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.     

增白牙膏去除牙面外源性色素临床实验

目的测试一种增白牙膏用于减少牙面外源性色素的效果. 方法 研究对象121例,年龄21～57岁.实验组60例,对照组61例,两组年龄和性别分布差异无显著性.采用双盲法两组平行设计,根据Lobene色斑指数(LSI)和性别均衡分为两组,随机分配使用实验牙膏或对照牙膏.实验组牙膏含3 %植酸钠和1.3 %焦磷酸钠,对照组牙膏不含相应成分.临床检查分别在基线、3周和6周后进行,由同一人测定LSI.问卷询问刷牙情况. 结果 基线检查、实验3周和6周后实验组LSI分别为3.00、2.16和1.47, 对照组分别为3.10、3.08和2.18.基线检查两组LSI差别无显著性意义, 实验3周和6周后两组LSI比较差异均有显著性意义. 实验组LSI在3周和6周后分别比基线时降低28 %和51 %. 结论含3 %植酸钠和1.3 %焦磷酸钠牙膏能有效减少牙面色素,效果随使用时间而增强.     

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.     

Bioactivation to an aldehyde metabolite—Possible role in the onset of toxicity induced by the anti-HIV drug abacavir

Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species.     

Dynamic changes in specific anti-L-asparaginase antibodies generation during acute lymphoblastic leukemia treatment

Background

L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity.