bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion
Authors: Levy Elad I. , Boulos Alan S. , Hanel Ricardo A. , Tio Fermin O. , Alberico Ronald A. , Fronckowiak Mary Duffy , Nemes Balazs , Paciorek Ann Marie , Guterman Lee R. , Hopkins L. Nelson 
Published: May 2009

Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices.
Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts (“jailing”) were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type.
Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm2 in the group treated with uncoated stents and 0.18 mm2 in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent.
Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.
Adenosine-induced modulation of excitatory amino acid transport across isolated brain arterioles
Authors: Grant Gerald A. , Meno Joseph R. , Nguyen Thien-Son , Stanness Kathe A. , Janigro Damir , Winn H. Richard 
Published: May 2009

Object. Excitatory amino acid (EAA) uptake by neurons and glia acts synergistically with stereoselective transport across the blood—brain barrier (BBB) to maintain EAA homeostasis in the brain. The endogenous neuroprotectant adenosine counteracts many aspects of excitotoxicity by increasing cerebral blood flow and by producing pre- and postsynaptic actions on neurons. In the present study, the authors explored the effect of adenosine on EAA transport across the BBB.
Methods. The effects of adenosine on the permeability of the BBB and transport of aspartate and glutamate across the BBB were studied in a well-characterized isolated penetrating cerebral arteriole preparation suitable for simultaneous investigations of changes in diameter and permeability. At concentrations within the physiological to low pathophysiological range (10−7–10−6 M), the net vectorial transport of [3H]l-glutamate or [3H]l-aspartate from blood to brain was significantly attenuated, whereas there was no effect of adenosine on paracellular BBB permeability to [14C]sucrose or [3H]d-aspartate. With higher concentrations of adenosine (10−4 M and 10−3 M) the net vectorial transport of [3H]l-glutamate and [3H]l-aspartate returned toward baseline. At 10−3 M, the permeability to [14C]sucrose was significantly altered, indicating a breakdown in the BBB. The effect of adenosine (10−6 M) was blocked by theophylline, a blocker of the A1 and A2 receptors of adenosine.
Conclusions. Adenosine-mediated modulation of glutamate and aspartate transport across the BBB is a novel physiological finding.
Delayed repletion of O6-methylguanine—DNA methyltransferase resulting in failure to protect the human glioblastoma cell line SF767 from temozolomide-induced cytotoxicity
Authors: Hirose Yuichi , Kreklau Emiko L. , Erickson Leonard C. , Berger Mitchel S. , Pieper Russell O. 
Published: May 2009

Object. Temozolomide (TMZ)-induced O6-methylguanine (MG) DNA lesions, if not removed by MG—DNA methyltransferase (MGMT), mispair with thymine, trigger rounds of futile mismatch repair (MMR), and in glioma cells lead to prolonged G2—M arrest and ultimately cell death. Depletion of MGMT by O6-benzylguanine (BG) sensitizes tumor cells to TMZ, and this combination is currently used in clinical trials. The use of the TMZ+BG combination in gliomas, however, is complicated by the prolonged TMZ-induced G2—M arrest, which may delay activation of poorly defined cell death pathways and allow for MGMT repletion and reversal of toxicity.
Methods. To address these issues, the actions of TMZ were monitored in DNA MMR-proficient SF767 glioma cells depleted of MGMT by BG, and in cells in which BG was removed at various times after TMZ exposure. In MGMT-depleted cells, TMZ exposure led to DNA single-strand breaks and phosphorylation of cdc2, followed by G2—M arrest, induction of p53/p21, and DNA double-strand breaks. Although DNA single-strand breaks, phosphorylation of cdc2, and G2—M arrest could be reversed by repletion of MGMT up to 5 days after TMZ exposure, TMZ-induced cytotoxicity could only be prevented if MGMT was replenished within 24 hours of the onset of G2—M arrest, and before the creation of DNA double-strand breaks.
Conclusions. These results indicate that although SF767 glioma cells undergo a prolonged G2—M arrest in response to TMZ, their ability to escape TMZ-induced cytotoxicity by MGMT repletion is limited to an approximately 24-hour period after the onset of G2—M arrest.
Assessment of long-term remission of acromegaly following surgery
Authors: Krieger Mark D. , Couldwell William T. , Weiss Martin H. 
Published: May 2009

