Oxygen uptake during early cardiogenesis of the chick.

Oxidative metabolism of the isolated embryonic heart of the chick has been determined using a spectrophotometric technique allowing global as well as localized micromeasurements of the O2 uptake. Entire hearts, excised from embryos of 10 somites (primordia fused, stage 10 HH) and 40 somites (S shaped, stage 20 HH) were placed in a special chamber under controlled metabolic conditions where they continued to beat spontaneously and regularly. During the 32 h of development, the O2 consumption of the whole heart increased from 0.9 +/- 0.1 to 5.3 +/- 0.8 nmol O2/h. These values corrected for protein content were, however, comparable (0.45 nmol O2.h-1.micrograms-1). At stage 10-12, the O2 uptake varied along the cardiac tube (from 0.74 to 1.0 nmol O2.h-1.mm-2). From stage 10 to 20, the O2 uptake per unit area of ventricle wall increased from 0.7 +/- 0.2 to 1.8 +/- 0.2 nmol O2.h-1.mm-2, and the O2 uptake per myocardial volume during one cardiac cycle varied from 7 to 2.5 nmol O2/cm3. These results indicate that, despite an intense morphogenesis, the cardiac tissue has a rather low and stable oxidative metabolism, although the O2 requirement of the whole heart increases significantly. Moreover, the normalized suprabasal aerobic energy expenditure decreases throughout early cardiogenesis. The functional integrity of the isolated embryonic heart combined with the experimental possibilities of the microtechnique make the preparation appropriate for studying the changes in cardiac metabolism during development.

Effects of dinner composition on postprandial macronutrient oxidation in prepubertal girls.

OBJECTIVE: To see whether a fat-rich (50%) evening meal promoted fat oxidation and a different spontaneous food intake on the following day at breakfast than a meal with a lower fat content (20%) in 10 prepubertal obese girls. RESEARCH METHODS AND PROCEDURES: The postabsorptive and postprandial (10.5 hours) energy expenditure after a low-fat (LF) (20% fat, 68% carbohydrate, 12% protein) and an isocaloric (2.1 MJ) and isoproteic high-fat (HF; 50% fat, 38% carbohydrate, 12% protein) meal were measured by indirect calorimetry. RESULTS: Fat oxidation was not significantly different after the two meals [LF, 31 +/- 9 vs. HF, 35 +/- 9 g/10.5 hours, p = not significant (NS)]. The girls oxidized 1.8 +/- 0.9 times more fat than that ingested (11.1 grams) with the LF meal vs. 0.3 +/- 0.3 times more fat than that ingested (27.1 grams) with the HF meal (p < 0.001). Carbohydrate oxidation was significantly higher after an LF than an HF meal (39 +/- 12 vs. 29 +/- 9 g/10.5 hours, p < 0,05). At breakfast, the girls spontaneously ingested a similar amount of energy (1.5 +/- 0.7 vs. 1.5 +/- 0.6 MJ, p = NS) and macronutrient proportions (fat, 23% vs. 26%, p = NS; protein, 9% vs. 10%; carbohydrate, 68% vs. 64%,) independently of their having eaten an HF or an LF dinner. DISCUSSION: An HF dinner did not stimulate fat oxidation, and no compensatory effect in spontaneous food intake was observed during breakfast the following morning. Cumulated total fat oxidation after dinner was higher than total fat ingested at dinner, but a much larger negative fat balance was observed after the LF meal. Spontaneous energy and nutrient intakes at breakfast were similar after LF and HF isocaloric, isoproteic dinners. This study points out the lack of sensitivity of short-term fat balance to subsequently readjust fat intake and emphasizes the importance of an LF meal to avoid transient positive fat imbalance.

Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial.

BACKGROUND: In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS: Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS: Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION: HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER: 2004-002245-12 and NCT00110123.

