环磷酰胺引起系统性红斑狼疮患者急性淤胆性肝炎1例报告及文献复习

1例26岁女性患者因系统性红斑狼疮、肺动脉高压入院,给予激素、环磷酰胺(cyclophosphamide,CTX)(0. 4 g,每周1次静脉滴注)、羟氯喹,以及呋塞米、螺内酯利尿,地高辛强心,西地那非靶向扩肺血管治疗。2个月后(CTX累积剂量3. 2 g),患者出现丙氨酸氨基转移酶大于800 U/L,停用CTX 1个月后好转。再次行CTX治疗,当CTX累积量达8. 0 g时,患者出现皮肤巩膜黄染等症状,经实验室检查及肝穿刺活检,结果证实为CTX引起的急性淤胆性肝炎,停用CTX 32 d后好转。本文对CTX致该患者的2种形式肝损伤原因进行了分析,并结合文献对CTX引起淤胆性肝炎的病例进行了总结。     

人巨细胞病毒通过调控自然杀伤细胞的免疫逃逸机制研究进展

人巨细胞病毒( human cytomegalovirus,HCMV)是疱疹病毒β亚科的DNA病毒,基因组为线状双链DNA,全长约240 kb,编码200种以上基因产物.这些基因产物除参与病毒复制增殖外,还与免疫逃逸有关.HCMV感染后,宿主终身带毒并表现为持续性感染.免疫系统对HCMV有持续的选择压力,HCMV存在于宿主体内的关键是逃逸免疫清除.自然杀伤(NK)细胞是人体的固有免疫淋巴细胞,是抵抗感染和清除病变细胞的第一道防线,在体内阻止感染的发生发展中起到重要作用.NK细胞表面表达多种抑制性和激活性受体,如杀伤细胞凝集素样受体(KLR)中的CD94/NKG2C和免疫球蛋白样转录体受体1( LIR1/ILT2)为抑制性受体;NKG2D、NKp30则为激活性受体.NK细胞清除靶细胞的能力由抑制性和激活性受体所产生的抑制和激活信号的平衡所控制.HCMV感染细胞对NK细胞介导的细胞毒具有明显的抗性作用.迄今为止,已经发现HCMV 7个基因(UL16、UL18、UL40、UL83、UL112、UL141和UL142)可以编码相应产物,通过不同机制调节NK细胞抑制或激活信号,抑制NK细胞激活,从而对抗NK细胞的清除作用.     

去甲万古霉素致白血病患者急性肾损害

1例75岁男性患者,因头晕、乏力、发热、咳嗽入院.诊为急性粒-单核细胞白血病,给予非格司亭和维A酸治疗.住院15 d后,患者慢性阻塞性肺病加重,给予美洛西林、五水头孢唑啉钠和头孢哌酮-舒巴坦治疗之后其症状缓解.又经16 d后,实验实检查示:WBC 4.38×109/L,N 0.71,SCr 78 μmol/L.患者体温为38.5℃.给予去甲万古霉素800 mg静脉滴注,每12 h 1次,共治疗7 d.治疗第5天患者尿量明显减少,为600 ml/d.第7天尿量减少至300 ml/d,SCr 362 μmol/L.尿常规:蛋白(+),红细胞(+).停用去甲万古霉素,给予利尿剂.2 d后患者肾功能恢复正常,SCr为120 μmol/L.     

氟康唑致HIV感染者重症多形性红斑型药疹

患者女,45岁。为治疗甲癣,于2005年6月11日服用氟康唑1次100mg。服后次日出现双上肢皮疹,伴搔痒,并逐渐增加。皮疹为红斑疹,疹间皮肤潮红,压之不褪色,伴搔痒,自感畏寒,未测体温。入院前5d皮疹明显增加,伴发热,T39.5℃,并全身出现浮肿,眼睑水肿,结膜充血及全身皮肤出现大水疱,汇合成片,局部破溃,T40℃,无畏寒,寒战。外院确诊“多形性红斑”,于2005年6月17日转入我院。患者既往有高血压病史10余年,长期服用贝那普利,氨氯地平降压治疗,对青霉素、磺胺类药物过敏,对桃等多种食物过敏,曾出现多次皮疹;10年前有输血史。入院前HIV抗体初筛阳性,尿…     

Agranulocytosis possibly caused by ranitidine in a patient with renal failure

A 70-year-old Japanese woman with renal dysfunction under hemodialysis presented with vomiting and chill with fever. Over the previous 24 weeks she had been taking 75 mg of ranitidine after hemodialysis. Other medications taken were prednisolone, furosemide, alpha-calcidol, amlodipine and calcium carbonate. Before starting ranitidine, she had been treated with famotidine for about 2 years without complication. Hematological inspection on admission revealed agranulocytosis with WBC of 400/mm3. Ranitidine was discontinued and granulocyte colony-stimulating factor (G-CSF) was started. On Day 3, laboratory data showed slight improvement of cytopenia with WBC of 1,000/mm3. On Day 6, her hemogram showed marked improvement with WBC of 11,700/mm3 and G-CSF was discontinued. She was discharged on Day 10. Several cases describing ranitidine-induced cytopenia are associated with the use of ranitidine at a dose of 150 mg/day or higher, and adverse reactions were found within 2-35 days after beginning ranitidine treatment. In the case described here, however, the adverse reaction occurred after a longer treatment period with ranitidine at a lower dose. In conclusion, ranitidine should be administered with great caution to patients with severe renal dysfunction.     

