Relationships of plasma factor VIIa-antithrombin complexes to manifest and future cardiovascular disease

Background

Low levels of free activated coagulation factor VII (VIIa) are normally present in plasma to prime the coagulation of blood in normal hemostasis and during thrombus formation. VIIa also circulates in inactive form, in complex with antithrombin (VIIaAT) formed when VIIa is bound to tissue factor (TF). This study evaluated VIIaAT in relation to cardiovascular disease (CVD).

Methods

We determined the plasma VIIaAT concentration in samples from the Stockholm Coronary Atherosclerosis Risk Factor (SCARF) study, a population-based case-control study of myocardial infarction (MI) and in samples from the Stockholm study of 60-years-old individuals, a prospective study of CVD. VIIaAT was measured with a sandwich ELISA that captures the complex between a monoclonal antibody to VIIa and a polyclonal antibody to AT.

Results

In the SCARF study (200 post-MI cases, 340 controls), VIIaAT was statistically significantly associated with patient status [odds ratio (95% confidence interval (CI)] 1.51 (1.09-2.08), p = 0.0126). The case-control differences were however small, with VIIaAT values that largely overlap between the two groups. When a nested case-control design (211 incident CVD cases and 633 matched controls) was applied on 5- to 7-year follow-up results of the Stockholm prospective study of 60-year-olds, plasma VIIaAT concentration was not associated with incident CVD (odds ratio (95% CI) 1.001 (0.997-1.005), p = 0.5447).

Conclusions

Plasma VIIaAT concentration had no predictive value for future CVD in our study population. Slightly increased plasma VIIaAT concentrations observed after MI may reflect processes that occur in connection with the acute event when TF and VIIa availability is increased.     

In vitro activity of ceftaroline and comparator antimicrobials against European and Middle East isolates from complicated skin and skin-structure infections collected in 2008-2009

The activities of ceftaroline, the active metabolite of the pro-drug ceftaroline fosamil, a novel anti-meticillin-resistant staphylococcal cephalosporin, and nine comparators were determined against surveillance isolates collected in 2008-2009. Over 3000 isolates associated with complicated skin and skin-structure infections (cSSSIs) were collected from 106 centres in 19 countries. MICs were determined using CLSI broth microdilution methodology. Clonal relatedness of meticillin-resistant Staphylococcus aureus (MRSA) with raised ceftaroline MICs (2mg/L) was assessed by MLST, PFGE and mec typing. The presence of Panton-Valentine leukocidin in these isolates was also determined. Ceftaroline was active against 500 MRSA and 479 meticillin-susceptible S. aureus, with MIC(50/90) values of 0.5/2mg/L and 0.25/0.25mg/L, respectively. For coagulase-negative staphylococci (CoNS), the ceftaroline MIC(50/90) values for meticillin-resistant strains (n=159) were the same as those seen for MRSA. Meticillin-susceptible CoNS (n=113) had the same MIC(90) as that seen with S. aureus, but the MIC(50) was lower at 0.06mg/L. Ceftaroline was also active against β-haemolytic streptococci (n=526; MIC(50/90)=0.004/0.015mg/L), other streptococci (n=75; 0.015/0.06mg/L), common Enterobacteriaceae (n=897; 0.25/≥128mg/L) and Enterococcus faecalis (n=329; 1/16mg/L). Those MRSA with ceftaroline MICs of 2mg/L were found to be from four clonal groups associated with the country of origin. These data confirm the broad-spectrum in vitro activity of ceftaroline against cSSSI pathogens. Ceftaroline is unique among clinically available cephalosporins, having good in vitro activity against MRSA and meticillin-resistant CoNS and moderate activity against Gram-negative bacteria.     

Ethnicity and depression treatment preferences of pregnant women

African American, Hispanic, and White women between 12 and 32 weeks gestation were recruited to examine their depression treatment preferences. The 73 women who participated were interviewed after their prenatal visit. Nineteen percent of women had symptoms of moderate or severe depression. Women with moderate or severe symptoms of depression were more likely to believe that antidepressants were an acceptable treatment than those without symptoms or with only minor depression symptoms. There were only small differences among the three ethnic groups for antidepressant use preference but most women found them to be unacceptable. In contrast, approximately half of the White women felt that herbal medicines were acceptable compared with 16 and 22 percent for African Americans and Hispanics, respectively. Only 44 percent of African American women felt that counseling from a mental health professional was an acceptable treatment for depression compared to 68 percent for White and 61 percent for Hispanic women. Similarly, African American women were less likely to believe that waiting and getting over depression symptoms naturally was acceptable compared to Hispanic and White women.     

The endovascular repair of abdominal aortic aneurysm: an update analysis of structural failure modes of endovascular stent grafts

Over the last decade, more than 25,000 endovascular stent grafts have been used to treat aortic aneurysms. Although results have been promising thus far, problems with endoleaks, material failure, device migration, and aneurysm rupture continue to be reported. Improvements in device material and design have contributed to the rapid growth and utility of these devices; however, material failure still remains a concerning mode for potential procedure failure. A review of the authors'experience with material failure and a review of the literature was conducted to help understand and comprehend the magnitude of this problem and try to determine its clinical significance.     

Endothelin and neonatal capsaicin regulate gastric resistance to injury in BDL rats

AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow was measured by laser-Doppler flow-metry. RESULTS: ET-3 and an ETB receptor antagonist sig- nificantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Cap-saicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET B receptor and by sensory afferent neurons.     

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