bluuebunny/crossref_metadata_2025_split huggingface dataset:
The quest for unbiased research: Randomized clinical trials and the CONSORT reporting guidelines
Authors: Schulz Kenneth F. 
Published: January 2005

AbstractThe large and increasing number of randomized clinical trials in all of medicine has prompted the introduction of guidelines that are intended to improve the quality of the research and of the published papers derived from such investigations. These guidelines for reporting clinical trials, the Consolidated Standards of Reporting Trials (the CONSORT statement) were set forth by a group of journal editors, statisticians, biomedical investigators, and editors. The CONSORT statement has been published in several major medical journals and is likely to have a major impact on editorial policies as well as the design of such investigations. I have invited Dr Kenneth F. Schulz of the Centers for Disease Control and Prevention, a leading investigator in the evaluation of clinical trials and a participant in the design of the CONSORT guidelines, to prepare this brief summary for the Annals. The CONSORT statement is expected to have a substantial effect on the peer review of clinical trials, and it promises to elevate the quality of such investigations. Future submissions to the Annals will be evaluated in the context of these guidelines.
Endoglin gene polymorphism as a risk factor for sporadic intracerebral hemorrhage
Authors: Alberts M. J. , Davis J. P. , Graffagnino C. , McClenny C. , Delong D. , Granger C. , Herbstreith M. H. , Boteva K. , Marchuk D. A. , Roses A. D. 
Published: January 2005

AbstractIntracerebral hemorrhage (ICH) is a common and serious type of stroke. Recent studies have shown that inherited factors that affect the devlopment of the vessel wall can increase the risk of ICH. We studied endoglin as a candidate gene in patients with sporadic ICH, since mutations in this gene can cause telangiectasia formation. One hundred three patients with sporadic ICH and 202 controls were studied. The polymerase chain reaction and single‐strand conformational polymorphism analysis were used to screen for mutations in exon 7 of the endoglin gene. No coding mutations in exon 7 were identified in the ICH patients or controls. A 6‐base intronic insertion was found 26 bases beyond the 3′ end of exon 7. The homozygous form of the insertion was present in 9 of 103 (8.7%) ICH patients compared with 4 of 202 (2.0%) controls, p = 0.012 (odds ratio 4.8 [95% confidence interval, 1.28, 21.60]). Analysis of the endoglin transcript around the insertion did not reveal any changes in the RNA sequence. There were no obvious clinical features that distinguished the ICH patients with the homozygous insertion from the other patients. The pathophysiologic mechanism underlying this association remains to be determined.
A subset of senile dementia with high incidence of the apolipoprotein E ϵ2 allele
Authors: Ikeda Kenji , Akiyama Haruhiko , Arai Tetsuaki , Sahara Naruhiko , Mori Hiroshi , Usami Mihoko , Sakata Masuhiro , Mizutani Toshio , Wakabayashi Koichi , Takahashi Hitoshi 
Published: January 2005

AbstractThere is a subset of very elderly patients with senile dementia in whom abundant neurofibrillary tangles are present, mainly in the hippocampal region, without a significant number of senile plaques. In a retrospective neuropathological examination of 239 dementia patients, 14 were found to have this type of senile dementia. The apolipoprotein E ϵ2, ϵ3, and ϵ4 allele frequencies in this patient group were 0.39, 0.50, and 0.11, respectively. Such a high frequency of the ϵ2 allele suggests that this type of dementia is distinct from Alzheimer's disease not only from a neuropathological but also from a genetic viewpoint.
Frontotemporal dementia and parkinsonism linked to chromosome 17: A consensus conference
Authors: Foster Norman L. , Wilhelmsen Kirk , Sima Anders A. F. , Jones Margaret Z. , D'Amato Constance J. , Gilman Sid ,   Conference Participants
Published: January 2005

AbstractWe held an international consensus conference on frontotemporal dementia, behavioral disturbances, and parkinsonism linked to chromosome 17 to determine whether these are homogeneous or heterogeneous disorders, to agree on terminology, and to develop strategies for further research. The group identified 13 kindreds with sufficient evidence for linkage, finding in common to all a critical 2 cM between markers D17S791 and D17S800. There was agreement that (1) despite previous descriptions that have emphasized one or another clinical or neuropathological feature, the kindreds share clinical and neuropathological features; (2) until more specific information about the genetic defects becomes available, this disorder is best termed frontotemporal dementia and parkinsonism linked to chromosome 17; and (3) further research will be enhanced by identifying the gene responsible for this disorder, detecting additional cases within known families and, in new families, correlating mutations with phenotypes and more fully delineating the clinical, neuropsychological, and neuropathological characteristics of this disorder.
Clinical trial of plasma exchange and high‐dose intravenous immunoglobulin in myasthenia gravis
Authors: Gajdos Philippe , Chevret Sylvie , Clair Bernard , Tranchant Christine , Chastang Claude ,   for the Myasthenia Gravis Clinical Study Group
Published: January 2005

