Post-exercise parasympathetic reactivation and sensibility to hypoxia

Introduction Exposure to hypoxia leads to several reactions of the organism, which try to compensate the reduced oxygen level in the blood. Acute response is characterized by an increase in pulmonary ventilation (Hypoxia Ventilatory Response, HVR) and in cardiac output (cardiac response to hypoxia). Heart rate (HR) at rest and during exercise is higher at high altitude than at sea level, whereas HRmax is lower. These cardiac adaptations are partially explained by an increased sympathetic stimulation associated with a reduced parasympathetic tone (12). The precise mechanisms of HRmax decline in acute hypoxia are however still to be identified, although several hypothesis have been suggested, such as a direct effect of hypoxia on the electrophysiological properties, an influence of skeletal maximal VO2 or a modulation of the autonomic nervous system (8). Some authors have reported that endurance trained athletes present an increased sensitivity to hypoxia shown by a large reduction in VO2max and an important decrease in arterial saturation. (9,11, 13) A hypoxia test can assess the sensibility of chemoreceptors to the reduction of oxygen by calculating hypoxic ventilatory and cardiac responses, knowing that low sensibility is correlated with poor acclimatization. Two parameters results from the differences in ventilation (and heart rate) divided by the difference in the arterial oxygen saturation between normoxia and hypoxia (18). Objective The hypothesis tested by this study is that parasympathetic reactivation after moderate effort in hypoxic condition can be used as a marker of individual sensibility to hypoxia. Parasympathetic reactivation is a marker of vagal tone that predict endurance capacity and aerobic fitness (2,7). Methods Subjects This study uses data obtained from two groups of athletes participating into two larger studies about adaptation to hypoxia. One group is composed of elite athletes (Swiss ski mountaineering team), the other one of mid-level athletes (ski mountaineering amateurs). The particularity of this target population is that they often train at high altitude, and therefore could show a better response to hypoxia than athleltes of other disciplines. Protocol The athletes performed a submaximal exercise (6min run at 9 km/h, flat) followed by 10 min of seated rest either in an hypoxic chamber (simulated altitude of 3000m) or in normoxic conditions. During the resting phase parasympathetic reactivation was assessed by beat-to-beat HR measurements.A test of tolerance to altitude was also performed. Analysis Parasympathetic reactivation, assessed by the calculation of the root mean square of successive differences in the R-R intervals (RMSSD)(4), is compared to individual responses at altitude, in order to appreciate the correlation between the two phenomena.

Cost evaluation of cardiac magnetic resonance imaging versus coronary angiography for the work-up of coronary artery disease

Background: CMR has recently emerged as a robust and reliable technique to assess coronary artery disease (CAD). A negative perfusion CMR test predicts low event rates of 0.3-0.5%/year. Invasive coronary angiography (CA) remains the "gold standard" for the evaluation of CAD in many countries.Objective: Assessing the costs of the two strategies in the European CMR registry for the work-up of known or suspected CAD from a health care payer perspective. Strategy 1) a CA to all patients or 2) a CA only to patients who are diagnosed positive for ischemia in a prior CMR.Method and results: Using data of the European CMR registry (20 hospitals, 11'040 consecutive patients) we calculated the proportion of patients who were diagnosed positive (20.6%), uncertain (6.5%), and negative (72.9%) after the CMR test in patients with known or suspected CAD (n=2'717). No other medical test was performed to patients who were negative for ischemia. Positive diagnosed patients had a coronary angiography. Those with uncertain diagnosis had additional tests (84.7%: stress echocardiography, 13.1%: CCT, 2.3% SPECT), these costs were added to the CMR strategy costs. Information from costs for tests in Germany and Switzerland were used. A sensibility analysis was performed for inpatient CA. For costs see figure. Results - costs.Discussion: The CMR strategy costs less than the CA strategy for the health insurance systems both, in Germany and Switzerland. While lower in costs, the CMR strategy is a non-invasive one, does not expose to radiation, and yields additional information on cardiac function, viability, valves, and great vessels. Developing the use of CMR instead of CA might imply some reduction in costs together with superior patient safety and comfort, and a better utilization of resources at the hospital level. Document introduit le : 01.12.2011

Detection of suspected placental invasion by MRI: Do the results depend on observer' experience?

