Hypothermie thérapeutique après arrêt cardio-respiratoire: bénéfices d'une prophylaxie antibiotique précoce

Contexte: Plusieurs études randomisées ont démontré que l'hypothermie thérapeutique modérée (33 à 34°C pendant 12 à 24H) diminue la mortalité intra-hospitalière et améliore le pronostic neurologique chez les patients comateux suite à un arrêt cardio-respiratoire (ACR). Néanmoins cette technique n'est pas dénuée d'effets secondaires au premier rang desquels on trouve les perturbations infectieuses, cardiovasculaires et hydroélectriques. L'introduction d'une prophylaxie antibiotique susceptible de diminuer l'incidence des complications infectieuses chez ces patients est préconisée par certains experts. Objectif: Evaluer si une prophylaxie antibiotique d'Augmentin® pendant 5 à 7 jours peut réduire l'incidence de pneumonies acquises sous ventilateur (VAP) au sein d'une cohorte de patients comateux hospitalisés à la suite d'un arrêt cardio-respiratoire et traités par hypothermie thérapeutique. Méthodologie: Analyse d'une base de données prospective comprenant des patients admis aux SI du Centre hospitalier universitaire vaudois (CHUV) entre juin 2007 et juillet 2011 en raison d'un ACR et traités par hypothermie thérapeutique, selon notre protocole standard de prise en charge. Pour définir si une infection était présente, nous avons analysé rétrospectivement le dossier informatique de chaque patient à la recherche des données nécessaires (radiographies du thorax, microbiologie, etc.). Nous avons également calculé le score CPIS (Clinical Pulmonary Infection Score) quotidien de chaque patient lorsque cela était possible. Le score CPIS a été validé comme outil visant à faciliter le diagnostic de VAP. Il est calculé sur la base de points attribués pour différents signes et symptômes de pneumonie. Résultats: 147 patients (âge moyen 62 ans, durée moyenne de l'arrêt circulatoire 26 min) ont été étudiés. 33% ont développé une infection (dont 30,5% de VAP) parmi lesquels 32/71 (45%) des patients qui n'ont pas reçu de prophylaxie et 17/76 (22%) de ceux qui en ont reçu une (P=0.0035). Il y a avait significativement plus de patients avec un CPIS >6 dans le groupe sans prophylaxie au jour 3 (36/65 [55%] vs. 17/69 [25%], P=0.003) et au jour 5 (24/42 [57%] vs. 17/51 [33%], P=0.02) après admission. Le CPIS médian était aussi plus bas chez les patients avec prophylaxie aux 5ème et 7ème jours (6 [range 0-10] vs. 4.5 [range 0-11], P=0.03 et 7 [range 0-10] vs. 4 [range 0-19], P=0.02, respectivement). La mortalité hospitalière était comparable entre les deux groupes (36/71 [51%] vs. 35/76 [46%], P=0.58). Conclusions: Une prophylaxie antibiotique est une mesure efficace pour réduire la survenue de VAP chez les patients avec ACR et hypothermie thérapeutique. Ce résultat devrait encourager des études à plus large échelle afin de démontrer si une antiobioprophylaxie peut également diminuer la mortalité hospitalière. Le score CPIS est un outil valide et utile dans ce contexte pour faciliter le diagnostic de pneumonie liée au ventilateur.

Evaluation of respiratory and dermal occupational exposures to monoethanolamine during cleaning