AbstractWe have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (IVIg) or plasma exchage (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of IVIg. Eighty‐seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or IVIg (n = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The main end point was the variation of a myasthenic muscular score (MSS) between randomization and day 15. The MSS variation was similar in both groups (median value, +18 in the PE group and +15.5 in the IVIg group; p = 0.65). Similar efficacy, although slightly reduced in the 5‐day group was observed with both IVIg schedules. The tolerance of IVIg was better than that of PE with a total of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the IVIg group (p = 0.01). Although our trial failed to show a pronounced difference in the efficacy of both treatments, it exhibited a very limited risk for IVIg. IVIg is an alternative for the treatment of myasthenic crisis. The small sample sizes in our trial, however, could explain why a difference in efficacy was not observed. Further studies are needed to compare PE with IVIg and to determine the optimal dosage of IVIg.
Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities
Authors: van der Knaap M. S. , Smit L. M. E. , Barth P. G. , Catsman‐Berrevoets C. E. , Brouwer O. F. , Begeer J. H. , de Coo I. F. M. , Valk J. 
Published: January 2005

AbstractA survey was performed of magnetic resonance imaging (MRI) findings in 21 patients with congenital muscular dystrophy (CMD) with cerebral abnormalities to evaluate the contribution of MRI to the classification of CMD patients. In 5 patients with Walker‐Warburg syndrome (WWS), MRI showed hydrocephalus due to aqueduct stenosis, generalized cerebral cortical agyric or pachygyric polymicrogyria, diffuse cerebral hemispheric white matter abnormalities, and malformations of posterior fossa structures. In 4 patients with muscle–eye–brain disease, MRI showed cortical dysplasia, but less severe than in WWS. The cerebral white matter either was normal or contained multiple focal abnormalities. Malformations of posterior fossa structures were present. Eight patients, classified as having classic merosin‐deficient CMD (MD‐CMD), had diffuse cerebral hemispheric white matter abnormalities, no other abnormalities. One patient with MD‐CMD had only a few, focal white matter abnormalities. Three CMD patients had occipital agyria, otherwise normal gyration, multifocal or more diffuse cerebral white matter changes, and variable hypoplasia of pons and vermis. Two of the 3 patients had negative muscle merosin staining. The conclusion of the study is that MRI is an important adjunct in the classification of CMD patients. CMD with occipital agyria can be regarded as a newly recognized, separate CMD subtype.
Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas
Authors: Wienecke Ralf , Guha Abhijit , Maize John C. , Heideman Richard L. , DeClue Jeffrey E. , Gutmann David H. 
Published: January 2005

AbstractIndividuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas. Tuberin, the protein product of the tuberous sclerosis complex‐2 (TSC2) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes. To determine whether TSC2 RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase–polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas. Eighteen of 40 (45%) high‐grade (World Health Organization [WHO] grade III/IV) astrocytomas and 4 of 8 (50%) adult low‐grade (WHO grade II) astrocytomas demonstrated reduced or absent TSC2 expression, including 1 gaint cell astrocytoma, whereas none of the 10 pediatric low‐grade astrocytomas anlayzed showed a reduction in TSC2 expression. Reduced or absent tuberin was observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the first time, that reduced or absent TSC2 expression may represent one of the critical genetic events associated with the development of sporadic adult, but not pediatric, astrocytomas.
Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects
Authors: Shults Clifford W. , Haas Richard H. , Passov David , Beal M. Flint 
Published: January 2005

AbstractThe activities of complex I and complex II/III in platelet mitochondria are reduced in patients with early, untreated Parkinson's disease. Coenzyme Q 10 is the electron acceptor for complex I and complex II. We found that the level of coenzyme Q 10 was significantly lower in mitochondria from parkinsonian patients than in mitochondria from age‐ and sex‐matched control subjects and that the levels of coenzyme Q 10 and the activities of complex I and complex II/III were significantly correlated.
Frataxin gene of Friedreich's ataxia is targeted to mitochondria
Authors: Priller Josef , Scherzer Clemens R. , Faber Peter W. , MacDonald Marcy E. , Yong Anne B. 
Published: January 2005

