bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes
Authors: Pretto Theresa E. , Dalvi Arif , Kang Un Jung , Penn Richard D. 
Published: August 2008

Object
The aim of this study was to provide an objective assessment of deep brain stimulation (DBS) for groups of patients with mixed secondary dystonia and primary torticollis syndromes by a blinded evaluation of 13 consecutive patients who underwent ineffective medical treatment and botulinum toxin injections.

Methods
Nine patients with secondary dystonia and 4 with cranial dystonia involving prominent spasmodic torticollis were selected for a DBS implant after they underwent unsuccessful medical treatment. Preoperative videos and neurological assessments were obtained and the DBS implant was inserted into the globus pallidus internus. Postoperatively, DBS parameters were adjusted to provide optimal benefit. Postoperative videotapes and quality of life scores were obtained. Blinded randomized evaluation of videotapes was performed by a neurologist specializing in movement disorders. Videos were scored using the Unified Dystonia Rating Scale, Toronto Western Spasmodic Torticollis Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale, or Abnormal Involuntary Movement Scale. Quality of life scoring was assessed using a standardized 7-point Global Rating Scale.

Results
All 13 patients completed preoperative videotaping, medical assessment, and surgery. Optimal DBS programming was completed in 6.5 visits over 5.9 months. Seven patients reported marked improvement, 3 reported moderate improvement, 2 reported slight improvement or no change, and 1 was lost to follow-up. Examiner scores on the Global Rating Scale reflected patient self-reported scores.

Conclusions
Global subjective gains and notable objective improvement were observed in 11 of 13 patients. Although the benefits were variable and not fully predictable, they were of sufficient magnitude to justify offering the procedure when medications and botulinum toxin injections have failed.
Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice
Authors: Xiong Ye , Lu Dunyue , Qu Changsheng , Goussev Anton , Schallert Timothy , Mahmood Asim , Chopp Michael 
Published: August 2008

Object
This study was designed to investigate the beneficial effects of recombinant human erythropoietin (rhEPO) treatment of traumatic brain injury (TBI) in mice.

Methods
Adult male C57BL/6 mice were divided into 3 groups: 1) the saline group (TBI and saline [13 mice]); 2) EPO group (TBI and rhEPO [12]); and 3) sham group (sham and rhEPO [8]). Traumatic brain injury was induced by controlled cortical impact. Bromodeoxyuridine (100 mg/kg) was injected daily for 10 days, starting 1 day after injury, for labeling proliferating cells. Recombinant human erythropoietin was administered intraperitoneally at 6 hours and at 3 and 7 days post-TBI (5000 U/kg body weight, total dosage 15,000 U/kg). Neurological function was assessed using the Morris water maze and footfault tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemical evaluation.

Results
Traumatic brain injury caused tissue loss in the cortex and cell loss in the dentate gyrus (DG) as well as impairment of sensorimotor function (footfault testing) and spatial learning (Morris water maze). Traumatic brain injury alone stimulated cell proliferation and angiogenesis. Compared with saline treatment, rhEPO significantly reduced lesion volume in the cortex and cell loss in the DG after TBI and substantially improved recovery of sensorimotor function and spatial learning performance. It enhanced neurogenesis in the injured cortex and the DG.

Conclusions
Recombinant human erythropoietin initiated 6 hours post-TBI provided neuroprotection by decreasing lesion volume and cell loss as well as neurorestoration by enhancing neurogenesis, subsequently improving sensorimotor and spatial learning function. It is a promising neuroprotective and neurorestorative agent for TBI and warrants further investigation.
Endoscopic anatomy of the fourth ventricle
Authors: Longatti Pierluigi , Fiorindi Alessandro , Feletti Alberto , D'Avella Domenico , Martinuzzi Andrea 
Published: August 2008

Object
Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the “inside” view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery.

Methods
The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation.

Results
The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen.

