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1.
QJM ; 110(10): 629-637, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28472518

ABSTRACT

BACKGROUND: Increases in physical activity ameliorate low-grade systemic inflammation in disease populations such as type 2 diabetes mellitus and coronary artery disease. The effects of aerobic and resistance training (RT) on inflammatory biomarker profiles in non-disease, physically inactive individuals are unknown. METHODS: A systematic review of randomized controlled trials measuring the effect of aerobic and resistance exercise on pro-inflammatory biomarkers in healthy, inactive adult populations was conducted. The available peer-reviewed literature was searched from January 1990 to June 2016 using the electronic databases PubMed and Scopus. A narrative synthesis of review findings was constructed with discussion of the impact of aerobic, resistance and combined training on C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8, interleukin-1ß and tumour necrosis factor-α. RESULTS: The initial search revealed 1596 potentially relevant studies. Application of the study eligibility criteria led to the full-text review of 54 articles with 11 studies deemed suitable for inclusion. Review of related articles and the reference lists of the 54 full-text articles led to the inclusion of 2 additional studies. The review revealed inconsistent findings relating to the effect of aerobic training and RT on CRP and IL-6. Studies of older-aged adults (>65 years old) demonstrated the greatest and most consistent reduction in inflammatory biomarkers post-training intervention. CONCLUSIONS: A paucity of evidence exists relating to the effect of exercise training on inflammatory markers in non-disease, physically inactive adults. The available evidence suggests potential for the greatest benefit to be seen in older populations and with higher intensity aerobic exercise.


Subject(s)
C-Reactive Protein/analysis , Exercise , Interleukin-6/blood , Resistance Training , Biomarkers/analysis , Healthy Volunteers , Humans , Randomized Controlled Trials as Topic
2.
Int J Sports Med ; 37(5): 359-63, 2016 May.
Article in English | MEDLINE | ID: mdl-26859645

ABSTRACT

Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p<0.05). Summation of the depths at these locations correlated strongly with percentage body fat by Dual-Energy X-ray Absorptiometry (R²=0.879). The triceps, biceps, anterior thigh and supraspinale sites are suitable anatomical landmarks for the estimation of %BF using B-mode ultrasound. Use of B-mode ultrasound in the assessment of athlete body composition confers many benefits including lack of ionising radiation and its potential to be used as a portable field tool.


Subject(s)
Adiposity , Athletes , Skinfold Thickness , Subcutaneous Fat/diagnostic imaging , Ultrasonography , Absorptiometry, Photon , Adolescent , Adult , Arm/diagnostic imaging , Female , Humans , Male , Middle Aged , Thigh/diagnostic imaging , Young Adult
3.
Ir J Med Sci ; 185(2): 521-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26026952

ABSTRACT

BACKGROUND: Concussion is a traumatic brain injury, resulting in the alteration of mental status with or without loss of consciousness. There is increasing awareness that recurrent concussion may contribute to long-term neurological complication. AIMS: To determine player knowledge and attitudes regarding concussion. To identify sources of information and medical care, and to estimate the incidence of concussion in this group. To determine if player gender and grade of competition are associated with differences in knowledge, attitudes, medical care, and incidence. METHODS: Five rugby teams were recruited and players invited to complete a paper-based questionnaire. The questionnaire sought information on player demographics, knowledge level, attitudes and concussion experience. RESULTS: 90.8 % of players knew they should not continue playing when concussed. 75 % of players would continue an important game even if concussed. Of those concussed, 39.1 % have tried to influence medical assessment with 78.2 % stating it is possible or quite easy to do so. Males are less likely to worry about long-term effects of concussion (χ (2) = 9.23, p = 0.026). Club players are less likely to have medical care at training (χ (2) = 28.2, p < 0.001) or matches (χ (2) = 19.47 p < 0.001). CONCLUSION: Despite good knowledge of concussion complications, management players engage in unsafe behaviour with little difference between gender and competition grades. Information regarding symptoms and management should be available to all players, coaches, and parents. Provision of medical care should be mandatory at every level of competition.


