[Maternal mortality due to cardiovascular disease in France 2013-2015]. / Mortalité maternelle par maladies cardiovasculaires en France 2013­2015.

Between 2013 and 2015, cardiovascular diseases became one of the two leading causes of maternal mortality, with 36 deaths (13.7% of maternal deaths). The overall maternal mortality ratio for cardiovascular diseases is 1.5 per 100,000 live births, stable compared to the 2010-2012 period. The etiologies in order of decreasing frequency are: pre-existing cardiomyopathies (n=10), aortic dissections (n=9), peripartum cardiomyopathies (n=6), myocardial infarction (n=4), valvular cardiopathies (n=4). Non-optimal care occurred in 72% of cases, increasing since the previous triennium (50%). Similarly, there is a significant increase in the proportion of preventable deaths (possibly or probably) from 35% to 66%. In women with known cardiovascular disease, the lack of multidisciplinary prepregnancy assessment and pregnancy follow-up is most frequent. In patients with unknown cardiovascular disease, the lack of diagnosis of a cardiac event is the most common failure. Cardiovascular conditions or cardiovascular risk factors should be investigated in early pregnancy in order to monitor and refer women to appropriate maternity hospitals. Recent dyspnea, worsening at the end of pregnancy and postpartum, should suggest a cardiac complication. In presence of chest pain, aortic dissection should be considered with the same degree of emergency as myocardial infarction or pulmonary embolism. Cardiac ultrasonography, chest CT, Nt-proBNP and troponin should be considered in case of chest pain or recent dyspnea. Women with cardiac symptoms should be referred to an emergency department (not necessarily to the local maternity) for a complete cardiovascular check-up.

[Maternal deaths due to sudden death. Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Mortalité maternelle par mort subite. Résultats de l'enquête nationale française confidentielle sur la mortalité maternelle, 2010­2012.

Sudden death is defined as unexpected cardiac arrest occurring less than one hour after the onset of the first symptoms. Between 2010 and 2012, 23 maternal deaths were considered as unexplained sudden deaths and three of them were not evaluated due to a lack of clinical data. In addition, 13 maternal deaths with an identified cause occurred in a clinical context of sudden death (7 cases of pulmonary embolism, 2 cases of epilepsy, and 2 cases of cardiomyopathy). The first maneuvers of resuscitation in the presence of bystanders were attempted in 8 of 22 cases (36%). This emphasizes the importance of teaching the non-medical resuscitation modalities of cardiac arrest in pregnant women. Pregnant women must receive accurate resuscitation as the whole population. An autopsy was performed in 10 of 33 cases (30%) and was considered incomplete in 3 patients. This result emphasizes the necessity to perform a systematic and specialized autopsy in the context of sudden maternal death, which is mostly unexplained.

Cerebral oxygenation during changes in vascular resistance and flow in patients on cardiopulmonary bypass - a physiological proof of concept study.

Despite a rise in blood pressure, cerebral oxygenation decreases following phenylephrine administration, and we hypothesised that phenylephrine reduces cerebral oxygenation by activating cerebral α1 receptors. We studied patients on cardiopulmonary bypass during constant flow. Phenylephrine raised mean arterial pressure (α1 -mediated) from mean (SD) 69 (8) mmHg to 79 (8) mmHg; p = 0.001, and vasopressin raised mean arterial pressure (V1 mediated) from 69 (8) mmHg to 83 (6) mmHg; p = 0.001. Both drugs elicited a comparable decrease in cerebral oxygenation from 61 (7)% to 60 (7)%; p = 0.023 and 61 (8)% to 59 (8)%; p = 0.022, respectively. This implies that after phenylephrine or vasopressin administration, cerebral oxygenation declines as a result of cerebral vasoconstriction, due to either both cerebral α1 and V1 receptors being equipotentially activated or to an intrinsic myogenic mechanism of cerebral vasculature in reaction to blood pressure elevation.

Effect of adipose tissue volume loss on circulating 25-hydroxyvitamin D levels: results from a 1-year lifestyle intervention in viscerally obese men.

