硼替佐米治疗多发性骨髓瘤诱发MAS样病变并引起SIADH 3例报告并文献复习北大核心CSCD

蛋白酶体抑制剂硼替佐米是多发性骨髓瘤(MM)的一线治疗药物。文献报道, 硼替佐米诱发低钠血症的发生率为15%~40%, 其原因尚不明确[1]。本文报道了本中心3例MM患者应用含硼替佐米方案化疗后出现低钠血症伴高热、IL-1β和IL-6炎症因子升高、铁蛋白显著升高及多系统损害。这些表现不完全符合巨噬细胞活化综合征(macrophage activation syndrome, MAS)的典型表现, 我们称其为"MAS样病变"。1例患者应用依托泊苷联合地塞米松治疗后临床症状缓解。本文旨在提示应用硼替佐米化疗期间应严密监测血清钠水平, 持续发热的患者需警惕是否诱发了MAS样病变及抗利尿激素分泌不当综合征(syndrome of inappropriate antidiuretic hormone secretion, SIADH)。     

硼替佐米治疗滤泡性淋巴瘤的不良反应及护理对策

目的 总结硼替佐米治疗滤泡性淋巴瘤(Follicular Lymphoma,FL)患者所致不良反应的观察要点及护理措施.方法 对我院11例复发难治性FL患者应用硼替佐米进行治疗,针对可能出现的不良反应进行预防性健康指导,密切监测给药进程,出现不良反应后及时给予对症治疗及护理.结果 11例患者均行5周期化疗,不良反应除周围神经病变、带状疱疹外主要为中性粒细胞及血小板减少、发热、疲乏、胃肠道反应,中重度不良反应较多.结论 硼替佐米治疗滤泡性淋巴瘤患者不良反应虽多,但通过有效治疗及护理,药物毒性可有效控制,患者耐受良好.     

硼替佐米联合地塞米松治疗多发性骨髓瘤11例的不良反应及护理对策

目的总结硼替佐米联合地塞米松治疗多发性骨髓瘤(MM)的不良反应及护理对策。方法采用硼替佐米联合地塞米松的方案治疗MM 11例,观察其治疗效果及不良反应,并提出相应的护理措施。结果胃肠道反应8例,骨髓抑制7例,神经毒性反应2例,转氨酶升高2例。结论临床使用硼替佐米联合地塞米松治疗MM时,应及时发现用药后出现的不良反应并做出相应的处置。     

硼替佐米治疗原发性浆细胞白血病两例报告及文献复习

目的探讨硼替佐米治疗原发性浆细胞白血病的疗效。方法报道两例经硼替佐米治疗的原发性浆细胞白血病病例并复习相关文献。结果和结论硼替佐米可明显改善患者临床症状,有效降低我们对2例原发性浆细胞患者采用硼替佐米联合化疗的治疗过程中,发现硼替佐米可改善临床症状,有效降低血清中M成分及骨髓异常浆细胞数量。对于因浆细胞白血病引起急性肾功能不全者,硼替佐米使用安全,并能改善肾功能。在硼替佐米的使用过程中,未发现有明显不良反应。     

硼替佐米皮下注射联合地塞米松治疗多发性骨髓瘤患者的护理体会

目的：探讨硼替佐米皮下注射联合地塞米松治疗28例多发性骨髓瘤患者的疗效,观察要点及护理;方法：硼替佐米1.3mg/m₂,第1,4,8,11天,地塞米松注射液20mg/d,第1,2,3,4,8,9,10,11天,11天为一个疗程,每两个疗程之间间隔14-28天;结果：28例患者化疗期间均未发生严重胃肠道反应,神经毒性,血液系统毒性,严重皮肤反应,以及与护理相关不良反应。周围神经病变比静脉注射后轻;结论：硼替佐米皮下注射联合地塞米松治疗多发性骨髓瘤患者疗效确切,做好化疗期间的观察及护理,对于提升疗效,延长患者生存期和提高生活质量,减少患者痛苦,节约住院费用,减轻经济负担尤为重要。     

可逆性后部脑病综合征的临床及影像学特征

可逆性后部脑病综合征(PRES)主要表现为头痛、意识障碍、抽搐及视力下降,神经影像学表现为可逆性大脑后部白质损害[1],病情严重时可导致患者昏迷或死亡.早期诊断、及时正确的治疗可使大多数患者的症状、体征及头颅神经影像学病灶消失.回顾性分析本院收治的8例确诊PRES患者的临床和影像学特点,旨在提高对本病的认识.     

