bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive phenotype observed in 1,3-bis(2-chloroethyl)-1-nitrosourea—resistant sublines of 9L rat glioma cells: a tumor model mimicking a recurrent malignant glioma
Authors: Saito Ryuta , Bringas John , Mirek Hanna , Berger Mitchel S. , Bankiewicz Krys S. 
Published: May 2009

Object. Chemotherapy is suspected of having an effect on the generation of phenotypical heterogeneity and the development of drug resistance in tumors. Recurrent gliomas feature drug resistance as well as greater invasive growth than original tumors. The authors investigated phenotypical changes in invasion observed in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)—resistant sublines of the 9L rat gliosarcoma.
Methods. Two established BCNU-resistant sublines, derived from 9L gliosarcoma cells by treating these cells with BCNU in vivo or in vitro, were used in the study. An in vitro examination confirmed the resistance of the cells to BCNU treatment. The cells were implanted into the striatum of Fisher 344 rats, and histological examinations were performed to compare the growth patterns of the resultant tumors. A new brain tumor model was established by implanting 9L-2 cells in Fisher 344 rats.
The 9L-2 and BTRC-19 cells displayed a distinct increase in BCNU resistance compared with the 9L cells. Both BCNU-resistant sublines developed a tumor mass with invasive margins, which is not the case with 9L tumor models. The newly developed 9L-2 tumor model demonstrated 100% tumor uptake with consistent growth patterns.
Conclusions. Cells that acquire drug resistance also demonstrated invasive growth. Because the 9L-2 and BTRC-19 cells were derived from 9L cells that had been treated with BCNU in vivo and in vitro, this change in phenotype was likely caused by the drug treatment, which may have implications for chemotherapy of gliomas. The tumor model that developed from the 9L-2 cells can be used as a model of a recurrent glioma, which features drug resistance and invasive growth.
Association between cerebrospinal fluid levels of asymmetric dimethyl-L-arginine, an endogenous inhibitor of endothelial nitric oxide synthase, and cerebral vasospasm in a primate model of subarachnoid hemorrhage
Authors: Jung Carla S. , Iuliano Brian A. , Harvey-White Judith , Espey Michael G. , Oldfield Edward H. , Pluta Ryszard M. 
Published: May 2009

Object. Decreased availability of nitric oxide (NO) has been proposed to evoke delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). Asymmetric dimethyl-l-arginine (ADMA) inhibits endothelial NO synthase (eNOS) and, therefore, may be responsible for decreased NO availability in cases of cerebral vasospasm. The goal of this study was to determine whether ADMA levels are associated with cerebral vasospasm in a primate model of SAH.
Methods. Twenty-two cynomolgus monkeys (six control animals and 16 with SAH) were used in this study. The levels of ADMA, l-arginine, l-citrulline, nitrites, and nitrates in cerebrospinal fluid (CSF) and serum were determined on Days 0, 7, 14, and 21 following onset of SAH. Cerebral arteriography was performed to assess the degree of vasospasm. Western blot analyses of the right and left middle cerebral arteries (MCAs) were performed to assess the expression of eNOS, type I protein—arginine methyl transferase (PRMT1) and dimethylarginine dimethylaminohydrolase (DDAH2).
Cerebrospinal fluid levels of ADMA remained unchanged in the control group (six animals) and in animals with SAH that did not have vasospasm (five animals; p = 0.17), but the levels increased in animals with vasospasm (11 animals) on Day 7 post-SAH (p < 0.01) and decreased on Days 14 through 21 (p < 0.05). Cerebrospinal fluid levels of ADMA correlated directly with the degree of vasospasm (correlation coefficient = 0.7, p = 0.0001; 95% confidence interval: 0.43–0.83). Levels of nitrite and nitrate as well as those of l-citrulline in CSF were decreased in animals with vasospasm. Furthermore, DDAH2 expression was attenuated in the right spastic MCA on Day 7 post-SAH, whereas eNOS and PRMT1 expression remained unchanged.
Conclusions. Changes in the CSF levels of ADMA are associated with the development and resolution of vasospasm found on arteriograms after SAH. The results indicate that endogenous inhibition of eNOS by ADMA may be involved in the development of delayed cerebral vasospasm. Inhibition of ADMA production may provide a new therapeutic approach for cerebral vasospasm after SAH.
Complex visual hallucinations (Charles Bonnet syndrome) in visual field defects following cerebral surgery
Authors: Freiman Thomas M. , Surges Rainer , Vougioukas Vassilios I. , Hubbe Ulrich , Talazko Jochen , Zentner Josef , Honegger Jürgen , Schulze-Bonhage Andreas 
Published: May 2009

