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Biomedical subjects

M Rooney

Publications and source records attributed to M Rooney.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

Arginine↗
PubMed2006

Neurological abnormalities in young adults born preterm.

OBJECTIVE: Individuals born before 33 weeks' gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. METHOD: We assessed 153 VPT individuals and 71 term-born controls at 17-18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. RESULTS: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. CONCLUSIONS: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

Adolescent↗
PubMed2005

Musculoskeletal ultrasound training in rheumatology: the Belfast experience.

OBJECTIVES: Despite the increasing use of musculoskeletal ultrasound (MSUS) as a clinical tool in rheumatology, there is no consensus yet regarding the standards required to achieve a basic level of competence in the use of this imaging technique. A number of sonographers worldwide are developing curricula and standardizing teaching methods in order to improve training in MSUS for rheumatologists. In the meantime, clinicians are devising informal means of training in order to acquire these new skills. Here we describe the informal team approach to MSUS training adopted by a group of rheumatologists from the Regional Rheumatology Centre in Belfast, UK. METHODS: Over a 5-yr period, eight rheumatologists from Musgrave Park Hospital in Belfast used a variety of means to learn the basic skills of MSUS. RESULTS: Seven of the team underwent a formal assessment of their competency in a practical examination devised by an experienced sonographer. All were judged to have attained a basic competency in MSU. CONCLUSIONS: This Belfast experience shows what can be achieved despite the absence of formal MSUS training. Nevertheless, the development of recognized training programmes and international standards of competency are important goals on the way to achieving more widespread acceptance of MSUS as a useful tool in everyday clinical practice.

Clinical Competence↗
PubMed2005

The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.

Adolescent↗
PubMed2003

Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis.

OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Adult↗
PubMed2003

Carbonated soft drink consumption and bone mineral density in adolescence: the Northern Ireland Young Hearts project.

UNLABELLED: In an observational study of 1335 boys and girls aged 12 and 15 years, higher intakes of carbonated soft drinks (CSDs) were significantly associated with lower bone mineral density at the heel, but only in girls. Owing to the upward trend in CSD intake in adolescence, this finding may be of concern. INTRODUCTION: High consumption of carbonated soft drinks (CSD) during adolescence may reduce bone mineral accrual and increase fracture risk. The aim of this study was to examine the relationship between CSD consumption and bone mineral density (BMD) in a representative sample of adolescents. MATERIALS AND METHODS: This was a cross-sectional observational study in 36 postprimary schools in Northern Ireland. Participants included 591 boys and 744 girls either 12 or 15 years old. BMD was measured by DXA, and usual beverage consumption was assessed by the diet history method. Adjusted regression modeling was used to investigate the influence of CSD on BMD. RESULTS: A significant inverse relationship between total CSD intake and BMD was observed in girls at the dominant heel (beta, -0.099; 95% CI, -0.173 to -0.025). Non-cola consumption was inversely associated with dominant heel BMD in girls (beta, -0.121; 95% CI, -0.194 to -0.048), and diet drinks were also inversely associated with heel BMD in girls (beta, -0.087; 95% CI, -0.158 to -0.016). However, no consistent relationships were observed between CSD intake and BMD in boys. Cola consumption and nondiet drinks were not significantly related to BMD in either sex. CONCLUSION: CSD consumption seems to be inversely related to BMD at the dominant heel in girls. It is possible that the apparent association results from the displacement of more nutritious beverages from the diet. Although the inverse association observed between CSD consumption and BMD is modest and confined to girls, this finding may have important public health implications given the widespread use and current upward trend in CSD consumption in Western populations.

Adolescent↗
PubMed2002

The functional significance of perinatal corpus callosum damage: an fMRI study in young adults.

We used functional MRI (fMRI) to establish the functional significance of corpus callosum damage in young adults who had been born very preterm. Seven subjects from a cohort of individuals who had been born at <33 weeks gestation and who had sustained callosal damage visualized on structural MRI were compared while they carried out auditory and visual tasks requiring callosal transfer with nine very preterm subjects with corpora callosa of normal appearance on structural MRI, and with seven full-term controls. The very preterm subjects with damaged corpora callosa had significantly different activation patterns compared with the two control groups. In the visual task, additional activity was seen in the right dorsolateral prefrontal cortex of the damaged callosum group, possibly because the task was accomplished by storing information in working memory. On the auditory task, a deficit of activity was seen in the right temporal lobe of the callosum group. The findings reveal a plasticity of function compensating for early damage to the corpus callosum.

Adolescent↗
PubMed2000

Pathways and outcomes of psychiatric care: does it depend on who you are, or what you've got?