糖皮质激素和硼替佐米体外干预多发性骨髓瘤细胞BAFF/APRIL mRNA表达的初步探索

本研究观察糖皮质激素和硼替佐米对U266骨髓瘤细胞株和多发性骨髓瘤(MM)患者骨髓单个核细胞(BMMNC)BAFF/APRIL mRNA表达的影响。分离MM患者BMMNC,对U266骨髓瘤细胞株和BMMNC进行药物干预(单用地塞米松100、200μg/ml,甲基强的松龙100、200μg/ml,硼替佐米0.1μg/ml,以及地塞米松或甲基强的松龙与硼替佐米联用)48小时,收集细胞,进行荧光定量实时PCR检测BAFF/APRIL mRNA表达的水平。采用SPSS 17.0进行统计学分析。结果表明,U266细胞及7例初治的MM患者BMMNC均高表达BAFF/APRIL基因。地塞米松,甲基强的松龙,硼替佐米单独作用于U266细胞或MM患者BMMNC后,BAFF/APRIL基因表达较未干预前降低(p<0.01),其中硼替佐米干预后BAFF/APRIL表达最低(p<0.05)。地塞米松或甲基强的松龙和硼替佐米联用后BAFF/APRIL基因表达较单独干预时低(p<0.01);地塞米松联用硼替佐米时BAFF/APRIL基因表达的抑制强度大于甲基强的松龙和硼替佐米联用的抑制强度(p<0.05)。结论:糖皮质激素和硼替佐米干预后的骨髓瘤细胞BAFF/APRIL基因表达下降,提示糖皮质激素和硼替佐米除了存在已知的糖皮质激素受体和蛋白酶体作用靶点外,可能还存在BAFF/APRIL及其受体这种新的作用靶点。     

以硼替佐米为主的联合方案成功治疗POEMS综合征一例报告附文献复习

POEMS综合征是一种较为少见的多系统损害的临床症候群,部分患者常会因逐渐进展的神经病变,大量的多浆膜腔积液和血栓性疾病而严重影响生存质量甚至危及生命[1].由于其发病机制不明,至今尚无标准的治疗方案.迄今为止,国内外尚无应用硼替佐米治疗POEMS综合征的报道.我院近期应用硼替佐米为主的联合方案治疗1例POEMS综合征患者,获得完全缓解.     

以硼替佐米为主的联合方案成功治疗POEMS综合征一例报告附文献复习

POEMS综合征是一种较为少见的多系统损害的临床症候群,部分患者常会因逐渐进展的神经病变,大量的多浆膜腔积液和血栓性疾病而严重影响生存质量甚至危及生命[1].由于其发病机制不明,至今尚无标准的治疗方案.迄今为止,国内外尚无应用硼替佐米治疗POEMS综合征的报道.我院近期应用硼替佐米为主的联合方案治疗1例POEMS综合征患者,获得完全缓解.     