AbstractFriedriech's ataxia is caused by a triplet repeat expanison in intron 1, a noncoding region of the frataxin gene (X25). We have generated a chimeric gene composed of the frataxin gene fused with the green fluorescent protein (GFP) gene as a reporter. Transfection of the fusion construct into living COS cells revealed that the frataxin–GFP construct localizes to organelles that double‐label with 8–(4′‐chloromethyl) phenyl‐2,3,5,6,11,12,14,15‐octahydro‐1H,4H,10H‐13H‐diquinolizino‐8H‐xanthylium chloride (CMXRos), a novel mitochondrial dye. Thus, frataxin appears to be a nuclear‐encoded mitochondrial protein.
Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease
Authors: Limousin Patricia , Greene John , Pollak Pierre , Rothwell John , Benabid Alim‐Louis , Frackowiak Richard 
Published: January 2005

AbstractHigh‐frequency electrical stimulation of the internal pallidum (GPi) or the subthalamic nucleus (STN) improves clinical symptoms of Parkinson's disease. In 12 parkinsonian patients, 6 with STN and 6 with GPi stimulators, we used H215O positron emission tomography to evaluate whether changes in movement performance were accompanied by change in regional cerebral blood flow (rCBF). Patients were scanned both at rest and while performing a free‐choice joystick movement, under conditions of effective and ineffective electrostimulation. During effective STN stimulation, movement‐related increases in rCBF were significantly higher in supplementary motor area, cingulate cortex, and dorsolateral prefrontal cortex (DLPFC) than during ineffective stimulation. No significant change was observed in any of these areas during GPi stimulation. The difference between the effect of STN and GPi stimulation on movement‐related activity was mainly localized to DLPFC. These results confirm the dominant role of nonprimary motor areas in the control of movement in parkinsonian patients and demonstraste the importance of STN input in the control of these areas.
Andersen's syndrome: A distinct periodic paralysis
Authors: Sansone V. , Griggs R. C. , Meola G. , Ptácek L. J. , Barohn R. , Iannaccone S. , Bryan W. , Baker N. , Janas S. J. , Scott W. , Ririe D. , Tawil R. 
Published: January 2005

AbstractA previous study of 4 patients defined Andersen's syndrome (AS) as a triad of potassium‐sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features. AS appears to be distinct in terms of its genetic defect from the α‐subunit of skeletal muscle sodium channel and the cardiac potassium channel responsible for most long QT syndromes (LQT1). We studied 11 additional patients with AS from 5 kindreds. Spontaneous attacks of paralysis were associated with hypokalemia, normokalemia, or hyperkalemia. All 11 patients had similar dysmorphic features. The QT interval was prolonged in all patients although only 4 were sympotomatic. Genetic linkage studies excluded linkage to the α‐subunit of the skeletal muscle sodium channel and to four distinct LQT loci. In addition, none of the common dihydropyridine receptor mutations responsible for hypokalemic periodic paralysis were present. We conclude that (1) AS is a genetically unique channelopathy affecting both cardiac and skeletal membrane excitability, (2) attacks of paralysis may be either hypokalemic or hyperkalemic, (3) a prolonged QT interval is an integral feature of this syndrome, and (4) a prolonged QT interval may be the only sign in an individual from an otherwise typical AS kindred. This may be confused with more common, potentially lethal LQT syndromes.
Functional and metabolic analysis of cerebral ischemia using magnetoencephalography and proton magnetic resonance spectroscopy
Authors: Kamada Kyousuke , Saguer Mark , Möller Martin , Wicklow Karsten , Katenhäuser Martin , Kober Helmut , Vieth Jürgen 
Published: January 2005

AbstractThe details of the relationship between brain function and metabolism in brain infarcts have not been studied. Using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI), we localized sources of abnormal magnetic activities in ischemic brain regions and biochemical changes in suspected lesions showing pathological characteristics. Twelve patients with ischemic stroke were examined and the results of MEG and 1H MRSI were superimposed onto the corresponding MR images. The signal intensities of N‐acetyl (NA) and lactate (Lac) were measured in the lesions with highly concentrated dipoles of slow wave activity. Eleven of 12 cases had increased slow wave activity in the cortical areas adjacent to the infarcts; 1 case was excluded because the infarct was too small (<1 cm in diameter). The signal intensity of NA in the regions with the highest slow wave activity was significantly reduced and was well correlated with the dipole density of slow waves. Though Lac was mildly accumulated in the lesions, the Lac level had no correlation with slow wave magnetic activity. The remaining and metabolically active cortical tissue showing NA signal produced the abnormal slow wave activity. The remaining and metabolically active cortical tissue showing NA signal produced the abnormal slow wave activity under lactic acidosis (mils accumulation of Lac).
Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death
Authors: Johnston S. Claiborne , Siedenberg Ralf , Min Jeffrey K. , Jerome E. Heidi , Laxer Kenneth D. 
Published: January 2005

