Exposure to Trihalomethanes through Different Water Uses and Birth Weight, Small for Gestational Age, and Preterm Delivery in Spain

BACKGROUND Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. OBJECTIVE We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery. METHODS Mother-child cohorts set up in five Spanish areas during the years 2000-2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis. RESULTS Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was -0.45 g (95% confidence interval: -1.36, 0.45 g) for chloroform and 0.16 g (-1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery. CONCLUSIONS Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.

Relation of cardiac troponin I measurements at 24 and 48 hours to magnetic resonance-determined infarct size in patients with ST-elevation myocardial infarction.

Levels of circulating cardiac troponin I (cTnI) or T are correlated to extent of myocardial destruction after an acute myocardial infarction. Few studies analyzing this relation have employed a second-generation cTnI assay or cardiac magnetic resonance (CMR) as the imaging end point. In this post hoc study of the Efficacy of FX06 in the Prevention of Mycoardial Reperfusion Injury (F.I.R.E.) trial, we aimed at determining the correlation between single-point cTnI measurements and CMR-estimated infarct size at 5 to 7 days and 4 months after a first-time ST-elevation myocardial infarction (STEMI) and investigating whether cTnI might provide independent prognostic information regarding infarct size at 4 months even taking into account early infarct size. Two hundred twenty-seven patients with a first-time STEMI were included in F.I.R.E. All patients received primary percutaneous coronary intervention within 6 hours from onset of symptoms. cTnI was measured at 24 and 48 hours after admission. CMR was conducted within 1 week of the index event (5 to 7 days) and at 4 months. Pearson correlations (r) for infarct size and cTnI at 24 hours were r = 0.66 (5 days) and r = 0.63 (4 months) and those for cTnI at 48 hours were r = 0.67 (5 days) and r = 0.65 (4 months). In a multiple regression analysis for predicting infarct size at 4 months (n = 141), cTnI and infarct location retained an independent prognostic role even taking into account early infarct size. In conclusion, a single-point cTnI measurement taken early after a first-time STEMI is a useful marker for infarct size and might also supplement early CMR evaluation in prediction of infarct size at 4 months.

Influences of body weight, body composition, and substrate oxidation rate on resting postabsorptive glucose production and gluconeogenesis.

OBJECTIVE: To determine the influence of body weight, fat mass, and fat distribution on resting endogenous glucose production in healthy lean and overweight individuals. DESIGN: measurements were performed in the resting postabsorptive state in individuals receiving an unrestricted diet. SETTING: Institute of Physiology of Lausanne University. MEASUREMENTS: resting post absorptive glucose production, glycogenolysis and gluconeogenesis; resting energy expenditure and net substrate oxidation. RESULTS: Endogenous glucose production was positively correlated with body weight, lean body mass, energy expenditure and carbohydrate oxidation. Gluconeogenesis was positively correlated with net lipid oxidation and energy expenditure, and negatively correlated with net carbohydrate oxidation. No correlation with body fat or fat distribution was observed. CONCLUSIONS: Gluconeogenesis shows a large interindividual variability. Net lipid oxidation and not body fat appears to be a major determinant of gluconeogenesis.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Cardiac patient

Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30-day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure.

Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss.

Objective: To analyze the expression of peroxisome proliferator-activated receptor-γ1 and 2 (PPARγ1 and 2), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), and leptin in adipose tissue (AT) of obese women during weight loss following Roux-en-Y gastric bypass (RYGB) and to compare these levels with those obtained in AT of nonobese subjects. Methods: Gene expression was determined by real-time RT-PCR prior to surgery and at 3, 6, and 12 months after RYGB. Results: All obese patients lost weight, reaching a mean BMI of 29.3 ± 1.0 kg/m(2) at 1 year after surgery (-33.9 ± 1.5% of their initial body weight). In obese subjects leptin and 11βHSD1 were over-expressed, whereas PPARγ1 was expressed at lower levels compared to controls. After surgery, leptin and 11βHSD1 gene expression decreased, whereas PPARγ1 expression increased. At 12 months after RYGB, these 3 genes had reached levels similar to the controls. In contrast, PPARγ2 gene expression was not different between groups and types of tissue and remained unchanged during weight loss. We found a positive correlation between BMI and levels of gene expression of leptin and 11βHSD1. Conclusion: Gene expression of leptin, PPARγ1, and 11βHSD1 in AT is modified in human obesity. This default is completely corrected by RYGB. Copyright © 2012 S. Karger GmbH, Freiburg.

