Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Unravelling the mysteries of sudden unexpected death in epilepsy. / Desentrañando los misterios de la muerte súbita en epilepsia.

INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of premature death in epileptic patients. Most SUDEP events occur at night and frequently go unnoticed; the exact pathophysiological mechanisms of this phenomenon therefore remain undetermined. Nevertheless, most cases of SUDEP are attributed to an infrequent yet extremely severe complication of epileptic seizures. DEVELOPMENT: We conducted a systematic literature search on PubMed. Our review article summarises scientific evidence on the classification, pathophysiological mechanisms, risk factors, biomarkers, and prevention of SUDEP. Likewise, we propose new lines of research and critically analyse findings that are relevant to clinical practice. CONCLUSIONS: Current knowledge suggests that SUDEP is a heterogeneous phenomenon caused by multiple factors. In most cases, however, SUDEP is thought to be due to postictal cardiorespiratory failure triggered by generalised tonic-clonic seizures and ultimately leading to cardiac arrest. The underlying pathophysiological mechanism involves multiple factors, ranging from genetic predisposition to environmental factors. Risk of SUDEP is higher in young adults with uncontrolled generalised tonic-clonic seizures. However, patients apparently at lower risk may also experience SUDEP. Current research focuses on identifying genetic and neuroimaging biomarkers that may help determine which patients are at high risk for SUDEP. Antiepileptic treatment is the only preventive measure proven effective to date. Night-time monitoring together with early resuscitation may reduce the risk of SUDEP.

Brain activity sustaining the modulation of pain by empathetic comments.

Empathetic verbal feedback from others has been shown to alleviate the intensity of experimental pain. To investigate the brain changes associated with this effect, we conducted 3T-fMRI measurements in 30 healthy subjects who received painful thermal stimuli on their left hand while overhearing empathetic, neutral or unempathetic comments, supposedly made by experimenters, via headsets. Only the empathetic comments significantly reduced pain intensity ratings. A whole-brain BOLD analysis revealed that both Empathetic and Unempathetic conditions significantly increased the activation of the right anterior insular and posterior parietal cortices to pain stimuli, while activations in the posterior cingulate cortex and precuneus (PCC/Prec) were significantly stronger during Empathetic compared to Unempathetic condition. BOLD activity increased in the DLPFC in the Empathetic condition and decreased in the PCC/Prec and vmPFC in the Unempathetic condition. In the Empathetic condition only, functional connectivity increased significantly between the vmPFC and the insular cortex. These results suggest that modulation of pain perception by empathetic feedback involves a set of high-order brain regions associated with autobiographical memories and self-awareness, and relies on interactions between such supra-modal structures and key nodes of the pain system.

Haptic simulation of tissue tearing during surgery.

We present a method for the real-time, interactive simulation of tissue tearing during laparoscopic surgery. The method is designed to work at haptic feedback rates (ie, around 1 kHz). Tissue tearing is simulated under the general framework of continuum damage mechanics. The problem is stated as a general, multidimensional parametric problem, which is solved by means of proper generalized decomposition methods. One of the main novelties is the reduction of history-dependent problems, such as damage mechanics, by resorting to an approach in which a reduced-order field of initial damage values is considered as a parameter of the formulation. We focus on the laparoscopic cholecystectomy procedure as a general example of the performance of the method.

Strong sesquiterpene emissions from Amazonian soils.

The Amazon rainforest is the world's largest source of reactive volatile isoprenoids to the atmosphere. It is generally assumed that these emissions are products of photosynthetically driven secondary metabolism and released from the rainforest canopy from where they influence the oxidative capacity of the atmosphere. However, recent measurements indicate that further sources of volatiles are present. Here we show that soil microorganisms are a strong, unaccounted source of highly reactive and previously unreported sesquiterpenes (C15H24; SQT). The emission rate and chemical speciation of soil SQTs were determined as a function of soil moisture, oxygen, and rRNA transcript abundance in the laboratory. Based on these results, a model was developed to predict soil-atmosphere SQT fluxes. It was found SQT emissions from a Terra Firme soil in the dry season were in comparable magnitude to current global model canopy emissions, establishing an important ecological connection between soil microbes and atmospherically relevant SQTs.

