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2.
World Neurosurg ; 176: 74-80, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36934870

ABSTRACT

OBJECTIVE: A cerebrospinal fluid (CSF) venous fistula (CVF) is an aberrant connection between the subarachnoid space and a vein resulting in CSF loss. The presentation and management of CVF with cognitive decline is incompletely understood. METHODS: A systematic review was completed following the PRISMA guidelines. Articles that included at least 1 case of imaging-confirmed CVF with details on patient treatment were included. A separate review of cases of patients with spontaneous intracranial hypotension (SIH) with frontotemporal dementia (FTD) or dementia symptoms was also completed. RESULTS: Ten CVF articles (69 patients; average age, 51.5 years) and 5 SIH with FTD or dementia articles (n = 41; average age, 55.9 years) were identified. Only 1 patients with CVF with cognitive abnormalities was identified. The most common symptom was headache in both reviews. Brain sag was identified in all patients, whereas CSF leak was identified in only 2 patients with SIH with FTD or dementia (4.9%). An epidural blood or fibrin glue patch was used in all patients with CVF and in 33 patients with SIH with FTD or dementia. Fifty-five patients with CVF (79.7%) and 27 patients with SIH with FTD or dementia (65.9%) had surgery. CONCLUSIONS: The 2 cases and literature reviews show the difficulty in diagnosis and treatment of CVF with cognitive decline. Novel imaging techniques should be used in patients with cognitive decline in whom a CSF leak is suspected. Transvenous embolization or surgery should be considered before patching for treatment of CVF-induced brain sag and resulting dementia.


Subject(s)
Cognitive Dysfunction , Fistula , Frontotemporal Dementia , Intracranial Hypotension , Humans , Middle Aged , Cerebrospinal Fluid Leak , Intracranial Hypotension/therapy , Cognitive Dysfunction/etiology , Magnetic Resonance Imaging
3.
Acta Oncol ; 60(11): 1392-1398, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34213401

ABSTRACT

BACKGROUND: Survivors of pediatric brain tumors are susceptible to neurovascular disease after radiotherapy, with dose to the chiasm or Circle of Willis (CW) as risk factors. The aims of this study were to develop a delineation atlas of neurovascular structures, to investigate the doses to these structures in relation to tumor location and to investigate potential dose surrogates for the CW dose. MATERIAL AND METHODS: An atlas of the CW, the large intracranial arteries and the suprasellar cistern (SC) was developed and validated. Thirty proton plans from previously treated pediatric brain tumor patients were retrieved and grouped according to tumor site: 10 central, 10 lateralized, and 10 posterior fossa tumors. Based on the atlas, neurovascular structures were delineated and dose metrics (mean dose (Dmean) and maximal dose (Dmax)) to these structures and the already delineated chiasm were evaluated. The agreement between dose metrics to the CW vs. chiasm/SC was investigated. The minimal Hausdorff distance (HDmin) between the target and SC was correlated with the SC Dmean. RESULTS: The median Dmean/Dmax to the CW were 53 Gy(RBE)/55 Gy(RBE) in the central tumors, 18 Gy(RBE)/25 Gy(RBE) in the lateralized tumors and 30 Gy(RBE)/49 Gy(RBE) in the posterior fossa tumors. There was a good agreement between the Dmax/Dmean to the CW and the SC for all cases (R2=0.99), while in the posterior fossa group, the CW Dmax was underestimated when using the chiasm as surrogate (R2=0.76). Across all patients, cases with HDmin < 10 mm between the target and the SC received the highest SC Dmean. CONCLUSION: The pattern of dose to neurovascular structures varied with the tumor location. For all locations, SC doses could be used as a surrogate for CW doses. A minimal distance larger than 10 mm between the target and the SC indicated a potential for neurovascular dose sparing.


Subject(s)
Brain Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Brain Neoplasms/radiotherapy , Child , Circle of Willis , Humans , Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
4.
BMC Cancer ; 19(1): 101, 2019 01 23.
Article in English | MEDLINE | ID: mdl-30674294

ABSTRACT

Following publication of the original article [1], we have been notified that the tagging of one of the author names was done incorrectly in the XML version of the paper. The online and pdf versions of this paper are not affected by the change. Original and corrected tagging can be seen below. The original article has been corrected.