Trypanosoma cruzi: parasite persistence in tissues in chronic chagasic Brazilian patients

Chagas disease in the chronic phase may develop into cardiac and/or digestive forms. The pathogenesis of the disease is not yet clear and studies have been carried out to elucidate the role of parasite persistence in affected organs. The aim of this study was to detect and quantify Trypanosoma cruzi in paraffin-embedded tissue samples from chronic patients using NPCR (nested polymerase chain reaction) and QPCR (quantitative polymerase chain reaction) methods. These results were correlated to anatomopathological alterations in the heart and gastrointestinal tract (GIT). Of the 23 patients studied, 18 presented the cardiac form and five presented the cardiodigestive form of Chagas disease. DNA samples were randomly isolated from formalin-fixed paraffin-embedded sections of heart and GIT tissue of 23 necropsies and were analyzed through NPCR amplification. T. cruzi DNA was detected by NPCR in 48/56 (85.7%) heart and 35/42 (83.3%) GIT samples from patients with the cardiac form. For patients with the cardiodigestive form, NPCR was positive in 12/14 (85.7%) heart and in 14/14 (100%) GIT samples. QPCR, with an efficiency of 97.6%, was performed in 13 samples (11 from cardiac and 2 from cardiodigestive form) identified previously as positive by NPCR. The number of T. cruzi copies was compared to heart weight and no statistical significance was observed. Additionally, we compared the number of copies in different tissues (both heart and GIT) in six samples from the cardiac form and two samples from the cardiodigestive form. The parasite load observed was proportionally higher in heart tissues from patients with the cardiac form. These results show that the presence of the parasite in tissues is essential to Chagas disease pathogenesis.

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity.

BACKGROUND Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). METHODS Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. RESULTS There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. CONCLUSIONS These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.

Gene transfer of interleukin-18-binding protein attenuates cardiac allograft rejection.

Interleukin (IL) 18 is a potent pro-inflammatory Th1 cytokine that exerts pleiotropic effector functions in both innate and acquired immune responses. Increased IL-18 production during acute rejection has been reported in experimental heart transplantation models and in kidney transplant recipients. IL-18-binding protein (IL-18BP) binds IL-18 with high affinity and neutralizes its biologic activity. We have analyzed the efficacy of an adenoviral vector expressing an IL-18BP-Ig fusion protein in a rat model of heart transplantation. IL-18BP-Ig gene transfer into Fisher (F344) rat donor hearts resulted in prolonged graft survival in Lewis recipients (15.8 +/- 1.4 days vs. 10.3 +/- 2.5 and 10.1 +/- 2.1 days with control virus and buffer solution alone, respectively; P < 0.001). Immunohistochemical analysis revealed decreased intra-graft infiltrates of monocytes/macrophages, CD4(+), CD8alpha(+) and T-cell receptor alphabeta(+) cells after IL-18BP-Ig versus mock gene transfer (P < 0.05). Real-time reverse transcriptase polymerase chain reaction analysis showed decreased cytokine transcripts for the RANTES chemokine and transforming growth factor-beta after IL-18BP-Ig gene transfer (P < 0.05). IL-18BP-Ig gene transfer attenuates inflammatory cell infiltrates and prolongs cardiac allograft survival in rats. These results suggest a contributory role for IL-18 in acute rejection. Further studies aiming at defining the therapeutic potential of IL-18BP are warranted.

Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study.

BACKGROUND This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. METHODS Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. RESULTS Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially ≥30 kg/m2, 1.26 (1.23; 1.29)). CONCLUSIONS Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.

Bi-ventricular axial micropump: impact on blood cell integrity.

