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B Mulcahy

Publications and source records attributed to B Mulcahy.

9 recordsLinked to original sources
PubMed1998

Modelling the major histocompatibility complex susceptibility to RA using the MASC method.

To explain the association between HLA-DRB1 gene and rheumatoid arthritis (RA), two main hypotheses have been proposed. The first, the shared epitope hypothesis, assumes a direct role of DRB1 in RA susceptibility. The second hypothesis assumes a recessive disease susceptibility gene in linkage disequilibrium with DRB1. To investigate these two hypotheses, we analysed data on the HLA-DRB1 and TNF-LT loci in 49 affected sib-pairs. We used the Marker Association Segregation Chi-square (MASC) method in which the genotype distribution of markers among index cases and the haplotype sharing in affected sib-pairs are jointly taken into account. With DRB1 data alone, both hypotheses were shown to fit but with analysis of TNF data, both hypotheses were strongly rejected. Thus the TNF data provided additional information for a better understanding of genetic susceptibility to RA than was previously possible using only HLA-DR data. A theoretical standpoint is addressed here on the advisability of using different linked markers in a candidate region for modelling the contribution of this region in disease susceptibility.

Adolescent↗
PubMed1998

Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women.

OBJECTIVES: Few data are available on the effects of combination therapy for the treatment of osteoporosis. The aim of this study was to compare the effects of intermittent cyclical etidronate (E) therapy alone with a combination of cyclical etidronate and calcitriol (E + C) on spine and femoral neck bone mineral density (BMD) at one year. METHODS: Postmenopausal women with at least one non-traumatic vertebral fracture or z score < -1.5 were randomly allocated to an E group (each cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily for 76 days) or an E + C group (as for E plus oral calcitriol 0.5 microgram daily). Lumbar spine and femoral neck BMDs were measured by dual energy x ray absorptiometry at baseline and at one year. The study design did not contain a placebo group. RESULTS: The mean % increase in lumbar spine BMD was 5.2% (95% CI = 3.4 to 7.0) in the E + C group (n = 24), which was significantly greater than the 2.7% (95% CI = 1.3 to 4.1) increase in the E group (n = 23) (p < 0.05). The femoral neck BMD in the E + C group increased by 2.0% (95% CI = 0.8 to 3.2), which was significantly different from the E group where there was a -0.4% (95% CI = -2.4 to 1.6) change (p = 0.046). CONCLUSIONS: These data show that a combination of cyclical etidronate and calcitriol is better than cyclical etidronate alone in terms of changes in BMD at both spine and femoral neck sites. Although further data are needed on fracture efficacy, this study suggests that combination therapies have additive therapeutic potential that may exceed that expected from their theoretical mode of action.

Absorptiometry, Photon↗
PubMed1996

New-onset atrial fibrillation: when is admission medically justified?

OBJECTIVE: To determine 1) the percentage of patients with new-onset atrial fibrillation for whom admission is medically justified and 2) whether those patients for whom hospitalization is medically justified can be reliably identified in the ED. METHODS: A retrospective, descriptive cohort analysis was performed using consecutive adult patients with new-onset atrial fibrillation seen in an urban, county hospital ED from 1987 through 1992. Admissions were categorized as medically justified if patients were hypotensive (systolic blood pressure < 90 mm Hg), had a diagnosis other than new-onset atrial fibrillation that warranted admission, or had a significant complication during the ED stay or during the subsequent hospitalization. The need for admission was considered to have been apparent during the ED evaluation if the patient fulfilled the above criteria for a medically justified admission while in the ED. RESULTS: Admission was medically justified for 143 of the 216 patients (66%; 95% CI 60-71%) admitted to our institution. For those patients whose admissions were medically justified, the most common concurrent conditions were congestive heart failure and chest pain suggestive of myocardial ischemia. The need for admission was apparent during the ED evaluation for 140 of the 143 patients (98%; 95% CI 94-100%) whose admissions were categorized as medically justified. CONCLUSION: Approximately one third of patients with new-onset atrial fibrillation may not require admission to the hospital. Most patients (98%) for whom admission is medically justified can be reliably identified during the ED evaluation.

Acute Disease↗
PubMed1996

Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.

The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.

Arthritis, Rheumatoid↗
PubMed1995

The role of T cell receptor beta chain genes in susceptibility to rheumatoid arthritis.

OBJECTIVE: To evaluate the role of the T cell receptor beta chain locus (TCRB) in genetic susceptibility to rheumatoid arthritis (RA). METHODS: Twenty-eight multiplex RA families were recruited from 3 rheumatology outpatient departments. All members were genotyped for a highly informative microsatellite (V beta 6.7), a V beta 12.2 SSCP marker, and a biallelic C beta restriction fragment length polymorphism. Data were analyzed by the SIBPAL program to assess identity-by-descent in affected sib-pairs. RESULTS: Using the V beta 12.2 marker, there was suggestive evidence of increased sib-pair sharing (P = 0.005) in affected offspring (a P value of 0.001 is generally taken to establish linkage). Data for V beta 6.7 and C beta yielded significance levels of 0.06 and 0.19, respectively. CONCLUSION: These data suggest that a gene in or linked to the TCRB complex may confer genetic susceptibility to RA in these families. Confirmation in a larger panel of families is required.

Adolescent↗
PubMed1995

Non-linkage of a T-cell receptor gamma chain microsatellite (D7S485) to rheumatoid arthritis in multiplex families.

A highly informative microsatellite marker, D7S485, from the T-cell receptor gamma (TCRG) locus, has been used to study segregation of TCRG genes in 26 multiplex rheumatoid arthritis (RA) families. We used the sib-pair method to assess excess identity-by-descent sharing among affected members in these families and the LINKAGE package of programs was used to calculate two-point lod scores for the D7S485 marker. There was no evidence for segregation of TCRG genes with RA in affected siblings and significantly negative lod scores were obtained from linkage analyses using both autosomal dominant and recessive models of inheritance.

Adolescent↗
PubMed1993

The sports' clinic: a one year review of new referrals.

The new presentations to the Cork Sports' Clinic over a one year period 1.1.90 to 31.12.90 were examined. We looked at the age and sex distribution of the presenting population, the type and site of injury, the sport played and the treatment and outcome of the injury. 126 new cases presented in 1990. 107 (85%) were male. The three commonest sports featured were all contact ones. The knee was the commonest site of injury (46.8% of cases) with 73.1% of injuries occurring in the lower limb. 73% of cases presented between the ages of 15 to 29 years. The majority of patients had improved on follow-up. Nine were referred to an orthopaedic service-five fractures and four serious ligamental injuries. The Cork Sports' Clinic works adjacent to a busy accident and emergency department. There is a definite need for our clinic in conjunction with the casualty department.

Adolescent↗