5.
BMC Cancer ; 18(1): 43, 2018 01 10.
Article in English | MEDLINE | ID: mdl-29316898

ABSTRACT

BACKGROUND: The circadian clock is the basis for biological time keeping in eukaryotic organisms. The clock mechanism relies on biochemical signaling pathways to detect environmental stimuli and to regulate the expression of clock-controlled genes throughout the body. MAPK signaling pathways function in both circadian input and output pathways in mammals depending on the tissue; however, little is known about the role of p38 MAPK, an established tumor suppressor, in the mammalian circadian system. Increased expression and activity of p38 MAPK is correlated with poor prognosis in cancer, including glioblastoma multiforme; however, the toxicity of p38 MAPK inhibitors limits their clinical use. Here, we test if timed application of the specific p38 MAPK inhibitor VX-745 reduces glioma cell invasive properties in vitro. METHODS: The levels and rhythmic accumulation of active phosphorylated p38 MAPK in different cell lines were determined by western blots. Rhythmic luciferase activity from clock gene luciferase reporter cells lines was used to test the effect of p38 MAPK inhibition on clock properties as determined using the damped sine fit and Levenberg-Marquardt algorithm. Nonlinear regression and Akaike's information criteria were used to establish rhythmicity. Boyden chamber assays were used to measure glioma cell invasiveness following time-of-day-specific treatment with VX-745. Significant differences were established using t-tests. RESULTS: We demonstrate the activity of p38 MAPK cycles under control of the clock in mouse fibroblast and SCN cell lines. The levels of phosphorylated p38 MAPK were significantly reduced in clock-deficient cells, indicating that the circadian clock plays an important role in activation of this pathway. Inhibition of p38 MAPK activity with VX-745 led to cell-type-specific period changes in the molecular clock. In addition, phosphorylated p38 MAPK levels were rhythmic in HA glial cells, and high and arrhythmic in invasive IM3 glioma cells. We show that inhibition of p38 MAPK activity in IM3 cells at the time of day when the levels are normally low in HA cells under control of the circadian clock, significantly reduced IM3 invasiveness. CONCLUSIONS: Glioma treatment with p38 MAPK inhibitors may be more effective and less toxic if administered at the appropriate time of the day.


Subject(s)
CLOCK Proteins/genetics , Circadian Clocks/genetics , Glioblastoma/drug therapy , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Cell Lineage/drug effects , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Luciferases , Mice , Neoplasm Invasiveness/genetics , Phosphorylation , Pyridazines/administration & dosage , Pyrimidines/administration & dosage , Signal Transduction/genetics , p38 Mitogen-Activated Protein Kinases/genetics
6.
Curr Biol ; 26(24): 3288-3302, 2016 12 19.
Article in English | MEDLINE | ID: mdl-27889261

ABSTRACT

Although the role of NF-κB-inducing kinase (NIK) in immunity is well established, its relevance in cancer is just emerging. Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to promote cell invasion. We show that NIK is localized to mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes mitochondrial fission, velocity, and directional migration, resulting in subcellular distribution of mitochondria to the periphery of migrating cells. Moreover, NIK is required for recruitment of Drp1 to mitochondria, forms a complex with Drp1, and regulates Drp1 phosphorylation at Ser-616 and dephosphorylation at Ser-637. Consistent with a role for NIK in regulating mitochondrial dynamics, we demonstrate that Drp1 is required for NIK-dependent, cytokine-induced invasion. Importantly, using MEFs, we demonstrate that the established downstream mediators of NIK signaling, IκB kinase α/ß (IKKα/ß) and NF-κB, are not required for NIK to regulate cell invasion, Drp1 mitochondrial localization, or mitochondrial fission. Our results establish a new paradigm for IKK-independent NIK signaling and significantly expand the current dogma that NIK is predominantly cytosolic and exclusively regulates NF-κB activity. Overall, these findings highlight the importance of NIK in tumor pathogenesis and invite new therapeutic strategies that attenuate mitochondrial dysfunction through inhibition of NIK and Drp1.


