Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik

Background: Methylmercury (MeHg) exposure has been linked to an increased risk of coronary heart disease (CHD). Paraoxonase 1 (PON1), an enzyme located in the high-density–lipoprotein (HDL) fraction of blood lipids, may protect against CHD by metabolizing toxic oxidized lipids associated with low-density liproprotein and HDL. MeHg has been shown to inhibit PON1 activity in vitro, but this effect has not been studied in human populations.Objectives: This study was conducted to determine whether blood mercury levels are linked to decreased plasma PON1 activities in Inuit people who are highly exposed to MeHg through their seafood-based diet.Methods: We measured plasma PON1 activity using a fluorogenic substrate and blood concentrations of mercury and selenium by inductively coupled plasma mass spectrometry in 896 Inuit adults. Sociodemographic, anthropometric, clinical, dietary, and lifestyle variables as well as PON1 gene variants (rs705379, rs662, rs854560) were considered as possible confounders or modifiers of the mercury–PON1 relation in multivariate analyses.Results: In a multiple regression model adjusted for age, HDL cholesterol levels, omega-3 fatty acid content of erythrocyte membranes, and PON1 variants, blood mercury concentrations were inversely associated with PON1 activities [β-coefficient = –0.063; 95% confidence interval (CI), –0.091 to –0.035; p < 0.001], whereas blood selenium concentrations were positively associated with PON1 activities (β-coefficient = 0.067; 95% CI, 0.045–0.088; p < 0.001). We found no interaction between blood mercury levels and PON1 genotypes.Conclusions: Our results suggest that MeHg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.     

Impact of routine percutaneous coronary intervention after out-of-hospital cardiac arrest due to ventricular fibrillation

Introduction

Since 2003, we have routinely used percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) to treat patients < 80 years of age after out-of-hospital cardiac arrest (OHCA) related to ventricular fibrillation. The aim of our study was to evaluate the prognostic impact of routine PCI in association with MTH and the potential influence of age.

Methods

We studied 111 consecutive patients resuscitated successfully following OHCA related to shock-sensitive rhythm. They were divided into five groups according to age: < 45 years (n = 22, group 1), 45 to 54 years (n = 27, group 2), 55 to 64 years (n = 22, group 3), 65 to 74 years (n = 23, group 4) and ≥75 years (n = 17, group 5). Emergency coronary angiography was performed in hemodynamically stable patients < 80 years old, regardless of the electrocardiogram pattern. MTH was targeted to a core temperature of 32°C to 34°C for 24 hours.

Results

Most patients (73%) had coronary heart disease, although its incidence in group 1 was lower than in other groups (41% versus 81%; P = 0.01). In group 1, all patients but one underwent coronary angiography, and 33% of them underwent associated PCI. In group 5, only 53% of patients underwent a coronary angiography and 44% underwent PCI. Overall in-hospital survival was 54%, ranging between 52% and 64% in groups 1 to 4 and 24% in group 5. Time from collapse to return of spontaneous circulation was associated with mortality (odds ratio (OR) = 1.05 (25th to 75th percentile range, 1.03 to 1.08); P < 0.001), whereas PCI was associated with survival (OR = 0.30 (25th to 75th percentile range, 0.11 to 0.79); P = 0.01).

Conclusions

We suggest that routine coronary angiography with potentially associated PCI may favorably alter the prognosis of resuscitated patients with stable hemodynamics who are treated with MTH after OHCA related to ventricular fibrillation. Although age was not an independent cause of death, the clinical relevance of this therapeutic strategy remains to be determined in older people.     

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig

Introduction  

Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig.     

Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury

Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.