Biomedical subjects

J Hughes

Publications and source records attributed to J Hughes.

At least 37 records · Page 2Linked to original sources

PubMed2005

An investigation into the health-related quality of life of individuals living with HIV who are receiving HAART.

The health authorities have recently accepted the routine provision of highly active antiretroviral therapy to persons living with AIDS in South Africa. There is a need to investigate the impact of HAART on the health-related quality of life of people living with HIV/AIDS (PLWHA) in a resource-poor environment, as this will have an influence on compliance and treatment outcome. The aim of this study was to explore whether HAART is efficacious in improving the self-reported health-related quality of life (HRQoL) in a group of PWLA in WHO Stages 3 and 4 living in a resource-poor community. A quasi-experimental, prospective repeated measures design was used to monitor the HRQoL over time in participants recruited to an existing HAART programme. The HRQoL of 117 participants was determined through the use of the Xhosa version of the EQ-5D and measurements were taken at baseline, one, six and 12 months. At the time of the 12-month questionnaire, 95 participants had been on HAART for 12 months. Not all participants attended all follow-up visits, but only two participants had withdrawn from the HAART programme, after two or three months. At baseline, the rank order of problems reported in all domains of the EQ-5D was significantly greater than at 12 months. The mean score on the global rating of health status increased significantly (p < 0.001) from a mean of 61.7 (SD = 22.7) at baseline to 76.1 at 12 months (SD = 18.5) It is concluded that, even in a resource-poor environment, HRQoL can be greatly improved by HAART, and that the possible side effects of the drugs seem to have a negligible impact on the wellbeing of the subjects. This bodes well for the anticipated roll-out of HAART within the public health sector in South Africa.

Antiretroviral Therapy, Highly Active↗

PubMed2005

Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase.

Type I recessive congenital methaemoglobinaemia (RCM), caused by the reduced form of nicotinamide adenine dinucleotide (NADH)-cytochrome b(5) reductase (cytb(5)r) deficiency, manifests clinically as cyanosis without neurological dysfunction. Two mutations, E255- and G291D, have been identified in the NADH-binding lobe of cytb(5)r in previously reported patients, and we have detected a further novel mutation, D239G, in this lobe in two unrelated Irish families. Although one family belongs to the genetically isolated Traveller Community, which separated from the general Irish population during the 1845-48 famine, the D239G mutation was present on the same haplotype in both families. Three known cytb(5)r mutations were also identified, including the R159- mutation, which causes loss of the entire NADH-binding lobe and had previously been reported in an individual with type II RCM. Characterization of the three NADH-binding lobe mutants using a heterologous expression system revealed that all three variants retained stoichiometric levels of flavin adenine dinucleotide with spectroscopic and thermodynamic properties comparable with those of native cytb(5)r. In contrast to the E255- and G291D variants, the novel D239G mutation had no adverse impact on protein thermostability. The D239G mutation perturbed substrate binding, causing both decreased specificity for NADH and increased specificity for NADPH. Thus cytb(5)r deficient patients who are heterozygous for an NADH-binding lobe mutation can exhibit the clinically less severe type I phenotype, even in association with heterozygous deletion of the NADH-binding lobe.

Adolescent↗

PubMed2005

Changing trends in US mesothelioma incidence.

The correspondence by Weillet al (below) refers to a letter by Greenberg, which was published in February's edition of the journal. We regret the late appearance of this printed response, which arises from an administrative error. An electronic version of this text was posted on the website on 1 February 2005.

Asbestosis↗

PubMed2005

Understanding alpha-globin gene regulation: Aiming to improve the management of thalassemia.

Over the past 50 years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the alpha- and beta-globin genes are normally regulated and documenting the effects of inherited mutations that cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found more often. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression that, in turn, may open up new avenues for improving the management of patients with common types of thalassemia.

Chromosomes, Human, Pair 11↗

PubMed2004

Antidepressants for smoking cessation.