BACKGROUND AND OBJECTIVE: Off-pump coronary artery bypass grafting has stimulated the development of micro-pumps designed to prevent the hemodynamic instability induced by heart luxation for the exposure of target vessels of the posterior wall. Impella (Aachen, Germany) developed micro-pumps with a miniaturized propeller system for both sides of the heart. The aim of this study was to analyze the impact of both pumps working together on blood cell integrity. MATERIALS AND METHODS: Both right and left-sided micro-pumps were implanted in 5 calves (body weight, 72_4 Kg) during 3 h. Blood samples for hematology and hemolysis parameters were drawn hourly. RESULTS: Both pumps performed well with a flow of 3.6 L +/- 0.3 L during the 3 h of the experiment with stable hemodynamic conditions. Mixed venous oxygen saturation was 63.4 +/- 15.2% at baseline and 63.8 +/- 16.3% at the end of the experiment (P = ns). Red cell count, LDH and free plasma hemoglobin were 6.7 +/- 2.1 x 10(12)/L, 1807 +/- 437 IU/L, and 32 +/- 9 mg/L at baseline vs. 6.1 +/- 2.1 x 10(12)/L, 1871 +/- 410 IU/L, and 52 +/- 9 mg/L at the end of the experiment (P = ns for all comparisons). Platelet count exhibited a non-significant drop (872 +/- 126 vs. 715 +/- 22 x 10(9)/L). CONCLUSIONS: This double pump system based on the Archimed screw principle is hematologically well tolerated under conditions of prolonged cardiac assist.

Integrating postoperative value of cardiac Troponin I for a better correlation with in-hospital outcomes after congenital heart surgery.

Objective: Cardiac Troponin-I (cTnI) is a well-recognized early postoperative marker for myocardial damage in adults and children after heart surgery. The present study was undertaken to evaluate whether the integrated value (area under the curve(AUC)) of postoperative cTnI is a better mode to predict long-term outcome than post operative cTnI maximum value, after surgery for congenital heart defects (CHD). Methods: retrospective cohort study. 279 patients (mean age 4.6 years; range 0-17 years-old, 185 males) with congenital heart defect repair on cardiopulmonary by-pass were retrieved from our database including postoperative cTnI values. Maximal post operative cTnI value, post operative cTnI AUC value at 48h and total post operative cTnI AUC value were calculated and then correlated with duration of intubation, duration of ICU stay and mortality. Results: the mean duration of mechanical ventilation was 5.1+/-7.2 days and mean duration of ICU stay was 11.0+/- 13.3 days,11 patients (3.9%) died in post operative period. When comparing survivor and deceased groups, there was a significant difference in the mean value for max cTnI (16.7+/- 21.8 vs 59.2+/-41.4 mcg/l, p+0.0001), 48h AUC cTnI (82.0+/-110.7 vs 268.8+/-497.7 mcg/l, p+0.0001) and total AUC cTnI (623.8+/-1216.7 vs 2564+/-2826.0, p+0.0001). Analyses for duration of mechanical ventilation and duration of ICU stay by linear regression demonstrated a better correlation for 48h AUC cTnI (ventilation time r+0.82, p+0.0001 and ICU stay r+0.74, p+0.0001) then total AUC cTnI (ventilation time r+0.65, p+0.0001 and ICU stay r+0.60, p+0.0001) and max cTnI (ventilation time r+0.64, p+0.0001 and ICU stay r+0.60, p+0.0001). Conclusion: Cardiac Troponin I is a specific and sensitive marker of myocardial injury after congenital heart surgery and it may predict early in-hospital outcomes. Integration of post operative value of cTnI by calculation of AUC improves prediction of early in-hospital outcomes. It probably takes into account, not only the initial surgical procedure, but probably also incorporates the occurrence of hypoxic-ischemic phenomena in the post-operative period.

