bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic source imaging of late evoked field responses to vowels: toward an assessment of hemispheric dominance for language
Authors: Szymanski Michael D. , Perry David W. , Gage Nicole M. , Rowley Howard A. , Walker John , Berger Mitchel S. , Roberts Timothy P. L. 
Published: May 2009

Object. The goal of this study was to determine whether the late neuromagnetic field elicited by simple speech sounds, which is detected by magnetoencephalography, may be used to estimate hemispheric dominance for language and to guide or constrain the intraoperative search for essential language sites. If sufficiently robust, a noninvasive method for assessing hemispheric dominance for language could reduce the necessity for amobarbital testing and the extent of intraoperative cortical stimulation—based mapping, both of which carry the risk of morbidity.
Methods. Fifteen patients undergoing surgery for tumors during which intraoperative language mapping would be performed and two additional patients in whom intracarotid amobarbital testing confirmed right-hemisphere language dominance participated. Following a primary auditory response sources of late neuromagnetic fields elicited by vowel stimuli were modeled and coregistered using magnetic resonance images to form magnetic source (MS) images. A laterality index (LI) was calculated by summing the number of equivalent current dipolar sources in the late fields detected from each hemisphere. In 14 right-handed patients, 10 displayed left asymmetric LIs (0.37 ± 0.16, mean ± standard error of the mean in 14 patients). For both right-hemisphere dominant patients in whom an LI was obtainable, the LI was rightward. Stimulation-mapped essential language sites were found in 7 of 15 patients. For six of these seven patients, the MS image—derived LI was leftward.
Conclusions. Asymmetry in single equivalent dipole modeling of the late neuromagnetic field evoked by simple speech sounds correlates with hemispheric language dominance, although not to the degree necessary for individual clinical predictions. With further development, MS imaging of simple language tasks may be used preoperatively to predict language dominance and even to identify or constrain the intraoperative search for likely sites of essential language cortex.
Bioabsorbable polymeric material coils for embolization of intracranial aneurysms: a preliminary experimental study
Authors: Murayama Yuichi , Viñuela Fernando , Tateshima Satoshi , Song Joon K. , Gonzalez Nestor R. , Wallace Michael P. 
Published: May 2009

Object. A new embolic agent, bioabsorbable polymeric material (BPM), was incorporated into Guglielmi detachable coils (GDCs) to improve long-term anatomical results in the endovascular treatment of intracranial aneurysms. The authors investigated whether BPM-mounted GDCs (BPM/GDCs) accelerated the histopathological transformation of unorganized blood clot into fibrous connective tissue in experimental aneurysms created in swine.
Methods. Twenty-four experimental aneurysms were created in 12 swine. In each animal, one aneurysm was embolized using BPM/GDCs and the other aneurysm was embolized using standard GDCs. Comparative angiographic and histopathological data were analyzed at 2 weeks and 3 months postembolization.
At 14 days postembolization, angiograms revealed evidence of neck neointima in six of eight aneurysms treated with BPM/GDCs compared with zero of eight aneurysms treated with standard GDCs (p < 0.05). At 3 months postembolization, angiograms demonstrated that four of four aneurysms treated with BPM/GDC were smaller and had neck neointima compared with zero of four aneurysms treated with standard GDCs (p = 0.05). At 14 days, histological analysis of aneurysm healing favored BPM/GDC treatment (all p < 0.05): the grade of cellular reaction around the coils was 3 ± 0.9 (mean ± standard deviation) for aneurysms treated using BPM/GDCs compared with 1.6 ± 0.7 for aneurysms treated using GDCs alone; the percentage of unorganized thrombus was 16 ± 12% compared with 37 ± 15%, and the neck neointima thickness was 0.65 ±0.26 mm compared with 0.24 ±0.21 mm, respectively. At 3 months postembolization, only neck neointima thickness was significantly different (p < 0.05): 0.73 ± 0.37 mm in aneurysms filled with BPM/GDCs compared with 0.16 ± 0.14 mm in aneurysms filled with standard GDCs.
Conclusions. In experimental aneurysms in swine, BPM/GDCs accelerated aneurysm fibrosis and intensified neck neointima formation without causing parent artery stenosis or thrombosis. The use of BPM/GDCs may improve long-term anatomical outcomes by decreasing aneurysm recanalization due to stronger in situ anchoring of coils by organized fibrous tissue. The retraction of this scar tissue may also decrease the size of aneurysms and clinical manifestations of mass effect observed in large or giant aneurysms.
Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma
Authors: Nakada Mitsutoshi , Kita Daisuke , Futami Kazuya , Yamashita Junkoh , Fujimoto Noboru , Sato Hiroshi , Okada Yasunori 
Published: May 2009