PURPOSE: To evaluate the diagnostic value of previously described MR features used for detecting suspected placental invasion according to observers' experience. MATERIALS AND METHODS: Our population included 25 pregnant women (mean age 35.16) investigated by prenatal MRI (1.5T, T1- and T2-weighted MR-sequences without i.v. contrast), among them 12 with histopathologically proven placental invasion and 13 women (52%) without placental invasion used as control group. Two senior and two junior radiologists blindly and independently reviewed MR-examinations in view of 6 previously defined MR-features indicating presence and degree of placental invasion (placenta increta, accreta or percreta). For each reader the sensibility, specificity, and receiver operating curve (ROC) were calculated. Interobserver agreements between senior and junior readers were determined. Stepwise logistic regression was performed including the 6 MR-features predictive of placental invasion. RESULTS: Demographics between both groups were statistically equivalent. Overall sensitivity and specificity for placental invasion was 90.9% and 75.0% for seniors and 81.8% and 61.8% for juniors, respectively. The best single MR-feature indicating placental invasion was T2-hypointense placental bands (r(2)=0.28), followed by focally interrupted myometrial border, infiltration of pelvic organs and tenting of the bladder (r(2)=0.36). Interobserver agreement for detecting placental invasion was 0.64 for seniors and 0.41 for juniors, thus substantial and moderate, respectively. Seniors detected placental invasion and depth of infiltration with significantly higher diagnostic certitude than juniors (p=0.0002 and p=0.0282, respectively). CONCLUSION: MRI can be a reliable and reproducible tool for the detection of suspected placental invasion, but the diagnostic value significantly depends on observers' experience.

Sensate lateral arm flap for defects of the lower leg.

Ideally, reconstruction of lower extremity soft tissue defects includes not only an esthetically pleasing 3-dimensional shape and solid anchoring to the underlying structures to resist shear forces, but should also address the restoration of sensation. Therefore, we present a prospective study on defect reconstruction of the lower leg and ankle to evaluate the role of sensate free fasciocutaneous lateral arm flap and the impact of sensory nerve reconstruction. Thirty patients were allocated randomly to the study group (n = 15) that obtained end-to-side sensate coaptation using the lower lateral cutaneous brachial nerve to the tibial nerve using the epineural window technique, or to the control group reconstructed without nerve coaptation. At 1-year follow-up the patients were evaluated for pain sensation, thermal sensibility, static and moving 2-point discrimination, and Semmes-Weinstein monofilament tests. Data from both groups were compared and statistically analyzed with the Mann-Whitney U test and the Fisher exact test. Flaps of the study group reached a static and moving 2-point discrimination and Semmes-Weinstein monofilament tests nearly equal to the contralateral leg area and significantly better than flaps of the control group. Donor damage morbidity of the tibial nerve did not occur. To our point of view resensation should be carried out by end-to-side neurorrhaphy to the tibial nerve because of the superior restoration of sensibility.

Chest wall syndrome among primary care patients: a cohort study.

BACKGROUND: The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS). METHODS: Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome. RESULTS: Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients. CONCLUSION: CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration.

Causes développementales dans la variabilité de l'efficacité et de la toxicité des antalgiques en pédiatrie [Developmental causes in variability of efficacy and toxicity of analgesics in pediatrics]

The intensity of pain perception and its sensibility to analgesic drugs is highly variable and unpredictable between individuals. Drug disposition varies during development due to the physiological maturation of enzymatic systems and physiological processes responsible for the absorption, distribution, elimination and effect at the site of action. Many of those developmental variables are not yet clearly defined, but their consideration is important for avoiding potential risks of ineffective or toxic treatment. Implications of those developmental changes for day-to-day clinical practice depend on the age of the child, on the type of drug, on the underlying disease and on the potential co-administration of other chemicals.

Brief DISCERN, six questions for the evaluation of evidence-based content of health-related websites.

