bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of p27 gene therapy for human malignant glioma potentiated by using mutant p27
Authors: Park Kyung-Ho , Lee Jaeho , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Kim Seung-Ki , Wang Kyu-Chang , Cho Byung-Kyu , Lee Choon-Taek 
Published: May 2009

Object. Malignant glioma could be an ideal candidate for local gene therapy because its invasion is local and it has little metastatic potential. A low expression level and high degradation activity of p27 are known to constitute an independent poor prognostic factor in patients with malignant glioma. In this study, the authors investigated the roles of wild-type p27 and mutant p27 on the treatment of malignant glioma.
Methods. The authors used two adenoviruses: one expressed wild-type p27 (ad-p27wt) and the other, containing a mutation at the major metabolic site, expressed mutant p27 (ad-p27mt). The antitumor effects of the two adenoviruses were compared with respect to cell growth arrest, cell cycle alteration, apoptosis induction, and in vitro tumorigenicity in three glioblastoma mutiforme (GBM) cell lines and in a primary GBM cell line. Transduction with ad-p27wt or ad-p27mt induced the production of p27 and the dephosphorylation of pRB. The protein level of mutant p27 was significantly higher than that of wild-type p27. The ad-p27wt induced cell cycle arrest at the G1—S transition point, whereas the ad-p27mt induced arrest at the G2—M point. Both ad-p27wt and ad-p27mt induced a growth-inhibiting effect, apoptosis, and suppression of in vitro tumorigenicity; however, ad-p27mt displayed a stronger antitumor effect than ad-p27wt in brain tumor cell lines.
Conclusions. Gene therapy involving p27, especially mutant p27, has the potential to become a novel and powerful therapy for malignant glioma.
A quiet hand for microneurosurgery: twiddle your thumb
Authors: Ferguson R. Lawrence , Jobe Kirk 
Published: May 2009

✓ Fatigue is both the most tremor-producing factor and the constant companion of a busy neurosurgeon. Because of the difficulty in controlling tremor-generating factors, the authors sought to develop a means of manipulating surgical instruments with minimal muscle movement while allowing accurate and repeatable movements in all conditions. The “quiet hand technique” is an isolation technique that creates a stable platform by forming the four fingers into a salute that thenceforth moves as one. Fine movements are supplied by the thumb. For instruments that open and close, the thumb abducts and adducts. For suture placement using a round needle holder, the thumb flexes and extends.
Because only the thumb moves, the extent of movement is decreased and therefore momentum and inertia are limited as well. Previously, microsurgeons favored ballistic movements. With the quiet hand technique, however, tension movements are easy. The greater control makes tying 10-0 and 11-0 sutures more predictable. Although the quiet hand technique was developed for use in small-vessel anastomosis, the neurophysiological principles on which it is based apply to movement at all levels and are applicable to working a bipolar coagulator, pickups, a vascular clip holder, or other soft-tissue manipulators.
Surgery for Rathke cleft cysts: technical considerations and outcomes
Authors: Benveniste Ronald J. , King Wesley A. , Walsh Jane , Lee Jacob S. , Naidich Thomas P. , Post Kalmon D. 
Published: May 2009

Object. The aim of this study was to identify the optimal surgical goals and techniques for managing symptomatic Rathke cleft cysts (RCCs).
Methods. The authors conducted a retrospective study of 62 consecutive patients who had undergone surgery for RCCs. Postoperative follow up was a mean of 28 months. Fifty-six patients underwent transsphenoidal cyst decompression and biopsy procedures, and six underwent cyst wall resection. Postoperatively, symptoms improved in 91% of patients with headaches and 92% of patients with visual deficits. Decompression and biopsy were associated with a 10% incidence of new anterior pituitary hormone deficiencies and a 6% incidence of new permanent diabetes insipidus; the incidence of new hormone deficiencies was significantly higher in the few patients who had undergone cyst wall resection. The incidence of relapse, defined as cyst regrowth with either recurrent symptoms or chiasmal compression, was 16%. Resection of the cyst wall was associated with a trend toward a decreased risk of relapse. Sellar packing, sellar floor reconstruction, and irrigation with absolute ethanol did not affect the likelihood of relapse. Squamous metaplasia and inflammation increased the risk of relapse. Residual cyst demonstrated on postoperative magnetic resonance imaging was associated with an increased risk of subsequent asymptomatic cyst regrowth. Seven patients (11%) underwent repeated operation with symptomatic improvement and minimal morbidity; only one patient relapsed following a second surgery.
Conclusions. Decompression and biopsy procedures in the treatment of RCCs lead to improvement in signs and symptoms, with low morbidity rates. Repeated operations will be required in as many as 16% of patients but are also associated with symptomatic improvement, low morbidity, and durable remission. Decompression and biopsy may represent the optimal surgical management of RCC.
Leksell Gamma Knife coordinate setting slippage: how often, how much?
Authors: Foote Robert L. , Pollock Bruce E. , Link Michael J. , Garces Yolanda I. , Kline Robert W. 
Published: May 2009

