Oxysterols are increased in plasma of end-stage renal disease patients

BACKGROUND/AIMS: Oxidative stress occurs in chronic renal failure patients undergoing hemodialysis (HD). The objective of our study was to measure oxidation products of cholesterols, so-called oxysterols, in the serum of HD patients in comparison to healthy control persons. METHODS: In 42 HD patients, plasma oxysterols were measured before and after HD. The values were compared with those in 40 healthy controls. The following cholesterol derivatives were analyzed: dienes, 7beta-OH, beta-epoxy, alpha-epoxy, 20alpha-OH, alpha-triol, and 7-keto cholesterol. RESULTS: In HD patients, serum levels of oxysterols are increased in comparison to controls. The highest values were measured for beta-epoxy cholesterol and for 20alpha-OH cholesterol. During HD oxysterol concentrations increased, obviously by water removal and concentration of nondialyzable compounds. CONCLUSION: Due to oxidative stress which is known as a typical sign of chronic renal failure the plasma concentrations of oxysterols are also significantly increased in comparison to healthy controls. This underlines the data on accelerated lipid peroxidation in end-stage renal disease (ESRD) patients. Accumulated oxysterols which are accused of exerting atherosclerosis-stimulating effects, which can contribute to the increased cardiovascular risk of ESRD patients, could either induce atherosclerosis via signaling or chronic effects. Direct chemical reactions stimulating plaque formation can be excluded because of the low levels of oxysterols. The share of oxysterols within the total cholesterol ranges from 4 to 15 per thousand.     

Recent progress in the treatment of lower limb defects

Technological and reconstructive surgical procedures improvments are limiting demolitive interventions on the lower limb for common pathologies and traumatology. From 1999 to 2002, 32 men and 14 women, from 18 to 54 years-old, were admitted at the Operative Unit of Plastic Surgery of ASL RMH. They were grouped according to cause and site of extremity defects and different surgical techniques. Seven cross-leg flaps, 31 proximity flaps, and 18 skin grafts were performed. The results were satisfactory except in two cases. The Authors are oriented towards the cross-leg flap for foot repair. For other anatomical districts, they prefer muscular flaps covered by skin grafts. Finally, for neoplastic lesions they choose proximity flaps.     

Retinal abnormalities in newly diagnosed adult acute myeloid leukemia

Retinal abnormalities (RA) are very frequently observed in adult patients with acute myeloid leukemia (AML), but the clinical significance of these findings has not been fully investigated. We examined the fundus oculi in a cohort of 122 adult patients with AML at presentation and analyzed some clinical and biological features to assess whether there was any association with RA. For this purpose, we subdivided the patients into two groups according to the presence or absence of RA (groups 1 and 2, respectively). We considered current laboratory parameters such as white blood cell (WBC) count, hemoglobin (Hb), platelets and serum lactate dehydrogenase (LDH). Moreover, we subdivided the patients into two groups according to age <60 (group A) or > or =60 years (group B) to evaluate a possible association between RA and response to treatment and/or overall survival (OS). In our series, a higher median age and a lower Hb value were associated with group 1 (p = 0.001 and p = 0.04, respectively); the median LDH value was 812 U/l (range 224-5,551) and 607 (range 181-5,244) for groups 1 and 2, respectively (p = 0.02). There was no association between RA and karyotypic alterations. In terms of outcome, in group A (<60 years), 80% patients who achieved complete remission (CR) were in group 2 vs. 13% nonresponders (NR) (p < 0.0001). Median OS of group 2 patients was 49.7 months compared with 7.2 months for those in group 1 (p = 0.002). In group B, 58% patients who achieved CR were in group 1 vs. 15% NR (p < 0.006). Median OS of patients in group 2 was 14.6 months compared with 2.9 months in group 1 (p = 0.02). Our data show that RA are significantly associated with some biological features and with shorter OS in AML patients and this parameter seems to be an effective clinical sign of poor prognosis in terms of CR.     

