阿德福韦酯治疗两年以上低血磷发生情况的横断面调查

目的了解长期使用阿德福韦酯(ADV)患者低磷血症的发生情况及临床特点。方法选择单用或者联合抗病毒治疗方案中含有阿德福韦酯治疗2年以上慢性乙型肝炎患者纳入观察,检测其血磷及尿磷、PTH、eGFR、ALP,分析低磷累计发生率及临床特点。结果 82例慢性乙型肝炎患者单用或含有ADV联合抗病毒治疗方案进行抗病毒治疗2年,累计低磷血症17例(20.7%);有骨关节疼痛症状4例,骨密度检测均提示骨质疏松,其中1例发生病理性骨折;尿磷升高31例(37.8%),尿磷和低血磷呈负相关,17例低血磷患者均存在尿磷升高;ALP升高只出现在部分低磷血症患者。血磷和尿磷呈负相关(Pearson相关性-0.690,P0.01),尿磷可预测低血磷发生:尿磷大于1.31 g为预测低血磷最佳临界点;阳性预测值为61.2%,阴性预测值为100%。结论长期应用ADV抗病毒治疗患者,应常规随访血磷水平,早期尿磷检测可预测低磷血症发生。     

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。     

慢性乙型肝炎患者长期服用阿德福韦酯与肾性低磷血症的相关性

目的分析慢性乙型肝炎(CHB)患者长期服用阿德福韦酯(ADV)发生肾性低磷血症的危险因素。方法选取10年来长期服用ADV的CHB患者120例,连续2次检测血清磷水平,分析与低磷血症的相关因素,为早期防控提供资料。结果低磷血症的发病率为24.17%,平均值为(0.79±0.18)mmol/L,平均服用ADV时间为(5.4±2.3)年。患者年龄>55岁、服药时间>5年、联合用药、合并肝硬化为低磷血症的高危因素。结论长期服用ADV的CHB患者的低磷血症发生率较高,年龄、服药时间、联合用药和合并肝硬化是高危因素,临床上应注重高危因素的存在,加强肾功能监测,及时补充钙磷,减轻肾损害。     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的临床观察

目的研究阿德福韦治疗HBeAg阴性慢性乙型肝炎的效果。方法 34例HBeAg阴性慢性乙型肝炎患者接受阿德福韦酯治疗,32例未经治疗的患者作为对照组。观察治疗1年时的疗效。结果阿德福韦酯治疗的患者HBVDNA转阴率为88.2%(30/34),非常显著地高于对照组(P0.001),ALT复常率为76.5%(26/34),显著高于对照组(P0.01)。结论阿德福韦酯治疗HBeAg阴性慢性乙型肝炎具有良好的效果。     

核苷（酸）类药物治疗慢性乙型肝炎和乙型肝炎肝硬化患者血清磷变化及其相关影响因素分析

目的探讨应用核苷（酸）类药物抗病毒治疗慢性乙型肝炎（CHB）和乙型肝炎肝硬化患者血清磷的变化及其相关影响因素。方法回顾性分析2012年3月至2015年3月我科诊治的HBV感染患者的临床资料。使用德国罗氏公司生产的MODULP800全自动生化分析仪测定血生化指标（血磷浓度正常值为0.82~1.62 mmol/L。血磷浓度至少2次<0.82 mmol/L即诊断为低磷血症）。应用SPSS 21.0软件包对临床资料进行多因素Logistic回归分析,筛选发生低磷血症的危险因素。结果本组纳入318例患者（慢性乙型肝炎197例,乙型肝炎肝硬化121例）,其中单药或联合应用阿德福韦酯(ADV)治疗的患者217例,服用其它核苷（酸）类药物患者101例;慢性乙型肝炎患者低磷血症发生率为11.7%,肝硬化患者为10.7%（P>0.05）;在应用ADV的126例慢性乙型肝炎患者中,20例（15.9%）发生,而在71例未服用ADV的患者中,3例（4.2%）发生低磷血症（x²=5.83,P<0.05）;在应用ADV的91例乙型肝炎肝硬化患者中,11例（12.1%）发生低磷血症,而在30例未联用ADV患者中2例（6.7%）发生低磷血症（x²=0.29,P>0.05）;在33例小于35岁的患者中,8例（24.2%）发生,而在33例大于55岁的患者中,3例（9.1%）发生低磷血症（P>0.05）;多因素Logistic回归分析结果显示性别（OR=7.36,P=0.007）和使用ADV（OR=3.51,P=0.015）为发生低磷血症的影响因素。结论青壮年HBV感染者应用ADV治疗可能发生低磷血症,应注意监测。     