Professional cleaning is a basic service occupation with a wide variety of tasks carried out in all kind of different sectors and workplaces by a large workforce. One important risk for cleaning workers is the exposure to chemical substances that are present in cleaning products.Monoethanolamine was found to be often present in cleaning products such as general purpose cleaners, bathroom cleaners, floor cleaners and kitchen cleaners. Monoethanolamine can injure the skin, and exposure to monoethanolamine was associated to asthma even when the air concentrations were low. It is a strong irritant and known to be involved in sensitizing mechanisms. It is very likely that the use of cleaning products containing monoethanolamine gives rise to respiratory and dermal exposures. Therefore there is a need to further investigate the exposures to monoethanolamine for both, respiratory and dermal exposure.The determination of monoethanolamine has traditionally been difficult and analytical methods available are little adapted for occupational exposure assessments. For monoethanolamine air concentrations, a sampling and analytical method was already available and could be used. However, a method to analyses samples for skin exposure assessments as well as samples of skin permeation experiments was missing. Therefore one main objective of this master thesis was to search an already developed and described analytical method for the measurement of monoethanolamine in water solutions, and to set it up in the laboratory. Monoethanolamine was analyzed after a derivatisation reaction with o-pthtaldialdehyde. The derivated fluorescing monoethanolamine was then separated with high performance liquid chromatography and detection took place with a fluorescent detector. The method was found to be suitable for qualitative and quantitative analysis of monoethanolamine. An exposure assessment was conducted in the cleaning sector to measure the respiratory and dermal exposures to monoethanolamine during floor cleaning. Stationary air samples (n=36) were collected in 8 companies and samples for dermal exposures (n=12) were collected in two companies. Air concentrations (Mean = 0.18 mg/m3, Standard Deviation = 0.23 mg/m3, geometric Mean = 0.09 mg/m3, Geometric Standard Deviation = 3.50) detected were mostly below 1/10 of the Swiss 8h time weighted average occupational exposure limit. Factors that influenced the measured monoethanolamine air concentrations were room size, ventilation system and the concentration of monoethanolamine in the cleaning product and amount of monoethanolamine used. Measured skin exposures ranged from 0.6 to 128.4 mg/sample. Some cleaning workers that participated in the skin exposure assessment did not use gloves and had direct contact with the solutions containing the cleaning product and monoethanolamine. During the entire sampling campaign, cleaning workers mostly did not use gloves. Cleaning workers are at risk to be regularly exposed to low air concentrations of monoethanolamine. This exposure may be problematic if a worker suffers from allergic reactions (e.g. Asthma). In that case a substitution of the cleaning product may be a good prevention measure as several different cleaning products are available for similar cleaning tasks. Currently there are no occupational exposure limits to compare the skin exposures that were found. To prevent skin exposures, adaptations of the cleaning techniques and the use of gloves should be considered. The simultaneous skin and airborne exposures might accelerate adverse health effects. Overall the risks caused by exposures to monoethanolamine are considered as low to moderate when the cleaning products are used correctly. Whenever possible, skin exposures should be avoided. Further research should consider especially the dermal exposure routes, as very high exposures might occur by skin contact with cleaning products. Dermatitis but also sensitization might be caused by skin exposures. In addition, new biomedical insights are needed to better understand the risks of the dermal exposure. Therefore skin permeability experiments should be considered.

Consequences of gestational stress on GABAergic modulation of respiratory activity in developing newborn pups.

The GABAergic system modulates respiratory activity and undergoes substantial changes during early life. Because this maturation process is sensitive to stress, we tested the hypothesis that gestational stress (GS) alters development of GABAergic modulation of respiratory control in rat pups. The respiratory responses to the selective GABAA receptor agonist muscimol were compared between pups born to dams subjected to GS (bright light and predator odor; 20 min/day from G9 to G19) or maintained under standard (control) conditions. Respiratory activity was measured on 1 and 4 days old pups of both sexes using in vivo (whole body plethysmography) and in vitro (isolated brainstem-spinal cord preparation) approaches. In intact pups, muscimol injection (0.75 mg/kg; i.p.) depressed minute ventilation; this response was less in GS pups, and at P4, muscimol augmented minute ventilation in GS females. Bath application of muscimol (0.01-0.5 μM) onto brainstem preparations decreased inspiratory (C4) burst frequency and amplitude in a dose-dependent manner; the responsiveness decreased with age. However, GS had limited effects on these results. We conclude that the results obtained in vivo are consistent with our hypothesis and show that GS delays maturation of GABAergic modulation of respiratory activity. The differences in the results observed between experimental approaches (in vivo versus in vitro) indicate that the effect of prenatal stress on maturation of GABAergic modulation of respiratory control mainly affects the peripheral/metabolic components of the respiratory control system.

Low incidence of severe respiratory syncytial virus infections in lung transplant recipients despite the absence of specific therapy.

