bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional topography of the low postcentral area
Authors: Boling Warren , Reutens David C. , Olivier André 
Published: May 2009

Object. The goal of this study was to establish a reliable method for identification of face and tongue sensory function in the lower central area.
Methods. All positron emission tomography (PET) clinical activation studies performed over a 3-year period at the Montreal Neurological Institute and Hospital were evaluated by coregistering the PET images with three-dimensional reconstructions of magnetic resonance images obtained in the same patients. In addition to stereotactic coordinates and measurements based on distance from the sylvian fissure, gyral and sulcal landmarks were analyzed to determine their reliability in localizing the sensory areas of the tongue and lower face.
The convolutional anatomy of the central area is an important guide to the identification of function. The sensory area of the tongue is recognized as a triangular region at the base of the postcentral gyrus; the sensory area of the lower face resides in the narrowed portion of the postcentral gyrus, immediately above the tongue area.
Conclusions. Cortical landmarks such as the substrata of tongue and face sensory impressions are more reliable guides than stereotactic coordinates or measurements for localizing function.
Volumetric quantification of Fisher Grade 3 aneurysmal subarachnoid hemorrhage: a novel approach to predict symptomatic vasospasm on admission computerized tomography scans
Authors: Friedman Jonathan A. , Goerss Stephan J. , Meyer Fredric B. , Piepgras David G. , Pichelmann Mark A. , McIver Jon I. , Toussaint L. Gerard , McClelland Robyn L. , Nichols Douglas A. , Atkinson John L. D. , Wijdicks Eelco F. M. 
Published: May 2009

Object. Predicting which patients with aneurysmal subarachnoid hemorrhage (SAH) will develop delayed ischemic neurological deficit (DIND) due to vasospasm remains subjective and unreliable. The authors analyzed the utility of a novel software-based technique to quantify hemorrhage volume in patients with Fisher Grade 3 aneurysmal SAH.
Methods. Patients with aneurysmal SAH in whom a computerized tomography (CT) scan was performed within 72 hours of ictus and demonstrated Fisher Grade 3 SAH were analyzed. Severe DIND was defined as new onset complete focal deficit or coma. Moderate DIND was defined as new onset partial focal deficit or impaired consciousness without coma. Fifteen consecutive patients with severe DIND, 13 consecutive patients with moderate DIND, and 12 consecutive patients without DIND were analyzed. Software-based volumetric quantification was performed on digitized admission CT scans by a single examiner blinded to clinical information.
There was no significant difference in age, sex, admission Hunt and Hess grade, or time to admission CT scan among the three groups (none, moderate, or severe DIND). Patients with severe DIND had a significantly higher cisternal volume of hemorrhage (median 30.5 cm3) than patients with moderate DIND (median 12.4 cm3) and patients without DIND (median 10.3 cm3; p < 0.001). Intraparenchymal hemorrhage and intraventricular hemorrhage were not associated with DIND. All 13 patients with cisternal volumes greater than 20 cm3 developed DIND, compared with 15 of 27 patients with volumes less than 20 cm3 (p = 0.004).
Conclusions. The authors developed a simple and potentially widely applicable method to quantify SAH on CT scans. A greater volume of cisternal hemorrhage on an admission CT scan in patients with Fisher Grade 3 aneurysmal SAH is highly associated with DIND. A threshold of cisternal hemorrhage volume (> 20 cm3) may exist above which patients are very likely to develop DIND. Prospective application of software-based volumetric quantification of cisternal SAH may predict which patients will develop DIND.
Role of magnesium in the reduction of ischemic depolarization and lesion volume after experimental subarachnoid hemorrhage
Authors: van den Bergh Walter M. , Zuur J. Karel , Kamerling Niels A. , van Asseldonk Jan Thies H. , Rinkel Gabriël J. E. , Tulleken Cornelis A. F. , Nicolay Klaas 
Published: May 2009