非诺贝特致甲状腺功能减低患者横纹肌溶解症1例

1例37a男性患者,因血脂高,给予非诺贝特缓释胶囊250mg,口服,每晚1次。服药前查：TG17.17mmol·L-1,CK45U·L-1,LDH98U·L-1,AST30IU·L-1,ALT21IU·L-1。服药第9天后患者出现右侧小腿肌肉酸痛、无力,急查CK2900.05U·L-1,LDH432U·L-1,AST121IU·L-1,ALT65.5IU·L-1,确诊为横纹肌溶解症。立即停用非诺贝特,给予碱化尿液、保护细胞膜等治疗。查甲状腺功能示：TT30.3nmol·L-1,TT47.5nmol·L-1,FT31.9pmol·L-1,FT47.8pmol·L-1,TSH237μIU·mL-1。甲状腺B超示甲状腺弥漫性病变。确诊为甲状腺功能减低,遂加用口服左甲状腺素钠片治疗。停非诺贝特3d后患者症状消失,27d后血CK、转氨酶基本恢复。     

1例甲巯咪唑致粒细胞缺乏症患者的药学监护

目的通过回顾1例甲状腺功能亢进患者应用甲巯咪唑致粒细胞缺乏症的诊疗过程的,探讨药师如何依据患者的病理生理情况完成药学监护。方法药师与临床医师密切配合,预估重组人粒细胞刺激因子治疗粒细胞缺乏症的治疗终点、合理选择和调整抗菌药物的品种、根据肾功能状况确定给药剂量,以及对患者进行的用药教育。结果患者共住院28d,粒细胞缺乏症得到纠正,感染得到控制,顺利地完成了131I放射治疗。结论临床药师加入临床治疗团队,提供药学服务可以提高临床药物治疗效果。     

Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo.

Novel non-nucleosidic compounds have recently been identified as potent inhibitors of the human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) in vitro. We have now investigated the antiviral activity of these compounds in MCMV-infected NOD/LtSz-scid/j mice that lack functional T, B and, in contrast to C.B-17/Icr scid/scid mice, natural killer cells, and represent a novel model for cytomegalovirus infection in immunocompromised hosts. BAY 38-4766 (3-hydroxy-2,2-dimethyl-N-[4(([5-(dimethylamino)-1-naphthyl]sulfonyl)amino)- phenyl]propanamide) was identified as the most potent representative of this class of antiviral compounds. Per os administration of BAY 38-4766 at dosages > or = 10 mg/kg body weight led to antiviral effects that were comparable to ganciclovir 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (Cymevene) as measured by survival and levels of viral DNA in organs of infected mice. In order to assess the anti-HCMV activity of BAY 38-4766 in vivo, we used a model, in which HCMV-infected human cells were entrapped in hollow fibers and subsequently transplanted into immunodeficient mice. Using this model, we demonstrated antiviral activity of BAY 38-4766 similar to that of ganciclovir. We conclude that BAY 38-4766 shows potential as an anti-HCMV drug.     

Bioelectric toxicity caused by chlorpromazine in human lung epithelial cells

Endogeneous and exogeneous amine-containing substances possess pneumophilic properties. Among them, tricyclic amphiphilic amine drugs like neuroleptics intensively accumulate in the lung cell membrane and occasionally cause severe respiratory disorders. In the present study, we examined the bioelectric toxicity of chlorpromazine (CPZ), a commonly used neuroleptic, in human lung epithelial cells. CPZ concentration-dependently inhibited the isoproterenol (ISO)-generated short-circuit current (I(sc)) sensitive to a nonselective K(+) channel blocker, clotrimazole (30 microM), but insensitive to a selective Ca(2+)-activated K(+) (K(Ca)) channel blocker, charybdotoxin (ChTx, 100 nM). The effects of apical CPZ on the ISO-induced responses were greater than those of basolateral CPZ. Forskolin- and 8-bromo-cyclic AMP-induced I(sc) were partially prevented by CPZ. Nystatin permeabilization of the monolayers revealed that CPZ attenuated the basolateral K(+) current elicited by ISO more than that elicited by forskolin and that the apical Cl(-) current elicited by forskolin was instead potentiated by CPZ, although it inhibited the ISO-induced Cl(-) current. 1-Ethyl-2-benzimdazolinone (1-EBIO, a K(Ca) channel opener, 500 microM)- and ionomycin (Ca(2+) ionophore, 1 microM)-evoked Cl(-) secretions were also sensitive to CPZ. These results indicate that CPZ inhibits transepithelial Cl(-) transport, affecting at least two different targets: the beta-adrenergic receptor and the basolateral K(+) channels (especially the K(Ca) channel). Electrostatic interactions at the inner surface of the membrane between the protonated amines of CPZ and negatively charged portions of the plasma membrane may be involved in the mechanisms.     