Subject(s)
Brain Concussion/etiology , Football/injuries , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Athletic Injuries/etiology , Brain Concussion/diagnosis , Brain Injuries, Traumatic/etiology , Cross-Sectional Studies , Female , Humans , Incidence , Male , Surveys and Questionnaires , Young Adult
5.
Emerg Med J ; 26(8): 590-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19625558

ABSTRACT

OBJECTIVE: To investigate the epidemiology of sports and recreation-related injury (SRI) among emergency department (ED) attendees. DESIGN: Descriptive epidemiology study. SETTING: An Irish university hospital ED. PARTICIPANTS: All patients aged over 4 years attending a large regional ED, during a 6-month period, for the treatment of SRI were prospectively surveyed. ASSESSMENT OF RISK FACTORS: In all cases identified as SRI the attending physician completed a specifically designed questionnaire. It was postulated that recreation-related injury is a significant proportion of reported SRI. RESULTS: Fracture rate was highest in the 4-9-year age group (44%). On multivariate logistic regression the adjusted odds ratio (OR; 95% CI) of fracture was higher for children (vs adults) at 1.21 (1.0 to 1.45). The adjusted OR was higher for upper-limb 5.8 (4.5 to 7.6) and lower-limb injuries 1.87 (1.4 to 2.5) versus axial site of injury and for falls 2.2 (1.6 to 2.9) and external force 1.59 (1.2 to 2.1) versus an overextension mechanism of injury. In the same model, "play" was independently associated with fracture risk, adjusted OR 1.98 (1.2 to 3.0; p = 0.001) versus low-risk ball sports 1.0 (reference); an effect size similar to that seen for combat sports 1.96 (1.2 to 3.3; p = 0.01) and greater than that seen for presumed high-risk field sports 1.4 (0.9 to 2.0) CONCLUSION: Fall and subsequent upper-limb injury was the commonest mechanism underlying SRI fracture. Domestic "play" in all age groups at the time of injury accorded a higher fracture risk than field sports. Patient education regarding the dangers of unsupervised play and recreation represents a means of reducing the burden of SRI.


Subject(s)
Athletic Injuries/epidemiology , Emergency Service, Hospital/statistics & numerical data , Exercise Therapy , Fractures, Bone/epidemiology , Recreation , Adolescent , Adult , Athletic Injuries/prevention & control , Child , Child, Preschool , Female , Fractures, Bone/prevention & control , Humans , Ireland , Male , Prospective Studies
6.
Ir Med J ; 102(2): 40-2, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19405315

ABSTRACT

The health benefits of exercise may be attenuated by sports and recreation related injury (SRI). Though the majority of SRI are mild and self-limiting, a significant number are serious and require orthopaedic intervention. The aims of this study were to assess the burden of these serious injuries on the orthopaedic inpatient service, and to investigate potential target areas for injury prevention. All 1,590 SRI seen in the ED over a 3-month period were analysed using the Patient Information Management System to determine which patients received inpatient orthopaedic care. The medical records of those 63 patients who required inpatient care under orthopaedics were reviewed and data collected on demographic features, history, operative procedure and theatre resources, and length of hospital stay. Data were analyzed using SPSS. SRI accounted for 12.3% of all ED presentations. The principal activities resulting in injury requiring orthopaedic care were soccer, hurling and informal play e.g. trampoline. Falls made up 37% of the overall mechanism of injury but 68% of the injuries severe enough to require operative management. Most operative procedures were performed as part of a routine day trauma list but 20% were performed out of hours. This group of injuries places a significant burden on a busy trauma service. Injury prevention measures such as public education regarding falls in sport may have a role in reducing this burden.


Subject(s)
Athletic Injuries/epidemiology , Athletic Injuries/surgery , Hospitalization/statistics & numerical data , Orthopedic Procedures/statistics & numerical data , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Fractures, Bone/epidemiology , Fractures, Bone/surgery , Humans , Information Management , Ireland/epidemiology , Male , Middle Aged , Retrospective Studies , Young Adult
7.
Br J Sports Med ; 42(6): 452-9, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18539659

