bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prefrontal dysfunction following unilateral posteroventral pallidotomy in Parkinson's disease
Authors: Yokoyama Tetsuo , Imamura Yoko , Sugiyama Kenji , Nishizawa Shigeru , Yokota Naoki , Ohta Seiji , Uemura Kenichi 
Published: May 2009

Object. Pre- and postoperative cognitive function was evaluated in patients with Parkinson's disease (PD) who underwent unilateral posteroventral pallidotomy (PVP) to clarify the effects of this operation on cognitive function.Methods. Cognitive function was assessed before surgery and 1 month and 3 months afterward by using a battery of neuropsychological tests consisting of orientation, digit span (forward and backward), digit learning, 5-minute memory of five words, similarities, serial sevens, animal name listing, and the kana pick-out test, as well as the Japanese version of the Mini-Mental State. Preoperative evaluation revealed that patients experienced difficulties in performing the neuropsychological tasks of reasoning and abstraction, working memory of numerals, word fluency, and concept formation compared with 36 healthy volunteers (p < 0.05). A simple regression analysis showed strong relationships in a negative fashion between preoperative (r = 0.81, p = 0.002) and 1-month (r = 0.79, p = 0.0059) and 3-month (r = 0.85, p = 0.0016) postoperative gross-total scores and Hoehn and Yahr staging. Preoperative and postoperative scores at 1 month and 3 months were analyzed by analysis of variance, but only the Fisher's post hoc test revealed the source of difference. All tasks except orientation (p = 0.0292) were unchanged in the 10 patients who underwent surgery on the right side. The scores for this task at 1 month postsurgery were significantly lower (p = 0.0203) but improved to preoperative values by 3 months. In the 15 patients who underwent surgery on the left side significant differences among tasks were revealed for serial sevens (p = 0.0471) and animal naming (p = 0.0425). The scores for these tasks were significantly lower at 1 month postoperatively (p = 0.0431 for serial sevens and p = 0.0408 for animal naming), but improved by 3 months after the operation.Conclusions. The present data revealed that cognitive dysfunction in patients with PD relates to advancement of Hoehn and Yahr stage, but PVP is not associated with significant long-lasting cognitive deficits.
Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial
Authors: Kelly Daniel F. , Goodale David B. , Williams John , Herr Daniel L. , Chappell E. Thomas , Rosner Michael J. , Jacobson Jeff , Levy Michael L. , Croce Martin A. , Maniker Allen H. , Fulda Gerald J. , Lovett James V. , Mohan Olga , Narayan Raj K. 
Published: May 2009

Object. Sedation regimens for head-injured patients are quite variable. The short-acting sedative—anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used.Methods. Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95 ± 87 hours) and 19 patients in the morphine group (mean time of morphine usage 70 ± 54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events.Conclusions. Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.
Effects of continuous localized infusion of granulocyte—macrophage colony—stimulating factor and inoculations of irradiated glioma cells on tumor regression
Authors: Wallenfriedman Margaret A. , Conrad John A. , DelaBarre Lance , Graupman Patrick C. , Lee Gina , Garwood Michael , Gregerson Dale S. , Jean Walter C. , Hall Walter A. , Low Walter C. 
Published: May 2009

Object. Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte—macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats.Methods. The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF—treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833 ± 2284 mm3, 3294 ± 1632 mm3, and 1979 ± 1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 106 gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF—irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging.Conclusions. These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.
Hormonal effects on glioblastoma multiforme in the nude rat model
Authors: Plunkett Robert J. , Lis Agnieszka , Barone Tara A. , Fronckowiak Mary Duffy , Greenberg Steven J. 
Published: May 2009