Selective antitumoural action of pressurized mango leaf extracts against minimally and highly invasive breast cancer.

Mango leaf tea has been traditionally used by different cultures to reduce inflammation in the body. There is evidence that chronic inflammation increases the risk of cancer. This study investigates the antitumoural effects of pressurized mango leaf extracts on minimally (MCF7) and highly invasive (MDA-MB-231) breast cancer cells as well as on non-tumourigenic cells (MCF10). Extracts showed protective properties against oxidation and cytotoxic effects against breast cancer cell lines, causing minor damage to non-carcinogenic cells. Nonetheless, some selective activity, depending on hormone receptor status, was observed. This was possibly related to the presence of minor compounds. Extracts with high levels of gallotannins showed cytotoxic action against MCF7 cells, while those which had methyl gallate and homomangiferin as common components were more effective against MDA-MB-231 cells. Therefore, the cytotoxic effect of mango leaf extracts might be attributed to the synergistic effect of different polyphenols and not just to mangiferin on its own as the predominant compound in mango leaves.

[Partial blockage of the inferior vena cava. Results apropos of 110 cases]. / Interruption partielle de la veine cave inférieure. Résultats à propos de 110 cas.

Rheoplethysmography with occlusion (RPO) is useful in the diagnosis of deep venous thrombosis. Bilateral phlebography with cavography performed afterwards as an emergency gives information as to the embolic potential of the thrombosis and orientates treatment towards surgical interruption of the inferior vena cava. In the C.H.U. at Grenoble 83 clips, 25 umbrella filters and 2 ligatures were placed on the inferior vena cava from 1974 to 1977. Prevention of pulmonary emboli was achieved in 99% cases with lower limb embolic foci. Follow-up by RPO and isotopic phlebography showed that the course of venous thrombosis of the lower limbs seemed to be unchanged by partial interruption of the inferior vena cava, provided that elastic stockings and adequate anticoagulant therapy adapted to venous haemodynamics are used.

[The respective roles of surgery and physiotherapy at the stage of intermittent claudication (author's transl)]. / Place respective de la chirurgie et de la rééducation au stade de la claudication intermittente.

The choice between rehabilitation and surgery must be made for each case after attentive consideration, and depends largely on the experience and the means of each therapeut. The proximal level represents the best field for surgery, above all in the case of instable or embolized atheroma. At medial level, both therapeutics may be discussed. At distal level, surgery is seldom indicated apart from lumbar sympathectomy. Practically, rehabilitation is most often indicated alone or associated with surgery.

[Results of the physiotherapy of arterial disease at the stage of intermittent claudication by programmed efforts training (author's transl)]. / Résultats de la rééducation des artériopathies au stade de la claudication intermittente, par entrainement programmé à l'effort.

The results of treatment of intermittent claudication by a physical training programmed during 30 to 45 days in a rehabilitation center, are assessed on 148 patients of whom 105 have followed a full program at first (32 cases) or after surgery (73 cases). Ankle pressures are not altered. Irrigraphy shows a significant increase of 10 to 14% of the proximal indexes. Walking distance is greatly increased. 13 patients had a walking distance of about 900 m at the beginning and 31 patients at the end of the course ("functional remission"). Out of 105 patients, 98 showed improvement, 4 remained unchanged and 3 slightly worsened. The appreciation of his own progress is a strong psychological stimulation for the patient, this helping him to accent his illness, and to fight the corrigible risk factors of atherosclerosis, all significantly reduced. The interpretation of the results is discussed and shows the importance of non-hemodynamic factors in the achieved progress. The programmed exercise training is one of the best non surgical symptomatic treatments of intermittent claudication.

[Drug abuse in pregnancy and neonatal morbidity: epidemiologic changes in the last ten years]. / Consumo de drogas durante el embarazo y morbilidad neonatal: cambios epidemiológicos en los últimos 10 años.