Object. Ischemia-induced tissue depolarizations probably play an important role in the pathophysiology of cerebral ischemia caused by parent vessel occlusion. Their role in ischemia caused by subarachnoid hemorrhage (SAH) remains to be investigated. The authors determined whether ischemic depolarizations (IDs) or cortical spreading depressions (CSDs) occur after SAH, and how these relate to the extent of tissue injury measured on magnetic resonance (MR) images. In addition, they assessed whether administration of MgSO4 reduces depolarization time and lesion volume.
Methods. By means of the endovascular suture model, experimental SAH was induced in 52 rats, of which 37 were appropriate for analysis, including four animals that underwent sham operations. Before induction of SAH, serum Mg++ levels were measured and 90 mg/kg intravascular MgSO4 or saline was given. Extracellular direct current potentials were continuously recorded from six Ag/AgCl electrodes, before and up to 90 minutes following SAH, after which serum Mg++ levels were again measured. Next, animals were transferred to the MR imaging magnet for diffusion-weighted (DW) MR imaging. Depolarization times per electrode were averaged to determine a mean depolarization time per animal.
No depolarizations occurred in sham-operated animals. Ischemic depolarizations occurred at all electrodes in all animals after SAH. Only two animals displayed a single spreading depression-like depolarization. The mean duration of the ID time was 41 ± 25 minutes in the saline-treated controls and 31 ± 30 minutes in the Mg++-treated animals (difference 10 minutes; p = 0.31). Apparent diffusion coefficient (ADC) maps of tissue H2O, obtained using DW images approximately 2.5 hours after SAH induction, demonstrated hypointensities in both hemispheres, but predominantly in the ipsilateral cortex. No ADC abnormalities were found in sham-operated animals. The mean lesion volume, as defined on the basis of a significant ADC reduction, was 0.32 ± 0.42 ml in saline-treated controls and 0.11 ± 0.06 ml in Mg++-treated animals (difference 0.21 ml; p = 0.045). Serum Mg++ levels were significantly elevated in the Mg++-treated group.
Conclusions. On the basis of their data, the authors suggest that CSDs play a minor role, if any, in the acute pathophysiology of SAH. Administration of Mg++ reduces the cerebral lesion volume that is present during the acute period after SAH. The neuroprotective value of Mg++ after SAH may, in part, be explained by a reduction in the duration of the ID of brain cells.
Failure of B7.1-modified tumor to evoke full activation of CD8+ tumor-infiltrating lymphocytes in the central nervous system: prevention of parental tumor growth in the subcutaneous environment
Authors: Ando Hiromichi , Saio Masanao , Tamakawa Noriyuki , Ohe Naoyuki , Nakayama Takashi , Yu Hai , Kaku Yasuhiko , Iwama Toru , Shinoda Jun , Sakai Noboru , Takami Tsuyoshi 
Published: May 2009

Object. It is well known that the central nervous system (CNS) is an immunologically privileged site. To characterize CD8+ tumor-infiltrating lymphocytes (TILs) recovered from the CNS, the authors compared these cells with TILs recovered from subcutaneous tissue by using a B7.1 gene—modified tumor implantation model.
Methods. The authors established a B7.1 gene—modified EL4 murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to observe the duration of tumor-free survival. Although EL4-B7.1 cells were completely rejected in a subcutaneous implantation model, 40% of animals died after the CNS implantation (all animals in which the parent tumor was implanted died within 16 days). Therefore, the authors isolated TILs from each implantation site and analyzed the expressions of activation antigens CD25 and CD69 by performing the anti-CD8 magnetic beads separation method and flow cytometric analysis. After implantation of the parent tumor, there was no difference in the number of TILs from each site (CD25 1.7–3.2%, CD69 21.9–34.3%). After implantation of the B7.1-modified tumor, the CD25-expressing TIL population from the subcutaneous site was 4.68 times higher than that from the CNS site (17.8% compared with 3.8%). Based on these findings, the authors used a mitomycin C—treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination before tumor challenge was sufficient to prevent the development of the tumor. For animals with established tumor, the vaccination protocol was able to prolong host survival (p = 0.0053).
Conclusions. The data clearly demonstrate that the CNS environment fails to activate CD8+ TILs fully. These are the first data indicating in detail a difference between CD8+ TILs from the CNS and those from other sites based on a B7.1-modified tumor model.
Gene therapy for meningioma: improved gene delivery with targeted adenoviruses
Authors: Dirven Clemens M. F. , Grill Jacques , Lamfers Martine L. M. , van der Valk Paul , Leonhart Angelique M. , van Beusechem Victor W. , Haisma Hidde J. , Pinedo Herbert M. , Curiel David T. , Vandertop W. Peter , Gerritsen Winald R. 
Published: May 2009

Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene transfer in meningioma cells.
Methods. The presence of the high-affinity Coxsackievirus and adenovirus receptor (CAR) for adenovirus type 5, as well as endothelial growth factor receptor (EGFR) and alphav integrins (ITGAVs), were analyzed in primary tumors by using immunohistochemical studies and in primary meningioma cell cultures by using fluorescence-activated cell sorting. Targeting of adenoviruses to EGFR was achieved using bispecific antibodies, whereas targeting of adenoviruses to the ITGAVs was accomplished by insertion of an RGD (arginine-glycine-aspartic acid) motif in the adenovirus fiber HI loop. Gene transfer efficiency of untargeted and targeted vectors was compared in primary cell cultures and in spheroids derived from patients' resected tumor material.
The presence of CARs was observed in all tumors and in all but one of the derived primary meningioma cells. The higher expression of EGFRs and ITGAVs indicated that these receptors could be used as alternative targets to redirect the adenoviruses. Redirection of adenoviruses to the EGFRs or integrins enhanced gene transfer threefold (range two—sevenfold) for EGFRs in primary meningioma cells and ninefold (range three—23-fold) for integrins (p = 0.002, analysis of variance). The effect of adenovirus targeting was confirmed in spheroids composed of primary meningioma cells.
Conclusions. Gene transfer with adenoviruses targeted to tumor-specific receptors is very effective in primary meningioma cells and spheroids. These vectors are promising agents for gene therapy of meningiomas.
Reduction of transfusion rates in the surgical correction of sagittal synostosis
Authors: Hentschel Stephen , Steinbok Paul , Cochrane D. Douglas , Kestle John 
Published: May 2009

Object. As public concern about the risks of blood transfusions increased in the mid-1990s, avoidance of transfusions became a goal of surgery for sagittal synostosis. This study was performed to confirm a hypothesized reduction in transfusion rates in recent years and to identify factors associated with both the need for transfusion and low postoperative levels of hemoglobin.
Methods. Sagittal synostosis operations performed in children between 1986 and 1999 were reviewed retrospectively. Patients underwent a minimum of vertex strip craniectomy and parietal craniectomies. There were 118 patients whose median age at surgery was 4.2 months. The primary end point for analysis was defined as either the receipt of a blood transfusion or a postoperative level of hemoglobin less than 70 g/L. Forty-two percent of patients (95% confidence interval [CI] 31–52%) treated before 1996 and 11% of patients (95% CI 0–23%) treated from 1996 onward received blood. The reduction in the blood transfusion rate in later years was, in part, related to the acceptance of a lower postoperative hemoglobin level, often below 70 g/L. A univariate analysis showed that the only patient or surgical factors that correlated with reaching the primary end point in a statistically significant manner were the year of surgery and the extent of surgery. A logistic regression of the age and weight of the child, length of surgery time (from skin opening to skin closure), preoperative hemoglobin level, extent of surgery, and surgeon against the primary end point revealed that the best predictor of the need for a blood transfusion or the presence of a postoperative hemoglobin level lower than 70 g/L was the extent of surgery (β = 1.4, standard error of the β statistic = 0.44). Once the extent of surgery was accounted for in the model, no other covariates significantly improved the model.
Techniques implemented to minimize blood loss since 1995 included the following: use of the Colorado needle for scalp incision, selection of the Midas Rex craniotome for cranial cuts, and application of microfibrillar collagen. Postoperative hemoglobin was allowed to decrease to 60 g/L if the child was stable hemodynamically, before blood was administered. There were no cardiovascular, wound healing, or infectious complications, and no surgeries were repeated for cosmetic reasons.
Conclusions. Low blood transfusion rates were achieved using simple intraoperative techniques and by accepting a low level of postoperative hemoglobin.
Regional differences in patient characteristics, case management, and outcomes in traumatic brain injury: experience from the tirilazad trials
Authors: Hukkelhoven Chantal W. P. M. , Steyerberg Ewout W. , Farace Elana , Habbema J. Dik F. , Marshall Lawrence F. , Maas Andrew I. R. 
Published: May 2009

