Institution
Mayo Clinic
Healthcare•Rochester, Minnesota, United States•
About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.
Topics: Population, Cancer, Medicine, Transplantation, Breast cancer
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The extent of nigrostriatal degeneration in patients with Parkinson's disease at different disease durations from time of diagnosis is investigated and loss of dopaminergic markers in the dorsal putamen occurs rapidly and is virtually complete by 4 years post-diagnosis.
Abstract: The pace of nigrostriatal degeneration, both with regards to striatal denervation and loss of melanin and tyrosine hydroxylase-positive neurons, is poorly understood especially early in the Parkinson's disease process. This study investigated the extent of nigrostriatal degeneration in patients with Parkinson's disease at different disease durations from time of diagnosis. Brains of patients with Parkinson's disease (n=28) with post-diagnostic intervals of 1-27 years and normal elderly control subjects (n=9) were examined. Sections of the post-commissural putamen and substantia nigra pars compacta were processed for tyrosine hydroxylase and dopamine transporter immunohistochemistry. The post-commissural putamen was selected due to tissue availability and the fact that dopamine loss in this region is associated with motor disability in Parkinson's disease. Quantitative assessments of putaminal dopaminergic fibre density and stereological estimates of the number of melanin-containing and tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (both in total and in subregions) were performed by blinded investigators in cases where suitable material was available (n=17). Dopaminergic markers in the dorsal putamen showed a modest loss at 1 year after diagnosis in the single case available for study. There was variable (moderate to marked) loss, at 3 years. At 4 years post-diagnosis and thereafter, there was virtually complete loss of staining in the dorsal putamen with only an occasional abnormal dopaminergic fibre detected. In the substantia nigra pars compacta, there was a 50-90% loss of tyrosine hydroxylase-positive neurons from the earliest time points studied with only marginal additional loss thereafter. There was only a ∼10% loss of melanized neurons in the one case evaluated 1 year post-diagnosis, and variable (30 to 60%) loss during the first several years post-diagnosis with more gradual and subtle loss in the second decade. At all time points, there were more melanin-containing than tyrosine hydroxylase-positive cells. Loss of dopaminergic markers in the dorsal putamen occurs rapidly and is virtually complete by 4 years post-diagnosis. Loss of melanized nigral neurons lags behind the loss of dopamine markers. These findings have important implications for understanding the nature of Parkinson's disease neurodegeneration and for studies of putative neuroprotective/restorative therapies.
892 citations
••
University College London1, University of Cambridge2, University of Cologne3, Leiden University4, Utrecht University5, National Institutes of Health6, University of Pennsylvania7, University of Glasgow8, University of Edinburgh9, Mayo Clinic10, University of London11, University of Bristol12, Cardiff University13, University of Oxford14, University of Ioannina15, University of Hamburg16, Lithuanian University of Health Sciences17, Jagiellonian University18, Russian Academy19, Karolinska Institutet20, Memorial Hospital of South Bend21, University of Groningen22, MedStar Washington Hospital Center23, Swansea University24, Brown University25, University of Iowa26, Harvard University27, University of Exeter28, University of North Carolina at Chapel Hill29, Boston University30, Medical Research Council31, University of California, San Diego32, University of Mississippi33, Fred Hutchinson Cancer Research Center34
TL;DR: IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials and could help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.
891 citations
••
TL;DR: It is shown that this ER degradation is sensitive to inhibitors of the cytosolic proteasome, including lactacystin and certain peptide aldehydes, which completely blocks the ATP-dependent conversion of the wild-type precursor to the native folded form that enables escape from degradation.
891 citations
••
University of California, San Diego1, Mayo Clinic2, New York University3, Georgetown University4, Rush University Medical Center5, University of Michigan6, Baylor College of Medicine7, Oregon Health & Science University8, Columbia University9, Eli Lilly and Company10, McGill University11, University of California, Irvine12, Yale University13, Medical University of South Carolina14, University of Alabama at Birmingham15, Brown University16
TL;DR: Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings.
Abstract: Background Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. Objective To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. Design Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. Setting Memory disorder centers in the United States and Canada. Patients A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. Main Outcome Measures Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. Results Mean ± SD Alzheimer's Disease Assessment Scale–Cognitive Subscale scores were 5.6 ± 3.3 for controls, 11.3 ± 4.4 for patients with MCI, 18.0 ± 6.2 for the AD CDR 0.5 group, and 25.2 ± 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E ϵ4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. Conclusions Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.
891 citations
••
University of Toronto1, Yale University2, Saarland University3, University of Utah4, Oregon Health & Science University5, University of Lyon6, University of Pennsylvania7, Georgia Regents University8, National Institutes of Health9, Harvard University10, Washington University in St. Louis11, Western General Hospital12, University of Bari13, Mayo Clinic14, Johns Hopkins University15, University Health Network16
TL;DR: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of H HT-related complications and treatment of symptomatic disease.
Abstract: Background HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.
Objective The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.
Methods The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.
Results The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
890 citations
Authors
Showing all 64325 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eugene Braunwald | 230 | 1711 | 264576 |
Peter Libby | 211 | 932 | 182724 |
Cyrus Cooper | 204 | 1869 | 206782 |
Rob Knight | 201 | 1061 | 253207 |
Robert M. Califf | 196 | 1561 | 167961 |
Eric J. Topol | 193 | 1373 | 151025 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Gordon B. Mills | 187 | 1273 | 186451 |
Julie E. Buring | 186 | 950 | 132967 |
Patrick W. Serruys | 186 | 2427 | 173210 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Paul G. Richardson | 183 | 1533 | 155912 |
John C. Morris | 183 | 1441 | 168413 |
Valentin Fuster | 179 | 1462 | 185164 |
Ronald C. Petersen | 178 | 1091 | 153067 |