Object. The criteria for remission of acromegaly following transsphenoidal adenoma resection are in evolution. In the present study the authors evaluate the utility of predicting long-term remission by reference to a single fasting growth hormone (GH) level on the 1st postoperative day.
Methods. A retrospective analysis was conducted on 181 patients with acromegaly who underwent transsphenoidal resection between 1973 and 1990 and completed a 5-year follow-up period. Fasting serum GH levels were obtained in all patients on the 1st postoperative day in the absence of exogenous glucocorticoids. All patients participated in a follow-up evaluation lasting at least 5 years, which included measurements of serum insulin-like growth factor—I (IGF-I) levels as an index of acromegalic activity.
Among the 181 patients, GH levels ranged from 0 to 8 ng/ml in 131 (72%) on the 1st postoperative day, suggesting biochemical remission. This group included 107 (84%) of the 127 patients with microadenomas, but only 24 (44%) of the 54 with macroadenomas. Nevertheless, 15 (11%) of the 131 patients who initially had attenuated GH levels displayed recurrent acromegaly within the first 2 years (with elevated levels of IGF-I in all cases, and abnormalities appearing on magnetic resonance images in nine cases). Only one of 116 patients in whom the initial postoperative GH level was lower than 2 ng/ml experienced a recurrence, whereas 14 (93%) of the 15 patients with postoperative GH levels between 2.2 and 8 ng/ml subsequently displayed biochemical evidence of acromegaly.
Conclusions. The findings indicate that a fasting morning serum GH level lower than 2 ng/ml on the 1st postoperative day portends long-term biochemical remission of acromegaly, whereas higher levels are a significant marker for recurrent disease.
Efficacy of antimicrobial-impregnated external ventricular drain catheters: a prospective, randomized, controlled trial
Authors: Zabramski Joseph M. , Whiting Donald , Darouiche Rabih O. , Horner Terry G. , Olson Jeffrey , Robertson Claudia , Hamilton Allan J. 
Published: May 2009

Object. Catheter-related infection of the cerebrospinal fluid (CSF) pathways is a potentially life-threatening complication of external ventricular drainage. A major source of infection is bacterial contamination along the external ventricular drain (EVD) catheter track. The authors examined the efficacy of EVD catheters impregnated with minocycline and rifampin in preventing these catheter-related infections.
Methods. The authors conducted a prospective, randomized clinical trial at six academic medical centers. All hospitalized patients 18 years or older who required placement of an EVD catheter were eligible for inclusion in the study. Patients were randomly assigned to undergo placement of an EVD with a catheter impregnated with minocycline and rifampin or a standard untreated catheter (control group). To assess primary outcome, CSF samples were collected using a sterile technique at the time of catheter insertion, at least every 72 hours while the catheter remained in place, and at the time of catheter removal. At the time of removal, CSF cultures were obtained from the tip and tunneled segments of each catheter by performing semiquantitative roll-plate and quantitative sonication techniques.
Of the 306 patients enrolled in the study, data from 288 were included in the final analysis. Eighteen patients were excluded from analysis: 14 because the ventricular catheter was in place less than 24 hours, and four because CSF cultures obtained at the time of catheter insertion were positive for infection. Of these 288 patients, 139 were assigned to the control group and 149 to the treatment group. The two groups were well matched with respect to all clinical characteristics, including patient sex and mean age, indication for catheter placement, and length of time the catheter remained in place. The antibiotic-impregnated catheters were one half as likely to become colonized as the control catheters (17.9 compared with 36.7%, respectively, p < 0.0012). Positive CSF cultures were seven times less frequent in patients with antibiotic-impregnated catheters compared with those in the control group (1.3 compared with 9.4%, respectively, p = 0.002).
Conclusions. The use of EVD catheters impregnated with minocycline and rifampin can significantly reduce the risk of catheter-related infections.
Clinical significance of elevated troponin I levels in patients with nontraumatic subarachnoid hemorrhage
Authors: Deibert Ellen , Barzilai Benico , Braverman Alan C. , Edwards Dorothy Farrar , Aiyagari Venkatesh , Dacey Ralph , Diringer Michael 
Published: May 2009

Object. Aneurysmal subarachnoid hemorrhage (SAH) is associated with electrocardiographic abnormalities, regional or focal wall-motion abnormalities on echocardiograms, and/or increased creatine kinase MB isoenzyme (CK-MB) or cardiac troponin I (cTnI). The goal of this prospective study was to compare the sensitivity and specificity of cTnI with those of CK-MB in the prediction of left ventricular dysfunction on echocardiograms in patients with nontraumatic SAH. In addition, those patients with abnormal findings on their echocardiograms and elevated cTnI levels were further evaluated for the presence of coronary artery disease (CAD) by a cardiologist and to determine whether any left ventricular dysfunction that had been detected was reversible.
Methods. The authors obtained electrocardiograms and echocardiograms, and measured serial levels of cardiac enzymes (CK-MB and cTnI) in 43 patients with nontraumatic SAH. Patients with known CAD were excluded. Those patients found to have elevated enzyme levels and abnormal findings on their echocardiograms underwent additional evaluation for CAD. The sensitivity and specificity of both cTnI and CK-MB for detecting left ventricular function were determined.
Twenty-eight percent of patients with SAH in the study had elevated cTnI levels within the first 24 hours after hemorrhage. Seven of the 12 patients had evidence of left ventricular dysfunction on echocardiograms. In all these patients a return to baseline function was found during follow-up examinations. The authors found that cTnI is much more sensitive than CK-MB (100% compared with 29%) in the detection of left ventricular dysfunction in patients with SAH.
Conclusions. An elevated level of cTnI is a good indicator of left ventricular dysfunction in patients with SAH. In this study cardiac dysfunction was reversible and should not necessarily preclude these patients from undergoing operative interventions or becoming heart donors. Clinical management may require more aggressive hemodynamic monitoring until cardiac function returns to normal.
Chronic stimulation of the globus pallidus internus for treatment of non-DYT1 generalized dystonia and choreoathetosis: 2-year follow up
Authors: Krauss Joachim K. , Loher Thomas J. , Weigel Ralf , Capelle H. Holger , Weber Sabine , Burgunder Jean-Marc 
Published: May 2009

