The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study.

OBJECTIVE: Metabolic syndrome is a condition that promotes atherosclerosis and increases the risk of cardiovascular mortality and morbidity. We evaluated whether leisure time physical activity is associated with the levels of inflammatory and coagulation markers, in people with metabolic syndrome. METHODS: From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women (>18 years old), without any clinical evidence of cardiovascular disease, stratified by age-gender (census 2001). The population of the study was divided into those who fulfilled the NCEP ATP III criteria for the metabolic syndrome (n=701 or 33% men and 13% women) and the rest of the participants (n=2341). We assessed the relationship between self-reported physical activity status and inflammatory, and coagulation markers [i.e., C-reactive protein (CRP), serum amyloid-A (SAA), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, white blood cell (WBC) counts, and fibrinogen (FIB)], after taking into account the effect of several confounders. RESULTS: Of the non-metabolic syndrome group, 56% of men and 58% of women were classified as sedentary, while of the metabolic syndrome group 58% men and 72% women were sedentary. After controlling for various potential confounders we found that physically active individuals with the metabolic syndrome had 36% lower levels of CRP, 15% lower levels of WBC, 19% lower levels of SAA, 15% lower levels of TNF-alpha, 30% lower levels of IL-6 and 15% lower levels of FIB, compared to sedentary (all P<0.05). Similar results were observed in the non-metabolic syndrome group. CONCLUSIONS: The adoption of a physically active lifestyle is independently associated with lower levels of the investigated biomarkers in individuals with the metabolic syndrome. The latter may suggest a pathway for reducing cardiovascular events, even in high-risk people.     

Stenting the distal anastomotic site of the left internal mammary artery graft: a case report

The major problem associated with the long-term patency of the internal mammary artery graft is the early occurrence of stenosis usually at its distal anastomotic site; its management by balloon angioplasty has been associated with a high success rate. We report the case of an unsuccessful balloon angioplasty of an anastomotic stenosis of a left internal mammary artery graft that was successfully managed by stenting with one-half of a Palmaz-Schatz stent. © 1994 Wiley-Liss,Inc..     

Phenotype reveals genotype in a Greek long QT syndrome family.

We aimed to verify the long QT syndrome (LQTS) genotype in a family with strong evidence of LQTS type 1 (LQT1) on the basis of so far established genotype-phenotype correlations. Genetic testing for mutations in the KCNQ1 potassium channel gene revealed an A341V mutation in three generations of the family. Existing genotype-phenotype correlations were correctly predictive of the genotype in the case of this family, despite the fact that there are no previously reported data for the Greek LQTS genetic pool. Thus, genotype-phenotype correlations are often a helpful tool in the management of LQTS patients and their families.     

Reduced Geminin levels promote cellular senescence

Cellular senescence is a permanent out-of-cycle state regulated by molecular circuits acting during the G1 phase of the cell cycle. Cdt1 is a central regulator of DNA replication licensing acting during the G1 phase and it is negatively controlled by Geminin. Here, we characterize the cell cycle expression pattern of Cdt1 and Geminin during successive passages of primary fibroblasts and compare it to tumour-derived cell lines. Cdt1 and Geminin are strictly expressed in distinct subpopulations of young fibroblasts, similarly to cancer cells, with Geminin accumulating shortly after the onset of S phase. Cdt1 and Geminin are down-regulated when primary human and mouse fibroblasts undergo replicative or stress-induced senescence. RNAi-mediated Geminin knock-down in human cells enhances the appearance of phenotypic and molecular features of senescence. Mouse embryonic fibroblasts heterozygous for Geminin exhibit accelerated senescence compared to control fibroblasts. In contrast, ectopic expression of Geminin in mouse embryonic fibroblasts delays the appearance of the senescent phenotype. Taken together, our data suggest that changes in Geminin expression levels affect the establishment of senescence pathways.     

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

Objective:

Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features.

Methods:

A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined.

Results:

Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC).

Conclusion:

The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making.

Advances in knowledge:

The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.     

Heart-type fatty acid-binding protein permits early risk stratification of pulmonary embolism.

AIMS: We investigated the value of a novel early biomarker, heart-type fatty acid-binding protein (H-FABP), in risk stratification of patients with acute pulmonary embolism (PE). METHODS AND RESULTS: We prospectively included 107 consecutive patients with confirmed PE. The endpoints were (i) PE-related death or major complications and (ii) overall 30-day mortality. Overall, 29 patients (27%) had abnormal (>6 ng/mL) H-FABP levels at presentation. Of those, 12 (41%) had a complicated course, whereas all patients with normal baseline H-FABP had a favourable 30-day outcome (OR, 71.45; P<0.0001). At multivariable analysis, H-FABP (P<0.0001), but not cardiac troponin T (P=0.13) or N-terminal pro-brain natriuretic peptide (P=0.36), predicted an adverse outcome. Evaluation of a strategy combining biomarker testing with echocardiography revealed that patients with a negative H-FABP test had an excellent prognosis regardless of echocardiographic findings. In contrast, patients with a positive H-FABP test had a complication rate of 23.1% even in the presence of a normal echocardiogram, and this rose to 57.1% if echocardiography also demonstrated right ventricular dysfunction (OR vs. a negative H-FABP test, 5.6 and 81.4, respectively). CONCLUSION: H-FABP is a promising early indicator of right ventricular injury and dysfunction in acute PE. It may help optimize risk stratification algorithms and treatment strategies.