Physical activity and pregnancy: cardiovascular adaptations, recommendations and pregnancy outcomes.

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery.

Munchausen's syndrome simulating reflex sympathetic dystrophy

A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admissions to hospital and multiple explorations we discovered that she had induced her symptoms herself and a diagnosis of Munchausen's syndrome was made. As far as we know this presentation has not been previously reported and might help to explain the physiopathology of some signs of reflex sympathetic dystrophy.

Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis.

To evaluate the incidence and characteristics of musculoskeletal manifestations in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS The records of 163 cases of PMR or TA diagnosed over a 15 year period in one area of Spain were reviewed for the presence and type of musculoskeletal manifestations. RESULTS Of 163 patients, 90 had isolated PMR and 73 had TA. Eighteen of the 90 patients (20%) with isolated PMR developed distal peripheral arthritis either at diagnosis or during the course of the disease. When it occurred, synovitis was mild, monoarticular or pauci-articular, asymmetrical, transient, and not destructive. Other distal manifestations observed in these patients were carpal tunnel syndrome and distal extremity swelling with pitting oedema. In all cases these manifestations occurred in conjunction with active PMR. As expected, PMR was the most frequent musculoskeletal manifestation in patients with TA, occurring in 56% of cases. On the contrary, only 11% of patients with TA developed peripheral arthritis. An important finding was that peripheral arthritis in these patients appears to be linked only temporally to the presence of simultaneous PMR and is not observed in its absence. Distal extremity swelling or defined polyarthritis were not observed. CONCLUSION The spectrum of distal musculoskeletal manifestations of PMR in our series is similar to that reported in other populations. By contrast, distal musculoskeletal symptoms are uncommon in TA. The almost complete absence of distal musculoskeletal manifestations in patients with pure TA suggests different mechanisms of disease in PMR and TA, supporting the view of two separate conditions or one common disease in which host susceptibility influences the clinical expression.

Prise en charge du traumatisme cranio-cérébral sévère [Update on the management of severe traumatic brain injury]

Prognosis after severe traumatic brain injury (TBI) is determined by the severity of initial injury and secondary cerebral damage. The main determinants of secondary cerebral damage are brain ischemia and oedema. Traumatic brain injury is a heterogeneous disease. Head CT-scan is essential in evaluating initial type of injury and severity of brain oedema. A standardised approach based on prevention and treatment of secondary cerebral damage is the only effective therapeutic strategy of severe TBI. We review the classification, pathophysiology and treatment of secondary cerebral damage after severe TBI and discuss the management of intracranial hypertension, cerebral perfusion pressure and brain ischemia.

Le point sur l'ergométrie en 2012 dans le diagnostic de la maladie coronarienne.

Background In patients presenting with acute cardiac symptoms, abnormal ECG and raised troponin, myocarditis may be suspected after normal angiography. Aims To analyse cardiac magnetic resonance (CMR) findings in patients with a provisional diagnosis of acute coronary syndrome (ACS) in whom acute myocarditis was subsequently considered more likely. Methods and results 79 patients referred for CMR following an admission with presumed ACS and raised serum troponin in whom no culprit lesion was detected were studied. 13% had unrecognised myocardial infarction and 6% takotsubo cardiomyopathy. The remainder (81%) were diagnosed with myocarditis. Mean age was 45615 years and 70% were male. Left ventricular ejection fraction (EF) was 58610%; myocardial oedema was detected in 58%. A myocarditic pattern of late gadolinium enhancement (LGE) was detected in 92%. Abnormalities were detected more frequently in scans performed within 2 weeks of symptom onset: oedema in 81% vs 11% (p<0.0005), and LGE in 100% vs 76% (p<0.005). In 20 patients with both an acute (<2 weeks) and convalescent scan (>3 weeks), oedema decreased from 84% to 39% (p<0.01) and LGE from 5.6 to 3.0 segments (p¼0.005). Three patients presented with sustained ventricular tachycardia, another died suddenly 4 days after admission and one resuscitated 7 weeks following presentation. All 5 patients had preserved EF. Conclusions Our study emphasises the importance of access to CMR for heart attack centres. If myocarditis is suspected, CMR scanning should be performed within 14 days. Myocarditis should not be regarded as benign, even when EF is preserved.

Bacterial translocation in cirrhotic rats. Its role in the development of spontaneous bacterial peritonitis

Bacterial translocation occurs in ascitic cirrhotic rats, but its association with ascites infection is unknown. The aim of this study was to assess the relation between bacterial translocation and ascites infection in cirrhotic rats. Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4. Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and spleen samples were cultured before death in those cirrhotic rats with less (group A) or more (group B) than 250 polymorphonuclear neutrophils/mm3 in ascitic fluid, as well as in healthy control rats. Histological examination of jejunum, ileum, and caecum was also performed. Bacterial translocation occurred in 45% of ascitic rats (without differences between groups A and B), but in 0% controls (p = 0.01). Bacterial translocation was associated with positive ascitic fluid culture in 60% of the cases. In all of them the same bacterial species was isolated in both mesenteric lymph node and ascitic fluid. Submucosal caecal oedema (100%), ileal lymphangiectasia (41%), and caecal inflammatory infiltrate (41%) occurred in ascitic rats, the last being associated with ascitic fluid positive culture (p = 0.04). These results suggests that bacterial translocation occurs frequently in ascitic cirrhotic rats, and may play a permissive, but not unique, part in a number of ascites infections. Whether histological changes seen in cirrhotic ascitic rats favour bacterial translocation remains to be elucidated.