BACKGROUND: There are at least two theoretical reasons to believe antidepressants might help in smoking cessation. Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction, independent of their antidepressant effects. OBJECTIVES: The aim of this review is to assess the effect of antidepressant medications in aiding long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; sertraline, tryptophan and venlafaxine. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in March 2004. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative therapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation and using pharmacotherapy to help smokers reduce cigarette consumption. We excluded trials with less than six months follow up. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the pharmacotherapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months follow up in patients smoking at baseline, expressed as an odds ratio (OR). We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effect model. MAIN RESULTS: There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these detected a significant long-term benefit. There were five trials of selective serotonin reuptake inhibitors; three of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant effects, and there was no evidence of a significant benefit when results were pooled. There were 24 trials of bupropion and six trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (19 trials, OR 2.06, 95% confidence intervals [CI] 1.77 to 2.40) and nortriptyline (four trials, OR 2.79, 95% CI 1.70 to 4.59) both doubled the odds of cessation. In one trial the combination of bupropion and nicotine patch produced slightly higher quit rates than patch alone, but this was not replicated in a second study. Two trials of extended therapy with bupropion to prevent relapse after initial cessation did not show a significant long-term benefit. There is a risk of about 1 in 1000 of seizures associated with bupropion use. Concerns that bupropion may increase suicide risk are currently unproven. REVIEWERS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. The fact that only some forms of antidepressants aid cessation and that they do so regardless of depressive symptoms strongly suggests that their mode of action is independent of their antidepressant effect.

Anti-Anxiety Agents↗

PubMed2004

Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta.

Restricted fetal growth is associated with postnatal mortality and morbidity and may be directly related to alterations in the capacity of the placenta to supply nutrients. We proposed previously that imprinted genes can regulate nutrient supply by the placenta. Here, we tested the hypothesis that the insulin-like growth factor 2 gene (Igf2) transcribed from the placental-specific promoter (P0) regulates the development of the diffusional permeability properties of the mouse placenta. Using mice in which placental-specific Igf2 had been deleted (P0), we measured the transfer in vivo of three inert hydrophilic solutes of increasing size (14C-mannitol, 51CrEDTA, and 14C-inulin). At embryonic day 19, placental and fetal weights in P0 conceptuses were reduced to 66% and 76%, respectively, of wild type. In P0 mutants, the permeability.surface area product for the tracers at this stage of development was 68% of that of controls; this effect was independent of tracer size. Stereological analysis of histological sections revealed the surface area of the exchange barrier in the labyrinth of the mouse placenta to be reduced and thickness increased in P0 fetuses compared to wild type. As a result, the average theoretical diffusing capacity in P0 knockout placentas was dramatically reduced to 40% of that of wild-type placentas. These data show that placental Igf2 regulates the development of the diffusional exchange characteristics of the mouse placenta. This provides a mechanism for the role of imprinted genes in controlling placental nutrient supply and fetal growth. Altered placental Igf2 could be a cause of idiopathic intrauterine growth restriction in the human.

Animals↗

PubMed2004

Biocatalytic scrubbing of gaseous acrylonitrile using Rhodococcus ruber immobilized in synthetic silicone polymer (ImmobaSil) rings.

Microbial detoxification of acrylonitrile vapor was performed using Rhodococcus ruber immobilized into rings of a synthetic silicone polymer (ImmobaSil ) sponge. The immobilization matrix was used as both the cell support material and also as the trickle-bed column packing. The elimination capacity of the biocatalytic scrubber was determined for different influent concentrations of gaseous acrylonitrile. The working life of the nongrowing biocatalyst was also examined under test conditions and was found to be at least 70 days before biocatalyst replacement was required. An elimination capacity of 4.0 kg m(-3) h(-1) was achieved with a 95% removal efficiency, and an elimination capacity of over 7.2 kg m(-3) h(-1) acrylonitrile was achieved with a removal efficiency of 90%. This elimination capacity is 10 times that previously published in the literature.

Acrylonitrile↗

PubMed2004

Milk drinking, ischaemic heart disease and ischaemic stroke I. Evidence from the Caerphilly cohort.