阿德福韦酯导致低血磷性骨软化症一例并文献复习

目的 探讨阿德福韦酯导致的低血磷性骨软化症的临床特征、治疗方案及转归.方法 对1例慢性乙型肝炎患者服用阿德福韦酯后发生的低血磷性骨软化症进行分析,并就其在全世界慢性乙型肝炎患者中的发生情况做相关文献复习.结果 本例患者的临床症状出现时间与服用阿德福韦酯时间平行,在停用阿德福韦酯并补充中性磷后,临床症状减轻,血磷恢复正常(症状较重时0.77mmol/L,停用阿德福韦酯10周时升至0.98 mmol/L),诊断为阿德福韦酯相关低血磷性骨软化症.复习文献发现阿德福韦酯导致的尿磷排泄增多存在剂量依赖性、时间依赖性、可逆性,而小剂量阿德福韦酯(10 mg/d)治疗慢性乙型肝炎后出现低血磷性骨软化症的报道均来自亚裔人群.结论 阿德福韦酯导致的低血磷性骨软化症为罕见疾病.凡因乙型肝炎服用阿德福韦酯的患者,无论剂量大小,均应定期进行相关检查,如血钙、血磷,以监测是否发生低血磷性骨软化,一旦发生,可换用其他抗病毒药物.

Abstract：

Objective To investigate the clinical features and treatment protocol and prognosis for the hypophosphataemic osteomalacia related to adefovir dipivoxil.Methods Analysis was made upon a case of patient with chronic hepatitis B developed hypophosphataemic osteomalacia after administration of adefovir dipivoxil.Literature review was carried out to survey the global prevalence of hypophosphataemic osteomalacia after administration of adefovir dipivoxil among patients with chronic hepatitis B.Results The clinical symptoms started paralleling to the time taking adefovir dipivoxil,and alleviated after the patient withdrawn adefovir dipivoxil 10 weeks and was given phosphorus.Meanwhile,serum inorganic phosphorus recovered to normal ( 0.98 mmol/L),which lowest level was 0.77 mmol/L.Systematic review of the literature showed that hyperphosphaturia related to adefovir dipivoxil was dose-dependent,time-dependent and reversible.All reported cases of hypophosphataemic osteomalacia secondary to adefovir dipivoxil ( 10mg/d) were from Asian population.ConclusionsAdefovir dipivoxil induced hypophosphataemic osteomalacia is rarely seen in clinical practice.Those patients with chronic hepatitis B who take adefovir dipivoxil,no matter dosages,should take periodical examinations including blood calcium and serium inorganic phosphorus to monitor whether hypophosphataemic osteomalacia occurs.Other anti-virus drugs could be used when it happens.     

替诺福韦酯和拉米夫定联合阿德福韦酯对乙型肝炎肝硬化患者疗效的比较

目的比较替诺福韦酯和拉米夫定联合阿德福韦酯对乙型肝炎肝硬化患者的疗效,为乙型肝炎肝硬化治疗提供一定的临床依据。方法选取我院乙型肝炎肝硬化患者共130例,实验组和对照组各65例。实验组接受替诺福韦酯(300 mg/d),对照组予以阿德福韦酯(10 mg/d)联合拉米夫定(100 mg/d),两组共治疗12个月,观察比较治疗前后肝功能、血清病毒学指标及甲胎蛋白(AFP)水平变化。结果经过治疗以后,两组患者ALT,AST,总胆红素(TBil),Child-Pugh评分,甲胎蛋白(AFP)较治疗前均显著降低,但实验组较对照组降低更加明显,其差异有统计学意义(P0.05)。治疗后,实验组HBV DNA、失代偿好转率明显高于对照组,其差异有统计学意义(P0.05)。两组患者在死亡率,肝癌发生率上差异无统计学意义(P0.05)。结论替诺福韦酯对于乙型肝炎肝硬化患者疗效优于拉米夫定联合阿德福韦酯,耐药发生率低。对于拉米夫定联合阿德福韦酯疗效欠佳的乙型肝炎肝硬化患者可以考虑改用替诺福韦酯。     