Effects of added dead space on sleep disordered breathing at high altitude

Introduction: Sleep disordered breathing with central apnea or hypopnea frequently occurs during sleep at high altitude. The aim of this study was to assess the effects of added dead space (DS) on sleep disordered breathing and transcutaneous CO2 (PtcCO2) level during sleep at high altitude. Methods: Full night sleep recordings were obtained on 12 unacclimatized mountaineers (11 males, 1 female, mean age 39 ± 12 y.o.) during one of the first 4 nights after arrival in Leh, Ladakh (3500 m). In random order, half of the night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other half without it. PtcCO2 was measured in 3 participants. Results: Baseline recordings reveled two clearly distinct groups: one with severe sleep disordered breathing (n = 5) and the other with mild or no disordered breathing (n = 7). Added dead space markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3 ± 25.8 vs 29.4 ± 6.9 (p = 0.013), oxygen desaturation index (ODI): 72.9 ± 24.1/h vs 42.5 ± 14.4 (p = 0.031), whereas it had no significant effect in the second group. Added dead space did not have a significant effect on mean oxygen saturation level. Respiratory events were almost exclusively central apnea or hypopnea except for one subject. Only a minor increase in mean PtcCO2 (n = 3) was observed: 33.6 ± 1.8 mm Hg at baseline and 35.0 ± 2.62 mm Hg with DS. Sleep quality was preserved under dead space condition, since the microarousal rate remained unchanged (16.8 ± 8.7/h vs 19.4 ± 18.6/h (p = 0.51). Conclusion: In mountaineers with severe sleep disordered breathing at high altitude, a 500 ml increase in dead space through a fitted mask significantly improves nocturnal breathing.

PHA urges 'freshers' to be smart and know their alcohol limits

As 'fresher's week' commences, the Public Health Agency is encouraging students across Northern Ireland to avoid binge drinking and to know their limits if they do choose to drink alcohol.Enjoying new freedoms, at college or university, means taking care of yourself and others and, if you choose to drink, staying within safe alcohol limits. Owen O'Neill, PHA Health and Social Wellbeing Improvement Manager for drugs and alcohol, said: "Some young people may drink more when they leave home, or join their friends in college or university for the first time. They might think that, as young people, they don't have to take care with alcohol, but staying within the safe drinking limits is important for everyone who drinks. Excessive and binge drinking can have lasting effects on health, such as damage to the liver, heart, brain and stomach. Drinking too much can also increase the risk of accidents and antisocial behaviour as well as sexually transmitted infections and unplanned pregnancy"."We would also strongly advise against drinking games. Although they are regarded as a 'bit of fun', in reality they can be very dangerous. As an extreme form of binge drinking, where large quantities of alcohol are consumed in a very short time, drinking games can result in alcohol poisoning, leading to brain damage, coma or death. The PHA encourages students to enjoy their new student life, but urges them to be aware of their alcohol intake and drink responsibly, especially throughout fresher's week, with the many cheap drink promotions currently available."Daily alcohol limits are recommended by the government in order to avoid the risks of excessive and binge drinking in any one session. These are:Men: No more than 3 to 4 units of alcohol a day and no more than 21 units over the course of the week.Women: No more than 2 to 3 units of alcohol a day and no more than 14 units over the course of the week.Examples of units:Can of extra strong lager - 4 unitsBottle of lager - 1.5 unitsPint of standard lager - 2.5 unitsPint of premium larger - 3 unitsSmall pub bottle of wine - 2.25 units70cl bottle of wine - 7 to 10 unitsStandard 275ml of alcopops - 1.5 to 1.8 units70cl bottle of alcopops - 3.75 to 4.5 unitsPub measure of spirits - 1.5 unitsPint of cider - 3 unitsPint of stout - 2.5 unitsIf you do choose to drink alcohol:DON'T:Ever drink and driveDrink on an empty stomachMix alcohol with other drugsDrink in rounds as this may speed up your drinkingLeave your drinks unattendedDO:Take sips rather than gulpsAlternate each alcoholic drink with a non alcoholic drink e.g. water or a soft drinkSet yourself a limit and try to stick to it (refer to daily alcohol limits) Take frequent breaks from drinking to give your body time to recoverTell friends and family where you are going and who you will be withRemember, that for each unit you drink over the daily limit, the risk to your health increases. It's important to spread the units throughout the week - you can't 'save up' your units for the weekend or your holiday. It is also important to drink plenty of water, ideally matching the amount of alcohol you have consumed.So students make smart choices this term - drink sensibly and know your limits!For further information on sensible drinking and alcohol units visit the Public Health Agency's website www.knowyourlimits.info

Assessing the Relationship between the Baseline Value of a Continuous Variable and Subsequent Change over Time

Analyzing the relationship between the baseline value and subsequent change of a continuous variable is a frequent matter of inquiry in cohort studies. These analyses are surprisingly complex, particularly if only two waves of data are available. It is unclear for non-biostatisticians where the complexity of this analysis lies and which statistical method is adequate.With the help of simulated longitudinal data of body mass index in children,we review statistical methods for the analysis of the association between the baseline value and subsequent change, assuming linear growth with time. Key issues in such analyses are mathematical coupling, measurement error, variability of change between individuals, and regression to the mean. Ideally, it is better to rely on multiple repeated measurements at different times and a linear random effects model is a standard approach if more than two waves of data are available. If only two waves of data are available, our simulations show that Blomqvist's method - which consists in adjusting for measurement error variance the estimated regression coefficient of observed change on baseline value - provides accurate estimates. The adequacy of the methods to assess the relationship between the baseline value and subsequent change depends on the number of data waves, the availability of information on measurement error, and the variability of change between individuals.

