硝呋太尔致溶血性黄疸

1例22岁女性患者因月经不调及阴道炎给予口服黄体酮40 mg,3次/d;甲睾酮5 mg,1次/d;硝呋太尔0.4 g,3次/d;裸花紫珠片2片,3次/d。3 d后患者出现全身皮肤及巩膜黄染,尿色呈浓茶色。实验室检查:红细胞3.02×1012/L,网织红细胞0.034,总胆红素141.3μmol/L,直接胆红素9.7μmol/L,间接胆红素131.6μmol/L。遂停用黄体酮、甲睾酮及硝呋太尔,继续使用裸花紫珠片,并给予多种药物治疗。患者黄疸逐渐消退,尿色逐渐恢复正常。停药后第11天黄染症状完全消退,实验室检查:红细胞2.94×1012/L,网织红细胞0.021;总胆红素15.2μmol/L,直接胆红素5.8μmol/L,间接胆红素9.4μmol/L。     

氯吡格雷相关非重型再生障碍性贫血

1例66岁男性患者因心肌梗死入院,并立即行经皮冠状动脉腔内成形术及支架术。术后当日规律口服氯吡格雷75 mg,1次/d;阿司匹林首剂量300 mg,之后100 mg,1次/d;氟伐他汀20 mg,1次/d;福辛普利钠10 mg,1次/d。1个月后,患者出现寒战、高热。血常规检查:白细胞1.1×109/L,中性粒细胞0.034,中性粒细胞绝对值0.037×109/L,红细胞3.6×1012/L,血红蛋白113 g/L,血小板119×109/L。骨髓穿刺及活检示非重型再生障碍性贫血。给予对症治疗,血常规各项水平继续下降。入院第44天血常规检查:白细胞2.6×109/L,中性粒细胞0.367,中性粒细胞绝对值0.954×109/L,红细胞3.6×1012/L,血红蛋白113 g/L,血小板84×109/L。立即停用氯吡格雷及阿司匹林,改用华法林2.5 mg,1次/d口服,西洛他唑100 mg,2次/d口服,其他药物继续服用。随后血常规检查示全血细胞计数下降至最低值后逐渐上升。再行2次骨髓穿刺检查,结果示骨髓象逐渐恢复。入院第102天血常规检查:白细胞5.8×109/L,中性粒细胞0.552,中性粒细胞绝对值3.202×109/L,红细胞4.2×1012/L,血红蛋白140 g/L,血小板170×109/L。再次加用氯吡咯雷50 mg,1次/d;阿司匹林100 mg,1次/d。1周后血常规检查示全血细胞计数明显下降,2周后血常规检查:白细胞3.4×109/L,中性粒细胞0.349,中性粒细胞绝对值1.187×109/L,红细胞4.0×1012/L,血红蛋白133 g/L,血小板176×109/L。随后,仅停用氯吡咯雷,改为西洛他唑100 mg,3次/d口服。1周后血象恢复正常。     

利奈唑胺致全血细胞减少

1例68岁女性患者,因感染性心内膜炎口服利奈唑胺0.6 g,2次/d,半个月后感觉疲乏、倦怠,血常规检查示白细胞4.18×109/L,红细胞3.23×1012/L,血红蛋白76 g/L,血小板40×109/L,遂停药。11 d后血象恢复正常,再次口服利奈唑胺0.6 g,2次/d,用药14 d复查血常规,白细胞3.50×109/L,红细胞2.51×1012/L,血红蛋白71 g/L,血小板36×109/L,遂再次停药。停药后患者连续5 d发热(体温最高时38.5℃),伴咳嗽、咯黄痰及鼻塞,遂入院。入院后未给予抗感染药物,先后3次输注浓缩红细胞(每次400 ml)。血常规示:白细胞5.90×109/L,红细胞3.33×1012/L,血红蛋白95 g/L,血小板158×109/L,故在入院第21天给予利奈唑胺0.6 g静脉注射,2次/d。入院第36天复查血常规,白细胞2.30×109/L,红细胞2.21×1012/L,血红蛋白61 g/L,血小板29×109/L,遂再次停用利奈唑胺。先后3次输注悬浮红细胞(每次400 ml),皮下注射重组人粒细胞集落刺激因子150μg,1次/d,共4 d。应患者要求准予出院。     