Subject(s)
Fibroblasts/metabolism , Mitochondria/metabolism , Neoplasm Invasiveness , Protein Serine-Threonine Kinases/metabolism , Protein Transport/physiology , Animals , Cell Line, Tumor , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic/physiology , Humans , Mice , Protein Serine-Threonine Kinases/genetics , NF-kappaB-Inducing Kinase
7.
Oncogenesis ; 5(6): e231, 2016 Jun 06.
Article in English | MEDLINE | ID: mdl-27270613

ABSTRACT

A growing body of evidence implicates the noncanonical NF-κB pathway as a key driver of glioma invasiveness and a major factor underlying poor patient prognoses. Here, we show that NF-κB-inducing kinase (NIK/MAP3K14), a critical upstream regulator of the noncanonical NF-κB pathway, is both necessary and sufficient for cell-intrinsic invasion, as well as invasion induced by the cytokine TWEAK, which is strongly associated with tumor pathogenicity. NIK promotes dramatic alterations in glioma cell morphology that are characterized by extensive membrane branching and elongated pseudopodial protrusions. Correspondingly, NIK increases the phosphorylation, enzymatic activity and pseudopodial localization of membrane type-1 matrix metalloproteinase (MT1-MMP/MMP14), which is associated with enhanced tumor cell invasion of three-dimensional collagen matrices. Moreover, NIK regulates MT1-MMP activity in cells lacking the canonical NF-κB p65 and cRel proteins. Finally, increased expression of NIK is associated with elevated MT1-MMP phosphorylation in orthotopic xenografts and co-expression of NIK and MT1-MMP in human tumors is associated with poor glioma patient survival. These data reveal a novel role of NIK to enhance pseudopodia formation, MT1-MMP enzymatic activity and tumor cell invasion independently of p65. Collectively, our findings underscore the therapeutic potential of approaches targeting NIK in highly invasive tumors.

8.
Anticancer Res ; 35(6): 3209-15, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26026080

ABSTRACT

BACKGROUND/AIM: Novel treatment strategies aiming to eliminate or attenuate the invasive phenotype of glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, could offer a profound therapeutic benefit to patients. We previously demonstrated one method to create invasive sub-populations of GBM cells (IM3 cells) and a positive regulatory role for the miR-143/-145 locus in enhancing the invasion of GBM cells. Herein, we investigated the correlation between miR-145 and srGAP1 (SLIT-ROBO Rho GTPase-activating protein1) that is purported to be a target of miR-145 and involved in migration and invasion. MATERIALS AND METHODS: IM3 cells were created by a serial selection by using Boyden chambers®. Antisense-miR-145 was transfected into IM3 cells by using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were employed to analyze the expression of srGAP1. RESULTS: The invasiveness of U87-IM3 and U251-IM3 is attenuated by transfection of antisense miR-145. In addition, srGAP1 was down-regulated in U87-IM3 and U251-IM3 cells compared to parental cells. CONCLUSION: The elevated miR-145 present in invasive glioblastoma cells (IM3 cells) targets and down-regulated srGAP1, thereby allowing downstream G-proteins to remain in their active state and promote the observed invasive phenotype.


Subject(s)
Brain Neoplasms/genetics , GTPase-Activating Proteins/biosynthesis , Glioblastoma/genetics , MicroRNAs/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Humans , MicroRNAs/antagonists & inhibitors , MicroRNAs/biosynthesis , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology
9.
Article in English | MEDLINE | ID: mdl-24348691

ABSTRACT

The objective of this study was to assess spiritual needs of patients with fibromyalgia syndrome (FMS) and to evaluate correlations with disease and health associated variables. Using a set of standardized questionnaires (i.e., Spiritual Needs Questionnaire, Fibromyalgia Impact Questionnaire, SF-36's Quality of Life, Brief Multidimensional Life Satisfaction Scale, etc.), we enrolled 141 patients (95% women, mean age 58 ± 10 years). Here, needs for inner peace and giving/generativity scored the highest, while existential needs and religious needs scored lowest. Particularly inner peace needs and existential needs correlated with different domains of reduced mental health, particularly with anxiety, the intention to escape from illness, and psychosocial restrictions. Thirty-eight percent of the patients stated needs to be forgiven and nearly half to forgive someone from their past life. Therefore, the specific spiritual needs of patients with chronic diseases should be addressed in clinical care in order to identify potential therapeutic avenues to support and stabilize their psychoemotional situation.