BACKGROUND: In the last few years, patterns of drug abuse have varied. This may have changed the problems presented by the infants of drug-abusing mothers. OBJECTIVES: To determine the incidence of prenatal drug-exposure in neonates in our health area in the last decade, to analyze possible changes in the drugs consumed, routes of administration and the infectious diseases affecting drug-abusing mothers, and to study possible changes in the clinical features presented by their offspring. PATIENTS AND METHODS: An observational, descriptive, retrospective study of all the infants born to drug-abusing mothers from January 1, 1992 to December 31, 2001 was performed. The series was analyzed and the periods 1992-1996 and 1997-2001 were compared. RESULTS: The mean incidence was 7.5 cases per 1000 live-born infants (8.7 in 1992-1996 and 6.3 in 1997-2001). Mothers in the second half of the study were less likely to use heroin and the intravenous route and were more likely to use methadone and cocaine than mothers in the 1997-2001 period. Hepatitis C virus infection and instrumental delivery were more frequent in the 1997-2001 period. No differences were found in neonates born in either period. Birthweight was less than 2500 g in 40 % and was low for gestational age in 20 %. Preterm deliveries were performed in 24 %. Congenital malformations were found in 6 %, neonatal withdrawal syndrome in 79 %, human immunodeficiency virus infection in 2 %, and hepatitic C virus infection in 3 %. Four percent were given in adoption. CONCLUSIONS: Maternal drug abuse patterns changed in the ten years under study, but outcome in their offspring showed no differences. Drug abuse by pregnant women is linked to a high rate of low birthweight, prematurity, neonatal withdrawal syndrome, vertical infection by human immunodeficiency virus and hepatitis C virus, as well as to social and family problems.

[Transcranial Doppler velocimeter in pregnant and later normotensive puerperal women]. / Velocimetría Doppler transcraneal en gestantes y posteriormente puérperas normotensas.

INTRODUCTION: The physiological changes that take place in blood flow in the brain during pregnancy and the puerperium are still only poorly understood. The harmlessness of transcranial Doppler (TCD) makes it a suitable method of study. AIMS: The purpose of this study was to determine the TCD velocimeter reading at the end of pregnancy and in the early puerperium of healthy expectant mothers. SUBJECTS AND METHODS: TCD was used to perform a bilateral study of the anterior (ACA), middle (MCA) and posterior cerebral arteries (PCA). Arterial blood pressure and haematocrit were also measured. Mean velocity (MV), the pulsatility index (PI), mean arterial blood pressure and haematocrit were employed as variables in the statistical analysis. Results from 44 normotensive pregnant women in the latter stages of gestation (week 33 to term) were compared with those of a control group made up of 58 women of a similar age, who were normotensive and not pregnant. The study was repeated in the group of pregnant women during the early puerperium (the first five days after labour) and the two different results were compared. RESULTS: Age and MAP were similar in the gestating and non-gestating groups. Haematocrit was significantly lower in the former (p < 0.001) and MV were significantly lower in the pregnant women in all the arteries (p < 0.001), whereas the PI were also significantly lower in four of the six territories that were studied (p < 0.005). During the puerperium, a significant rise in MV was observed in all the arteries (p < 0.001) and the PI increased in three of them (p < 0.05). In this phase, the mean arterial pressure rose (p < 0.05), although haematocrit levels dropped (p < 0.001). CONCLUSIONS: The low MV and PI seen at the end of pregnancy are compatible with cerebral vasodilatation. MV increase during the early puerperium and is probably linked to a relative hyperperfusion.

[Anomalies in brain haemodynamics in pre-eclamptic expectant mothers]. / Anomalías hemodinámicas cerebrales en gestantes con preeclampsia.