拉米夫定致贫血

1例24岁男性重型乙型肝炎患者口服拉米夫定100 mg、1次/d,水飞蓟宾70 mg、3次/d;同时静脉滴注还原型谷胱甘肽1.2 g、复方甘草酸苷80 ml、促肝细胞生长素120 mg,1次/d。1周后,其红细胞计数由4.52×1012/L降至3.29×1012/L,血红蛋白由120 g/L降至102 g/L。3周后复查:红细胞计数3.00×1012/L,血红蛋白81 g/L。停服拉米夫定,改为口服恩替卡韦0.5 mg,1次/d,其他药物维持不变。16 d后复查血常规:红细胞计数3.84×1012/L,血红蛋白120 g/L。     

利奈唑胺致全血细胞减少

1例75岁男性患者因房室传导阻滞行永久起搏器植入术,术后出现感染性心内膜炎。首先单独给予头孢哌酮钠-舒巴坦钠3.0 g1、次/12 h静脉滴注4 d,然后改为万古霉素1.0 g1、次/12 h静脉滴注3 d,最后单独应用利奈唑胺600 mg1,次/12 h静脉滴注44 d。应用利奈唑胺前实验室检查示患者外周血白细胞12.00×109/L,红细胞3.92×1012/L,血小板158×109/L,血红蛋白115 g/L。用药第19天血常规示白细胞2.81×109/L,红细胞3.39×1012/L,血小板74×109/L,血红蛋白102 g/L。其后血常规检查显示各项指标均低于正常范围,最低值如下:白细胞2.69×109/L,红细胞2.51×1012/L,血小板48×109/L,血红蛋白69 g/L。由于病情需要未停用利奈唑胺,给予重组人粒细胞集落刺激因子、琥珀酸亚铁及红细胞悬液等对症治疗。患者应用利奈唑胺共44 d。停药后18 d血常规恢复正常:白细胞5.07×109/L,红细胞3.02×1012/L,血小板156×109/L,血红蛋白102 g/L。     

头孢曲松钠致婴儿溶血性贫血

1例9月龄男婴因发热、咳嗽静脉滴注头孢曲松钠后体温降至正常,但出现面色苍白,哭闹不安,食欲减退。2 d后停用头孢曲松钠,改为肌内注射青霉素,患儿再次出现低热。2 d后血常规检查:血红蛋白67 g/L,红细胞2.95×1012/L,白细胞22.16×109/L,中性粒细胞0.30,淋巴细胞0.60,单核细胞0.07,异性淋巴细胞0.03。给予头孢曲松钠0.9 g入10%葡萄糖注射液100 ml静脉滴注,氨溴索15 mg入莫菲滴管滴注。输液约70 ml时,患儿出现面色苍白、烦躁哭闹,排棕红色尿,呼吸喘促。实验室检查:血红蛋白27 g/L,红细胞1.75×1012/L,网织红细胞0.045;直接抗人球蛋白试验C3 1∶4;尿潜血(+++),红细胞2～8个/HP。立即停用头孢曲松钠,输注红细胞及甲泼尼龙冲击治疗。第6天血常规示血红蛋白111 g/L,红细胞3.83×1012/L,患儿病情好转。     