Object. Acquisition of invasive and metastatic potentials through proteinase expression is an essential event in tumor progression. Among proteinases, matrix metalloproteinases (MMPs) are thought to play a key role in tumor progression through the degradation of the extracellular matrix. In the present study, the authors examined the role of MMP-2 (gelatinase A) and membrane type 1 MMP (MT1-MMP), an activator of the zymogen of MMP-2, proMMP-2, together with tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in the invasion of astrocytic tumors in humans.
Methods. Analyses performed using sandwich enzyme immunoassays demonstrated that the production levels of proMMP-2 and TIMP-1, but not TIMP-2, are significantly higher in glioblastomas multiforme than in other grades of astrocytic tumors. Quantitative reverse transcription-polymerase chain reaction indicated that MT1-MMP is expressed predominantly in glioblastoma tissues, and its expression levels are significantly enhanced as tumor grade increases. In addition, the expression levels and proMMP-2 activation ratio were remarkably higher in glioblastomas associated with cerebrospinal fluid (CSF) dissemination than in those not associated with CSF dissemination. In contrast, an examination of TIMP-2 levels showed a reverse correlation. Like MT1-MMP, TIMP-1 and TIMP-2 were immunolocalized to neoplastic cells in glioblastoma samples. To study the roles of these molecules in the invasion of astrocytic tumors more fully, stable transfectants expressing the MT1-MMP gene were developed in a U251 human glioblastoma cell line. The MT1-MMP transfectants displayed prominent activation of proMMP-2 and invasive growth in three-dimensional collagen gel; however, mock transfectants and parental cells displayed noninvasive growth without the activation. The invasion and gelatinolytic activity of the transfectants were completely inhibited by addition of recombinant TIMP-2, but not recombinant TIMP-1.
Conclusions. These results indicate that MT1-MMP may contribute to tumor invasion and CSF dissemination of glioblastoma cells on the basis of an imbalance of TIMP-2.
Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semliki Forest virus—mediated complementary DNA
Authors: Yamanaka Ryuya , Zullo Susan A. , Tanaka Ryuichi , Blaese Michael , Xanthopoulos Kleanthis G. 
Published: May 2009

Object. The aim of this study was to further investigate dendritic cell (DC)—based immunotherapy for malignant glioma to improve its therapeutic efficacy.
Methods. Dendritic cells were isolated from the bone marrow and pulsed with phosphate-buffered saline, tumor RNA, tumor lysate, Semliki Forest virus (SFV)-LacZ, SFV-mediated B16 complementary (c)DNA, or SFV-mediated 203 glioma cDNA, respectively, to treat mice bearing tumors of the 203 glioma cell line. The results indicated that preimmunization with DCs pulsed with the same type of cDNA as in the tumor by a self-replicating RNA vector (that is, SFV) protected mice from tumor challenge, and that therapeutic immunization prolonged the survival of mice with established tumors. The SFV induced apoptosis in DCs and their death 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 tumor cDNA may be an excellent procedure for the development of new cancer vaccines.
Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice
Authors: McCutcheon Ian E. , Flyvbjerg Allan , Hill Holly , Li Jessica , Bennett William F. , Scarlett John A. , Friend Keith E. 
Published: May 2009

