77 research outputs found

    The relationship between aortic wall distensibility and rupture of infrarenal abdominal aortic aneurysm

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    AbstractObjective: A more accurate means of prediction of abdominal aortic aneurysm (AAA) rupture would improve the clinical and cost effectiveness of prophylactic repair. The purpose of this study was to determine whether AAA wall distensibility can be used to predict time to rupture independently of other recognized risk factors. Methods: A prospective, six-center study of 210 patients with AAA in whom blood pressure (BP), maximum AAA diameter (Dmax), and AAA distensibility (pressure strain elastic modulus [Ep] and stiffness [β]) were measured at 6 months with an ultrasound scan-based echo-tracking technique. A stepwise, time-dependent, Cox proportional hazards model was used to determine the effect on time to rupture of age, gender, BP, Dmax, BP, Ep, β, and change in Dmax, Ep, and β adjusted for time between follow-up visits. Results: Median (interquartile range) AAA diameter was 48 mm (41 to 54 mm), median age was 72 years (68 to 77 years), and median follow-up period was 19 months (9 to 30 months). In the Cox model, female gender (hazards ratio [HR], 2.78; 95% CI, 1.23 to 6.28; P =.014), larger Dmax (HR, 1.36 for 10% increase in Dmax; 95% CI, 1.12 to 1.66; P =.002), higher diastolic BP (HR, 1.13 for 10% increase in BP; 95% CI, 1.13 to 1.92; P =.004), and a decrease in Ep (increase in distensibility) over time (HR, 1.38 for 10% decrease in Ep over 6 months; 95% CI, 1.08 to 1.78; P =.010) significantly reduced the time to rupture (had a shorter time to rupture). Conclusion: Women have a shorter time to AAA rupture. The measurement of AAA distensibility, diastolic BP, and diameter may provide a more accurate assessment of rupture risk than diameter alone. (J Vasc Surg 2003;37:112-7.

    Amylin and Diabetic Cardiomyopathy – Amylin-Induced Sarcolemmal Ca\u3csup\u3e2+\u3c/sup\u3e Leak Is Independent of Diabetic Remodeling of Myocardium

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    Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca2+ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the hypothesis that aggregated amylin accumulates in the heart in the absence of diabetes. AKO mice infused with human, but not rodent amylin, showed amylin deposits in the myocardium. Cardiac amylin level was larger in males compared to females. Sarcolemmal Ca2+ leak and Ca2+ transients were increased in myocytes isolated from males infused with human amylin while no significant changes occurred in either females injected with human amylin or in rat amylin-infused mice. In isolated cardiac myocytes, the amylin receptor antagonist AC-187 did not effectively block the interaction of amylin with the sarcolemma. In conclusion, circulating aggregated amylin accumulates preferentially in male vs. female hearts and its effects on myocyte Ca2+ cycling do not require diabetic remodeling of the myocardium

    The relationship between aortic wall distensibility and rupture of infrarenal abdominal aortic aneurysm

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    AbstractObjective: A more accurate means of prediction of abdominal aortic aneurysm (AAA) rupture would improve the clinical and cost effectiveness of prophylactic repair. The purpose of this study was to determine whether AAA wall distensibility can be used to predict time to rupture independently of other recognized risk factors. Methods: A prospective, six-center study of 210 patients with AAA in whom blood pressure (BP), maximum AAA diameter (Dmax), and AAA distensibility (pressure strain elastic modulus [Ep] and stiffness [β]) were measured at 6 months with an ultrasound scan-based echo-tracking technique. A stepwise, time-dependent, Cox proportional hazards model was used to determine the effect on time to rupture of age, gender, BP, Dmax, BP, Ep, β, and change in Dmax, Ep, and β adjusted for time between follow-up visits. Results: Median (interquartile range) AAA diameter was 48 mm (41 to 54 mm), median age was 72 years (68 to 77 years), and median follow-up period was 19 months (9 to 30 months). In the Cox model, female gender (hazards ratio [HR], 2.78; 95% CI, 1.23 to 6.28; P =.014), larger Dmax (HR, 1.36 for 10% increase in Dmax; 95% CI, 1.12 to 1.66; P =.002), higher diastolic BP (HR, 1.13 for 10% increase in BP; 95% CI, 1.13 to 1.92; P =.004), and a decrease in Ep (increase in distensibility) over time (HR, 1.38 for 10% decrease in Ep over 6 months; 95% CI, 1.08 to 1.78; P =.010) significantly reduced the time to rupture (had a shorter time to rupture). Conclusion: Women have a shorter time to AAA rupture. The measurement of AAA distensibility, diastolic BP, and diameter may provide a more accurate assessment of rupture risk than diameter alone. (J Vasc Surg 2003;37:112-7.

    Gestational Diabetes Triggers Postpartum Cardiac Hypertrophy via Activation of Calcineurin/NFAT Signaling

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    Population-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during both pregnancy and postpartum periods. Hypertrophic Ca2+-dependent calcineurin/NFAT signaling was stimulated two months after giving birth in HIP females but not in the WT. In contrast, the CaMKII/HDAC hypertrophy pathway was active immediately after giving birth and returned to the baseline by two months postpartum in both WT and HIP females. Myocytes from two months postpartum HIP females exhibited slower Ca2+ transient relaxation and higher diastolic Ca2+ levels, which may explain calcineurin activation. No such effects occurred in the WT. These results suggest that a GDM-complicated pregnancy accelerates the development of pathological cardiac remodeling likely through activation of calcineurin/NFAT signaling

    Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population

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    Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution. Methods: To assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression. Results: One thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8% of children 53.2% of 5–14 year-olds post-PCV13, compared with pre-PCV13 prevalence of 72.2% and 49.4%, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children 13.5% pre-PCV13 to 5.8% post-PCV13 (p \u3c 0.01), and from 8.4% to 6.1% in children 5–14 years old (p \u3e 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%). Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95% confidence interval [CI] 2.39–7.33), with nasal discharge (OR 2.49 [95% CI 2.00–3.09]), residence in a remote community (OR 2.21 [95% CI 1.67–2.92]) and household crowding (OR 1.36 [95% CI 1.11–1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33–0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%, 100.0% and 93.3% for 7B). Conclusion: Since PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among childrenold, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population

    High Nasopharyngeal Carriage of Non-Vaccine Serotypes in Western Australian Aboriginal People Following 10 Years of Pneumococcal Conjugate Vaccination

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    BackgroundInvasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program. MethodsWe collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. ResultsStreptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml) was found in 1.6% of serotype 19A (5.2%), 19F (4.9%) and 16F (3.2%) isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml) in 24.9% of isolates, particularly 19F (92.7%), 19A (41.3%), 16F (29.0%). Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin.ConclusionsTen years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried pneumococci. A large proportion of circulating serotypes are not covered by any currently licensed vaccine

    Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians

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    Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians

    Practice development plans to improve the primary care management of acute asthma: randomised controlled trial

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    Background: Our professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal. Methods: We invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering. Results: 23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02). Conclusion: We demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care
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