Conclusions
On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle.
Magnetic resonance imaging for quantitative flow measurement in infants with hydrocephalus: a prospective study
Authors: Leliefeld Paul H. , Gooskens Rob H. J. M. , Vincken Koen L. , Ramos Lino M. P. , van der Grond Jeroen , Tulleken Cees A. F. , Kappelle L. Jaap , Hanlo Patrick W. 
Published: August 2008

Object
Raised intracranial pressure (ICP) that is associated with hydrocephalus may lead to alterations in cerebral hemodynamics and ischemic changes in the brain. In infants with hydrocephalus, defining the right moment for surgical intervention based on clinical signs alone can sometimes be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. Furthermore, when sutures are closed, ICP does not always correlate with the size of the ventricles or with the clinical signs or symptoms. In this study the authors investigated whether cerebral blood flow (CBF) can be measured by using quantitative MR angiography in infants with progressive hydrocephalus. In addition, the authors investigated the relationship between CBF and ICP, before and after cerebrospinal fluid (CSF) diversion.

Methods
Fifteen infants with progressive hydrocephalus (age range 1 day–7 months) were examined. All patients underwent anterior fontanel pressure measurement, MR angiography, and mean arterial blood pressure measurements before and after CSF diversion. Brain volume was measured to compensate for the physiological increase in CBF during brain maturation in infants.

Results
The mean preoperative ICP was 19.1 ± 8.4 cm H2O (± standard deviation). The mean postoperative ICP was 6.7 ± 4.0 cm H2O (p < 0.005). The mean preoperative CBF was 25.7 ± 11.3 ml/100 cm3 brain/min. After CSF diversion, CBF increased to 50.1 ± 12.1 ml/100 cm3 brain/min (p < 0.005). The mean arterial blood pressure did not change after surgical intervention.

Conclusions
Magnetic resonance imaging can be used to measure CBF in infants with hydrocephalus. Raised ICP was related to a decrease in CBF. After CSF diversion, CBF and ICP improved to values within the normal range.
Magnetic field interactions in adjustable hydrocephalus shunts
Authors: Lavinio Andrea , Harding Sally , Van Der Boogaard Floor , Czosnyka Marek , Smielewski Peter , Richards Hugh K. , Pickard John D. , Czosnyka Zofia H. 
Published: August 2008

Object
Exposing patients with ventricular shunts to magnetic fields and MR imaging procedures poses a significant risk of unintentional changes in shunt settings. Shunt valves can also generate considerable imaging artifacts. The purpose of this study was to determine the magnetic field safety and MR imaging compatibility of 5 adjustable models of hydrocephalus shunts.

Methods
The Codman Hakim (regular and with SiphonGuard), Miethke ProGAV, Medtronic Strata, Sophysa Sophy and Polaris programmable valves were tested in a low-intensity magnetic field, and then translational attraction (TA), magnetic torque (MT), and volume of artifacts on T1-weighted spin echo (SE) and gradient echo (GE) pulse sequences in a 3-T MR imaging unit were measured.

Results
The ProGAV and Polaris valves were immune to unintentional reprogramming by magnetic fields up to 3 T. Other valves randomly changed settings, starting from the intensity of field: Sophy valve 24 mT, Strata valve 30 mT, and both Codman Hakim programmable valves from 42 mT. Shunt performances in the 3-T MR imaging unit are reported in the order of compatibility: 1) Codman Hakim regular, TA = 0.005 N, MT = 0.000 Nm, GE = 30 cm3, SE = 2 cm3; 2) Miethke ProGAV, TA = 0.001 N, MT = 1.4 × 10−3 Nm, GE = 231 cm3, SE = 13 cm3; 3) Codman Hakim with SiphonGuard, TA = 0.005 N, MT = 2.3 × 10−3 Nm, GE = 233 cm3, SE = 19 cm3; 4) Medtronic Strata, TA = 0.27 N, MT = 18.0 × 10−3 Nm, GE = 484 cm3, SE = 86 cm3; 5) Sophysa Sophy, TA = 0.82 N, MT = 38.9 × 10−3 Nm, GE = 758 cm3, SE = 72 cm3; and 6) Sophysa Polaris, TA = 0.80 N, MT = 39.6 × 10−3 Nm, GE = 954 cm3, SE = 100 cm3.