Object. The authors studied the effect of gender and hormonal status on survival in nude rats implanted with human glioblastoma multiforme (GBM) cell lines.Methods. Nude rats received intracerebral implants of either wild-type U87MG cells or U87MG cells transfected with the gene for endothelin-1 (U87/ET-1). In the initial study, survival was compared in males and females for each of the two cell lines. The six second-phase study groups were composed of: 1) males; 2) females; 3) ovariectomized females; 4) sham ovariectomized females; 5) ovariectomized rats given 10 µg/day estradiol benzoate for 21 days; and 6) ovariectomized rats given 20 mg/kg/day progesterone for 21 days. All rats in the second phase were implanted with U87/ET-1 cells. Animals were killed when they exhibited initial signs of neurological deterioration. Female nude rats survived longer than male rats implanted with either U87 or U87/ET-1 cells. In the second phase, ovariectomized, male, and progesterone-treated rats died at approximately 19 days, whereas the female, sham-treated, and estrogen-treated animals died 23 to 25 days after tumor cell implantation.Conclusions. The authors demonstrate that female nude rats implanted with human GBM cells have a survival advantage over male rats and that estrogen provides the advantage.
Immediate early gene expression in vascular smooth-muscle cells synergistically induced by hemolysate components
Authors: Wang Xiaoyu , Marton Linda S. , Weir Bryce K. A. , Macdonald R. Loch 
Published: May 2009

Object. Vasospasm after subarachnoid hemorrhage is associated with changes in modulators of vascular tone in the arterial wall and is related to the presence of erythrocyte hemolysate in the subarachnoid space. The purpose of this study was to determine the compounds in erythrocyte hemolysate that are responsible for changing smooth-muscle cell gene expression.Methods. Rat aorta smooth-muscle cells were exposed to erythrocyte hemolysate in vitro and the effects on immediate early gene messenger (m)RNA levels were determined by competitive reverse transcriptase—polymerase chain reaction.Message levels for c-fos, jun B, and c-jun were increased in the presence of hemolysate, reaching maximum expression between 30 and 60 minutes, whereas the level of jun D mRNA was unaffected. Increasing doses of hemolysate caused greater expression of c-fos and jun B, but not c-jun. Adenosine triphosphate and hemoglobin, possible spasmogens present in hemolysate, caused much smaller and more rapid increases in c-fos expression than whole hemolysate. Size fractionation showed that all of the c-fos mRNA—inducing activity of hemolysate was recovered with molecules greater than 6 kD. Following separation of hemolysate proteins by hydrophobic interaction chromatography, only one of the three fractions had partial activity. Recombining the three fractions, however, yielded greater c-fos activation than any combination of two.Conclusions. Multiple high-molecular-weight components present in erythrocytes have synergistic effects on gene expression in smooth-muscle cells. The differences in patterns of gene induction suggest that multiple signaling pathways are activated.
Antisense preproendothelin-oligoDNA therapy for vasospasm in a canine model of subarachnoid hemorrhage
Authors: Ohkuma Hiroki , Parney Ian , Megyesi Joseph , Ghahary Aziz , Findlay J. Max 
Published: May 2009

Object. The purpose of this study is twofold: 1) to test antisense genetic techniques used in the prevention of cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH), targeting the endothelin-1 (ET-1) gene; and 2) to determine if fibrinolysis of subarachnoid clot with recombinant tissue plasminogen activator (rtPA) could enhance the effect of antisense treatment.Methods. A total of 39 dogs were studied in this experiment. Placebo (six animals), rtPA (six animals), antisense preproET-1 oligodeoxynucleotide (ASOD; five animals), or rtPA plus ASOD (combined treatment; six animals) was injected into the cisterna magna 30 minutes after a second SAH was induced on the 2nd day of the experiment. The animals were observed until Day 7, when they underwent follow-up angiography and then were killed; their basilar arteries were removed for analysis. Control animals included in this study (two animals in each group) received placebo, rtPA, ASOD, or rtPA plus ASOD without induction of SAH, or rtPA with mismatched (nonsense) preproET-1 oligodeoxynucleotide following SAH. Six additional dogs were analyzed earlier following SAH.Dogs that received placebo developed severe vasospasm (51 ± 8% of baseline caliber). Administration of ASOD alone resulted in a mild reduction in vasospasm (64 ± 13% of baseline caliber) and rtPA alone resulted in a moderate reduction in vasospasm (81 ± 5% of baseline caliber); however, the combined therapy of rtPA plus ASOD almost completely prevented vasospasm (95 ± 6% of baseline caliber), which was significantly different from all other groups (p < 0.05). Morphological analysis of the basilar arteries yielded results similar to angiography with respect to vasospasm severity. The ASOD treatment combined with rtPA resulted in reduced ET-1 expression, as demonstrated by immunohistochemical staining of the arteries, and reduced preproET-1 levels on Day 4, as measured by reverse transcription—polymerase chain reaction. Nonsense DNA sequences had no effect on the vessels.Conclusions. Antisense preproET-1 oligodeoxynucleotide treatment, when combined with clot lysis caused by rtPA, reduced vasospasm in the canine model of SAH, and this effect appeared to be related to reduced ET-1 synthesis. The results of this experiment support a causative role for ET-1 early in the course of vasospasm development in dogs. The apparent additive therapeutic effects of antisense and fibrinolytic treatments could be due to clot lysis, which allows better delivery of oligodeoxynucleotides to arteries within the subarachnoid space.
Treatment of intracranial gliomas with bone marrow—derived dendritic cells pulsed with tumor antigens
Authors: Liau Linda M. , Black Keith L. , Prins Robert M. , Sykes Steven N. , DiPatre Pier-Luigi , Cloughesy Timothy F. , Becker Donald P. , Bronstein Jeff M. 
Published: May 2009

