Mantle redox state drives outgassing chemistry and atmospheric composition of rocky planets.

Volcanic degassing of planetary interiors has important implications for their corresponding atmospheres. The oxidation state of rocky interiors affects the volatile partitioning during mantle melting and subsequent volatile speciation near the surface. Here we show that the mantle redox state is central to the chemical composition of atmospheres while factors such as planetary mass, thermal state, and age mainly affect the degassing rate. We further demonstrate that mantle oxygen fugacity has an effect on atmospheric thickness and that volcanic degassing is most efficient for planets between 2 and 4 Earth masses. We show that outgassing of reduced systems is dominated by strongly reduced gases such as [Formula: see text], with only smaller fractions of moderately reduced/oxidised gases ([Formula: see text], [Formula: see text]). Overall, a reducing scenario leads to a lower atmospheric pressure at the surface and to a larger atmospheric thickness compared to an oxidised system. Atmosphere predictions based on interior redox scenarios can be compared to observations of atmospheres of rocky exoplanets, potentially broadening our knowledge on the diversity of exoplanetary redox states.

[Returning to work after an acute coronary syndrome: When waiting is wasting]. / Retour au travail après un accident coronarien aigu.

BACKGROUND: Return to work (RTW) after acute coronary syndrome (ACS) is an important issue for the patient's future. AIMS: The study aim was to determine whether RTW practice complies with guidelines or is delayed by failure in patient management. We analysed the factors influencing RTW beyond the 90-day period recommended by guidelines. METHODS: We conducted a survey of 216 self-employed workers admitted to the hospital for ACS using self-report questionnaires and medical examination. Factors influencing RTW, occupational and cardiac features, and recall and source of medical information were investigated. RESULTS: Ninety-three of 216 patients did not return to work by 90 days, despite good cardiac performance in 30 cases (32 %). The mean sick leave duration was 93.3±103.7 days. Advice concerning return to work was completely missing for 44 % of patients. Cardiac performance was independent of sick leave duration, but was correlated with the likelihood of RTW (P<0.001). Patients assimilated about 70 % of the medical information they were provided, but only 53 % of work-related information. Recall of work-related information was better among patients admitted to a rehabilitation facility (65 %) compared to those who did not receive rehabilitation (P<0.05). CONCLUSION: Cardiologists should assess the patient's cardiac performance within 2 months after ACS. Patient management should also include cardiac rehabilitation or therapeutic education toward improving information recall.

[Practical issues in the management of tuberculosis disease]. / Description des pratiques en matière de prise en charge de la tuberculose maladie.

INTRODUCTION: Tuberculosis disease warrants standard therapeutic management as detailed in a guide published by the High Authority for Health (HAS) following the publication of the Public Health Law in 2004. METHODS: The medical services of the régime social des indépendants (RSI) carried out a national survey by targeting patients who, in 2011, were reimbursed for tuberculosis treatment or were admitted for long-term tuberculosis disease. Their physicians were contacted to detail the care pathway and treatment they had received. RESULTS: A total of 148 tuberculosis disease patients were enrolled, of whom 71.6% had respiratory localization of their disease. The diagnosis was made in healthcare institutions in 84.5% of cases. Standard treatment (phases 1 and 2) was used in 30.1% of cases. The recommended quadruple therapy was given in 55.2% of treatments in phase 1 and in accordance with the time recommended in 62.9% of cases. Phase 2 was the recommended two drugs combination therapy 80.4% of the time with the treatment duration respected in 51.0% of treatments. The difference from standard treatment was explained by the detection of health or social events in only 39.0% of cases. CONCLUSION: This survey allows us to highlight a relative lack of knowledge of standard treatment as recommended by the HAS.

Reproductive decision making after the diagnosis of multiple sclerosis (MS).

OBJECTIVE: This study aimed to determine reproductive practices and attitudes of North Americans diagnosed with multiple sclerosis (MS) and the reasons for their reproductive decision making. METHODS: A self-administered questionnaire on reproductive practices was mailed to 13,312 registrants of the North American Research Committee on Multiple Sclerosis (NARCOMS) database who met inclusion criteria for the study. Completed questionnaires were then returned to the authors in an anonymous format for analysis. RESULTS: Among 5949 participants, the majority of respondents (79.1%) did not become pregnant following diagnosis of MS. Of these, 34.5% cited MS-related reasons for this decision. The most common MS-related reasons were symptoms interfering with parenting (71.2%), followed by concerns of burdening partner (50.7%) and of children inheriting MS (34.7%). The most common reason unrelated to MS for not having children was that they already have a "completed family" (55.6%). Of the 20.9% of participants who decided to become pregnant (or father a pregnancy) following a diagnosis of MS, 49.5% had two or more pregnancies. CONCLUSION: This study indicates that an MS diagnosis does not completely deter the consideration of childbearing in MS patients of both genders.