Object. The authors have previously demonstrated that modulation of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect meningioma growth in vitro. These studies were performed to evaluate the efficacy of GH receptor blockade in vivo.
Methods. Primary cultures from 15 meningioma tumors obtained in humans were xenografted into athymic mice. Approximately 1.5 million cells from each of the 15 tumors were implanted into the flanks of two female mice, one pair for each tumor. One animal from each of the 15 pairs was then treated with the GH receptor antagonist pegvisomant and the other with vehicle alone for 8 weeks. The tumor volume was measured using digital calipers three times per week. The mean tumor volume at the initiation of injections was 284 ± 18.8 mm3 in the vehicle group and 291.1 ± 20 mm3 in the pegvisomant group. After 8 weeks of treatment, the mean volume of tumors in the pegvisomant group was 198.3 ± 18.9 mm3 compared with 350.1 ± 23.5 mm3 for the vehicle group (p < 0.001). The serum IGF-I concentration in the vehicle group was 319 ± 12.9 µg/L compared with 257 ± 9.7 in the pegvisomant group (p < 0.02). A small but significant decrease was observed in circulating IGF binding protein (IGFBP)—3 levels, whereas slight increases occurred with respect to serum IGFBP-1 and IGFBP-4 levels. In the placebo group the tumor weight was 0.092 ± 0.01 g compared with 0.057 ± 0.01 g in the pegvisomant group (p < 0.02). The IGF-I and IGF-II concentrations were measured in the tumors by using a tissue extraction method. These human-specific immunoassays demonstrated that there was no autocrine production of IGF-I in any of the tumors, either in the pegvisomant or vehicle group. The IGF-II levels were highly variable (0–38.2 ng/g tissue) and did not differ significantly between treatment groups.
Conclusions. In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression. Because the concentrations of IGF-II in tumor did not vary with pegvisomant treatment and there was no autocrine IGF-I production by the tumors, the mechanism of the antitumor effect is most likely a decrease of IGF-I in the circulation and/or surrounding host tissues. Because the authors have previously demonstrated that the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the GH receptor on the tumors may also be contributing to inhibitory actions.
Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A
Authors: Suehiro Eiichi , Povlishock John T. 
Published: May 2009

Object. Although considerable attention has been focused on the use of posttraumatic hypothermia, little consideration has been given to the issue of posthypothermic rewarming and its potentially damaging consequences. In this communication, the authors examine the issue of rapid posthypothermic rewarming compared with gradual rewarming while exploring the potential utility of cyclosporin A (CsA) administration for attenuating any rapid rewarming—induced axonal change.
Methods. Male Sprague—Dawley rats were subjected to impact-acceleration injury and then their body temperature was lowered to 32°C for 1 hour postinjury. After hypothermia, rewarming to normothermic levels was accomplished either within a 20-minute period (rapid rewarming) or over a 90-minute period (slow rewarming). Some animals in the rapid rewarming group received intrathecal infusion of either CsA or its vehicle, whereas the rats in the slow rewarming group received vehicle alone. Both the CsA and its vehicle were administered immediately before initiation of rewarming. Twenty-four hours postinjury the animals' brains were processed for visualization of amyloid precursor protein (APP), a marker of traumatic axonal injury. The APP-positive axonal density in the gradually rewarmed group receiving vehicle was statistically significantly reduced in comparison with the rapidly rewarmed, vehicle-treated group. For the group undergoing rapid rewarming and treatment with CsA, a statistically significant reduction was also found in the density of the APP profiles compared with the rapidly rewarmed, vehicle-treated group.
Conclusions. The results of this study show that rapid rewarming exacerbates traumatically induced axonal injury, which can be significantly attenuated by administering CsA.
Cerebrospinal fluid immunocytochemical analysis and neuroimaging in the diagnosis of primary leptomeningeal melanoma
Authors: Tosaka Masahiko , Tamura Masaru , Oriuchi Noboru , Horikoshi Mieko , Joshita Takashi , Sugawara Kenichi , Kobayashi Satoshi , Kohga Hideaki , Yoshida Takatomo , Sasaki Tomio 
Published: May 2009