10.
Lung Cancer ; 82(2): 340-5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24007627

ABSTRACT

UNLABELLED: Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n = 27), 80-100 Karnofsky PS (n = 27), adenocarcinoma (n = 20), stage IV (n = 30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p = 0.05). Using a linear combination of the miR CT values with Cox's regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n = 18) and poor (n = 20) prognosis with respective median survival times of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p < 0.001; hazard ratio 21.1, 95% CI 4.7-94.9). CONCLUSIONS: miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , MicroRNAs/genetics , Transcriptome , Adult , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
11.
World Neurosurg ; 79(3-4): 558-67, 2013.
Article in English | MEDLINE | ID: mdl-22120374

ABSTRACT

BACKGROUND: Neurocysticercosis (NCC) is the most common worldwide parasitic infection of the central nervous system, and ventricular cysts are particularly problematic, carrying the risk of acute obstructive hydrocephalus. Herein, we present a typical case in which complete resection was possible and explore the evidence supporting the use of postoperative oral antihelminthic therapy. METHODS: We performed a systematic review of the medical literature. Articles were included if they provided: 1) documentation of intraventricular disease, 2) discussion of management strategy, and 3) a presentation of outcomes. Available data were analyzed based on the primary therapy for NCC. RESULTS: Data from 264 patients were abstracted from 32 references. Of all patients undergoing surgical resection of an isolated neurocysticercal cyst, 33.5% received postoperative antihelminthic therapy, most commonly albendazole. Among patients who had undergone surgical resection of a single intraventricular lesion (as was the case with our own patient), those who received postoperative antihelminthic therapy had a significantly lower risk of developing delayed hydrocephalus (18.8%, compared to 59.1% for those who received no medical therapy) (P = 0.02). The total mortality rate in our review was 3%. CONCLUSIONS: This review produced surprising results: 1) the generous proportion of patients who underwent medical therapy as first-line treatment for intraventricular NCC (20.8%), and 2) the significant overall mortality. The data found in this review also provided for a strong consensus for the use of postresection antihelminthic therapy, and thus we elected to treat our index case with albendazole, assuming the risk to be low and the potential benefit meaningful.


Subject(s)
Anthelmintics/therapeutic use , Cerebral Ventricles/parasitology , Neurocysticercosis/drug therapy , Neurocysticercosis/surgery , Neurosurgical Procedures , Adult , Albendazole/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Combined Modality Therapy , Cysts/parasitology , Dexamethasone/therapeutic use , Female , Humans , Magnetic Resonance Imaging , Meningocele/etiology , Neurocysticercosis/mortality , Neurocysticercosis/parasitology , Postoperative Care , Treatment Outcome
12.
Mol Cancer ; 11: 32, 2012 May 14.
Article in English | MEDLINE | ID: mdl-22583806

ABSTRACT

BACKGROUND: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype. METHODS: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype. RESULTS: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10-8) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival. CONCLUSIONS: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Galectin 1/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Animals , Brain Neoplasms/mortality , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Extracellular Matrix/metabolism , Galectin 1/metabolism , Gene Expression Profiling , Glioblastoma/mortality , Humans , Mice , Mice, Nude , Neoplasm Invasiveness/genetics , Transplantation, Heterologous
13.
BMC Cancer ; 12: 143, 2012 Apr 10.
Article in English | MEDLINE | ID: mdl-22490015

ABSTRACT

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary central nervous system malignancy and its unique invasiveness renders it difficult to treat. This invasive phenotype, like other cellular processes, may be controlled in part by microRNAs - a class of small non-coding RNAs that act by altering the expression of targeted messenger RNAs. In this report, we demonstrate a straightforward method for creating invasive subpopulations of glioblastoma cells (IM3 cells). To understand the correlation between the expression of miRNAs and the invasion, we fully profiled 1263 miRNAs on six different cell lines and two miRNAs, miR-143 and miR-145, were selected for validation of their biological properties contributing to invasion. Further, we investigated an ensemble effect of both miR-143 and miR-145 in promoting invasion. METHODS: By repeated serial invasion through Matrigel®-coated membranes, we isolated highly invasive subpopulations of glioma cell lines. Phenotypic characterization of these cells included in vitro assays for proliferation, attachment, and invasion. Micro-RNA expression was compared using miRCURY arrays (Exiqon). In situ hybridization allowed visualization of the regional expression of miR-143 and miR-145 in tumor samples, and antisense probes were used investigate in vitro phenotypic changes seen with knockdown in their expression. RESULTS: The phenotype we created in these selected cells proved stable over multiple passages, and their microRNA expression profiles were measurably different. We found that two specific microRNAs expressed from the same genetic locus, miR-143 and miR-145, were over-expressed in our invasive subpopulations. Further, we also found that combinatorial treatment of these cells with both antisense-miRNAs (antimiR-143 and -145) will abrogated their invasion without decreasing cell attachment or proliferation. CONCLUSIONS: To best of our knowledge, these data demonstrate for the first time that miR-143 and miR-145 regulate the invasion of glioblastoma and that miR-143 and -145 could be potential therapeutic target for anti-invasion therapies of glioblastoma patients.