Object. An approach toward the treatment of intracranial gliomas was developed in a rat experimental model. The authors investigated the ability of “professional” antigen-presenting cells (dendritic cells) to enhance host antitumor immune responses when injected as a vaccine into tumor-bearing animals.Methods. Dendritic cells, the most potent antigen-presenting cells in the body, were isolated from rat bone marrow precursors stimulated in vitro with granulocyte—macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Cultured cell populations were confirmed to be functional antigen-presenting cells on the basis of expressed major histocompatibility molecules, as analyzed by fluorescence-activated cell sorter cytofluorography. These dendritic cells were then pulsed (cocultured) ex vivo with acid-eluted tumor antigens from 9L glioma cells. Thirty-eight adult female Fischer 344 rats harboring 7-day-old intracranial 9L tumors were treated with three weekly subcutaneous injections of either control media (10 animals), unpulsed dendritic cells (six animals), dendritic cells pulsed with peptides extracted from normal rat astrocytes (10 animals), or 9L tumor antigen—pulsed dendritic cells (12 animals). The animals were followed for survival. At necropsy, the rat brains were removed and examined histologically, and spleens were harvested for cell-mediated cytotoxicity assays.The results indicate that tumor peptide-pulsed dendritic cell therapy led to prolonged survival in rats with established intracranial 9L tumors implanted 7 days prior to the initiation of vaccine therapy in vivo. Immunohistochemical analyses were used to document a significantly increased perilesional and intratumoral infiltration of CD8+ and CD4+ T cells in the groups treated with tumor antigen—pulsed dendritic cells compared with the control groups. In addition, the results of in vitro cytotoxicity assays suggest that vaccination with these peptide-pulsed dendritic cells can induce specific cytotoxic T lymphocytes against 9L tumor cells.Conclusions. Based on these results, dendritic antigen-presenting cells pulsed with acid-eluted peptides derived from autologous tumors represent a promising approach to the immunotherapy of established intracranial gliomas, which may serve as a basis for designing clinical trials in patients with brain tumors.
Hemodynamic characterization of intracranial pressure plateau waves in head-injured patients
Authors: Czosnyka Marek , Smielewski Piotr , Piechnik Stefan , Schmidt Eric A. , Al-Rawi Pippa G. , Kirkpatrick Peter J. , Pickard John D. 
Published: May 2009

Object. Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves.Methods. One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed.The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p <0.05) and TCD pulsatility increased (p <0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury.Conclusions. The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.
Ventricular volume following third ventriculostomy
Authors: Schwartz Theodore H. , Ho Brian , Prestigiacomo Charles J. , Bruce Jeffrey N. , Feldstein Neil A. , Goodman Robert R. 
Published: May 2009

