Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional grey matter volume reductions in relapsing‐remitting multiple sclerosis

The association of white matter (WM) lesions and grey matter (GM) atrophy is a feature in relapsing‐remitting multiple sclerosis (RRMS). The spatiotemporal distribution pattern of WM lesions, their relations to regional GM changes and the underlying dynamics are unclear. Here we combined parametric and non‐parametric voxel‐based morphometry (VBM) to clarify these issues. MRI data from RRMS patients with progressive (PLV, n = 45) and non‐progressive WM lesion volumes (NPLV, n = 44) followed up for 12 months were analysed. Cross‐sectionally, the spatial WM lesion distribution was compared using lesion probability maps (LPMs). Longitudinally, WM lesions and GM volumes were studied using FSL‐VBM and SPM5‐VBM, respectively. WM lesions clustered around the lateral ventricles and in the centrum semiovale with a more widespread pattern in the PLV than in the NPLV group. The maximum local probabilities were similar in both groups and higher for T2 lesions (PLV: 27%, NPLV: 25%) than for T1 lesions (PLV: 15%, NPLV 14%). Significant WM lesion changes accompanied by cortical GM volume reductions occured in the corpus callosum and optic radiations (P = 0.01 corrected), and more liberally tested (uncorrected P < 0.01) in the inferior fronto‐occipital and longitudinal fasciculi, and corona radiata in the PLV group. Not any WM or GM changes were found in the NPLV group. In the PLV group, WM lesion distribution and development in fibres, was associated with regional GM volume loss. The different spatiotemporal distribution patterns of patients with progressive compared to patients with non‐progressive WM lesions suggest differences in the dynamics of pathogenesis. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

新灰色关联法对高额住院费用的影响因素分析

目的分析了解本院近4年来高额住院费用的影响因素及发展态势,为合理控制高额住院费用提供量化的评价依据及有意义的参考。方法运用新灰色关联分析法,结合Excel汇总分析本院2006-2009年住院费用大于10万元的626例患者住院费用的9类构成进行定量分析。结果分析结果显示,治疗费用是影响高额住院费用的最主要的因素,其次是药费。结论新灰色关联法能为系统发展变化的态势提供量化提供指标,方法可靠、合理,适合因素间关联度的衡量及动态历程分析。     

The Mu-Opioid Receptor and the NMDA Receptor Associate in PAG Neurons: Implications in Pain Control

The capacity of opioids to alleviate inflammatory pain is negatively regulated by the glutamate-binding N-methyl--aspartate receptor (NMDAR). Increased activity of this receptor complicates the clinical use of opioids to treat persistent neuropathic pain. Immunohistochemical and ultrastructural studies have demonstrated the coexistence of both receptors within single neurons of the CNS, including those in the mesencephalic periaqueductal gray (PAG), a region that is implicated in the opioid control of nociception. We now report that mu-opioid receptors (MOR) and NMDAR NR1 subunits associate in the postsynaptic structures of PAG neurons. Morphine disrupts this complex by protein kinase-C (PKC)-mediated phosphorylation of the NR1 C1 segment and potentiates the NMDAR–CaMKII, pathway that is implicated in morphine tolerance. Inhibition of PKC, but not PKA or GRK2, restored the MOR–NR1 association and rescued the analgesic effect of morphine as well. The administration of N-methyl--aspartic acid separated the MOR–NR1 complex, increased MOR Ser phosphorylation, reduced the association of the MOR with G-proteins, and diminished the antinociceptive capacity of morphine. Inhibition of PKA, but not PKC, CaMKII, or GRK2, blocked these effects and preserved morphine antinociception. Thus, the opposing activities of the MOR and NMDAR in pain control affect their relation within neurons of structures such as the PAG. This finding could be exploited in developing bifunctional drugs that would act exclusively on those NMDARs associated with MORs.     

护士开展护理科研选题的思考:统计与分析

目的:探索护士开展护理科研选题的途径,介绍一种护士开展护理科研选题的实用方法。方法:建立等时距观测数据序列,计算灰色关联度。结果:利用灰色关联度的计算值,分析引起患者病情变化的因素。结论:护士开展护理科研选题,应该着眼日常护理工作、立足于科研成果直接服务于临床工作。     

高压放电环境中产生的X射线照射量的灰色预测方法

介绍灰色系统GM(l,l)模型,并应用于高电压放电实验环境中有害因素X射线照射量的预测分析。此模型具有所需样本量小,无需型概率分布,其适用性强,易掌握等优点。可作为高压放电环境中有害因素预测和提供有关人员控制选择的良好工具。     

Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze

The β-adrenergic blocker and 5-HT_1A receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT_1A receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0 mg/kg, i.p.) and paroxetine (1.5 mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT_1A antagonist, WAY-100635 (0.4 μg) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT_1A receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder.     