OBJECTIVE: To extract and to validate a brief version of the DISCERN which could identify mental health-related websites with good content quality. METHOD: The present study is based on the analysis of data issued from six previous studies which used DISCERN and a standardized tool for the evaluation of content quality (evidence-based health information) of 388 mental health-related websites. After extracting the Brief DISCERN, several psychometric properties (content validity through a Factor analysis, internal consistency by the Cronbach's alpha index, predictive validity through the diagnostic tests, concurrent validity by the strength of association between the Brief DISCERN and the original DISCERN scores) were investigated to ascertain its general applicability. RESULTS: A Brief DISCERN composed of two factors and six items was extracted from the original 16 items version of the DISCERN. Cronbach's alpha coefficients were more than acceptable for the complete questionnaire (alpha=0.74) and for the two distinct domains: treatments information (alpha=0.87) and reliability (alpha=0.83). Sensibility and specificity of the Brief DISCERN cut-off score > or =16 in the detection of good content quality websites were 0.357 and 0.945, respectively. Its predictive positive and negative values were 0.98 and 0.83, respectively. A statistically significant linear correlation was found between the total scores of the Brief DISCERN and those of the original DISCERN (r=0.84 and p<0.0005). CONCLUSION: The Brief DISCERN seems to be a reliable and valid instrument able to discriminate between websites with good and poor content quality. PRACTICE IMPLICATIONS: The Brief DISCERN is a simple tool which could facilitate the identification of good information on the web by patients and general consumers.

Role of the epithelial sodium channel (ENaC) in the epidermal barrier function of the skin

Abstract In humans, the skin is the largest organ of the body, covering up to 2m2 and weighing up to 4kg in an average adult. Its function is to preserve the body from external insults and also to retain water inside. This barrier function termed epidermal permeability barrier (EPB) is localized in the functional part of the skin: the epidermis. For this, evolution has built a complex structure of cells and lipids sealing the surface, the stratum corneum. The formation of this structure is finely tuned since it is not only formed once at birth, but renewed all life long. This active process gives a high plasticity and reactivity to skin, but also leads to various pathologies. ENaC is a sodium channel extensively studied in organs like kidney and lung due to its importance in regulating sodium homeostasis and fluid volume. It is composed of three subunits α, ß and r which are forming sodium selective channel through the cell membrane. Its presence in the skin has been demonstrated, but little is known about its physiological role. Previous work has shown that αENaC knockout mice displayed an abnormal epidermis, suggesting a role in differentiation processes that might be implicated in the EPB. The principal aim of this thesis has been to study the consequences for EPB function in mice deficient for αENaC by molecular and physiological means and to investigate the underlying molecular mechanisms. Here, the barrier function of αENaC knockout pups is impaired. Apparently not immediately after birth (permeability test) but 24h later, when evident water loss differences appeared compared to wildtypes. Neither the structural proteins of the epithelium nor the tights junctions showed any obvious alterations. In contrary, stratum corneum lipid disorders are most likely responsible for the barrier defect, accompanied by an impairment of skin surface acidification. To analyze in details this EPB defect, several hypotheses have been proposed: reduced sensibility to calcium which is the key activator far epidermal formation, or modification of ENaC-mediated ion fluxes/currents inside the epidermis. The cellular localization of ENaC and the action in the skin of CAPl, a positive regulator of ENaC, have been also studied in details. In summary, this study clearly demonstrates that ENaC is a key player in the EPB maintenance, because αENaC knockout pups are not able to adapt to the new environment (ex utero) as efficiently as the wildtypes, most likely due to impaired of sodium handling inside the epidermis. Résumé Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses pathologies. ENaC est un canal sodique très étudié dans le rein et le poumon pour son importance dans la régulation de l'homéostasie sodique et la régulation du volume du milieu intérieur. Il est composé de 3 sous unités, α, ß et y qui forment un pore sélectif pour le sodium dans les membranes. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris dont le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la différentiation et pourrait même être impliqué dans la barrière épithéliale. Le but de cette thèse fut l'étude de la barrière dans ces souris knockouts avec des méthodes moléculaires et physiologiques et la caractérisation des mécanismes moléculaire impliqués. Dans ce travail, il a été montré que les souris mutantes présentaient un défaut de la barrière. Ce défaut n'est pas visible immédiatement à la naissance (test de perméabilité), mais 24h plus tard, lorsque les tests de perte d'eau transépithéliale montrent une différence évidente avec les animaux contrôles. Ni les protéines de structures ni les jonctions serrées de l'épiderme ne présentaient d'imperfections majeures. A l'inverse, les lipides de la couche cornée présentaient un problème de maturation (expliquant le phénotype de la barrière), certainement consécutif au défaut d'acidification à la surface de la peau que nous avons observé. D'autres mécanismes ont été explorées afin d'investiguer cette anomalie de la barrière, comme la réduction de sensibilité au calcium qui est le principal activateur de la formation de l'épiderme, ou la modification des flux d'ions entre les couches de l'épiderme. La localisation cellulaire d'ENaC, et l'action de son activateur CAPl ont également été étudiés en détails. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des knockouts ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme. Résumé tout public Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses maladies. ENaC est une protéine formant un canal qui permet le passage sélectif de l'ion sodium à travers la paroi des cellules. Il est très étudié dans le rein pour son importance dans la récupération du sel lors de la concentration de l'urine. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris où le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la peau et plus particulièrement la fonction de barrière de l'épiderme. Le but de cette thèse fut l'étude de la fonction de barrière dans ces souris mutantes, au niveau tissulaire et cellulaire. Dans ce travail, il a été montré que les souris mutantes présentaient une peau plus perméable que celle des animaux contrôles, grâce à une machine mesurant la perte d'eau à travers la peau. Ce défaut n'est visible que 24h après la naissance, mais nous avons pu montrer que les animaux mutants perdaient quasiment 2 fois plus d'eau que les contrôles. Au niveau moléculaire, nous avons pu montrer que ce défaut provenait d'un problème de maturation des lipides qui composent la barrière de la peau. Cette maturation est incomplète vraisemblablement à cause d'un défaut de mouvement des ions dans les couches les plus superficielles de l'épiderme, et cela à cause de l'absence du canal ENaC. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des mutants ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme.