Object. The aim of this study was to determine the incidence and magnitude of coordinate setting slippage during gamma knife surgery (GKS).
Methods. Thirty-six consecutive patients undergoing GKS with a Leksell unit between June and December 2000 had their coordinates (right and left x-, y-, and z-coordinates; 1548 coordinates; 258 isocenters) and gamma angles checked after the delivery of treatment to each isocenter to determine whether the coordinate settings had slipped and, if so, which settings and the magnitude of the slippage.
Conclusions. Coordinate setting slippage during GKS with a Leksell unit does occur but is rare. The magnitude of such slippage is typically within the error of the stereotactic system and coordinate reading. The authors noted that coordinate setting slippage is significantly correlated with patient weight.
Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and a histopathological analysis
Authors: Cohen-Gadol Aaron A. , Pan Jullie W. , Kim Jung H. , Spencer Dennis D. , Hetherington Hoby H. 
Published: May 2009

Object. Proton magnetic resonance (MR) spectroscopy imaging of the ratio of N-acetylaspartate (NAA) to creatine (Cr) has proved efficacious as a localizing tool in demonstrating the metabolic changes associated with temporal lobe epilepsy. To analyze the significance of these MR spectroscopy findings further, the authors explored the relationship between regional alterations in the NAA/Cr ratio in hippocampi measured preoperatively and histopathological findings in hippocampi resected in patients with intractable mesial temporal lobe epilepsy (MTLE).
Methods. Twelve patients in whom the diagnosis of MTLE had been made and 12 healthy volunteers with no known history of neurological disease underwent high-resolution 1H MR spectroscopy imaging of NAA and Cr (0.64 cm3 nominal voxel resolution) in five voxels spanning the anteroposterior length of the hippocampus. The authors correlated the NAA/Cr ratio with neuropathological findings in resected hippocampi, specifically glial fibrillary acidic protein (GFAP) immunoreactivity and pyramidal neuronal loss. A linear regression analysis of the ipsilateral NAA/Cr ratio revealed a statistically significant relation to the extent of hippocampal neuronal loss in only the CA2 sector (correlation coefficient [r] = −0.66, p < 0.03). The ipsilateral NAA/Cr ratio displayed significant regressions with GFAP immunoreactivity from all the CA sectors (r values ranged from −0.69 and p < 0.01 for the CA4 sector to −0.88 and p < 0.001 for the CA2 sector) except for the CA1. The extent of neuronal cell loss in every hippocampal subfield (r = 0.71−0.74, p < 0.007), except the CA2 (p = 0.08), correlated to the extent of neuronal cell loss in the dentate gyrus. There was no significant relationship between the duration or frequency of seizures and the mean ipsilateral NAA/Cr ratio; however, the mean density of GFAP-immunopositive cells correlated with seizure frequency (p < 0.03).
Conclusions. The NAA/Cr ratio may not measure the full extent of hippocampal neuronal cell loss. The significant association of the NAA/Cr ratio with the GFAP immunoreactivity of most CA sectors indicates that the NAA/Cr ratio may provide a more accurate measurement of recent neuronal injury caused by epileptic activity. The coupling between neuronal impairment and astroglial GFAP expression may indicate the close association between neuronal and glial dysfunction in patients with epilepsy.
Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas
Authors: Ueda Shigeo , Mineta Toshihiro , Nakahara Yukiko , Okamoto Hiroaki , Shiraishi Tetsuya , Tabuchi Kazuo 
Published: May 2009

