Methotrexate for the treatment of unruptured tubal pregnancy: a prospective nonrandomized study.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare in a prospective nonrandomized study, the efficacy of 2 methods of administering methotrexate (MTX) in the treatment of ectopic pregnancy (EP): transvaginal injection under sonographic control or intramuscular injection (IM). METHODS: Patients with EP who met specific inclusion criteria for medical treatment were treated with MTX: 63 patients (group 1) were treated by IM and 47 patients (group 2) by transvaginal local injection. In group 1, 50 mg/m2 of MTX was injected intramuscularly; in group 2, transvaginal injection of 1 mg/kg of MTX was injected into the ectopic sac under sonographic control. When an additional dose of MTX was required, it was administrated IM at the dosage of 50 mg/m2 in both groups. RESULTS: The overall success rate, defined by a posttreatment normal hCG level (< 10 mUI/mL) was 71.4% in group 1 versus 91.5% in group 2 (P < 0.01); for patients with hCG levels < 2000 mUI/mL, 83% and 96%, respectively (not significant); for patients with hCG > or = 2000 mUI/mL, 37.5% and 86.4%, respectively (P < 0.01). CONCLUSION: In the medical treatment of EP, the efficacy of MTX is greater when administered by local transvaginal injection than by IM injection. We propose local treatment every time EP can be punctured, especially when hCG levels are > or = 2000 mUI/mL.     

Predictive value of the transtheoretical model to smoking cessation in hospitalized patients with cardiovascular disease.

BACKGROUND: Several authors have questioned the transtheoretical model. Determining the predictive value of each cognitive-behavioural element within this model could explain the multiple successes reported in smoking cessation programmes. The purpose of this study was to predict point-prevalent smoking abstinence at 2 and 6 months, using the constructs of the transtheoretical model, when applied to a pooled sample of individuals who were hospitalized for a cardiovascular event. DESIGN: The study follows a predictive correlation design. METHODS: Recently hospitalized patients (n=168) with cardiovascular disease were pooled from a randomized, controlled trial. Independent variables of the predictive transtheoretical model comprise stages and processes of change, pros and cons to quit smoking (decisional balance), self-efficacy, and social support. These were evaluated at baseline, 2 and 6 months. RESULTS: Compared to smokers, individuals who abstained from smoking at 2 and 6 months were more confident at baseline to remain non-smokers, perceived less pros and cons to continue smoking, utilized less consciousness raising and self-re-evaluation experiential processes of change, and received more positive reinforcement from their social network with regard to their smoke-free behaviour. Self-efficacy and stages of change at baseline were predictive of smoking abstinence after 6 months. Other variables found to be predictive of smoking abstinence at 6 months were an increase in self-efficacy; an increase in positive social support behaviour and a decrease of the pros within the decisional balance. CONCLUSIONS: The results partially support the predictive value of the transtheoretical model constructs in smoking cessation for cardiovascular disease patients.     

Le suicide par saut et les stratégies de prévention

The topic of this article is to probe into the specificities of suicide by jumping. This means of suicide hasn't been studied much and isn't well known yet.We reviewed the international scientific literature so as to take an in-depth look at this type of auto-aggressive action and highlight the characteristics of the subjects likely to commit suicide by jumping. We thus focus on the available epidemiological data and risk factors associated to suicide jumping. We also describe the prevention strategies most often evoked to deal with this public health issue, which are respectively about improving safety on the identified suicide sites and providing medical and psychological care to individuals likely to commit suicide by jumping.This meta-analysis presents our critical analysis of the methodological limits in the studies exposed. We provide further hints for researching this field of study; they're based on both the taking into account of variables that could be risk factors for this particular means of suicide and the evaluation of the efficiency for the preventive measures used.     

Efficacy and Costs of Patient-controlled Analgesia versus Regularly Administered Intramuscular Opioid Therapy

Background: Many studies have shown in the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy.

Methods: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfactory were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements.

Results: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times of ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment.     

Auditory evoked potentials to tones and syllables in adults: evidence of specific influence on N250 wave

Brain-derived neurotrophic factor (BDNF) is involved in the differentiation and the survival of neurons. It has also been shown to be associated with the regrowth of neurons of damaged spinal cord and the modulation of ionic currents by acting on sodium channels and NMDA receptors through tyrosine kinase B (TrkB) receptors. We investigated the effects of BDNF on rhythm generation induced by disinhibition in dissociated cultures from embryonic rat spinal cord (E14), with extracellular multisite recordings (MultiElectrode Arrays, MEAs) or intracellular patch-clamp recordings. Exogenous BDNF had only minor effects on the bursting by increasing the activity during the burst. This increase of activity is suggested to be mediated by a potentiation of the postsynaptic NMDA receptors because it has been found that BDNF potentiates the NMDA-evoked depolarization in cultures incubated with BDNF for 10 min. Possible direct effects of BDNF on sodium channels were also investigated by local application of BDNF to the soma of patched neurons but no depolarization was observed. Long-term application of BDNF strongly decreased the activity during the burst and also the number of active electrodes, possibly due to a decrease in network density.     

The TL MHC class Ib molecule has only marginal effects on the activation, survival and trafficking of mouse small intestinal intraepithelial lymphocytes

Thymus leukemia antigen (TL) is an MHC class Ib molecule that is highly conserved in rats and mice with no obvious human homolog. TL is expressed in mouse small intestinal epithelial cells and is known to interact with CD8alphaalpha homodimers, which are expressed by intraepithelial lymphocytes (IELs), some other T cell subsets and some non-T cells such as a subset of dendritic cells. We show here that TL is abundantly expressed on the basolateral surface of mouse small intestinal epithelial cells and that expression is abrogated in beta2m-/- mice but unaffected in TCR-/- mice or CD8alpha chain-/- mice. We demonstrate that the interaction between TL and CD8alphaalpha is not necessary for IEL survival in vitro or in vivo and does not modulate IEL trafficking in vivo. TL co-stimulation of alpha-CD3 antibody-activated IELs resulted in modestly enhanced production of IFN-gamma in one subset of IELs. The lack of effect on IEL survival and trafficking and the modest effect on IFN-gamma production suggest that the functional consequences of TL interaction with CD8alphaalpha as well as the more general biological role of TL in mucosal immunity remains to be discovered.     

Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.     

Functional characterization of a Ca2+-activated non-selective cation channel in human atrial cardiomyocytes

Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current ( I _ti). I _ti is the result of three different [Ca]_i-sensitive currents: the Na⁺–Ca²⁺ exchange current, a Ca²⁺-activated chloride current and a Ca²⁺-activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca²⁺-activated non-selective cation channel (NSC_Ca) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I–V relationship with a conductance of 19 ± 0.4 pS. It discriminated poorly among monovalent cations (Na⁺ and K⁺) and was slightly permeable to Ca²⁺ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K _d for [Ca²⁺]_i was 20.8 μ m . Channel activity was reduced in the presence of 0.5 m m ATP or 10 μ m glibenclamide on the cytoplasmic side to 22.1 ± 16.8 and 28.5 ± 8.6%, respectively, of control. It was also inhibited by 0.1 m m flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSC_Ca channel is a serious candidate to support the delayed after-depolarizations observed in [Ca²⁺] overload and thus may be implicated in the genesis of arrhythmias.     

Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.