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Biomedical subjects

A McCarthy

Publications and source records attributed to A McCarthy.

At least 19 recordsLinked to original sources
PubMed2007

A study of idiopathic generalised epilepsy in an Irish population.

UNLABELLED: Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on clinical and EEG features. PURPOSE: The aim of this study was to characterise all cases of IGE with supportive EEG abnormalities in terms of gender differences, seizure types reported, IGE syndromes, family history of epilepsy and EEG findings. We also calculated the limited duration prevalence of IGE in our cohort. METHODS: Data on abnormal EEGs were collected retrospectively from two EEG databases at two tertiary referral centres for neurology. Clinical information was obtained from EEG request forms, standardised EEG questionnaires and medical notes of patients. RESULTS: two hundred twenty-three patients met our inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic seizures were the most common seizure type reported, 162 (72.65%) having a generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA) was the most common syndrome in our cohort being present in 94 patients (34 male, 60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG studies in all patients showed generalised epileptiform activity. CONCLUSIONS: More women than men were diagnosed with generalised epilepsy. Tonic clonic seizures were the most common seizure type reported. EGTCSA was the most frequent syndrome seen. Gender differences were evident for JAE and JME as previously reported and for EGTCSA, which was not reported to date, and reached statistical significance for EGTCA and JME.

Adult↗
PubMed2007

A mouse model of basal-like breast carcinoma with metaplastic elements.

Breast cancers arising in carriers of germline BRCA1 mutations frequently have a basal-like phenotype. Basal-like cancers are characterized by high histological grade, central necrotic areas, foci with metaplastic differentiation, lack of hormone receptor and HER2 (ErbB2) expression, and consistent positivity for basal markers, including CK5/6, CK14, and EGFR. We have used germline manipulation to generate a conditional mouse model of Brca1 deficiency. Transgenic expression of Cre recombinase in the mammary gland of these mice results in deletion of exons encoding the C-terminus of Brca1 and leads to tumour formation when combined with heterozygosity for a p53 mutation. Histologically, these mammary gland tumours were characterized by high histological grade, central necrotic areas, and presence of homologous metaplastic elements. These metaplastic elements consisted of neoplastic spindle cells or squamous cell differentiation in the form of keratin pearls or individual cell keratinization. Immunohistochemical analysis revealed expression of basal-like markers in all cases. The tumour phenotype generated in our mouse model was compared with published data on human basal-like breast carcinomas and also with metaplastic breast cancers with a basal-like phenotype; the comparison showed that we have generated a mouse model of basal-like breast cancer, which should prove useful in testing new and targeted treatments for this type of breast cancer.

Animals↗
PubMed2006

High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline.

An automatic data-collection system has been implemented and installed on seven insertion-device beamlines and a bending-magnet beamline at the ESRF (European Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In Europe) development of an automated structure-determination pipeline. The system allows remote interaction with beamline-control systems and automatic sample mounting, alignment, characterization, data collection and processing. Reports of all actions taken are available for inspection via database modules and web services.

Data Collection↗
PubMed2005

The care and nurture of undulator data sets.

Undulator radiation is the X-ray source of choice for modern macromolecular crystallography beamlines. Here, the basic properties of undulator sources are described and it is indicated why they make such good X-ray sources for macromolecular crystallography. Collection of excellent data from these beamlines is not always straightforward; therefore, a number of rules are postulated for undulator data collection and guidelines are offered which will help to ensure a satisfactory experiment.

Crystallization↗
PubMed2004

Dietary restraint and the mis-reporting of anthropometric measures by middle-aged adults.

OBJECTIVE: To assess whether levels of dietary restraint are associated with mis-reporting measures of adiposity by middle-aged adults. DESIGN: Cross-sectional study of middle-aged men and women, the parents of a group of young adults followed up since birth. METHODS: In all, 631 couples were mailed questionnaires and asked to record their height, weight and waist circumference. A paper tape measure with instructions for use was attached. Couples also completed the dietary restraint section of the Dutch Eating Behaviour Questionnaire, and provided information on employment and lifestyle habits. A subsample of participants was then invited to attend a clinic where detailed anthropometric measures were taken. RESULTS: In all, 435 women (69%) and 332 men (55%) completed the questionnaire; of those invited, 182 (85%) women and 102 (61%) men attended a clinic session. Regression analyses showed that the dietary restraint score was associated with the mis-reporting of BMI by women (P<0.01), but not men (test for interaction with gender, P=0.11). In women, the difference between the measured and reported BMI increased by 0.36 kg/m(2) (0.11-0.61) per unit increase in restraint score. This association was independent of age, smoking, social class, slimming, exercise frequency or television viewing time, but was attenuated in models controlling for measured BMI. The dietary restraint score was not associated with mis-reporting of waist circumference in men or women. CONCLUSIONS: Dietary restraint score may be a useful tool for identifying individuals more likely to mis-report anthropometric measurements, although associations may vary by gender.