Object.The DNA repair enzymeO6-methylguanine—DNA methyltransferase (MGMT) inhibits the cytotoxic effect of alkylating agents on tumor cells. The presence of two nonconsensus glucocorticoid-responsive elements in the humanMGMTpromoter region indicates the potential regulation of MGMT expression by glucocorticoid agents. This study was performed to elucidate whether dexamethasone affects the expression of MGMT in glioblastoma multiforme (GBM) cells, thereby limiting the benefit of chemotherapeutic alkylating agents.Methods.Four GBM cell lines (A172, T98G, U138MG, and U87MG) were exposed to the alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) with or without dexamethasone. The expression levels ofMGMTwere correlated with the cytotoxic effects of ACNU in GBM cells. In the presence of ACNU alone, dexamethasone alone, and the combination of both agents, messenger RNA expression ofMGMTwas induced to varying degrees with the highest increases seen in the later conditions. This dexamethasone-dependent induction of theMGMTgene was even observed in U87MG cells in which the promoter is methylated, although the absolute expression ofMGMTmRNA was the lowest in that cell line. The induction ofMGMTby dexamethasone was associated with an increased resistance of these cells to ACNU.Conclusions.These results indicate that dexamethasone-mediated upregulation ofMGMTlimits the efficiency of alkylating agents in the treatment of malignant gliomas.
Optimal blood glucose levels while using insulin to minimize the size of infarction in focal cerebral ischemia
Authors: Zhu Chang Z. , Auer Roland N. 
Published: May 2009

Object. Insulin has been shown to ameliorate cerebral necrosis in global and, more recently, in focal cerebral ischemia. The goal of this study was to determine the relationship between this neuroprotective effect and blood sugar levels in a rat model of focal ischemia.
Methods. Thirty-four rats were subjected to 80 minutes of transient middle cerebral artery occlusion at a mean arterial blood pressure of 60 mm Hg and a temperature of 37°C. Insulin (3.5 IU/kg) was administered 1 hour before (12 rats) and 20 minutes after (12 rats) ischemia; 10 animals served as controls. A quantitative histopathological study conducted after 1 week of survival showed that insulin was not beneficial in reducing the size of the infarction or selective neuronal necrosis in the penumbra when administered before or after ischemia. In addition to infarction, six animals from the insulin-treated groups had bilateral selective neuronal necrosis in the hippocampus or the neocortex. A nonlinear regression analysis in which glucose levels were compared with both cortical necrosis and total infarction yielded a U-shaped curve with a nadir for cerebral necrosis that lay in the 6- to 7-mM blood glucose range. The increased brain damage induced by insulin occurred in animals with very low blood sugar values in the range of 2 to 3 mM.
Conclusions. These results in rats indicate that if insulin is used following ischemia, blood glucose levels should be maintained at approximately 6 to 7 mM. From these data one can infer that hypoglycemia of less than 3 mM should be avoided in situations of focal cerebral ischemia in which insulin is used. Additional animal studies and clinical trials in humans are needed to study the effects of insulin on ischemia.
Prophylactic administration of ceftriaxone for the prevention of meningitis after traumatic pneumocephalus: results of a clinical trial
Authors: Eftekhar Behzad , Ghodsi Mohammad , Nejat Farideh , Ketabchi Ebrahim , Esmaeeli Babak 
Published: May 2009