Subject(s)
Central Nervous System Neoplasms/metabolism , Glioblastoma/metabolism , MicroRNAs/metabolism , Animals , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Central Nervous System Neoplasms/pathology , Glioblastoma/pathology , Humans , Neoplasm Invasiveness , RNA, Antisense/pharmacology , Rats
14.
World Neurosurg ; 78(3-4): 318-25, 2012.
Article in English | MEDLINE | ID: mdl-22120562

ABSTRACT

BACKGROUND: Occipitocervical disease (OCD) in elderly patients will become increasingly common as the population ages. Our experience with occipitocervical fusions (OCF) in this population suggests mixed outcomes. METHODS: Twenty consecutive patients over 65 years old underwent OCF between 1995 and 2005. A retrospective review of demographic, presentation, surgical and outcome data was performed. RESULTS: Twenty patients averaging 75.3 years of age (range 65 to 91) were identified. All patients had evidence of myelopathy; however, the primary surgical indications were progressive spinal cord dysfunction (15), brainstem compression (3), and pain (2). Surgical approach was isolated posterior (9), or anterior transoral odontoidectomy followed by posterior stabilization (11). Overall, surgery improved function modestly; average modified Japanese Orthopedic Association functional score (improved 0.9 grades), average Ranawat Myelopathy Score (improved 0.4 grades), and average Nurick Myelopathy Grade (improved 0.6 grades). However, patients with poor preoperative functional assessment (Ranawat grade ≥ III) had greater neurologic improvement than those with good preoperative function, measured by Nurick grade improvement (1 vs. -0.28; P = .03) and Ranawat grade improvement (0.7 vs. -0.2; P = .03). Additionally, the posterior approach demonstrated significant improvement in Japanese Orthopedic Association functional assessment over patients with anterior/posterior approaches (2.2 vs. -0.3; P = .03), with fewer complications (posterior: 1 minor; anterior/posterior: 1 death, 2 major, 8 minor). Perioperative mortality occurred in 5%, and major morbidity in 10% of patients. CONCLUSIONS: Preventing or stabilizing neurologic deficit in patients with OCD may require OCF, despite the patient's age. In the elderly population, our data favor using the posterior approach when possible, and demonstrate greater neurologic improvement in patients with poor preoperative function.


Subject(s)
Atlanto-Axial Joint/surgery , Atlanto-Occipital Joint/surgery , Joint Instability/surgery , Spinal Fusion/methods , Spinal Stenosis/surgery , Age Factors , Aged , Aged, 80 and over , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/pathology , Atlanto-Occipital Joint/diagnostic imaging , Atlanto-Occipital Joint/pathology , Female , Humans , Joint Instability/mortality , Male , Postoperative Complications/etiology , Postoperative Complications/mortality , Radiography , Retrospective Studies , Spinal Fusion/mortality , Spinal Stenosis/mortality , Treatment Outcome
15.
J Neurosurg ; 113(6): 1284-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20433273

ABSTRACT

The authors present a unique case of a patient with communicating hydrocephalus and repeated ventriculoperitoneal shunt obstructions resulting from mucin-secreting enterogenous cell deposits at the cervicomedullary junction. Pathological examinations revealed that these cellular deposits lacked characteristic cystic architecture and the patient had no history of previous cyst with dissemination. Because of the repeated shunt obstructions and inability to surgically resect the lesion in its entirety, the authors elected radiation therapy to the cervicomedullary junction, encompassing the radiological abnormality. As of this writing, the patient has remained at neurological baseline and has not required further shunt revisions for obstruction.


