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Richard O'Brien

Publications and source records attributed to Richard O'Brien.

11 recordsLinked to original sources
PubMed2006

Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly.

OBJECTIVE: Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. METHODS: Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. RESULTS: Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. INTERPRETATION: Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly.

Aged↗
PubMed2005

Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of Children's Cancer Group Study 9933.

BACKGROUND: High-grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high-dose chemotherapy (HDCT) in the treatment of HGA remains unclear. METHODS: In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty-six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18). RESULTS: Of 76 evaluable patients (median age, 11.95 yrs; range, 3-20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% +/- 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five-year, event-free survival (EFS) rate for all patients was 8% +/- 3% and 14% +/- 7% for Regimen A (P = 0.07). CONCLUSIONS: OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor.

Adolescent↗
PubMed2005

Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA).

Alpha-synuclein (alpha-synuclein) lesions are characteristic of idiopathic Parkinson disease (PD) and other alpha-synucleinopathies. To study the frequency of alpha-synuclein lesions in normal aging and how frequently they coexist with lesions of Alzheimer disease (AD), we examined the autopsy brains from normal and demented subjects in the Baltimore Longitudinal Study of Aging (BLSA) (n = 117). We found that the overall frequency of alpha-synuclein lesions was 25%, with 100% in 7 cases of PD, 31.5% in 56 cases with AD lesions, and 8.3% among 36 older control brains. Among brains with AD lesions, the frequency of alpha-synuclein pathology was higher in those with higher scores for neuritic plaques, but not in those with higher scores for neurofibrillary tangles. Our observations indicate that alpha-synuclein lesions are uncommon in aged control subjects. Finally, the coexistence of Abeta amyloid and alpha-synuclein pathology in AD brains suggests that the pathogenic mechanism/s leading to the accumulation of Abeta and alpha-synuclein may be similar.

Aged↗
PubMed2005

Satisfaction with and perceived cultural competency of healthcare providers: the minority experience.

It is well known that nonwhite minority participation in clinical research is lower than their representation in the community. The goal of this study was to assess satisfaction of minority community members in Omaha with the care received and cultural competency of healthcare providers. We sought input from Omaha minority communities on how to improve the care they received and asked why they did not participate in healthcare research. Seventy-two minority members representing African Americans, Hispanic Americans, Native Americans, Sudanese, and Vietnamese; and eight whites were surveyed. The results of this study indicated that the majority of our respondents were satisfied with the care they received, but for a small percentage, language, communication and/or culture contributed to dissatisfaction. In addition, some respondents did not think the provider was culturally competent, i.e., not sufficiently knowledgeable about their racial, ethnic and/or cultural background. Some participants indicated that they preferred a provider of similar racial, ethnic and/or cultural background, and/or thought some diseases were better treated by a provider of the same racial, ethnic and/or cultural background. Regardless of the cultural competency of the provider, the overwhelming majority of our respondents (with the exception of African Americans) indicated a willingness to participate in healthcare research. In conclusion, this study found that satisfaction with healthcare providers was not associated with perceived cultural competency and that the cultural competency of the provider did not affect patient willingness to participate in healthcare research; however, we acknowledge that the Hawthorne effect may be in operation.

Adolescent↗
PubMed2005

Pond4Kids - an multi-site online Pediatric Oncology Research Database for collaborative protocol research.

Abstract: The Pediatric Oncology Networked Database (POND4Kids) is an online, multilingual database for pediatric hematology/oncology patients. Its purpose is to improve the care of pediatric oncology patients in countries with limited resources by the exchange of information and experience between oncologists in diverse geographic regions who practice in a similar medical environment.

Child↗
PubMed2004

Neuronal pentraxin 1: a novel mediator of hypoxic-ischemic injury in neonatal brain.

Neonatal hypoxic-ischemic brain injury is a major cause of neurological disability and mortality. Its therapy will likely require a greater understanding of the discrete neurotoxic molecular mechanism(s) triggered by hypoxia-ischemia (HI). Here, we investigated the role of neuronal pentraxin 1 (NP1), a member of a newly recognized subfamily of "long pentraxins," in the HI injury cascade. Neonatal brains developed marked infarcts in the ipsilateral cerebral hemisphere at 24 hr and showed significant loss of ipsilateral striatal, cortical, and hippocampal volumes at 7 d after HI compared with the contralateral hemisphere and sham controls. Immunofluorescence analyses revealed elevated neuronal expression of NP1 in the ipsilateral cerebral cortex from 6 hr to 7 d and in the hippocampal CA1 and CA3 regions from 24 hr to 7 d after HI. These same brain areas developed infarcts and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells within 24-48 hr of HI. In primary cortical neurons, NP1 protein was induced >2.5-fold (p < 0.001) after their exposure to hypoxia that caused approximately 30-40% neuronal death. Transfecting cortical neurons with antisense oligodeoxyribonucleotides directed against NP1 mRNA (NP1AS) significantly inhibited (p < 0.01) hypoxia-induced NP1 protein induction and neuronal death (p < 0.001), demonstrating a specific requirement of NP1 in hypoxic neuronal injury. NP1 protein colocalized and coimmunoprecipitated with the fast excitatory AMPA glutamate receptor subunit (GluR1) in primary cortical neurons, and hypoxia induced a time-dependent increase in NP1-GluR1 interactions. NPIAS also protected against AMPA-induced neuronal death (p < 0.05), implicating a role for NP1 in the excitotoxic cascade. Our results show that NP1 induction mediates hypoxic-ischemic injury probably by interacting with and modulating GluR1 and potentially other excitatory glutamate receptors.

Animals↗
PubMed2003

Cure4Kids - building online learning and collaboration networks.

The International Outreach Program of St. Jude Childrens' Research Hospital has been developing programs to help countries with limited resources develop treatment centers to treat children with catastrophic diseases such as pediatric cancer and AIDS. Cure4Kids (www.cure4kids.org) is the Internet learning network that delivers medical education to doctors and nurses on pediatric cancer and AIDS. The objective of Cure4Kids is not only education, but also to provide tools for communications and collaborations among individuals.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Synaptically targeted narp plays an essential role in the aggregation of AMPA receptors at excitatory synapses in cultured spinal neurons.

Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In the present paper, we examine the role of endogenous Narp in excitatory synapse formation by using novel, dominant-negative Narp mutants (dnNarp) that selectively bind endogenous Narp and prevent its accumulation at synapses. Axons from neurons transfected with wild-type Narp showed an increase in their ability to cluster AMPA receptors on spinal neurons, whereas axons from neurons transfected with dnNarp showed a marked decrease in their ability to induce GluR1 clusters on contacted dendrites. Despite their marked effect at excitatory synapses, dnNarp and wild-type Narp had no effect on the postsynaptic clustering of the inhibitory protein gephyrin or the percentage of contacts associated with staining for the presynaptic vesicle proteins GAD or synaptophysin. Use of the dnNarp mutants to suppress endogenous Narp expression by postsynaptic dendrites showed a complementary role for dendritic Narp in the clustering of synaptic AMPA receptors, as well as a reduction in the total number of excitatory synapses on transfected neurons. Together these experiments suggest an important role for Narp in the formation of excitatory synapses in cultured spinal neurons.

Animals↗