INTRODUCTION: Transcranial Doppler (TCD) is being used more and more frequently in the study of brain haemodynamics in pre-eclampsia/eclampsia. It has received less attention in the puerperium of these patients. AIMS: The aim of our study was to compare pre-eclamptic (PE) and normotensive (NT) patients at the end of gestation, using a Doppler velocimeter, and also to compare the results from PE women in two consecutive periods of time: at the end of gestation and in early puerperium (EP). PATIENTS AND METHODS: TCD was performed with bilateral evaluation of the anterior, middle and posterior cerebral arteries (ACA, MCA and PCA, respectively). Average speed (AS) and the pulsatility index (PI) were used as Doppler parameters. Arterial blood pressure (BP) and haematocrit were also measured. The AS, PI, average BP (ABP) and haematocrit were used as variables in the statistical analysis. At the end of gestation (33 weeks to full term) we compared the average values of these variables in PE (n=38) against those of NT (n=44). We also compared the results obtained for PE (n=30) in two consecutive periods: at the end of gestation and EP (the first five days following childbirth). RESULTS: At the end of gestation, AS were significantly higher in the PE than in the NT in all the arteries that were examined. The ABP was higher in the first group but there was no significant correlation between ABP and AS. PI were lower in the first group, with statistical signification in four of the six arteries. The AS rose significantly in the EP of the PE women, in spite of the existence of a drop in the ABP. Conversely, the PI remained unaltered. CONCLUSIONS: A pattern of high AS and low PI was found in PE women at the end of gestation and may be due to a primary failure of the brain's capacity to regulate itself. Anomalies in the TCD increased in the EP, despite a drop in the ABP, and this could account for the predominance of the neurological symptoms that are reported in the later forms of the syndrome.

[Association of carpal tunnel syndrome and tuberculosis]. / Asociación de síndrome del túnel del carpo y tuberculosis.

Extrapulmonary tuberculosis, and especially articular, is less frequent than their pulmonary form. We report a 59 year-old men that requests medical attention for suggestive symptoms of carpal tunnel syndrome, of which is operated, being demonstrated in the carpo a granulomatous tissue including the median nerve suggestive of sarcoidosis or tuberculosis. In sputum the presence of Micobacterium tuberculosis was demonstrated. The respiratory symptoms of pulmonary tuberculosis were for the patient less excellent symptoms in relation to those produced by compression of the median nerve. The relationship between the tuberculosis and the carpal tunnel syndrome is demonstrated.

[Report of 39 traumatic and iatrogenic lesions of the extra-cranial carotid artery (author's transl)]. / Bilan de 39 lésions traumatiques et iatrogènes de l'axe carotidien extra-crânien.

The authors present 39 carotid lesions from various and sometimes unusual origins: ski accident, cervical irradiation. The lesions have a preferential topography according to etiology: internal carotid for blunt trauma and arteriographic lesions, common carotid for penetrating injuries, common and bifurcation for X-ray lesions. Arteriography and surgical exploration confirm this notion. Macroscopic lesions don't always accord to the classical aspect: thus, only one intimal lesion has been found in blunt trauma. Symptomatology is orientated by etiology: neurological symptoms in blunt trauma and X-ray lesions, vascular symptoms in penetrating injuries. The diagnosis has sometimes been made at a distance from the initial accident and in unusual circumstances, mainly in blunt trauma. The treatment has been a surgical one except for usual countra-indications. The results are favourable on young subjects and above all for particular lesions such as penetrating injuries and X-ray lesions. Lastly, the authors insist on the post-operative evolutivity which is often misunderstood, and on the interest of an angiographic control.

[Our experience of mesenterico-caval anastomosis with prosthetic interposition (report of 30 cases) (author's transl)]. / Notre expérience des anastomoses mésentérico-caves avec interposition prothétique 30 observations.

The authors report their experience of 30 mesenterico-caval anastomoses with prosthetic interposition according to Drapanas's technic. From the point of view of the operative indications, they have never carried out a prophylactic operation. In 19 cases, the operation was carried out as an emergency for inefficacy of the medical treatment. In 11 cases, a cold operation was performed, either to prevent eventual hemorrhagic recurrence (8 cases) or for chronic ascites (3 cases). Half the patients belonged to group C with a poor surgical risk. There was only one case of post-operative thrombosis due to a technical error, and two cases of secondary thrombosis. The overall mortality was 60%. But when the patient was of group A or B the mortality was only 20%. The survivors are those in whom the operation was rapid and the blood loss minimal. To conclude, the authors the necessity of better selection of patients, and rapid operation without bleeding.

