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Long-term posterior and anterior segment complications of immune recovery uveitis associated with cytomegalovirus retinitis

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2000年第1期130卷 57-64页

作者： Karavellas, MP Song, M MacDonald, JC Freeman, WR Univ Calif San Diego Dept Ophthalmol Shiley Eye Ctr La Jolla CA 92093 USA

PURPOSE: To identify and describe long-term posterior and anterior segment complications of immune recovery uveitis in patients with inactive cytomegalovirus retinitis who are undergoing highly active antiretroviral therapy-mediated recovery of immune function. METHODS: A prospective cohort study at a university medical center. Twenty-nine eyes of 21 patients with immune recovery uveitis and inactive cytomegalovirus retinitis were followed for 14.5 to 116 weeks (median, 43 weeks) after diagnosis of immune recovery uveitis, RESULTS: Nine eyes of nine patients developed visually important complications involving the posterior segment, anterior segment, or a combination of both. Posterior segment complications included severe proliferative vitreoretinopathy in three eyes and spontaneous vitreous hemorrhage from avulsion of a blood vessel secondary to tory syndrome that may result in complications months to years after the onset of inflammation. (C) 2000 by Elsevier Science Inc. All rights reserved.

关键词：眼前半段/病理学抗逆转录病毒治疗高效抗病毒药/治疗应用 CD4淋巴细胞计数 CD4阳性T淋巴细胞/生理学白内障/病因学白内障/病理学队列研究巨细胞病毒视网膜炎/并发症巨细胞病毒视网膜炎/药物疗法巨细胞病毒视网膜炎/免疫学巨细胞病毒视网膜炎/病毒学免疫系统/生理学虹膜炎/病因学虹膜炎/病理学虹膜炎/外科学前瞻性研究复发时间因素葡萄膜炎/并发症葡萄膜炎/药物疗法葡萄膜炎/免疫学葡萄膜炎/病毒学视敏度玻璃体视网膜病增生性/病因学玻璃体视网膜病增生性/病理学玻璃体视网膜病增生性/外科学玻璃体出血/病因学玻璃体出血/病理学玻璃体出血/外科学成年人人类男(雄)性

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Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia

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ANTIVIRAL THERAPY 2003年第1期8卷 57-63页

作者： Mangoni, ED Marrone, A Saviano, D Del Vecchio, C Utili, R Ruggiero, G Univ Naples 2 Cattedra & Div Med Interna Epatol Naples Italy Studio Diagnost Nucl Naples Italy Univ Sannio Dipartimento Ingn Benevento Italy

Background: Ribavirin administration for chronic hepatitis C is associated with the development of haemolytic anaemia, which affects treatment efficacy and tolerability. In a pilot study, the exogenous administration of erythropoietin has been shown to be beneficial, reducing the rate of ribavirin dose reduction. How ribavirin administration affects normal erythropoietin production has not been determined. Aim: To investigate the endogenous erythropoietin response in hepatitis C patients with ribavirin-induced anaemia. Methods: Serum erythropoietin was measured before and during interferon-ribavirin treatment in 18 HCV-positive subjects. Mathematical analysis and modelling were applied to compare the degree of erythropoietin increase in HCV-positive and in otherwise healthy anaemic patients, and estimate the endogenous excess erythropoietin production in response to ribavirin-induced anaemia. Results: Erythropoietin concentration increased significantly in response to anaemia caused by ribavirin. The physiological erythropoietin response to the ribavirin-induced anaemia was as adequate in HCV-positive subjects as it is in anaemic subjects without liver disease. The recommended exogenous erythropoietin dose appears three-times greater than the endogenous erythropoietin boost. Conclusion: Chronic liver damage by HCV does not affect the physiological erythropoietin response to ribavirin-induced anaemia. While the rationale for erythropoietin treatment of ribavirin-induced anaemia is not straightforward, the currently recommended dosing regimen should be reassessed.