Object. The purpose of this study was to compare the efficacy of the prophylactic use of ceftriaxone for the prevention of meningitis in patients with acute traumatic pneumocephalus.
Methods. In this prospective, single-institution, randomized clinical trial, 109 patients with mild head injury and traumatic pneumocephalus were randomly assigned to receive or not receive an antibiotic medication (ceftriaxone, 1 g given twice a day) until occurrence of meningitis or at least 5 days after trauma. The patients were followed up for 1 month posttrauma.
The 109 patients were divided into two groups: 53 were assigned to the prophylactic antibiotics therapy group and 56 to the control group. The overall rate of meningitis was 20.1% and the rates of meningitis in the two groups were not significantly different. The results were the same when adjusted for the patient's Glasgow Coma Scale score, sex, and age, as well as for an intradural location of air, air volume, presence of cerebrospinal fluid (CSF) rhinorrhea or CSF otorrhea, radiological sign of a skull base fracture, or intracranial hemorrhage.
Conclusions. The results of this study do not substantiate the efficacy of ceftriaxone used in the prevention of meningitis in patients with traumatic pneumocephalus after mild head injury or in any specific subgroup of these patients. Cerebrospinal fluid rhinorrhea and intracranial hemorrhage may be considered primary risk factors for the development of meningitis in patients with posttraumatic pneumocephalus and, in the absence of these symptoms, intradural location of air and air volume greater than 10 ml may be considered secondary risk factors. Further studies in this area are warranted.
Chorioretinal atrophy in a patient with moyamoya disease
Authors: Harissi-Dagher Mona , Sebag Mikael , Dagher Jehan H. , Moumdjian Robert 
Published: May 2009

✓ Moyamoya disease is characterized by constrictions of segments of the internal carotid arteries (ICAs) and a resultant abnormal anastomotic network. In the literature, visual disturbances from cerebrovascular accidents in patients with moyamoya disease have been described, but very few reports of intraocular pathological conditions have been published. The authors describe a patient with moyamoya disease who presented with chorioretinal atrophy; an association between these two diseases has not previously been reported in the literature.Findings of a clinical ophthalmological evaluation and angiographic series are presented. During the fundic examination, evidence of chorioretinal atrophy was found in this patient. Choroidal vascular insufficiency was revealed by intravenous fluorescein angiography and occlusion of the ICAs proximal to the origin of the posterior communicating arteries by selective carotid and vertebral arteriography. The vertebrobasilar system provided anastomotic connections via the posterior communicating arteries.This is the first case report of chorioretinal atrophy associated with moyamoya disease. It is believed that the vasoocclusive effects of moyamoya disease may predispose the patient to atrophic changes in the peripheral retina. The development of an anastomotic network precludes the progression of this fundic anomaly.
Intracarotid Amytal memory test and hippocampal magnetic resonance imaging volumetry: validity of the Wada test as an indicator of hippocampal integrity among candidates for epilepsy surgery
Authors: Cohen-Gadol Aaron A. , Westerveld Michael , Alvarez-Carilles Juan , Spencer Dennis D. 
Published: May 2009

Object. Intracarotid Amytal testing (the Wada test) has been used to lateralize language and identify patients who may be at risk for memory impairment after temporal lobectomy. The goal of this study was to determine the validity of the Wada test in the assessment of pathological conditions of the hippocampus among candidates for epilepsy surgery. The authors examined the correlation between the functional integrity of the hippocampus, measured using the Wada test, and quantitative measures of hippocampal pathology, determined by obtaining volumetric measurements of the hippocampus with the aid of magnetic resonance (MR) imaging.
Methods. The authors reviewed the relationship between memory scores on the Wada test and hippocampal volumes measured on preoperative MR images in 76 patients who underwent anteromedial temporal lobectomy and amygdalohippocampectomy for the treatment of medically refractory temporal lobe epilepsy. The data were analyzed with respect to their usefulness in lateralizing the seizure focus and predicting the long-term postoperative memory outcome.
Right and left hippocampal volume measurements did not correlate with one another (p > 0.1). Similarly, following a left carotid artery injection of Amytal the patients' right hemisphere memory was not significantly related to their left hemisphere memory on the Wada test (p > 0.1). On the other hand, the patients' right hemisphere memory significantly correlated with their right hippocampal volume (r = 0.51; p < 0.001) and their left hemisphere memory significantly correlated with their left hippocampal volume (r = 0.51; p < 0.001). Both right and left hemisphere memory scores correlated with the hippocampal volumetry ratio (r = 0.47 and r = 0.45, respectively; both p < 0.001). Lateralization of a seizure focus based on hippocampal volumetry results was significantly related to lateralization based on the results of the Wada test (r = 0.49; p < 0.01). The disparity between the Wada memory scores on ipsilateral and contralateral sides was significantly and inversely related to the change in verbal memory following temporal lobectomy (r = −0.28; p < 0.02). The preoperative hippocampal volumetry ratio also significantly and inversely correlated with the change in verbal memory after surgery (r = −0.31; p < 0.01).
Conclusions. The Wada memory test may be a valuable method of measuring the functional integrity of the hippocampus. The systematic study of MR imaging—acquired morphological data and Wada-acquired neuropsychological data may increase our understanding of the location of material-specific memory and the selection of eligible candidates for epilepsy surgery.
A patient-specific computer model to predict outcomes of the balloon occlusion test
Authors: Charbel Fady T. , Zhao Meide , Amin-Hanjani Sepideh , Hoffman William , Du Xinjian , Clark Marlyn E. 
Published: May 2009

