Biomedical subjects

Richard Atkinson

Publications and source records attributed to Richard Atkinson.

11 recordsLinked to original sources

PubMed2007

The CAPTURE registry: results of carotid stenting with embolic protection in the post approval setting.

BACKGROUND: Pivotal study data examining carotid stenting with embolic protection as a less invasive alternative to endarterectomy for high surgical risk patients have been acquired under controlled conditions with highly selected physicians and hospitals. This report examines outcomes of carotid stenting post-approval after diffusion of this technology to a broader cross-section of physicians and hospitals. METHODS: The Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE) is a prospective, multi-center registry to assess two important aspects of the post-IDE experience: the safety of carotid stenting by physicians with varying levels of experience as a measure of the adequacy of physician training, and the identification of rare/unexpected device-related complications. The primary endpoint was a composite of death, any stroke, or myocardial infarction within 30 days post-procedure. RESULTS: 3,500 patients were enrolled by 353 physicians at 144 sites. The 30-day primary endpoint event rate was 6.3% (95% CI: 5.5-7.1%) and did not differ among the three operator experience levels (5.3%, 6.0%, and 7.4%; P = 0.31) from most to least experienced, respectively. There were no differences in outcomes among physician specialties when adjusted for case mix. There were no unanticipated device related adverse events. CONCLUSIONS: The results of the CAPTURE study compare favorably to those achieved in the predicate pivotal investigations, and suggest that the post-approval transfer of this new therapy to the community practice setting via carotid stent training programs is effective in preparing physicians with varying experience levels and specialty training backgrounds.

Aged↗

PubMed2006

Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.

Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.

Animals↗

PubMed2006

Protected carotid stenting in high-surgical-risk patients: the ARCHeR results.

BACKGROUND: Carotid endarterectomy is the standard of care for most patients with severe extracranial carotid bifurcation disease. However, its safety and efficacy in patients with significant surgical risk are unclear. The ARCHeR (ACCULINK for Revascularization of Carotids in High-Risk patients) trial was performed to determine whether carotid artery stenting with embolic protection is a safe and effective alternative to endarterectomy in high-surgical-risk patients. METHODS: The ARCHeR trial is a series of three sequential, multicenter, nonrandomized, prospective studies. Forty-eight sites enrolled 581 high-surgical-risk patients between May 2000 and September 2003. Patients with severe carotid artery stenosis (angiographically defined, symptomatic > or =50%, or asymptomatic > or =80%) had an ACCULINK nitinol stent implanted. The ACCUNET filter embolic protection system was added to the procedure in the final 2 studies (422 patients). The primary efficacy end point was a composite of periprocedural (< or =30 days) death, stroke, and myocardial infarction, plus ipsilateral stroke between days 31 and 365. RESULTS: The 30-day rate of death/stroke/myocardial infarction was 8.3% (95% confidence interval [CI], 6.2%-10.8%), and that of stroke/death was 6.9% (95% CI, 5.0%-9.3%). Most (23/32) strokes were minor, of which more than half (12/23) returned to baseline National Institutes of Health Stroke Scale scores within 30 days. The 30-day major/fatal stroke rate was 1.5% (95% CI, 0.7%-2.9%). No hemorrhagic strokes were observed in the study. Ipsilateral cerebrovascular accident occurred in 1.3% between 30 days and 1 year, thus giving a primary composite end point of 30-day death/stroke/myocardial infarction plus ipsilateral stroke at 1 year of 9.6% (95% CI, 7.2%-12.0%), which is below the 14.4% historical control comparator. Target lesion revascularization at 12 months and 2 years was 2.2% and 2.9%, respectively. CONCLUSIONS: The ARCHeR results demonstrate that extracranial carotid artery stenting with embolic filter protection is not inferior to historical results of endarterectomy and suggest that carotid artery stenting is a safe, durable, and effective alternative in high-surgical-risk patients.

Angioplasty, Balloon↗

PubMed2004

ICF Core Sets for obesity.

OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of the Comprehensive ICF Core Set and the Brief ICF Core Set for obesity. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 219 ICF categories at the second, third and fourth ICF levels with 87 categories on body functions, 34 on body structures, 53 on activities and participation and 45 on environmental factors. Twenty-one experts attended the consensus conference on obesity (18 physicians with various sub-specializations and 3 physical therapists). Altogether 109 categories (108 second-level and one third-level categories) were included in the Comprehensive ICF Core Set with 30 categories from the component body functions, 18 from body structures, 28 from activities and participation and 33 from environmental factors. The Brief ICF Core Set included a total of 9 second-level categories with 3 on body functions, 4 on activities and participation and 2 on environmental factors. No body-structures categories were included in the Brief ICF Core Set. CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for obesity. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.

Activities of Daily Living↗

PubMed2003

SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity.

We targeted 266 CAG repeats (a number that causes infantile-onset disease) into the mouse Sca7 locus to generate an authentic model of spinocerebellar ataxia type 7 (SCA7). These mice reproduced features of infantile SCA7 (ataxia, visual impairments, and premature death) and showed impaired short-term synaptic potentiation; downregulation of photoreceptor-specific genes, despite apparently normal CRX activity, led to shortening of photoreceptor outer segments. Wild-type ataxin-7 was barely detectable, as was mutant ataxin-7 in young animals; with increasing age, however, ataxin-7 staining became more pronounced. Neurons that appeared most vulnerable had relatively high levels of mutant ataxin-7; it is interesting, however, that marked dysfunction occurred in these neurons weeks prior to the appearance of nuclear inclusions. These data demonstrate that glutamine expansion stabilizes mutant ataxin-7, provide an explanation for selective neuronal vulnerability, and show that mutant ataxin-7 impairs posttetanic potentiation (PTP).

Animals↗

PubMed2003

The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (The Aphea-II study).

The objective of this study is to assess the short-term effect of sulfur dioxide (SO(2)) air pollution levels on hospital admissions for cardiovascular diseases. Daily mean hospital admissions for cardiovascular diseases, ischemic heart diseases (IHDs), and stroke in seven European areas (the cities of Birmingham, London, Milan, Paris, Rome, and Stockholm, and in The Netherlands) participating in the multicenter European study of air pollution (Aphea-II), were measured. Time series analysis of daily hospital admission counts was performed using poison autoregressive models. A summary regression coefficient for all cities was provided. Daily numbers of all cardiovascular admissions except stroke, and particularly IHDs, rose significantly with an increase of daily SO(2)levels of the same day and day before. After adjusting for PM(10)(i.e. particles with size <10 microm), the association of SO(2)with IHD admissions remained significant (i.e. an increase of 0.7%; 95% confidence interval=0.1-1.3, per each 10 microg/m(3)increase of SO(2)) among subjects younger than 65 years, but not among subjects older than 65. In the older group the increase was only significant for particles (1.3%; CI 0.7-1.8, per each increase in 10 microg/m(3)of PM(10)). This study provides new evidence for the effects of urban air pollution on cardiac diseases in Europe, and suggests that SO(2)pollution may play an independent role in triggering ischemic cardiac events. From a Public Health perspective these results suggest that reduction in SO(2)levels in European cities could imply a reduction of admissions for IHDs.

Adult↗

PubMed2002

A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration.

To faithfully recreate the features of the human neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) in the mouse, we targeted 154 CAG repeats into the endogenous mouse locus. Sca1(154Q/2Q) mice developed a progressive neurological disorder that resembles human SCA1, featuring motor incoordination, cognitive deficits, wasting, and premature death, accompanied by Purkinje cell loss and age-related hippocampal synaptic dysfunction. Mutant ataxin-1 solubility varied with brain region, being most soluble in the neurons most vulnerable to degeneration. Solubility decreased overall as the mice aged; Purkinje cells, the most affected in SCA1, did not form aggregates of mutant protein until an advanced stage of disease. It appears that those neurons that cannot sequester the mutant protein efficiently and thereby curb its toxicity suffer the worst damage from polyglutamine-induced toxicity.