硼替佐米对小鼠急性移植物抗宿主病作用及其机制研究

目的 探讨硼替佐米(Bortezomib)对小鼠急性移植物抗宿主病(aGVHD)的预防作用及其机制.方法 建立小鼠aGVHD动物模型,将小鼠随机分3组,A:移植对照组;B:移植+早期输注硼替佐米组;C:移植+延期输注硼替佐米组.比较各组受鼠aGVHD临床及病理改变、生存率,流式细胞术检测移植后供鼠来源细胞(H-2b+)率.体外建立单向混合淋巴细胞培养(MLC)体系,植物血凝素刺激后,分别用0、2、4、8 nmol/L的硼替佐米作用于反应体系,在不同的时间点收集细胞,采用CCK-8法检测细胞活性,流式细胞术检测细胞凋亡率,ELISA法检测培养上清IL-2、IFN-γ、TNF-α含量.结果 移植对照组小鼠出现典型的aGVHD症状,3周内死于aGVHD,平均存活时间为16.1 d,移植加早期输注硼替佐米组小鼠aGVHD症状明显减轻,平均生存时间较移植对照组显著延长,60 d时生存率为70%,高于其他组(P<0.05),60 d时H-2b+细胞的百分率为(98.1±1.1)%.移植加延期输注硼替佐米组小鼠aGVHD症状明显较移植对照组加重,平均存活时间较A组缩短.硼替佐米对MLC体系细胞活性的抑制作用表现为剂量依赖关系,8 nmol/L硼替佐米作用24 h后细胞活性抑制率为(41.4±6.0)%;硼替佐米作用于细胞后12、24、36 h的凋亡率逐渐增加,8 nmol/L硼替佐米作用36 h后细胞凋亡率为(62.8±7.0)%;硼替佐米作用24 h后上清液中IL-2、IFN-γ、TNF-α浓度减少.结论 移植后早期输注硼替佐米可显著减轻小鼠异基因移植后的aGVHD、提高生存率,同时不影响骨髓植入;而移植后延期给予硼替佐米则加重aGVHD,导致受鼠死亡率增加.其机制可能是通过抑制淋巴细胞活性,诱导淋巴细胞凋亡,抑制同种反应性细胞分泌IL-2、IFN-γ、TNF-α.     

A patient with severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis-associated involvement of the central nervous system

Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS.     

可复性后部脑病综合征MRI诊断及临床分析

目的探讨脑后部可逆性脑病综合征（posteriorreversibleencephalopathysyndrome,PRES）的临床及MRI表现,提高对PRES的认识。方法回顾性分析2007年1月-2010年12月期间5例PRES患者的MRI资料并进行追踪随访。5例PRES患者中男1例,女4例,肾性高血压及产后子痫各1例、妊娠高血压3例。5例均行MRI多序列平扫检查及弥散加权成像（diffusionweightedimaging,DWI）,其中4例同时行磁共振血管造影（magneticresonanceangiography,MRA）,2例行MRI增强检查。结果5例发病时均有高血压,以突发头痛、子痫或癫痫发作、意识障碍及视觉障碍为临床特点,及时正确治疗后症状于3～5d左右消失,1例遗留肢体功能障碍。MRI显示5例多发病灶主要位于双侧顶枕叶皮质下白质内,额叶及颞叶后部各2例,两侧小脑及脑干1例,皮质受累2例,病变呈长T1、长T2信号、液体衰减反转恢复序列呈高信号,5例患者病灶DWI图呈高或等信号,表观弥散系数（apparentdiffusioncoefficient,ADC）图呈略高信号;1例顶叶及1例基底节区部分病灶DWI图呈高信号,ADC图呈低信号,提示弥散受限。2例增强无强化,脑膜呈线状强化。随访MRI显示3例病灶完全消失。1例左侧基底节区部分病灶发展为脑梗死。结论PRES是一种临床一影像综合征,正确认识这一综合征对其早期诊断和治疗具有非常重要的意义。MRI能够提供较为可靠明确的诊断,其扩散成像对判断PRES预后亦很有价值。     

多系统萎缩合并抗利尿激素分泌不当综合征1例及文献复习

目的 探讨多系统萎缩(multiple system atrophy,MSA)合并抗利尿激素分泌不当综合征(syndrome of inappropriate antidiuresis,SIAD)的临床特征,为该病的临床诊断及治疗提供依据。方法 回顾性分析1例MSA合并SIAD患者的临床资料、诊疗经过并复习相关文献。结果 患者为男性,58岁,间断意识障碍伴咳嗽、咳痰1月余,再发2天。结合患者病史、体格检查及辅助检查,入院诊断:①重度低钠血症;②肺部感染;③MSA。后完善相关辅助检查并结合其临床表现,确诊为SIAD。给予抗感染、限水、补钠等治疗后,患者肺部感染治愈,但低钠血症仍持续存在。结论 MSA可能是SIAD病因,而肺部感染可能是MSA合并SIAD的易感因素。对MSA患者,尤其是合并肺部感染时应加强水钠平衡管理。     

The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options

Hyponatremia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuresis (SIAD) is one of the most common causes of hyponatremia: it is a disorder of sodium and water balance characterized by urinary dilution impairment and hypotonic hyponatremia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce antidiuretic hormone (ADH) release; according to its definition, it is diagnosed through an exclusion algorithm. SIAD is usually observed in hospitalized patients and its prevalence may be as high as 35%. The understanding of the syndrome has notably evolved over the last years, as reflected by the significant change in the name, once the syndrome of inappropriate secretion of ADH (SIADH), today SIAD. This review is up to date and it analyses the newest notions about pathophysiological mechanisms, classification, management and therapy of SIAD, including vaptans.     

