bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syncope: A videometric analysis of 56 episodes of transient cerebral hypoxia
Authors: Lempert T. , Bauer M. , Schmidt D. 
Published: January 2005

AbstractTo investigate the clinical features of transient cerebral hypoxia, syncope was induced in 56 of 59 healthy volunteers through a sequence of hyperventilation, orthostasis, and Valsalva maneuver. All events were monitored on video by two cameras. Complete syncope with falling and loss of consciousness was observed in 42 subjects, lasting 12.1 ± 4.4 seconds. Myoclonic activity occurred in 38 of these 42 episodes (90%). The predominant movement pattern consisted of multifocal arrhythmic jerks both in proximal and distal muscles. Superposition of generalized myoclonus was common. Additional movements such as head turns, oral automatisms, and righting movements occurred in 79%. Eyes remained open throughout syncope in most subjects and initial upward deviation was common. Sixty percent reported visual and auditory hallucinations. Thirteen subjects had incomplete syncope with falls but partially preserved consciousness. These episodes were shorter and usually not accompanied by myoclonus and hallucinations. Transient amnesia and unresponsiveness without falling occurred in 1 subject.
Decreased dopamine transporters with age in healthy human subjects
Authors: Volkow N. D. , Fowler J. S. , Wang G. J. , Logan J. , Schlyer D. , MacGregor R. , Hitzemann R. , Wolf A. P. 
Published: January 2005

AbstractThe effects of aging on brain dopamine transporters was evaluated in 26 healthy male volunteers (age range, 21–63 years) using positron emission tomography and [11C]cocaine. The ratio of the distribution volume for [11C]cocaine in basal ganglia to that in cerebellum was used as a model parameter for dopamine transporter availability and showed a significant negative correlation with age (r = 0.65, p < 0.0005). This results document an age‐related decline in dopamine transporters in healthy individuals.
In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging
Authors: Husted C. A. , Matson G. B. , Adams D. A. , Goodin D. S. , Weiner M. W. 
Published: January 2005

AbstractThe goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal‐appearing white matter by evaluating the spectral broad component from phosphorus 31 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p <001) in both lesions and in normal‐appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times.
Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia
Authors: Sian Jeswinder , Dexter David T. , Lees Andrew J. , Daniel Susan , Agid Yves , Javoy‐Agid France , Jenner Peter , Marsden C. David 
Published: January 2005

AbstractReduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured in various brain areas (substantia nigra, putamen, caudate nucleus, globus pallidus, and cerebral cortex) from patients dying with Parkinson's disease, progressive supranuclear palsy, multiple‐system atrophy, and Huntington's disease and from control subjects with no neuropathological changes in substantia nigra. GSH levels were reduced in substantia nigra in Parkinson's disease patients (40% compared to control subjects) and GSSG levels were marginally (29%) but insignificantly elevated; there were no changes in other brain areas. The only significant change in multiple‐system atrophy was an increase of GSH (196%) coupled with a reduction of GSSG (60%) in the globus pallidus. The only change in progressive supranuclear palsy was a reduced level of GSH in the caudate nucleus (51%). The only change in Huntington's disease was a reduction of GSSG in the caudate nucleus (50%). Despite profound nigral cell loss in the substantia nigra in Parkinson's disease, multiple‐system atrophy, and progressive supranuclear palsy, the level of GSH in the substantia nigra was significantly reduced only in Parkinson's disease. This suggests that the change in GSH in Parkinson's disease is not solely due to nigral cell death, or entirely explained by drug therapy, for multiple‐system atrophy patients were also treated with levodopa. The altered GSH/GSSG ratio in the substantia nigra in Parkinson's disease is consistent with the concept of oxidative stress as a major component in the pathogenesis of nigral cell death in Parkinson's disease.
Voluntary movement at the elbow in spastic hemiparesis
Authors: Fellows S. J. , Kaus C. , Thilmann A. F. 
Published: January 2005