✓ The development of visual hallucinations after loss of vision is known as the Charles Bonnet syndrome. This phenomenon was first described in 1760 by Charles Bonnet and others during their observations of elderly patients with degeneration of the retina or cornea. To date a clear association between visual hallucinations and neurosurgical procedures has not been reported. Because of their clear demarcation, however, surgical lesions in the cerebrum offer a unique opportunity to determine the pathoanatomical aspects of visual hallucinations. During a 3-year period, 41 consecutive patients who acquired visual field defects after neurosurgery were examined for the occurrence of visual hallucination. Postoperatively, four of these patients experienced visual hallucinations. In two of them an upper quadrantanopia developed after the patients had undergone selective amygdalohippocampectomy. In the other two patients a complete hemianopia developed, in one case after resection of a parietal astrocytoma and in the other after resection of an occipital glioblastoma multiforme. The visual hallucinations were transient and gradually disappeared between 4 days and 6 months postoperatively. The patients were aware of the fact that their hallucinations were fictitious and displayed no psychosis. Electroencephalographic recordings were obtained in only two patients and epileptic discharges were found.
Deafferentiation of cortical association areas may lead to the spontaneous generation of complex visual phenomena. In the present series this phenomenon occurred in approximately 10% of patients with postoperative visual field defects. In all four cases the central optic radiation was damaged between the lateral geniculate nucleus and the primary visual cortex. The complex nature of the visual hallucination indicates that they were generated in visual association areas.
Incidence and risk factors for the growth of unruptured cerebral aneurysms: observation using serial computerized tomography angiography
Authors: Matsubara Shunji , Hadeishi Hiromu , Suzuki Akifumi , Yasui Nobuyuki , Nishimura Hiromi 
Published: May 2009

Object. The goal of this study was to examine the growth of unruptured intracranial aneurysms with the focus on the risk factors and incidence of these lesions.
Methods. One hundred sixty-six untreated cerebral saccular aneurysms were analyzed in 140 patients. The age of the patients ranged from 29 to 82 years (mean 62.8 years), the female/male ratio was 94:46, and the mean follow-up period was 17.7 months. Aneurysms were located at the internal carotid artery (ICA) in 68 patients, the middle cerebral artery (MCA) in 43, the anterior cerebral artery in 38, the basilar artery (BA) in 13, and the vertebral artery in four patients. The maximum diameter of the lesions ranged from 2 to 20 mm (mean 4.1 mm). All patients were examined using serial computerized tomography angiography to evaluate signs of aneurysm growth.
Although growth was identified in 10 aneurysms (nine patients [6.4%]), no bleeding occurred. Growth-related changes were significantly associated with the size of the aneurysm and occurred in three (2.4%) of 125 aneurysms measuring 2 to 4 mm, three (9.1%) of 33 lesions measuring 5 to 9 mm, and four (50%) of eight lesions measuring 10 to 20 mm. These changes were more frequently found in aneurysms located at the BA bifurcation (two [40%] of five lesions) and the ICA (six [8.8%] of 68 lesions) than in those located at the MCA (zero of 43 lesions, p < 0.05). The 1-, 2-, and 3-year cumulative growth rates calculated using the Kaplan—Meier method were 2.5, 8, and 17.6%, respectively.
Conclusions. A diameter of at least 10 mm and a location at the BA bifurcation or the ICA were significant risk factors for aneurysm growth. The incidence of growth was 2.5% in the 1st year and this risk increased yearly. Computerized tomography angiography is useful for follow up of patients with aneurysms because it allows the detection of even subtle morphological changes.
Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage
Authors: Toussaint L. Gerard , Friedman Jonathan A. , Wijdicks Eelco F. M. , Piepgras David G. , Pichelmann Mark A. , McIver Jon I. , McClelland Robyn L. , Nichols Douglas A. , Meyer Fredric B. , Atkinson John L. D. 
Published: May 2009

