bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis
Authors: Jacobs Lawrence D. , Cookfair Diane L. , Rudick Richard A. , Herndon Robert M. , Richert John R. , Salazar Andres M. , Fischer Jill S. , Goodkin Donald E. , Granger Carl V. , Simon Jack H. , Alam John J. , Bartoszak David M. , Bourdette Dennis N. , Braiman Jonathan , Brownscheidle Carol M. , Coats Michael E. , Cohan Stanley L. , Dougherty David S. , Kinkel Revere P. , Mass Michele K. , Munschauer Frederick E. , Priore Roger L. , Pullicino Patrick M. , Scherokman Barbara J. , Weinstock‐Guttman Bianca , Whitham Ruth H. 
Published: January 2005

AbstractThe accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta‐1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double‐blinded, placebo‐controlled, multicenter phase I11 trial of interferon beta‐la. Interferon beta‐la, 6.0 million units (30 μg), was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression (p equals; 0.02). The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta‐la‐treated group. Patients treated with interferon beta‐la also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images (pvalues ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients. There were no major adverse events related to treatment. Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images. This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis.
Human α‐tocopherol transfer protein: Gene structure and mutations in familial vitamin E deficiency
Authors: Hentati Afif , Deng Han‐Xiang , Hung Wu‐Yen , Nayer Muhammad , Ahmed M. Said , He Xiaoxuan , Tim Richard , Stumpf David A. , Siddique Teepu 
Published: January 2005

AbstractFamilial vitamin E deficiency (AVED) causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. AVED is thought to be caused by a defect in the transport of vitamin E in liver cells, which is the probable function of αtocopherol transfer protein (αTTP). We have cloned the cDNA and several genomic phage clones covering the entire human αTTP gene and determined the junctions between the five exons and four introns that composed the gene for human αTTP. Three mutations in three unrelated North American families with AVED were identified. Two mutations, 485delT and 513insTT, cause a frame shift and a premature stop codon and the third mutation 574G→A would substitute Arg192 to His in αTTP. The 2 patients with a severe form of AVED were homozygous with 485delT and 513insTT, respectively, while the patient with a mild form o f the disease was compound heterozygous with 513insTT and 574G→A. These findings have identified the underlying genetic defect in AVED and have confirmed the role of αTTP in AVED.
Risk of stroke during long‐term anticosgulant therapy in patients after myocardial infarction
Authors: Azar Aida J. , Koudstaal Peter J. , Wintzen Axel R. , Bergen Paul F. Van , Jonker Jan J. , Deckers Jaap W. 
Published: January 2005

AbstractMyocardial infarction survivors have an increased risk of stroke, which is reduced with long‐term anticoagulant therapy. However, an estimated 10‐times increase in risk of bleeding during such treatment has been reported. We evaluated the risk of stroke in patients after a myocardial infarction and examined the relationship of the risk of intracranial hemorrhage or cerebral infarction and the intensity of anticoagulant therapy. The study population consisted of 3,404 post‐myocardial infarction patients who took part in a randomized, double‐blind, placebo‐controlled trial. Patients were randomized to treatment with anticoagulants (international normalized ratio range, 2.8–4.8) or matching placebo. Mean follow‐up was more than 3 years. The incidence of stroke analyzed on “intention‐to‐treat” was 0.7 per 100 patient‐years in the anticoagulant patients against 1.2 in placebo, a hazard ratio of 0.60, with 95% confidence interval of 0.40 to 0.90. In the anticoagulation group, 15 patients had cerebral infarction and 17 an intracranial bleeding, 3 of which occurred after withdrawal of treatment. In the placebo group, the numbers were 43 and 2. Of the 14 intracranial bleeds during anticoagulation, 6 occurred at an international normalized ratio between 3.0 and 4.0 and 8 at greater than 4.0. These results confirm that long‐term anticoagulant therapy substantially reduces the risk of stroke in post‐myocardial infarction patients. The increased risk of bleeding complications associated with anticoagulant therapy is offset by a marked reduction in ischemic events. The risk of intracranial bleeding is directly related to the intensity of anticoagulant treatment.
The role of spreading depression in focal ischemia evaluated bv dffusion mapping
Authors: Takano Kentaro , Latour Lawrence L. , Formato James E. , Carano Richard A. D. , Helmer Karl G. , Hasegawa Yasuhiro , Sotak Christopher H. , Fisher Marc 
Published: January 2005