OBJECTIVES: To investigate predictors of outcome and cost for patients treated by Mental Health Services in the south metropolitan area of Perth using logistic regression to control for potential confounding factors. METHOD: Data were collected over a 3-month period on 2691 subjects (47% male, 53% female) as part of the Mental Health Classification and Services Cost Project. RESULTS: The average age of subjects was 44.3 years. Nearly 80% of care occurred in community settings and virtually all inpatient care was for acute emergencies. The most common diagnosis was schizophrenia (33%) followed by mood disorders (30%). Within the study period, 88% of patients had only one episode of care (n = 2361) and a further 8% two (n = 223). Patients with schizophrenia were one-third as likely to be discharged from care (95% CI = 0.2-0.4) and 30% as likely to have longer episodes of care (95% CI = 1.1-1.6). Patients with personality, substance or adjustment disorders spent less time in treatment, and those with personality or substance disorders were more likely to be discharged from psychiatric care. A past history of inpatient care was associated with a worse outcome in terms of length of care, or not being successfully discharged. Severity of illness as determined by involuntary treatment or elevated Health of the Nation Outcome Scales and Life Skills Profile (LSP) scores was associated with increased costs. Greater disability on the LSP was also associated with increased length of care. Sociodemographic factors were as least as important as diagnosis in predicting the cost and outcome of treatment. CONCLUSIONS: Demographic factors may better predict increased health service use than diagnostic casemix. Since sociodemographic variables contribute as much to outcome as diagnosis, comparing results between units is likely to be misleading unless adjusted for these factors.

Adult↗
PubMed2000

Tumour necrosis factor alpha and its soluble receptors in juvenile chronic arthritis.

OBJECTIVE: To identify possible imbalance of tumour necrosis factor alpha (TNFalpha) and its soluble receptors in the different subgroups of juvenile chronic arthritis (JCA). METHODS: Serum and synovial fluid samples from 45 children were examined, 25 pauciarticular JCA, 13 polyarticular JCA and seven spondyloarthropathy. TNFalpha, sTNFRI and sTNFRII levels were measured by EASIA and enzyme-linked immunosorbent assay (ELISA). Analysis of the results was carried out using non-parametric tests: Kruskal-Wallis one-way analysis of variance was used to compare the three clinical subgroups; the Mann-Whitney U-test was used to compare group medians. RESULTS: Thirty-three serum samples were assayed for TNFalpha. There was no significant difference between the three groups using the Kruskal-Wallis analysis of variance. Analysis of synovial fluid TNF levels showed significantly lower levels in the spondyloarthropathy group compared with the pauciarticular JCA (P = 0.01) and the polyarticular group (P = 0.002). Significantly higher levels of sTNFRI were observed in the synovial fluid of the polyarticular JCA group compared with the pauciarticular JCA group (P = 0.004) and similarly for sTNFRII (P = 0.03). Molar ratios were calculated for TNF vs sTNFRI. The sTNFRI/TNFalpha ratio was significantly higher in the spondyloarthropathy group compared with the pauci- (P 0.003) and the polyarticular JCA subgroups (P = 0.003). The combined soluble receptor levels expressed as molar ratio to TNF again showed a significantly higher ratio in the spondyloarthropathy group compared with the pauciarticular group (P = 0.01) and compared with the polyarticular group (P = 0.05). CONCLUSION: These results suggest that the increased joint destruction observed in polyarticular disease compared with the other two subtypes may be related to the lower sTNFR/TNFalpha ratios observed.

Adolescent↗
PubMed2000

Open peer review: a randomised controlled trial.

BACKGROUND: Most scientific journals practise anonymous peer review. There is no evidence, however, that this is any better than an open system. AIMS: To evaluate the feasibility of an open peer review system. METHOD: Reviewers for the British Journal of Psychiatry were asked whether they would agree to have their name revealed to the authors whose papers they review; 408 manuscripts assigned to reviewers who agreed were randomised to signed or unsigned groups. We measured review quality, tone, recommendation for publication and time taken to complete each review. RESULTS: A total of 245 reviewers (76%) agreed to sign. Signed reviews were of higher quality, were more courteous and took longer to complete than unsigned reviews. Reviewers who signed were more likely to recommend publication. CONCLUSIONS: This study supports the feasibility of an open peer review system and identifies such a system's potential drawbacks.

Feasibility Studies↗
PubMed2000

Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis.

OBJECTIVE: To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. METHODS: BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after one year of rhGH. Children were randomized to receive either low dose (12 IU/m2/week) or high dose (24 IU/m2/week) for one year. Three monthly assessments were made of disease activity and anthropomorphic measurements. Blood and urine samples were also obtained to measure indicators of disease activity, bone remodeling, and vitamin D and parathyroid hormone (PTH) status. RESULTS: BMC increased during the treatment period and correlated with increasing height. Osteocalcin levels, normally indicators of bone formation, increased after rhGH treatment and correlated significantly with height velocity, particularly for the high dose treatment group. In contrast, osteocalcin levels were negatively correlated with C-reactive protein levels, both before and during treatment. Height velocity, vitamin D, PTH, and osteocalcin levels were significantly lower than age matched controls before treatment. CONCLUSION: Steroid treated children with both JCA and severe growth retardation have reduced vitamin D, PTH, and osteocalcin levels. After treatment with rhGH, height velocity increased, as did BMC. Growth hormone might be a useful adjunct in the treatment of severe growth retardation and osteoporosis in children with JCA. The longterm benefits of rhGH in the treatment of osteoporosis remain unclear.