Object. Previous studies have indicated an increased incidence of death in patients with subarachnoid hemorrhage (SAH) who are currently receiving anticoagulation therapy. The significance of previous aspirin use in patients with SAH is unknown. The authors analyzed the effects of prior aspirin use on clinical course and outcomes following aneurysmal SAH.
Methods. The medical records of 305 patients with angiogram-confirmed aneurysmal SAH who consecutively presented to our institution between 1990 and 1997 within 7 days of ictus were analyzed. Twenty-nine (9.5%) of these patients had a history of regular aspirin use before onset of the SAH. The Glasgow Outcome Scale (GOS) was used to measure patient outcome at the longest available follow up.
Aspirin users were older on average than nonusers (59 years of age compared with 53 years; p = 0.018). The mean admission Hunt and Hess grades of patients with and without aspirin use were similar (2 compared with 2.3; p = 0.51). Two trends, which did not reach statistical significance, were observed. 1) The rebleeding rate in aspirin users was 14.3%, compared with a 4.7% rebleeding rate in nonusers (p = 0.06). 2) Permanent disability from vasospasm was less common among aspirin users (23% compared with 50%; p = 0.069). Outcomes did not differ between aspirin users and nonusers (mean GOS Score 3.83 compared with GOS Score 3.86, respectively; p = 0.82).
Conclusions. Despite trends indicating increased rebleeding rates and a lower incidence of permanent disability due to delayed ischemic neurological deficits, there was no significant effect of previous aspirin use on overall outcome following aneurysmal SAH. Based on these preliminary data, the presence of an intracranial aneurysm is not a strict contraindication to aspirin use.
Craniofacial resections in the elderly: an outcome study
Authors: Hentschel Stephen J. , Nader Remi , Suki Dima , Dastgir Amer , Callender David L. , DeMonte Franco 
Published: May 2009

Object. The elderly population is increasing in number and is healthier now than in the past. The purpose of this study was to examine complications and outcomes following craniofacial resection (CFR) in elderly patients and to compare findings with those of a matched younger cohort.
Methods. All patients 70 years of age or older undergoing CFR at the M. D. Anderson Cancer Center (elderly group) between December 1992 and July 2003 were identified by examining the Department of Neurosurgery database. A random cohort of 28 patients younger than 70 years of age (control group) was selected from the overall population of patients who underwent CFR.
There were 28 patients ranging in age from 70 to 84 years (median 74 years). Major local complications occurred in seven elderly patients (25%) and in six control patients (21%) (p = 0.75), and major systemic complications occurred in nine elderly patients (32%) and in three control patients (11%) (p = 0.05). There was one perioperative death in both groups of patients. The median duration of disease-specific survival for the elderly patients was not reached (mean 6.8 years); however, it was 8.3 years for control patients (p = 0.24). Predictors of poorer overall survival from a multivariate analysis of the elderly group included presence of cardiac disease (p = 0.005), a major systemic perioperative complication (p = 0.03), and a preoperative Karnofsky Performance Scale score less than 100 (p = 0.04).
Conclusions. In this study of elderly patients who underwent CFR, there was no difference in disease-specific survival when compared with a matched cohort of younger patients. There was, however, an increased incidence of perioperative major systemic complications in the elderly group.
Intraoperative infrared imaging of brain tumors
Authors: Gorbach Alexander M. , Heiss John D. , Kopylev Leonid , Oldfield Edward H. 
Published: May 2009