Object. Balloon occlusion tests (BOTs) are performed to identify patients who are at risk for ischemia and stroke following permanent internal carotid artery (ICA) occlusion. The object of this work was to determine whether patient-specific blood flow modeling can be used to identify patients in whom the BOT would not be tolerated.
Methods. The test was performed in 16 patients who underwent BOT with continuous neurological and electroencephalographic monitoring, followed by a hypotensive challenge. During hypotension a tracer was injected so that single-photon emission tomography (SPECT) scans could be obtained. Each individual brain circulation was modeled using information gained from phase-contrast magnetic resonance (MR) angiography and digital subtraction (DS) angiography, and the predicted effect of the BOT was evaluated.
Six patients did not tolerate the BOT; in these patients, decreases in middle cerebral artery (M1 segment) blood flow of 41 ± 27% (mean ± standard deviation), anterior cerebral artery (A3 segment) flow of 56 ± 33%, and posterior cerebral artery (P2 segment) flow of 4 ± 13% ipsilateral to the site of occlusion were found with modeling; these changes were significantly greater than the percentage of changes measured in the contralateral hemisphere (p < 0.05). Ten patients who tolerated the BOT well had calculated decreases in ipsilateral flows of only 9 ± 6% for the M1 segment, 12 ± 40% for the A3 segment, and 17 ± 21% for the P2 segment during BOT modeling.
Conclusions. A decrease in blood flow in both the ipsilateral M1 and A3 segments that was greater than 20%, calculated by flow modeling of the BOT, was 100% sensitive and 100% specific in identifying patients who could not tolerate the BOT. Blood flow modeling, coupled with DS angiography and noninvasive phase-contrast MR angiography measurements to make calculations patient specific, can be used to identify patients who have an elevated risk of ischemia during the BOT.
Role of apoptosis in intracranial aneurysm rupture
Authors: Pentimalli Luigi , Modesti Andrea , Vignati Andrea , Marchese Enrico , Albanese Alessio , Di Rocco Federico , Coletti Anna , Di Nardo Paolo , Fantini Cristina , Tirpakova Barbara , Maira Giulio 
Published: May 2009

Object. Mechanisms involved in the rupture of intracranial aneurysms remain unclear, and the literature on apoptosis in these lesions is extremely limited. The hypothesis that apoptosis may reduce aneurysm wall resistance, thus contributing to its rupture, warrants investigation. The authors in this study focused on the comparative evaluation of apoptosis in ruptured and unruptured intracranial aneurysms. Peripheral arteries in patients harboring the aneurysms and in a group of controls were also analyzed.
Methods. Between September 1999 and February 2002, specimens from 27 intracranial aneurysms were studied. In 13 of these patients apoptosis was also evaluated in specimens of the middle meningeal artery (MMA) and the superficial temporal artery (STA). The terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling technique was used to study apoptosis via optical microscopy; electron microscopy evaluation was performed as well. Apoptotic cell levels were related to patient age and sex, aneurysm volume and shape, and surgical timing.
Significant differences in apoptosis were observed when comparing ruptured and unruptured aneurysms. High levels of apoptosis were found in 88% of ruptured aneurysms and in only 10% of unruptured lesions (p < 0.001). Elevated apoptosis levels were also detected in all MMA and STA specimens obtained in patients harboring ruptured aneurysms, whereas absent or very low apoptosis levels were observed in MMA and STA specimens from patients with unruptured aneurysms. A significant correlation between aneurysm shape and apoptosis was found.
Conclusions. In this series, aneurysm rupture appeared to be more related to elevated apoptosis levels than to the volume of the aneurysm sac. Data in this study could open the field to investigations clarifying the causes of aneurysm enlargement and rupture.