BACKGROUND/OBJECTIVES: Although weight loss has been associated with changes in circulating 25-hydroxyvitamin D (25(OH)D) levels, the quantification of the increase in 25(OH)D levels as a function of adipose tissue volume loss precisely assessed by imaging has not been reported before. The objective of this substudy was to describe the effects of a 1-year lifestyle intervention on plasma 25(OH)D levels. The relationships between changes in 25(OH)D levels and changes in adiposity volume (total and by adipose tissue compartment) were studied. SUBJECTS/METHODS: This intervention study was performed between 2004 and 2006 and participants were recruited from the general community. Sedentary, abdominally obese and dyslipidemic men (n=103) were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500-kcal daily energy deficit and to increase physical activity/exercise habits. Body weight, body composition and fat distribution were assessed by dual-energy X-ray absorptiometry and computed tomography, whereas the 25(OH)D levels were measured with an automated assay. RESULTS: The 1-year intervention resulted in a 26% increase in circulating 25(OH)D (from 48±2 nmol l(-1) or 19±0.8 ng ml(-1) (±s.e.m.) to 58±2 nmol l(-1) or 23±0.8 ng ml(-1), P<0.0001) along with a 26% decrease in visceral adiposity volume (from 1947±458 to 1459±532 cm3). One-year increases in 25(OH)D levels correlated inversely with changes in all adiposity indices, especially Δvisceral (r=-0.36, P<0.0005) and Δtotal abdominal (r=-0.37, P<0.0005) adipose tissue volumes. CONCLUSIONS: These results indicate that there is a linear increase in circulating 25(OH)D levels as a function of adiposity volume loss, and therefore suggest a role of adiposity reduction in the management of obesity-associated vitamin D insufficiency.

Brain hemodynamic response to somatosensory stimulation in Neuroligin-1 knockout mice.

Neuroligin 1 (NLGN1) is a postsynaptic adhesion molecule that determines N-methyl-d-aspartate receptor (NMDAR) function and cellular localization. Our recent work showed that Nlgn1 knockout (KO) mice cannot sustain neuronal activity occurring during wakefulness for a prolonged period of time. Since NMDAR-dependent neuronal activity drives an important vascular response, we used multispectral optical imaging to determine if the hemodynamic response to neuronal stimulation is modified in Nlgn1 KO mice. We observed that Nlgn1 KO mice show a 10% lower response rate to forepaw electrical stimulation compared to wild-type (WT) and heterozygote (HET) littermates on both the contra- and ipsilateral sides of the somatosensory cortex. Moreover, Nlgn1 mutant mice showed an earlier oxyhemoglobin peak response that tended to return to baseline faster than in WT mice. Analysis of the time course of the hemodynamic response also showed that HET mice express a faster dynamics of cerebrovascular response in comparison to WT. Taken together, these data are indicative of an altered immediate response of the brain to peripheral stimulation in Nlgn1 KO mice, and suggest a role for NLGN1 in the regulation of cerebrovascular responses.

The effects of surfing behaviour on the development of external auditory canal exostosis.

To examine how individual surfing behaviour affects the development of external auditory canal exostosis and to produce a model to predict exostosis severity. A standardised questionnaire was completed and each participant underwent an otoscopic examination. Surfers were recruited from August to October 2011 from surfing competitions and from colleges in the South West of England. 207 surfers were included, 53 % had evidence of external auditory canal; exostosis: grade 1, 23%; grade 2, 16%, grade 3, 16%. This risk of exostosis significantly increased with (1) surfing for 6 or more years, (2) surfing in the winter months, (3) surfing five or more times per month in the winter and (4) reported ear symptoms. Interestingly, participation in other water sports and wearing earplugs or a hood reduced the risk of developing exostosis. Surfers who surf in England are at significant risk of exostosis. A probability model was designed, incorporating different surfing behaviours and ear symptoms, the first of its kind in exostosis research. This model will be a useful tool for raising awareness of external ear canal exostosis in the surfing community and in assessing individual need for surgical intervention.

Neurovascular deconvolution of optical signals as a proxy for the true neuronal inputs.