✓ A 20-year-old man presented with slowly progressing symptoms indicative of increased intracranial pressure. Two weeks later he underwent surgery for placement of a ventriculoperitoneal shunt. Cytological examination of the patient's cerebrospinal fluid (CSF) revealed atypical cells that contained no detectable melanin deposits, but proved to be immunocytochemically positive for monoclonal antibodies to melanocytic cells (HMB-45) and S-100 protein. Dermatological and ophthalmological examinations failed to demonstrate any abnormalities. On the basis of these findings, a diagnosis of primary leptomeningeal melanoma was made. Gadolinium-enhanced magnetic resonance (MR) images of the brain and spinal regions obtained 2 months after admission demonstrated typical widespread leptomeningeal enhancement. Results of technetium-99m-hexakis (2-methoxyisobutyl isonitrile) single-photon emission computerized tomography (99mTc-MIBI SPECT) scanning revealed intense uptake of the isotope in the leptomeningeal regions and some cisterns. The patient's condition progressively worsened and he died 5 months after admission. The diagnosis was confirmed at autopsy.
Immunocytochemical analysis of CSF performed using HMB-45 and S-100 protein antibodies is important for the diagnosis of leptomeningeal melanoma because of the test's simplicity, high specificity, and sensitivity. Gadolinium-enhanced MR imaging is used to demonstrate the extent of the leptomeningeal melanoma. An additional and supplemental neuroimaging modality, 99mTc-MIBI SPECT scanning has good potential for the detection and diagnosis of leptomeningeal melanoma.
Developmental venous anomaly with an arteriovenous shunt and a thrombotic complication
Authors: Agazzi Siviero , Regli Luca , Uske Antoine , Maeder Philippe , de Tribolet Nicolas 
Published: May 2009

✓ Developmental venous anomalies (DVAs) are common congenital variations of normal venous drainage that are known for their benign natural history. Isolated cases of symptomatic DVAs with associated arteriovenous (AV) shunts have recently been reported. The present case, in which thrombosis occurred in a DVA involving an AV shunt, raises intriguing questions regarding the clinical characteristics of these lesions and can be used to argue in favor of considering such lesions to be arteriovenous malformations (AVMs).
A 39-year-old man presented with acute thrombosis in a complex system of anomalous hemispheric venous drainage, which included two distinct DVAs, one of which involved an AV shunt. The hemodynamic turbulences induced by a communication between shunted and normal venous outflows were the possible predisposing factor of the thrombosis. Follow-up angiographic and magnetic resonance images revealed complete recanalization of the thrombosed vessel and provided a thorough visualization of the particular angioarchitecture of the DVA.
Acute thrombosis within a DVA with an AV shunt has not been reported previously and, thus, this case can be added to other reports of complications that arise in this particular type of DVA. The authors hypothesize that the presence of an AV shunt in a DVA is a risk factor for aggressive clinical behavior of the anomaly, rendering those lesions prone to complications similar to AVMs.
Although no treatment can be offered, the presence of an AV shunt in a DVA warrants close follow-up observation because such lesions may represent a particular subtype of AVM and, therefore, may exhibit an aggressive clinical behavior.
Cerebral hemodynamics in patients with carotid artery occlusion and contralateral moderate or severe internal carotid artery stenosis
Authors: Vernieri Fabrizio , Pasqualetti Patrizio , Diomedi Marina , Giacomini Patrizia , Rossini Paolo M. , Caltagirone Carlo , Silvestrini Mauro 
Published: May 2009