Conclusions
All valves, with the exception of the Polaris and ProGAV models, are prone to unintentional reprogramming when exposed to heterogeneous magnetic fields stronger than 40 mT. All tested valves can be considered safe for 3-T MR imaging. All valves generated a distortion of the MR image, especially the GE sequences.
The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon‐α activity and low tumor necrosis factor α levels in patients with lupus
Authors: Kariuki Silvia N. , Crow Mary K. , Niewold Timothy B. 
Published: August 2008

AbstractObjectiveThe C1858T polymorphism in PTPN22 has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon‐α (IFNα) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the PTPN22 risk variant may shift serum cytokine profiles to higher IFNα activity, resulting in risk of disease.MethodsIFNα was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor α (TNFα) was measured by enzyme‐linked immunosorbent assay. The rs2476601 single‐nucleotide polymorphism in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFNα predominant, IFNα and TNFα correlated, TNFα predominant, and both IFNα and TNFα low).ResultsSLE patients carrying the risk allele of PTPN22 had higher serum IFNα activity than patients lacking the risk allele (P = 0.027). TNFα levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFNα‐predominant and IFNα and TNFα‐correlated groups as compared with patients in the TNFα‐predominant and both IFNα and TNFα‐low groups (P = 0.001). Twenty‐five percent of male patients carried the risk allele, compared with 10% of female patients (P = 0.024); however, cytokine skewing was similar in both sexes.ConclusionThe autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFNα activity and lower TNFα levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele.
Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis
Authors: Hamada Takashi , Torikai Motofumi , Kuwazuru Ai , Tanaka Motoyuki , Horai Naoto , Fukuda Takeshi , Yamada Shingo , Nagayama Shinichi , Hashiguchi Kanehisa , Sunahara Nobuhiko , Fukuzaki Koichiro , Nagata Ryoichi , Komiya Setsuro , Maruyama Ikuro , Fukuda Takeo , Abeyama Kazuhiro 
Published: August 2008

AbstractObjectiveTissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB‐1) released from injured cells also has a role in arthritis development. This study was thus undertaken to investigate the hypothesis that extracellular HMGB‐1 may be a coupling factor between hypoxia and inflammation in arthritis.MethodsConcentrations of tumor necrosis factor α, interleukin‐6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, and HMGB‐1 were measured in synovial fluid (SF) samples from patients with inflammatory arthropathy (rheumatoid arthritis and pseudogout) and patients with noninflammatory arthropathy (osteoarthritis). The localization of tissue hypoxia and HMGB‐1 was also examined in animal models of collagen‐induced arthritis (CIA). In cell‐based experiments, the effects of hypoxia on HMGB‐1 release and its associated cellular events (i.e., protein distribution and cell viability) were studied.ResultsIn SF samples from patients with HMGB‐1–associated inflammatory arthropathy (i.e., samples with HMGB‐1 levels >2 SD above the mean level in samples from patients with noninflammatory arthropathy), concentrations of HMGB‐1 were significantly correlated with those of lactic acid, a marker of tissue hypoxia. In CIA models in which the pathologic phenotype could be attenuated by HMGB‐1 neutralization, colocalization of HMGB‐1 with tissue hypoxia in arthritis lesions was also observed. In cell‐based experiments, hypoxia induced significantly increased levels of extracellular HMGB‐1 by the cellular processes of secretion and/or apoptosis‐associated release, which was much more prominent than the protein release in necrotic cell injury potentiated by oxidative stress.ConclusionThese findings indicate that tissue hypoxia and its resultant extracellular HMGB‐1 might play an important role in the development of arthritis.
Repression of chondrogenesis through binding of notch signaling proteins HES‐1 and HEY‐1 to N‐box domains in the COL2A1 enhancer site
Authors: Grogan Shawn P. , Olee Tsaiwei , Hiraoka Koji , Lotz Martin K. 
Published: August 2008

