PubMed Health⌕ Search

Biomedical subjects

Anthony Hughes

Publications and source records attributed to Anthony Hughes.

10 recordsLinked to original sources

Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer's disease.

Interleukin 10 (IL-10) is an important anti-inflammatory cytokine produced in response to neuroinflammation and might be involved in modulating the progression of Alzheimer's disease (AD) through inhibiting the action of pro-inflammatory cytokines. We have used immunohistochemistry, Western blotting, real time-PCR (RT-PCR) on frontal (BA 6/24) and temporal (BA 20-22) neocortex and hippocampus from AD and control brains as well as genetic association analysis to address the possible involvement of IL-10 in AD. Expression of IL-10 in AD and control brains at both protein and mRNA levels were detected. However, the level of expression, particularly of IL-10 protein, varied considerably in individual brains and we did not find a significant difference between AD and controls. Using direct sequencing we examined five single nucleotide polymorphisms (SNPs) (-3538, -1354, -1087, -824, -597) and two microsatellites (IL-10-G, IL-10-R) in the promoter region of the IL-10 gene. None of the identified SNPs were found to be associated with AD either individually or as haplotypes. Levels of IL-10 protein and gene expression examined also did not appear to be related to AD. Despite this being a relatively small sample, these data suggest that IL-10 does not play a major role in the development of AD.

Aged↗

Comparing outcomes of voice therapy: a benchmarking study using the therapy outcome measure.

The quality cycle requires clinicians to assess the outcomes of interventions. Benchmarking is an approach that has been advocated to compare current performance across different services to identify commonalities and significant differences. This article gives the results of a study of outcomes in speech and language therapy (SLT) using the therapy outcome measure (TOM) for patients with voice disorder (dysphonia) comparing outcomes of seven separate speech and language therapy services. The study aimed to identify the similarities and differences in outcomes of care provided by different services. Two hundred and forty patients with dysphonia (age range 3-87.5 years, average 51.9 years) were treated. The results indicated that although there was no significant difference in the profile of the severity of symptomology of patients referred to speech and language therapy in different geographical areas, there was a significant difference in the treatment outcomes across the services and in the stated reason for discharge from treatment. Nevertheless, most patients with dysphonia had a good outcome and this was associated with completion of the course of treatment. There were significant differences in the number of treatment contacts provided by the different services and in the duration (between admission and discharge) of treatment across the services. Benchmarking can provide useful information through use of routinely collected clinical data.

Adolescent↗

Effect of divalproex sodium on behavioural and cognitive problems in elderly dementia.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) occur in up to 90% of individuals with dementia at some point in their illness. BPSD reduce patient quality of life, cause great distress to caregivers and are the most common reason for institutionalisation. In nursing homes, pharmacological measures (usually antipsychotics or benzodiazepines) are often required to control agitation and aggression in patients with dementia. However, no medications have been approved by the US Food and Drug Administration for this indication as yet. The antiepileptic agent divalproex sodium may have advantages in this setting because of lower rates of drug interactions and adverse effects in this patient population. OBJECTIVE: The aim of the study was to assess the impact of treatment with divalproex sodium on behavioural, mood and cognitive measures in a population of elderly nursing home residents with a history of behaviour problems associated with dementia. MATERIALS AND METHODS: The study was a retrospective analysis of a long-term care database which allowed assessment of the impact of divalproex sodium therapy on behavioural, mood and cognitive measures in elderly nursing home residents with a history of dementia-related behaviour problems. Minimum Data Set items relating to problems of behaviour, cognition and mood were collected prior to and after divalproex sodium treatment over a 1-year period. Two-phase generalised linear regression, with fixed intersections at the time of divalproex sodium initiation, was used to estimate trends in each measure prior to and after divalproex sodium initiation. Monotherapy, combination therapy with benzodiazepines and antipsychotics, and dose comparisons of divalproex sodium were studied. RESULTS: In all three situations (i.e. as monotherapy, in combination with benzodiazepines and antipsychotics, and at both higher and lower doses), divalproex sodium therapy was shown to have multiple beneficial effects on various behavioural, mood and cognition indicators in elderly nursing home residents. In general, the data seemed to support more favourable results for the higher divalproex sodium dose group. CONCLUSIONS: These data support the use of divalproex sodium in elderly nursing home residents with a history of dementia and behaviour problems and warrant conduct of prospective, randomised trials of the drug in this setting.

