甲巯咪唑致肝损害及粒细胞减少

1例36岁女性患者,因患甲状腺机能亢进症给予甲巯咪唑10 mg,3次/d,普萘洛尔10 mg,3次/d治疗.服药23 d后,患者出现皮疹、食欲下降和恶心.实验室检查示:WBC 1.6×109/L,中性粒细胞绝对值0.80×109/L;ALT 125.0 U/L,AST 62.0 U/L.停用甲巯咪唑,给予还原型谷胱甘肽、水飞蓟宾、氯雷他定及非格司亭治疗后好转.患者WBC为4.30×109/L,中性粒细胞绝对值为3.1×109/L,ALT和AST分别为27.0 U/L和17.0 U/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。     

清开灵注射液致白细胞减少2例

2例精神病患者因上呼吸道感染,静脉滴注清开灵治疗时出现白细胞减少。例1,1名30岁女性因偏执性人格障碍长期服用文拉法辛(150mg/d)及富马酸喹硫平(0.2mg/d)。入院后第3天,患者发生"上呼吸道感染",查WBC 5.7×109/L,给予清开灵注射液40ml加入0.9%氯化钠注射液500ml静脉滴注,1次/d。次日WBC 3.2×109/L,继续滴注清开灵5d后,WBC 2.0×109/L。停用清开灵后第6天,查WBC 4.7×109/L。此后多次复查WBC均正常。例2,1名35岁女性因患"双相情感障碍"入院,2个月后伴发"上呼吸道感染",查WBC 7.8×109/L,给予清开灵注射液30ml 5%葡萄糖注射液500ml静脉滴注,1次/d,维C银翘片2片,3次/d。第5天上呼吸道感染症状消失,体温恢复正常,查WBC 3.1×109/L。停用清开灵,1周后复查WBC 5.8×109/L。随访3个月WBC均正常。     

头孢克洛致小儿皮肤关节型过敏性紫癜

患儿男,7岁。因腹痛3d,于2003年11月3日下午来我院就诊。家长代述病史:3d前患儿开始腹痛,曾呕吐过1次,为胃内容物,大便正常,仅于来诊当日解稀便1次。在外院检查:WBC14.0×109/L,腹部B超未见异常。给予头孢曲松静滴治疗,效果不明显,遂来我院诊治。查体:体温正常,神志清醒,精神较好,无皮疹,咽部充血,心肺听诊正常,腹平软,无明确压痛,肝、脾未触及,肠鸣音正常。实验室检查:WBC12.0×109/L,N0.64、L0.03,Hb144g/L,BPC48.8×109/L,C反应蛋白(CRP)<8mg/L,尿常规正常,因无大便,故大便常规未查。诊断:腹痛待查,肠炎(?)。11月4日患儿服用头…     

双黄连注射剂致过敏反应2例

例1:患男,28岁,因发热咳嗽就诊.查体:T39℃,R 30次·min-1,P 100次·min-1,咽充血,扁桃体肿大,肺纹理增粗.化验:WBC 6.8×109·L-1,MID 85%,LYD 26%.诊断:上呼吸道感染.给予双黄连注射剂(哈药集团中药二厂,批号0104505),3 h后患者全身出现米粒样红色丘疹,瘙痒,躯干部明显.患者无过敏史,也未服用其它药物.立即给予抗过敏治疗,2 h后症状消失.次日继静滴双黄连注射剂,患者全身又出现皮疹,复给予抗过敏治疗,并停用双黄连注射剂,皮疹消失. 例2:患男,56岁.因咽痛、发热伴咳嗽半月余就诊.查体:T38℃,P 124次·min-1,R 28次*min-1.X光检查:肺纹理增粗.化验:WBC 9.8×109·L-1,LYM 30%,MID 80%.诊断:上呼吸道感染.给予双黄连注射剂(哈药集团中药二厂,批号0104505),用药后5 h患者面部潮红,皮肤及躯干出现少量皮疹,有轻度瘙痒,次日继静滴双黄连注射剂,皮疹增多,部分融合成片,有明显瘙痒;停用双黄连注射剂,im地塞米松5 mg,iv葡萄糖酸钙注射液10 mL,症状消失. 双黄连注射剂是由中药提取而成的灭菌制剂,成分复杂,其中绿原酸可能是引起过敏反应的主要原因之一.有报道认为制剂中的附加剂原料掺进少量花粉等,都易导致过敏反应.     

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。     

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。     

头孢美唑钠致白细胞和粒细胞减少

1例17岁女性患者因感染性心内膜炎静脉滴注头孢美唑钠（2 g,3次/d）和阿米卡星（0.4 g,1次/d）。用药6天血常规检查示白细胞计数23.4×109/L,中性粒细胞0.92,中性粒细胞绝对值21.6×109/L。用药第13天血常规检查示白细胞计数6.6×109/L,中性粒细胞0.70,中性粒细胞绝对值4.6×109/L。第14天停用阿米卡星,继续原剂量静脉滴注头孢美唑钠。用药第28天血常规检查示白细胞计数2.6×109/L,中性粒细胞0.37,中性粒细胞绝对值1.0×109/L。停用头孢美唑钠,更换为万古霉素粉针0.5 g,1次/8 h静脉滴注。更换药物后第7天,血白细胞计数6.1×109/L,中性粒细胞0.60,中性粒细胞绝对值3.7×109/L。     

误诊为多发性骨髓瘤的食管癌1例

<正>患者,男,54岁。因乏力、纳差1个月余,发现血钙升高3 d余,于2020年12月6日入院。患者1个月前无明显诱因出现纳差、乏力,伴头皮发麻、发痒,其余无特殊不适。既往体健,无特殊病史。外院就诊,血常规示：白细胞计数11.8×109/L,中性粒细胞百分比83.1%,红细胞计数3.07×1012/L,血红蛋白109 g/L,血小板计数266×109/L。肝功能示：丙氨酸氨基转移酶43.2 U/L,天冬门氨酸氨基转移酶29.2 U/L,     

克林霉素磷酸酯引起药疹1例

患男,35岁,因发热、咳嗽、咽喉肿痛,引起支气管感染在我院门诊就诊.查体:T38.9℃,P 96次/min,R 24次/min;血常规:RBC 5.12×10北/L,WBC10.8×109/L,尿粪常规均正常,诊断为上呼吸道感染.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.