UNLABELLED: Since the Kalman filter and Monte Carlo techniques, much theoretical work has been put into the development of signal deconvolution tools. Among recent developments taking place in neuroscience are Dynamic Expectation Maximization, Generalized Filtering and the Cubature Kalman Filter. While there are exciting prospects to use these tools for Dynamic Causal Modeling and other analyses of networks, there has been comparatively little work to validate the algorithms on controlled experimental data. In this work, the latest evolution of these tools, the square-root cubature Kalman smoother (SCKS), is tested for its effectiveness on multimodal neurovascular data. Multispectral intrinsic optical imaging and electrophysiological measurements of Wistar rats are used in combination with somatosensory stimulation. The Buxton-Friston (B-F) balloon model is then deconvolved with the SCKS algorithm to obtain the estimated neuronal inputs u(t) from the hemodynamic measurements (flow, oxy- and deoxygenated hemoglobin). RESULTS: The estimated neuronal inputs are compared to the stimulation protocol and a sensitivity and specificity analysis is carried out. SCKS succeeds in recovering most of the stimulations. Next, the estimated inputs are compared to actual measures of neuronal activity: local field potentials (LFPs) and multiunit activity (MUA). Good sensitivity of the technique is obtained with both LFPs and MUA over the whole recordings, with the area of the ROC curves favoring LFPs. A weak correlation between SCKS estimated inputs and LFPs is found outside stimulation periods, significant at one standard deviation. Finally, the accuracy of state reconstructions is studied and SCKS reconstructed states are highly concordant with measured states.

Plasticity of rat motoneuron rhythmic firing properties with varying levels of afferent and descending inputs.

Hindlimb motoneuron excitability was compared among exercise-trained (E), sedentary (S), and spinal cord transected (T) Sprague-Dawley rats by examining the slope of the frequency-current (F/I) relationship with standard intracellular recording techniques in rats anesthetized with ketamine-xylazine. The T group included spinal transected and spinal isolated rats; the E animals were either spontaneously active (exercise wheel) or treadmill trained; and rats in the S group were housed in pairs. An analysis of motoneuron initial [1st interspike interval (ISI)], early (mean of 1st three ISIs), and steady-state (mean of last 3 ISIs) discharge rate slopes resulting from increasing and decreasing 500-ms injected square-wave depolarizing current pulses was used to describe rhythmic motoneuron properties. The steepest slope occurred in the S group (55.3 ± 22.2 Hz/nA), followed by the T group (35.5 ± 15.3 Hz/nA), while the flattest slope was found in the E group (25.4 ± 10.9 Hz/nA). The steepest steady-state slope occurred in the S group but was found to be similar between the T and E groups. Furthermore, a spike-frequency adaptation (SFA) index revealed a slower adaptation in motoneurons of the E animals only (∼40% lower). Finally, evidence for a secondary range of firing existed more frequently in the T group (41%) compared with the S (12%) and E (31%) groups. The lower F/I slope and lower SFA index of motoneurons for E rats may be a result of an increase in Na(+) conductance at the initial segment. The results show that motoneuronal rhythmic firing behavior is plastic, depending on the volume of daily activation and on intact descending pathways.

Right ventricular function declines after cardiac surgery in adult patients with congenital heart disease.

Right ventricular function (RVF) is often selectively declined after coronary artery bypass graft surgery. In adult patients with congenital heart disease (CHD) the incidence and persistence of declined RVF after cardiac surgery is unknown. The current study aimed to describe RVF after cardiac surgery in these patients. Adult CHD patients operated between January 2008 and December 2009 in the Academic Medical Centre in Amsterdam were studied. Clinical characteristics, laboratory tests, surgical data and intensive care unit outcome were obtained from medical records. RVF was measured by trans-thoracic echocardiography (TTE) and expressed by tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (RV S') and myocardial performance index (MPI) pre-operatively and direct, at intermediate and late follow up. Of a total of 185 operated, 86 patients (mean age 39 ± 13 years, 54% male) had echo data available. There was a significant fall in RVF after cardiac surgery. TAPSE and RV S' were significantly higher and MPI was significantly lower pre-operatively compared to direct post-operative values (TAPSE 22 ± 5 versus 13 ± 3 mm (P < 0.01), RV S' 11 ± 4 versus 8 ± 2 cm/s (P < 0.01) and MPI 0.36 ± 0.14 vs 0.62 ± 0.25; P < 0.01). There were no significant differences in left ventricular function pre-operatively compared to post-operative values. Right-sided surgery was performed in 33, left-sided surgery in 37 and both sided surgery in 16 patients. Decline in RVF was equal for those groups. Patients with severe decline in RVF, were patients who underwent tricuspid valve surgery. Decline in RVF was associated with post-operative myocardial creatine kinase level and maximal troponin T level. There was no association between decline in RVF and clinical outcome on the intensive care unit. 18 months post-operatively, most RVF parameters had recovered to pre-operative values, but TAPSE which remained still lower (P < 0.01). CHD patients have a decline in RVF directly after cardiac surgery, regardless the side of surgery. Although a gradual improvement was observed, complete recovery was not seen 18 months post-operatively.