OBJECTIVE: To test the hypothesis that milk drinking increases the risk of ischaemic heart disease (IHD) and ischaemic stroke in a prospective study. DESIGN: In the Caerphilly Cohort Study dietary data, including milk consumption, were collected by a semiquantitative food frequency questionnaire in 1979-1983. The cohort has been followed for 20-24 y and incident IHD and stroke events identified. SUBJECTS: A representative population sample in South Wales, of 2512 men, aged 45-59 y at recruitment. MAIN OUTCOME MEASURES: In total, 493 men had an IHD event and 185 an ischaemic stroke during follow-up. RESULTS: After adjustment, the hazard ratio in men with a milk consumption of one pint (0.57 l) or more per day, relative to men who stated that they consumed no milk, is 0.71 (0.40-1.26) for IHD and 0.66 (0.24-1.81) for ischaemic stroke. At baseline, 606 men had had clinical or ECG evidence of vascular disease, and in these the vascular risk was even lower (0.37; 0.15-0.90). The hazard ratio for IHD and ischaemic stroke combined is 0.64 (0.39-1.06) in all men and 0.37 (0.15-0.90) in those who had had a prior vascular event. CONCLUSION: The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk. Evidence from an overview of all published cohort studies on this topic should be informative. SPONSORSHIP: : The Medical Research Council, the University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

Aged↗

PubMed2004

Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies.

OBJECTIVE: Milk consumption is considered a risk factor for vascular disease on the basis of relevant biological mechanisms and data from ecological studies. The aim was to identify published prospective studies of milk drinking and vascular disease, and conduct an overview. DESIGN: The literature was searched for cohort studies, in which an estimate of the consumption of milk, or the intake of calcium from dairy sources, has been related to incident vascular disease. MAIN OUTCOME MEASURES: Ischaemic heart disease and ischaemic stroke. RESULTS: In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk. A pooled estimate of relative odds in these subjects, relative to the risk in subjects with the lowest consumption, is 0.87 (95% CI 0.74-1.03) for ischaemic heart disease and 0.83 (0.77-0.90) for ischaemic stroke. The odds ratio for any vascular event is 0.84 (0.78-0.90). CONCLUSIONS: Cohort studies provide no convincing evidence that milk is harmful. While there still could be residual confounding from unidentified factors, the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk. SPONSORSHIP: The University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

Aged↗

PubMed2004

A review of the epidemiological evidence for the 'antioxidant hypothesis'.

OBJECTIVE: The British Nutrition Foundation was recently commissioned by the Food Standards Agency to conduct a review of the government's research programme on Antioxidants in Food. Part of this work involved an independent review of the scientific literature on the role of antioxidants in chronic disease prevention, which is presented in this paper. BACKGROUND: There is consistent evidence that diets rich in fruit and vegetables and other plant foods are associated with moderately lower overall mortality rates and lower death rates from cardiovascular disease and some types of cancer. The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients afford protection against chronic diseases by decreasing oxidative damage. RESULTS: Although scientific rationale and observational studies have been convincing, randomised primary and secondary intervention trials have failed to show any consistent benefit from the use of antioxidant supplements on cardiovascular disease or cancer risk, with some trials even suggesting possible harm in certain subgroups. These trials have usually involved the administration of single antioxidant nutrients given at relatively high doses. The results of trials investigating the effect of a balanced combination of antioxidants at levels achievable by diet are awaited. CONCLUSION: The suggestion that antioxidant supplements can prevent chronic diseases has not been proved or consistently supported by the findings of published intervention trials. Further evidence regarding the efficacy, safety and appropriate dosage of antioxidants in relation to chronic disease is needed. The most prudent public health advice remains to increase the consumption of plant foods, as such dietary patterns are associated with reduced risk of chronic disease.

Adult↗

PubMed2004

The use of assessment scales in Old Age Psychiatry Services in England and Northern Ireland.