埃克替尼相关局灶增生型IgA肾病和急性肾小管损伤

1例68岁男性肺腺癌患者接受埃克替尼125 mg口服、3次/d和康莱特软胶囊2.7 g口服、4次/d治疗。用药前血清肌酐(Scr)91 μmol/L。用药29 d后患者出现泡沫尿、乏力、胸闷、食欲下降、颈部及胸前皮肤出现红色皮疹等, 未予干预, 共用药76 d。实验室检查示Scr 167 μmol/L, 免疫球蛋白A(IgA)4 090 mg/L, 尿蛋白2 g/L, 24 h尿蛋白2.61 g, 尿红细胞6.8个/高倍视野, 尿α微球蛋白66.9 mg/L。病理检查结果示局灶增生型IgA肾病和急性肾小管损伤, 考虑由埃克替尼引起可能性大。嘱患者低蛋白饮食并予对症治疗, 80 d后, 患者Scr 189 μmol/L、尿蛋白2 g/L。此后患者失访。     

卡马西平致再生障碍性贫血1例报告

患者女性 ,2 0岁。因发热 ,鼻、牙龈出血 1周入院。出现症状前 ,患者因癫痫于 2年前口服卡马西平 (0 .2 g/ d)至今。入院时查血常规示 :Ret(网织红细胞 ) 1 4 .4× 1 0 9/ L,Hb9.5 g/ L ,RBC3.2 7× 1 0 1 2 / L,WBC1 .9× 1 0 9/ L,PLT8.6× 1 0 9/ L,结合骨髓细胞学检查 ,诊断为再生障碍性贫血 (卡马西平所致 )。考虑突停卡马西平会导致癫痫样大发作 ,治疗予卡马西平 2 5mg口服 ,每日1次同时予 ,输血、止血、刺激骨髓造血及对症治疗。治疗过程中病人出血倾向得到控制 ,无癫痫发作。治疗半月后将卡马西平改为 2 5mg口服每 2日一次 ,…     

罗格列酮与二甲双胍联合应用致贫血

1例76岁糖尿病女性患者,口服二甲双胍10年后,加用瑞格列奈1mg,2次/d治疗,后又加服罗格列酮4mg,1次/d,5个月后出现出汗、乏力、气短、面色苍白等症状。实验室检查:Hb84g/L,RBC2.87×1012/L,HCT0.26。停用罗格列酮并对症治疗,1个半月后血红蛋白上升至110g/L,红细胞及红细胞压积正常。     

青霉素V钾片引起溶血性贫血

患者男,34岁。因乏力、纳差、尿黄于2003年10月8日入院治疗。患者于8d前因上呼吸道感染口服青霉素V钾片,每次500mg,共用3次。因效果不明显而停药,其后逐渐出现恶心、厌油腻、食欲差、四肢无力症状,自觉有低热,未测体温。继而发现尿色加深,呈浓茶色,大便灰白。3d后乏力加重,检查发现肝功异常,以急性黄疸性肝炎收入院。查体:T37℃,P82次/min,BP112/67mmHg(1mmHg=0.133kPa),R18次/min。ALT800U/L,AST588U/L,T-Bil147.4μmol/L,D-Bil15.5μmol/L;血常规WBC11.7×109/L,RBC1.88×1012/L,HGB54g/L,PLT357×109/L,网织红细胞3%;病…     

口服安宫牛黄丸致过敏性紫癜1例

1病例资料患者,女,70岁,2019年3月2日因头昏、头痛在家自服“安宫牛黄丸,1日1次,1次1丸”治疗,后出现双下肢小腿上段皮肤片状红色瘀点、瘀斑,双侧对称分布,无瘙痒,3月5日至云南昆钢医院皮肤科就诊,考虑过敏性紫癜,建议停用相关药物并住院治疗。患者拒绝住院,停用安宫牛黄丸的同时,予口服“雷尼替丁胶囊0.15 g bid,枸地氯雷他定1片qn”治疗,在家服药2 d后症状无缓解,皮肤瘀点、瘀斑进行性增多,逐渐蔓延至双下肢小腿下段、双侧大腿、臀部、腰背部、双上肢,部分融合成片,为紫红色,按压不退缩,无疼痛及瘙痒,余无特殊。遂于3月7日以“过敏性紫癜”收入云南昆钢医院。     