BACKGROUND: Respiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with significant morbidity and mortality. Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre-emptive and therapeutic purposes. However, in the absence of randomized, placebo-controlled trials, efficacy is controversial and there is toxicity as well as cost concerns. METHODS: We retrospectively reviewed cases of lower respiratory tract RSV infections in adult LTRs. Diagnosis was based on clinical history, combined with a positive polymerase chain reaction (PCR) and/or viral cultures of bronchoalveolar lavage (BAL) specimens. RESULTS: Ten symptomatic patients were identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized for community-acquired respiratory tract infections. Two patients had a concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment because of clinical stability and/or improvement at the time of RSV diagnosis. Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical ventilation) received ribavirin and palivizumab. All patients recovered without complications and with no persistent RSV infection. However, bronchiolitis obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45 months. CONCLUSIONS: Our data suggest that mild RSV infections in LTRs might evolve favorably in the absence of specific anti-viral therapy. However, this observation needs confirmation in a large clinical trial specifically investigating the development of BOS in untreated vs treated patients.

Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients.

Nutrition assessment is important during chronic respiratory insufficiency to evaluate the level of malnutrition or obesity and should include body composition measurements. The appreciation of fat-free and fat reserves in patients with chronic respiratory insufficiency can aid in designing an adapted nutritional support, e.g., nutritional support in malnutrition and food restriction in obesity. The purpose of the present study was to cross-validate fat-free and fat mass obtained by various bioelectric impedance (BIA) formulas with the fat-free and fat mass measured by dual-energy X-ray absorptiometry (DXA) and determine the formulas that are best suited to predict the fat-free and fat mass for a group of patients with severe chronic respiratory insufficiency. Seventy-five patients (15 women and 60 men) with chronic obstructive and restrictive respiratory insufficiency aged 45-86 y were included in this study. Body composition was calculated according to 13 different BIA formulas for women and 12 for men and compared with DXA. Because of the variability, calculated as 2 standard deviations, of +/- 5.0 kg fat-free mass for women and +/- 6.4 kg for men for the best predictive formula, the use of the various existing BIA formulas was considered not clinically relevant. Therefore disease-specific formulas for patients with chronic respiratory insufficiency should be developed to improve the prediction of fat-free and fat mass by BIA in these patients.

Répercussions de l'agression sur le métabolisme et la composition corporelle chez l'individu obèse : Nutrition de l'obèse agressé. [Repercussions of injury on metabolic and body composition factors in obese individuals : Nutrition and obese critical patients]

La réponse métabolique de l'obèse apparemment « sainen situation d'agression aiguë (polytraumatisés, traumatisés crâniens, patients chirurgicaux, grands brûlés, opérations électives) ne se distingue pas ou peu de celle de l'individu non-obèse. Cependant, les complications médicales liées à l'agression (insuffisances respiratoire et cardiaque, bronchopneumonie, infections de plaies, thrombophlébites et embolies) demeurent plus importantes chez l'obèse morbide que chez l'individu de poids normal. Grâce à l'inflation de ses réserves énergétiques, l'obèse apparemment sain est avantagé, par rapport au sujet mince, au cours d'une agression nutritionnelle chronique telle que le jeûne prolongé. Le facteur fonctionnel limitant la survie dépend avant tout de la composition corporelle initiale et du degré d'adaptation métabolique (et comportementale) en particulier du degré de conservation de la masse maigre par rapport à la masse grasse. La mobilisation accrue de la masse grasse associée à la perte de poids chez l'obèse (par rapport à son homologue non-obèse) est favorable à une prolongation de la vie, car, en brûlant davantage de graisse corporelle, la part des protéines corporelles endogènes utilisée à des fins énergétiques est plus faible. Il s'ensuit chez l'obèse qu'un niveau de masse maigre critique pour la survie n'est atteint qu'après une réduction très marquée de ses réserves énergétiques. En revanche, le sujet mince perd davantage de masse maigre lors de l'amaigrissement et, par conséquent, son métabolisme de repos diminuera plus rapidement que celui du sujet obèse. Cela peut constituer un avantage énergétique évident en termes d'économie d'énergie consécutive à l'adaptation métabolique, mais un inconvénient majeur quant à la durée de la survie. The metabolic response of « apparently healthyobese individuals following acute injury (multiple trauma, head injury and surgical patients, extended burns, elective surgery) is not dramatically different from that of a non-obese individuals. However, the medical complications following the injury (respiratory and cardiac insufficiency, broncho-pneumonia, infections of wounds, trombophlebitis and embolism) are more prevalent in morbid obese patients than in individuals of normal body weight. Because of a large increase in their individuals energy store, "apparently healthy" obese individuals have an advantage over very lean subjects when exposed to a chronic nutritional aggression such as total fasting. The functional limiting factor for survival depends primarily on initial body composition and the magnitude of metabolic adaptation (including behavioral adaptation). The key factor is the extent to which the fat-free mass is maintained (versus to the fat mass) during weight loss. The increased proportion of body fat mobilized during weight loss in obese patients, compared with their non-obese counterparts, favors prolonged survival, because more adipose tissue is burned off, the fraction of body protein endogenously utilized for energy purpose individuals, is smaller. This implies that obese individuals do not reach a fat-free mass "critical" for their survival until their energy stores reach very low values. In contrast, lean subject tend to lose more fat-free mass during weight loss than obese subjects and, as a result, their energy expenditure drops more rapidly. This may offer a potential advantage in terms of energy economy (more energy saving) but a major disadvantage in terms of duration of survival.