Analysis of Variance↗
PubMed2004

Barriers to effective cancer pain management: a survey of Australian family caregivers.

Cancer pain continues to be an important focus of health research and intervention development. The continuing shift of cancer care to the community increases the family caregiver's role in pain management and highlights the need to understand family experiences and also family barriers to effective pain management. This paper presents the findings of an Australian study exploring attitudinal barriers to effective pain management amongst 75 family caregivers of people with cancer attending an outpatient clinic. Approximately 75% of the caregivers demonstrated concerns or were unsure about addiction, a belief likely to impact on the use of prescribed opioids in the home. Caregivers demonstrated similar levels of concern about side-effects or whether the presence of pain indicated disease progression. These findings support research in other populations and are further evidence of the need to include family caregivers, along with patients, in intervention studies aimed at reducing the impact of these barriers on effective pain management.

Adult↗
PubMed2004

Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity.

BACKGROUND: Northern Ireland has a high and rising prevalence rate of multiple sclerosis (MS). The most recent survey in 1996 found a rate of 168.7/100 000. Recorded prevalence rates for the south of Ireland, including County Wexford, have been markedly lower and seemed to suggest the existence of a prevalence gradient within the island. OBJECTIVES: To compare the prevalence of multiple sclerosis in Co. Wexford in the south east of Ireland and Co. Donegal in the north west, and to establish whether a variation in prevalence of MS exists within Ireland. METHODS: Patients were referred from multiple sources. Review of clinical case records and/or patient examination confirmed the diagnosis. RESULTS: In Co. Wexford, 126 patients were found to have clinically definite or probable multiple sclerosis with a prevalence rate of 120.7/100 000 (95% confidence intervals (CI) 100.6 to 143.8), which is similar to other areas of similar latitude within the British Isles. In Co. Donegal, 240 people had clinically definite or probable MS with a prevalence rate of 184.6/100 000 (95% CI 162.0 to 209.5). The difference in prevalence rates is statistically significant (Z = 3.94, p = <0.001). CONCLUSION: There is a latitudinal variation in the prevalence rate of MS between the north and the south of Ireland. The increased prevalence of MS seen in Co. Wexford is likely to represent better case ascertainment and improved diagnostic accuracy rather than an actual increase in prevalence. The north/south variation in prevalence may represent a variation in the genetic predisposition to MS between the background populations of the two counties.

Adolescent↗
PubMed2004

The chlamydia screening studies: rationale and design.

BACKGROUND: Screening has been recommended to reduce the prevalence and morbidity associated with genital chlamydia infection in the United Kingdom. METHODS: We describe the rationale and study design of the Chlamydia Screening Studies (ClaSS), a collaborative project designed to evaluate screening outside genitourinary medicine clinics. A non-selective, active screening approach in 16-39 year olds randomly sampled from 27 general practice lists in the Bristol and Birmingham areas formed the basis of interlinked studies: a case-control study was used to investigate factors to improve the targeting of screening; participants with chlamydia were invited to enroll in a randomised controlled trial to evaluate partner notification conducted in primary care; and laboratory based studies were used to assess the best specimens and tests. We also explored psychosocial effects of screening and partner notification and modelled the cost effectiveness of the programme. CONCLUSION: Results from four pilot practices show that mailing of specimens for chlamydia testing is feasible but that it is difficult to achieve high response rates with postal screening. The high prevalence of asymptomatic infection in men suggests that efforts to screen men for chlamydia should be strengthened.

Adolescent↗
PubMed2003

An investigation of fetal, postnatal and childhood growth with insulin-like growth factor I and binding protein 3 in adulthood.