Implementation of the Single Assessment Process in the UK is designed to ensure that more standardized assessment procedures are in place across all areas and agencies, that practice improves and older people's needs are comprehensively assessed. This study provides a unique picture of the range and prevalence of standardized scales used within Old Age Psychiatry Services in England and Northern Ireland, reported by 73% of old age psychiatrists. Most services (64%) used three or more standardized assessment scales (range 1-12). Sixty-two separate instruments were identified. The six most used measures were the Mini Mental State Examination (95%), the Geriatric Depression Scale (52%) and the Clock Drawing (50%), the Clifton Assessment Procedures for the elderly (26%), the Barthel Index (18%) and the Health of the Nation Outcome Scales (HoNOS) 65 + (18%). A number of factors were associated with greater use of certain standardized assessment scales. Shared documentation, along with other indicators of integration between health and social care were associated with greater use of standardized scales. The provision of a memory clinic was associated with greater use of neuropsychiatric scales and lower levels of use of cognitive scales. These results provide key material for shaping the provision of psychiatric services for older people

Aged↗

PubMed2004

Endolaryngeal cysts presenting with acute respiratory distress.

This is a retrospective review of benign cysts of the adult endolarynx that presented as airway emergencies in four teaching hospitals of Dublin, Ireland, over 2 years. During that period nine patients with endolaryngeal cysts necessitating emergency airway intervention were managed. All cases were treated by endoscopic microlaryngeal marsupialization after securing the airway either at the same time or as a staged procedure. Four of these patients required tracheostomies, one performed under local anaesthesia and the others after initial endotracheal intubation. Definitive treatment was carried out in six cases at initial endoscopic diagnosis. Three of the tracheostomized patients had a staged management, two because of their medical status and one for further investigations. On the basis of our findings we suggest that all benign cysts around the endolarynx should simply be called 'endolaryngeal cysts' instead of the current practice of trying to classify them into various histological and morphological types with no prognostic or management differences. Benign cysts of the endolarynx presenting with airway obstruction would appear to be more frequent than is generally maintained in the literature.

Adult↗

PubMed2004

The long-term effect of dietary advice on the diet of men with angina: the diet and angina randomized trial.

INTRODUCTION: The long-term effects on diet of dietary advice to eat fruit and vegetables or fatty fish are not well described. MATERIALS AND METHODS: From 1990 to 1996 3114 men aged 37-70 with treated angina were recruited from general practices in South Wales. A dietitian randomly allocated the eligible men to receive advice to eat more fruit and vegetables, or advice to eat more fatty fish, or both these types of advice or neither. In 2000, a brief self-completion questionnaire was sent to a sample of 1191 of the men known to be alive at the end of March 1999. RESULTS: The questionnaire was returned by 944 of the 1036 men alive at the time the questionnaire was sent. Those given fish advice were consuming more fatty fish but the difference was modest 21.9 g day(-1) vs. 14.0 g day(-1) (P < 0.01). The differences in fruit and vegetables intake between those given fruit advice and those not given fruit advice were small 373.2 g day(-1) vs. 351.7 g day(-1) (P = 0.05). DISCUSSION: Men of this age group may be particularly resistant to fruit and vegetables advice; population-based interventions or interventions targeted at women might be more effective.

Adult↗

PubMed2004

Fatal calcific uraemic arteriolopathy (CUA): a case report and review of the literature.

Calciphylaxis, now better known as Calcific uraemic arteriolopathy (CUA), is an uncommon condition characterised by small vessel calcification and occlusion with resultant painful violaceous skin lesions that typically ulcerate to form non-healing gangrenous ulcers. The syndrome is usually found in patients with renal failure. In this report we describe a 61 year old lady who developed lower limb ulceration secondary to calciphylaxis and discuss the current treatment options for this serious condition.

Calcinosis↗

PubMed2004

Complicated otitis media caused by Fusobacterium necrophorum.

Fusobacterium necrophorum is implicated as an aetiological agent in a variety of necrotic diseases, such as Lemièrre's syndrome (LS) in humans. LS was initially described as septic thrombophlebitis of the internal jugular vein secondary to an acute oropharyngeal infection. Other primary sources of infection include parotitis, otitis media, sinusitis, odontogenic infection and mastoiditis. In the pre-antibiotic era LS carried a high mortality. This has been reduced as a result of the widespread use of antibiotics, but there is still a definite morbidity and mortality associated with infection with this virulent organism. We report three cases of complicated otitis media caused by Fusobacterium necrophorum. The patients were treated successively with intravenous metronidazole and surgery.

Anti-Infective Agents↗

PubMed2003

Development of a conductimetric biosensor using immobilised Rhodococcus ruber whole cells for the detection and quantification of acrylonitrile.

