Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents?

A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer's (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these numbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death pathways as those activated by environmental factors that trigger most sporadic disease cases. In this article we present a countervailing view that environmental neurotoxins may be the sole sufficient factor in at least three neurological disease clusters. For each, neurotoxins have been isolated and characterized that, at least in animal models, faithfully reproduce each disorder without the need for genetic co-factors. Based on these data, we will propose a set of principles that would enable any potential toxin to be evaluated as an etiological factor in a given neurodegenerative disease. Finally, we will attempt to put environmental toxins into the context of possible genetically-determined susceptibility.     

Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial

BACKGROUND: Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism. METHODS: The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. RESULTS: All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg. CONCLUSION: In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia.     

Legionnaire's pneumonia: Is there really an interstitial disease?

OBJECTIVE: Legionella pneumonia is usually classified as "atypical pneumonia", which suggests a predominance of interstitial patterns in chest X-rays. Based on a selection of recent clinical cases and a brief review of the literature, the aim of the study is to clarify, how far the actual radiological findings would be consistent with these expectations. PATIENTS AND METHODS: A retrospective analysis of 18 epidemic personal cases and a review of the literature data were performed to describe the chest X-ray findings of Legionella pneumophila (LP) community acquired pneumonia. X-ray review was performed simultaneously and in consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). RESULTS: From our series, 17 patients had an abnormal chest X-ray on admission. Among these pathological X-ray cases, infiltrates were more often confluent (n=16), or patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates involving the lower lung fields. Bilateral distribution of abnormalities and pleural effusion were each observed in three cases. Radiological findings deteriorated between the second and seventh days following admission, particularly in the form of patchy infiltrates with pleural effusion. The review of the literature is consistent with these findings, by reporting prevalent confluent or patchy infiltrates. CONCLUSIONS: These findings are consistent with the physiopathological particularity of this affection and incite us to avoid the classification "atypical pneumonia" in radiologic terminology. This term is more appropriate for clinical and microbiological use.     

Differentiation of fibroblastic meningiomas from other benign subtypes using diffusion tensor imaging

PURPOSE: To differentiate fibroblastic meningiomas, usually considered to be of a hard consistency, from other benign subtypes using diffusion tensor imaging (DTI). MATERIALS AND METHODS: From DTI data sets of 30 patients with benign meningiomas, we calculated diffusion tensors and mean diffusivity (MD) and fractional anisotropy (FA) maps as well as barycentric maps representing the geometrical shape of the tensors. The findings were compared to postoperative histology. The study was approved by the local ethics committee, and informed consent was given by the patients. RESULTS: According to one-way analysis of variance (ANOVA), FA was the best parameter to differentiate between the subtypes (F=32.2; p<0.0001). Regarding tensor shape, endothelial meningiomas were represented by spherical tensors (80%) corresponding to isotropic diffusion, whereas the fibroblastic meningiomas showed a high percentage (43%) of nonspherical tensors, indicating planar or longitudinal diffusion. The difference was highly significant (F=28.4; p<0.0001) and may be due to the fascicular arrangement of long spindle-shaped tumor cells and the high content of intra- and interfascicular fibers as shown in the histology. In addition, a capsule-like rim of the in-plane diffusion surrounded most meningiomas irrespective of their histological type. CONCLUSION: If these results correlate to the intraoperative findings of meningioma consistency, DTI-based measurement of FA and analysis of the shape of the diffusion tensor is a promising method to differentiate between fibroblastic and other subtypes of benign meningiomas in order to get information about their "hard" or "soft" consistency prior to removal.     

A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients

BACKGROUND: We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in "real world" patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials. METHOD: 92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5+/-12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted> or =2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection. RESULTS: Two hours after IM olanzapine was administered, a mean decrease of -9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6+/-5.3) was observed as compared with values at study entry (26.5+/-5.9) and at 2 hours endpoint (16.9+/-9.3), which represent a mean decrease of -14.9 and -5.3, respectively. CONCLUSION: The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.     

