The isolated perfused lung--a critical evaluation

Recent refinement and application of the technique of perfusing isolated intact lung preparations from suitable experimental animal has enhanced our knowledge of the non-respiratory functions of the lung. The technique consists of perfusion with whole blood or constituted media via pulmonary artery or artificially ventilated lungs. Such preparations have been known to be especially useful for studies of uptake, metabolism and disposition of exogenous and endogenous substances. Recent advances in unilateral, split-lung perfusion in which left and right lungs are unilaterally perfused simultaneously have enabled investigators to maintain paired controls during perfusion. Such techniques are useful in the study of the interactions of endogenous and exogenous chemicals in the lung tissue. Differences between subcellular or lung slice preparations and intact lung perfusion are to be expected on the basis of distorting natural vascular and extra-vascular barriers in the case of in vitro preparations. Areas in which perfused lungs have not been extensively used include uptake and disposition of gases, solvents and vapors, effects of toxic chemicals on respiratory and non-respiratory functions of the lung and alteration of pulmonary mechanisms and hemodynamics in the presence of interacting chemical or physical stimuli. With suitable modifications, application of isolated perfused lung preparations for these investigations should be technically feasible in the future.     

霉酚酸酯对局灶节段性肾小球硬化(FSGS)治疗作用的研究

目的:用霉酚酸酯(MMF)对以阿霉素肾病大鼠建立的局灶节段性肾小球硬化(FSGS)模型,进行干预,检测结缔组织生长因子(CTGF)的表达,研究霉酚酸酯对FSGS的治疗作用,并探讨作用机理。方法:SD大鼠18只,分为对照组、阿霉素肾病组、MMF治疗组(每组大鼠6只)。肾病组、治疗组大鼠尾静脉一次性注入阿霉素7.5mg/kg,对照组大鼠尾静脉注入等量生理盐水。治疗组于第6周起MMF 20mg.kg-1.d-1混悬于1mL蒸馏水灌胃,其他组等量蒸馏水灌胃。第10周处死所有大鼠,观察肾组织病理变化,并以免疫组织化学、Western blot方法检测肾组织CTGF蛋白水平。结果:阿霉素肾病组大鼠较对照组大鼠肾小球系膜及基质明显增生,免疫组织化学染色及western blot显示肾小球和肾小管区CTGF蛋白表达明显上升(P<0.05),霉酚酸酯治疗组肾小球系膜和基质增生较肾病组明显减轻,肾小球和肾小管区CTGF蛋白表达明显低于肾病组(P<0.05)。结论:霉酚酸酯可以减轻肾脏间质纤维化病变,机理与抑制CTGF的表达有关。     

Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients

In 2012, the U.S. Food and Drug Administration issued guidelines advising kidney transplant recipients (KTRs) to discontinue mycophenolate (MPA) in preparation for pregnancy. Little is known about how this guidance has affected pregnancy and graft outcomes. The purpose of this retrospective cohort study was to investigate any association between the discontinuation of MPA and KTR pregnancy and graft outcomes. Data from the National Transplantation Pregnancy Registry included 382 cases in which KTRs managed on MPA became pregnant. Overall, 22 variables, including the time in which a KTR discontinued MPA, were assessed across four end points: miscarriages, birth defects, and 2‐ and 5‐year postpartum graft loss. Birth defects and miscarriages were similar among KTRs who discontinued MPA >6 and <6 weeks prior to pregnancy and during the first trimester. In contrast, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages (odds ratio [OR] 9.35, 95% confidence interval [CI] 4.31–20.00, p < 0.001) and birth defects (OR 6.06, 95% CI 1.96–18.87, p = 0.002). Discontinuing MPA <6 weeks prior to pregnancy was associated with an increased risk of 5‐year graft loss. For the fetus, there is value to discontinuing MPA anytime prior to the second trimester. Adhering to current guidelines does not negatively affect graft survival.     

Broad Concepts in Management of Systemic Lupus Erythematosus

Systemic lupus erythematosus is a multisystem autoimmune disease with protean manifestation. Although commonly seen in young women, it can affect men as well as elderly patients. Approach to treatment is multidisciplinary, involves defining the extent of organ involvement, and distinguishing between active manifestations and damage. The mainstay of therapy is judicious use of immunosuppressive medications. Long-term follow-up to address morbidity arising from treatment complications, disease damage, and increased cardiovascular risk is essential.     