Biophysical model estimation of neurovascular parameters in a rat model of healthy aging.

Neuronal, vascular and metabolic factors result in a deterioration of the cerebral hemodynamic response with age. The interpretation of neuroimaging studies in the context of aging is rendered difficult due to the challenge in untangling the composite effect of these modifications. In this work we integrate multimodal optical imaging in biophysical models to investigate vascular and metabolic changes occurring in aging. Multispectral intrinsic optical imaging of an animal model of healthy aging, the LOU/c rat, is used in combination with somatosensory stimulation to study the modifications of the hemodynamic response with increasing age. Results are fitted with three macroscopic biophysical models to extract parameters, providing a phenomenological description of vascular and metabolic changes. Our results show that 1) biophysical parameters are estimable from multimodal data and 2) parameter estimates in this population change with aging.

Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury.

Traumatic human spinal cord injury (SCI) causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after spinal cord injury are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus (VLF) express 3'-5'-cyclic adenosine monophosphate-dependent phosphodiesterase 4 (PDE4) subtypes and that their death was attenuated up to 3 days after contusive cervical SCI when rolipram, a specific inhibitor of PDE4, was administered. Here, we report that (1) there are more oligodendrocyte somata in the adult rat epicenter VLF, (2) descending and ascending axonal conductivity in the VLF improves, and that (3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical SCI when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a SCI with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with SCI.

[Complications of an unrecognized myocardial infarction]. / Complicaties van een niet herkend hartinfarct.

Patients with an untreated myocardial infarction may present with serious late complications. 3 patients are described. A 63-year-old woman became progressively more short of breath 4 days after an acute episode of chest pain accompanied by nausea and sweating. It proved to be a cardiogenic shock following a rupture of a papillary muscle. A man aged 65 collapsed 5 days after an episode of back pain and nausea. This was a cardiac tamponade due to rupture of the left ventricle. A woman aged 74 had transient aphasia and during investigations for this was seen to have anomalies on ECG. She had cerebral emboli and a cardiac aneurysm with associated thrombus. All 3 patients recovered following mitral-valve replacement, repair of the rupture and medicinal treatment for the clot, respectively. Around one-third of patients who have a myocardial infarction do not have chest pain but experience shortness of breath, autonomic nervous symptoms (sweating, nausea, vomiting), extreme and inexplicable tiredness and fainting. These atypical symptoms should suggest myocardial infarction. In order to avoid high morbidity and death from complications such as arrhythmias, heart failure, rupture and aneurysm formation it is important that a patient who has had a myocardial infarction should be treated as soon as possible, preferably by reperfusion therapy.

Evaluation of the quality of care for severe obstetrical haemorrhage in three French regions.