Disease onset in familial and sporadic primary progressive multiple sclerosis.

The pathophysiology of primary progressive (PP) multiple sclerosis (MS) involves diffuse axonal degeneration which is believed to start early in the disease process, even before the onset of clinical symptoms. Symptomatic onset then occurs when this process reaches a threshold after which the axonal loss can no longer be compensated. A preliminary study showed that patients with familial PPMS had an earlier clinical onset than patients with sporadic disease, suggesting a hereditary component to the disease process of PPMS. In this study, we combined data from two large, population-based, longitudinal MS databases to investigate disease onset in familial and sporadic PPMS. We examined 411 patients with PPMS. There were no differences in gender distribution or onset symptoms between familial and sporadic PPMS. Patients with familial PPMS were significantly younger at disease onset (n = 84, median age: 37.6 years) than patients with sporadic disease (n = 327, median age: 42.7, p = 0.007). This difference was due to a greater proportion of familial cases with a disease onset before the age of 30 and a smaller proportion with disease onset between 40 and 50 years of age (p = 0.002). Gender had no significant effect on the age at disease onset. Further analyses showed that these findings were unlikely to be due to ascertainment bias towards an earlier diagnosis in familial cases. Our findings suggest a hereditary component to the disease process of PPMS. It would be worthwhile to identify patients with familial PPMS for future research on disease modifying genes in MS.

Sex ratio of multiple sclerosis and clinical phenotype.

BACKGROUND AND PURPOSE: In a longitudinal population-based dataset of patients with multiple sclerosis (MS), we have previously observed a substantial increase in the female to male sex ratio in Canada over the last 50 years. Here, we aimed to determine whether this change in sex ratio is related to the clinical course of MS. METHODS: We calculated sex ratios by birth year in 11 868 patients with relapsing-remitting (RR) MS and 2825 patients with primary progressive (PP) MS identified as part of the Canadian Collaborative Project on the Genetic Susceptibility to MS. RESULTS: Year of birth was a significant predictor for sex ratio in RR MS (P < 0.0001, chi(2) = 21.2; Spearman's rank correlation r = 0.67), but not for PP MS (P = 0.44, chi(2) = 0.6; Spearman's rank correlation r = 0.11). CONCLUSIONS: An increase in the number of female RR MS patients over time accounts for the increasing sex ratio of MS. This has implications for pathogenesis, for assessment of clinical trial results and for disease prevention. The factors underlying the selective increase in MS in females need to be uncovered.

Incidence of acquired demyelination of the CNS in Canadian children.

BACKGROUND: The incidence of acquired demyelination of the CNS (acquired demyelinating syndromes [ADS]) in children is unknown. It is important that physicians recognize the features of ADS to facilitate care and to appreciate the future risk of multiple sclerosis (MS). OBJECTIVE: To determine the incidence, clinical features, familial autoimmune history, and acute management of Canadian children with ADS. METHODS: Incidence and case-specific data were obtained through the Canadian Pediatric Surveillance Program from April 1, 2004, to March 31, 2007. Before study initiation, a survey was sent to all pediatric health care providers to determine awareness of MS as a potential outcome of ADS in children. RESULTS: Two hundred nineteen children with ADS (mean age 10.5 years, range 0.66-18.0 years; female to male ratio 1.09:1) were reported. The most common presentations were optic neuritis (ON; n = 51, 23%), acute disseminated encephalomyelitis (ADEM; n = 49, 22%), and transverse myelitis (TM; n = 48, 22%). Children with ADEM were more likely to be younger than 10 years, whereas children with monolesional ADS (ON, TM, other) were more likely to be older than 10 years (p < 0.001). There were 73 incident cases per year, leading to an annual incidence of 0.9 per 100,000 Canadian children. A family history of MS was reported in 8%. Before study initiation, 65% of physicians indicated that they considered MS as a possible outcome of ADS in children. This increased to 74% in year 1, 81% in year 2, and 87% in year 3. CONCLUSION: The incidence of pediatric acquired demyelinating syndromes (ADS) is 0.9 per 100,000 Canadian children. ADS presentations are influenced by age.

The interaction of MS and pregnancy: a critical review.

Previous research on the effects of pregnancy on multiple sclerosis (MS) is somewhat flawed, and well-controlled, well-designed studies are needed to validate trial findings. In general, pregnancy appears to have a protective effect on MS course, with fewer, less severe relapses, especially in the third trimester. The exacerbation rate is increased in the first 3 months after delivery, but the overall relapse rate is no different to that observed in non-pregnant MS patients. A woman's past history of relapses may be the best indicator of clinical course during and immediately after pregnancy. Pregnancy does not appear to affect the long-term course of MS.