[Isotopic angiography. Method of early post-operative control in peripheral vascular surgery. Report of 200 cases (author's transl)]. / L'angiographie isotopique. Méthode de contrôle post-opératoire précoce en chirurgie vasculaire périphérique. A propos de 200 cas.

The authors report their experience of isotopic angiography as means of post-operative control in peripheral vascular surgery in 200 cases. This investigation is very simple and non-traumatic. It gives very satisfactory morphological information and a good idea of the hemodynamics of the acts carried out.

[Assessment of 81 traumatic vascular lesions of the limbs (author's transl)]. / Bilan de 81 lésions vasculaires traumatiques des membres.

A review of 81 cases of vascular trauma of the limbs in 75 patients treated at the Grenoble University Hospital from 1967 to 1975 confirms the classical etiological, pathological and clinical findings. Analysis of the results led us to emphasise the necessity of bone and vascular repair which should be complete from the start, verified by peroperative radiological control. The application of now well-established rules to the treatment of vascular trauma should lead to a better prognosis in the case of popliteal lesions (76 p. cent of good results out of 17 revascularisations).

[Hypothermia risk factors in the very low weight newborn and associated morbidity and mortality in a neonatal care unit]. / Factores de riesgo de hipotermia al ingreso en el recién nacido de muy bajo peso y morbimortalidad asociada.

INTRODUCTION: Heat loss in the newborn after delivery could interfere with post-natal adaptation due to metabolic and hemodynamic instability. Associated perinatal factors and their relationship with morbidity and mortality during the neonatal period have not been systematically studied in our unit. OBJECTIVES: To determine the temperature of very low birth weight (VLBW) infants on admission to our NICU, and to determine the associated perinatal variables, and the association of temperature with morbidity and mortality. PATIENTS AND METHODS: Infants born in our maternity from January 2006 to November 2012, with birth weights (BW) 401 g to 1,499 g and/or less than 30 weeks gestational age, were included. A multivariate analysis was performed using the perinatal variables and the temperature on admission, as well as a logistic regression between these and the morbidity-mortality variables, in order to detect any independent associations. RESULTS: A total of 635 infants were included, with a mean (± SD) birth weight and gestational age of 1,137.6 ± 257.6g, and 29.5 ± 2.0 weeks, respectively. The mean admission temperature was 35.8 ± 0.6°C (range: 33.0-37.8°C). The proportion of infants with a temperature < 36°C was 44.4%. Independently associated perinatal variables were chorioamnionitis, birth weight, vaginal delivery, and advanced cardiopulmonary resuscitation (CPR). Admission hypothermia was associated with severe intraventricular haemorrhage (IVH) (grades 3 and 4) (OR: 0.377; 95% CI: 0.221-0.643; P<.001), and mortality (OR: 0.329; 95% CI: 0.208-0.519; P=.012). CONCLUSIONS: Hypothermia on admission is frequent among our VLBW infants. Birth weight, vaginal delivery, and advanced CPR were the principal variables associated with hypothermia. A low temperature on admission was related to an increased risk of IVH and mortality.

Artificially-induced organelles are optimal targets for optical trapping experiments in living cells.

Optical trapping supplies information on the structural, kinetic or rheological properties of inner constituents of the cell. However, the application of significant forces to intracellular objects is notoriously difficult due to a combination of factors, such as the small difference between the refractive indices of the target structures and the cytoplasm. Here we discuss the possibility of artificially inducing the formation of spherical organelles in the endoplasmic reticulum, which would contain densely packed engineered proteins, to be used as optimized targets for optical trapping experiments. The high index of refraction and large size of our organelles provide a firm grip for optical trapping and thereby allow us to exert large forces easily within safe irradiation limits. This has clear advantages over alternative probes, such as subcellular organelles or internalized synthetic beads.