Etiological assessment of status epilepticus.

Status epilepticus (SE) is a potentially serious condition that can affect vital and functional prognosis and requires urgent treatment. Etiology is a determining factor in the patient's functional outcome and in almost half of all cases justifies specific treatment to stop progression. Therefore, identifying and addressing the cause of SE is a key priority in SE management. However, the etiology can be difficult to identify among acute and remote causes, which can also be multiple and interrelated. The most common etiologies are the discontinuation of antiepileptic medication in patients with a prior history of epilepsy, and acute brain aggression in cases of new onset SE (cerebrovascular pathologies are the most common). The list of remaining possible etiologies includes heterogeneous pathological contexts. Refractory SE and especially New-Onset Refractory Status Epilepticus (NORSE) lead to an extension of the etiological assessment in the search for encephalitis of autoimmune or infectious origin in adults and in children, as well as a genetic pathology in children in particular. This is an overview of current knowledge of SE etiologies and a pragmatic approach for carrying out an etiological assessment based on the following steps: - Which etiological orientation is identified according to the field and clinical presentation?; - Which etiologies to look for in an inaugural SE?; - Which first-line assessment should be carried out? The place of the biological, EEG and imaging assessment is discussed; - Which etiologies to look for in case of refractory SE?

Combined spiroergometry and 31 P-MRS of human calf muscle during high-intensity exercise.

Simultaneous measurements of pulmonary oxygen consumption (VO2 ), carbon dioxide exhalation (VCO2 ) and phosphorus magnetic resonance spectroscopy (31 P-MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO2 and VCO2 whilst simultaneously performing 31 P-MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR-compatible pedal ergometer. The use of a non-magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO2 and VCO2 . Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO2 = 1.05 ± 0.31 L/min; VCO2 = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τPCr fast and pH; R2 = 0.73, p < 0.005) and global respiration (τPCr fast and VO2 ; R2  = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.

Low-molecular-weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study.

The management of anticoagulation in pregnant women with mechanical heart valves is complex. The maternal and fetal outcomes of 32 pregnancies in 15 women on three different anticoagulation regimens were compared. Anticoagulation with low-molecular-weight heparin (n=4), warfarin (n=22) and combination therapy (n=6) resulted in adverse maternal events in four (100%), three (50%) and three (14%) women, and resulted in fetal losses in one (25%), 17(77%) and three (50%) pregnancies, respectively. Whereas the rate of fetal loss in the warfarin group was high, all women in the LMWH and half of those in the combination group had serious adverse maternal events, including valve thrombosis, maternal death and postpartum haemorrhage.

Differential organization of open field behavior in mice following acute or chronic simulated GCR exposure.

Astronauts undertaking deep space travel will receive chronic exposure to the mixed spectrum of particles that comprise Galactic Cosmic Radiation (GCR). Exposure to the different charged particles of varied fluence and energy that characterize GCR may impact neural systems that support performance on mission critical tasks. Indeed, growing evidence derived from years of terrestrial-based simulations of the space radiation environment using rodents has indicated that a variety of exposure scenarios can result in significant and long-lasting decrements to CNS functionality. Many of the behavioral tasks used to quantify radiation effects on the CNS depend on neural systems that support maintaining spatial orientation and organization of rodent open field behavior. The current study examined the effects of acute or chronic exposure to simulated GCR on the organization of open field behavior under conditions with varied access to environmental cues in male and female C57BL/6 J mice. In general, groups exhibited similar organization of open field behavior under dark and light conditions. Two exceptions were noted: the acute exposure group exhibited significantly slower and more circuitous homeward progressions relative to the chronic group under light conditions. These results demonstrate the potential of open field behavior organization to discriminate between the effects of select GCR exposure paradigms.

Amiodarone-induced Ataxia: A Case Report of Severe Cerebellar Dysfunction and Review of Literature.

Amiodarone therapy is widely prescribed in patients with atrial fibrillation. The higher prevalence of this arrhythmic heart disease, and the specific age-related issues of homeostasis in the elderly population, makes this group particularly exposed to its adverse effects. Among the many described side-effects, neurological impairments are the less documented and studied. Because amiodarone can be responsible for severe complications, as described in the case below, a close monitoring is necessary throughout its prescription. Awareness should be brought on the amiodarone-induced neurological side-effects as they could be overlooked.

Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: wheat breeding may have contributed to increased prevalence of celiac disease.

Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of 'low CD toxic' as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD.

Climate-induced variability in South Atlantic wave direction over the past three millennia.

Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~ 3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.

Distribution of anionic sites on the oviduct ciliary membrane.

Polycationic ferritin (PCF) was used as a visual probe for anionic sites on the oviduct ciliary membrane. The binding of PCF to ciliary membranes was dependent on the concentration of the probe in the incubation media. At low concentrations (0.08-0.16 mg/ml), PCF was bound exclusively to the tip of the cilium whereas at higher concentrations (0.32-0.64 mg/ml), ferritin was located at the tip and at the base around the transition region, with occasional scattered clumps on the remainder of the membrane. The base and tip binding was fount to be associated with special surface modifications of the membrane in these regions. At the tip, PCF was bound to a filamentous glycocalyx termed the ciliary crown. Base binding was associated with a system of five to six 140-A high ridges, each of which encircled the membrane of the transition region. The ridges were equally spaced (approxamately 245 A spacing) along the length of the transition region. Since pretreatment of oviduct with either neuraminidase or protease blocked the binding of the probe, the PCF-binding sites appear to be negatively charged glycoproteins or mucopolysaccharides.

Sleep disorders and their impacts on healthy, dependent, and frail older adults.

BACKGROUND: Sleep disorders differ widely in the heterogeneous older adult population. Older adults can be classified into three groups based upon their overall level of disability: healthy, dependent, and frail. Frailty is an emerging concept that denotes older persons at increased risk for poor outcomes. OBJECTIVE: The aim of this consensus review is to describe the sleep disorders observed in healthy and dependent older adults and to discuss the potential sleep disorders associated with frailty as well as their potential consequences on this weakened population. METHODS: A review task force was created including neurologists, geriatricians, sleep specialists and geriatric psychiatrists to discuss age related sleep disorders depending on the three categories of older adults. All published studies on sleep in older adults on Ovid Medline were reviewed and 106 articles were selected for the purpose of this consensus. RESULTS: Many healthy older adults have complains about their sleep such as waking not rested and too early, trouble falling asleep, daytime napping, and multiple nocturnal awakenings. Sleep architecture is modified by age with an increased percentage of time spent in stage one and a decreased percentage spent in stages three and four. Insomnia is frequent and its mechanisms include painful medical conditions, psychological distress, loss of physical activity and iatrogenic influences. Treatments are also involved in older adults' somnolence. The prevalence of primary sleep disorders such as restless legs syndrome, periodic limb movements and sleep disordered breathing increases with age. Potential outcomes relevant to these sleep disorders in old age include mortality, cardiovascular and neurobehavioral co-morbidities. Sleep in dependent older adults such as patients with Alzheimer Disease (AD) is disturbed. The sleep patterns observed in these patients are often similar to those observed in non-demented elderly but alterations are more severe. Nocturnal sleep disruption and daytime sleepiness are the main problems. They are the results of Sleep/wake circadian rhythm disorders, environmental, psychological and iatrogenic factors. They are worsened by other sleep disorders such as sleep disordered breathing. Sleep in frail older adults per se has not yet been formally studied but four axes of investigation should be considered: i) sleep architecture abnormalities, ii) insomnia iii) restless legs syndrome (RLS), iv) sleep disordered breathing. CONCLUSION: Our knowledge in the field of sleep disorders in older adults has increased in recent years, yet some groups within this heterogeneous population, such as frail older adults, remain to be more thoroughly studied and characterized.

Hospitalization Drug Regimen Changes in Geriatric Patients and Adherence to Modifications by General Practitioners in Primary Care.