Premature epiphyseal closure in an adolescent treated by retinoids for acne: An unusual cause of anterior knee pain

Introduction.- Retinoids are effective and widely used for the treatment of severe acne. Their use can be, however, associated with numerous side effects. For example, some rare cases of premature epiphyseal closure were reported.Observation.- A sixteen-year-old soccer player consulted for bilateral progressive anterior knee pain, since two months, evoking a femoro-patellar origin. After physiotherapy, the pain decreases on the right but remained on the left. The history taking brought out the use of isotretinoin for more than 6 months (0.5 mg/kg). Magnetic resonance imaging (MRI) findings showed an irregularity of the growth plate and an important metaphyso-epiphyseal oedema, more marked on the left. The diagnosis of retinoid induced premature ephysieal closure was retained. The treatment was stopped, with a resolution of symptoms within two months. The control MRI of the left knee present persisting small sequelar thumbprint-like growth plate lesion. Eighteen months later, neither limb-length discrepancy nor static disorder was noticed.Discussion.- Premature epiphyseal closure is a rare complication of retinoid treatment of acne. Retinoids induce an invasion of the growth plate by osteoclasts and a decrease in proteoglycans synthesis. The knee seems the most involved joint. The clinical presentation is aspecific, sometimes lightly symptomatic. A careful pharmacological history and an appropriate imaging are necessary. MRI is now the gold standard. It shows an irregularity of the growth plate with an oedema on both sides. In chronic phase, a thumbprint-like image may persist. The symptoms resolution arises in few weeks after the treatment interruption. A single case of static disorder was reported until now. The small size of the growth plate interruptions, insufficient to lead to a growth disorder if the medicament is stopped early enough, explains probably it. This complication being rare, a radiological follow-up of the young patients treated by retinoids is not proposed.

Assessment of cardiac ischaemia and viability: role of cardiovascular magnetic resonance.

Over the past years, cardiovascular magnetic resonance (CMR) has proven its efficacy in large clinical trials, and consequently, the assessment of function, viability, and ischaemia by CMR is now an integrated part of the diagnostic armamentarium in cardiology. By combining these CMR applications, coronary artery disease (CAD) can be detected in its early stages and this allows for interventions with the goal to reduce complications of CAD such as infarcts and subsequently chronic heart failure (CHF). As the CMR examinations are robust and reproducible and do not expose patients to radiation, they are ideally suited for repetitive studies without harm to the patients. Since CAD is a chronic disease, the option to monitor CAD regularly by CMR over many decades is highly valuable. Cardiovascular magnetic resonance also progressed recently in the setting of acute coronary syndromes. In this situation, CMR allows for important differential diagnoses. Cardiovascular magnetic resonance also delineates precisely the different tissue components in acute myocardial infarction such as necrosis, microvascular obstruction (MVO), haemorrhage, and oedema, i.e. area at risk. With these features, CMR might also become the preferred tool to investigate novel treatment strategies in clinical research. Finally, in CHF patients, the versatility of CMR to assess function, flow, perfusion, and viability and to characterize tissue is helpful to narrow the differential diagnosis and to monitor treatment.

Standardizing the diagnosis of inhalation injury using a descriptive score based on mucosal injury criteria.

INTRODUCTION: Inhalation injury is an important determinant of outcome in patients with major burns. However the diagnostic criteria remain imprecise, preventing objective comparisons of published data. The aims were to evaluate the utility of an inhalation score based on mucosal injury, while assessing separately the oro-pharyngeal sphere (ENT) and tracheobronchial tree (TB) in patients admitted to the ICU with a suspicion of inhalation injury. METHODS: Prospective observational study in 100 patients admitted with suspicion of inhalation injury among 168 consecutive burn admissions to the ICU of a university hospital. Inclusion criteria, endoscopic airway assessment during the first hours. ENT/TB lesion grading was 1: oedema, hyperemia, hypersecretion, 2: bullous mucosal detachment, erosion, exudates, 3: profound ulcers, necrosis. RESULTS: Of the 100 patients (age 42±17 years, burns 23±19%BSA), 79 presented an ENT inhalation injury ≥ENT1 (soot present in 24%): 36 had a tracheobronchial extension, 33 having a grade ≥TB1. Burned vibrissae: 10 patients "without" suffered ENT injury, while 6 patients "with" had no further lesions. Length of mechanical ventilation was strongly associated with the first 24 hrs' fluid resuscitation volume (p<0.0001) and the presence of inhalation injury (p=0.03), while the ICU length of stay was correlated with the %BSA. Soot was associated with prolonged mechanical ventilation (p=0.0115). There was no extubation failure. CONCLUSIONS: The developed inhalation score was simple to use, providing a unified language, and drawing attention to upper airway involvement. Burned vibrissae and suspected history proved to be insufficient diagnostic criteria. Further studies are required to validate the score in a larger population.