AbstractObjectiveNotch signaling is implicated in the repression of mesenchymal stem cell (MSC) chondrogenic differentiation. The purpose of this study was to examine the mechanism of this repression and how it is modulated to permit chondrogenesis.MethodsNotch intracellular domain (NICD) protein levels were monitored via Western blotting throughout chondrogenic differentiation of human MSCs in pellet cultures. Overexpression of Notch signaling components and their effect on chondrogenesis was achieved by transfecting plasmids coding for NICD, HES‐1, and HERP‐2/HEY‐1. COL2A1 and AGGRECAN expression was monitored via quantitative polymerase chain reaction analysis. Chromatin immunoprecipitation (ChIP) was used to test whether HES‐1 and HEY‐1 bind putative N‐box domains in intron 1 of COL2A1.ResultsHigh levels of NICD proteins were reduced during chondrogenesis of human MSCs, and this was mediated by transforming growth factor β3 (TGFβ3). COL2A1 gene expression was repressed following overexpression of NICD (2‐fold) and HES‐1 (3‐fold) and was markedly repressed by overexpression of HEY‐1 (80‐fold). HEY‐1 repressed AGGRECAN expression 10‐fold, while NICD and HES‐1 had no effect. We identified 2 putative N‐box domains adjacent to, and part of, the SOX9 enhancer binding site located in intron 1 of COL2A1. ChIP studies showed that endogenous HES‐1 and HEY‐1 bound to these sites. Transducin‐like enhancer, the HES‐1 corepressor protein, was displaced during chondrogenic differentiation and following TGFβ3 treatment.ConclusionThese results reveal novel mechanisms by which Notch signaling represses gene expression. Notch signaling proteins act on the SOX9 binding site in the COL2A1 enhancer and prevent SOX9‐mediated transcriptional activation of COL2A1 and, thus, chondrogenic differentiation.
Ocrelizumab, a humanized anti‐CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I/II randomized, blinded, placebo‐controlled, dose‐ranging study
Authors: Genovese Mark C. , Kaine Jeffrey L. , Lowenstein Mitchell B. , Giudice José Del , Baldassare Andrew , Schechtman Joy , Fudman Edward , Kohen Michael , Gujrathi Sheila , Trapp Robert G. , Sweiss Nadera J. , Spaniolo Greg , Dummer Wolfgang ,   ACTION Study Group
Published: August 2008

AbstractObjectiveOcrelizumab, a humanized anti‐CD20 monoclonal antibody, was studied in a first‐in‐human trial in rheumatoid arthritis (RA) patients receiving concomitant methotrexate (MTX).MethodsThe ACTION trial was a combined phase I/II study of placebo plus MTX versus ocrelizumab plus MTX in 237 RA patients (intent‐to‐treat population). During phase I, 45 patients were treated with 1 of 5 escalating doses of study drug (infusions on days 1 and 15, 10–1,000 mg per each infusion). An additional 192 patients were randomized during phase II. Eligible patients had active disease, an inadequate response to treatment with at least MTX, rheumatoid factor positivity, and elevated levels of acute‐phase reactants. The total study duration was 72 weeks. B cell pharmacodynamics over time was investigated.ResultsBaseline demographics were similar among the treatment groups. Based on the entire 72‐week data set, the incidence of serious adverse events in the ocrelizumab‐treated patients was 17.9%, as compared with 14.6% in placebo‐treated patients. The incidence of serious infections was 2.0% in all ocrelizumab‐treated patients and 4.9% in placebo‐treated patients. Infusion‐associated adverse events were mostly grade 1 or grade 2 and were more frequent around the time of the first infusion. No serious infusion‐associated adverse events were reported in the ocrelizumab group. Evidence of clinical activity was observed at all doses evaluated. Peripheral B cell depletion after infusion was rapid at all doses, with earlier repletion of B cells at doses of 10 mg and 50 mg. Human anti‐human antibodies were detected in 19% and 10%, respectively, of those receiving 10 mg and 50 mg of ocrelizumab, compared with 0–5% of those receiving 200, 500, and 1,000 mg.ConclusionOcrelizumab therapy in combination with MTX was well tolerated. Doses of 200 mg (2 infusions) and higher showed better clinical responses, better reduction of C‐reactive protein levels, and very low immunogenicity.
Correlation of COL10A1 induction during chondrogenesis of mesenchymal stem cells with demethylation of two CpG sites in the COL10A1 promoter
Authors: Zimmermann Peter , Boeuf Stéphane , Dickhut Andrea , Boehmer Sandra , Olek Sven , Richter Wiltrud 
Published: August 2008