Arrested kinetic Li isotope fractionation at the margin of the llimaussaq complex, South Greenland: Evidence for open-system processes during final cooling of peralkaline igneous rocks

Li contents [Li] and isotopic composition (delta Li-7) of mafic minerals (mainly amphibole and clinopyroxene) from the alkaline to peralkaline Ilimaussaq plutonic complex, South Greenland, track the behavior of Li and its isotopes during magmatic differentiation and final cooling of an alkaline igneous system. [Li] in amphibole increase from < 10 ppm in Caamphiboles of the least differentiated unit to >3000 ppm in Na-amphiboles of the highly evolved units. In contrast, [Li] in clinopyroxene are comparatively low (<85 ppm) and do not vary systematically with differentiation. The distribution of Li between amphibole and pyroxene is controlled by the major element composition of the minerals (Ca-rich and Na-rich, respectively) and changes in oxygen fugacity (due to Li incorporation via coupled substitution with ferric iron) during magmatic differentiation. delta(7) Li values of all minerals span a wide range from + 17 to - 8 parts per thousand, with the different intrusive units of the complex having distinct Li isotopic systematics. Amphiboles, which dominate the Li budget of whole-rocks from the inner part of the complex, have constant delta Li-7 of + 1.8 +/- 2.2 parts per thousand (2 sigma, n = 15). This value reflects a homogeneous melt reservoir and is consistent with their mantle derivation, in agreement with published O and Nd isotopic data. Clinopyroxenes of these samples are consistently lighter, with Delta Li-7(amph-cpx). as large as 8 parts per thousand and are thus not in Li isotope equilibrium. These low values probably reflect late-stage diffusion of Li into clinopyroxene during final cooling of the rocks, thus enriching the clinopyroxene in 6 Li. At the margin of the complex delta(7) Li in the syenites increases systematically, from +2 to high values of + 14 parts per thousand. This, coupled with the observed Li isotope systematics of the granitic country rocks, reflects post-magmatic open-system processes occurring during final cooling of the intrusion. Although the shape and magnitude of the Li isotope and elemental profiles through syenite and country rock are suggestive of diffusion-driven isotope fractionation, they cannot be modeled by one-dimensional diffusive transport and point to circulation of a fluid having a high 67 Li value (possibly seawater) along the chilled contact. In all, this study demonstrates that Li isotopes can be used to identify complex fluid- and diffusion-governed processes taking place during the final cooling of such rocks. (c) 2007 Elsevier B.V All rights reserved.

Health at a glance: Europe 2012.