The immune system and hormones: review and relevance to pregnancy and contraception in women with MS.

Two-thirds of multiple sclerosis (MS) patients are women, and the average age of onset overlaps the childbearing years. Clinicians are frequently asked, therefore, about the most appropriate form of contraception and the risk of an MS relapse/exacerbation during pregnancy and the post-partum period. This paper reviews the literature on the immune system and the effects of pregnancy, oral contraceptives and hormone replacement therapy on MS.

Reproductive counselling for MS: a rationale.

Many questions arise when counselling multiple sclerosis (MS) patients on the effects of MS on pregnancy, and vice versa. Reassurance can often be given regarding contraception, fertility, pregnancy management, pregnancy outcome, and the risk of the child developing MS. Much more information is needed, however, on the effects and implications of MS therapies on pregnancy and breast-feeding.

Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite-resistant Leishmania.

The levels of trypanothione, a glutathione-spermidine conjugate, are increased in the protozoan parasite Leishmania selected for resistance to the heavy metal arsenite. The levels of putrescine and spermidine were increased in resistant mutants. This increase is mediated by overexpression of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Gene overexpression is generally mediated by gene amplification in Leishmania but, here, the mRNA and the enzymatic activity of ODC are increased without gene amplification. This RNA overexpression is stable when cells are grown in the absence of the drug and does not result from gene rearrangements or from an increased rate of RNA synthesis. Transient transfections suggest that mutations in the revertant cells contribute to these elevated levels of RNA. Stable transfection of the ODC gene increases the level of trypanothione, which can contribute to arsenite resistance. In addition to ODC overexpression, the gene for the ABC transporter PGPA is amplified in the mutants. The co-transfection of the ODC and PGPA genes confers resistance in a synergistic fashion in partial revertants, also suggesting that PGPA recognizes metals conjugated to trypanothione.

Characterization of the peripheral action of neurokinins and neurokinin receptor selective agonists on the rat cardiovascular system.

The effects on mean arterial pressure (MAP) and heart rate (HR) of increasing doses (0.65-65 nmol/kg) of substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and selective agonists for neurokinin receptors were measured after intravenous (i.v.) injection in urethane anaesthetized rats. Neurokinins (NKs) elicited a vasodepressor effect with the following rank order of potency: SP (100%) greater than NKB (17.5%) greater than NKA (10%). The two undecapeptide NK-1 selective agonists, [Pro9, Met(O2)11]SP (787%) and [Sar9, Met(O2)11]SP (697%), evoked a significantly (P less than 0.05) greater vasodepressor response than SP, while the potency of the octapeptide NK-1 selective agonist [beta-Ala4, Sar9, Met(O2)11]SP (4-11) (316%) was not significantly different from SP. Conversely, the NK-2 selective agonist NKA (4-10) (less than 2%) caused only a small effect. The vasodepressor effect elicited by [MePhe7]NKB (112%) and [beta-Asp4, MePhe7]NKB (4-10) (92%), two NK-3 selective agonists, were not significantly different from that of SP. Senktide (1,095%) is the most potent NK-3 agonist, and is significantly (P less than 0.01) more potent than SP. No cross-desensitization, of the vasodepressor response, was observed between NK-1 and NK-3 selective agonists. I.V. injection of 32.5 nmol/kg of NKA, NKA (4-10) and [beta-Ala4, Sar9, Met(O2)11]SP (4-11) raised HR, while NKB and the NK-3 selective agonists produced a rapid and marked bradycardia. SP and the two undecapeptide, NK-1 selective agonists, produced an initial increase in HR and a latent long-lasting bradycardia. The bradycardia elicited by [Sar9, Met(O2)11]SP (32.5 nmol/kg) was blocked by methylatropine, hexamethonium, indomethacin and by treatment with capsaicin or compound 48/80. Although the bradycardia elicited by [beta-Asp4, MePhe7]NKB (4-10) (32.5 nmol/kg) was also blocked by hexamethonium, methylatropine, and by bilateral vagotomy, it remained unaffected after indomethacin, or in rats pretreated with either capsaicin or compound 48/80. The drop in MAP produced by the NK-1 and NK-3 agonists were reduced by hexamethonium, methylatropine and bilateral vagotomy (NK-3 agonist), but remained unaffected by indomethacin, capsaicin, and compound 48/80. The tachycardia to NKA (4-10) (65 nmol/kg) was blocked entirely by sotalol or metoprolol and potentiated by hexamethonium. Guanethidine and bilateral adrenalectomy (48 h) failed to affect the tachycardia induced by the agonist, whereas the combination of both treatments abolished the response. Rats sympathectomized with 6-hydroxydopamine (48 h) reduced the increase in HR to NKA (4-10) only at 1 min post-administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Streptokinase thrombolysis of a chronically thrombosed mitral prosthetic valve.