OBJECTIVE: Weight at birth and adult height are positively associated with cancer risk. These patterns may be mediated by the insulin-like growth factor (IGF) axis. We have examined whether pre- and postnatal growth patterns have a long-term influence on adult IGF-I and IGFBP-3 levels. DESIGN: A follow-up study of a randomized controlled trial of milk supplementation in pregnancy and childhood. SUBJECTS: A total of 951 individuals took part in a study of diet and growth in South Wales between 1972 and 1974 followed up from birth until their mid-20s. MEASUREMENTS: Anthopometric measures at birth, postnatally up to 5 years of age and in adulthood, and serum measures of IGF-I and IGF-I to IGFBP-3 ratio at mean age of 25 years. RESULTS: A total of 63 subjects (70%) provided blood for analysis. We found no association between birth dimensions and adult IGF-I. Subjects who exhibited 'catch-down growth' had lower IGF-I levels (P-value for trend 0.02). Adult height was positively related to IGF-I, for every one standard deviation increase in adult height, IGF-I increased by 3.75 ng/dl (95% CI 0.46-7.08, P = 0.03). Adiposity was inversely associated with the IGF-I and IGF-I to IGFBP-3 ratio and positively associated with IGFBP-3. The strength of the associations increased with age. Downward centile crossing at any time in childhood was associated with lower IGF-I whilst the highest levels were observed in subjects who were tall throughout their early life course. Adult height remained a significant predictor of IGF-I even after adjustment for earlier growth. CONCLUSIONS: Our results indicate that IGF-I levels in early adulthood are associated with patterns of childhood growth as well as adult stature and adiposity. These associations suggest the IGFs may contribute to anthropometric associations with cancer risk.

Adult↗
PubMed2002

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study.

In a historical cohort study of all singleton live births in Northern Ireland from 1971-86 (n=434,933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age. High birth weight (> or =3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous miscarriage or increased gestation (> or =40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95% CI=0.48--0.94). Children born into more crowded households (> or =1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91 and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.

Abortion, Spontaneous↗
PubMed2001

Pharmacogenetics.

Explore the source record for details and available documents.

Cooperative Behavior↗
PubMed2001

Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers.

AIMS: To evaluate the pharmacokinetic interaction between ritonavir and mefloquine. METHODS: Healthy volunteers participated in two separate, nonfasted, three-treatment, three-period, longitudinal pharmacokinetic studies. Study 1 (12 completed): ritonavir 200 mg twice daily for 7 days, 7 day washout, mefloquine 250 mg once daily for 3 days then once weekly for 4 weeks, ritonavir restarted for 7 days simultaneously with the last mefloquine dose. Study 2 (11 completed): ritonavir 200 mg single dose, mefloquine 250 mg once daily for 3 days then once weekly for 2 weeks, ritonavir single dose repeated 2 days after the last mefloquine dose. Erythromycin breath test (ERMBT) was administered with and without drug treatments in study 2. RESULTS: Study 1: Ritonavir caused less than 7% changes with high precision (90% CIs: -12% to 11%) in overall plasma exposure (AUC(0,168 h)) and peak concentration (Cmax) of mefloquine, its two enantiomers, and carboxylic acid metabolite, and in the metabolite/mefloquine and enantiomeric AUC ratios. Mefloquine significantly decreased steady-state ritonavir plasma AUC(0,12 h) by 31%, Cmax by 36%, and predose levels by 43%, and did not affect ritonavir binding to plasma proteins. Study 2: Mefloquine did not alter single-dose ritonavir pharmacokinetics. Less than 8% changes in AUC and Cmax were observed with high variability (90%CIs: -26% to 45%). Mefloquine had no effect on the ERMBT whereas ritonavir decreased activity by 98%. CONCLUSIONS: Ritonavir minimally affected mefloquine pharmacokinetics despite strong inhibition of CYP3A4 activity from a single 200 mg dose. Mefloquine had variable effects on ritonavir pharmacokinetics that were not explained by hepatic CYP3A4 activity or ritonavir protein binding.

Administration, Oral↗
PubMed2001

(13)C incorporation into DNA as a means of identifying the active components of ammonia-oxidizer populations.

AIMS: To identify active CO2-assimilating species of ammonia-oxidizing bacteria in fresh water sediment. METHODS AND RESULTS: Enrichment cultures were incubated in the presence of 13C labelled CO2, and 13C-DNA successfully resolved from 12C-DNA by caesium chloride density gradient ultracentrifugation of DNA extracts. Ammonia-oxidizer DNA recovered from these gradients was amplified and characterised by Temporal Temperature Gradient Gel Electrophoresis (TTGE), with confirmatory sequence analysis to identify the metabolically active components of the population. CONCLUSION: The 12C-DNA fraction was dominated by nitrosospiras, in contrast to the 13C-DNA fraction which was largely nitrosomonad DNA, in support of the hypothesis that nitrosomonads out-compete nitrosospiras in laboratory culture. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of stable isotype incorporation into ammonia-oxidizer DNA could therefore circumvent the problems associated with RNA detection to identify metabolically active species in situ.

Carbon Dioxide↗