Cutaneous squamous cell carcinoma in two pediatric lung transplant patients on prolonged voriconazole treatment

Oral voriconazole is commonly used for treatment and prophylaxis of invasive fungal disease post‐LTx. Development of cutaneous SCC has been described in adult LTx recipients, although it is extremely rare in children. We describe two Caucasian children who developed cutaneous SCC beyond three yr post‐LTx. Both developed severe photosensitivity, actinic keratosis and required curative surgical excision of the cutaneous SCC lesions. Neither patient developed metastatic lesions nor had allograft dysfunction as a result of the SCC or the change in medical treatments. The effect of voriconazole on the development of malignant skin lesions is discussed and a recommendation on dermatologic surveillance, preventive measures against phototoxicity and early treatment of SCC are provided.     

Frostbite of the liver: An unrecognized cause of primary non‐function?

Appropriate hypothermic packaging techniques are an essential part of organ procurement. We present a case in which deviation from standard packaging practice may have caused sub‐zero storage temperatures during transport, resulting in a clinical picture resembling PNF. An 18‐month‐old male with alpha‐1‐antitrypsin deficiency underwent liver transplant from a size‐matched pediatric donor. Upon arrival at the recipient hospital, ice crystals were noted in the UW solution. The transplant proceeded uneventfully with short ischemia times. Surprisingly, transaminases, INR, and total bilirubin were markedly elevated in the postoperative period but returned to near normal by discharge. Follow‐up of over five yr has demonstrated normal liver function. Upon review, it was discovered that organ packaging during recovery included storage in the first bag with only 400 mL of UW solution, and pure ice in the second bag instead of slush. This suggests that the postoperative delayed graft function was related to sub‐zero storage of the graft during transport. This is the first report of sub‐zero cold injury, or frostbite, following inappropriate packaging of an otherwise healthy donor liver. The clinical picture closely resembled PNF, perhaps implicating this mechanism in other unexpected cases of graft non‐function.     

一种创伤感染致多器官功能障碍综合征动物模型的建立

目的 复制符合临床特征且简便易行的创伤感染双相打击致多器官功能障碍综合征(MODS)动物模型,为进一步探讨其发病机制和治疗方法奠定基础.方法 6月龄Wistar雄性大鼠,体重(203.5±11.4)g.随机分为单纯创伤组(T组)和创伤感染序贯致MODS组(M组).钳夹大鼠肢体造成多发性闭合型骨折和广泛性软组织挫伤,M组12 h后致背部30%总体表面积(TBSA)Ⅲ度烫伤,并创面涂布绿脓杆菌.分别于创伤前以及创伤后24、48、96和120 h观察动物活动和创面情况,测定体重、体温、心率,并检测各时间点大鼠血浆及肝脏内毒素水平以及心、肝、肾、脑、小肠的功能变化,全身炎症反应发生率、MODS发生率及死亡率,同时对重要脏器进行组织病理学观察.结果 M组大鼠创伤48 h后,丙氨酸转氨酶(ALT)、总胆红素(Tbil)、血尿素氮(BUN)、血肌酐(Cr)、天冬氨酸转氨酶(AST)、肌酸磷酸激酶(CPK)的最高值均显著高于伤前自身对照值(P均＜0.05),且与T组比较差异有统计学意义(P均＜0.05);48 h后病理变化明显,大鼠处于若干脏器功能衰竭早期伴若干脏器功能受损期;内毒素水平在伤后96 h增至峰值,达到基础值的8.36倍;伤后96 h内毒素水平与脏器功能的变化具有明显的相关性(r=0.927 2),MODS发生率为86%,死亡率30%;伤后120 h,MODS发生率为100%,死亡率50%.结论 本模型较好地模拟了临床创伤继发感染后发展为MODS的过程,感染过程符合临床经过,内毒素释放稳定,机体反应充分,是用于创伤导致MODS发病机制和治疗方法研究较好的动物模型.     