Object. The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene.
Methods. Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery.
The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease.
Conclusions. Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.
Hyperemia prior to acute brain swelling during rewarming of patients who have been treated with moderate hypothermia for severe head injuries
Authors: Iida Koji , Kurisu Kaoru , Arita Kazunori , Ohtani Minako 
Published: May 2009

Object. The goal of this study was to elucidate the optimal time for rewarming of patients who have been treated with hypothermia for severe head injury.
Methods. Eleven patients with severe head injuries who had been treated by hypothermia underwent transcranial Doppler (TCD) ultrasonography examinations. The patients were divided into two groups: Group A consisted of three patients in whom acute brain swelling occurred during the rewarming period and Group B was composed of eight patients who displayed no significant intracranial hypertension during or after hypothermia therapy. In all patients, the mean flow velocity of the middle cerebral artery (FVMCA) recorded transcranially and the mean flow velocity of the internal carotid artery (FVICA), recorded high in the neck, were monitored at 24-hour intervals after the patient was admitted to the hospital. In Group A, the FVMCA was normal at 48 hours (maintenance state of hypothermia) in each patient, and abnormal increases and peak values (> 100 cm/second) occurred from 96 to 144 hours postinjury (rewarming period). The FVICA, which was monitored concurrently also varied as the FVMCA increased. The pulsatility indices in the arteries decreased at the time of the peak FVMCA. The enhanced FVMCA was consistent with hyperemia because of the low FVMCA/FVICA ratios (< 3). Two patients in whom jugular venous oxygen saturation was monitored were found to have high values (> 80%), representing hyperemia. All intracranial pressures (ICPs) that lay within the normal range at 48 hours postinjury elevated acutely after the peak FVMCA. In Group B, both FVMCA and FVICA values were normal at 48 hours postinjury and remained stable throughout the rewarming period. Values of ICP were also maintained within the normal range until the patients were weaned from hypothermia therapy.
Conclusions. Hyperemia, detectable by TCD ultrasonography, may serve as an index in the prediction of acute brain swelling, and rewarming should be terminated when such a hemodynamic phenomenon is observed.
Chordoma of the skull base: predictors of tumor recurrence
Authors: Pallini Roberto , Maira Giulio , Pierconti Francesco , Falchetti Maria Laura , Alvino Ester , Cimino-Reale Graziella , Fernandez Eduardo , D'Ambrosio Ettore , Larocca Luigi Maria 
Published: May 2009

Object. Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker.
Methods. In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas.
Conclusions. Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.
Microvascular pathological features of immediate perinidal parenchyma in cerebral arteriovenous malformations: giant bed capillaries
Authors: Attia Walid , Tada Tsuyoshi , Hongo Kazuhiro , Nagashima Hisashi , Takemae Toshiki , Tanaka Yuichiro , Kobayashi Shigeaki 
Published: May 2009

Object. The behavior of brain tissue in cases of arteriovenous malformations (AVMs) is a matter of debate. The authors believe that the local microvascular environment in the AVM bed shares the hemodynamic changes influencing that behavior in one way or another. The purpose of this study was to investigate the microvascular pathological features in the immediate perinidal brain tissue.
Methods. This retrospective study was conducted using excised AVM specimens obtained in 35 patients, from which the authors selected 20 specimens that fulfilled the criteria for sufficient brain tissue around the excised nidus. Specimens were stained with hematoxylin and eosin, and the immediate perinidal microvascular environment was examined using light microscopy.
Conclusions. Eighty-five percent of the AVMs studied showed the presence of huge, dilated capillaries, and 65% showed severe congestion of these capillaries. The authors have named these capillaries “giant bed capillaries.” In this study capillary bleeding was shown in AVMs, and a pericapillary space was seen around some vessels. The brain parenchyma containing AVMs with these findings proved to be significantly ischemic.