可逆性后部脑病综合征患者血压与影像学表现的关系及发病机制

目的探讨可逆性后部脑病综合征（PRES）患者发病时毒性血压与脑水肿范围及水肿程度的相关性,并进一步研究其发病机制。方法回顾性分析48例PRES患者的临床和影像学资料,按患者发病时平均动脉压（MAP）水平将其分为血压正常组（7例）、血压升高组（32例）及严重高血压组（9例）三组。将水肿累及的脑内部位范围按解剖分为9个区域（额叶、颞叶、顶叶、枕叶、小脑、脑干、基底节、胼胝体及深部白质）,每个区域记1分;由两位神经放射医师对脑水肿程度分级独立做出评价,分别记作1、2、3、4、5分。结果三组间脑水肿累及部位比较,差异无统计学意义（P〉0.05）,脑水肿程度评分亦无统计学意义（P〉0.05）。所有患者脑水肿累及范围及程度评分与MAP无明显相关性（r=0.16,P=0.29）。结论 PRES患者脑血管源性水肿与血压值无直线相关性,高血压并不是导致脑水肿形成的决定性因素或必备条件。     

Methotrexate-induced posterior reversible encephalopathy syndrome

WHAT IS KNOWN AND OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is described clinically as an acute neurologic deterioration characterized by headache, change in mental status and seizures. Although the mechanism(s) for this syndrome is not fully understood, PRES results from vasogenic edema in areas of the brain supplied by the posterior circulation. Methotrexate (MTX)-induced neurotoxicity is a well-known complication of therapy in the paediatric population but is uncommon in adults. DETAILS OF THE CASE: We describe a 55-year-old woman with an acute presentation of PRES caused by intrathecal MTX given as part of a treatment regimen for diffuse large B-cell type lymphoma. Both clinical symptoms and radiographic abnormalities resolved 5 days after cessation of treatment. WHAT IS NEW AND CONCLUSION: We describe what we believe to be the first report of intrathecal MTX-induced PRES in an adult. Clinicians should include MTX-induced PRES in the differential diagnosis of acute neurologic changes in patients receiving this medication. The incidence of MTX-induced neurotoxicity may be under recognized in adults.     

胎儿透明隔腔缺如的产前超声诊断

目的探讨产前超声诊断胎儿透明隔腔（CSP）缺如的临床意义。方法采用二维及三维超声对南京医科大学附属苏州医院产前未显示透明隔腔的63例胎儿行颅脑超声重点观察,并对相关畸形超声特征进行总结分析。结果 63例胎儿产前颅脑二维超声均未显示透明隔腔,透明隔腔缺如胎儿相关畸形包括：（1）胼胝体缺失5例（完全性胼胝体缺失4例,部分性胼胝体缺失1例）;（2）前脑无裂畸形27例（无叶型前脑无裂畸形18例,半叶型前脑无裂畸形5例,叶状型前脑无裂畸形4例）;（3）脑裂畸形1例;（4）孔洞脑2例;（5）积水型无脑畸形5例;（6）严重脑积水23例（中脑导水管狭窄所致5例,开放性脊柱裂所致18例）。二维及三维超声显示透明隔腔缺如胎儿合并其他畸形包括：Dandy-Walker畸形1例、Dandy-Walker变异1例、中央型唇裂14例、单鼻孔5例、喙鼻2例、单心室2例、足内翻3例、单脐动脉4例等。63例胎儿超声检查后均进行随访,58例产前超声诊断结果与随访结果均一致,1例视-隔发育不良误诊为叶状型前脑无裂畸形,4例失随访。结论透明隔腔是中、晚孕期超声观测胎儿中枢神经系统发育的重要指标,透明隔腔缺如多伴发胎儿前脑病变和中线结构发育不良等多种颅脑畸形。产前超声在双顶径平面即可观察透明隔腔,超声是观察有无透明隔腔的首选方法。     

