Phenytoin desensitization monitored by antigen specific T cell response using carboxyfluorescein succinimidyl ester dilution assay

We evaluated drug-specific T cell responses in a patient with refractory partial seizures and paroxysmal kinesigenic choreoathetosis successfully treated with clinical desensitization to phenytoin. Drug-induced lymphocyte transformation test before desensitization was negative with a stimulation index of 130%. The frequencies and cytokine-producing phenotypes of phenytoin-specific T cells were examined simultaneously by using a carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Before desensitization, the proportion of CFSElow CD4+ cells in whole CD4+ was 3.09%; 13.6% of CFSElow CD4+ cells were stained with anti-interferon gamma antibody. After desensitization, phenytoin-specific CFSElow CD4+ cells decreased to background level. These results indicate that CFSE dilution assay will be useful for the diagnosis and monitoring of drug hypersensitivity.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

香烟烟对变态反应性疾病的影响

为探讨香烟烟对变态反应性疾病的影响，以香烟烟作为变应原，采用特异性体内皮肤试验测定了１６０６例变态反应性疾病患者对香烟烟的反应，并对香烟烟呈阳性反应与各种变态反应性疾病的关系以及与性别和年龄的关系进行了多元回归分析。结果表明，对香烟烟的皮试阳性的反应率为３４．６％（５５６例患者对香烟烟呈阳性反应），香烟烟的阳性反应与变应性疾病的发病有关，而与性别、年龄、病程、外周血白细胞计数和嗜酸性粒细胞计数相关性不大。对５８例香烟烟呈阳性反应的支气管哮喘患者，用乙酰甲胆碱做了气道激发试验，其结果为，激发后的最大肺活量（ＦＶＣ）、一秒钟用力呼气量（ＦＥＶ１）、最大呼气流速（ＰＥＦＲ）低于激发前。对２２３例香烟烟阳性反应者（其中支气管哮喘患者１８４例、变应性鼻炎８７例、过敏性皮肤病５２例），采用ＥＬＩＳＡ方法测定血清总ＩｇＥ，并与正常对照组比较，香烟反应的病人组血清总ＩｇＥ显著增高。由此可见，香烟烟可以引起变态反应性疾病。     

Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.     

Cardiovascular and respiratory mechanisms in anaphylactic and anaphylactoid shock reactions

Summary Different mediators such as histamine, leukotrienes, prostaglandins and bradykinin are involved in different reaction mechanisms such as cytotropic anaphylaxis (CA), immune complex anaphylaxis (ICA), reactions due to direct histamine liberation or activation of the complement system or hyperosmolarity induced anaphylactoid reactions.In the monkey CA induces systemic vasodilatation, a transient pulmonary hypertension and increase of cardiac output followed by peripheral blood pooling and depression of cardiac output. ICA induces peripheral vasoconstriction, a severe increase in pulmonary vascular resistance and decreased cardiac output, the latter possibly being partially due to decreased cardiac contractility.In hypersensitivity reactions in man cutaneous vasodilatation as well as vasoconstriction may occur alternatively. Peripheral blood pooling and increased vascular permeability are the cause of severe relative and absolute hypovolemia, respectively. Pulmonary vasoconstriction seems to occur in connection with serious bronchospasm. Decreased venous return, myocardial ischemia and hypoxemia can contribute to a reduction of cardiac performance. The most frequent changes in the ECG are sinus tachycardia, sinus bradycardia, extrasystoles, conduction disturbances as A-V block and bundle branch block; lethal or sublethal shock is often associated with malign arrhythmias or cardiac arrest.Almost normal blood gas values are seen in anaphylactic shock without clinical signs of respiratory obstruction. The very few documented cases of anaphylactic shock with respiratory obstruction indicate that increased airway resistance and reduced lung compliance may be present as well as mild to moderate hypoxemia with normal or subnormal CO₂ values.     