Identification of the pathological alterations underlying respiratory failure in myotonic dystrophy transgenic mice

AbstractMyotonic dystrophy type 1 (DM1), also known as Steinert's disease, is an inherited autosomal dominant disease. DM1 is characterized by myotonia, muscular weakness and atrophy, but it has a multisystemic phenotype. The genetic basis of the disease is the abnormal expansion of CTG repeats in the 3' untranslated region of the DM protein kinase (DMPK) gene on chromosome 19. The size of the expansion correlates to the severity of the disease and the age of onset.Respiratory problems have long been recognized to be a major feature of the disease and are the main factor contributing to mortality ; however the mechanisms are only partly known. The aim of our study is to investigate whether respiratory failure results only from the involvement of the dystrophic process at the level of the respiratory muscles or comes also from abnormalities in the neuronal network that generates and controls the respiratory rhythm. The generation of valid transgenic mice displaying the human DM1 phenotype by the group of Dr. Gourdon provided us a useful tool to analyze the brain stem respiratory neurons, spinal phrenic motoneurons and phrenic nerves. We examined therefore these structures in transgenic mice carrying 350-500 CTGs and displaying a mild form of the disease (DM1 mice). The morphological and morphometric analysis of diaphragm muscle sections revealed a denervation of the end-plates (EPs), characterized by a decrease in size and shape complexity of EPs and a reduction in the density of acetylcholine receptors (AChRs). Also a strong and significant reduction in the number of phrenic unmyelinated fibers was detected, but not in the myelinated fibers. In addition, no pathological changes were detected in the cervical motoneurons and medullary respiratory centers (Panaite et al., 2008). These results suggest that the breathing rhythm is probably not affected in mice expressing a mild form of DM1, but rather the transmission of action potentials at the level of diaphragm NMJs is deficient.Because size of the mutation increases over generations, new transgenic mice were obtained from the mice with 350-500 CTGs, resulting from a large increase of CTG repeat in successive generations, these mice carry more than 1300 CTGs (DMSXL) and display a severe DM1 phenotype (Gomes-Pereira et al., 2007). Before we study the mechanism underlying the respiratory failure in DMSXL mice, we analyzed the peripheral nervous system (PNS) in these mice by electrophysiological, histological and morphometric methods. Our results provide strong evidence that DMSXL mice have motor neuropathy (Panaite et al., 2010, submitted). Therefore the DMSXL mice expressing severe DM1 features represent for us a good tool to investigate, in the future, the physiological, structural and molecular alterations underlying respiratory failure in DM1. Understanding the mechanism of respiratory deficiency will help to better target the therapy of these problems in DM1 patients. In addition our results may, in the future, orientate pharmaceutical and clinical research towards possible development of therapy against respiratory deficits associated with the DM1.RésuméLa dystrophic myotonique type 1 (DM1), aussi dénommée