Object. Ventricular size often shows no obvious change following third ventriculostomy, particularly in the early postoperative period, making postoperative evaluation difficult without expensive and often invasive testing in patients with equivocal clinical responses. The authors hypothesized that performing careful volumetric measurements would show decreases in size within the first 3 weeks after surgery.Methods. Volumetric measurements were calculated from standard 3 × 3—mm axial computerized tomography (CT) scans obtained immediately before and 3 and 21 days after surgery. Two independent investigators measured third ventricular volume in a series of 16 patients and lateral ventricular volume in 10 of the patients undergoing stereotactically guided endoscopic third ventriculostomy for noncommunicating hydrocephalus.Fifteen patients were symptomatically improved at the time the follow-up scan was obtained. Third ventricular volume decreased in all patients by a mean of 35% (range 7.8–95.1%) and lateral ventricular volume decreased in all patients by a mean of 33% (range 4.5–80.3%). The degree of change correlated with the length of preoperative symptoms (p <0.005). The one patient who experienced no improvement showed no decrease in third ventricular volume. In seven of 10 patients, the decrease in third ventricular volume exceeded the decrease in lateral ventricular volume. Repeated measurements indicated that the 95% confidence interval for the authors' calculations varied around the mean by 2.5% for third ventricular volume and 1.2% for lateral ventricular volume. Long-term outcome was excellent, with only one case of delayed failure. The mean follow-up duration was 12 months.Conclusions. Volumetric measurements calculated from standard CT scans will show a demonstrable decrease in ventricular volume soon after successful third ventriculostomy and can be helpful in assessing patients postoperatively. Although the third ventricle may exhibit a greater decrease, the lateral ventricular measurements are more accurate. Patients with more indolent symptoms show the smallest change.
Low incidence of delayed intracerebral hemorrhage secondary to ventriculoperitoneal shunt insertion
Authors: Savitz Martin H. , Bobroff Lewis M. 
Published: May 2009

Object. Bleeding into the brain parenchyma or ventricles is an infrequently reported complication in adults who undergo insertion of a ventriculoperitoneal (VP) shunt. The purpose of this study was to establish the incidence of delayed intracerebral hemorrhage secondary to ventricular cannulation during shunting procedures.Methods. Over a 24-year period, in a series of 125 adult patients with hydrocephalus, postoperative computerized tomography scans were obtained in every case within 48 hours of shunt surgery performed by the same neurosurgeon. The rate of delayed intracerebral hematoma or intraventricular hemorrhage after VP shunt placement was documented by routine neuroradiological follow up to be 4%.Conclusions. In adult patients with no coagulopathy or occult vascular lesions, the rate of bleeding after VP shunt insertion may be low if the procedure is uncomplicated by multiple attempts at perforation, puncture of the choroid plexus, or improper placement of the tubing within the parenchyma of the brain.
Inhibition of NF2-negative and NF2-positive primary human meningioma cell proliferation by overexpression of merlin due to vector-mediated gene transfer
Authors: Ikeda Keiro , Saeki Yoshinaga , Gonzalez-Agosti Charo , Ramesh Vijaya , Chiocca E. Antonio 
Published: May 2009

Object. The absence of in vitro models of neurofibromatosis Type 2 (NF2)—defective meningiomas has limited investigative efforts to study the biological effects of this gene in the pathogenesis of these tumors. The goals of this report are to show that gene transfer vectors can efficiently express the wild-type NF2 transgene into primary meningioma cells and to determine effects on cellular proliferation.Methods. In this study, the authors have compared the transducing capacities of a retrovirus, an adenovirus, and a herpes simplex virus amplicon vector for use in primary human meningioma cells harvested from human tumors excised from patients with and without NF2. Transduction efficiencies with the latter vector approached 100% and it was selected to transfer the wild-type NF2 transgene into these cells. Western blot analysis confirmed that vector-mediated gene transfer mediated the expression of the NF2-encoded polypeptide merlin. Overexpression of merlin significantly inhibited the proliferation of both NF2-negative and NF2-positive human meningioma cells when compared to the proliferation of cells transduced with a control vector.Conclusions. This study demonstrates the feasibility of using vector-mediated gene transfer to study wild-type NF2 gene function in short-term cultures of primary human meningioma cells.