OBJECTIVES: To evaluate the overall rate of adherence by general practitioners (GPs) to treatment modifications suggested at discharge from hospital and to assess the way communication between secondary and primary care could be improved. DESIGN: Observational prospective cohort study. SETTING: Patients hospitalized from the emergency department to the acute geriatric care unit of a university hospital. PARTICIPANTS: 206 subjects with a mean age of 85 years. MEASUREMENTS: Changes in drug regimen undertaken during hospitalization were collected with the associated justifications. Adherence at one month by GPs to treatment modifications was assessed as well as modifications implemented in primary care with their rationale in case of non-adherence. Community pharmacists' and GPs' opinions about quality of communication and information transfer at hospital-general practice interface were investigated. RESULTS: 5.5 ± 2.8 drug regimen changes were done per patient during hospitalization. The rate of adherence by GPs to treatment modifications suggested at discharge from hospital was 83%. In most cases, non-adherence by GPs to treatment modifications done during hospitalization was due to dosage adjustments, symptoms resolution but also worsening of symptoms. The last of which was particularly true for psychotropic drugs. All GPs received their patients' discharge letters but the timely dissemination still needs to be improved. Only 6.6% of community pharmacists were informed of treatment modifications done during their patients' hospitalization. CONCLUSION: Our findings showed a successful rate of adherence by GPs to treatment modifications suggested at discharge from hospital, due to the fact that optimization was done in a collaborative way between geriatricians and hospital pharmacists and that justifications for drug regimen changes were systematically provided in discharge letters. Communication processes at the interface between secondary and primary care, particularly with community pharmacists, must be strengthened to improve seamless care.

[Prudent use of antimicrobial prophylaxis : Prevention of increasing antibiotic resistance]. / Sinnvolle Antibiotikaprophylaxe in der Urologie : Vermeidung von zunehmender Resistenzentwicklung.

BACKGROUND: The use of peri-operative antimicrobial prophylaxis during urological procedures to prevent postoperative complications is very common. OBJECTIVES: What kind of recommendations for reasonable use of peri-operative antimicrobial prophylaxis during urological procedures to prevent increasing antibiotic resistance and postoperative complications exist? METHODS: Review of evidence-based recommendations from literature and current Guidelines of the EAU. RESULTS: For urological procedures there are evidenced-based recommendations for using antimicrobial prophylaxis, although the evidence is not always sufficiently high. For endourological procedures it is recommended to use Cephalosporines group 2 (or 3), Aminopenicillin/Beta-lactamase inhibitor or Cotrimoxazole. For transrectal core biopsy of the prostate, depending on the risk, Fluoroquinolones, Cotrimoxazole or targeted prophylaxis are recommended. For laparoscopic or open procedures, partly optional, Cephalosporines group 2 (or 3), Aminopenicillin/Beta-lactamase inhibitor or Cotrimoxazole and for a cystectomy with opening of the intestinal tract Cephalosporines group 2 or an Aminopenicillin/Beta-lactamase inhibitor, together with Metronidazole are recommended. CONCLUSIONS: Using prudent peri-operative antimicrobial prophylaxis patient surgical risk factors as well as the expected spectrum of pathogens and the local resistance profile should be considered. Perioperative antibiotic prophylaxis on the one hand aims at preventing postoperative infections, and on the other hand plays an important role in the total antibiotic consumption. It is therefore a pivotal aspect of "Antimicrobial Stewardship" strategies in the health-care system.

Pure and Oxidized Copper Materials as Potential Antimicrobial Surfaces for Spaceflight Activities.

Microbial biofilms can lead to persistent infections and degrade a variety of materials, and they are notorious for their persistence and resistance to eradication. During long-duration space missions, microbial biofilms present a danger to crew health and spacecraft integrity. The use of antimicrobial surfaces provides an alternative strategy for inhibiting microbial growth and biofilm formation to conventional cleaning procedures and the use of disinfectants. Antimicrobial surfaces contain organic or inorganic compounds, such as antimicrobial peptides or copper and silver, that inhibit microbial growth. The efficacy of wetted oxidized copper layers and pure copper surfaces as antimicrobial agents was tested by applying cultures of Escherichia coli and Staphylococcus cohnii to these metallic surfaces. Stainless steel surfaces were used as non-inhibitory control surfaces. The production of reactive oxygen species and membrane damage increased rapidly within 1 h of exposure on pure copper surfaces, but the effect on cell survival was negligible even after 2 h of exposure. However, longer exposure times of up to 4 h led to a rapid decrease in cell survival, whereby the survival of cells was additionally dependent on the exposed cell density. Finally, the release of metal ions was determined to identify a possible correlation between copper ions in suspension and cell survival. These measurements indicated a steady increase of free copper ions, which were released indirectly by cells presumably through excreted complexing agents. These data indicate that the application of antimicrobial surfaces in spaceflight facilities could improve crew health and mitigate material damage caused by microbial contamination and biofilm formation. Furthermore, the results of this study indicate that cuprous oxide layers were superior to pure copper surfaces related to the antimicrobial effect and that cell density is a significant factor that influences the time dependence of antimicrobial activity. Key Words: Contact killing-E. coli-S. cohnii-Antimicrobial copper surfaces-Copper oxide layers-Human health-Planetary protection. Astrobiology 17, 1183-1191.

