拉米夫定联合阿德福韦酯治疗耐药株感染慢性乙型肝炎37例临床观察

目的观察拉米夫定联合阿德福韦酯治疗耐药株感染慢性乙型肝炎患者的疗效。方法耐拉米夫定慢性乙型肝炎患者11例换用阿德福韦酯,耐阿德福韦酯患者6例换用拉米夫定和耐拉米夫定28例/耐阿德福韦酯9例给予拉米夫定联合阿德福韦酯,观察治疗48周的疗效。结果在治疗48周时,拉米夫定联合阿德福韦酯组患者血清HBV DNA阴转率（76%）和ALT复常率（92%）明显高于阿德福韦（45%,73%）和拉米夫定（50%,83%）治疗患者。结论拉米夫定联合阿德福韦酯治疗耐药的慢性乙型肝炎患者,优于单用拉米夫定或阿德福韦酯治疗。     

阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎的临床观察

目的 观察阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎临床疗效.方法 首先在充分告知符合研究对象的患者(80例)病情后根据患者的意愿选择分为:(1)对照组(单药治疗组,n=38例),在拉米夫定应用基础上重叠阿德福韦酯治疗12周后,停用拉米夫定,单独使用阿德福韦酯治疗132周;(2)观察组(联合治疗组,n=42例),出现拉米夫定耐药后联合应用阿德福韦酯144周.每3个月检测患者的HBV-DNA、HBV-M、肝功能、肾功能及血常规等.结果 144周疗程结束后联合治疗组患者HBV-DNA转阴率明显优于对照组,疗效差异有统计学意义(P＜0.01),HbeAg在两组间未见明显差异(P>0.05),联合治疗组治疗后肝功能复常率较单药治疗组高(P<0.05).结论 阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎有较好的疗效.     

阿德福韦酯初治与挽救治疗拉米夫定耐药的慢性乙型肝炎观察

目的观察阿德福韦酯初治与拉米夫定治疗耐药后联合阿德福韦酯治疗慢性乙型肝炎患者的疗效。方法将45例入选患者分为两组,其中A组为拉米夫定治疗耐药后加用阿德福韦酯治疗组,B组为阿德福韦酯初治组。治疗前及治疗后12、24、36、48周均检测肝功能、肾功能、HBV DNA载量。结果在治疗12、24周时,A组患者的HBV DNA低于检测下限的比率明显高于B组,差异有统计学意义;治疗48周时,两组HBV DNA载量变化、低于检测下限的比率、ALT复常率的差异均无统计学意义。在治疗期间两组患者的肾功能均正常,均未发现不良反应。结论阿德福韦酯初治与联合拉米夫定治疗拉米夫定耐药后慢性乙型肝炎患者同样有效,值得继续探索。     

替比夫定联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎患者疗效观察

目的探讨拉米夫定耐药患者的治疗方法。方法选取拉米夫定治疗失效的慢性乙型肝炎患者60例,28例接受阿德福韦酯治疗,32例接受替比夫定联合阿德福韦酯治疗,观察52周。结果在治疗52周时,联合治疗组HBV DNA转阴率为98%,阿德福韦治疗组为90%（P〉0.05）,无统计学差异;联合治疗组HBeAg转阴率为37.5%,阿德福韦治疗组为7.0%,联合治疗组HBeAg血清学转换率为18.8%,阿德福韦治疗组为3.5%较（P〈0.01）,具有统计学差异;联合治疗组ALT复常率为93%,阿德福韦治疗组为75%（P〈0.01）,存在统计学差异。结论替比夫定联合阿德福韦酯联合治疗拉米夫定治疗失效的慢性乙型肝炎患者具有显著的临床疗效,无明显的不良反应。     

拉米夫定耐药慢性乙型肝炎患者改用阿德福韦酯单药治疗后发生耐药及处理

目的 探讨拉米夫定耐药慢性乙型肝炎患者改用阿德福韦酯治疗后发生耐药的临床过程及挽救治疗疗效.方法 回顾性分析15例慢性乙型肝炎患者拉米夫定耐药后,在阿德福韦酯单药治疗期间出现的病毒学突破,采用基因测序法检测到HBV聚合酶基因阿德福韦酯相关突变位点,接受挽救治疗措施.结果 15例拉米夫定耐药患者经中位时间为16个月的阿德福韦酯单药治疗,14例出现与阿德福韦酯耐药相关的rtA181T/V和(或)rtN236T突变,1例出现rtM204I+rtL180M+rtA181T联合突变.耐药后15例患者均给予挽救性治疗措施,其中7例接受拉米夫定联合阿德福韦酯治疗的患者,3个月时HBV DNA平均下降(2.2±0.6)lg拷贝/mL,6个月时,5例HBV DNA低于检测限;另3例接受恩替卡韦治疗患者,6个月时HBV DNA水平下降2.8～3.5 lg拷贝/mL.结论 拉米夫定联合阿德福韦酯是拉米夫定耐药慢性乙型肝炎患者改用阿德福韦酯单药治疗发生阿德福韦酯耐药后的有效挽救治疗措施.     

膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床研究

目的 观察膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎患者的疗效和安全性.方法 选择拉米夫定耐药的慢性乙型肝炎患者70例,随机分为联合组(膦甲酸钠和阿德福韦酯组)36例,对照组(阿德福韦酯组)34例,完成4周和12周治疗时,分别检测血清HBV DNA水平和肝功能变化.结果 在治疗4周和12周时,联合组肝功能恢复及病毒应答率,均显著高于对照组.两组均未发生与研究药物相关的严重不良反应.两组不良事件发生率无统计学差异.结论 膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎,可在生物化学及病毒学方面取得较好疗效,且安全性好.     

