米夫定治疗活动性乙型肝炎肝硬化的疗效和安全性。方法 65例活动性乙型肝炎肝硬化患者被随机分为治疗组（30例）和对照组（35例）。在常规综合治疗的基础上,治疗组给予替比夫定600mg/d口服,对照组给予拉米夫定100mg/d口服,观察72周。结果两组随治疗时间延长,患者血清HBVDNA水平下降,肝功能改善,Child-Pugh计分降低;替比夫定组治疗24周、48周和72周时,患者血清HBV DNA水平及治疗72周时ALT和Child-Pugh计分下降均优于拉米夫定组（P〈0.05或P〈0.01）;两组ALT复常、HBV DNA阴转和HBeAg阴转率无统计学差异（P〉0.05）。结论替比夫定和拉米夫定均可有效地抑制乙型肝炎肝硬化患者体内的HBV复制,改善肝功能。     

拉米夫定或阿德福韦酯选择性治疗失代偿性乙型肝炎肝硬化3年临床观察

目的观察拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者长疗程疗效及治疗方案的选择。方法乙型肝炎肝硬化失代偿期患者65例,HBV DNA5 log10拷贝/mL者服用拉米夫定(100mg/d)或再联用阿德福韦酯(10mg/d);HBV DNA5 log10拷贝/mL者可单用拉米夫定或阿德福韦酯;病毒持续不下降或反弹要求拉米夫定联用阿德福韦酯。观察治疗前后患者临床症状体征、生化指标、病毒学改变情况。结果65例患者中43例生存至研究结束,3年生存率为66.1%。患者治疗后肝功能正常或好转,病情缓解稳定,生活质量改善,HBV DNA下降约3 log10拷贝/mL,Child-Pugh积分下降3。结论拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者,可延长患者生存时间,改善肝功能,阻止病情进展,提高生活质量。     

恩替卡韦治疗104例乙型肝炎肝硬化患者96周的疗效观察

目的 观察恩替卡韦治疗乙型肝炎肝硬化的临床疗效.方法 随机选择就诊于长春市中日联谊医院消化内科未经过抗病毒治疗的乙型肝炎肝硬化患者104例,给予恩替卡韦0.5 mg,每日1次口服,连续口服96周时总结临床疗效.观察患者治疗前、后血清HBV DNA水平、肝功能及HBV标志物,其中37例患者治疗前及治疗96周后行肝组织学检查.率的比较采用χ~2检验,相关性分析采用Pearson相关系数.结果 恩替卡韦治疗4周时,HBV DNA水平平均下降3.1 log_(10),至96周时平均下降幅度达到5.1 log_(10),HBV DNA不可测率达到98.1%,ALT复常率达到80.7%;72例HBeAg阳性患者96周时HBeAg/抗-Hbe血清转换率为13.9%.104例乙型肝炎肝硬化患者中,C基因型HBV感染者64例,占61.5%,B基因型28例,占26.9%.不同基因型HBV感染者患者接受恩替卡韦治疗后的HBV DNA不可测率、ALT复常率以及HBeAg血清转换率差异无统计学意义.Child-Pugh C级2例(2/21,9.5%),Child-Pugh B级1例(1/52,1.9%)出现疾病进展,Child-Pugh A级患者31例,未出现疾病进展.37例行肝组织学检查的乙型肝炎肝硬化患者治疗96周时,肝组织学改善者Child-Pugh A级17例(17/21,81.0%),B级6例(6/9,66.7%),C级3例(3/7,42.9%).治疗前HBV DNA水平越高,Knodell HAI评分越高,r=0.80.抗病毒治疗96周后血清HBV DNA下降水平与Knodell HAI评分下降水平仍呈正相关,r=0.93.结论 恩替卡韦抗病毒治疗乙型肝炎肝硬化患者疗效显著,可延缓及阻止肝硬化患者的疾病进展.     

拉米夫定联合安络化纤丸治疗乙型肝炎肝硬化30例临床观察

目的探讨乙型肝炎肝硬化患者通过拉米夫定和安络化纤丸联合治疗的效果。方法随机选择45例乙型肝炎肝硬化患者，分别给予拉米夫定联合安络化纤丸和拉米夫定治疗1年6个月。结果治疗结束时，联合组的血清谷丙酶和透明质酸水平下降比单用拉米夫定组优；治疗组30例中17例（56．7％）HBV DNA阴转，17例HBeAg阴转，7例出现抗-HBc（＋）；对照组15例中8例HBV DNA阴转（53．3％），8例HBeAg阴转，2例出现抗-HBc（＋）。结论拉米夫定联合安络化纤丸治疗慢性乙型肝炎肝硬化疗效确切，安络化纤丸有较好抗肝纤维化及改善肝功能，缓解临床症状作用。但抗乙型肝炎毒复制作用不突出。     

拉米夫定治疗乙型肝炎后活动性肝硬化的临床应用

目的 应用拉米夫定抑制乙型肝炎病毒复制,从而缓解肝脏炎症.方法 拉米夫定100 mg/d,口服,1年后观察ALT、AST、TBIL、ALB、肝纤维化指标(HA、PCⅢ)、HBV DNA定量(PCR法)等指标,数据均以均值±标准差(-x±s)表示,所得均数比较用t检验处理;并对30例乙型肝炎后活动性肝硬化患者治疗前后用Child-Pugh评分,以观察疗效.结果 治疗结束后,HBeAg转阴6例(20.0%),HBV DNA转阴27例27%),ALT、AST、TBIL、ALB、肝纤维化指标(HA、PCⅢ)治疗前后相比,P＜0.01,有显著性差异,Child-Pugh评分得到提高,A级病例人数由治疗前的8例提高到19例.结论 拉米夫定治疗乙型肝炎后活动性肝硬化1年,患者生化指标明显改善,病毒载量明显下降,而且在治疗中未发现对肝脏功能的明显损害,可作为治疗乙型肝炎后活动性肝硬化的抗病毒药物.     

拉米夫定在失代偿期肝硬化的临床应用研究

为观察拉米夫定对慢性乙型肝炎所致失代偿期肝硬化的疗效对9例失代偿肝硬化患者应用拉米夫定的治疗结果进行总结。9例患者，HBsAg、HBV－DNA均阳性，其中6例Child-Pugh分级为B级，3例为C级。口服用拉米夫定每日100mg，疗程半年。8例患者拉米夫定治疗后血清HBV－DNA均转为阴性，肝功能保持持续稳定，Child-Pugh分级下降≥2。1例患者死亡。拉米夫定通过有效抑制HBV－DNA复制，而改善失代偿肝硬化的肝功能。     

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.     

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.     

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.