Adolescent↗
PubMed1999

Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer.

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non-squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

Adult↗
PubMed1998

Unemployment rates, single parent density, and indices of child poverty: their relationship to different categories of child abuse and neglect.

OBJECTIVE: There were two main research questions: First, is there a relationship between rates of child physical abuse, child sexual abuse and child neglect and levels of female and male unemployment, single-parent density and child poverty in the immediately local area; and second, is this relationship different for different categories of abuse and neglect and different categories of deprivation? METHOD: Using archival data--registered cases of abuse and neglect and official data on child population, social worker ratio, unemployment rates, single-parent density, means-tested clothing grants and free school meals for children--a multiple correlational analysis was carried out of the 5,551 referrals and 1,450 registered cases of abuse and neglect in Glasgow, Scotland for the years 1991 through to 1993. RESULTS: Substantial correlations were found with all indices of deprivation but particularly physical abuse with rates of male unemployment. Lower and more variable correlations were found with female unemployment rates. Sexual abuse and neglect rates showed a less consistent relationship with the indices of deprivation. In general male unemployment rates alone accounted for two-thirds of the variance in total abuse and neglect rates, other factors adding little or nothing to this. CONCLUSIONS: The results demonstrate the importance of selecting small and relatively homogeneous areas for this kind of analysis to achieve ecological validity. Male unemployment rates at this level allow for the ranking of areas in terms of priority need.

Child↗
PubMed1998

Atypical juvenile generalized scleroderma presenting as polyarthritis and failure to thrive.

In this Grand Round, two children are described with atypical generalized scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti-inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was unsuccessful in reversing the sclerodermatous changes and growth arrest. Dietary intake analysis and extensive GI investigation were performed in both. In one case, resting energy expenditure (Ee) was repeatedly measured. His intake did not meet requirements for growth. Supplemental tube feeding (900 kcal in 6 h) was commenced, causing an increase in weight from 11 to 16 kg. The other patient refused supplementary tube feeding and no weight gain has been observed for 5 yr. In conclusion, early-onset generalized scleroderma in the absence of visceral involvement, but with growth failure, may represent an atypical form of systemic sclerosis. The response of the two patients to conventional therapy was disappointing. However, the rapid catch-up growth induced by tube feeding observed in one patient underlines the importance of adequate dietary management.

Arthritis↗
PubMed1997

Diagnosis and monitoring of Whipple disease by polymerase chain reaction.

BACKGROUND: Whipple disease is a chronic, multisystem disorder associated with infection with Tropheryma whippelii, an organism that has not yet been grown on artificial media. In some cases, the diagnosis of Whipple disease is uncertain if it is based on histology alone. Although antibiotic regimens of various durations have been used, the disease recurs in about one third of cases. No test for cure is available. OBJECTIVE: To develop a test that is more sensitive and specific than histologic examination to diagnose Whipple disease and monitor the effects of antibiotic therapy. DESIGN: Retrospective, laboratory-based evaluations of stored tissue specimens. PATIENTS: 30 patients with clinically diagnosed, histologically confirmed Whipple disease and 8 patients in whom Whipple disease was clinically suspected but who did not have definitive histologic evidence. MEASUREMENTS: Pretreatment and post-treatment biopsy specimens of the small bowel and lymph node were tested by polymerase chain reaction for the presence of T. whippeli DNA. RESULTS: Results on PCR were positive in 29 of the 30 specimens from patients with histologically confirmed disease (sensitivity, 96.6%; specificity, 100%) and in 7 of the 8 specimens from patients in whom disease was clinically suspected. Small-bowel biopsy specimens were obtained after treatment from 17 patients (median duration of follow-up, 119 months); specimens from 12 of these patients had positive results on PCR. When these cases were correlated with therapeutic outcome, it was found that 7 of the 12 patients had clinical relapse during subsequent follow-up or had never responded to treatment (positive predictive value, 58% [95% CI, 28% to 85%]). In contrast, none of the 5 patients whose post-treatment biopsy specimens had negative results on PCR had relapse (negative predictive value, 100% [CI, 48% to 100%]; P = 0.044). No correlation was found between post-treatment histology and clinical outcome (P > 0.2). CONCLUSIONS: Polymerase chain reaction is highly sensitive and specific when used to confirm the diagnosis of Whipple disease, to identify inconclusive and suspicious cases, and to monitor response to therapy. A negative result on PCR may predict a low likelihood of clinical relapse; a positive test result that remains positive despite therapy may be associated with a poor clinical outcome. Histopathologic evaluation of post-treatment specimens does not predict clinical cure or relapse.

Actinobacteria↗