Biomedical subjects

Joanne Collins

Publications and source records attributed to Joanne Collins.

4 recordsLinked to original sources

PubMed2005

Association of the TSHR gene with Graves' disease: the first disease specific locus.

The development of autoimmune thyroid disease (AITD) is associated with autoantibodies directed against the thyroid stimulating hormone receptor (TSHR). Previous studies have failed to demonstrate a consistent association between the TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD 'blocks' and SNPs, which capture the majority of intra-block haplotype diversity. The haplotype tagging SNPs, plus all common SNPs reported in previous studies were genotyped in 1,059 AITD Caucasian cases and 971 Caucasian controls. A haplotype, across two LD blocks, showed association (P<1 x 10(-6), OR 1.7) with Graves' disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these findings by genotyping the most associated GD SNP, rs2268458, in a separate UK Caucasian cohort of 1,366 AITD cases and 1,061 controls (GD, P=2 x 10(-6), OR 1.3; AIH, P=NS). These results in two independent Caucasian data sets suggest that the TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants.

Case-Control Studies↗

PubMed2004

Biventricular implantable cardioverter defibrillators improve survival compared with biventricular pacing alone in patients with severe left ventricular dysfunction.

INTRODUCTION: Biventricular cardiac pacemakers provide important hemodynamic benefit in selected patients with heart failure and severe left ventricular (LV) dysfunction. Nevertheless, these patients remain at high mortality risk. To address this issue, we examined mortality outcome in patients with heart failure treated with biventricular pacemakers alone and those treated with biventricular implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: The study population consisted of 126 consecutive patients with LV dysfunction and heart failure who received either a biventricular ICD (n = 62) or a biventricular pacemaker (n = 64) between January 1998 and December 2002. A minimum 12 months of follow-up was obtained in all survivors. ICD indications were conventional in all patients. Kaplan-Meier actuarial method and log rank statistics were used to calculate and compare survival rates in both groups. Comparison of mortality rates utilized Chi-square test. The two groups had similar clinical and demographic features, LV ejection fraction, and medication use. Average follow-up times were 13 +/- 11.8 months (range 4-60) and 18 +/- 13.2 months (range 0.5-53) for biventricular ICD and pacemaker groups, respectively. Overall mortality rate was significantly lower in the biventricular ICD group (13%, 8 deaths) compared to the pacemaker group (41%, 26 deaths) (P = 0.01). Further, the predominant survival benefit for ICD-treated patients becomes evident after the first 12 months of follow-up. CONCLUSION: The findings in this study, although necessarily limited in their interpretation by the absence of treatment randomization, suggest that biventricular ICDs offer a survival benefit compared to biventricular pacing alone. Furthermore, this benefit may be most apparent if other clinical factors do not preclude patient survival >1 year postimplant.

Aged↗

PubMed2003

Improved survival of cardiac transplantation candidates with implantable cardioverter defibrillator therapy: role of beta-blocker or amiodarone treatment.

INTRODUCTION: Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. METHODS AND RESULTS: Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rank x2, P = 0.0001). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rank x2, P = 0.003). CONCLUSION: ICD therapy is associated with improved survival in high-risk cardiac transplant candidates, and ICD benefit appears to be independent of concomitant treatment.

Adrenergic beta-Antagonists↗

PubMed2002

Autoimmunity in thyroid disease.

The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, represent the two ends of a disease spectrum where an immune response is directed against the thyroid gland. In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and thyroid hormone deficiency. The mechanisms by which these diseases develop are unknown, although it is likely that both diseases occur in genetically susceptible individuals exposed to a permissive environment. A number of environmental factors have been postulated to be involved in the development of autoimmune thyroid disease. There is, however, no direct evidence to support clear causality. Susceptibility loci within immune response genes have been identified although a significant component of the genetic predisposition to disease remains unknown. This review will focus on some of the studies designed to identify genes that confer susceptibility to the autoimmune disease process within the thyroid gland.

Abatacept↗