ABSTRACT

OBJECTIVE: to determine the incidence, nature and causes of injuries sustained during the International Rugby Board (IRB) Rugby World Cup 2007. DESIGN: Pospective, whole-population survey. POPULATION: 626 international rugby players representing 20 teams competing at the IRB Rugby World Cup 2007 in France. METHODS: The survey followed the international consensus procedures for studies of injuries in rugby union; the main outcome measures were incidence of match and training injuries (number of injuries/1000 player hours), severity (days absence), location, type and cause of injury. RESULTS: the incidence of injuries was 83.9/1000 player-match hours (forwards 84.0; backs 83.7) and 3.5/1000 player-training hours (forwards 3.5; backs 3.6). The average severity of injuries was 14.7 days (forwards 14.0; backs 15.5) during matches and 17.8 (forwards 15.9; backs 19.8) during training. Lower limb muscle and ligament injuries were the main injuries during both matches and training. Most injuries were sustained in the tackle during matches and in full-contact skills activities during training. CONCLUSIONS: This study shows the application of the methodology described in the international consensus statement on injury surveillance studies in rugby union and provides benchmark values for the incidence, severity, nature and causes of match and training injuries sustained during the IRB Rugby World Cup.


Subject(s)
Football/injuries , Athletic Injuries/epidemiology , Athletic Injuries/etiology , Athletic Injuries/physiopathology , Competitive Behavior/physiology , Football/physiology , Humans , Incidence , Injury Severity Score , Physical Education and Training/methods , Prospective Studies , Risk Factors
8.
Br J Sports Med ; 42(6): 447-51, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18424486

ABSTRACT

BACKGROUND: Although there have been reports of injury rates in men's World Cup rugby, there has been no research into injury rates in women's international rugby. OBJECTIVE: To determine the rate of injury at the 2006 Women's Rugby World Cup (WRWC). METHODS: All participating teams in the 2006 WRWC were enrolled prospectively in this study. Healthcare workers for each team collected data on training and game exposure and information on injuries. RESULTS: 55 players (16%) sustained at least one injury (10.0/1000 player hours); 4 players (1%) sustained two injuries. 45 injuries occurred during games (37.5/1000 player hours) and 14 injuries occurred during practice (12.5/1000 player hours), a statistically significant difference (RR = 12.5, 95% CI 6.9 to 22.8). The injury rate was 39.3/1000 player hours for the forwards and 42.2/1000 player hours for the backs (RR = 1.3, 95% CI 0.7 to 2.3). The front row had the highest injury rate (62.5/1000 player hours). 63.6% of injuries occurred during the tackle. Most injuries occurred to the neck, knee and head/face. The majority of injuries were sprains, muscle injuries and contusions. There were five fractures during the event and four reported concussions. CONCLUSION: Female players sustained a considerable rate of injury during the 2006 WRWC. Backs had a slightly higher rate of injury than forwards, but the players most often injured were in the front row. The neck/cervical spine and knee were the most commonly injured regions, followed by the head and face. This is the first study to examine injury rates in female rugby players at a World Cup and reports valuable data in this population.


Subject(s)
Football/injuries , Adult , Athletic Injuries/epidemiology , Competitive Behavior/physiology , Female , Humans , Injury Severity Score , Prospective Studies
9.
Clin J Sport Med ; 17(3): 177-81, 2007 May.
Article in English | MEDLINE | ID: mdl-17513907

ABSTRACT

Wide variations in the definitions and methodologies used for studies of injuries in rugby union have created inconsistencies in reported data and made interstudy comparisons of results difficult. The International Rugby Board established a Rugby Injury Consensus Group (RICG) to agree on appropriate definitions and methodologies to standardize the recording of injuries and reporting of studies in rugby union. The RICG reviewed the consensus definitions and methodologies previously published for football (soccer) at a meeting in Dublin to assess their suitability for and application to rugby union. Following this meeting, iterative draft statements were prepared and circulated to members of the RICG for comment; a follow-up meeting was arranged in Dublin at which time all definitions and procedures were finalized. At this stage, all authors confirmed their agreement with the consensus statement. The agreed-on document was presented to and approved by the International Rugby Board Council. Agreement was reached on definitions for injury, recurrent injury, nonfatal catastrophic injury, and training and match exposures together with criteria for classifying injuries in terms of severity, location, type, diagnosis, and causation. The definitions and methodology presented in this consensus statement for rugby union are similar to those proposed for football. Adoption of the proposals presented in this consensus statement should ensure that more consistent and comparable results will be obtained from studies of injuries within rugby union.