Amiodarone pulmonary toxicity: clinical and subclinical features

In a prospective study of lung function of 34 patients taking amiodarone, 24 showed no functional changes but 10 developed a sustained fall in CO transfer factor (TLCO) exceeding 15 per cent. These patients had on average received a higher dose of drug in the first three months of treatment. Seven showed no clinical or radiographic changes and TLCO improved with reduction in drug dose. The other three patients developed florid clinical and radiographic features of amiodarone pulmonary toxicity. All three had impaired TLCO before receiving amiodarone. During the course of the prospective study amiodarone pulmonary toxicity was diagnosed in four other patients. Lung tissue was examined in five of the seven patients with clinical toxicity and showed alveolar wall thickening, exudation and interstitial and intra-alveolar fibrosis with prominent 'foamy' macrophages. Electron microscopy of macrophages showed numerous lysosomal multilamellar bodies, which were demonstrated by energy dispersive X-ray analysis to contain iodine, a constituent of the amiodarone molecule. Two of the patients with clinical toxicity died of respiratory failure; the other five showed gradual improvement on withdrawal of the drug and treatment with corticosteroids. Subsequent withdrawal of steroids was associated with clinical and/or functional deterioration in five patients. A separate autopsy study of the lungs of eight patients dying during treatment with amiodarone, but without clinically-recognised toxicity, showed that an alveolitis had been present in two and prominent 'foamy' macrophages were seen in the lungs of six patients. We conclude that clinical and subclinical effects of amiodarone on the lung are common. The clinical syndrome may be easily misdiagnosed as pulmonary oedema. Subclinical changes in lung function are usually reversible, but whether they herald clinical toxicity if treatment is continued without modification is not established. The presence of 'foamy' macrophages may simply reflect exposure to the drug rather than clinically-important toxicity.     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

本研究观察硼替佐米治疗多发性骨髓瘤的疗效及不良反应。7例初治患者均采用硼替佐米联合地塞米松治疗；另3例复发难治患者中2例采用硼替佐米联合地塞米松，1例同时加用米托蒽醌和沙利度胺治疗。结果显示，根据EMBT标准判定疗效，7例初治患者中1例完全缓解（CR），5例部分缓解（PR），1例轻微缓解（MR）；3例复发难治患者中2例部分缓解（PR），1例轻微缓解（MR）。总缓解率（CR＋PR）80％。3例患者在治疗过程中出现血小板减少，1例出现腹泻，1例足部麻木，经对症处理后均恢复。结论：硼替佐米治疗初发及复发难治多发性骨髓瘤均有较好的疗效，对治疗相关的副反应患者可耐受。     

肿胀手综合征介入治疗及复发分析

目的 探讨血液透析患者肿胀手综合征的发病特点、介入治疗方法和肿胀手复发影响因素.方法 88位肿胀手患者,按肿胀手在治疗后于观察期限内是否复发分为未复发组和复发组.采用介入下造影方式明确中心静脉病变位置,球囊扩张或植入支架治疗.考察透析患者置管史与中心静脉病变的关系,观察治疗方式和治疗后复发情况.结果 88位患者共行116例次介入检查治疗,15人因导丝无法通过或采用其他手术方式,3人未见中心静脉异常,其余70人中心静脉经过球囊扩张或支架植入后即刻开放;50位患者有同侧颈内静脉置管史,肿胀手症状出现距离内瘘手术时长26.4±32.5月,中心静脉病变的位置多位于锁骨下静脉和头臂静脉.经介入治疗后,观察期内23例患者35次肿胀手复发,再次复发距离上次治疗时间6.9±4.9月,复发组与未复发组一般资料上相比差异无统计学意义（P＞0.05）.虽然治疗上选择球囊扩张还是支架植入差别亦无统计学意义,但复发组支架植入的比例相对更高.结论 血液透析患者由于中心静脉置管、动静脉内瘘术后血流动力学改变等原因,导致中心静脉狭窄或闭塞,引起肿胀手综合征.球囊或支架植入治疗后,肿胀手综合征仍有较高的复发率,支架植入治疗者复发率可能更高.