This second edition of Health at a Glance: Europe presents a set of key indicators of health and health systems in 35 European countries, including the 27 European Union member states, 5 candidate countries and 3 EFTA countries. The selection of indicators is based largely on the European Community Health Indicators (ECHI) shortlist, a list of indicators that has been developed by the European Commission to guide the development and reporting of health statistics. It is complemented by additional indicators on health expenditure and quality of care, building on the OECD expertise in these areas. Contents: Introduction 12 Chapter 1. Health status 15 1.1. Life expectancy and healthy life expectancy at birth 1.2. Life expectancy and healthy life expectancy at age 65 1.3. Mortality from all causes 1.4. Mortality from heart disease and stroke 1.5. Mortality from cancer 1.6. Mortality from transport accidents 1.7. Suicide 1.8. Infant mortality 1.9. Infant health: Low birth weight 1.10. Self-reported health and disability 1.11. Incidence of selected communicable diseases 1.12. HIV/AIDS 1.13. Cancer incidence 1.14. Diabetes prevalence and incidence 1.15. Dementia prevalence 1.16. Asthma and COPD prevalence Chapter 2. Determinants of health 49 2.1. Smoking and alcohol consumption among children 2.2. Overweight and obesity among children 2.3. Fruit and vegetable consumption among children 2.4. Physical activity among children 2.5. Smoking among adults 2.6. Alcohol consumption among adults 2.7. Overweight and obesity among adults 2.8. Fruit and vegetable consumption among adults Chapter 3. Health care resources and activities 67 3.1. Medical doctors 3.2. Consultations with doctors 3.3. Nurses 3.4. Medical technologies: CT scanners and MRI units 3.5. Hospital beds 3.6. Hospital discharges 3.7. Average length of stay in hospitals 3.8. Cardiac procedures (coronary angioplasty) 3.9. Cataract surgeries 3.10. Hip and knee replacement 3.11. Pharmaceutical consumption 3.12. Unmet health care needs Chapter 4. Quality of care 93 Care for chronic conditions 4.1. Avoidable admissions: Respiratory diseases 4.2. Avoidable admissions: Uncontrolled diabetes Acute care 4.3. In-hospital mortality following acute myocardial infarction 4.4. In-hospital mortality following stroke Patient safety 4.5. Procedural or postoperative complications 4.6. Obstetric trauma Cancer care 4.7. Screening, survival and mortality for cervical cancer 4.8. Screening, survival and mortality for breast cancer 4.9. Screening, survival and mortality for colorectal cancer Care for communicable diseases 4.10. Childhood vaccination programmes 4.11. Influenza vaccination for older people Chapter 5. Health expenditure and financing 117 5.1. Coverage for health care 5.2. Health expenditure per capita 5.3. Health expenditure in relation to GDP 5.4. Health expenditure by function. 5.5. Pharmaceutical expenditure 5.6. Financing of health care 5.7. Trade in health services Bibliography 133 Annex A. Additional information on demographic and economic context 143 Most European countries have reduced tobacco consumption via public awareness campaigns, advertising bans and increased taxation. The percentage of adults who smoke daily is below 15% in Sweden and Iceland, from over 30% in 1980. At the other end of the scale, over 30% of adults in Greece smoke daily. Smoking rates continue to be high in Bulgaria, Ireland and Latvia (Figure 2.5.1). Alcohol consumption has also fallen in many European countries. Curbs on advertising, sales restrictions and taxation have all proven to be effective measures. Traditional wine-producing countries, such as France, Italy and Spain, have seen consumption per capita fall substantially since 1980. Alcohol consumption per adult rose significantly in a number of countries, including Cyprus, Finland and Ireland (Figure 2.6.1).This resource was contributed by The National Documentation Centre on Drug Use.

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10  mg kg(-1) dose of each fungicide was applied on 80  cm(2) of the forearm and left without occlusion or washing for 24  h. Blood samples were withdrawn at fixed time periods over the 72  h following application and complete urine voids were collected over 96  h post-dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24  h for THPI and 10  h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t(½) of 28.8 and 29.6  h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t(½) of 18.7  h. Over the 96  h period post-application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet.

Lymphocyte subset analyses in healthy adults vaccinated with yellow fever 17DD virus

In this study the kinetics of humoral and cellular immune responses in first-time vaccinees and re-vaccinees with the yellow fever 17DD vaccine virus was analyzed. Flow cytometric analyses were used to determine percentual values of T and B cells in parallel to the yellow fever neutralizing antibody production. All lymphocyte subsets analyzed were augmented around the 30th post vaccination day, both for first-time vaccinees and re-vaccinees. CD3+ T cells increased from 30.8% (SE ± 4%) to 61.15% (SE ± 4.2%), CD4+ T cells from 22.4% (SE ± 3.6%) to 39.17% (SE ± 2%) with 43% of these cells corresponding to CD4+CD45RO+ T cells, CD8+ T cells from 15.2% (SE ± 2.9%) to 27% (SE ± 3%) with 70% corresponding to CD8+CD45RO+ T cells in first-time vaccinees. In re-vaccinees, the CD3+ T cells increased from 50.7% (SE ± 3%) to 80% (SE ± 2.3%), CD4+ T cells from 24.9% (SE ± 1.4%) to 40% (SE ± 3%) presenting a percentage of 95% CD4+CD45RO+ T cells, CD8+ T cells from 19.7% (SE ± 1.8%) to 25% (SE ± 2%). Among CD8+CD38+ T cells there could be observed an increase from 15 to 41.6% in first-time vaccinees and 20.7 to 62.6% in re-vaccinees. Regarding neutralizing antibodies, the re-vaccinees presented high titers even before re-vaccination. The levels of neutralizing antibodies of first-time vaccinees were similar to those presented by re-vaccinees at day 30 after vaccination, indicating the success of primary vaccination. Our data provide a basis for further studies on immunological behavior of the YF 17DD vaccine.