Subject(s)
Consensus , Football , Wounds and Injuries/classification , Humans , Research Design/standards , United Kingdom
10.
Ir J Med Sci ; 175(2): 32-6, 2006.
Article in English | MEDLINE | ID: mdl-16872026

ABSTRACT

BACKGROUND: Rheumatoid arthritis is a common, disabling, autoimmune disease with significant psychiatric sequelae. AIMS: We aimed to identify the prevalence of depression and anxiety in patients with rheumatoid arthritis attending hospitals, and to elucidate the role played by illness variables, disability variables and psychosocial variables in predicting levels of depression and anxiety. METHODS: We assessed depression, anxiety, arthritis-related pain, arthritis-related disability and perceived social support in 68 adults with rheumatoid arthritis. RESULTS: Sixty-five per cent of patients had evidence of depression (37.5% moderate or severe) and 44.4% had evidence of anxiety (17.8% moderate or severe). Both depression and anxiety were highly correlated with several measures of arthritis-related pain and functional impairment. After controlling for age, gender, marital status and duration of arthritis, perceived social support was a highly significant independent predictor of both depression and anxiety. CONCLUSIONS: These findings suggest that increasing social support may be particularly important in the management of depression and anxiety in rheumatoid arthritis.


Subject(s)
Anxiety Disorders/epidemiology , Arthritis, Rheumatoid/psychology , Depressive Disorder/epidemiology , Social Perception , Social Support , Arthritis, Rheumatoid/complications , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Sick Role
11.
Clin Rheumatol ; 25(6): 789-93, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16572289

ABSTRACT

To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.


Subject(s)
Arthritis, Rheumatoid/metabolism , Synovial Membrane/metabolism , bcl-X Protein/metabolism , Aged , Aging/metabolism , Arthritis, Rheumatoid/pathology , Blotting, Western , Endothelial Cells/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Osteoarthritis/metabolism , Osteoarthritis/pathology , Plasma Cells/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Staining and Labeling , Synovial Membrane/pathology , Time Factors , bcl-X Protein/genetics
12.
Immunogenetics ; 57(12): 893-903, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16362817

ABSTRACT

Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase-polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-gamma and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.


Subject(s)
Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Blood Proteins/genetics , Receptors, Immunologic/genetics , Arthritis, Rheumatoid/pathology , Base Sequence , Case-Control Studies , Dendritic Cells/drug effects , Dendritic Cells/immunology , Gene Expression , Genetic Variation , Humans , In Vitro Techniques , Interferon-gamma/pharmacology , Intracellular Signaling Peptides and Proteins , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Lipopolysaccharides/pharmacology , Membrane Proteins , Natural Cytotoxicity Triggering Receptor 3 , Pseudomonas aeruginosa/immunology , Pseudomonas aeruginosa/pathogenicity , RNA, Messenger/genetics , RNA, Messenger/metabolism , Recombinant Proteins , Staphylococcus aureus/immunology , Staphylococcus aureus/pathogenicity , Synovial Membrane/immunology , Synovial Membrane/pathology , U937 Cells
13.
Postgrad Med J ; 80(944): 366-7, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15192176

ABSTRACT

Lupus myocarditis is a life threatening complication of systemic lupus erythematosus (SLE). A case of left ventricular failure secondary to myocarditis occurring in a patient with SLE is reported. Despite resolution of the cardiac failure with pulsed cyclophosphamide and steroids, she eventually died of non-cardiac complications 18 months later. The literature is also reviewed.


