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1.
1.患者资料:男性,53岁,体质量83kg.6年前,出现肝区不适、食欲不振、肝功能异常,HCV RNA为5×106IU/ml,确诊为慢性丙型肝炎.曾接受干扰素(IFN)α-2b联合利巴韦林(RBV)1000 mg/d治疗,IFN α-2b初始剂量为3 MU,隔天肌注,治疗至12周时HCV RNA降至6×104 IU/ml,期间出现皮肤、黏膜干燥的轻微症状.由于病毒学应答情况不佳,当时采取IFN o-2b强化治疗方案(6 MU)继续治疗4周后,HCV RNA降至5×103IU/ml,但同时出现较严重的皮肤炎症反应,注射部位出现明显的泡状红疹,脸部、头颈部、肢端、手背、躯干部、臀部出现瘙痒性丘疹样红疹.随后,IFN α-2b剂量恢复至3 MU,给予皮质激素对症治疗.48周治疗结束时,HCV RNA阴转,皮肤炎症恢复正常,但随访6周后复发.  相似文献   

2.
目的 探讨据聚乙二醇干扰素α-2a联合利巴韦林应答情况指导治疗的个体化策略在基因1型HCV感染慢性丙型肝炎患者中的应用效果. 方法 140例基因1型HCV感染慢性丙型肝炎患者注射聚乙二醇干扰素α-2a 180 μg,每周一次;联合利巴韦林800~1200 mg/d.治疗4周达到快速病毒学应答(RVR)患者(定为A组)随机分为两组,分别接受24周治疗(A1组)、48周治疗(A2组);未达到RVR者在12周达到完全早期病毒学应答(cEVR)的患者(B组)再随机分为两组,分别接受48周治疗(B1组)、72周治疗(B2组); 24周延迟病毒学应答(PVR)的患者接受72周治疗(C1组),24周无PVR的患者终止治疗(C2组).治疗停止后随访24周.用荧光定量PCR法检测不同时间点的HCV RNA水平,比较不同疗程组的疗效.计量资料两组间比较采用t检验,计数资料采用x2检验.结果 治疗24周患者的治疗结束时病毒学应答(ETR)率为100%,持续病毒学应答(SVR)率为65.9%,复发率为34.1%;治疗48周患者的ETR率为95.3%,SVR率为82.8%,复发率为12.5%;治疗72周患者的ETR率为82.1%,SVR率为67.9%,复发率为14.3%.A1组、A2组患者的SVR率分别是65.9%和84.4%,差异有统计学意义(P<0.00).A组中HCV RNA<1×106拷贝/ml的患者接受24周和48周疗程的SVR率分别为72.7%和100%,差异无统计学意义(P>0.05); HCV RNA≥1 × 106拷贝/ml的患者接受24周和48周疗程的SVR率分别是63.6%和85.3%,差异有统计学意义(P<0.05).B1组、B2组患者的SVR率分别是78.9%和73.7%,差异无统计学意义(P>0.05).C1组患者的SVR率是55.6%.在治疗期间均无特殊不良事件发生.结论 RVR、cEVR是慢性丙型肝炎应答指导的预测因子.获得RVR者,治疗48周比24周的SVR率高;但获得RVR且基线HCV RNA<2×106拷贝/ml患者,可缩短疗程,接受24周的治疗.未获得RVR而达到cEVR的患者,延长治疗至72周并未提高SVR率.24周延迟应答者,延长疗程至72周可以提高SVR率.  相似文献   