关键词：贫血溶血性/化学诱导抗病毒药/副作用抗病毒药/治疗应用药物疗法联合红细胞生成素/血液丙型肝炎慢性/药物疗法丙型肝炎慢性/代谢干扰素α/治疗应用模型生物学重组蛋白质类利巴韦林/副作用利巴韦林/治疗应用成年人老年人女(雌)性人类男(雄)性中年人

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ISDR pattern and evolution in patients with chronic hepatitis C treated with standard or Peg-IFN plus ribavirin

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ANTIVIRAL THERAPY 2003年第2期8卷 105-110页

作者： Cappiello, G Abbate, I Lo Iacono, O Longo, R Solmone, M Ferraro, D Antonucci, G Di Marco, V Di Stefano, R Croxi, A Ippolito, G Capobianchi, MR Natl Inst Infect Dis L Spallanzani Rome Italy S Pertini Hosp Rome Italy Univ Palermo Palermo Italy

The aim of the study was to characterize the interferon sensitivity determining region (ISDR) mutation pattern and its changes at 4 weeks of treatment in a population of patients infected with hepatitis C virus (HCV) genotype 1b receiving standard or PEG-IFN plus ribavirin (RBV), to find possible early correlates of therapy outcome. Forty-five patients with chronic hepatitis due to HCV 1b were treated by PEG-IFN-alpha 2b (n=23) or IFN-alpha 2b (n=22) plus RBV 1000-1200 mg/day. They were classified 24 weeks after stopping therapy as sustained responders (SR), relapsers (REL) or non-responders (NR). Sixteen patients were SIR, 12 REL and 17 *** mutations were evaluated by direct sequencing at baseline in all and after 4 weeks in patients with detectable viraemia (n=30).

关键词：氨基酸序列抗病毒药/治疗应用队列研究药物疗法联合基因型肝炎病毒属/药物作用肝炎病毒属/遗传学丙型肝炎慢性/药物疗法干扰素α/治疗应用分子序列数据突变聚乙烯二醇类/治疗应用重组蛋白质类利巴韦林/治疗应用序列比对治疗结果病毒非结构蛋白质类/遗传学女(雌)性人类男(雄)性中年人

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Stealth virus epidemic in the Mohave Valley: Severe vacuolating encephalopathy in a child presenting with a behavioral disorder

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EXPERIMENTAL AND MOLECULAR PATHOLOGY 1999年第1期66卷 19-30页

作者： Martin, WJ Anderson, D Ctr Complex Infect Dis Rosemead CA 91770 USA

An infectious illness, attributed to atypically structured cytopathic "stealth" viruses, occurred in 1996 in the Mohave Valley region of the United States. A stealth virus-infected child from this region has developed a severe noninflammatory, vacuolating (spongiform) encephalopathy. The illness initially presented as a behavioral problem without overt neurological signs. Extensive investigations, including repeated magnetic resonance imaging, two brain biopsies, and stealth virus cultures, have helped define the disease process occurring in this child. Significant clinical benefit with apparent retardation of disease progression occurred during a 6-week course of ganciclovir therapy. The potential contributing role of stealth virus infections in children presenting with behavioral problems needs to be addressed. (C) 1999 Academic Press.

关键词：抗病毒药/治疗应用脑/病理学脑/超微结构加利福尼亚/流行病学更昔洛韦/治疗应用磁共振成像精神障碍/病因学精神障碍/病毒学朊病毒病/药物疗法朊病毒病/流行病学朊病毒病/心理学朊病毒病/病毒学回顾性研究空泡/病理学空泡/超微结构病毒性疾病/诊断病毒性疾病/药物疗法病毒性疾病/流行病学病毒性疾病/心理学儿童人类男(雄)性

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Response to retreatment with interferon-α plus ribavirin in chronic hepatitis C patients is independent of the NS5A gene nucleotide sequence

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第9期94卷 2487-2495页

作者： Ibarrola, N Moreno-Monteagudo, JA Sáiz, M Garciá-Monzón, C Sobrino, F García-Buey, L Lo Iacono, O Moreno-Otero, R Martínez-Salas, E Univ Autonoma Madrid Hosp Princesa Liver Unit Madrid Spain Univ Autonoma Madrid CSIC Ctr Biol Mol Severo Ochoa Madrid Spain INIA Ctr Invest Senidad Anim Madrid Spain