Overall survival in patients with malignant glioma may be significantly longer with tumors located in deep grey matter

BACKGROUND: The aim of this study was to assess the correlation of overall survival with tumor location (lobar vs. deep grey matter) and with other clinical and imaging variables in a cohort of patients with high grade gliomas. METHODS: Adult patients with newly diagnosed supratentorial WHO grade 3 and 4 gliomas were evaluated. Clinical data included demographics, symptoms at presentation, treatment variables, and overall survival. Radiological data included tumor side, site (deep vs. lobar) and size, extent of peritumoral edema, and presence of midline shift. Biostatistics were carried out using log rank tests and univariate and multivariate Cox regression models. RESULTS: A total of 121 patients were investigated, 23 (19.0%) with WHO grade 3 and 98 (81.0%) with WHO grade 4 gliomas. Tumors had lobar location in 96 cases (79.3%) and deep grey matter location in 25 cases (20.7%). Median survival time for all patients was 26 weeks (IQR: 14-53). Patients with deep tumors survived significantly longer than those with lobar gliomas (log rank test, p=0.0083). Extensive brain edema significantly shortened survival (log rank test, p=0.0003). Presence of midline shift (>1 cm) was a statistically significant risk factor for shorter survival (log rank test, p<0.0001). The univariate Cox regression model demonstrated statistical significance for the variables age, side, site and size of tumor, presence of extensive edema, and presence of mass effect (>1 cm). In the multivariate Cox models, tumor grade, site and size showed statistical significance. CONCLUSIONS: This study suggests that patients with deep grey matter gliomas may survive significantly longer after the initial diagnosis than those with tumors in a lobar location. This is a potentially novel finding, which may corroborate the theory of differential invasion of glioma cells in different microenvironments of the brain, but remains to be confirmed in future prospective studies.     

Normal-appearing white and grey matter damage in MS

Abstract The aims of this study were to improve, using a 3.0 Tesla (T) scanner and diffusion tensor (DT) magnetic resonance imaging (MRI) with sensitivity encoding, our understanding of: 1) the possible pathological substrates of normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis (MS) and 2) the factors associated to WM and GM atrophy in this condition. Conventional and DT MRI of the brain were acquired from 32 relapsing-remitting (RR) MS patients and 16 controls. Lesion load, WM (WMV), overall GM (GMV), and neocortical GM (NCV) volumes were measured. NAWM mean diffusivity (MD) and fractional anisotropy (FA), and GM MD were calculated. GMV and NCV were lower (p ≤ 0.001) in MS patients than controls, whereas WMV did not differ significantly. MS patients had higher NAWM and GM average MD and lower NAWM average FA (p ≤ 0.001) than controls. Moderate correlations were found between intrinsic lesion and tissue damage with both GM volumetric and diffusivity changes ()0.41 ≤ r ≤ 0.42, p ≤ 0.04). DT MRI and volumetry measurements at 3.0 T confirm the presence of NAWM and GM abnormalities in RRMS patients. Although histopathology was not available, axonal and neuronal damage and consequent reactive glial proliferation are the most likely substrates of the changes observed.     

The thalamic nucleus submedius and ventrolateral orbital cortex are involved in nociceptive modulation: A novel pain modulation pathway

Recently, a series of studies have given rise to and provided evidence for the hypothesis that the nucleus submedius (Sm) in the medial thalamus is involved in modulation of nociception. The Sm, ventrolateral orbital cortex (VLO) and the periaqueductal gray (PAG) constitute a pain modulatory pathway, activation of which leads to activation of the PAG–brainstem descending inhibitory system and depression of the nociceptive inputs in the spinal cord and trigeminal nucleus. Other studies have indicated that the Sm–VLO–PAG pathway plays an important role in the analgesia induced by electroacupuncture stimulation of the acupuncture point (acupoint) for exciting small diameter fiber (A-δ and C group) afferents. Opioid peptides, serotonin, dopamine, glutamate and their related receptors are involved in Sm- and/or VLO-mediated descending antinociception, and a GABAergic disinhibitory mechanism participates in mediating the antinociception induced by activation of μ-opioid receptors, serotonin 1_A receptors, and dopamine D₂-like receptors. This review describes these findings, which provide important new insights into the roles of the thalamus and cerebral cortex in descending pain modulation.