3.
目的 比较聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者的疗效,并对影响抗病毒疗效的因素进行分析。方法 2010年5月~2014年8月我院收治的慢性丙型肝炎患者116例,随机将患者分为研究组和对照组,每组58例。给予对照组患者普通干扰素α-2b 联合利巴韦林治疗,给予研究组患者聚乙二醇α-2a干扰素联合利巴韦林治疗。采用实时荧光定量PCR法检测血清HCV RNA定量,对两组病毒学应答率以及性别、年龄、体质指数和病毒载量对治疗效果的影响进行比较分析。结果 在治疗12周、24周、48周以及停药后12周和24周,研究组患者血清HCV RNA转阴率分别为51.72%、60.34%、72.41%、68.97%和65.52%,显著高于对照组患者的31.03%、48.27%、55.17%、48.27%和41.38% (P<0.05);研究组患者快速病毒学应答率、早期病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为75.86%、84.48%、86.20%和74.14%,显著高于对照组的51.72%、60.34%、63.79%和55.17%(P<0.05);在治疗4周、12周、24周和48周,研究组患者血清HCV RNA水平分别为(4.72±1.30) IU/ml、(4.09±1.21) IU/ml、(3.79±1.18) IU/ml和(3.26±1.08) IU/ml,显著低于对照组患者的(5.27±1.52) IU/ml、(4.68±1.41) IU/ml、(4.15±1.37) IU/ml和(3.99±1.16) IU/ml(P<0.05);两组患者在治疗过程中,均出现发热、失眠、肌肉酸痛、乏力和白细胞下降等不良反应,但差异均不具有统计学意义(P>0.05);研究组获得SVR患者治疗前血清HCV RNA水平为(3.57±0.45) IU/ml,显著低于未获得SVR患者的(4.92±0.09) IU/ml(P<0.05)。讨论 聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者有效且安全,治疗前患者病毒载量低将预示疗效好。  相似文献   

4.
目的比较聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者的疗效,并对影响抗病毒疗效的因素进行分析。方法 2010年5月~2014年8月我院收治的慢性丙型肝炎患者116例,随机将患者分为研究组和对照组,每组58例。给予对照组患者普通干扰素α-2b联合利巴韦林治疗,给予研究组患者聚乙二醇α-2a干扰素联合利巴韦林治疗。采用实时荧光定量PCR法检测血清HCV RNA定量,对两组病毒学应答率以及性别、年龄、体质指数和病毒载量对治疗效果的影响进行比较分析。结果在治疗12周、24周、48周以及停药后12周和24周,研究组患者血清HCV RNA转阴率分别为51.72%、60.34%、72.41%、68.97%和65.52%,显著高于对照组患者的31.03%、48.27%、55.17%、48.27%和41.38%(P0.05);研究组患者快速病毒学应答率、早期病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为75.86%、84.48%、86.20%和74.14%,显著高于对照组的51.72%、60.34%、63.79%和55.17%(P0.05);在治疗4周、12周、24周和48周,研究组患者血清HCV RNA水平分别为(4.72±1.30)IU/ml、(4.09±1.21)IU/ml、(3.79±1.18)IU/ml和(3.26±1.08)IU/ml,显著低于对照组患者的(5.27±1.52)IU/ml、(4.68±1.41)IU/ml、(4.15±1.37)IU/ml和(3.99±1.16)IU/ml(P0.05);两组患者在治疗过程中,均出现发热、失眠、肌肉酸痛、乏力和白细胞下降等不良反应,但差异均不具有统计学意义(P0.05);研究组获得SVR患者治疗前血清HCV RNA水平为(3.57±0.45)IU/ml,显著低于未获得SVR患者的(4.92±0.09)IU/ml(P0.05)。讨论聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者有效且安全,治疗前患者病毒载量低将预示疗效好。  相似文献   

5.
目的 分析聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV)治疗慢性丙型肝炎患者的病毒学应答情况及其影响因素.方法 入组对象为接受PEG-IFNα-2a或PEG-IFNα-2b联合RBV治疗的慢性丙型肝炎患者130例,收集患者基线、治疗4、12、48周和停药24周的资料,包括年龄、性别、体质指数(BMI)、脾指数(SPI)、门静脉内径(PV)、HCV基因型、HCV RNA载量等.比较获得持续性病毒学应答( SVR)与未获得持续性病毒学应答(NSVR)的情况,对SVR的影响因素进行相关分析.数据处理采用t检验、x2检验和Logistic回归分析.结果 总SVR率为84% (109/130),其中快速病毒学应答(RVR)率为21%(27/130),早期病毒学应答(EVR)率为72% (94/130),治疗结束时病毒学应答(ETVR)率为93%(121/130).HCV基因1型患者SVR率为82%(45/55),非基因1型SVR率为87%(13/15);患者年龄、基线HCV RNA载量、BMI、SPI与SVR负相关(回归系数<0,均OR<1,均P<0.05),EVR与RBV总量和SVR呈正相关(回归系数>0,均OR>1,均P<0.05),而RVR、PV及PEG-IFN总量与SVR不相关(均P>0.05).结论 PEG-IFN联合RBV治疗慢性丙型肝炎患者的SVR率较高,超过80%患者可治愈;年龄大于35岁、既往治疗失败、基线病毒载量高于6×105 IU/mL、BMI>26 kg/m2、SPI>40 cm2、RBV累计量不超过标准量80%的患者SVR率较低.  相似文献   