AbstractThis study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCI group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15‐minute intervals, evaluated by continuous apparent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15‐minute time epochs with a single SD episode (36.5 ± 12.9 mm3 mean ± SD) or multiple SD episodes (39.8 ± 22.3) compared with those without SD (13.9 ± 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after MCAO was significantly larger in the KCl group, with more total SDs (237.8 ± 13.8) than the NaCl group (190.5 ± 12.6) (p = 0.0001). This study demonstrates that ischemia‐related and induced SDs increase significantly ischemic lesion volume in vivo, supporting the hypothesis for a causative role of SD in extending focal ischemic injury.
Sensory nerve pathology in multifocal motor neuropathy
Authors: Corse Andrea M. , Chaudhry Vinay , Crawford Tom O. , Cornblath David R. , Kuncl Ralph W. , Griffin John W. 
Published: January 2005

AbstractThe nosological status of multifocal motor neuropathy remains controversial. The clinical and electrodiagnostic hallmarks suggest selective motor fiber involvement. In this study, we asked to what extent sensory nerves might be involved pathologically in multifocal motor neuropathy. Examination of sensory nerve biopsy specimens from II patients did reveal pathological findings in all, but they were very mild. An increased number of thinly myelinated, large‐caliber fibers was the unifying feature common to each specimen. By electron microscopy, each biopsy specimen had thinly myelinated fibers surrounded by minor onion bulbs. Active demyelination, though scant, was seen in 3 nerves. Myelinated fiber density was normal. Subperineurial edema and inflammation were not present. We conclude that multifocal motor neuropathy is not an exclusively motor abnormality, although it appears to be so clinically and electrophysiologically. The frequent, albeit mild, pathological abnormalities in sensory fibers suggest that the demyelinating pathophysiology also affects sensory fibers, but to a lesser degree than motor fibers. Some investigators maintain that multifocal motor neuropathy is within the spectrum of chronic inflammatory demyelinating polyneuropathy. The very mild degree of sensory fiber involvement, the absence of inflammation or edema, and the distinctive clinical features support the concept of multifocal motor neuropathy as distinct from chronic inflammatory demyelinating polyneuropathy.
Disorders of affective and linguistic prosody in children after early unilateral brain damage
Authors: Trauner Doris A. , Ballantyne Angela , Friedland Susan , Chase Christopher 
Published: January 2005

AbstractProsody is that quality of speech that imparts meaning by changes in intonation, pitch, and stress. The right hemisphere (RH) appears to be dominant for affective prosody in adults, while the left hemisphere (LH) mediates the more linguistic aspects of nonverbal communication. Few similar studies have been reported of individuals who suffered early unilateral brain damage, when brain reorganization or plasticity might be expected to play a role in ameliorating the adverse effects of focal brain damage. In this study, comprehension and expression of affective and linguistic prosody were tested in subjects with documented unilateral brain damage of pre‐ or perinatal onset and in matched controls. Both RH‐ and LH‐lesion groups demonstrated difficulty on tasks involving expression of affective prosody, and on tests of linguistic prosody, compared with controls. Only the RH‐lesion group was impaired on an affective comprehension task. The results indicate that even after very early unilateral brain damage, prosodic deficits may be present. However, only for affective comprehension does the side of the lesion appear to determine such deficits. The findings suggest that during brain development there is not clear brain lateralization for prosody and there may be bilateral representation for these skills during early development. There may be limitations to the ability of the developing brain to reorganize after early injury.
Dynamic properties of horizontal and vertical eye movements in parkinsonian syndromes
Authors: Rottach Klaus G. , Riley David E. , DiScenna Alfred O. , Zivotofsky Ari Z. , Leigh R. John 
Published: January 2005

AbstractWe studied dynamic properties of horizontal, vertical, and oblique eye movements in 23 patients with the following parkinsonian syndromes: idiopathie parkinsonism (PD), multiple system atrophy (MSA), pure akinesia (PA), progressive supranuclear palsy (PSP), and cortical‐basal ganglionic degeneration (CBGD). Compared with age‐matched controls, only PSP patients showed slowing of saccades. Patients in all groups showed saccadic hypometria that was most marked vertically. The trajectories of saccades made to diagonal target jumps were deviated toward the horizonal plane, due to the vertical hypometria; this was most marked in PA and PSP groups. Saccade latency was only increased in the CBGD group. Sinusoidai smooth pursuit did not differentiate between controls and patients; however, with step‐ramp stimuli, pursuit eye acceleration was impaired in all patient groups compared with controls. The vestibulo‐ocular reflex, with or without visual enhancement, was similar in patients and controls. These findings indicate that (1) in parkinsonian syndromes apart from PSP, the saccade‐generating brainstem burst neurons are probably spared, but the signals that they receive, specifying the size and direction of saccades, are flawed; and (2) measurements of the gain and trajectory of oblique saccades, and initiation of smooth pursuit, may aid in diagnosing these different types of parkinsonism.
Experimental sensory neuropathy induced by sensitization with ganglioside GD1b
Authors: Kusunoki Susumu , Shimizu Jun , Chiba Atsuro , Ugawa Yoshikazu , Hitoshi Seiji , Kanazawa Ichiro 
Published: January 2005