Subject(s)
Lupus Erythematosus, Systemic/complications , Myocarditis/etiology , Adult , Fatal Outcome , Female , Humans , Prognosis , Ventricular Dysfunction, Left/etiology
15.
Bone ; 33(6): 970-4, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14678857

ABSTRACT

Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. An increased prevalence of subclinical CD has been reported in many populations. Even among asymptomatic patients a reduction in bone mineral density (BMD) has been observed. The aim of this study was to evaluate the prevalence of silent CD in a cohort of consecutive individuals referred for bone densitometry measurement. Serum samples were taken from 454 women attending for bone densitometry (mean age: 56 +/- 11 years). Of the individuals evaluated, 89 had normal BMD and 365 had low BMD (T score < -1.0). Subjects were screened for the presence of serum IgA anti-endomysial antibodies (EMA) and IgA tissue transglutaminase (tTG) antibodies by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA), respectively. BMD was measured by dual X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Eight EMA tTG-positive individuals were identified in this population (1.8% or 1:57). Serologically positive women had a lower mean Z score at both the lumbar spine and femoral neck than EMA tTG-negative women. But this did not approach significance. There was no significant difference in the incidence of CD between the normal- and low-BMD groups in this dataset (P = 0.365). In conclusion, our study indicates that the prevalence of CD in our dataset is high. However, the frequency of asymptomatic CD among low-BMD individuals is similar to that among normal-BMD individuals in our population. These observations do not support the hypothesis that serological testing for CD may be a good accompaniment to DEXA scanning.


Subject(s)
Bone Density , Celiac Disease/epidemiology , Absorptiometry, Photon , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Autoantibodies/immunology , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/immunology , Celiac Disease/diagnosis , Data Interpretation, Statistical , Esophagus/immunology , Female , GTP-Binding Proteins/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Ireland/epidemiology , Lumbar Vertebrae/chemistry , Mass Screening , Middle Aged , Protein Glutamine gamma Glutamyltransferase 2 , Transglutaminases/immunology
16.
Calcif Tissue Int ; 72(6): 651-8, 2003 Jun.
Article in English | MEDLINE | ID: mdl-14562992

ABSTRACT

Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1alpha) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score < or = -1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores >1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.


Subject(s)
Bone Density/genetics , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 2 , Lod Score , Lumbar Vertebrae/metabolism , Adult , Aged , Aged, 80 and over , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/genetics , Family Health , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Osteoporosis, Postmenopausal/epidemiology , Osteoporosis, Postmenopausal/genetics , Siblings
17.
Calcif Tissue Int ; 71(1): 26-35, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12073153

ABSTRACT

Low bone mineral density (BMD) is a major risk factor for the development of osteoporosis and there is strong evidence to suggest that the procurement and preservation of peak BMD is genetically determined. In an effort to identify factors responsible for susceptibility to low BMD in the Irish population, we investigated its possible association with polymorphisms in the Osteoprotegerin (OPG) gene, Type I collagen alpha 1 (COLIA1) Sp1 binding site and vitamin D receptor (VDR) start codon. Following a systematic screening of the regulatory and coding regions of the OPG gene, we identified a novel G1181C polymorphism in exon 1 and a T950C polymorphism in the promoter region of the OPG gene. Participants were recruited from the Bone Densitometry Unit of Cork University Hospital, including 381 postmenopausal women aged 61.26 +/- 8.50 (mean +/- SD) and 130 premenopausal women aged 46.30 +/- 6.50 (mean +/- SD). Following association analysis using both the premenopausal and postmenopausal cohorts we found that postmenopausal women carrying one or more C alleles of the G1181C polymorphism had 14.8% lower BMD (P = 0.05) at the lumbar spine and 14.4% lower BMD (P = 0.04) at the FN. However, both were nonsignificant when the Bonferroni correction factor (0.01 significance level) was applied to correct for multiple hypothesis testing. We found no association between alleles of the T950C OPG polymorphism and BMD. Similarly, we have found a lack of association between the VDR (fok1) polymorphism or COLIA1 Sp1 polymorphism and low BMD in either postmenopausal or premenopausal women in this population.


Subject(s)
Bone Density/physiology , Collagen Type I/genetics , Glycoproteins/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Receptors, Calcitriol/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Base Sequence , Body Height , Body Weight , Codon, Initiator/genetics , DNA Primers , Female , Humans , Ireland , Mass Screening , Menopause , Middle Aged , Osteoprotegerin , Postmenopause , Premenopause , Promoter Regions, Genetic , Receptors, Tumor Necrosis Factor , Retrospective Studies
18.
Genes Immun ; 2(2): 82-7, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11393661