Progress in the development of new drugs in Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with a global prevalence estimated at 26.55 million in 2006. During the past decades, several agents have been approved that enhance cognition of AD patients. However, the effectiveness of these treatments are limited or controversial and they do not modify disease progression. Recent advances in understanding AD pathogenesis have led to the development of numerous compounds that might modify the disease process. AD is mainly characterized neuropathologically by the presence of two kinds of protein aggregates: extracellular plaques of Abeta-peptide and intracellular neurofibrillary tangles. Abeta and tau could interfere in an original way contributing to a cascade of events leading to neuronal death and transmitter deficits. Investigation for novel therapeutic approaches targeting the presumed underlying pathogenic mechanisms is major focus of research. Antiamyloid agents targeting production, accumulation, clearance, or toxicity associated with Abeta peptide, are some approaches under investigation to limit extracellular plaques of Abeta-peptide accumulation. We can state as an example: Abeta passive and active immunization, secretases modulation, Abeta degradation enhancement, or antiaggregation and antifibrillization agents. Tau-related therapies are also under clinical investigation but few compounds are available. Another alternative approach under development is neuroprotective agents such as antioxidants, anti-inflammatory drugs, compounds acting against glutamate mediated neurotoxicity. Neurorestorative approaches through neurotrophin or cell therapy also represent a minor avenue in AD research. Finally, statins, receptor for advanced glycation end products inhibitors, thiazolidinediones, insulin, and hormonal therapies are some other ways of research for a therapeutic approach of Alzheimer's disease. Taking into account AD complexity, it becomes clear that polypharmacology with drugs targeting different sites could be the future treatment approach and a majority of the recent drugs under evaluation seems to act on multiple targets. This article exposes general classes of disease-modifying therapies under investigation.

[Key points of the follow-up plan in the care of Alzheimer's disease patients]. / Enjeux et moyens du suivi des malades souffrant de la maladie d'Alzheimer.

The following article presents the main points of the follow-up plan of Alzheimer's disease (AD) and related syndromes patients. The general objective of this follow-up plan is to improve the quality of live of these subjects and their family. The key points are assessments of cognitive decline, functional decline and complications such as behavioural and psychological symptoms of dementia (BPSD), malnutrition and gait and balance disorders. In clinical practice, different tools are available, but frequency of evaluation is not consensual. However, the aim of this follow-up is to detect, prevent and treat complications and to improve the use of residual functional abilities in basic activities of daily living. The physician also needs to detect and prevent caregiver's exhaustion and to consider the ethical issues raised by the disease. The care plan is based on non pharmacological and pharmacological measures. The non pharmacological approach must be implemented first. The place of anti-dementia drugs is considered. Lastly, this follow-up plan aims to limit iterative admissions to emergency room and to increase the access to geriatric units. Communication and collaboration between specialist, family practitioner and caregivers are needed in order to reach the objective of quality of life improvement in AD patients.

Evaluation of the SLIPA (streamlined liner of the pharynx airway), a single use supraglottic airway device, in 60 anaesthetized patients undergoing minor surgical procedures.