螺内酯致乏力和嗜睡

1例24岁男性继发性高血压病患者,为排除原发性醛固酮增多症而接受螺内酯的诊断性治疗,分别于午餐后、晚餐后、次日清晨口服螺内酯各20mg。第1次服药后约3h患者突然出现四肢乏力、眩晕、头痛,经卧床休息和吸氧,约30min后症状缓解。第2次服药后3h出现乏力。第3次服药后约2h上述症状复现并伴嗜睡,2h后自行缓解。停用螺内酯。5d后患者于晚餐后口服螺内酯20mg,服药后约2h以及次日清晨再现眩晕、乏力及嗜睡,后自行缓解。     

口服奥硝唑致谵妄

1例67岁男性患者因牙龈炎口服奥硝唑（1.0 g,1次/d）、头孢拉啶（0.5 g,3次/d）和对乙酰氨基酚（0.5 g,2次/d）。3 d后疼痛减轻,但出现头晕、头痛及乏力症状。停用头孢拉啶和对乙酰氨基酚,继续服用奥硝唑。4 d后患者突然出现精神异常,症状昼轻夜重,脑电图检查示α波频率变慢,出现散在不规则θ波,诊断为谵妄。停用奥硝唑,给予氟哌啶醇5 mg,1次/d肌内注射;维生素B_6 0.2 g、三磷酸腺苷40 mg、辅酶A 200 U以及维生素C 2.0 g加入10%葡萄糖氯化钠注射液1000 ml中静脉滴注,1次/d;奥氮平5~10 mg,2次/d口服。3 d后患者神志恢复,停用氟哌啶醇;奥氮平减量至0.25 g,1次/d口服。治疗第6天患者头晕、头痛及乏力消失,体力恢复,脑电图检查正常。第7天停用抗精神病药。随访3个月余,患者精神状态正常。     

沙丁胺醇过量致中毒

1例30岁男性患者因与家属争吵后自服沙丁胺醇约300片（2mg／片）后急诊入院,自述有头晕、头痛、目眩、心悸及口干等。予催吐、导泻、口服药用炭片吸附毒物,纠正电解质紊乱及维持酸碱平衡,血液灌流联合血液透析等治疗。3d后症状好转出院。7d后随访,患者无不适。     

Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model

Oxidative stress is implicated in the pathogenesis of pulmonary damage during viral infections. In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. This suggest that antioxidant therapy can increase survival by either improving the defenses against virus or by protecting from the pathogenesis of lung inflammation.     

奥美拉唑致严重心动过缓4例

4例男性患者(年龄分别为20、40、22和28岁)分别因慢性浅表性胃炎、十二指肠球部溃疡或胃溃疡服用奥美拉唑20 mg,2次/d,其中3例单独口服奥美拉唑,1例合并应用奥美拉唑、阿奇霉素和胶体果胶铋。2 d后均出现头晕、乏力、胸闷、气短等症状,心率分别下降为44、46、46和44次/min。停用奥美拉唑并肌内注射阿托品0.5 mg,3次/d后,4例患者心率均恢复至用药前水平。     

A sensitive and specific method for the determination of total ribavirin in monkey liver by high-performance liquid chromatography with tandem mass spectrometry