OBJECTIVE: Interferon-alpha plus ribavirin is an effective treatment for chronic hepatitis C patients. We evaluated whether the response to this combined therapy correlated with the presence of mutations in a region of 372 nucleotides within the NS5A gene. METHODS: Sixty-two patients, 42 nonresponders and 20 relapsers to a previous course of interferon-alpha, received 3 million units thrice weekly of interferon-alpha-2b and 1-1.2 g daily of ribavirin for 12 months. Basal biochemical and virological (HCV RNA and genotype) parameters were determined. Clinical examinations were carried out at 1, 2, 3, 6, and 12 months. In addition, nucleotide sequencing of the NS5A gene was determined for viral samples obtained from 38 of these patients at the baseline of the combined therapy, as well as in 15 of them before initiating the previous course of interferon as monotherapy. RESULTS: On finishing the 12 months, 36 patients (58.1%) had normal aminotransferases and 25 (40.3%) cleared viremia. Nucleotide sequencing indicated the same level of genetic variability within the group of responder and nonresponder patients all along the 124 amino acid residues of the NS5A gene studied. Neither the type of amino acid substitution nor the number of them was significantly different in one group relative to the other. CONCLUSIONS: Therapy with interferon-alpha-2b plus ribavirin was well tolerated, achieving an end-of-treatment response in 25 (40.3%) patients. Response did not correlate with the presence of mutations in the NS5A gene analyzed, including the interferon sensitivity determining region (ISDR) and its flanking sequences. (Am J Gastroenterol 1999;94:2487-2495. (C) 1999 by Am. Coll. of Gastroenterology).

关键词：抗病毒药/治疗应用碱基序列药物疗法联合肝炎丙型慢性/药物疗法干扰素α-2b/治疗应用分子序列数据试验预期值 RNA复制酶/遗传学利巴韦林/治疗应用治疗结果病毒非结构蛋白质类/遗传学成年人女(雌)性人类男(雄)性中年人

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Enhanced antiviral benefit of combination therapy with lamivudine and alpha interferon against WHV replication in chronic carrier woodchucks

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ANTIVIRAL THERAPY 2000年第2期5卷 95-104页

作者： Korba, BE Cote, P Hornbuckle, W Schinazi, R Gangemi, JD Tennant, BC Gerin, JL Georgetown Univ Med Ctr Div Mol Virol & Immunol Rockville MD USA Cornell Univ Coll Vet Med Ithaca NY 14853 USA Emory Univ Dept Pediat Decatur GA USA Clemson Univ Biomed Cooperat Greenville Hosp Clemson SC USA

Cell culture studies in our laboratory previously demonstrated synergistic antiviral activity for the combinations of lamivudine and a novel recombinant hybrid human alpha BID interferon (rHu alpha B/D IFN) against hepatitis B virus (HBV) replication. Based on these results, a study was designed to determine if an enhanced antiviral effect with this drug combination could be demonstrated in vivo using the woodchuck hepatitis virus (WHV)/woodchuck experimental model of chronic HBV infection, Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers during previous studies by our laboratories. Two combination treatment regimens were compared to matched monotherapies in a placebo-controlled trial. The first used simultaneous administration of rHu alpha B/D IFN and lamivudine for 24 weeks, The other combination treatment regimen used a staggered dosing schedule of 12 weeks of administration of lamivudine alone, followed by 12 weeks of simultaneous dosing with both drugs, followed by 12 weeks of therapy with rHu alpha B/D IFN alone, Both treatment regimens with combinations of lamivudine and rHu alpha B/D IFN were more effective at reducing WHV replication in chronically infected woodchucks than the corresponding monotherapies. Both combination treatments produced antiviral effects that were at least equal to that expected for additive activity based on estimations generated by Bliss Independence calculations. The staggered treatment regimen reduced viraemia and intrahepatic WHV replication significantly more than that expected for additive interactions, indicating synergistic antiviral effects. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapies and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent.