AbstractObjectiveHuman articular chondrocytes do not express COL10A1 and do not undergo hypertrophy except in close vicinity to subchondral bone. In contrast, chondrocytes produced in vitro from mesenchymal stem cells (MSCs) show premature COL10A1 expression and cannot form stable ectopic cartilage transplants, which indicates that they may be phenotypically unstable and not suitable for treatment of articular cartilage lesions. CpG methylation established during natural development may play a role in suppression of COL10A1 expression and hypertrophy in human articular chondrocytes. This study was undertaken to compare gene methylation patterns and expression of COL10A1 and COL2A1 in chondrocyte and MSC populations, in order to determine whether failed genomic methylation patterns correlate with an unstable chondrocyte phenotype after chondrogenesis of MSCs.MethodsCOL10A1 and COL2A1 regulatory gene regions were computationally searched for CpG‐rich regions. CpG methylation of genomic DNA from human articular chondrocytes, MSCs, and MSC‐derived chondrocytes was analyzed by Combined Bisulfite Restriction Analysis and by sequencing of polymerase chain reaction fragments amplified from bisulfite‐treated genomic DNA.ResultsThe CpG island around the transcription start site of COL2A1 was unmethylated in all cell groups independent of COL2A1 expression, while 9 tested CpG sites in the sparse CpG promoter of COL10A1 were consistently methylated in human articular chondrocytes. Induction of COL10A1 expression during chondrogenesis of MSCs correlated with demethylation of 2 CpG sites in the COL10A1 promoter.ConclusionOur findings indicate that methylation‐based COL10A1 gene silencing is established in cartilage tissue and human articular chondrocytes. Altered methylation levels at 2 CpG sites of COL10A1 in MSCs and their demethylation during chondrogenesis may facilitate induction of COL10A1 as observed during in vitro chondrogenesis of MSCs.
Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish
Authors: McArdle Patrick F. , Parsa Afshin , Chang Yen‐Pei C. , Weir Matthew R. , O'Connell Jeffery R. , Mitchell Braxton D. , Shuldiner Alan R. 
Published: August 2008

AbstractObjectiveUric acid is the primary end product of purine metabolism. Increased serum uric acid levels have been associated with gouty arthritis as well as with a variety of cardiovascular‐related phenotypes. This study was undertaken to investigate associations between uric acid levels and single‐nucleotide polymorphisms (SNPs).MethodsA 500,000‐SNP genome‐wide association study of serum uric acid levels was performed in a cohort of Old Order Amish from Lancaster County, Pennsylvania.ResultsThe scan confirmed a previously identified region on chromosome 4 to be strongly associated with uric acid levels (P = 4.2 × 10−11 for rs10489070). Followup genotyping revealed that a nonsynonymous coding SNP (Val253Ile; rs16890979) in GLUT9 was most strongly associated with uric acid levels, with each copy of the minor allele associated with a decrease of 0.47 mg/dl in the uric acid level (95% confidence interval 0.31–0.63 [P = 1.43 × 10−11]). The effect of this variant tended to be stronger in women than in men (P = 0.16 for sex–genotype interaction). The genotype effect was not modified by the inclusion of several cardiovascular risk factors, suggesting that GLUT9 is directly related to uric acid homeostasis. The SNP identified in the genome‐wide scan in the Amish population (rs10489070) was also significantly associated with gout in the Framingham Heart Study (P = 0.004).ConclusionOur findings indicate that GLUT9, which is expressed in the kidney, may be a novel regulator of uric acid elimination and that a common nonsynonymous variant in this gene contributes to abnormalities in uric acid homeostasis and gout.