Object. Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear.
Methods. An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis—astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow.
Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery.
Conclusions. Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion.
Endovascular treatment of intracranial aneurysms: comparative evaluation in a terminal bifurcation aneurysm model in dogs
Authors: Yoshino Yoshikazu , Niimi Yasunari , Song Joon K. , Silane Michael , Berenstein Alejandro 
Published: May 2009

Object. The authors investigated whether HydroCoils decreased coil compaction and aneurysm recanalization in a canine model of a large, wide-necked, high-flow bifurcation aneurysm.
Methods. Eleven experimental aneurysms were created. Two aneurysms were untreated (Group 1); three were treated with standard platinum coils (Guglielmi Detachable Coils; Group 2); and six were treated with platinum framing coils and filling HydroCoils (Group 3). Comparative angiographic and histopathological data were analyzed at 2 weeks and again at 3 months.
At 3 months, the Group 1 aneurysms remained patent without spontaneous thrombosis. After coil placement the percentage of aneurysm filling by volume ranged from 59 to 90% (mean 75.4%) for Group 3 (HydroCoil-treated) and 34.3 to 48.9% (mean 39.6%) for Group 2 (GDC-treated) (p < 0.05). At 14 days, two of the three Group 2 aneurysms exhibited coil compaction and aneurysm recanalization at the neck; in both cases the condition worsened at 3 months. At 14 days and 3 months, five of the six Group 3 aneurysms were 100%, and one of six was 90% occluded and remained stable. At 3 months, the neointima of the aneurysm neck was significantly thicker in the Group 3 lesions, which had been treated by HydroCoils (0.329 ± 0.191 mm), than in Group 2 lesions, which had been treated with GDCs (0.026 ± 0.018 mm) (p , 0.001). No thrombus formation occurred in Group 2; however, in two of the six aneurysms in Group 3, thrombus formed at the coil—neck interface.
Conclusions. The experimental canine bifurcation aneurysm model overcomes the limitations of side-wall aneurysm models. In this model, HydroCoils resulted in significantly denser coil packing, less follow-up coil compaction, and thicker neointimal tissue at the neck of the lesion. HydroCoils also appeared more thrombogenic at the aneurysm neck—parent artery interface.
Distribution kinetics of targeted cytotoxin in glioma by bolus or convection-enhanced delivery in a murine model
Authors: Kawakami Koji , Kawakami Mariko , Kioi Mitomu , Husain Syed R. , Puri Raj K. 
Published: May 2009

Object.Interleukin-13 receptor (IL-13R)—targeted cytotoxin (IL-13—PE38) displays a potent antitumor activity against a variety of human tumors including glioblastoma multiforme (GBM) and, thus, this agent is being tested in the clinical trial for the treatment of recurrent GBM. In this study, the authors determined the safety and distribution kinetics of IL-13 cytotoxin when infused intracranially by a bolus injection and by convection-enhanced delivery (CED) in an athymic nude mouse model of GBM.Methods.For the safety studies, athymic nude mice were given intracranial infusions of IL-13 cytotoxin into normal parenchyma by either a bolus injection or a 7-day-long CED. Toxicity was assessed by performing a histological examination of the mouse brains. For the drug distribution studies, nude mice with intracranially implanted U251 GBM tumors were given an intratumor bolus or a CED infusion of IL-13 cytotoxin. Brain tumor samples obtained between 0.25 and 72 hours after the infusion were assessed for drug distribution kinetics by performing immunohistochemical and Western blot analyses.Based on the histological changes in the tumor and brain, the maximum tolerated dose of intracranial IL-13 cytotoxin infusion in nude mice was determined to be 4 µg when delivered by a bolus injection and 10 mg when CED was used. Drug distribution reached the maximum level 1 hour after the bolus injection and the volume of distribution was determined to be 19.3 ± 5.8 mm3. Interleukin-13 cytotoxin was barely detectable 6 hours after the injection. Interestingly, when delivered by bolus injections IL-13 cytotoxin exhibited superior distribution in larger rather than smaller tumors. Convection-enhanced delivery was superior for drug distribution in the U251 tumors because when CED was used the drug remained in the tumors 6 hours after the infusion.Conclusions.These studies provide confirmation of a previous hypothesis that CED of IL-13 cytotoxin is superior to bolus injections not only for the safety of the normal brain but also for maintaining drug levels for a prolonged period in infused brain tumors. These findings are highly relevant and important for the optimal clinical development of IL-13 cytotoxin or any other targeted antitumor agent for GBM therapy, in which multiple routes of delivery of an agent are being contemplated.
Bilirubin as a cerebrospinal fluid marker of sentinel subarachnoid hemorrhage: a preliminary report in pigs
Authors: Morgan Chad J. , Pyne-Geithman Gail J. , Jauch Edward C. , Shukla Rakesh , Wagner Kenneth R. , Clark Joseph F. , Zuccarello Mario 
Published: May 2009