关键词：抗病毒药/治疗应用带病原状态药物疗法联合肝炎病毒乙型旱獭/药物作用肝炎乙型慢性/药物疗法肝炎乙型慢性/病毒学干扰素Ⅰ型重组/治疗应用拉米夫定/治疗应用旱獭属 RNA 病毒/血液病毒血症病毒复制/药物作用动物女(雌)性人类

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A humanized monoclonal antibody against respiratory syncytial virus (palivizumab) inhibits RSV-induced neurogenic-mediated inflammation in rat airways

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PEDIATRIC RESEARCH 2000年第3期47卷 351-356页

作者： Piedimonte, G King, KA Holmgren, NL Bertrand, PJ Rodriguez, MM Hirsch, RL Univ Miami Sch Med Dept Pediat Miami FL 33136 USA Univ Miami Sch Med Dept Med Miami FL 33136 USA Univ Miami Sch Med Dept Pharmacol Miami FL 33136 USA Univ Miami Sch Med Dept Pathol Miami FL 33136 USA Medimmune Inc Gaithersburg MD 20878 USA

Respiratory syncytial virus (RSV) is the most important respiratory pathogen in infancy and early childhood and may predispose to subsequent lower respiratory tract illness. Recent data indicate that RSV up-regulates the substance P receptor, making the airways abnormally susceptible to the proinflammatory effects of this peptide released from sensory nerves. The present study was designed to determine whether the administration of RSV antibodies prevents the potentiation of neurogenic inflammation in rat airways. Five days after inoculation, sensory nerve-mediated extravasation of Evans blue-labeled albumin was significantly greater in the airways of RSV-infected rats than in pathogen-free controls. Polyclonal immune globulin enriched for RSV-neutralizing antibodies (RSVIG) reduced neurogenic extravasation when injected 24 h before intranasal inoculation of the virus but not when injected before endotracheal inoculation. PI humanized MAb against RSV fusion protein (palivizumab) was twice as potent as RSVIG when given before intranasal inoculation and also caused significant inhibition after endotracheal inoculation. Furthermore, palivizumab inhibited neurogenic inflammation in RSV-infected rats when given 72 h after virus inoculation. These data suggest that palivizumab protects the respiratory tract from RSV-induced inflammation when given before or in the early phase of the viral infection. The administration of palivizumab to high-risk infants may limit the severity of the acute airway inflammation and may protect against subsequent lower respiratory tract illness.

关键词：抗体单克隆/治疗应用抗体单克隆人抗病毒药/治疗应用细胞系免疫酶技术大鼠近交F344 呼吸道合胞体病毒感染/药物疗法呼吸道合胞体病毒感染/预防和控制呼吸道合胞病毒/免疫学动物人类男(雄)性大鼠

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ACQUIRED-IMMUNODEFICIENCY-SYNDROME AND OPHTHALMOLOGY - THE 1ST DECADE

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1992年第1期114卷 86-95页

作者： HOLLAND, GN UNIV CALIF LOS ANGELES SCH MEDDEPT OPHTHALMOLLOS ANGELESCA 90024

Ten years ago, The American Journal of Ophthalmology published the first patient series describing the ophthalmic manifestations of the acquired immunodeficiency syndrome (AIDS).1 At that time, AIDS was a newly described, and still unnamed, disorder.2-5 There were fewer than 300 cases nationwide and its cause remained a mystery. Few could have imagined the magnitude of the AIDS epidemic to come, or the enormous changes in society and health care that it would engender. The current statistics on AIDS are staggering. The rate at which new cases were reported began to slow in the late 1980s, but the number of new cases has increased every year since the syndrome was initially described. By late 1991, there had been approximately 200,000 patients with AIDS in the United States, 65% of whom had died.6 The acquired immunodeficiency syndrome is now the second leading cause of death among men 25 to 44 years of age.7 It is estimated that one in 75 men and one in 700 women in the United States between the ages of 15 and 49 years are infected with human immunodeficiency virus (HIV), the agent responsible for AIDS.8 Over 1 million people in this country are believed to be infected with HIV. It is estimated that 58,000 to 85,000 of them will develop the full AIDS illness in 1992.9,10 Homosexual/bisexual men still account for most cases, but the groups whose numbers are increasing most rapidly include patients exposed through intravenous drug use or heterosexual contact and children infected by perinatal transmission.11

关键词：获得性免疫缺陷综合征/并发症抗病毒药/治疗应用巨细胞病毒感染/药物疗法眼感染/并发症眼感染/药物疗法 HIV感染/并发症生活质量视网膜疾病/药物疗法视网膜疾病/微生物学人类

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Interferon-α therapy exerts selective pressure on hepatitis C virus quasispecies equilibrium

