Homocysteine and carotid atherosclerosis in chronic renal failure--the confounding effect of renal function

Since total homocysteine (tHcy) level is markedly elevated in patients with chronic renal failure (CRF), it has been presented as a potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was to examine the significance of elevated tHcy level and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. In this cross-sectional study, 135 study patients with CRF (52 +/- 11 years) included 58 patients with moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant recipients. In addition, 58 control subjects were examined. The association of tHcy level and classic risk factors for atherosclerosis with common carotid artery intima-media thickness (IMT) or carotid artery plaque score was examined. We found no association between tHcy and carotid IMT or a high carotid plaque score in the CRF patient groups. No consistent association was found between elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral arterial disease. Renal function, described as creatinine clearance, was the strongest determinant for tHcy level. Significant predictors of carotid atherosclerosis were age, duration of hypertension and elevated low-density lipoprotein cholesterol level. In conclusion, the present study shows no apparent association between tHcy level and atheromatous carotid findings in patients with CRF. However, because of the changing renal function in the course of renal disease, the strong confounding effect of renal function may not be adequately controlled for the analysis of the significance of elevated tHcy level for CVD in patients with CRF.     

Possible role for mast cell-derived cathepsin G in the adverse remodelling of stenotic aortic valves

Aims Aortic stenosis (AS) is characterized by extensive remodellingof the valves, including infiltration of inflammatory cells,extracellular matrix degradation, and fibrosis. The molecularmechanisms behind this adverse remodelling have remained obscure.In this article, we study whether cathepsin G, an angiotensinII (Ang II)-forming elastolytic enzyme, contributes to progressionof AS. Methods and results Stenotic aortic valves (n=86) and controlvalves (n=17) were analysed for cathepsin G, transforming growthfactor-ß1 (TGF-ß1), and collagens I andIII with RT–PCR and immunohistochemistry. Valvular collagen/elastinratio was quantified by histochemistry. In stenotic valves,cathepsin G was present in mast cells and showed increased expression(P<0.001), which correlated positively (P<0.001) withthe expression levels of TGF-ß1 and collagens I andIII. TGF-ß1 was also present in mast cell-rich areasand cathepsin G induced losartan-sensitive TGF-ß1expression in cultured fibroblasts. Collagen/elastin ratio wasincreased in stenotic valves (P<0.001) and correlated positivelywith smoking (P=0.02). Nicotine in cigarette smoke activatedmast cells and induced TGF-ß1 expression in culturedfibroblasts. Fragmented elastin was observed in stenotic valvescontaining activated cathepsin G-secreting mast cells and innormal valves treated with cathepsin G. Conclusion In stenotic aortic valves, mast cell-derived cathepsinG may cause adverse valve remodelling and AS progression.     

Shortened hospital stay for childhood bone and joint infections: Analysis of 265 prospectively collected culture-positive cases in 1983-2005

Abstract Background: In recent decades the treatment of childhood acute bone and joint infections has shifted towards shorter antibiotic courses and rapid transition to oral therapy. Methods: We prospectively collected 265 culture-positive cases of non-neonatal bone and joint infections in Finnish children during 1983-2005. The duration of antimicrobial treatment and the extent of surgery were defined in the study protocol, but for ethical reasons, the liaison clinician determined the time of discharge using normalization of the serum C-reactive protein (CRP) level as a yardstick. We examined changes during the study in the distribution of causative organisms, severity of disease, and length of hospital stay. Results: Staphylococcus aureus was overwhelmingly the most common causative agent throughout the study, whereas Haemophilus influenzae type b was eliminated soon after the introduction of vaccination. The mean time from initial symptoms to presentation remained the same at 4 days, and no significant change was observed in the severity of disease, CRP, or the rate of sequelae. The mean duration of intravenous antibiotic administration was only 4 days. The average hospital stay shortened significantly from 13 days to 9 days (p =?0.0001). Conclusions: The shortened hospital stay was not due to a change in the anatomical site of these infections, but to simplified treatment. Considerable savings in hospital stay, and thus costs, are feasible in osteoarticular infections of childhood by using CRP in monitoring the disease and shortening intravenous treatment by a swift move to per oral administration.