Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.     

泪腺上皮细胞凋亡与丙酸睾酮的抑制效应

目的:分析丙酸睾酮抑制泪腺上皮细胞凋亡的机制,为干眼症的性激素防治提供科学的理论依据。方法:实验于2003-09/2004-01在重庆医科大学附属第一医院中心实验室完成。①实验材料:二三月龄新西兰健康白色家兔30只,无眼疾,雌性,体质量1.5～2.5kg。丙酸睾酮(产品批号:020902,上海通用药业股份有限公司产品),用DMSO配成储存液,-70℃保存。分析纯过氧化氢购自北方同正生物技术发展有限公司。②实验方法:经耳缘静脉注射空气处死家兔,按常规无菌操作行泪腺摘除术,酶消化法分离兔泪腺上皮细胞。取二三代培养的泪腺上皮细胞,按约1×108L-1密度接种于预置小玻片的24孔板内,培养4d后,加入浓度为1×10-8,1×10-7,1×10-6,1×10-5mol/L丙酸睾酮,继续培养24h,另以未加丙酸睾酮的培养液培养的同期传代的泪腺上皮细胞作空白对照。培养24h后,再分别加入终浓度为100μmol/LH2O2于不同浓度丙酸睾酮组继续培养60min,另以未加丙酸睾酮的DMEM/F12培养液培养的同期传代的泪腺上皮细胞作对照。③实验评估:应用TUNEL法检测泪腺上皮细胞凋亡,采用免疫细胞化学法检测泪腺上皮细胞Bax和Bcl-2表达。结果:①丙酸睾酮对过氧化氢诱导的泪腺上皮细胞凋亡的影响:与单纯加入100μmol/LH2O2组比较,加入不同浓度丙酸睾酮组泪腺上皮细胞凋亡率均明显下降且丙酸睾酮的抗凋亡作用呈现一定范围内的剂量依赖性[(15.15±1.05)%,(13.94±0.73)%,(12.51±0.91)%,(10.63±0.78)%,(8.19±0.85)%,P<0.01]。②免疫细胞化学法检测Bcl-2和Bax蛋白表达:与单纯加100μmol/LH2O2组相比较,同时加入1×10-8,1×10-7,1×10-6,1×10-5mol/L丙酸睾酮各组均可使泪腺上皮细胞Bcl-2的表达明显增强和Bax的表达明显减弱,且与丙酸睾酮的剂量呈正相关(Bcl-2:0.92±0.10,1.01±0.08,1.12±0.06,1.24±0.12,1.37±0.11;Bax:2.28±0.09,2.17±0.11,2.06±0.07,1.91±0.13,1.77±0.10,P<0.01)。结论:丙酸睾酮抑制泪腺上皮细胞凋亡的机制可能与凋亡调节相关基因Bcl-2表达上调和Bax表达下调有关。     

Using Geographic Information Systems to investigate variations in accessibility to ‘extended hours’ primary healthcare provision

There are ongoing policy concerns surrounding the difficulty in obtaining timely appointments to primary healthcare services and the potential impact on, for example, attendance at accident and emergency services and potential health outcomes. Using the case study of potential access to primary healthcare services in Wales, Geographic Information System (GIS)‐based tools that permit a consideration of population‐to‐provider ratios over space are used to examine variations in geographical accessibility to general practitioner (GP) surgeries offering appointment times outside of ‘core’ operating hours. Correlation analysis is used to explore the association of accessibility scores with potential demand for such services using UK Population Census data. Unlike the situation in England, there is a tendency for accessibility to those surgeries offering ‘extended’ hours of appointment times to be better for more deprived census areas in Wales. However, accessibility to surgeries offering appointments in the evening was associated with lower levels of working age population classed as ‘economically active’; that is, those who could be targeted beneficiaries of policies geared towards ‘extended’ appointment hours provision. Such models have the potential to identify spatial mismatches of different facets of primary healthcare, such as ‘extended’ hours provision available at GP surgeries, and are worthy of further investigation, especially in relation to policies targeted at particular demographic groups.     

