导致成人与儿童患者30天脑室腹腔分流失败的原因分析（英文）

OBJECTIVE The aim of this study was to provide a comprehensive benchmark of 30-day ventriculoperitoneal(VP)shunt failure rates for a single institution over a 5-year study period for both adult and pediatric patients,to compare this with the results in previously published literature,and to establish factors associated with shunt failure.METHODS A retrospective database search was undertaken to identify all VP shunt operations performed in a single,regional neurosurgical unit during a 5-year period.Data were collected regarding patient age,sex,origin of hydrocephalus,and whether the shunt was a primary or secondary shunt.Operative notes were used to ascertain the type of valve inserted,which components of the shunt were adjusted/replaced(in revision cases),level of seniority of the most senior surgeon who participated in the operation,and number of surgeons involved in the operation.Where appropriate and where available,postoperative imaging was assessed for grade of shunt placement,using a recognized grading system.Univariate and multivariate models were used to establish factors associated with early(30-day)shunt failure.RESULTS Six hundred eighty-three VP shunt operations were performed,of which 321 were pediatric and 362 were adult.The median duration of postoperative follow-up for nonfailed shunts(excluding deaths)was 1263 days(range 525-2226 days).The pediatric 30-day shunt failure rates in the authors'institution were 8.8%for primary shunts and 23.4%for revisions.In adults,the 30-day shunt failure rates are 17.7%for primary shunts and 25.6%for revisions.In pediatric procedures,the number of surgeons involved in the operating theater was significantly associated with shunt failure rate.In adults,the origin of hydrocephalus was a statistically significant variable.Primary shunts lasted longer than revision shunts,irrespective of patient age.CONCLUSIONS A benchmark of 30-day failures is presented and is consistent with current national databases and previously published data by other groups.The number of surgeons involved in shunt operations and the origin of the patient's hydrocephalus should be described in future studies and should be controlled for in any prospective work.The choice of shunt valve was not a significant predictor of shunt failure.Most previous studies on shunts have concentrated on primary shunts,but the high rate of early shunt failure in revision cases(in both adults and children)is perhaps where future research efforts should be concentrated.     

The connection between lymphangiogenic signalling and prostglandin biology: A missing link in the metastatsic pathway

Substantial evidence supports important independent roles for lymphangiogenic growth factor signaling and prostaglandins in the metastatic spread of cancer. The significance of the lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, is well established in animal models of metastasis, and a strong correlation exits between an increase in expression of VEGF-C and VEGF-D, and metastatic spread in various solid human cancers. Similarly, key enzymes that control the production of prostaglandins, cyclooxygenases (COX-1 and COX-2, prototypic targets of Non-steroidal anti-inflammatory drugs (NSAIDs)), are frequently over-expressed or de-regulated in the progression of cancer. Recent data have suggested an intersection of lymphangiogenic growth factor signaling and the prostaglandin pathways in the control of metastatic spread via the lymphatic vasculature. Furthermore, this correlates with current clinical data showing that some NSAIDs enhance the survival of cancer patients through reducing metastasis. Here, we discuss the potential biochemical and cellular basis for such anti-cancer effects of NSAIDs through the prostaglandin and VEGF signaling pathways.     

Correlation of acetylcholinesterase activity in the brain and blood of wistar rats acutely infected with Trypanosoma congolense

ObjectiveTo investigate the neurotransmitter enzyme Acetylcholinesterase (AChE) activity in the brain and blood of rats infected with Trypanosoma congolense (T. congo).MethodsPresence and degree of parasitemia was determined daily for each rat by the rapid matching method. AChE activity was determined by preparing a reaction mixture of brain homogenate and whole blood with 5, 5-dithiobisnitrobenzioc acid (DTNB or Ellman's reagent) and Acetylthiocholine (ATC). The increase in absorbance was recorded at 436 nm over 10 min at 2 min intervals. Trypanosome species identification (before inoculation and on day 10 post infection) was done by Polymerase chain reaction using specific primers.ResultsThe AChE activity in the brain and blood decreased significantly as compared with the uninfected control. The AChE activity dropped to 0.32 from 2.20 μmol ACTC min^?1mg protein^?1 in the brain and 4.57 to 0.76 μmol ACTC min-1mg protein^?1 in the blood. The animals treated with Diminaveto at 3.5 mg/kg/d were observed to have recovered significantly from parasitemia and were able to regain AChE activity in the blood but not in the brain as compared to the control groups. We also observed, that progressive parasitemia resulted to alterations in PCV, Hb, RBC, WBC, neurophils, total protein, lymphocytes, monocytes and eosinophil in acute infections of T. congo. Polymerase chain reaction (PCR) of infected blood before inoculation and on day 10 post infection revealed 600 bp on agarose gel electrophoresis.ConclusionsThis finding suggest that decrease in AChE activity increases acetylcholine concentration in the synaptic cleft resulting to neurological failures in impulse transfer in T. congo infection rats.     