6.
目的 应用干扰素α-2b联合利巴韦林治疗由一名献血员所致62例慢性丙型肝炎(CHC)患者,评估其疗效.方法 62例输血后CHC患者给予干扰素α-2b联合利巴韦林治疗(标准干扰素3~5MU,隔日一次注射,口服利巴韦林0.6~ 1.0g/d),疗程48周,随访96周.以持续病毒应答(SVR)率、早期病毒学应答(EVR)率、治疗结束时病毒学应答(ETVR)率、停药后生物化学应笞率为考核指标,同时观察药物不良反应.计量资料用均数±标准差(x-±s)表示,计数资料用x2检验.结果 SVR率为83.9% (52/62),EVR率为95.2% (59/62),ETVR率为87.1% (54/62),停药后生物化学应答率为100.0%.不同病毒载量(x 2=10.13,P<0.05)和不同年龄(x 2=14.58,P<0.01)患者SVR率差异明显.干扰素所致8例甲状腺功能轻度异常者经内分泌专科协助能坚持完成抗病毒治疗.结论 干扰素α-2b联合利巴韦林治疗CHC患者疗效显著,获得SVR的52例停药后随访96周均无复发,疗效与感染HCV时较年轻、感染时间较短、多数患者病毒载量较低、治疗依从性较好等因素有关,与性别无关.只要患者血清HCV RNA阳性,均应抗病毒治疗,以清除病毒、阻断和延缓病情进展.  相似文献   

7.
Fan XH  Wang LF  Liu LC  Yao Y  Shan Y  Lu HY  Wu CH  Xu XY  Wei L 《中华肝脏病杂志》2011,19(10):721-725
目的 探讨在应用聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗的慢性丙型肝炎(CHC)患者中,冷球蛋白血症对抗病毒治疗效果的影响. 方法 40例接受聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗的CHC患者进入研究,检测HCV基因型与基线、用药后4周、12周及治疗结束后24周患者血清HCV RNA水平,并检测基线患者血清中的冷球蛋白.连续型变量用独立样本t检验或秩和检验,分类资料用x2检验或Fisher' s精确概率法,对抗病毒治疗效果相关影响因素的分析用多元logistic回归分析.结果 治疗4周后快速病毒学应答发生率在冷球蛋白阳性患者(6/18,33.3%)低于阴性患者(15/22,68.2%,P=0.028).冷球蛋白阳性患者的持续病毒学应答发生率也低于阴性患者(0对比6/6,P=0.012).结论 冷球蛋白阳性的CHC患者快速病毒学及持续病毒学应答疗效低于冷球蛋白阴性的CHC患者.  相似文献   

8.
林芳  王慧芬 《中华肝脏病杂志》2006,14(3):163-163,166
一、病例资料患者女性,44岁,1997年单位体检发现抗丙型肝炎病毒 (HCV)阳性,2004年12月复查肝功能,丙氨酸氨基转移酶 (ALT)108 U/L,天冬氨酸氨基转移酶(AST)89 U/L;2005 年3月底轻度乏力,化验检查:ALT 46 U/L,AST 46U/L, 凝血酶原时间(PT)13s,凝血酶原活动度(PTA)93%,抗- HCV阳性,HCV RNA 6.85×10~6拷贝/ml,HCV RNA未分出型,B超提示慢性肝损害,诊断为慢性丙型肝炎。化验检查甲状腺功能五项均正常,自身抗体阴性。2005年4月14日开始皮下注射长效α干扰素50μg(美国先灵葆雅公司产品),每周1次;利巴韦林0.4g,2次/d,口服。用药2周后复查肝功能正常,HCV RNA阴转(<10~3拷贝/ml),甲状腺功能正常,出院。出院后在当地医院定期复查,每2周复查血常规,每月复查肝功能均为正常,未复查甲状腺功能。2005年8月初明  相似文献   