AbstractThe etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well‐established sheep model of status epilepticus showed that more than one‐third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypooventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.
Prospective study of neurological responses to treatment with macrophage‐targeted glucocerebrosidase in patients with type 3 Gaucher's disease
Authors: Schiffmann Raphael , Heyes Melvyn P. , Aerts J. M. , Dambrosia James M. , Patterson Marc C. , DeGraba Thomas , Parker Colette C. , Zirzow Gregory C. , Oliver Katherine , Tedeschi Gioacchino , Brady Roscoe O. , Barton Norman W. 
Published: January 2005

AbstractWe prospectively evaluated the clinical and biochemical responses to enzyme‐replacement therapy (ERT) with macrophage‐targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5–8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain–CSF compartment in some patients.
Modulation of the age at onset of Parkinson's disease by apolipoprotein E genotypes
Authors: Zareparsi Sepideh , Kaye Jeffrey , Camicioli Richard , Grimslid Holly , Oken Barry , Litt Michael , Nutt John , Bird Thomas , Schellenberg Gerard , Payami Haydeh 
Published: January 2005

AbstractParkinson's disease (PD) patients often develop dementia, and Alzheimer's disease (AD) patients frequently develop parkinsonian signs. The apolipoprotein E σ4 allele is associated with increased risk and earlier onset of AD. We studied 137 unrelated white PD patients. Those with σ4 had the earliest onset (52.7 · 9.8 years), σ3/σ3 patients had an intermediate onset (56.1 · 11.1 years), and those with σ2 had the latest onset (59.1 · 13.4 years). The age at onset distribution for σ4/σ – was significantly earlier than for σ3/σ3 and σ2/σ3. These preliminary results suggest that apolipoprotein E genotypes modulate the age at onset of PD.
Apolipoprotein E—associated risk for Alzheimer's disease in the African‐American population is genotype dependent
Authors: Sahota Amrik , Yang Min , Gao Sujuan , Hui Siu L. , Baiyewu Olusegun , Gureje Oyewusi , Oluwole Steven , Ogunniyi Adesola , Hall Kathleen S. , Hendrie Hugh C. 
Published: January 2005

AbstractAs a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age‐adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.
New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency
Authors: Dionisi‐Vici C. , Ruitenbeek W. , Fariello G. , Bentlage H. , Wanders R. J. A. , Schägger H. , Bosman C. , Piantadosi C. , Sabetta G. , Bertini E. 
Published: January 2005

AbstractTwo siblings presented with a new phenotype consisting of fatal progressive macrocephaly and hypertrophic cardiomyopathy. Onset of symptoms started in both patients at the end of the first month of life with massive brain swelling causing macrocephaly and evolving to extensive brain destruction. Light microscopy of the lesions showed extensive small‐vessel proliferation and gliosis. A distinct deficiency of complex I of mitochondrial respiratory chain was established in cultured fibroblasts, skeletal muscle, and heart muscle. Specific lack of complex I protein was demonstrated by two‐dimensional gel electrophoresis.
Differential distribution of the normal and mutated forms of huntingtin in the human brain
Authors: Gourfinkel‐An Isabelle , Cancel Géraldine , Trottier Yvon , Devys Didier , Tora Laszlo , Lutz Yves , Imbert Georges , Saudou Frédéric , Stevanin Giovanni , Agid Yves , Brice Alexis , Mandel Jean‐Louis , Hirsch Etienne C. 
Published: January 2005

AbstractHuntington's disease is an inherited disorder caused by expansion of a CAG trinucleotide repeat in the IT15 gene, which leads to expansion of a polyglutamine tract within the protein called huntingtin. Despite the characterization of the IT15 gene and the mutation involved in the disease, the normal function of huntingtin and the effects of the mutation on its function and on its neuronal location remain unknown. To study whether mutated huntingtin has the same neuronal distribution and intracellular location as normal huntingtin, we analyzed immunohistochemically both forms of this protein in the brain of 5 controls and 5 patients with Huntington's disease. We show that the distribution of mutated huntingtin is, like that of the normal form, heterogeneous throughout the brain, but is not limited to vulnerable neurons in Huntington's disease supporting the hypothesis that the presence of the mutated huntingtin in a neuron is not in itself sufficient to lead to neuronal death. Moreover, whereas normal huntingtin is detected in some neuronal perikarya, nerve fibers, and nerve endings, the mutated form is observed in some neuronal perikarya and proximal nerve processes but is not detectable in nerve endings. Our results suggest that the expression or processing of the mutated huntingtin in perikarya and nerve endings differs quantitatively or qualitatively from the expression of the normal form in the same neuronal compartments.