Early detection of the chemical changes occurring during the induction and prevention of autoimmune-mediated demyelination detected by FT-IR imaging

Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Despite progress in understanding immunogenetic aspects of this disease, the mechanisms involved in lesion formation are unknown. To gain new insights into the neuropathology of MS, we used an innovative integration of Fourier transform infrared (FT-IR) microspectroscopy, bioinformatics, and a synchrotron light source to analyze macromolecular changes in the CNS during the course and prevention of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We report that subtle chemical and structural changes not observed by conventional histology were detected before the onset of clinical signs of EAE. Moreover, trained artificial neural networks (ANNs) could discriminate, with excellent sensitivity and specificity, pathology from surrounding tissues and the early stage of the disease progression. Notably, we show that this novel measurement platform can detect characteristic differences in biochemical composition of lesion pathology in animals partially protected against EAE by vaccination with Nogo-A, an inhibitor of neural outgrowth, demonstrating the potential for automated screening and evaluation of new therapeutic agents.     

Breast Fibroblasts Modulate Early Dissemination,Tumorigenesis, and Metastasis through Alteration of Extracellular Matrix Characteristics

A wealth of evidence has now demonstrated that the microenvironment in which a tumorigenic cell evolves is as critical to its evolution as the genetic mutations it accrues. However, there is still relatively little known about how signals from the microenvironment contribute to the early events in the progression to malignancy. To address this question, we used a premalignant mammary model to examine how fibroblasts, and the extracellular matrix (ECM) proteins they secrete, influence progression to malignancy. Their effect on metastatic malignant cells was also assessed for comparison. We found that carcinoma-associated fibroblasts, and the distinct aligned ECM they deposit, can cause both premalignant and malignant mammary epithelial cells to assume a mesenchymal morphology that is associated with increased dissemination and metastasis, while benign reduction mammoplasty fibroblasts favor the maintenance of an epithelial morphology and constrain early dissemination, tumor growth, and metastasis. Our results suggest that normalizing the organization of the ECM could be effective in limiting systemic dissemination and tumor growth.     

The nitric oxide pathway in pre-eclampsia: pathophysiological implications

Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with N^G-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined.     

神经调节素对阿尔茨海默病大鼠模型海马细胞凋亡和核转录因子κB表达的影响

目的 研究神经调节素1β( neuregulin 1β,NRG1β)对β-淀粉样蛋白1-40(beta-amyloid protein,Aβ1-40)所致的模拟阿尔茨海默病模型大鼠空间学习记忆能力、神经元凋亡、核转录因子κB( nuclear factor kappa B,NFκB)表达的影响,探讨NRG改善学习记忆能力的作用机制.方法 成年健康雄性Wistar 大鼠30只,随机数字表法分为对照组、模型组和治疗组,每组10只,经侧脑室微量注射Aβ1-40建立实验性阿尔茨海默病模型大鼠,经侧脑室注射NRG1β(0.3μg·kg-1)干预治疗.各组大鼠实验前及造模7d后、治疗14d后均用Y型迷宫检测大鼠学习和记忆功能,利用HE染色观察海马神经细胞的结构变化,原位TUNEL法检测海马神经细胞凋亡,免疫组织化学法检测海马神经细胞NFκB的表达.结果 模型组大鼠学习能力[ (57.50±1.58)次]和记忆能力[(7.20±1.03)次]较对照组学习[(59.50±2.79)次]和记忆能力[(7.50±1.08)次]明显下降(=20.36,5.28,P＜0.05),海马区神经细胞排列稀疏、紊乱,有明显神经元脱失,TUNEL阳性细胞数明显增多、NFκB表达增加(P＜0.05).NRG1β治疗组大鼠学习记忆能力[ (67.70±4.90)次,(5.80±0.63)次]及细胞结构较模型组[(79.10±4.12)次,(4.40±0.69)次]显著改善( t=5.63,4.69,P＜0.05).相对于模型组[(41.10±7.95)次,(29.30±7.24)个],NRG1β治疗组NFκB表达(25.90±6.67)明显减弱、细胞凋亡数量[(23.50±3.89)个]明显减少(t=4.63,2.23,P＜0.05).结论 NRG1β能抑制海马神经细胞NFκB表达,减少细胞凋亡,从而改善阿尔茨海默病大鼠的学习和记忆能力.     

Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective

While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors.

Methods

Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children''s Hospital of Bern, Switzerland 1999-2006.

Results

Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score.

Conclusions

Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.