AbstractThree of six rabbits immunized with purified GD1b developed ataxic sensory neuropathy. They laid on the floor with their limbs splayed out, and their movements were awkward; but muscle power, tonus, and superficial sensation appeared to be intact. Sciatic nerve motor conduction studies were normal. Axonal degeneration was present in the dorsal column of the spinal cord, in the dorsal roots, and in the sciatic nerve. Some of the nerve cell bodies in the dorsal root ganglia had degenerated and disappeared. No demyelinative lesions or mononuclear cell infiltrations were seen in those regions. No pathological changes were present in the other three immunized rabbits that showed no clinical symptoms. Control rabbits inoculated only with adjuvants showed neither clinical symptoms nor pathological changes. Anti‐GD1b antibody was raised in the sera from all six rabbits immunized with GD1b. The monoclonal anti‐GD1b antibody GGR12 immuno‐stained about one‐half the rabbit primary sensory neurons. Sensitization with GD1b, therefore, may cause ataxic sensory neuropathy in rabbits due to antibody‐mediated damage to the primary sensory neurons.
Relations of genetic and environmental factors in the etiology of epilepsy
Authors: Ottman Ruth , Annegers John F. , Risch Neil , Hauser W. Allen , Susser Mervyn 
Published: January 2005

AbstractWe assessed the relations of genetic and environmental factors in the etiology of epilepsy. The study population comprised 9,705 first‐degree relatives of 1,951 adults with epilepsy ascertained from voluntary organizations. We calculated standardized morbidity ratios for specific etiologies of epilepsy in the relatives of probands with the same etiologies, using population incidence rates from Rochester, MN, as the reference. Relatives of probands with idiopathic/cryptogenic epilepsy had increased risk for idiopathic/cryptogenic epilepsy and for epilepsy associated with neurological deficit presumed present at birth (cerebral palsy or mental retardation) but not for symptomatic epilepsy associated with postnatal central nervous system insults. Relatives of probands with neurodeficits had increased risks for idiopathic/ cryptogenic epilepsy. Risk for epilepsy was not increased among relatives of probands with postnatal symptomatic epilepsy. The degree of increased risk of idiopathic/cryptogenic epilepsy in relatives of probands with idiopathiclcryptogenic epilepsy diminished with increasing age of the relatives; risk was not increased at age 35 or older. These findings support the possibility of a shared genetic susceptibility to epilepsy and cerebral palsy, and suggest that the genetic contributions to postnatal symptomatic epilepsy are minimal.
Regional metabolic correlates of surgical outcomes following unilateral pallidotomy for parkinson's disease
Authors: Eidelberg D. , Moeller J. R. , Ishikawa T. , Dhawan V. , Spetsieris P. , Silbersweig D. , Stern E. , Woods R. P. , Fazzini E. , Dogali M. , Beric A. 
Published: January 2005

AbstractStereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age, 60.0 ± 6.1 years; mean Hoehn and Yahr stage, 3.8 ± 1.0) with quantitative F‐fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor scores at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p <0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p <0.01) and increases in lateral frontal metabolism (p< 0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increases in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.0005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site.
Thalamic metabolism and corticospinal tract integrity determine motor recovery in stroke
Authors: Binkofski F. , Seitz R. J. , Arnold S. , Classen J. , Benecke R. , Freund H.‐J. 
Published: January 2005