Relationship between types of asthmatic reaction,nonspecific bronchial reactivity,and specific IgE antibodies in patients with red cedar asthma

We studied the relationship between specific IgE antibodies, nonspecific bronchial reactivity to methacholine, and the type of asthmatic reaction in patients with red cedar asthma. The level of circulating specific IgE antibodies (expressed as RAST ratios) was not related to the type of asthmatic reaction, the degree of nonspecific bronchial hyperreactivity [expressed by the provocative concentration of methacholine producing a 20% decrease in the forced expiratory volume in 1 sec (PC₂₀)] or the index of reactivity to plicatic acid. On the other hand, methacholine PC₂₀ was found to correlate with the index of reactivity to plicatic acid in the late asthmatic reaction (LAR) and both the immediate and late components of the dual asthmatic reaction (DAR). Development of the LAR is associated with increase in nonspecific bronchial hyperreactivity. Repeated inhalation challenge with plicatic acid in eight patients with LAR resulted in DAR in all. The results suggest that the mechanism responsible for the LAR is associated with an increase in nonspecific bronchial reactivity; furthermore, the immediate component of DAR could also be related to heightened bronchial hyperreactivity.     

Hypersensitivity reactions to grain dust

Allergic and respiratory investigations were performed in 17 subjects with respiratory symptoms and occupational exposure to grain dust. Common symptoms included chronic cough and sputum production, grain fever, wheezing and dyspnea on exposure to grain dust. Results of pulmonary function tests demonstrated a pattern of obstructive airway disease. Immediate hypersensitivity to grain dust was common. Both immediate and late reactions were observed on inhalation challenge studies. There was a good correlation between the hypersensitivity reactions on skin testing and on bronchial provocation. Inhalation of crude grain dust extract may produce systemic symptoms of malaise, myalgia, headache, and leukocytosis even in normal subjects. There was no evidence of precipitin-mediated hypersensitivity.     

Novel Approaches to Therapy for SLE

Systemic lupus erythermatosus (SLE) is an autoimmune disease manifested by multi-organ involvement and elevated titers of anti-DNA antibodies. Current therapies for SLE are broadspectrum, and include steroids and immunosuppresive cytotoxic agents that are counterbalanced by the toxicity and side effects of the medications. One of the goals is to target thrapeies by altering specific known mechanisms of inflammation and autoimmunity. Although the inciting antigen is still unknown in SLE, it may be possible to alter the regulation of the immune response by targeted molecular therapy. Methods under investigation, which may be beneficial, are manipulation of second-signal stimulation of the immune response (anti-CD40L) manipulation of cytokines (monoclonal anti-IL-10), inducing tolerance by administration of blocking peptides (LJP394), and the manipulation of idiotypes (IVIg). In this article, we also discuss modalities that are steroid-sparing (MTX), and selective immunosuppression (stem-cell restoration and MMF). We review the ongoing literature from 2000–2002, utilizing the MEDLINE search. Controlled trials, open trials, and trials in phase I and II have been included, and anecdotal reports were excluded. The major advances have been with mycophenolate mofetil (MMF) and LJP 394     

血必净注射液联合利奈唑胺治疗重症肺炎的疗效观察

目的探讨血必净注射液联合利奈唑胺治疗重症肺炎的临床效果。方法选取海口市人民医院在2015年4月—2017年4月收治的重症肺炎患者81例,随机分成对照组(40例)和治疗组(41例)。对照组患者静脉滴注利奈唑胺注射液,600mg/次,2次/d。治疗组患者在对照组的基础上静脉滴注血必净注射液,50 m L加入生理盐水100 m L,2次/d。两组患者均治疗14 d。观察两组患者临床疗效,比较治疗前后两组患者细菌清除率、临床症状和生化指标改善时间及肺功能指标。结果治疗后,对照组和治疗组临床总有效率分别为77.50%、95.12%,两组比较差异具有统计学意义(P0.05)。治疗后,对照组和治疗组细菌清除率分别为55.00%、80.49%;两组比较差异具有统计学意义(P0.05)。治疗后,治疗组临床症状和生化指标恢复时间均明显短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者最大呼气中期流速(MMF)和用力呼气量占用力肺活量比值(FEV1/FVC)明显升高,呼气峰流速(PEF)明显降低,同组比较差异具有统计学意义(P0.05);且治疗组肺功能各指标改善后情况明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论血必净注射液联合利奈唑胺治疗重症肺炎疗效显著,可有效改善患者肺功能指标,具有一定的临床推广应用价值。     

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity

Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis.In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.