Animals↗

PubMed2002

Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release.

We have identified mutations in Drosophila endophilin to study its function in vivo. Endophilin is required presynaptically at the neuromuscular junction, and absence of Endophilin dramatically impairs endocytosis in vivo. Mutant larvae that lack Endophilin fail to take up FM1-43 dye in synaptic boutons, indicating an inability to retrieve synaptic membrane. This defect is accompanied by an expansion of the presynaptic membrane, and a depletion of vesicles from the bouton lumen. Interestingly, mutant larvae are still able to sustain release at 15%-20% of the normal rate during high-frequency stimulation. We propose that kiss-and-run maintains neurotransmission at active zones of the larval NMJ in endophilin animals.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila.

Signaling through tyrosine kinase receptors (TKRs) is thought to be modulated by receptor-mediated endocytosis and degradation of the receptor in the lysosome. However, factors that regulate endosomal sorting of TKRs are largely unknown. Here, we demonstrate that Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) is one such factor. Electron microscopy studies of hrs mutant larvae reveal an impairment in endosome membrane invagination and formation of multivesicular bodies (MVBs). hrs mutant animals fail to degrade active epidermal growth factor (EGF) and Torso TKRs, leading to enhanced signaling and altered embryonic patterning. These data suggest that Hrs and MVB formation function to downregulate TKR signaling.

Amino Acid Motifs↗

PubMed2002

The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement.

Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.

Air Pollutants↗

PubMed2002

Recommendations for improving the quality of care through stroke centers and systems: an examination of stroke center identification options: multidisciplinary consensus recommendations from the Advisory Working Group on Stroke Center Identification Options of the American Stroke Association.

BACKGROUND AND PURPOSE: The American Stroke Association (ASA) assembled a multidisciplinary group of experts to develop recommendations regarding the potential effectiveness of establishing an identification program for stroke centers and systems. "Identification" refers to the full spectrum of models for assessing and recognizing standards of quality care (self-assessment, verification, certification, and accreditation). A primary consideration is whether stroke center identification might improve patient outcomes. METHODS: In February 2001, ASA, with the support of the Stroke Council's Executive Committee, decided to embark on an evaluation of the potential impact of stroke center identification. HealthPolicy R&D was selected to prepare a comprehensive report. The investigators reported on models outside the area of stroke, ongoing initiatives within the stroke community (such as Operation Stroke), and state and federal activities designed to improve care for stroke patients. The investigators also conducted interviews with thought leaders in the stroke community, representing a diverse sampling of specialties and affiliations. In October 2001, the Advisory Working Group on Stroke Center Identification developed its consensus recommendations. This group included recognized experts in neurology, emergency medicine, emergency medical services, neurological surgery, neurointensive care, vascular disease, and stroke program planning. RESULTS: There are a variety of existing identification programs, generally falling within 1 of 4 categories (self-assessment, verification, certification, and accreditation) along a continuum with respect to intensity and scope of review and consumption of resources. Ten programs were evaluated, including Peer Review Organizations, trauma centers, and new efforts by the National Committee on Quality Assurance and the Joint Commission on the Accreditation of Healthcare Organizations to identify providers and disease management programs. The largest body of literature on clinical outcomes associated with identification programs involves trauma centers. Most studies support that trauma centers and systems lead to improved mortality rates and patient outcomes. The Advisory Working Group felt that comparison to the trauma model was most relevant given the need for urgent evaluation and treatment of stroke. The literature in other areas generally supports the positive impact of identification programs, although patient outcomes data have less often been published. In the leadership interviews, participants generally expressed strong support for pursuing some form of voluntary identification program, although concerns were raised that this effort could meet with some resistance. CONCLUSIONS: Identification of stroke centers and stroke systems competencies is in the best interest of stroke patients in the United States, and ASA should support the development and implementation of such processes. The purpose of a stroke center/systems identification program is to increase the capacity for all hospitals to treat stroke patients according to standards of care, recognizing that levels of involvement will vary according to the resources of hospitals and systems.

Accreditation↗