AbstractThe relative importance of hyperreflexia and paresis in disturbances of voluntary arm movement was studied in a group of patients (n = 25) with spasticity arising from a unilateral ischemic cerebral lesion. Patient performance was evaluated against data obtained from normal subjects (n = 15). Spastic patients achieved lower maximum movement velocities during flexion or extension than did normal subjects. The more marked the paresis of the elbow flexor and extensor muscles of the patients, relative to the strength of the normal subjects, the greater was this reduction in maximum velocity. For a given velocity, however, the time taken to complete a movement and the time to reach the peak velocity were normal. No relationship was found between the degree of impairment of voluntary movement and the level of passive muscle hypertonia in the antagonist. Although overactivity of the antagonist muscle may play some role in disturbance of movements made at low velocities without an opposing load, antagonist activity during movements made against a load (i.e., under more natural conditions) was at or below normal levels, even in those patients with the most marked passive muscle hypertonia. It is concluded that agonist muscle paresis, rather than antagonist muscle hypertonia, plays the dominant role in the disturbance of voluntary elbow movement following stroke.
Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus
Authors: Giannini Caterina , Dyck Peter James 
Published: January 2005

AbstractWe evaluated 433 transversely sectioned microvessels from 54 sural nerves of diabetic patients with (43) and without (11) polyneuropathy and compared the findings with those of 366 microvessels from 50 sural nerves from controls, spanning the same ages. Whereas the number of microvessels per square millimeter and lumen areas and their size distribution were not significantly different between diabetic patients and controls, striking changes of the vessel wall were found in the nerves of diabetic patients. Mural area containing reduplicated basement membranes and pericyte degeneration were significantly increased in diabetic when compared with control nerves. A very low frequency of microvessel degeneration and endothelial cell separation was also encountered but only in diabetics with polyneuropathy. The microvessel changes we have found in nerve largely confirm and strengthen our previous findings. This study provides additional strong support for the idea that the mural changes of endoneurial microvessels do not relate to aging but do relate to diabetes mellitus. The structural alterations of endoneurial microvessel mirror changes seen in diabetic retinopathy and are sufficiently severe that they may accompany and account for functional alterations of the blood–nerve barrier and endoneurial microenvironment. It remains to be shown whether and how these changes relate to the development of polyneuropathy.
Homozygous inheritance of the Machado‐Joseph disease gene
Authors: Lang Anthony E. , Rogaeva E. A. , Tsuda T. , Hutterer J. , St George‐Hyslop Peter 
Published: January 2005

AbstractWe report a patient presenting at age 16 years with postural instability and falls who developed severe generalized dystonia by the age of 20 years. He was the product of a consanguineous marriage. Maternal grandfather and paternal grandmother (brother and sister) living in the Azores were both affected by Machado‐Joseph disease (MJD) beginning late in life. To date neither of the patient's parents are clinically affected. Linkage studies in this family and others of Azorean descent have confirmed the recent mapping of the MJD gene to chromosome 14q. Genotyping of the members of this pedigree provides strong genetic evidence that our patient is homozygous for the MJD gene. Our results combined with experience in 2 putative homozygotes previously reported in the literature suggest that gene dosage is an important determinant of age of onset and clinical phenotype in MJD. Other possible influencing factors are discussed.
Effects of edrophonium on saccadic velocity in normal subjects and myasthenic and nonmyasthenic ocular palsies
Authors: Barton Jason J. S. , Huaman Ana G. , Sharpe James A. 
Published: January 2005

AbstractWe measured saccadic peak velocities in 8 patients with myasthenia gravis, 9 patients iwth proven nonmyasthenic ocular palsies, and 3 controls. Patients followed a target moving to and from primary position at 1‐second intervals for 8 minutes. We measured the amplitudes and velocities of centrifugal saccades at the start of the task, after 3 minutes of the task (fatigue) and 1 minute after receiving IV edrophonium. The effects of fatigue, though prominent in some myasthenic patients, did not distinguish between the groups. However, edrophonium increased saccadic peak velocities in myasthenic patients but decreased them in both controls and nonmyasthenic patients. Analysis of saccades by amplitude bins showed that these changes in peak velocity reflected shifts in the velocity–amplitude relationship.
Magnetic stimulation of corticospinal pathways at the foramen magnum level in humans
Authors: Ugawa Yoshikazu , Uesaka Yoshikazu , Terao Yasuo , Hanajima Ritsuko , Kanazawa Ichiro 
Published: January 2005