A conductimetric biosensor for the detection of acrylonitrile in solution was designed and characterised using whole cells of Rhodococcus ruber NCIMB 40757, which were immobilised into a disc of dimethyl silicone sponge (ImmobaSil). The biosensor described was capable of the detection and quantification of acrylonitrile in aqueous solution, having a linear response to concentrations between 2 and 50 mM (106-2650 ppm) acrylonitrile. The biosensor has been shown to be reproducible with respect to the data obtained over a number of days, and retains stability for a minimum period of at least 5 days before recalibration of the biosensor is required.

Acrylonitrile↗

PubMed2003

Does integration really make a difference? A comparison of old age psychiatry services in England and Northern Ireland.

OBJECTIVE: This paper seeks to address whether integrated structures are associated with more integrated forms of service. Northern Ireland has one of the most structurally integrated and comprehensive models of health and personal social services in Europe. Social and health services are jointly administered and this arrangement should, in theory, promote collaborative working and interdisciplinary arrangements. DESIGN: The study employed a cross-sectional survey of consultants in old age psychiatry in England and Northern Ireland. Potential respondents were sourced from the UK Royal College of Psychiatrists membership list and locally collected information. MEASURES: A self-administered postal questionnaire. Along with general service arrangements, the domains measured reflect core policy issues for older people's services. Under particular scrutiny in this study were the degree of integration of health and social service provision, as well as inter-professional team working. RESULTS: The integrated health and social care services in Northern Ireland do appear to provide more integrated patterns of working, primarily in managerial arrangements and in the location of staff. There was no evidence of the impact of integration on practice in areas such as: assessment, referral and medical screening. The factors found to be associated with greater integration of health and social care in the prediction model fell into three categories: provision of specialist services; provision of outreach activities; and shared policies by which the whole team worked. CONCLUSIONS: Health and personal social services in Northern Ireland have a distinct advantage over their counterparts in comparable areas of England. The results indicate that integrated structures in old age psychiatry services are associated more with integrated management systems and less with integrated practice-related activities. Further research is required on the effectiveness and cost effectiveness of integrating services in general. It is important that future intervention studies systematically measure the component parts, nature and extent of integration and their individual and joint contribution to the effectiveness and efficacy of services.

Aged↗

PubMed2003

Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol.

A retrospective 12-year study (May 1988-July 2000) was undertaken in children with cystic fibrosis (CF) to evaluate 1) the magnitude of methicillin-resistant Staphylococcus aureus (MRSA) in these children; 2) the clinical impact of MRSA on CF; and 3) the efficacy of an MRSA protocol aimed at the eradication of the carrier state. The study maneuver comprised of 1) surveillance cultures of throat/rectum to detect the MRSA carrier state; 2) life-long cephradine rather than flucloxacillin to lift selection pressure; 3) topical application of oral and nebulized vancomycin for 5 days to clear the carriage of MRSA; and 4) a strict antistaphylococcal hygiene program, including handwashing and device policy. Fifteen children with CF (11 boys, with median age 117 months) positive for MRSA were enrolled. The current prevalence of MRSA among children with CF in our hospital is 6.5%. Of 15 children identified, only 12 (18 episodes of MRSA colonization) were treated according to protocol. Median age of MRSA acquisition was 73 months (interquartile range, 43-134 months). In 7 patients (55%), MRSA was eradicated. Of a total of 18 MRSA episodes, the protocol was successful in 10 episodes. The mean period of MRSA-free status was 12 months (range, 6-36 months). Pulmonary function (measured by FEV(1)) was not affected (68% of predicted before treatment, and 68% of predicted after treatment). All children were oropharyngeal carriers of both MRSA and ceftazidime-resistant P. aeruginosa. We believe that an effort has to be made to limit MRSA in CF clinics for the following reasons: 1) MRSA carriage in any individual is an abnormal condition; 2) limitation of systemic vancomycin use is desirable; 3) MRSA carriage may be a contraindication for lung transplantation; and 4) epidemiologically, a CF unit with a substantial MRSA problem functions as a source of dissemination for other patients.

Administration, Topical↗