Object. Regional differences have been shown in patient characteristics and case management within multiple unselected series of patients suffering from traumatic brain injury (TBI). One might expect that such regional heterogeneity would be small in a more selected population of a randomized clinical trial. The goal of this study was to examine what regional differences in patient characteristics, case management, and outcomes exist between continents and among countries within a patient population included in a randomized clinical trial.
Methods. Data were extracted from two concurrently conducted randomized clinical trials of the drug tirilazad; the designs of these studies were similar. The studies included 1701 patients with severe and 476 patients with moderate TBI. Differences were primarily investigated between studies performed in Europe and North America, but also among European regions and between Canada and the United States. Associations among regions and outcomes (6-month mortality rate and Glasgow Outcome Scale scores) were studied using multivariable logistic regression analysis.
Comparisons between continents and among regions within Europe showed differences in the distribution of patient ages, causes of injury, and several clinical characteristics (motor score, pupillary reactivity, hypoxia, hypotension, intracranial pressure [ICP]), and findings on computerized tomography scans. Secondary referrals occurred 2.5 times more frequently in Europe. Within Europe secondary referral was mainly associated with an increased proportion of patients with mass lesions (46% in the European Study compared with 40% in the North American Study). Therapy for lowering ICP was more frequently applied in North America. After adjustments for case mix and management, mortality and unfavorable outcomes were significantly higher in Europe (odds ratios = 1.58 and 1.46, respectively). Significant differences in outcome between regions within Europe or within North America were not observed.
Conclusions. Despite the use of a strict study protocol, considerable differences in patient characteristics and case management exist between continents and among countries, reflecting variations in social, cultural, and organizational aspects. Outcomes of TBI may be worse in Europe compared with North America, but this finding requires further study.
Rapid identification of the primary motor area by using magnetic resonance axonography
Authors: Kamada Kyousuke , Houkin Kiyohiro , Iwasaki Yoshinobu , Takeuchi Fumiya , Kuriki Shinya , Mitsumori Kenji , Sawamura Yutaka 
Published: May 2009