Pulmonary thrombembolism as cause of death on unenhanced postmortem 3T MRI.

OBJECTIVES: To investigate unenhanced postmortem 3-T MR imaging (pmMRI) for the detection of pulmonary thrombembolism (PTE) as cause of death. METHODS: In eight forensic cases dying from a possible cardiac cause but with homogeneous myocardium at cardiac pmMRI, additional T2w imaging of the pulmonary artery was performed before forensic autopsy. Imaging was carried out on a 3-T MR system in the axial and main pulmonary artery adapted oblique orientation in situ. In three cases axial T2w pmMRI of the lower legs was added. Validation of imaging findings was performed during forensic autopsy. RESULTS: All eight cases showed homogeneous material of intermediate signal intensity within the main pulmonary artery and/or pulmonary artery branches. Autopsy confirmed the MR findings as pulmonary artery thrombembolism. At lower leg imaging unilateral dilated veins and subcutaneous oedema with or without homogeneous material of intermediate signal intensity within the popliteal vein were found. CONCLUSIONS: Unenhanced pmMRI demonstrates pulmonary thrombembolism in situ. PmMR may serve as an alternative to clinical autopsy, especially when consent cannot be obtained. KEY POINTS: ? Postmortem MRI (pmMRI) provides an alternative to clinical autopsy ? Fatal pulmonary thrombembolism (PTE) can now be diagnosed using postmortem MRI (pmMRI). ? Special attention has to be drawn to the differentiation of postmortem clots.

Lower limb high arterial flow induced by tenofovir and emtricitabine treatment.

Here, we describe a case of an HIV-infected patient with right lower limb oedema that appeared after initiation of tenofovir and emtricitabine treatment. The patient was fully investigated by serial heart and vessel echo-Doppler examination. Oedema of the lower limb was attributed to a transient drug-induced fivefold increase in peripheral artery flow, which was induced by a reduction in peripheral arterial resistance. The possible mechanisms of disease are discussed.

Syndromic algorithms for detection of gambiense human african trypanosomiasis in South Sudan.

BACKGROUND: Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. METHODOLOGY/PRINCIPAL FINDINGS: Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9-92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4-8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. CONCLUSIONS/SIGNIFICANCE: In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere.

Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption.

Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na(+) channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells. Using a rat in situ lung liquid clearance assay, CNG channel activation with 1 mM 8Br-cGMP resulted in an approximate 1.8-fold stimulation of lung liquid absorption. There was no stimulation by 8Br-cGMP when applied in the presence of either 100 μM L: -cis-diltiazem or 100 nM pseudechetoxin (PsTx), a specific inhibitor of CNGA1 channels. Channel specificity of PsTx and amiloride was confirmed by patch clamp experiments showing that CNGA1 channels in HEK 293 cells were not inhibited by 100 μM amiloride and that recombinant αβγ-ENaC were not inhibited by 100 nM PsTx. Importantly, 8Br-cGMP stimulated lung liquid absorption in situ, even in the presence of 50 μM amiloride. Furthermore, neither L: -cis-diltiazem nor PsTx affected the β(2)-adrenoceptor agonist-stimulated lung liquid absorption, but, as expected, amiloride completely ablated it. Thus, transport through alveolar CNGA1 channels, located in type I cells, underlies the amiloride-insensitive component of lung liquid reabsorption. Furthermore, our in situ data highlight the potential of CNGA1 as a novel therapeutic target for the treatment of diseases characterised by lung liquid overload.

Brain multimodality monitoring: an update.

PURPOSE OF REVIEW: An important goal of neurocritical care is the management of secondary brain injury (SBI), that is pathological events occurring after primary insult that add further burden to outcome. Brain oedema, cerebral ischemia, energy dysfunction, seizures and systemic insults are the main components of SBI. We here review recent data showing the clinical utility of brain multimodality monitoring (BMM) for the management of SBI. RECENT FINDINGS: Despite being recommended by international guidelines, standard intracranial pressure (ICP) monitoring may be insufficient to detect all episodes of SBI. ICP monitoring, combined with brain oxygen (PbtO(2)), cerebral microdialysis and regional cerebral blood flow, might help to target therapy (e.g. management of cerebral perfusion pressure, blood transfusion, glucose control) to patient-specific pathophysiology. Physiological parameters derived from BMM, including PbtO(2) and microdialysis lactate/pyruvate ratio, correlate with outcome and have recently been incorporated into neurocritical care guidelines. Advanced intracranial devices can be complemented by quantitative electroencephalography to monitor changes of brain function and nonconvulsive seizures. SUMMARY: BMM offers an on-line comprehensive scrutiny of the injured brain and is increasingly used for the management of SBI. Integration of monitored data using new informatics tools may help optimize therapy of brain-injured patients and quality of care.

Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy.

AIMS/HYPOTHESIS: Disruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo. METHODS: ARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase (MEK, also known as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato-retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE. RESULTS: In vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasm translocation of junction proteins. CONCLUSIONS/INTERPRETATION: Our results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.