阿德福韦酯联合胸腺肽α1治疗拉米夫定耐药慢性乙型肝炎患者的研究

目的观察阿德福韦酯联合胸腺肽α1治疗疑有拉米夫定临床耐药慢性乙型肝炎的疗效。方法将入选病例随机分为阿德福韦酯组和联合治疗组,阿德福韦酯组给予阿德福韦酯10mg/d,连用48周;联合治疗组在阿德福韦酯组治疗基础上加用胸腺肽α11.6mg,皮下注射,每周2次,连用48周。观察2组患者的病毒应答率、生化应答率、HBeAg阴转率及HBe转换率。结果阿德福韦酯组24周时病毒应答率为53%,生化应答率为53%,HBeAg阴转率为15%,HBe转换率为6%;48周时病毒应答率为59%,生化应答率为68%,HBeAg阴转率为26%,HBe转换率为12%。联合治疗组24周时病毒应答率为68%,生化应答率为74%,HBeAg阴转率为38%,HBe转换率为21%;48周时病毒应答率为85%,生化应答率为91%,HBeAg阴转率为56%,HBe转换率为38%。结论阿德福韦酯治疗对拉米夫定耐药的慢性乙型肝炎效果显著,且随时间延长而疗效提高;与胸腺肽%1联合,其疗效更加显著。     

阿德福韦酯联合拉米夫定治疗YMDD变异慢性乙型肝炎的临床研究

目的:对经拉米夫定治疗出现YMDD变异的慢性乙型肝炎患者采用阿德福韦酯联合拉米夫定治疗48周,观察其疗效及不良反应,探讨慢性乙型肝炎YMDD变异后的治疗方案.方法:将72例患者随机分为3组,A组单用阿德福韦酯治疗48周;B组采用阿德福韦酯与拉米夫定联合治疗12周,后单用阿德福韦酯治疗36周;C组采用阿德福韦酯与拉米夫定联合治疗48周.结果:3组治疗12周内ALT水平进一步反弹升高的患者比例分别为29.2%(7/24)、12.5%(3/24)、4.2%(1/24)(P＜0.05),A组1例患者出现重型肝炎;治疗12周3组患者YMDD变异株检测阳性率分别有17.4%、0、0.治疗48周与治疗前比较3组患者血清ALT水平均显著下降(P＜0.05);但3组之间比较差异均无显著性意义(P＞0.05),HBV DNA水平较基线值显著下降(P＜0.05),均未检测出YMDD变异株;治疗48周3组间e抗原阳性患者血清转换率比较,差异均无显著性意义(P＞0.05);C组患者HBV DNA转阴率与A组比较,差异有显著性意义(P＜0.05),3组患者的HBV DNA反弹率分别为8.3%(2/24)、4.2%(1/24)、0.A组2例耐药患者测序结果为rtN236T变异,B组rtA181V+rtN236变异和rtN236T变异各1例.结论:YMDD变异后采用阿德福韦酯与拉米夫定联合治疗更安全有效.     

阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床观察

目的观察拉米夫定治疗慢性乙型肝炎发生病毒基因变异后,单用或联合阿德福韦酯治疗的疗效以及安全性。方法 35例拉米夫定治疗失败的慢性乙型肝炎患者接受阿德福韦酯治疗,另30例患者采用拉米夫定联合阿德福韦酯治疗,观察2年。结果联合组与阿德福韦酯治疗组比,在治疗2年时,ALT复常率和HBVDNA阴转率均明显高于阿德福韦酯治疗组(P0.05);阿德福韦酯治疗无严重不良反应发生。结论阿德福韦酯联合拉米夫定治疗拉米夫定治疗失败的慢性乙型肝炎患者,远期疗效优于单用阿德福韦酯组。     

阿德福韦酯联合恩替卡韦优化治疗拉米夫定和阿德福韦酯联合治疗失败的慢性乙型肝炎临床疗效分析

目的 探讨阿德福韦酯联合恩替卡韦对拉米夫定联合阿德福韦酯治疗失败（包括发生疗效欠佳及病毒学突破）的慢性乙型肝炎患者的临床疗效及安全性.方法 将70例对拉米夫定联合阿德福韦酯治疗失败的慢性乙型肝炎患者随机分为对照组和优化组.对照组继续予拉米夫定（100 mg/d）联合阿德福韦酯（10 mg/天）治疗;优化组在服用阿德福韦酯（10 mg/d）的同时,联合使用恩替卡韦（0.5 mg/d）优化治疗.所有患者均治疗48周.治疗前、治疗12周、24周和48周分别进行生物化学、病毒学、血清学检测.回顾性分析、比较两组患者上述治疗时间点的生物化学应答率（BR）、完全病毒学应答率（CVR）、病毒学突破率（VBR）和HBeAg/HBeAb血清学转换率.结果 优化组患者治疗48周后BR、CVR、VBR分别为75.0％（12/16）、81.8％ （27/33）、3.0％（1/33）,对照组分别为26.3％ （5/19）、32.4％ （12/37）和21.6％ （8/37）,两组比较差异具有统计学意义（P值均＜0.01）.但两组患者治疗48周后,HBeAg/HBeAb血清学转换率分别为5.9％（1/17）和13.3％ （2/15）,两组比较差异无统计学意义（P＞0.05）.两组患者耐受性良好,无1例患者出现严重不良反应而导致停药.结论 对于拉米夫定联合阿德福韦酯治疗失败的慢性乙型肝炎患者,阿德福韦酯联合恩替卡韦是一种行之有效的优化治疗方案.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.