maladie de Steinert, est une maladie héréditaire autosomique dominante. Elle est caractérisée par une myotonie, une faiblesse musculaire avec atrophie et se manifeste aussi par un phénotype multisystémique. La base génétique de la maladie est une expansion anormale de répétitions CTG dans une région non traduite en 3' du gène de la DM protéine kinase (DMPK) sur le chromosome 19. La taille de l'expansion est corrélée avec la sévérité et l'âge d'apparition de DM1.Bien que les problèmes respiratoires soient reconnus depuis longtemps comme une complication de la maladie et soient le principal facteur contribuant à la mortalité, les mécanismes en sont partiellement connus. Le but de notre étude est d'examiner si l'insuffisance respiratoire de la DM1 est dû au processus dystrophique au niveau des muscles respiratoires ou si elle est entraînée aussi par des anomalies dans le réseau neuronal qui génère et contrôle le rythme respiratoire. La production par le groupe du Dr. Gourdon de souris transgéniques de DM1, manifestant le phénotype de DM1 humaine, nous a fourni un outil pour analyser les nerfs phréniques, les neurones des centres respiratoires du tronc cérébral et les motoneurones phréniques. Par conséquence, nous avons examiné ces structures chez des souris transgéniques portant 350-500 CTG et affichant une forme légère de la maladie (souris DM1). L'analyse morphologique et morphométrique des sections du diaphragme a révélé une dénervation des plaques motrices et une diminution de la taille et de la complexité de la membrane postsynaptîque, ainsi qu'une réduction de la densité des récepteurs à l'acétylcholine. Nous avons aussi détecté une réduction significative du nombre de fibres nerveuses non myélinisées mais pas des fibres myélinisées. Par ailleurs, aucun changement pathologique n'a été détecté pour les neurones moteurs médullaires cervicaux et centres respiratoires du tronc cérébral (Panaite et al., 2008). Ces résultats suggèrent que le iythme respiratoire n'est probablement pas affecté chez les souris manifestant une forme légère du DM1, mais plutôt que la transmission des potentiels d'action au niveau des plaques motrices du diaphragme est déficiente.Comme la taille du mutation augmente au fil des générations, de nouvelles souris transgéniques ont été générés par le groupe Gourdon; ces souris ont plus de 1300 CTG (DMSXL) et manifestent un phénotype sévère du DM1 (Gomes-Pereira et al., 2007). Avant d'étudier le mécanisme sous-jacent de l'insuffisance respiratoire chez les souris DMSXL, nous avons analysé le système nerveux périphérique chez ces souris par des méthodes électrophysiologiques, histologiques et morphométriques. Nos résultats fournissent des preuves solides que les souris DMSXL manifestent une neuropathie motrice (Panaite et al., 2010, soumis). Par conséquent, les souris DMSXL représentent pour nous un bon outil pour étudier, à l'avenir, les modifications physiologiques, morphologiques et moléculaires qui sous-tendent l'insuffisance respiratoire du DM1. La connaissance du mécanisme de déficience respiratoire en DM1 aidera à mieux cibler le traitement de ces problèmes aux patients. De plus, nos résultats pourront, à l'avenir, orienter la recherche pharmaceutique et clinique vers le développement de thérapie contre le déficit respiratoire associé à DM1.