视盘血管炎的治疗

目的：研究视盘血管炎的发病机制,病因,病程经过,治疗方法及预后。方法：系统治疗和观察了视盘血管炎４６例,其中视乳头水肿２６例、３０眼,中央静脉血栓型２０例、２０眼。对患者视力、视野、眼压、视乳头改变、眼底荧光血管造影及血象等进行了检查。对视乳头水肿型行ＣＴ颅脑扫描,眼压测量和脑脊液检查以除外颅内病变。所有患者均予以抗感染和抑制免疫反应疗法。结果：患者均在１８个月内治愈。视乳头水肿型视盘血管炎半数视     

Concomitant alveolitis and asthma following exposure to triphenylmethane triisocyanate

A 36-year-old man was admitted to hospital with increasing breathlessness.He had been exposed to triphenylmethane triisocyanate. Pulmonaryfunction tests demonstrated physiological abnormalities consistentwith both asthma and alveolitis. Exposure to less common isocyanatesmay not be immediately apparent. Asthma developing after isocyanateexposure is well recognized. Pneumonitis is a relatively rarecomplication. Measurement of gas transfer may be helpful inthe investigation of isocyanate toxicity.     

中药注射剂不良反应监测的初步报告

目的 了解中药注射剂不良反应情况，探讨与不良反应的发生有关的影响因素。方法 采用医院集中监测方法，收集医院内所有使用中药注射剂的住院病人的临床资料和所有相关的不良事件，对不良反应因果关系进行判断，分析各种影响因素与不良反应发生的关系。结果 收集到3375例住院患者资料，发生与中药注射剂有关的不良事件共有51例，因果关系判断为“可能”者有11例，判断为“很可能”者有40例。与中药注射剂有关的可能不良反应的发生率为1．51％，92％的不良反应属于过敏反应。所监测的中药注射剂有31种，其中以鸦胆子油乳注射液、灯盏花素注射液和参附注射液的不良反应发生率较高。Logistic逐步回归分析表明，退休相对于体力劳动、较高的教育程度相对于文盲来说，不良反应发生的危险性较高。结论 中医内科病房住院病人中药注射剂不良反应的发生较少，但个别中药注射剂不良反应发生率较高，应引起注意。     

奥沙利铂致过敏反应分析

目的 研究奥沙利铂在治疗胃肠道肿瘤患者中出现的过敏反应的临床表现、机制及治疗方法.方法 回顾性分析2007年3月至2013年4月在大连大学附属新华医院肿瘤内科住院、应用奥沙利铂治疗的502例胃肠道肿瘤患者的过敏反应发生情况.结果 本组奥沙利铂致过敏的发生为为 3.8%（19/502）,Ⅲ~IV度过敏反应的发生率为2.6%（13/502）,无死亡病例.对出现过敏反应的患者给予抗过敏及抗休克治疗后,患者过敏反应均解除,过敏反应完全解除时间为20 min~48 h.结论 奥沙利铂致过敏反应发生率相对较高,有时可能导致患者出现过敏性休克或严重哮喘,多周期应用奥沙利铂后过敏反应风险增高,一旦发生过敏反应要及时停药,并给予患者相应治疗.     

变应性真菌性鼻窦炎CT影像特征

目的回顾性总结变应性真菌性鼻窦炎CT影像表现,并与手术中所见比较,探讨其CT影像特征及其在诊断中的参考作用。方法收集21例确诊为变应性真菌性鼻窦炎患者的CT影像资料。男17例,女4例;年龄15岁～50岁。鼻窦CT扫描采用骨窗和软组织窗扫描。术前行鼻内镜检查、皮肤点刺变态反应皮试、总IgE及鼻分泌物嗜酸粒细胞涂片检查。手术中记录鼻窦和鼻腔病变且与CT影像对照。术后行组织病理学检查和真菌涂片＋培养。结果鼻内镜检查见所有病例鼻腔单发或多发半透明粉白色息肉,周围稀薄黄色或黏白色分泌物。9例11侧鼻腔可见果酱样黄褐色黏着分泌物。鼻窦CT扫描提示单侧鼻窦发病10例（10侧）,双侧病变为11例（22侧）;单侧或双侧病变全组鼻窦均受累;鼻窦腔散在均匀高密度影,呈毛玻璃样特征,周边为软组织影,3例4侧颅底骨质吸收,1例颅内侵犯。20例行鼻内镜手术,1例行双冠经路＋鼻内镜手术。术中见17例窦腔有果酱样黄褐色黏着分泌物（黏蛋白）,4例窦腔为褐绿色泥样分泌物。随访6个月至7年,治愈14例,好转7例,其中3例术后2年再手术。结论鼻窦CT扫描显示鼻窦腔内片状毛玻璃样高密度影,可伴骨质吸收或侵袭性生长,为变应性真菌性鼻窦炎具有诊断意义的影像检查特征。