Thrombus obstruction of a prosthetic heart valve is usually treated surgically. We report a well-documented case of an obstructed mitral prosthetic valve where fibrinolytic treatment was successful. Furthermore the thrombus formation probably had occurred 6 months earlier. Thus fibrinolysis appears to be a safe alternative to surgery although late occurrence of thrombosis may be possible.

Intracardiac electrophysiological study of S-2395 in intact and chemically sympathectomized dogs.

S-2395 is a new, long-acting, non-selective beta-receptor blocking agent without apparent intrinsic cardiodepressive action and no receptor selectivity. Its electrophysiological actions were studied in intact and chemically sympathectomized dogs. In normal dogs, S-2395 very slightly increased atrial monophasic action potential (MAPa) duration, atrioventricular functional (FRP) and ventricular effective (ERP) refractory periods. The onset of the atrial supernormal conduction phenomenon (SNCP) was delayed and the ventricular SNCP was abolished. These results are consistent with the action of low concentrations of beta-blocking agents. In contrast S-2395 reduced the ventricular MAPv and increased the ERP/MAPv ratio of sympathectomized animals. Such modifications are usually seen with concentrations higher than necessary for simple beta-receptor blockade. In conclusion S-2395, like several others beta-blockers, had minor effects on the classical electrophysiological parameters of normal dogs. However, it suppressed ventricular SNCP and had a more pronounced action in sympathectomized dogs who are known to have higher levels of circulating catecholamines and who present post-synaptic supersensitivity. The SNCP has been linked with re-entrant arrhythmias. Considering that beta-blockers prevent arrhythmias specially in hyperadrenergic states, the suppression of the ventricular SNCP by S-2395 could thus be the mechanism by which this drug and possibly other beta-blockers might exert their antiarrhythmic action.

Electrophysiological effects of ouabain in 6-hydroxydopamine pretreated dogs.

Chemical sympathectomy and bilateral vagotomy were used to evaluate the contribution of each division of the autonomic nervous system in the electrophysiological actions of ouabain. Intact and chemically sympathectomized dogs were given successive and cumulative doses of ouabain until toxicity became manifest (ventricular extrasystoles and (or) ventricular tachycardia). An additional group of normal and sympathectomized animals was also submitted to bilateral vagotomy in the presence of a therapeutic dose of ouabain. Sinus cycle length, AH interval of the His bundle electrogram, atrioventricular junctional effective and functional refractory periods were increased by ouabain at therapeutic doses. These effects were no different in sympathectomized dogs than in intact dogs, indicating the absence of any significant contribution of efferent sympathetic neural activity. However, our results suggested that vagal enhancement was the main mechanism whereby ouabain produced sinus bradycardia and depression of atrioventricular conduction. Sympathectomy with 6-OHDA did not modify nor abolish ouabain toxicity. However, toxic doses were significantly higher in sympathectomized animals than in normal animals. Considering that increasing heart rate by cardiac pacing or vagotomy significantly lowered toxic doses of ouabain in both intact and sympathectomized dogs, it is possible that sympathectomy could influence ouabain toxicity by altering heart rate alone.

Electrophysiology of the chemically sympathectomised dog.

The contribution of the sympathetic nervous system in the definition of various electrophysiological variables was studied in chemically sympathectomised dogs. Chemical sympathectomy was obtained following intravenous injection of 50 mg X kg-1 of 6-hydroxydopamine. Sympathectomised dogs presented significant increases in: basic sinus period, sino-atrial conduction time (SACT), AH and HV intervals of the His bundle electrogram, atrial functional (AFRP) and effective (AERP) refractory periods, atrio-ventricular node functional (AVNFRP) and effective (AVNERP) refractory periods, ventricular functional (VFRP) and effective (EVRP) refractory periods and atrial (AMAP) and ventricular (VMAP) monophasic action potential durations. Corrected sinus recovery time (CSRT) was not affected by chemical sympathectomy. Neither was the atrial ERP/MAP duration ratio. This new form of sympathectomy affects all the levels of the cardiac conduction system. Such results are in accordance with those obtained with surgical sympathectomy or the use of beta-blocking agents.

Computer processing of intracardiac electrograms for conduction studies.

Computer techniques developed to process intracardiac signals recorded in dogs are presented. The signals under measurement are the auricular and ventricular monophasic action potentials and the His bundle electrogram. Computerized measurement of significant timing parameters on simultaneous recordings of these signals can assess quite precisely changes in the normal conduction scheme of the heart provoked by different experimental protocols. Increased accuracy is mainly due to the objective way of defining wave onsets and the processing power of the system used. Signal recording, signal acquisition, automatic waveform measurements, interactive process and production of end result graphs by computer are all described.