标准外伤大骨瓣开颅术在急性硬膜下血肿救治中的应用

目的评价标准外伤大骨瓣开颅术救治急性硬膜下血肿的疗效。方法采用标准外伤大骨瓣开颅术救治58例急性硬膜下血肿患者,对其临床资料进行回顾性分析、总结。结果全组58例中,恢复良好26例,中残14例,重残8例,死亡10例。术后并发症：迟发性血肿5例,外伤性脑梗塞2例,硬膜下积液5例,皮片坏死2例,颅内感染2例,外伤性癫痫3例。结论标准外伤大骨瓣开颅术暴露良好、止血彻底,有利于清除血肿、脑疝复位和缓解颅压,是救治急性硬膜下血肿的有效手段。     

120例肺结核不典型临床表现与病理分析

目的：分析肺结核不典型临床表现与病理.方法：120例均拍正侧位胸片和CT扫描,31例做增强扫描,30例做纤维支气管镜检查.摄胸部正位72例,侧位58例,定期复查胸片.结果：68例位于下叶基底段,32例位于舌叶,20例变位于结核好发部位.大小不等的单发或多发片状较淡薄病灶有33例,孤立肺段或肺叶阴影39例.结论：不典型肺结核的临床症状表现为全身或呼吸道症状,部分患者无临床症状,因而容易造成误诊.     

Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium

Microscopic distinction of normal choroid plexus (CP) from choroid plexus tumors (CPT) may be difficult, especially in small samples of well-differentiated CP papillomas. So far, there are no established markers that reliably distinguish normal and neoplastic CP epithelium. Recently, a correlation between expression/function of glial glutamate transporters EAAT-1 (GLAST) and EAAT-2 (Glt-1) and tumor proliferation has been reported. Furthermore, we previously found that CPTs frequently express EAAT-1, but not EAAT-2. We now compared expression of EAAT-1, EAAT-2 and GFAP in non-neoplastic CP (n = 68) and CPT (n = 79) by immunohistochemistry. Tissue of normal CP was obtained from 50 autopsy cases (20 normal and 30 pathologic brains) and 18 neurosurgical specimens that included 17 fetal, 21 pediatric and 30 adult cases. In non-neoplastic postnatal CP (n = 51), focal expression of EAAT-1 was found in only two pediatric cases (4%). In CPT, expression of EAAT-1 was found in 64 of 79 (81%) tumor samples and was significantly age-dependent (P < 0.0001). Hence, EAAT-1 expression distinguishes neoplastic from normal CP, both in children (P = 0.0032) and in adults (P < 0.0001). Immunostaining for EAAT-2 in selected samples from cases of different ages showed that normal CP (n = 15) or CPT (n = 16) lacked EAAT-2 expression. GFAP expression was found in 3 of 32 (10%) normal CP and in 28 of 73 (38%) tumor samples. In conclusion, in contrast to neoplastic CP samples, expression of EAAT-1 is exceptionally rare in non-neoplastic CP. Thus, EAAT-1 is superior to GFAP as a helpful diagnostic tool in CP samples.     

大脑镰矢状窦大型脑膜瘤的显微手术治疗

目的总结大脑镰矢状窦部大型脑膜瘤的显微手术经验。方法回顾性分析67例大脑镰矢状窦大型脑膜瘤的临床资料。肿瘤起源于矢状窦26例,大脑镰30例,同时累及矢状窦和大脑镰11例。肿瘤主体位于镰窦前1/3段15例,中1/3段41例,后1/3段11例。瘤体大小为3cm×3cm×4cm～11cm×8cm×7cm。采用显微手术切除肿瘤,同时处理受累矢状窦和大脑镰。结果肿瘤全切除66例,其中SimpsonⅠ级19例,Ⅱ级47例;大部切除1例。无死亡病例。术后发生静脉性脑梗死和严重脑水肿4例,其余病人神经功能不同程度改善。随访6个月～9年,肿瘤复发4例(6.0%)。结论全切肿瘤和有效处理受累矢状窦和大脑镰是防止肿瘤复发的重要手段。在术中保护主要引流静脉是防止术后静脉性脑梗死和严重脑水肿肿胀的关键措施。