Elevated serum concentration of cardiotoxic lipid peroxidation products in chronic renal failure in relation to severity of renal anemia

Patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) and 4-hydroxylnonenal (HNE) were found in plasma of uremic patients indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The catabolism and action of those products was already intensively studied. As highly reactive metabolites they are able to bind to proteins, nucleic acids, and other molecules. Doing so, they exert molecular signal effects in cells and are able to exacerbate tissue and organ damage, e.g. cardiotoxic effects. Since renal anemia was shown to promote oxidative stress as well, the aim of our investigation was to examine its role in HD patients. Therefore, two groups of HD patients were investigated (group I Hb < 10 g/dl, group II Hb > 10 g/dl) and serum concentrations of MDA, HNE, and of protein carbonyls, a marker for protein oxidation, were determined. All HD patients had significantly higher levels of the LPO products MDA and HNE compared with controls. However, group I patients showed higher MDA and HNE concentrations compared to group II patients. The same result could be seen for protein carbonyls. During HD concentration of both LPO products decreased. However, this was not the case for protein carbonyls. These results lead to the conclusion that optimized correction of the renal anemia may result in a significant reduction of oxidative stress and therefore in the reduction of organ tissue damage. In this way correction of renal anemia will reduce the cardiovascular risk and comorbidity of HD patients improving their prognosis.     

Oxidative stress in chronic renal failure as a cardiovascular risk factor

Myocardial injury has been shown to be the most critical factor influencing quality of life and mortality in patients with chronic renal failure. Oxidative stress has been postulated to be an important risk factor for cardiovascular disorders. One reason for oxidative stress in patients with renal failure is the underlying disease itself. Renal toxicity, ischemia/reperfusion and immunological disorders of the kidney result in an elevated formation of reactive oxygen species active in the pathogenesis of kidney disease. However, treatment procedures were also shown to induce oxidative stress. Increased formation of free radicals leads to an accelerated lipid peroxidation (LPO). Furthermore, secondary aldehydic LPO products, e.g. malondialdehyde (MDA) and 4-hydroxynonenal (HNE), are formed which were shown to deplete antioxidants, inhibit protein syntheses, mitochondrial respiration, and enzyme functions. F2-isoprostanes, also metabolites of polyunsaturated fatty acids, represent an additional in vivo marker of oxidative stress. Both isoprostanes and aldehydic LPO products can be removed by hemodialysis, however, this suggests only in part their binding to other molecules which cause tissue damage. Protein carbonyls are end-products of such interventions. Oxysterols, another form of free-radical initiated oxidation products, were shown to initiate atherosclerosis and plaque formation increasing dramatically the risk of coronary heart disease. Today there is no doubt that the correction of the oxidant/antioxidant imbalance in patients with chronic renal failure is an important approach for the reduction of the risk of those patients to develop cardiovascular disorders. The complete correction of renal anemia represents an effective means of strengthening antioxidant capacity and, therefore, of reducting cardiovascular risk potential.     

Improved cardiovascular risk stratification by a simple ECG index in hypertension

BACKGROUND: We determined the prognostic value of the Cornell/strain [C/S] index, a simple electrocardiographic (ECG) index for left ventricular hypertrophy (LVH) defined by the presence of either a classic strain pattern or a Cornell voltage (sum of R in aVL + S in V(3)) >2.0 mV in women or 2.4 mV in men, or both. METHODS: In a prospective, cohort study, 2190 initially untreated subjects (age 51 [+/- 12], 47% women) with essential hypertension without prior events were followed for up to 14 years (median, 5 years). RESULTS: Prevalence of LVH at entry was 16.3% by using the C/S index, which yielded 33.6% sensitivity and 91.0% specificity. Other ECG criteria for LVH including Sokolow-Lyon, Romhilt-Estes, Framingham, Cornell, and strain alone, achieved a lower sensitivity and prevalence. Over the subsequent follow-up, 244 patients experienced a first major cardiovascular event. Event rate (x 100 person-years) was 2.01 in those without and 4.44 in those with LVH by the C/S index (P <.001). After adjustment for age, sex, smoking, and other counfounders, the C/S index identified subjects at increased risk of events (relative risk 1.76; 95% confidence interval 1.32-2.33). The C/S index achieved the highest population-attributable risk (16.1%) for cardiovascular events. CONCLUSIONS: A simple ECG index that can be quickly measured from nondigital machines and without algorithms identifies LVH in a consistent proportion (16.3%) of hypertensive subjects. The LVH defined by such technique allows identification of individuals at high risk for cardiovascular events.