Object. A model of subarachnoid hemorrhage (SAH) in pigs was developed to investigate bilirubin concentration in cerebrospinal fluid (CSF) as a potential marker of sentinel SAH.
Methods. Seven male Yorkshire pigs received a 250-µl injection of either whole autologous arterial blood (four animals) or isotonic saline (three animals) into the cisternae magna in an effort to produce volumetrically a model of sentinel SAH and a control injection model, respectively. Cerebrospinal fluid volumes of 100 µl were then collected from both the lumbar cistern and cisternae magna at 1 to 2-hour intervals for a total of 24 hours postinjection. The CSF was then tested for bilirubin.
Mean concentrations of bilirubin (± standard deviation [SD]) obtained from the lumbar cistern 24 hours following the injection of blood or saline were 4.38 ± 1.04 µM in the SAH animals and 1.02 ± 0.05 µM in the controls. At 24 hours postinjection, mean concentrations (± SD) of cisternae magna bilirubin were 7.29 ± 1.33 ÉM and 1.33 ± 0.14 µM in the SAH animals and controls, respectively. In the SAH group, both the lumbar cistern and cisternae magna bilirubin concentrations differed significantly from baseline values 12 hours following SAH.
Conclusions. Elevated concentrations of CSF bilirubin can be detected following a low-volume SAH, and the production of bilirubin occurred over a predictable time course. Twelve hours after hemorrhage, an elevated CSF bilirubin concentration was an indicator of hemolysis occurring in the subarachnoid spaces. The presence of bilirubin in CSF is a potential marker for differentiating SAHs from traumatic lumbar punctures in humans.
Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination
Authors: Miyashita Katsuyoshi , Hayashi Yutaka , Fujisawa Hironori , Hasegawa Mitsuhiro , Yamashita Junkoh 
Published: May 2009

✓ Solitary fibrous tumor (SFT) is a benign and rare neoplasm. To date, only 37 patients with intracranial SFTs have been reported. Although a number of the tumors were recurrent and some later underwent malignant transformation, none of these lesions progressed to cerebrospinal fluid (CSF) dissemination. In this paper the authors report a case of SFT in which the lesion recurred several times and ultimately was disseminated by the CSF. The patient was a 63-year-old woman with multiple intracranial and spinal tumors. Fifteen years before this presentation, at the age of 48 she had been hospitalized for resection of a falcotentorial tumor. During the ensuing 15 years she underwent multiple surgeries and sessions of radiation therapy for recurrent lesions. The exclusive location of her tumors in the subarachnoid space at the end of this 15-year period indicate CSF dissemination of the tumor.
The tumor that was resected when the patient was 48 years old and the latest resected lesion were analyzed by performing immunohistological CD34, epithelial membrane antigen, vimentin, S100 protein, and reticulin staining, and determining the MIB-1 labeling index (LI). Most of the results were identical, and both tumors were diagnosed as SFT according to a staining pattern that showed a strong and diffuse positive reaction for CD34. Nevertheless, the authors noted that the MIB-1 LI increased from less than 1% in the original tumor to 13% in the latest tumor. The increased proliferation of MIB-1 indicates that the malignant transformation could have occurred during tumor recurrence with CSF dissemination.