AbstractMagnetic stimulation done with a double cone coil placed over the back of the head activated descending motor pathways and produced electromyographic responses in muscles of the arms and legs. The latencies of these responses were the same as those of responses to electrical brainstem stimulation. The threshold was lowest when the coil was placed over the inion or below it on the median line. Placement of the coil on the side ipsilateral to the muscle was more effective than placement on the contralateral side. These results indicate that activation occurs at the foramen magnum level (just below the pyramidal decussation). Collision experiments that used cortical and magnetic brainstem stimulation indicated that the major part of the responses to the latter stimulation were conducted via the large diameter component of the corticospinal tract. Collision experiments done with the peripheral nerve and magnetic brainstem stimulation showed that this stimulation produced a single descending volley in the descending tract. We conclude that magnetic brainstem stimulation produces a single descending volley in the corticospinal tract at the foramen magnum level with less discomfort.
Prevalence of the 1.5‐Mb 17p deletion in families with hereditary neuropathy with liability to pressure palsies
Authors: Mariman E. C. M. , Gabreëls‐Festen A. A. W. M. , van Beersum S. E. C. , Valentijn L. J. , Baas F. , Bolhuis P. A. , Jongen P. J. H. , Ropers H. H. , Gabreëls F. J. M. 
Published: January 2005

AbstractHereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder of the peripheral nerves leading to increased susceptibility to mechanical traction or compression. Some patients have been shown to be carriers of a 1.5‐Mb deletion in chromosome 17p11.2, which corresponds to the duplicated region present in most patients with Charcot‐Marie‐Tooth disease type 1A. Recently, evidence has been presented that the deletion is not the only cause of HNPP. To determine the prevalence of the 1.5‐Mb deletion, we have examined 22 unrelated families with HNPP in the following two ways: by polymerase chain reaction analysis of marker loci D17S122 and D17S261, and by gene dosage measurements with DNA probes for D17S122 (VAW409R3a) and D17S125 (VAW412R3a) and for the PMP‐22 gene. The efficiency and sensitivity of these methods is discussed. Our results show that the prevalence of the 17p deletion in our families with HNPP is 68%. One patient, presenting as a sporadic case, was found to be affected by a de novo deletion in the paternal chromosome. Single‐strand conformation analysis of the protein‐coding region of the PMP‐22 gene did not reveal any mutation in patients from the 7 families lacking the 17p deletion. As a group, these families could not be distinguished by clinical, electrophysiological, or morphological features from the families with the deletion.
The retinoblastoma gene is involved in malignant progression of astrocytomas
Authors: Henson John W. , Schnitker Bernd L. , Correa Katia M. , von Deimling Andreas , Fassbender Frank , Xu Hong‐Ji , Benedict William F. , Yandell David W. , Louis David N. 
Published: January 2005

AbstractLoss of chromosome 13q occurs in up to 50% of human astrocytomas, suggesting the presence of an astrocytoma tumor suppressor gene on that chromosome. To determine whether the retinoblastoma susceptibility gene (Rb) on 13q 14 contributes to the formation of astrocytomas, we examined 85 tumors for loss of heterozygosity (LOH) at the intragenic Rb 1.20 locus. LOH was detercted in 16 of 54 informative high‐grade astrocytomas (30%), but was not detected in 12 low‐grade gliomas. Deletion mapping with flanking markers on 13q revealed that the Rb 1.20 region was preferentially targeted by the deletions. Tumors with LOH at Rb 1.20 were examined for mutations in the remaining Rb allele using single‐strand conformational polymorphism (SSCP) analysis and direct DNA sequencing. Mutations were detected in exon 8 (1 tumor), exon 24 (2 tumors), and intron 24 (1 tumor). Rb protein expression, as assessed by immunohistochemistry, was altered in 3 of 9 cases with LOH and in 1 tumor without LOH. Our results demonstrate that Rb inactivation contributes to the formation of high‐grade astrocytomas, and therefore implicate a second, known tumor suppressor gene in astrocytoma tumorigenesis.
Dystonia in Ashkenazi Jews: Clinical characterization of a founder mutation
Authors: Bressman Susan B. , de Leon Deborah , Kramer Patricia L. , Ozelius Laurie J. , Brin Mitchell F. , Greene Paul E. , Fahn Stanley , Breakefield Xandra O. , Risch Neil J. 
Published: January 2005