The Streamlined Liner of the Pharyngeal Airway, SLIPA (Hudson RCI) is a new disposable supraglottic airway device that has no inflatable cuff and has features designed to reduce aspiration risk. This study aimed to assess the insertion success and effectiveness of the SLIPA in 60 patients who presented for elective surgery. Ethics committee approval was obtained. Patients were excluded if they were less than 18 years, had not provided written consent or were at risk of pulmonary aspiration. The first 20 SLIPA were inserted by the principal investigator (Group A) followed by another 40 inserted by medical officers and anaesthetists of varying experience (Group B). Twenty-one males and 39 females were recruited into the study. Median time to ventilation was 20.4 seconds in Group A (range 12.9-109) and 24.8 seconds in Group B (range 8.2-82.5). Overall success rate was 100% in Group A and 92.5% in Group B. The lowest recorded SpO2 was 91% in Group B. The incidence of blood and sore throat score >3 (0-10 scale) was 23% and 7% respectively (Groups A and B). Group B reported that use of the device was very easy in 16%, easy in 76%, difficult in 5%, and very difficult in 3%. The SLIPA proved to be a reliable airway providing adequate ventilation in both spontaneous breathing and assisted respiration. Most users found the SLIPA to be easy or very easy to use.

Content of educational programmes for men.

PIP: Based on previous experience UNFPA/ILO Projects in Asia, Middle East and Africa, it can be affirmed that men all tend to be interested in learning about sexual matters and contraception. Cultural sensitivity of motivational messages is to some extent ensured by the use of peer educators so men are talking to similar men. Entertaining stories, which can be presented in many ways (flip-charts, audio cassettes, theater groups, puppets, videos), are a good way of stimulating discussion. A scenario developed by a UNFPA/ILO project with cooperatives in rural Niger, for example, emphasizes how a father feels proud when his three children are well dressed and fed. Women's health can be seriously impaired by frequent and closely spaced pregnancies, which affects their ability to cope with existing children and domestic chores. Although they may feel that contraceptive use is the women's problem since most methods apply to women, the majority of men feel that they should be the ones who decide whether to use them or not. Lack of communication between husband and wife as it concerns sexual relations, birth spacing and family size is a major barrier to joint decision-making in many countries. In the Philippines some companies have been inviting spouses to meetings as they feel this generates greater interest and makes behavior change more likely. The Zimbabwe Confederation of Trade Unions has concluded that its HIV prevention activities targeting men and women as individuals were less effective than couples' workshops. In contrast, the Organisation Syndicale des Travailleurs du Cameroun experienced difficulties with mixed groups discussing sexual matters as the women seemed to be embarrassed to talk. In any case, there are numerous nonsexual family issues that can be usefully addressed.^ieng

Family planning in Mauritius: a national survey.

In the context of the Mauritian government's policy of encouraging fertility reduction, in 1975 the Ministry of Health requested the University of Mauritius to conduct the first national survey of contraceptive knowledge and use. The results for the 1,821 ever-married women under age 50 who were interviewed indicated high levels of knowledge and use of contraception. Nevertheless, there is still a need for increased efforts to retrieve dropouts and to improve the efficiency of contraceptive use.

A C-terminal di-leucine motif and nearby sequences are required for NH4(+)-induced inactivation and degradation of the general amino acid permease, Gap1p, of Saccharomyces cerevisiae.

The general amino acid permease, Gap1, of Saccharomyces cerevisiae is very active in cells grown on proline as the sole nitrogen source. Adding NH4+ to the medium triggers inactivation and degradation of the permease via a regulatory process involving Npi1p/Rsp5p, a ubiquitin-protein ligase. In this study, we describe several mutations affecting the C-terminal region of Gap1p that render the permease resistant to NH4(+)-induced inactivation. An in vivo isolated mutation (gap1pgr) causes a single Glu-->Lys substitution in an amino acid context similar to the DXKSS sequence involved in ubiquitination and endocytosis of the yeast alpha-factor receptor, Ste2p. Another replacement, substitution of two alanines for a di-leucine motif, likewise protects the Gap1 permease against NH4(+)-induced inactivation. In mammalian cells, such a motif is involved in the internalization of several cell-surface proteins. These data provide the first indication that a di-leucine motif influences the function of a plasma membrane protein in yeast. Mutagenesis of a putative phosphorylation site upstream from the di-leucine motif altered neither the activity nor the regulation of the permease. In contrast, deletion of the last eleven amino acids of Gap1p, a region conserved in other amino acid permeases, conferred resistance to NH4+ inactivation. Although the C-terminal region of Gap1p plays an important role in nitrogen control of activity, it was not sufficient to confer this regulation to two NH4(+)-insensitive permeases, namely the arginine (Can1p) and uracil (Fur4p) permeases.