A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t) ¼ b 0 Â exp(Àb 1 t), where t represents the age (day). This regression model was applied to C57BL/6 Â DBA/2 (B Â D) recombinant inbred strains of mice to identify the genetic loci influencing agerelated thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the agerelated thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.

No abstract

In black Africans, eGFR derived from the CKD-EPI equation is better at detecting end-organ measures than eGFR derived from either the MDRD or alternative equations. To enhance risk prediction in black African communities, eGFR calculated from the CKD-EPI equation may be preferred to other equations.

ObjectiveTo determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA).MethodsWe calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients.ResultsThe CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold.ConclusionReduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.

Aim We hypothesized that arterial function and N‐terminal natriuretic peptide (NT‐proBNP) levels as a marker of volume overload, relate differently to E/e′ as an index of diastolic function in dialysis compared with non‐dialysis patients with chronic kidney disease. We further examined whether cardiovascular risk factors attenuated these relationships. Methods We assessed cardiovascular risk factors and determined arterial function indices by applanation tonometry using SphygmoCor software and E/e′ by echocardiography in 103 (62 non‐dialysis and 41 dialysis) patients. Results In established confounder adjusted analysis, dialysis status impacted the pulse wave velocity‐E/e′ relationship (interaction p = .01) but not the NT‐proBNP level‐E/e′ association (interaction p = .1). Upon entering arterial function measures and NT‐proBNP levels simultaneously in regression models, arterial function measures were associated with E/e′ (p = .008 to .04) in non‐dialysis patients whereas NT‐proBNP levels were related to E/e′ in dialysis patients (p = .009 to .04). Bivariate associations were found between diabetes (p < .0001) and E/e′ in non‐dialysis patients, and haemoglobin concentrations and E/e′ (p = .02) in those on dialysis. Upon adjustment for diabetes in non‐dialysis patients, only central pulse pressure remained associated with E/e′ (p = .02); when haemoglobin concentrations were adjusted for in dialysis patients, NT‐proBNP levels were no longer associated with E/e′ (p = .2). In separate models, haemoglobin levels were associated with E/e′ independent of left ventricular mass index and preload and afterload measures (p = .02 to .03). Conclusion The main determinants of E/e′ may differ in non‐dialysis compared with dialysis patients. These include arterial function and diabetes in non‐dialysis patients, and volume overload and anaemia in dialysis patients.