AbstractA gene (DYT1) for idiopathic torsion dystonia maps to chromosome 9q34 in Ashkenazi Jewish families with early onset of symptoms. Further, there is linkage disequilibrium between DYT1 and a particular haplotype of alleles at 9q34 loci in this population. This implies that a large proportion of early‐onset idiopathic torsion dystonia in Ashkenazi Jews is due to a founder mutation in DYT1. To characterize the phenotypic range of this mutation, we studied 174 Ashkenazi Jewish individuals affected with idiopathic torsion dystonia. We used GT(n) markers on chromosome 9q34 (D9S62, D9S63, and ASS) and classified individuals as having (“carriers”), not having (“noncarriers”), or being ambiguous with respect to a DYT1‐associated haplotype. We assessed clinical features and found marked clinical differences between haplotype carriers and noncarriers. There were 90 carriers, 70 noncarriers, and 14 ambiguous individuals. The mean age at onset of symptoms was significantly lower in carriers than in noncarriers (12.5 ± 8.2 vs 36.5 ± 16.4 years). In 94% of carriers, symptoms began in a limb (arm or leg equally); rarely the disorder started in the neck (3.3%) or larynx (2.2%). In contrast, the neck, larynx, and other cranial muscles were the sites of onset in 79% of noncarriers; onset in the arms occurred in 21% and onset in the legs never occurred. Limb onset, leg involvement in the course of disease, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In conclusion, there are clinical differences between Ashkenazi Jewish individuals with idiopathic torsion dystonia who do or do not have a unique DYT1 mutation, as determined by a DYT1‐associated haplotype of 9q34 alleles. These differences suggest that early, limb‐onset idiopathic torsion dystonia and late, cervical cranial–onset idiopathic torsion dystonia are genetically distinct entities.
The role of calcium‐binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis
Authors: Alexianu Maria E. , Ho Bao‐Kuang , Mohamed A. Habib , La Bella Vincenzo , Smith R. Glenn , Appel Stanley H. 
Published: January 2005

AbstractThe factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium‐binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin‐D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin‐D28K and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin‐D28K and/or parvalbumin. Motoneuron–neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin‐D28K and parvalbumin following dibutyryl‐cyclic AMP–induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin‐reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin‐D28K and parvalbumin immunoreactivity (substantia nigra–neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin‐D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.
Childhood Guillain‐Barré syndrome in Paraguay, 1990 to 1991
Authors: Hart David E. , Rojas Laura A. , Rosàrio Joana A. , Recalde Humberto , Romà Gustavo C. 
Published: January 2005

AbstractDuring 1990 to 1991, through a national surveillance program for poliomyelitis, the Paraguayan Ministry of Health received reports of 50 children with incident acute flaccid paralysis (< 15 years old). On the basis of established criteria, 37 were diagnosed with Guillian‐Barré syndrome. The average annual incidence rate for 1990 to 1991 was 1.1/100,000 children. The clinical course was more benign than reported in other pediatric series. There were low rates of hospitalization (57%), respiratory compromise (8%), and intubation (5%). The overall severity, however, was similar to that described in previous reports, with a 3% case‐fatality rate and an 81% total recovery rate at 12 months. Seventy‐six percent of patients had symptom onset during January to April, the warmest months of the year. Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillian‐Barré syndrome There was no correlation between occurrence of Guillian‐Barré syndrome and prior immunization.
Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate
Authors: Beal M. Flint , Henshaw D. Ross , Jenkins Bruce G. , Rosen Bruce R. , Schulz Jourg B. 
Published: January 2005