阿德福韦酯相关肾脏损害

目的:探讨阿德福韦酯引起的肾脏损害临床病理特点。方法:回顾性分析4例因慢性乙型肝炎长期使用阿德福韦酯出现肾脏损害患者的临床病理资料。结果:4例均为男性患者,年龄34～44岁,3例慢性乙型肝炎病史10年,1例慢性乙型肝炎病史20年,使用阿德福韦酯治疗3～6年。肾脏疾病病程3～23月,患者血压均正常。4例血清肌酐(SCr)均轻度升高(116.7～158.3μmol/L),1例出现低磷血症,2例伴低尿酸血症,2例少量蛋白尿(0.54g/24h和0.57g/24h),1例蛋白尿0.79～1.72g/24h,1例尿蛋白阴性,1例尿糖阳性,4例患者均无镜下血尿,肝功能正常,无低白蛋白血症和高脂血症。肾活检病理示3例患者光镜下肾小球节段轻度系膜增生,1例合并IgA肾病。4例患者肾小管间质病变均较轻,见小灶性近端肾小管上皮细胞刷状缘脱落,其中3例伴慢性病变轻～中度,灶性肾小管萎缩、基膜增厚。电镜下均见肾小管上皮细胞胞质内线粒体外形不规则、变形、体积增大。药物停用后,随访3～25月,3例患者SCr恢复正常,1例SCr稳定,血磷恢复正常,所有患者尿蛋白阴性。结论:长期使用阿德福韦酯可导致肾脏损害,患者表现轻度肾功能下降,部分患者血清磷、尿酸减低,伴肾小管功能损伤。阿德福韦酯肾脏损害可单独出现,也可和原发性肾脏疾病同时出现。形态学主要表现肾小管损伤,肾小管上皮细胞刷状缘脱落,电镜下肾小管上皮细胞胞质内异常增大和变形的线粒体。     

不同核苷类似物序贯方案对干扰素治疗无应答伴肝功能损害慢性乙型肝炎的疗效比较

目的探讨核苷类似物序贯方案对干扰素治疗无应答伴肝脏损害慢性乙型肝炎的作用。方法随机选取我院2012年5月至2015年5月收治的90例干扰素治疗无应答伴肝脏损害慢性乙型肝炎患者,依据随机数字表法将患者分为替比夫定组(n=30)、恩替卡韦组(n=30)及阿德福韦酯组(n=30)3组。治疗后对三组患者的临床疗效及不良反应发生情况进行统计分析。结果替比夫定组和阿德福韦酯组患者的完全应答率均显著高于恩替卡韦组(P0.05),部分应答率均显著低于恩替卡韦组(P0.05),复发率均显著高于恩替卡韦组(P0.05),而替比夫定组患者的复发率又显著高于阿德福韦酯组(P0.05);替比夫定组患者的不良反应发生率显著高于恩替卡韦组和阿德福韦酯组(P0.05)。结论替比夫定、恩替卡韦、阿德福韦酯序贯治疗干扰素治疗无应答伴肝脏损害慢性乙型肝炎的效果均较好。     

阿德福韦酯片联合安络化纤丸治疗慢性乙型肝炎疗效观察

目的评价阿德福韦酯片联合安络化纤丸治疗慢性乙型肝炎的疗效及安全性。方法将45例慢性乙型肝炎患者随机分成治疗组(30例)和对照组(15例),治疗组接受阿德福韦酯片联合安络化纤丸治疗,对照组单用阿德福韦酯片治疗,疗程均为24周。两组患者在治疗前后均行肝纤维化血清学指标、肝功能、血清病毒学指标检测。结果治疗结束时,治疗组患者的主要症状和体征、肝功能、肝纤维化血清指标改善优于对照组患者(P0.05),但两组HBV DNA低于检测下限的比率和血生化指标的改善差异无统计学意义(P0.05)。结论阿德福韦酯片联合安络化纤丸治疗慢性乙型肝炎能明显改善患者的症状、体征、肝纤维化血清学指标、肝功能、血清病毒学指标,且比单用阿德福韦酯片治疗慢性乙型肝炎的肝纤维化血清学指标疗效更好,能明显改善肝功能和改善患者生活质量,值得临床推广应用。     

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.