Subject(s)
Hydrocephalus/etiology , Neural Tube Defects/complications , Ventriculoperitoneal Shunt/adverse effects , Endothelial Cells/pathology , Equipment Failure , Female , Humans , Hydrocephalus/surgery , Neural Tube Defects/pathology , Treatment Failure , Young Adult
16.
Neurocrit Care ; 10(2): 253-6, 2009.
Article in English | MEDLINE | ID: mdl-19224404

ABSTRACT

INTRODUCTION: The reported intracerebral hemorrhage rate due to ventriculostomy placement varies widely. As studies emerge regarding alternative techniques of ventriculostomy placement, and placement by non-neurosurgeons, further definition of the true intracerebral hemorrhage rate associated with ventriculostomy is warranted. We performed a meta-analysis of the existing literature to further elucidate the incidence of intracerebral hemorrhage due to ventriculostomy. METHODS: We performed an extensive literature search using Ovid MEDLINE and PubMed for relevant studies published after 1970. Only studies with more than 25 ventriculostomy procedures were included. Data were extracted regarding number of hemorrhages, clinically significant hemorrhages, and the use of routine post-ventriculostomy CT scanning. We performed subgroup analyses based on the use of routine post-ventriculostomy CT scanning. Chi-squared test was used to determine statistical significance. RESULTS: Overall, 102 hemorrhagic complications from 1,790 ventriculostomies were reported, a hemorrhage rate of 5.7%. Of the 102 hemorrhages, 11 were clinically significant (clinically significant hemorrhage rate = 0.61%). In studies that used routine post-placement CT scans, the hemorrhage rate was 10.06%, compared to a hemorrhage rate of 1.53% in studies in which routine CT scans were not performed (P < 0.001). Eight clinically significant hemorrhages (0.91%) were identified in the studies utilizing routine post-procedural CT scanning, compared to three clinically significant hemorrhages (0.33%) in studies without routine CT scans (P = 0.113). CONCLUSION: The overall hemorrhage risk associated with ventriculostomy placement based on the existing literature is 5.7%. Clinically significant hemorrhage due to ventriculostomy is less than 1%. Modifications of technique that might reduce hemorrhage risk, and the utility of routine post-procedural CT scanning, merit further investigation.


Subject(s)
Cerebral Hemorrhage/epidemiology , Hydrocephalus/epidemiology , Hydrocephalus/surgery , Ventriculostomy/adverse effects , Ventriculostomy/statistics & numerical data , Humans , Risk Factors
17.
J Biol Inorg Chem ; 14(1): 35-49, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18766385

ABSTRACT

Iron uptake by the ubiquitous iron-storage protein ferritin involves the oxidation of two Fe(II) ions located at the highly conserved dinuclear "ferroxidase centre" in individual subunits. We have measured X-ray absorption spectra of four mutants (K86Q, K86Q/E27D, K86Q/E107D, and K86Q/E27D/E107D, involving variations of Glu to Asp on either or both sides of the dinuclear ferroxidase site) of recombinant human H-chain ferritin (rHuHF) in their complexes with reactive Fe(II) and redox-inactive Zn(II). The results for Fe-rHuHf are compared with those for recombinant Desulfovibrio desulfuricans bacterioferritin (DdBfr) in three states: oxidised, reduced, and oxidised/Chelex-treated. The X-ray absorption near-edge region of the spectrum allows the oxidation state of the iron ions to be assessed. Extended X-ray absorption fine structure simulations have yielded accurate geometric information that represents an important refinement of the crystal structure of DdBfr; most metal-ligand bonds are shortened and there is a decrease in ionic radius going from the Fe(II) to the Fe(III) state. The Chelex-treated sample is found to be partly mineralised, giving an indication of the state of iron in the cycled-oxidised (reduced, then oxidised) form of DdBfr, where the crystal structure shows the dinuclear site to be only half occupied. In the case of rHuHF the complexes with Zn(II) reveal a surprising similarity between the variants, indicating that the rHuHf dinuclear site is rigid. In spite of this, the rHuHf complexes with Fe(II) show a variation in reactivity that is reflected in the iron oxidation states and coordination geometries.


Subject(s)
Ceruloplasmin/chemistry , Ceruloplasmin/metabolism , Desulfovibrio/chemistry , Ferric Compounds/chemistry , Ferritins/chemistry , Zinc/chemistry , Binding Sites , Ceruloplasmin/genetics , Cloning, Molecular , Crystallography, X-Ray , Genetic Variation , Humans , Models, Molecular , Molecular Conformation , Mutation , Oxidation-Reduction , Polymerase Chain Reaction , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Spectrophotometry , X-Rays
18.
Climacteric ; 10(1): 51-62, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17364605