AbstractA potential mechanism of neuronal injury in neurodegenerative diseases is a defect in energy metabolism that may lead to slow excitotoxic neuronal death. Consistent with this possibility, we showed that specific inhibitors of the electron transport chain produce excitotoxic lesions in vivo. In the present study we examined whether agents that improve energy metabolism can block lesions produced by the mitochondrial toxin malonate. Striatal lesions produced by the complex II inhibitor malonate were blocked in a dose‐dependent manner by oral pretreatment with coenzyme Q10. Administration of nicotinamide by Alzet pump for 1 week attenuated malonate‐induced lesions, but riboflavin had no effect. Administration of nicotinamide intraperitoneally just prior to and following induction of the lesions produced dose‐dependent neuroprotection. A combination of coenzyme Q10 with nicotinamide was more effective than either compound alone, as shown by both lesion size and magnetic resonance imaging in vivo. Both coenzyme Q10 and nicotinamide blocked adenosine triphosphate depletions and lactate increases. These results confirm that mitochondrial toxins produce striatal excitotoxic lesions by a mechanism involving energy depletion in vivo. Furthermore, they suggest novel neuroprotective strategies that may be useful in the treatment of both mitochondrial encephalopathies and neurodegenerative diseases.
High‐dose dextromethorphan in amyotrophic lateral sclerosis: Phase I safety and pharmacokinetic studies
Authors: Hollander Dave , Pradas Jesus , Kaplan Richard , McLeod Howard L. , Evans William E. , Munsat Theodore L. 
Published: January 2005

AbstractMuch interest has focused on the role of glutamate‐mediated excitotoxicity in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We therefore conducted a phase I study of high‐dose dextromethorphan (DM) in ALS. DM is a selective, noncompetitive antagonist of the N‐methyl‐D‐aspartate subtype of the glutamate receptor. Thirteen patients were given DM in an escalating dose fashion, to a target of 10 mg/kg/day or the maximum tolerable dose, and then maintained on this dose for up to 6 months. Total daily doses ranged from 4.8 to 10 mg/kg (median, 7 mg/kg). Side effects were dose limiting in most patients. The most common side effects were light‐headedness, slurred speech, and fatigue. Detailed pharmacokinetic and neuropsychology studies were performed. This study demonstrates the feasibility of long‐term administration of high‐dose DM in ALS, as well as in other conditions associated with glutamate excitotoxicity.
Ragged Red Fibers in Normal Aging and Inflammatory Myopathy
Authors: Rifai Ziad , Welle Stephen , Kamp Cornelia , Thornton Charles A. 
Published: January 2005

AbstractRagged red fibers are an important marker for mitochondrial disease. To evaluate the hypothesis that mitochondrial dysfunction may play a role in the pathogensis of aging and inclusion body myositis, we studied the frequency of ragged red fibers in muscle biopsy specimens from 15 young and 13 old normal adults, and from 27 patients with inclusion body myositis, polymyositis, or dermatomyositis. Serial transverse cryostat sections were stained with modified Gomori trichrome, modified succinic dehydrogenase, and cytochrome c oxidase. The frequency of ragged red fibers, determined by measuring the percent number of succinic dehydrogenase–positive ragged red fiber equivalents, was significantly higher in old compared to young normal subjects (0.33 vs. 0.02%, p < 0.0001). With the exception of a single polymyositis biopsy specimen showing a large number of ragged red fibers, the frequency of ragged red fibers in patients with polymyositis or dermatomyositis was similar to that of age‐matched normal control subjects. The frequency of ragged red fibers was more than 1% in 7 of 8 patients with inclusion body myositis (maximum, 15%). The modified succinic dehydrogenase stain was more sensitive than the modified Gomori trichrome in detecting accumulation of mitochondria in muscle fibers. Cytochrome c oxidase activity was deficient in most ragged red fibers. We conclude that the number of ragged red fibers increases with normal aging and may reflect an age‐related decline in muscle mitochondrial oxidative metabolism. The frequent occurrence of ragged red fibers in inclusion body myositis suggests that mitochondrial function may be impaired in this disease.