OBJECTIVE: To determine what factors related to health services in France might explain substandard care of severe morbidity due to obstetric haemorrhage. DESIGN: Retrospective questionnaire survey. SETTING: Three administrative regions of France. POPULATION: All women who were pregnant or had recently given birth during the year before the survey. METHODS: A European survey (MOMS-B) defined severe haemorrhages as blood loss > or = 1500mL. A specific questionnaire was added in France to analyse the quality of care of these haemorrhages. The survey was carried out in three different administrative regions: Champagne-Ardenne, the Centre and Lorraine. An expert committee was appointed and began by establishing a framework for qualitative assessment. One hundred and sixty-five cases of severe haemorrhage were reviewed and classified into one of three levels of care: appropriate, inadequate or mixed. Inadequate care and 'mixed' care were both considered substandard. The 165 cases were coded and then studied with uni- and multivariate analysis (logistic regression with SAS and SPSS software). RESULTS: Of the 165 cases identified, 51% (85/165) were vaginal, 19% (31/165) operative vaginal, and 30% (49/165) caesarean. The leading cause of haemorrhage was uterine atony. Overall, 62% of the cases received appropriate care, 24% received totally inadequate care and 14% mixed care. After adjustment for sociodemographic factors, antenatal care and organisational aspects, the lack of a 24-hour on-site anaesthetist at the hospital and a low volume of deliveries (<500 births per year) were the factors associated with substandard care. CONCLUSION: Organisational features are so important that application of good clinical practices for safer motherhood reinforce the need for new organisation of obstetric services. For the first time, the presence of an anaesthetist is shown to have a measurable effect on the quality of care for women giving birth. These results need to be confirmed by others.

Teaching colleagues and the general public about automatic external defibrillators.

Every year 250,000 or more people with cardiovascular disease die within an hour of symptom onset and before they arrive at a hospital. With appropriate early defibrillation and follow-up treatment many people who might have died can now live. Nurses are key health care professionals for using automatic external defibrillators in hospitals and for teaching other first responders--inside and outside hospitals--how to use automatic external defibrillators. Features of automatic and semiautomatic external defibrillators are reviewed as well as ethical considerations for the use of automatic external defibrillators.

FAD insertion is essential for attaining the assembly competence of the dihydrolipoamide dehydrogenase (E3) monomer from Escherichia coli.

Dihydrolipoamide dehydrogenase (E3) from Escherichia coli, an FAD-linked homodimer, can be fully reconstituted in vitro following denaturation in 6 m guanidinium chloride. Complete restoration of activity occurs within 1-2 h in the presence of FAD, dithiothreitol, and bovine serum albumin. In the absence of FAD, the dihydrolipoamide dehydrogenase monomer forms a stable folding intermediate, which is incapable of dimerization. This intermediate displays a similar tryptic resistance to the native enzyme but is less heat-stable, because its ability to form native E3 is lost after incubation at 65 degrees C for 15 min. The presence of FAD promotes slow, additional conformational rearrangements of the E3 subunit as observed by cofactor-dependent decreases in intrinsic tryptophan fluorescence. However, after 2 h, the tryptophan fluorescence spectrum and far UV CD spectrum of E3, refolded in the absence of FAD, are similar to that of the native enzyme, and full activity can still be recovered on addition of FAD. Cross-linking studies show that FAD insertion is necessary for the monomeric folding intermediate to attain an assembly competent state leading to dimerization. Thus cofactor insertion represents a key step in the assembly of this enzyme, although its initial presence appears not to be required to promote the correct folding pathway.

Heparin-protamine complexes and C-reactive protein induce activation of the classical complement pathway: studies in patients undergoing cardiac surgery and in vitro.

The administration of protamine to patients undergoing cardiopulmonary bypass (CPB) to neutralize heparin and to reduce the risk of bleeding, induces activation of the classical complement pathway mainly by heparin-protamine complexes. We investigated whether C-reactive protein (CRP) contributes to protamine-induced complement activation. In 24 patients during myocardial revascularization, we measured complement, CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo. We also incubated plasma from healthy volunteers and patients with heparin and protamine in vitro to study CRP-mediated complement activation. During CPB, CRP levels remained unchanged while C3 activation products increased. C4 activation occurred after protamine administration. CRP-complement complexes increased at the end of CPB and upon protamine administration. Incubation of plasma with heparin and protamine in vitro generated complement-CRP complexes, which was blocked by phosphorylcholine and stimulated by exogenous CRP. C4d-CRP complex formation after protamine administration correlated clinically with the incidence of postoperative arrhythmia. Protamine administration during cardiac surgery induces complement activation which in part is CRP-dependent, and correlates with postoperative arrhythmia.