Object. To identify the primary motor area (PMA) quickly and correctly, the authors used magnetic resonance (MR) axonography, including anisotropic diffusion-weighted (DW) MR imaging and three-dimensional anisotropic contrast (3DAC) imaging, which was performed to visualize the corticospinal tract mainly originating from the PMA.
Methods. All studies were obtained in 10 normal volunteers and in 17 patients with brain tumors affecting the central motor system. Data sets of anisotropic DW imaging and anatomical and functional (f)MR imaging were acquired while the participants executed simple hand movements. Offline processing of 3DAC MR axonography images was subsequently done to extract only the anisotropic components of the tract fibers. Somatosensory evoked fields (SSEFs) and intraoperative cortical somatosensory evoked potentials (SSEPs) were recorded after electrical stimulation of the median nerve.
Conclusions. In normal volunteers, anisotropic DW imaging, 3DAC imaging, fMR imaging, and magnetoencephalography consistently localized the PMA in both hemispheres. In contrast, fMR imaging and SSEFs failed to identify the PMA in seven and one of the 17 patients, respectively, because of cortical dysfunctions due to brain tumor. The anisotropic DW imaging data acquired within 30 seconds with no patient tasks successfully identified the PMA in 12 patients, and failed in five patients because of the lesions involving the frontal lobe. The anisotropic axonal components were distinctly visualized on 3DAC images and indicated the PMA location, which was confirmed on intraoperative SSEPs in all 17 affected hemispheres. Swift and noninvasive PMA identification by rapid scanning with MR axonography is a promising method for routine clinical use and is especially beneficial for patients who have severe cortical dysfunction in the PMA.
Lack of agreement between direct magnetic resonance imaging and statistical determination of a subthalamic target: the role of electrophysiological guidance
Authors: Cuny Emmanuel , Guehl Dominique , Burbaud Pierre , Gross Christian , Dousset Vincent , Rougier Alain 
Published: May 2009

Object. The goal of this study was to determine the most suitable procedure(s) to localize the optimal site for high-frequency stimulation of the subthalamic nucleus (STN) for the treatment of advanced Parkinson disease.
Methods. Stereotactic coordinates of the STN were determined in 14 patients by using three different methods: direct identification of the STN on coronal and axial T2-weighted magnetic resonance (MR) images and indirect targeting in which the STN coordinates are referred to the anterior commissure—posterior commissure (AC—PC) line, which, itself, is determined either by using stereotactic ventriculography or reconstruction from three-dimensional (3D) MR images. During the surgical procedure, electrode implantation was guided by single-unit microrecordings on multiple parallel trajectories and by clinical assessment of stimulations. The site where the optimal functional response was obtained was considered to be the best target. Computerized tomography scanning was performed 3 days later and the scans were combined with preoperative 3D MR images to transfer the position of the best target to the same system of stereotactic coordinates. An algorithm was designed to convert individual stereotactic coordinates into an all-purpose PC-referenced system for comparing the respective accuracy of each method of targeting, according to the position of the best target.
Conclusions. The target that is directly identified by MR imaging is more remote (mainly in the lateral axis) from the site of the optimal functional response than targets obtained using other procedures, and the variability of this method in the lateral and superoinferior axes is greater. In contrast, the target defined by 3D MR imaging is closest to the target of optimal functional response and the variability of this method is the least great. Thus, 3D reconstruction adjusted to the AC—PC line is the most accurate technique for STN targeting, whereas direct visualization of the STN on MR images is the least effective. Electrophysiological guidance makes it possible to correct the inherent inaccuracy of the imaging and surgical techniques and is not designed to modify the initial targeting.
Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus—mediated interleukin-12
Authors: Yamanaka Ryuya , Zullo Susan A. , Ramsey Jay , Yajima Naoki , Tsuchiya Naoto , Tanaka Ryuichi , Blaese Michael , Xanthopoulos Kleanthis G. 
Published: May 2009

Object. The authors evaluated dendritic cell (DC)—based immunotherapy for malignant brain tumor to improve its therapeutic efficacy.
Methods. Dendritic cells were isolated from bone marrow and pulsed with phosphate-buffered saline, Semliki Forest virus (SFV)—LacZ, retrovirus vector GCsap—interleukin (IL)-12, and SFV—IL-12, respectively, to treat mice bearing brain tumors of the B16 cell line. The results indicated that therapeutic immunization with DCs pulsed with SFV—IL-12 prolonged the survival of mice with established tumors. Semliki Forest virus induced apoptosis in DCs, which in turn facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity.
Conclusions. Therapy with DCs that have been pulsed with SFV-mediated IL-12 may be an excellent step in the development of new cancer vaccines. Intratumorally injected DCs that have been transiently transduced with IL-12 do not require pulsing of a source of tumor antigens to induce tumor regression.