9.
目的 探讨干扰素治疗慢性丙型肝炎的快速病毒学应答(RVR)对疗效的预测及其相关因素.方法 对139例慢性丙型肝炎患者,根据其临床特点,给予标准干扰素(IFN)或聚乙二醇干扰素(PEG-IFN)治疗.IFN α3~5MU隔日注射1次;PEG-IFNα-2a 135~180 μg,或PEG-IFNα-2b 50~80 μg,每周注射1次.并根据患者的体质量给予600~1500 mg/d的利巴韦林,在治疗的0、4,12周和以后每间隔12周、治疗结束后的24周进行HCV RNA含量检测,根据患者治疗过程中的病毒学应答情况给予24~72周的疗程,以持续病毒学应答(SVR)作为疗效的评判指标.根据资料不同采用χ2检验或t检验.结果 132例患者完成了全程观察,其中4例治疗无效(3.0%),12例复发(9.1%),获得SVR有116例(87.9%).120例在治疗4周时检测了病毒学指标,101例(84.2%)获得了RVR,治疗前病毒载量为(5.883±1.246)lg拷贝/ml,19例无RVR,治疗前病毒载量为(6.502±0.693)lg拷贝/ml,两组比较,t:2.15,P=0.034,差异有统计学意义.97例完成全程观察的RVR患者中,88例(90.7%)获得SVR,17例无RVR的患者,14(82.4%)例获得了SVR,x3=0.371,P=0.543,差异无统计学意义.基因1型HCV感染患者的RVR为80.7%(46/57),非基因1型HCV感染患者的RVR率为92.6%(25/27),两组间比较,χ2=6.00,P=0.112,差异无统计学意义.初治患者的RVR率为87.8%,干扰素再治疗者的RVR率为65.0%,两组比较,χ2=4.651,P=0.031,差异有统计学意义. 结论 干扰素个体化抗病毒治疗慢性丙型肝炎,有较高的RVR获得率.RVR的获得与治疗前HCV RNA载量和患者是否为初次治疗相关,与基因型无关,RVR的获得可预测SVR的获得.  相似文献   

10.
干扰素联合利巴韦林治疗慢性丙型肝炎患者的疗效   总被引:2,自引:0,他引:2  
Tao J  Liu J  Pu D  Lei H 《中华肝脏病杂志》2011,19(9):683-685
目的 研究昆明地区HCV感染者的病毒基因型分布,观察干扰素和利巴韦林联合治疗慢性丙型肝炎的疗效。 方法 采集60例慢性丙型肝炎患者的血液样品,采用特异性探针杂交法进行HCV基因分型,根据基因分型结果将患者分为HCV 1b型感染的长效干扰素治疗组(皮下注射聚乙二醇干扰素α-2a 180μg,1次/周)和非1b型感染的普通干扰素治疗组(皮下注射普通干扰素α-1b50μg,隔日1次),两组患者均口服利巴韦林,剂量为900 ~ 1200 mg/d。治疗前后和随访中检测患者血浆HCV RNA和ALT水平作为疗效评价的指标。用x2检验比较治疗结束后HCV 1b基因型与HCV非1b基因型感染患者肝功能异常率的差异。结果 60例患者的血液样本中,HCV 1b基因型感染患者13例(21.7%),HCV 2a基因型3例(5.0%),HCV 3a基因型10例(16.7%),HCV 3b基因型29例(48.3%),HCV 6a基因型5例(8.3%);60例患者均完成治疗48周,长效干扰素治疗组和普通干扰素治疗组获得持续病毒学应答率分别为46.1%、74.5%;获得早期病毒学应答的患者全部获得持续病毒学应答。长效干扰素治疗组和普通干扰素治疗组在治疗后肝功能仍异常的患者分别占15.4%、14.9%,两组比较,x2=0.01,P>0.05,差异无统计学意义。结论 (1)昆明地区HCV感染基因型以3b和1b为主;(2)聚乙二醇干扰素α-2a联合利巴韦林治疗HCV 1b型感染患者的疗效不理想;(3)早期病毒学应答是获得持续病毒学应答的重要预测因素。  相似文献   

11.
The immunoneuroendocrine role of melatonin   总被引:19,自引:0,他引:19  
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.  相似文献   

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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.  相似文献   

14.
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.  相似文献   

15.
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.  相似文献   

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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 Mr 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 (Ka 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 Mr 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.  相似文献   

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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.  相似文献   

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