Effects of sub-minimum inhibitory concentrations of ciprofloxacin on enteroaggregative Escherichia coli and the role of the surface protein dispersin

Enteroaggregative Escherichia coli (EAEC) are bacterial pathogens that cause watery diarrhoea, which is often persistent and can be inflammatory. The antibiotic ciprofloxacin is used to treat EAEC infections, but a full understanding of the antimicrobial effects of ciprofloxacin is needed for more efficient treatment of bacterial infections. In this study, it was found that sub-minimum inhibitory concentrations (sub-MICs) of ciprofloxacin had an inhibitory effect on EAEC adhesion to glass and mammalian HEp-2 cells. It was also observed that bacterial surface properties play an important role in bacterial sensitivity to ciprofloxacin. In an EAEC mutant strain where the hydrophobic positively charged surface protein dispersin was absent, sensitivity to ciprofloxacin was reduced compared with the wild-type strain. Identified here are several antimicrobial effects of ciprofloxacin at sub-MIC concentrations indicating that bacterial surface hydrophobicity affects the response to ciprofloxacin. Investigating the effects of sub-MIC doses of antibiotics on targeted bacteria could help to further our understanding of bacterial pathogenicity and elucidate future antibiotic treatment modalities.     

Subchondral cysts of the atlantoaxial joint: a risk factor for odontoid fractures in the elderly

Background contextScholars have postulated that cervical degeneration can predispose the upper cervical spine to injury after minor trauma. Subchondral cysts have previously been recognized as potentiators of fracture in the hip and knee but no cases of cervical degenerative cysts contributing to fracture have been reported.PurposeThis report documents a case series in which patients sustained significant injury to the upper cervical spine in the setting of subchondral cervical cysts.Study design/settingCase series/academic level I trauma center.MethodsBetween 2004 and 2008, six patients (ages 73–91 years) with cervical pathology were admitted to the trauma service at our Level I trauma center. The most common mechanism of injury was a low velocity fall, which occurred in 5 out of 6 patients. All patients suffered an odontoid fracture. In all cases, there was radiographic evidence of cyst formation, and computed tomographic imaging demonstrated fracture communication with the subchondral cyst.ResultsOf the six cases, four were treated definitively with immobilization in a cervical orthosis and two required surgery. One patient was treated with an occipital-cervical fusion, whereas the other underwent Brooks wiring. All patients ultimately went on to heal their fractures.ConclusionsDegenerative changes in the cervical spine have previously been recognized to potentiate injury. This report raises the question of whether degenerative processes at the C1–C2 articulation predispose elderly patients to injury at this level. The presence of cystic degeneration at the atlantoaxial joint should be recognized as a potential risk factor for cervical injury after relatively minor trauma.     

The cerebellum: Comparative and animal studies

The cerebellum has a uniform cellular structure and microcircuitry, but the size of its subdivisions varies greatly among vertebrates. This variability is a challenge to anatomists to attempt to relate size differences to differences in characteristic behaviour. Here we review the early work of Lodewijk Bolk on the mammalian cerebellum and relate his observations to unfolded maps of the rodent cerebella. We further take insights from the comparative anatomy of the bird cerebella and find that cerebellar enlargement in large brains is not a passive consequence of overall brain enlargement, but is related to specific behaviour. We speculate that for some rodents (e.g., squirrels), primates and some large-brained birds (crows, parrots and woodpeckers), specifically enlarged cerebella are associated with either the elaboration of forelimb control (squirrels and primates) or in the case of the birds with beak control. The elaboration of such motor behaviour combined with increased visual control could have helped to furnish manipulative skills in these animals. Finally, we review the connections of the mammalian cerebellum and show that several pieces of experimental evidence point to an important function of the cerebellum in sensory control of movement reflex adjustment, and motor learning.     

Contribution of Notch signaling activation to human glioblastoma multiforme

OBJECT: Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth. METHODS: Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation. CONCLUSIONS: Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.