Signifiant decrease in in-hospital mortality and major adverse cardiac events in Swiss STEMI patients between 2000 and December 2007

Rapport de synthèse : Objectifs : évaluer la survie intra-hospitalière des patients présentant un infarctus du myocarde avec sus-décalage du segment ST admis dans les hôpitaux suisses entre 2000 et 2007, et identifier les paramètres prédictifs de mortalité intra-hospitalière et d'événements cardio-vasculaires majeurs (infarctus, réinfarctus, attaque cérébrale). Méthode : utilisation des données du registre national suisse AMIS Plus (Acute Myocardial lnfarction and Unstable Angina in Switzerland). Tous les patients admis pour un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau dans un hôpital suisse participant au registre entre janvier 2000 et décembre 2007 ont été inclus. Résultats: nous avons étudié 12 026 patients présentant un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau admis dans 54 hôpitaux suisses différents. L'âge moyen est de 64+-13 ans et 73% des patients inclus sont des hommes. L'incidence de mortalité intra-hospitalière est de 7.6% en 2000 et de 6% en 2007. Le taux de réinfarctus diminue de 3.7% en 2000 à 0.9% en 2007. L'utilisation de médicaments thrombolytiques chute de 40.2% à 2% entre 2000 et 2007. Les paramètres prédictifs cliniques de mortalité sont : un âge> 65-ans, une classe Killips Ill ou IV, un diabète et un infarctus du myocarde avec onde Q (au moment de la présentation). Les patients traités par revascularisation coronarienne percutanée ont un taux inférieur de mortalité et de réinfarctus (3.9% versus 11.2% et 1.1% versus 3.1%, respectivement, p<0.001) sur la période de temps étudiée. Le nombre de patients traités par revascularisation coronarienne percutanée augmente de 43% en 2000 à 85% en 2007. Les patients admis dans les hôpitaux bénéficiant d'une salle de cathétérisme cardiaque ont un taux de mortalité plus bas que les patients hopitalisés dans les centres sans salle de cathétérisme cardiaque. Mais les caractéristiques démographiques de ces deux populations sont très différentes. La mortalité intra-hospitalière ainsi que le taux de réinfarctus diminuent significativement au cours y de la période étudiée, parallèlement à l'augmentation de |'utilisation de la revascularisation coronarienne percutanée. La revascularisation coronarienne percutanée est le paramètre prédictif de survie le plus important. Conclusion: la mortalité intra-hospitalière et le taux de réinfarctus du myocarde ont diminué de manière significative chez les patients souffrant d'un infarctus du myocarde avec sus-décalage du segment ST au cours de ces sept dernières années, parallèlement à l'augmentation significative de la revascularisation coronarienne percutanée en plus de la thérapie médicamenteuse. La survie n'est È pas liée au lieu d'hospitalisation mais à l'accès à une revascularisation coronarienne percutanée.

Do socioeconomic factors shape weight and obesity trajectories over the transition from midlife to old age? Results from the French GAZEL cohort study

BACKGROUND: Obesity is a contemporary epidemic that does not affect all age groups and sections of society equally. OBJECTIVE: The objective was to examine socioeconomic differences in trajectories of body mass index (BMI; in kg/m(2)) and obesity between the ages of 45 and 65 y. DESIGN: A total of 13,297 men and 4532 women from the French GAZEL (Gaz de France Electricité de France) cohort study reported their height in 1990 and their weight annually over the subsequent 18 y. Changes in BMI and obesity between ages 45 and 49 y, 50 and 54 y, 55 and 59 y, and 60 and 65 y as a function of education and occupational position (at age 35 y) were modeled by using linear mixed models and generalized estimating equations. RESULTS: BMI and obesity rates increased between the ages of 45 and 65 y. In men, BMI was higher in unskilled workers than in managers at age 45 y; this difference in BMI increased from 0.82 (95% CI: 0.66, 0.99) at 45 y to 1.06 (95% CI: 0.85, 1.27) at 65 y. Men with a primary school education compared with those with a high school degree at age 45 y had a 0.75 (95% CI: 0.51, 1.00) higher BMI, and this difference increased to 1.32 (95% CI: 1.03,1.62) at age 65 y. Obesity rates were 3.35% and 7.68% at age 45 y and 9.52% and 18.10% at age 65 y in managers and unskilled workers, respectively; the difference in obesity increased by 4.25% (95% CI: 1.87, 6.52). A similar trend was observed in women. Conclusions: Weight continues to increase in the transition between midlife and old age; this increase is greater in lower socioeconomic groups.

Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.