PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The epidemiology of gonorrhoea in Norway, 1993–2007: past victories, future challenges

<p>Abstract</p> <p>Background</p> <p>Gonorrhoea, a bacterial infection caused by <it>Neisseria gonorrhoeae</it>, has been increasing in several European countries, particularly among men who have sex with men (MSM) and teenagers. We describe the epidemiology of gonorrhoea in Norway in the recent 15 years in order to guide recommendations on the diagnosis, treatment and prevention of gonorrhoea. An evaluation of the Norwegian Surveillance System for Communicable Diseases (MSIS) in 1994, involving GPs and microbiological laboratories, suggested that the system has a high coverage, capturing over 90% of patients diagnosed with gonorrhoea.</p> <p>Methods</p> <p>Using MSIS data on gonorrhoea cases we analysed specific trends by route of transmission, age, gender, anatomical sampling site, antimicrobial resistance and travel history from 1993–2007 and, to focus on more recent trends, from 2003–2007. MSM and heterosexual cases were defined by route of transmission.</p> <p>Results</p> <p>From 1993 to 2007, 3601 gonorrhoea cases were reported. MSM cases increased from 10 in 1994 to 109 cases in 2004. From 2003–2007, the incidence of gonorrhoea was 5.4/100,000 person-years (95%CI: 4.9–6.0). Over these five years, MSM accounted for an average of 80 cases per year, of which 69% were infected by casual partners. In the same period, 98% of heterosexually infected had a positive swab from urethra only and only two (0.3%) from the pharynx. Only one woman (0.5%) was positive from the rectum. From 1993 – 2007, antimicrobial resistance results were reported for 3325 <it>N. gonorrhoeae </it>isolates (98% of cultured samples). The proportion resistant to quinolone has risen from 3% in 1995 to 47% in 2007, with 81% of the latter isolated from patients infected in Asia.</p> <p>Conclusion</p> <p>The overall incidence of gonorrhoea in Norway remains low, but the increasing number of MSM cases calls for new, more effective approaches to prevention. Infections originating from abroad represent a constant risk of importing antimicrobial resistant <it>N. gonorrhoeae</it>. Due to the prevalence of quinolone resistant <it>N. gonorrhoeae </it>in Norway, third-generation cephalosporins should replace quinolones as the first choice in treatment guidelines. We advocate antimicrobial susceptibility testing for all cases and recommend taking samples for culture from all exposed anatomical sites.</p