多器官功能障碍综合征52例尸检脾及脾树突状细胞的病理学观察

目的探讨多器官功能障碍综合征（MODS）脾及其树突状细胞的病变特点与作用。方法收集52例MODS死亡病例与25例正常脾标本,应用光镜、电镜和免疫组化（S-100、CD1a、CD80及HLA-DR）方法观察脾及其树突状细胞的病理变化。结果镜下见脾小体消失,白髓消散伴淋巴细胞大量凋亡,树突状细胞数目增加而活性减退,CD4（＋）/CD8（＋）T淋巴细胞比例显著下降。结论MODS终末期外周免疫器官脾及其树突状细胞严重损伤和功能耗竭,而且不同诱因所致MODS病例的病变基本一致。提示脾树突状细胞的病变与免疫抑制及MODS形成有重要关系。     

Red blood cell rheology in sepsis

Changes in red blood cell (RBC) function can contribute to alterations in microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and neutrophil deformability impair the passage of these cells through the microcirculation. While the role of leukocytes has been the focus of many studies in sepsis, the role of erythrocyte rheological alterations in this syndrome has only recently been investigated. RBC rheology can be influenced by many factors, including alterations in intracellular calcium and adenosine triphosphate (ATP) concentrations, the effects of nitric oxide, a decrease in some RBC membrane components such as sialic acid, and an increase in others such as 2,3 diphosphoglycerate. Other factors include interactions with white blood cells and their products (reactive oxygen species), or the effects of temperature variations. Understanding the mechanisms of altered RBC rheology in sepsis, and the effects on blood flow and oxygen transport, may lead to improved patient management and reductions in morbidity and mortality.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

The cyclopentenone prostaglandin 15-deoxyΔ12,14-prostaglandin J2 attenuates the development of zymosan-induced shock

Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-^12,14-PGJ₂ (15d-PGJ₂), a PPAR- ligand, in a model of zymosan-induced nonseptic shock in mice.Materials and methods Mice were randomly assigned to one of four groups (n=10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ₂ (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ₂ (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ₂ (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis.Measurements and results 15d-PGJ₂ inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological injury in mice. A significant protection was demonstrated in kidney, liver, and pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ₂ also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ₂ treated mice.Conclusions Our findings demonstrate that 15d-PGJ₂ exerts potent anti-inflammatory effects on zymosan-induced shock.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

新生儿缺氧缺血性脑病合并多器官损害临床分析

【目的】了解缺氧缺血性脑病 (HIE)新生儿心、肝、肾功能及钙、镁、血糖水平的变化状况。【方法】应用日立 7170A全自动生化分析仪对HIE患儿及无窒息新生儿于出生后 3d内所采血样的心肌酶谱、肝功能、尿素氮、钙、镁、血糖进行检测 ,同时检查尿常规。【结果】HIE组患儿心肌酶、肝酶、血总胆红素水平均明显高于对照组 (P <0 .0 5 ) ;HIE组血钙、镁低于对照组 (P <0 .0 1) ;HIE组肾损害发生率、高血糖发生率均高于对照组 (P <0 .0 5 )。【结论】HIE同时可并发多器官功能损害 ,在治疗脑损伤的同时 ,应对其它各器官功能密切监测并加以保护。     

连续性静脉-静脉血液透析/滤过治疗儿童多器官功能障碍综合征

目的 探讨持续性静脉.静脉血液透析滤过(CVVHD/F)救治儿童严重感染,并评估疗效.方法 对2002年12月至2007年11月上海交通大学附属儿童医院收治的符合脓毒性休克及MODS诊断标准参考按国际脓毒症会议或我国小儿多器官功能衰竭(MOSF)诊断标准的19例脓毒性休克合并多器官功能障碍综合征(MOOS)进行CVVHD/F治疗.观察患儿的血液电解质、血气指标、尿量、血肌酐(Cr)及尿素氮(BUN)、血管活性药物使用、氧合指数等变化和预后.结果 19例患儿平均危重评分为(69.1±10.4)分;平均PRISM Ⅲ(12.66±7.85)分.平均CWHD/F治疗时间为92 h(16 h～480 h).CVVHD/F治疗12～24 h后,成人型呼吸窘迫综合征或肺水肿患儿FiO2/PO2、PCO2、PO2好转(P<0.05),24 h后血液K+、Na+、HCO-3恢复正常水平,48 h后Cr、BUN恢复正常范围.病死率为63.2%.结论 CVVHD/F治疗脓毒性休克合并NODS可以迅速纠正体液电解质紊乱、改善循环功能,清除Cr、BUN,减轻肺水肿、脐水肿等.