AbstractWe studied the role of remote metabolic depressions and pyramidal tract involvement regarding motor recovery following a first hemiparetic ischemic stroke. In 23 patients the regional cerebral glucose metabolism (rCMRGlu) was measured with positron emission tomography and the location and spatial extent of the stroke lesions were assessed by magnetic resonance imaging. Motor impairment during the acute and chronic stages (4 weeks after stroke) was determined by a motor score and recordings of magnetic evoked motor potentials. Twelve patients recovered significantly, whereas 11 patients retained a disabling hemiparesis. In contrast to patients with good motor recovery, rCMRGlu was severely depressed in the thalamus on the lesion side in patients with poor motor recovery. This patient group also showed more severe damage to the pyramidal tract on magnetic resonance images and a more pronounced reduction of the magnetic evoked motor potential amplitude. Neither the size of the stroke lesions nor the spatial extent of the lesional and remote rCMRGlu depressions outside the thalamus correlated with the thalamic hypometabolism and the improvement of the motor score. We conclude that preservation both of parts of the pyramidal tract and of the thalamic circuitry is a major determinant for the quality of hand motor recovery following acute brain ischemia in the adult.
Chromosome 12‐linked autosomal dominant scapuloperoneal muscular dystrophy
Authors: Wilhelmsen K. C. , Blake D. M. , Lynch T. , Mabutas J. , Vera M. De , Neystat M. , Bernstein Ba M. , Hirano M. , Gilliam T. C. , Murphy P. L. , Sola M. D. , Bonilla E. , Schotland D. L. , Hays A. P. , Rowland L. P. 
Published: January 2005

AbstractScapuloperoneal syndromes are characterized by their distribution of muscle weakness and wasting. The reported pattern of inheritance has been variable. Both neurogenic and myopathic forms of autosomally dominantly inherited scapuloperoneal syndrome have been described. It has been suggested that these are variants of other neuromuscular diseases. We examined 44 members from a family with 14 members affected with a scapuloperoneal syndrome. Physiological and histological analysis implied that this condition is predominantly myopathic. Linkage analysis was done to confirm the genetic etiology of the disease in this family and to evaluate the possibility that it is an allelic variant of other neuromuscular diseases. Genetic analysis demonstrated linkage of the disease to chromosome 12, which makes it genetically distinct from other loci known to cause neuromuscular disease. Muscle fibers with hyaline desmin‐containing cytoplasmic inclusions in combination with focal myopathic changes may be a disease‐specific morphological marker of the disease.
Gamma knife pallidotomy in advanced parkinson's disease
Authors: Friedman Joseph H. , Epstein Mel , Sanes Jerome N. , Lieberman Phillip , Cullen K. , Lindquist C. , Daamen Maxim 
Published: January 2005

AbstractPosteroventral pallidotomy as a treatment for Parkinson's disease (PD) has been the subject of increasing interest. We treated 4 nondemented patients with advanced PD, 2 with severe bradykinesia and a declining response to medication, and 2 with marked clinical fluctuations. All patients received 180 Gy delivered in one sitting to the right posteroventral pallidum site, used by Laitinen and colleagues, adjusted as needed, to avoid the optic tract. Only 1 patient changed significantly. Dyskinesia completely resolved on the side contralateral to the lesion in this patient. This same patient also became transiently demented and psychotic. The other 3 patients suffered no clearly identifiable beneficial or harmful effects. Fol‐low‐up magnetic resonance imaging scans of the brain at 1 year revealed lesions exactly where targeted although of unequal sizes. Our negative experience forces us to conclude that either larger volumes of tissue must be ablated, that physiologic monitoring is required for placing a lesion, that our subjects were poor candidates for the procedure, or that surgical ablation and radiation cause tissue damage of different types with different results.
High apolipoprotein E ε4 allele frequency in Age‐related memory decline
Authors: Blesa Rafael , Adroer Rosa , Santacruz Pilar , Ascaso Carlos , Tolosa Eduardo , Oliva Rafael 
Published: January 2005

AbstractMany studies have demonstrated a strong association between the presence of one or two ε4 alleles and Alzheimer's disease (AD), although few data are available on the apolipoprotein E (APOE) ε4 frequencies at the preclinical stages of AD. Thus, with a view to determining whether APOE genotyping could be useful in the early detection of AD, we determined the APOE allele frequencies in patients with memory complaints without dementia (age‐related memory decline, ARMD). We found an APOE ε4 allele frequency of 0.315 in the ARMD group, similar to 0.293 in the AD group, in contrast to 0.057 in the control group. Significant differences (t= −2.91, df=25,p=0.008) were found between the Alzheimer's Disease Assessment Scale (ADAS) total scores in the ARMD patients with at least one ε4 allele (mean=24.2) compared with the ARMD patients without the ε4 allele (mean= 14.7). Our results suggest that the patients with memory complaints, a high ADAS score, and the presence of one or two APOE‐4 alleles could be at high risk for developing AD. Thus, we propose that genotyping in conjunction with the ADAS scale may prove useful as diagnostic markers of AD in the presymptomatic stages.