A sensitive and specific method using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the analysis of total ribavirin in monkey liver is developed and validated. In this method, ribavirin and its phosphorylated metabolites are extracted with perchloric acid. The metabolites are converted to ribavirin using acid phosphatase and further purified using a NH2 solid-phase extraction (SPE) cartridge prior to LC-MS/MS analysis. [13C]Ribavirin is added with the extraction solution as an internal standard to obtain better accuracy and precision of the analysis. The MS/MS was selected to monitor 245-->113 and 250-->113 transitions using positive electrospray ionization for ribavirin and [(13)C]ribavirin. The calibration curve is linear over a concentration of 1.0-100 microg/g with a limit of quantitation (LOQ) of 1.0 microg/g. Mean inter-assay accuracy for QC at 1.0, 10 and 100 microg/g are 108, 99.7 and 99.7%, respectively. Mean inter-assay precision (CV) for QC at 1.0, 10 and 100 microg/g are 5.34, 5.24 and 4.59%, respectively. Extractability of total ribavirin from liver has been confirmed with liver obtained from monkey dosed with [14C]ribavirin. The method has been proven to be useful in the determination of total ribavirin concentration in liver from monkeys in mass balance study (10 mg/kg) and in 28 days toxicology study (300 mg/kg/day). It is also used to determine the total ribavirin concentration in human livers from hepatitis C patients received dose of 600 mg ribavirin twice daily.     

复方妥英麻黄茶碱片致苯妥英中毒4例

4例有哮喘症状的患者,男、女各2例,年龄54～65岁,口服复方妥英麻黄茶碱片4～9片/d,每片含苯妥英钠50mg,每日总剂量为200～450mg,服药时间1～4年。服药期间患者逐渐出现头晕、眼球震颤、步态不稳等症状及小脑性共济失调的体征。检测苯妥英血药浓度34.15～94.12μg/mL,为治疗血药浓度的1.7～4.7倍,诊断为苯妥英钠中毒。停用复方妥英麻黄茶碱片,4～7d后患者中毒症状消失。2例患者复查血药浓度,分别降至1.03、1.14μg/mL。     

国产甲磺酸托烷司琼正常人体耐受性试验

目的考察国产甲磺酸托烷司琼正常人体耐受性。方法24名健康志愿者,随机分为7组,分别参加单次静脉注射甲磺酸托烷司琼3,6,12mg组以及分别po3,6,12,24mg*d-1,连续5d。结果2种剂型在所试剂量范围内都可耐受。对于神经系统、心血管、肝肾功能及实验室指标无明显影响;≤6mg     

Effects of four antiviral substances on lethal vaccinia virus (IHD strain) respiratory infections in mice

Intranasal infection of BALB/c mice with the IHD strain of vaccinia virus was found to cause pneumonia, profound weight loss and death. Cidofovir, hexadecyloxypropyl-cidofovir (HDP-CDV), the diacetate ester prodrug of 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (HOE961), and ribavirin were used to treat the infections starting 24h after virus exposure. Single intraperitoneal (i.p.) cidofovir treatments of 100 and 30 mg/kg led to 90-100% survival compared with no survivors in the placebo group, whereas a 10 mg/kg dose was ineffective. The 100 mg/kg treatment reduced lung and snout virus titres on day 3 of the infection by 20- and 8-fold, respectively. Mean arterial oxygen saturation levels in these two cidofovir treatment groups were significantly higher than placebo on days 4 through 6 of the infection, indicating an improvement in lung function. Effects of cidofovir on viral pathogenesis were studied on days 1, 3 and 5 of the infection, and demonstrated statistically significant reductions in lung consolidation scores, lung weights, lung virus titre and snout virus titres on days 3 and 5. Cidofovir treatment also reduced virus titres in other tissues and body fluid, including blood, brain, heart, liver, salivary gland and spleen. HDP-CDV was given by oral gavage at 100, 50 and 25mg/kg doses one time only, resulting in 80-100% survival. Lower daily oral doses of 10 and 5mg/kg per day given for 5 days protected only 30% of animals from death. Oral doses (100, 50 and 25 mg/kg per day) of HOE961 for 5 days protected all animals, whereas equivalent oral doses of ribavirin were completely ineffective. The rapidity of recovery from weight loss during the infection was a function of dose of compound administered. These data indicate the utility of parenteral cidofovir, oral HDP-CDV and oral HOE961 in treating severe respiratory infections caused by this virus.