ABSTRACT

OBJECTIVES: Sleep disturbance in polio survivors is a common complaint, yet little is known about the effects of the interaction of physical disability and menopause on sleep. The purpose of this study was to understand the relative contribution of menopause factors and disability to subjective sleep disturbance. METHODS: Participants were 465 women aged 50-65 years who had physical disabilities due to poliomyelitis. Hierarchical regression modeling was used to examine menopause (symptoms, status, hormone replacement use, ovarectomy status) and disability factors (post-polio symptoms) in sleep disturbance. RESULTS: In the final model, 19% (frequency) and 17% (severity) of sleep disturbance variance was explained. Psychological symptoms exerted the most influence (for both outcomes) followed by post-polio symptoms, vasomotor symptoms, an interaction of vasomotor and post-polio symptoms and estrogen use. For women with fewer post-polio symptoms, vasomotor symptoms exerted greater influence on sleep disturbance than for women with greater post-polio symptoms. CONCLUSIONS: Psychological symptoms had the strongest association with sleep disturbance in these women. Controlling for the influence of various menopause factors, our findings show that vasomotor symptoms were only one of several influences on sleep disturbance.


Subject(s)
Menopause/physiology , Postpoliomyelitis Syndrome/complications , Sleep Wake Disorders/etiology , Vasomotor System/physiopathology , Female , Hot Flashes/complications , Humans , Middle Aged , Regression Analysis , Severity of Illness Index , Sleep Wake Disorders/epidemiology
19.
J Sports Sci ; 25(5): 519-30, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17365539

ABSTRACT

The perception of a human actor performing movements may involve processes related to action execution. This resonance of the motor system may support observational learning and imitation, and could also explain the fact that observers'/actors' movements are disturbed by the observation of a human model making different movements (Kilner et al., 2003). In this study, we tried to specify what information available in the model's behaviour triggers this influence on an observer's behaviour. In two experiments, we had participants make horizontal or vertical arm movements while observing similar movements. In the first experiment, the observers' pattern of behaviour was affected by the observation of a human model making incongruent movements. In the second experiment, similar results were obtained with participants observing a moving dot depicting either biological or non-biological motion. Movement execution was affected differentially by biological and non-biological motion observation. These results show that an observer's behaviour is sensitive to information available in biological motion.


Subject(s)
Motion Perception/physiology , Movement/physiology , Observation , Task Performance and Analysis , Adult , Analysis of Variance , Arm/physiology , Humans , Imitative Behavior/physiology
20.
Neurosurgery ; 57(1): 25-31; discussion 25-31, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15987537

ABSTRACT

OBJECTIVE: Survival of cardiac arrest (CA) after aneurysmal subarachnoid hemorrhage (SAH) is poorly characterized. We analyzed the clinical course and outcome of patients who survived resuscitation for CA after aneurysmal SAH. METHODS: Medical records of all patients with acute SAH treated at Mayo Clinic between 1990 and 1997 were reviewed. Three hundred five consecutive patients with angiographically proven aneurysmal SAH presenting within 7 days of ictus were analyzed. CA was defined as a pulseless state, documented by medical personnel, for which resuscitation was performed. Outcome was measured with the Glasgow Outcome Scale score at longest follow-up (mean, 16 mo). RESULTS: Data from 11 patients (3.6%) who had 14 episodes of CA were analyzed. Six patients had CA before reaching the hospital and were successfully resuscitated. Nine of 14 CA episodes occurred at hemorrhage or rehemorrhage. No patient with in-hospital CA failed to be resuscitated. Overall mortality in patients who had CA (46%) was higher than that of patients without CA (15%; P = 0.019). Outcome for all patients who had CA (mean Glasgow Outcome Scale score, 2.5) was worse than for patients without CA (mean Glasgow Outcome Scale score, 3.9; P = 0.005). However, half of the survivors of CA after SAH were living independently with limited deficit at longest follow-up. CONCLUSION: Most cases of CA occur at the time of initial or recurrent SAH. Resuscitation for in-hospital CA is likely to be successful. Although CA after aneurysmal SAH is associated with significantly higher mortality, the outcome of survivors of CA is not worse than that for other patients after aneurysmal SAH.


Subject(s)
Heart Arrest/etiology , Heart Arrest/mortality , Subarachnoid Hemorrhage/complications , Survival , Adult , Angioplasty, Balloon , Female , Follow-Up Studies , Glasgow Outcome Scale/statistics & numerical data , Humans , Male , Medical Records/statistics & numerical data , Middle Aged , Retrospective Studies , Subarachnoid Hemorrhage/therapy , Treatment Outcome
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