瑞巴派特片致多汗症1例

Medical Records;     

临床药师参与1例氯氮平所致肠梗阻患者会诊的案例分析

目的探讨临床药师通过临床会诊参与临床治疗的方法和作用。方法临床药师参与1例氯氮平所致肠梗阻患者的会诊,从患者肠梗阻的原因、治疗等方面进行综合分析。结果临床药师根据分析结果协助医师合理用药,提出的会诊意见和建议得到了临床认可。结论临床药师参与临床查房和会诊,对提高临床诊疗水平及保障患者用药安全、有效、经济、合理具有极大的帮助和促进作用。     

Merkel cell carcinoma in a patient with autoimmune hepatitis

Merkel cell carcinoma (MCC) has been shown to have a higher incidence in many etiologically distinct immunosuppressed populations. We report a case of aggressive MCC diagnosed in a man with autoimmune hepatitis who was treated with immunosuppressive therapy for more than 30 years.     

Telbivudine myopathy in a patient with chronic hepatitis B

CASE: A 25-year-old man with hepatitis B virus (HBV) infection received antiviral treatment with telbivudine 600 mg daily. Six months after starting treatment, the patient developed progressive weakness and myalgia. Physical examination showed symmetrical proximal weakness. Blood tests at admission revealed positive hepatitis b surface antigen (HBs Ag), and, elevated creatine kinase (CK) level (1,614 U/L, normal range: 38-174 U/L). Aspartate aminotransferase was 64.7 U/L (normal range: 8-40 U/L), and LDH was 293 U/L (normal range: 80-285 U/L). Electrodiagnostic studies indicated myopathic changes. A muscle biopsy revealed myositis and no mitochondrial changes were found. Drug-induced myopathy was suspected and telbivudine was changed to entecavir. The muscle weakness and laboratory findings improved. CONCLUSION: A patient developed drug-induced myopathy during long-term treatment with telbivudine for chronic HBV. To promptly detect this reversible adverse event, monitoring of serum CK level and recognition of myopathic signs and symptoms are necessary. Further investigations are needed to clarify the possible mechanism of telbivudine-induced myopathy.     

1例脓肿分枝杆菌致跟骨骨髓炎的药学监护

临床药师参与1例脓肿分枝杆菌致跟骨骨髓炎的全程治疗,参与药物治疗方案制订及实施,针对病例的特殊性和复杂性,及时调整抗脓肿分枝杆菌的药物,分析不良反应发生的原因,运用药学专业知识与临床实践有机地结合,经过多次调整药物治疗方案,患者好转出院。临床药师提供的药学服务提高了临床药物治疗效果并减少了用药风险。     

结核性脑膜炎患者抗结核治疗致药物性肝炎临床分析

目的：探讨结核性脑膜炎患者抗结核治疗致药物性肝炎的发病规律及临床特点。方法：分析本院119例结核性脑膜炎患者的规则抗结核治疗,住院＋门诊随访观察至疗程24周的临床资料。结果：119例结核性脑膜炎患者在抗结核治疗24周期间有39例出现药物性肝炎,发生率为32．8％,其中32例发生在强化期（16周内）,经加强护肝、调整抗结核方案等个体化治疗,药物性肝炎治愈率94．9％,结核性脑膜炎治疗有效率90.3％。结论：重视结核性脑膜炎抗结核治疗过程中出现的药物性肝损害,早期制定个体化用药对策,即能使肝功能恢复正常,又使抗结核治疗有效。     

大剂量肾上腺糖皮质激素致SARS患者多种并发症个案

这是一例激素致骨坏死等多种并发症的典型个案，典型得让人心生怜悯。让编者无法克制去联系患者本人——内蒙古胸科医院黄耆副院长，想要知道他的近况。但是当电话拨通，听到的是黄院长爽朗的声音：“激素在去年SARS的治疗中功不可没，它挽回了许多人的生命，但是我本人和像我一样的很多患者没有得到正确的治疗，如剂量太大，时间太长。”黄院长说，他并不是要抱怨过去，只是希望卫生部门和有关专家像去年重视SARS本身一样，在总结经验教训的同时，更加要正视和重视由激素治疗带来的一系列问题!在此，我们也希望所有SARS患者能够像黄耆副院长一样拥有一个乐观的、积极的心态。     

干扰素治疗丙型肝炎患者引起房颤

患者男,69岁。2001年经检查发现感染丙型肝炎病毒,于2003年10月15日来我院治疗。化验检查:HCV-RNA1.88×106 copies/mL(正常值<2×102 copies/mL),ALT78U/L。既往病史:1984年因支气管扩张并咯血,曾输血400mL;1989年因左肾结石切除左肾。在此之后肝功反复异常,ALT波动于100～200U/L。患者既往最高血压为150/90mmHg(1mmHg=0.133kPa),无心脏疾病史。为治疗丙型肝炎,给予干扰素α(英特龙)300万u,肌内注射,1次/d治疗。在注射第1针干扰素后0.5h左右,患者突然出现心慌、头晕、发热、面色苍白。查体:T38.8℃,BP120/80mmHg,P140次/min,R2…