Biomedical subjects

Gillian Hamilton

Publications and source records attributed to Gillian Hamilton.

7 recordsLinked to original sources

PubMed2006

Polymorphisms in the phosphate and tensin homolog gene are not associated with late-onset Alzheimer's disease.

The varepsilon4 allele of the APOE locus is the only confirmed risk factor for late-onset Alzheimer's disease (LOAD). The phosphate and tensin homolog (PTEN) gene is both a biological and positional candidate gene for LOAD. Eight polymorphisms spanning this gene were selected from dbSNP and genotyped in pooled DNA samples of both cases and controls. No evidence for association with LOAD was obtained in this study although further investigation revealed low levels of linkage disequlibrium (LD) between the genotyped SNPs. Our results suggest that it is unlikely that genetic variation within the PTEN gene contributes to risk of LOAD.

Aged↗

PubMed2006

Outcome evaluation of a randomized trial of the PhoenixCare intervention: program of case management and coordinated care for the seriously chronically ill.

OBJECTIVE: To document outcomes of a randomized trial of the PhoenixCare demonstration program of palliative care and coordinated care/case management for seriously chronically ill individuals who simultaneously received active treatment from managed care organizations (MCOs). DESIGN: Patients, continuously enrolled between July 1999, and March 2001, were randomly assigned to the PhoenixCare program or a control group receiving usual MCO care. SETTING: Hospice of the Valley, Phoenix, Arizona. PARTICIPANTS: Participants were 192 patients with chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF), who had an estimated 2-year life expectancy. INTERVENTION: Intensive home-based case management provided by registered nurse casemanagers, in coordination with patients' existing source of medical care, comprised the intervention. Program foci included disease and symptom management, patient self-management of illness and knowledge of illness-related resources, preparation for end-of life, physical and mental functioning, and utilization of medical services. OUTCOME MEASURES: Outcomes, assessed every 3 months by telephone interview, included measures related to all program foci; the SF-36 was used to evaluate physical and mental functioning; emergency department visits exemplified medical service utilization. RESULTS: Compared to controls, PhoenixCare patients exhibited significantly better outcomes on self-management of illness, awareness of illness-related resources, and legal preparation for end of life. They reported lower symptom distress, greater vitality, better physical functioning and higher self-rated health than randomized controls. Emergency department utilization was equivalent across groups. Patients with COPD showed stronger responsiveness to the intervention. CONCLUSION: A novel model of patient care that combined greatly enhanced palliative carefocused case management with ongoing MCO-based treatment was associated with improved functioning of chronically severely ill patients in the last years of life.

Adult↗

PubMed2005

A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.

Strong evidence of linkage to late-onset Alzheimer disease (LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10-specific association study with 1,412 gene-based single-nucleotide polymorphisms (SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P < .05). Five of these markers replicated at P < .05 in the validation sample sets. One marker, rs498055, located in a gene homologous to RPS3A (LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples. One of the case-control samples with significant association to rs498055 was derived from the linkage sample (P = .0165). These results indicate that variants in the RPS3A homologue are associated with LOAD and implicate this gene, adjacent genes, or other functional variants (e.g., noncoding RNAs) in the pathogenesis of this disorder.

Alleles↗

PubMed2005

Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing.

The hypothesis that polymorphisms in the gene for nicastrin (NCSTN) are associated with differences in cognitive level and ageing was tested in 462 relatively healthy surviving participants of the Scottish Mental Survey 1932. None had a history of dementia. They were tested on the Moray House Test of verbal reasoning at age 11 in 1932 and at age 79 between 1999 and 2001. At age 79 they also took tests of non-verbal reasoning, short- and long-term verbal declarative memory, Verbal Fluency, and a short screening test for dementia. Subjects who possessed at least one copy of the NCSTN B haplotype (Hap B) had higher scores on the Moray House Test (a test principally of verbal reasoning) at age 11 (p=0.036) and age 79 (p=0.027). The effect of Hap B on cognition at age 79 was non-significant after adjusting for the effect at age 11. Therefore, the effect of Hap B in this sample is on the life-long stable trait of cognitive ability, and not on age-related cognitive change. The possibility that this result might be a selection effect was not supported by the samples being in Hardy-Weinberg equilibrium with respect to the distribution of NCSTN genotypes.

Aged↗

PubMed2005

Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease.

Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a disease modifying treatment. As increasing evidence has suggested a role for glycogen synthase kinase-3 (GSK-3) in the pathogenesis of the condition we measured total GSK-3 protein (alpha and beta isoforms) and GSK-3 activity (serine 9 phosphorylation) in a group of healthy elderly people, in AD and in mild cognitive impairment (MCI). Total GSK-3 protein was increased in both AD and in MCI without a compensatory decrease in activity. These data suggest that GSK-3 assays might be a useful diagnostic marker in a readily available tissue and moreover that GSK-3 activity is increased in the prodromal phase of the disorder suggesting that inhibition of GSK-3 might be a useful therapeutic strategy.

Aged↗

PubMed2004

Alpha-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease.

The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.

Aged↗

PubMed2003

The PhoenixCare Program.

In response to a perceived need for patient access to palliative care and supportive services prior to hospice eligibility, Phoenix-based Hospice of the Valley (HOV) applied for and received a 3-year demonstration grant (1999-2001) from The Robert Wood Johnson (RWJ) Promoting Excellence in End-Of-Life Care Project. HOV established the PhoenixCare project as a demonstration of palliative and coordinated care (case management) services for seriously chronically ill individuals still undergoing active treatment of their disease within a managed care setting. The model emphasized patient/family self-empowerment and prevention. The goal was to demonstrate that it was possible to expand the scope of care for the seriously chronically ill, add palliative care, and improve patient quality of life at less (or no more) cost than that for a comparable group of managed care patients not receiving PhoenixCare services. The model proved most useful to patients willing and able to assume a degree of control over their own care. Physicians referred fewer than 5% of the patients enrolled while managed care plan case managers and hospital discharge planners referred 83%, suggesting that in organized systems of care physicians are not a primary source for patient referrals. The structure and content of the PhoenixCare model, its general acceptability to patients, physicians and managed care plans, and its applicability to other sites are discussed in this article. Outcomes from the study will be published in a subsequent paper.

Arizona↗