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ANTIVIRAL THERAPY 1999年第1期4卷 15-19页

作者： Mizokami, M Ohno, T Ohba, K Davis, GL Suzuki, K Orito, E Lau, JYN Univ Florida Dept Med Sect Hepatobiliary Dis Div Gastroenterol Hepatol & Nutr Gainesville FL 32610 USA Univ Florida Dept Mol Genet & Microbiol Gainesville FL 32610 USA Nagoya City Univ Sch Med Dept Med 2 Nagoya Aichi 467 Japan Schering Plough Corp Inst Res Kenilworth NJ 07033 USA

Two patients with chronic hepatitis C virus (HCV) genotype 2b infection were studied. They responded biochemically to interferon (IFN) but had early virological and later biochemical relapse. The HCV quasispecies equilibrium in these patients was studied by a combination of cloning, sequencing and construction of phylogenetic trees. Another patient with chronic HCV genotype 2b infection was followed every 6 months for 30 months (induding one episode of biochemical exacerbation) to serve as the control. Quasispecies equilibrium drifted during IFN therapy but moved back in the direction of the original equilibrium during biochemical relapse. In the control patient, there was no significant drifting throughout the follow-up period. These data suggest that IFN therapy exerts selective pressure on HCV quasispecies equilibrium.

关键词：丙氨酸转氨酶/血液抗病毒药/治疗应用肝炎病毒属/分类肝炎丙型慢性/药物疗法肝炎丙型慢性/病毒学干扰素α/治疗应用种系发生成年人女(雌)性人类男(雄)性中年人

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Herpes simplex virus esophagitis in the immunocompetent host: An overview

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第9期95卷 2171-2176页

作者： Ramanathan, J Rammouni, M Baran, J Khatib, R St John Hosp & Med Ctr Dept Med Detroit MI 48236 USA

OBJECTIVE: The aim of this study was to delineate the characteristics of herpes simplex virus esophagitis (HSVE) in the immunocompetent host. METHODS: The study entailed a case report and a review of relevant literature through a MEDLINE search back to 1966. All cases with documented HSVE in patients without immunosuppression were selected and their characteristics defined. RESULTS: A total of 38 cases were identified. The age range was 1-76 yr and the male/female ratio 3.2/1. Antecedent exposure to HSV disease was described in eight cases (21.1%). A prodrome of systemic manifestations preceded the onset of esophageal symptoms in nine subjects (23.6%). Manifestations included acute odynophagia (76.3%), heartburn (50%), and fever (44.7%). Concurrent oropharyngeal lesions were uncommon (n = 8, 21.1%). Endoscopically, extensive involvement was common, showing friable mucosa (84.2%), numerous ulcers (86.8%), and whitish-exudates (39.5%). The distal esophagus was most commonly affected (63.8%). Microscopic examination showed characteristic viral cytopathology in 26 (68.4%) cases. Virus was recovered from esophageal-brushes or biopsies in 23 of 24 (95.8%) patients and immunocytochemistry was positive in seven of eight (87.5%) cases. Immune status was consistent with primary HSV infection in eight (21.1%) cases. The disease was self-limiting, although esophageal perforation and upper GI bleeding were reported in one case each. CONCLUSIONS: HSVE in the immunocompetent host is a rare but distinct entity, and is significantly more common in male subjects. It represents either primary infection or reactivation, and is characterized by acute onset, systemic manifestations, and extensive erosive-ulcerative involvement of the mid-distal esophagus. Histopathological examination alone may miss the diagnosis;adding tissue-viral culture optimizes the diagnostic sensitivity. It is usually self-limiting;whether antiviral therapy is beneficial remains unknown. (Am J Gastroenterol 2000;9

关键词：阿昔洛韦/治疗应用抗体病毒/分析抗病毒药/治疗应用活组织检查 CD4-CD8比值诊断鉴别食管炎/药物疗法食管炎/免疫学食管炎/病毒学食管镜检查食管/病毒学疱疹单纯/药物疗法疱疹单纯/免疫学疱疹单纯/病毒学疱疹病毒1型人/免疫学疱疹病毒1型人/分离和提纯免疫减弱宿主/免疫学免疫球蛋白G/免疫学免疫球蛋白M/免疫学回顾性研究人类男(雄)性中年人

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