Aged↗

Living with HIV in New Zealand: balancing health and quality of life.

AIM: This paper characterises the health and wellbeing of HIV-positive people in New Zealand. METHODS: The HIV Futures New Zealand Survey is a self-complete anonymous questionnaire distributed in a variety of ways. Data were collected on health, clinical, and social variables. RESULTS: There were 226 responses, estimated to be approximately 25% of the HIV positive population. Respondents were aged between 18 and 68, and 56% were homosexual men. Most (68%) reported a viral load on most recent test of below 500 copies/mL and 59% had a CD4 lymphocyte count on most recent test of over 250 cells/mcL. However, 28% reported a major health condition in addition to HIV and 21% had a mental health condition. Most respondents (64%) were currently using antiretroviral therapy. Many (84%) knew other people with HIV and had contact with an HIV/AIDS organisation (77%). Forty-two percent of respondents had stopped working because of HIV, and 47% reported their main source of income as a Government benefit. CONCLUSIONS: This research has demonstrated that, while the HIV-positive population of New Zealand generally has improved health as a result of antiretroviral therapy, there are still significant social and economic barriers to their quality of life.

Anti-Retroviral Agents↗

APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease.

Polymorphisms in the APOE promoter, ACE1 and CYP46 genes have all been reported to be associated with Alzheimer's disease (AD). We studied the relationship of these polymorphisms to the presence of AD in 86 neuropathologically confirmed cases of AD and 58 controls. In addition, we assessed the effects of these polymorphisms on the accumulation of beta-amyloid (Abeta) in the cerebral parenchyma and vasculature. No association was observed between any of the polymorphisms and the presence of AD, the parenchymal Abeta load or the severity of cerebral amyloid angiopathy (CAA). Here we report that polymorphisms within the APOE promoter, ACE1 and CYP46 gene are not risk factors for AD and are not associated with parenchymal or vascular accumulation of Abeta.

Aged↗

Gastrointestinal adverse events in a general population sample of nursing home residents taking cholinesterase inhibitors.

OBJECTIVE: To assess the occurrence of gastrointestinal (GI) adverse events in a national sample of nursing home residents taking donepezil, galantamine, or rivastigmine. DESIGN: A retrospective analysis of the Minimum Data Set (MDS) was performed. SETTING: Four hundred-fifty-two nursing facilities across the United States. PARTICIPANTS/INTERVENTIONS: During 2000, 2001, and 2002, eligible residents began donepezil, galantamine, or rivastigmine monotherapy. Among these treatment groups, 5,846, 750, and 1,672 residents, respectively, were included in the analysis. All MDS assessments were analyzed if completed. Analyses were conducted at baseline and within one year of initiating therapy. MAIN OUTCOME MEASURES: Occurrence of vomiting, stomach pain, diarrhea, weight loss, and insomnia. RESULTS: Overall, GI adverse events ranged from 2% to 9% and were comparable among the groups. Residents taking galantamine were more likely to experience diarrhea relative to those taking rivastigmine or donepezil (8.9% versus 6.8% versus 6.4%, respectively; P = 0.035), and less likely to lose weight relative to these groups (15.6% versus 20.0% versus 20.3%, respectively; P = 0.01). GI adverse events were less frequent during the maintenance phase compared with the initial drug-titration phase. CONCLUSION: GI events generally occurred with similar frequency in a national sample of nursing home residents taking donepezil, galantamine, or rivastigmine in the usual clinical practice setting.

Journal Article↗

Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease.

Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-alpha gene to respectively examine TNF-alpha polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-alpha point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when -308/A, -238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P = 0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD.

Aged↗

APOE and cerebral amyloid angiopathy in the elderly.

Over 30% of normal elderly people have cerebral amyloid angiopathy (CAA). Possession of APOE epsilon4 is associated with increased prevalence and severity of CAA in Alzheimer's disease (AD) and in cerebral haemorrhage. We examined CAA in relation to APOE genotype in brains from 152 people aged 60-102 years, without AD or cerebral haemorrhage. Prevalence of CAA increased with age (p = 0.003). CAA was not associated with APOE genotype. The frequency of epsilon4 showed a significant negative association with age (p = 0.016). Age at death was significantly lower in those with than without epsilon4 (p = 0.028). Possession of epsilon4 does not by itself confer an increased risk of CAA but may be associated with reduced longevity even in the absence of AD or cerebral haemorrhage.

Aged↗