高容血液稀释对正颌外科病人血液动力学和凝血功能的影响

目的 探讨术前急性高容量血液稀释对正颌外科病人血液动力学和凝血功能的影响，评估该方法临床应用的价值。方法 选择择期行正颌外科双颔手术的病人40例，随机分为ABCD四组，每组10例。A为贺斯实验组。术前输注6％羟乙基淀粉和乳酸林格液各占总量1／2，行急性高容血液稀释；B为贺斯对照组，用6％羟乙基淀粉和乳酸林格液补充术中丢失血液和体液；C为佳乐施实验组，术前输注4％琥珀酰明胶和乳酸林格液各占总量1／2，行急性高容血液稀释；D为佳乐施对照组，用4％琥珀酰明胶和乳酸林格液补充术中丢失血液和体液。四组病例术中均采用硝普钠控制性降压，平均动脉压（MAP）控制在50～60mmHg。实验组在插管后稀释前即刘（T0），稀释后手术开始前即刻（T1），手术结束即刻（T2），术后第一日8AM（T3）时；对照组在手术开始前即刻（T1），手术结束即刘（T2），术后第一日8AM（T3）时，记录RBC、HBG、HCT及凝血指标的变化，以及血液动力学的变化。结果 MAP：A、C组T1低于T0（P〈0．01）；T2高于T1（P〈0．01）。HR：A、C组T2高于T0、T1（P〈0．01）。RBC、HGB、HCT和PLT：A、C组T1低于T0（P〈0．01），T3升高超过T1且接近T0。结论 术前急性高容量血液稀释对正颌外科病人血液动力学的稳定影响小，能减少血液的丢失。贺斯与佳乐施两种胶体液均可引起部分凝血指标的改变，但二者均不影响凝血功能。可以作为正颌外科手术选择性应用的一种有效的辅助方法。     

Spectrum of Restrictive and Infiltrative Cardiomyopathies: Part 2 of a 2-Part Series

Restrictive cardiomyopathies are the least common form of heart muscle disease. They are characterized as infiltrative and noninfiltrative, storage diseases, and endomyocardial disorders. Genetic diseases commonly present during childhood or adolescence. However, a growing percentage of elderly patients with heart failure with preserved ejection fraction are being recognized as having forms of restrictive cardiomyopathy, particularly cardiac amyloidosis. Noninvasive evaluation has replaced endomyocardial biopsy in the diagnostic evaluation of most suspected etiologies. The detection of infiltrative cardiomyopathies, particularly primary and secondary forms of iron overload, as well as inflammatory diseases such as sarcoidosis has slowly led to improved outcomes via disease-specific therapies.     

Myenteric plexus alterations downstream from a prenatal intestinal obstruction in a rat model

The enteric nervous system maturation occurs during embryonic life and continues after birth. Some prenatal events on the digestive tract such as intestinal atresia have been shown to dramatically alter this maturation. Thus, we developed a fetal rat model of intestinal atresia by surgically obstructing the small bowel at embryonic day E18. Fetuses were removed at day E21, and small bowels sections were examined by immuno-histochemistry. Synaptophysin and smooth muscle actin staining was used to define the cellular aspect. Labeling revealed marked alterations of the myenteric plexus in the lower extremity of the occluded small bowel. At day E21, the myenteric plexus of the lower part and the 2 muscle layers surrounding it, retained the staining pattern observed at day E17. This cellular pattern was classified as: immature (aspect at day E17) vs. mature (aspect of day E21) by 3 pathologists not familiar with the study. The number of samples with an immature cellular pattern at the lower end of the occluded bowel was different from that observed for the upper end (Mac Nemar test, p < 0.008). Our study suggests that a prenatal obstruction induces a maturation delay of the myenteric plexus downstream of the obstruction. This might be important for pediatric purposes.     

The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid leukaemia

Deregulated NOTCH1 has been reported in lymphoid leukaemia, although its role in chronic myeloid leukaemia (CML) is not well established. We previously reported BCR‐ABL down‐regulation of a novel haematopoietic regulator, CCN3, in CML; CCN3 is a non‐canonical NOTCH1 ligand. This study characterizes the NOTCH1–CCN3 signalling axis in CML. In K562 cells, BCR‐ABL silencing reduced full‐length NOTCH1 (NOTCH1‐FL) and inhibited the cleavage of NOTCH1 intracellular domain (NOTCH1‐ICD), resulting in decreased expression of the NOTCH1 targets c‐MYC and HES1. K562 cells stably overexpressing CCN3 (K562/CCN3) or treated with recombinant CCN3 (rCCN3) showed a significant reduction in NOTCH1 signalling (> 50% reduction in NOTCH1‐ICD, p < 0.05). Gamma secretase inhibitor (GSI), which blocks NOTCH1 signalling, reduced K562/CCN3 colony formation but increased that of K562/control cells. GSI combined with either rCCN3 or imatinib reduced K562 colony formation with enhanced reduction of NOTCH1 signalling observed with combination treatments. We demonstrate an oncogenic role for NOTCH1 in CML and suggest that BCR‐ABL disruption of NOTCH1–CCN3 signalling contributes to the pathogenesis of CML. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis

Spondylocostal dysostosis (SCD) is an inherited disorder with abnormal vertebral segmentation that results in extensive hemivertebrae, truncal shortening and abnormally aligned ribs. It arises during embryonic development by a disruption of formation of somites (the precursor tissue of the vertebrae, ribs and associated tendons and muscles). Four genes causing a subset of autosomal recessive forms of this disease have been identified: DLL3 (SCDO1: MIM 277300), MESP2 (SCDO2: MIM 608681), LFNG (SCDO3: MIM609813) and HES7 (SCDO4). These genes are all essential components of the Notch signalling pathway, which has multiple roles in development and disease. Previously, only a single SCD-causative missense mutation was described in HES7. In this study, we have identified two new missense mutations in the HES7 gene in a single family, with only individuals carrying both mutant alleles being affected by SCD. In vitro functional analysis revealed that one of the mutant HES7 proteins was unable to repress gene expression by DNA binding or protein heterodimerization.     

The hypereosinophilic syndromes: current concepts and treatments

The hypereosinophilic syndromes (HES) encompass a spectrum of diseases that have increased blood eosinophils and tissue damage in common. The clinical manifestations are protean and may involve any organ system, but especially the skin. Our understanding of these diseases has drastically changed over the past 15 years, along with new classifications that characterize patients with marked eosinophilia. One HES variant, myeloproliferative, is actually chronic eosinophilic leukaemia with a unique genetic marker, FIP1L1-PDGFRA . Such patients are well-controlled by administration of the kinase inhibitor, imatinib, and remissions appear durable with continued imatinib therapy. FIP1L1-PDGFRA is expressed in several cell lineages, thus explaining increases in neutrophils and mast cells in HES. The lymphocytic HES variant is associated with T-cell clones producing interleukin-5 (IL-5) and can evolve into lymphoma. While myeloproliferative and lymphocytic HES are well established and permit elimination of the term, idiopathic, to these varieties, most HES patients do not fall into these categories and are classified as complex (using the 2006 Workshop Report). A recent study showed that a monoclonal antibody to IL-5, mepolizumab, reduced glucocorticoid therapy in HES patients who did not possess the FIP1L1-PDGFRA mutation while controlling eosinophilia and preventing recurrence or progression of tissue damage. These advances augur well for continued progress in the understanding and treatment of HES.