Segmentation of foot and ankle complex based on kinematic criteria.

Although various foot models were proposed for kinematics assessment using skin makers, no objective justification exists for the foot segmentations. This study proposed objective kinematic criteria to define which foot joints are relevant (dominant) in skin markers assessments. Among the studied joints, shank-hindfoot, hindfoot-midfoot and medial-lateral forefoot joints were found to have larger mobility than flexibility of their neighbour bonesets. The amplitude and pattern consistency of these joint angles confirmed their dominancy. Nevertheless, the consistency of the medial-lateral forefoot joint amplitude was lower. These three joints also showed acceptable sensibility to experimental errors which supported their dominancy. This study concluded that to be reliable for assessments using skin markers, the foot and ankle complex could be divided into shank, hindfoot, medial forefoot, lateral forefoot and toes. Kinematics of foot models with more segments must be more cautiously used.

Superior pedicle breast reduction for hypertrophy with massive ptosis.

Breast hypertrophy, combined with massive ptosis with a suprasternal notch-to-nipple distance of more than 40 cm, remains an endeavour. Different refinements of the initial technique with free nipple grafts have been described to circumvent the problems of nipple underprojection, areolar hypopigmentation and loss of sensibility secondary to nipple grafting, as well as lacking breast projection due to scarce glandular tissue. Techniques relying on nipple areola complex transposition, rather than grafting, have been described with inferior, superomedial and medial pedicles. The aim of this study is to present the results obtained in a series of 10 patients suffering from bilateral breast hypertrophy with massive ptosis, which was defined as a distance >40 cm from the suprasternal notch-to the nipple. All breasts were managed with a superior pedicle and inverted T technique. The mean preoperative suprasternal notch-to-nipple distance was 44 ± 2 cm, and the resection weight ranged from 800 to 2490 g per breast with an average of about 1450 g in this patient population presenting with overweight or obesity. With a mean nipple areola complex (NAC) lift of 20 ± 3 cm, neither nipple nor areola necrosis was observed. One partial epidermolysis of the areola and two cases of delayed wound healing at the trifurcation point of the inverted T were conservatively managed. Only one re-operation was necessary for an important wound dehiscence of the lateral part of the horizontal scar. These results underscore the safety of the superior pedicle technique in cases of massive ptosis with transposition of the NAC of approximately 20 cm, that is, a pedicle length of about 25 cm.