ABSTRACT

Tumour necrosis factor (TNF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and it has been shown that the TNF-lymphotoxin (TNF-LT) region influences susceptibility to RA. To investigate the role of the TNF-LT locus further, inheritance of TNF 5' promoter alleles was determined in multiplex RA families. Six previously defined TNF promoter single nucleotide polymorphisms (SNPs) (-238, -308, -376, -857, -863, -1031) were observed in these families and in addition, a heretofore undocumented adenine (A) to cytosine (C) substitution at position -572 relative to the transcription start site was defined. TNF 5' promoter SNPs were found to co-segregate with specific TNF microsatellite haplotypes. In particular, the SNP -308A allele was found to be inherited with the TNF a2, b3, c1, d1, e3 (H2) microsatellite haplotype (P < 0.001) which had previously been found to be associated with RA in individuals heterozygous for the HLA-DR 'shared epitope' (SE). When the data were stratified by the presence of the SE with further stratification according to SE DR subtypes and analysed by transmission disequilibrium test (TDT) for which offspring were assumed independent, the -308A and -857T alleles were found to be associated with RA in patients carrying the SE (P = 0.0076 and 0.0063 respectively). The data were further stratified to analyse for association in individuals homozygous or heterozygous for SE alleles. Results showed that the -308A allele was significantly associated with RA susceptibility in individuals heterozygous for the SE (P < 0.001) with the significance only occurring in patients carrying HLA-DR4 (P < 0.001), while the -857T allele was significant in individuals homozygous for the SE (P = 0.0039). Further analysis using the pedigree disequilibrium test (PDT) which conservatively adjusts for all sources of familial correlation except that conferred by linkage disequilibrium still indicated a significant role for the -308A and -857T alleles. These data provide evidence that TNF promoter SNPs may play an independent role in RA susceptibility in specific immunogenetically-defined groups of RA patients.


Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Tumor Necrosis Factor-alpha/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/physiopathology , HLA-DR Antigens/genetics , Haplotypes , Humans , Microsatellite Repeats/genetics
19.
Ir Med J ; 94(10): 310, 2001.
Article in English | MEDLINE | ID: mdl-11837631

ABSTRACT

Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic sclerosis. We report a case of gastrointestinal bleeding due to gastric antral vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to recognise the condition as a cause of gastrointestinal bleeding may delay the instigation of appropriate treatment. GAVE should be considered in the differential diagnosis of anaemia in patients with autoimmune conditions such as systemic sclerosis and primary biliary cirrhosis.


Subject(s)
Anemia, Refractory/etiology , Gastric Antral Vascular Ectasia/complications , Scleroderma, Systemic/complications , Aged , Blood Transfusion , Female , Gastric Antral Vascular Ectasia/diagnosis , Gastric Antral Vascular Ectasia/therapy , Gastroscopy , Hemorrhage/etiology , Hemorrhage/therapy , Humans , Light Coagulation
20.
J Med Genet ; 36(3): 214-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10204847

ABSTRACT

Tumour necrosis factor (TNF) is a key proinflammatory mediator in rheumatoid arthritis (RA). The TNF locus, situated in the class III region of the MHC, is flanked by five microsatellite markers. It has previously been shown that this region influences susceptibility to RA; two TNF microsatellite haplotypes were found to be associated with RA. Evidence from murine studies has indicated that variation in the TNF 3' untranslated region (UTR) could be associated with altered regulation of TNF biosynthesis. In order to identify possible RA associated polymorphisms, more than 800 bp of the TNF 3' UTR was genetically analysed in RA affected and unaffected subjects possessing specific RA and non-RA associated TNF microsatellite haplotypes. The TNF 3' UTR region was analysed using two mutation detection methods, PCR-SSCP and NIRCA analysis and DNA sequencing. No genetic differences were observed in the human TNF 3' UTR between subjects, that is, irrespective of RA status or TNF haplotype, and also compared with previously published TNF sequences from human sources. Therefore it can be concluded that the TNF 3' UTR in this population was highly conserved and did not influence susceptibility to RA.


Subject(s)
3' Untranslated Regions , Arthritis, Rheumatoid/genetics , Tumor Necrosis Factor-alpha/genetics , Arthritis, Rheumatoid/immunology , Conserved Sequence , Humans , Polymerase Chain Reaction/methods , Polymorphism, Single-Stranded Conformational
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