Object. The purpose of this study was to evaluate cerebral hemodynamics in patients suffering from occlusion of the carotid artery (CA) and contralateral CA stenosis.
Methods. Using transcranial Doppler ultrasonography, the cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was evaluated by calculating the breath-holding index (BHI) of 69 symptomatic patients suffering from internal CA (ICA) occlusion and moderate or severe contralateral ICA stenosis. To evaluate which variables influenced BHIs ipsilateral to the site of ICA occlusion, a multiple stepwise linear regression analysis was performed that included the following factors: patient age, percentage of contralateral ICA stenosis, contralateral BHI, number of collateral pathways, and presence of hypertension, diabetes, smoking, and hyperlipidemia. An analysis of variance was conducted to evaluate the impact of the type of collateral vessels on the BHI. A regression analysis showed that the BHI ipsilateral to the site of ICA occlusion could be accounted for by the contralateral BHI (which was entered at the first step of the analysis, p < 0.001) and by the number of collateral pathways (which was entered at the second step, p = 0.033). Neither the degree of contralateral ICA stenosis nor the other variables could be added to improve the model. The analysis demonstrated that the absence of collateral pathways and the presence of the anterior communicating artery (ACoA) alone were associated with lower BHI values than those found in the presence of two or three collateral vessels, regardless of the presence of an anterior collateral pathway.
Conclusions. On the basis of these data one can infer that the cerebral hemodynamic status of patients with occlusive disease of the CA is influenced by individual anatomical and functional characteristics. Because improvement in contralateral hemodynamics after surgical correction of an ICA stenosis can only be expected in the presence of an ACoA, the planning of strategies for influencing cerebral blood flow distal to an ICA occlusion and, in particular, the consideration of a contralateral carotid endarterectomy, should be preceded by a careful evaluation of the intracranial hemodynamic adaptive status of the patient. Particular attention should be paid to cerebrovascular reactivity and the number and type of collateral vessels that are present.
Effects of ventriculoperitoneal shunt removal on cerebral oxygenation and brain compliance in chronic obstructive hydrocephalus
Authors: Fukuhara Toru , Luciano Mark G. , Brant Christine L. , Klauscie Jennifer 
Published: May 2009

Object. The pathophysiology of shunt malfunction has not been fully examined, probably because of the paucity of appropriate animal models. Using a canine model of chronic obstructive hydrocephalus, the effects of shunt placement and removal on physiological parameters were evaluated.
Methods. Fifteen dogs, nine in which chronic hydrocephalus was induced and six controls, were used in the experiment. Thirteen weeks after the induction of hydrocephalus, intracranial pressure (ICP), tissue and cerebrospinal fluid O2 saturation, response to hyperventilation, and brain compliance at low (5–15 mm Hg) and high (15–25 mm Hg) pressures were measured (untreated stage). Following this procedure, ventriculoperitoneal shunts were implanted in the dogs suffering from hydrocephalus. Two weeks later, the same series of measurements were repeated (shunted stage), following which the shunt systems were removed. One week after shunt removal, the last measurements were obtained (shunt-removed stage). All dogs underwent magnetic resonance imaging four times: before induction of hydrocephalus and before each measurement. All dogs with hydrocephalus also had ventriculomegaly (1.42 ± 0.89 ml before induction of hydrocephalus compared with 3.4 ± 1.64 ml 13 weeks after induction, p = 0.0064). In dogs in the untreated hydrocephalus stage, ICP remained within the normal range (8.33 ± 2.60 mm Hg)—although it was significantly higher than that in the control group (5 ± 1.41 mm Hg, p = 0.014). Tissue O2 saturation in the dogs in the hydrocephalus group (26.1 ± 5.33 mm Hg) was lower than that in the dogs in the control group (48.7 ± 4.27 mm Hg, p < 0.0001). After the dogs underwent shunt placement, significant improvement was observed in their ICP (5.22 ± 2.17 mm Hg, p = 0.012) and tissue O2 saturation (35.2 ± 6.80 mm Hg, p = 0.0084). However, removal of the shunt reversed these improvements back to the preshunt status. Hyperventilation induced significant decreases in ICP and O2 saturation at every measurement time and induced a significant decrease in tissue O2 saturation during the shunted stage, but not during the untreated and shunt-removed stages. Brain compliance measured at high pressure demonstrated a significant gradual decrease at every measurement.
Conclusions. In chronic obstructive hydrocephalus, shunt placement improves ICP and cerebral oxygenation as well as the response to hyperventilation in the tissue. Shunt removal reverses these improvements back to levels present during the untreated stage. The decrease in brain compliance may be one of the factors responsible for symptoms in shunt malfunction.