Respiratory failure in a mouse model of myotonic dystrophy does not correlate with the CTG repeat length.

Myotonic dystrophy (DM1) is a multisystemic disease caused by an expansion of CTG repeats in the region of DMPK, the gene encoding DM protein kinase. The severity of muscle disability in DM1 correlates with the size of CTG expansion. As respiratory failure is one of the main causes of death in DM1, we investigated the correlation between respiratory impairment and size of the (CTG)n repeat in DM1 animal models. Using pressure plethysmography the respiratory function was assessed in control and transgenic mice carrying either 600 (DM600) or >1300 CTG repeats (DMSXL). The statistical analysis of respiratory parameters revealed that both DM1 transgenic mice sub-lines show respiratory impairment compared to control mice. In addition, there is no significant difference in breathing functions between the DM600 and DMSXL mice. In conclusion, these results indicate that respiratory impairment is present in both transgenic mice sub-lines, but the severity of respiratory failure is not related to the size of the (CTG)n expansion.

Primary fluid bolus therapy for infection-associated hypotension in the emergency department.

OBJECTIVES: The physiological changes associated with fluid bolus therapy (FBT) for patients with infection-associated hypotension in the emergency department (ED) are poorly understood. We describe the physiological outcomes of FBT in the first 6 hours (primary FBT) for patients presenting to the ED with infection-associated hypotension. METHODS: We studied 101 consecutive ED patients with infection and a systolic blood pressure (SBP)<100 mmHg who underwent FBT in the first 6 hours. RESULTS: We screened 1123 patients with infection and identified 101 eligible patients. The median primary FBT volume given was 1570 mL (interquartile range, 1000- 2490 mL). The average mean arterial pressure (MAP) did not change from admission to 6 hours in the whole cohort, or in patients who were hypotensive on arrival at the ED. However, the average MAP increased from its lowest value during the first 6 hours (66 mmHg [SD, 10 mmHg]) to its value at 6 hours (73 mmHg [SD, 12 mmHg]; P<0.001). The mean heart rate, body temperature, respiratory rate and plasma creatinine level decreased (P<0.05). In patients who were severely hypotensive (SBP<90 mmHg) on arrival at the ED, the MAP increased from 54 mmHg (SD, 8 mmHg) to 70 mmHg (SD, 14 mmHg) (P<0.001). At 6 hours, however, SBP was still <100 mmHg in 44 patients and <90 mmHg in 17 patients. When noradrenaline was used, in 10 patients, hypotension was corrected in all 10 and the MAP increased from 58 mmHg (SD, 9 mmHg) to 75 mmHg (SD, 13 mmHg). CONCLUSION: Among ED patients admitted to an Australian teaching hospital with infection, hypotension was uncommon. FBT for hypotension was limited in volumes given and failed to achieve a sustained SBP of >100 mmHg in 40% of cases. In contrast, noradrenaline therapy corrected hypotension in all patients who received it.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Mutations in NDUFB11, Encoding a Complex I Component of the Mitochondrial Respiratory Chain, Cause Microphthalmia with Linear Skin Defects Syndrome.

Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations.

A bovine model of a respiratory Parachlamydia acanthamoebae infection.

The aim of this study was to evaluate the pathogenicity of Parachlamydia (P.) acanthamoebae as a potential agent of lower respiratory tract disease in a bovine model of induced lung infection. Intrabronchial inoculation with P. acanthamoebae was performed in healthy calves aged 2-3 months using two challenge doses: 10(8) and 10(10) bacteria per animal. Controls received 10(8) heat-inactivated bacteria. Challenge with 10(8) viable Parachlamydia resulted in a mild degree of general indisposition, whereas 10(10) bacteria induced a more severe respiratory illness becoming apparent 1-2 days post inoculation (dpi), affecting 9/9 (100%) animals and lasting for 6 days. The extent of macroscopic pulmonary lesions was as high as 6.6 (6.0)% [median (range)] of lung tissue at 2-4 dpi and correlated with parachlamydial genomic copy numbers detected by PCR, and with bacterial load estimated by immunohistochemistry in lung tissue. Clinical outcome, acute phase reactants, pathological findings and bacterial load exhibited an initial dose-dependent effect on severity. Animals fully recovered from clinical signs of respiratory disease within 5 days. The bovine lung was shown to be moderately susceptible to P. acanthamoebae, exhibiting a transient pneumonic inflammation after intrabronchial challenge. Further studies are warranted to determine the precise pathophysiologic pathways of host-pathogen interaction.

Reduction of respiratory motion artifacts for free-breathing whole-heart coronary MRA by weighted iterative reconstruction.

PURPOSE: To combine weighted iterative reconstruction with self-navigated free-breathing coronary magnetic resonance angiography for retrospective reduction of respiratory motion artifacts. METHODS: One-dimensional self-navigation was improved for robust respiratory motion detection and the consistency of the acquired data was estimated on the detected motion. Based on the data consistency, the data fidelity term of iterative reconstruction was weighted to reduce the effects of respiratory motion. In vivo experiments were performed in 14 healthy volunteers and the resulting image quality of the proposed method was compared to a navigator-gated reference in terms of acquisition time, vessel length, and sharpness. RESULT: Although the sampling pattern of the proposed method contained 60% more samples with respect to the reference, the scan efficiency was improved from 39.5 ± 10.1% to 55.1 ± 9.1%. The improved self-navigation showed a high correlation to the standard navigator signal and the described weighting efficiently reduced respiratory motion artifacts. Overall, the average image quality of the proposed method was comparable to the navigator-gated reference. CONCLUSION: Self-navigated coronary magnetic resonance angiography was successfully combined with weighted iterative reconstruction to reduce the total acquisition time and efficiently suppress respiratory motion artifacts. The simplicity of the experimental setup and the promising image quality are encouraging toward future clinical evaluation. Magn Reson Med 73:1885-1895, 2015. © 2014 Wiley Periodicals, Inc.