[In process]. / Insomnie, anxiété: faut-il réguler la prescription des benzodiazépines?

Benzodiazepine hypnotics bear a higher risk of high dose dependence than benzodiazepine anxiolytics, according to a recent study in Luxemburg. This article summarizes the main indications of these molecules and the current treatment recommendations. It provides an overview of public health actions of the past and the future to reduce their excessive consumption.

Association of gamma-glutamyltransferase with severity of disease at diagnosis and prognosis of ovarian cancer.

BACKGROUND: Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. METHODS: In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological parameters and uni- and multivariate survival analyses were performed. Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. RESULTS: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 (38.24) U l(-1)) than in patients with BTO (20.01 (12.78) U l(-1), P=0.01). High GGT serum levels were associated with advanced FIGO stage (P<0.001) and with worse overall survival in univariate (P<0.001) and multivariable analysis (P=0.02, HR 1.2 (1.1-1.5)). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumour tissue and observed an association between these two parameters (P=0.03). CONCLUSION: High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma-glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels.

Corrigendum to "Improving contrast enhancement in pulmonary CTA: The value of breathing maneuvers" [Eur J Radiol Open 7 (2020) 100280].

[This corrects the article DOI: 10.1016/j.ejro.2020.100280.].

Improving Contrast Enhancement in Pulmonary CTA: The value of breathing maneuvers.

PURPOSE: To investigate contrast dynamics and artifacts associated with different breathing maneuvers during pulmonary computed tomography angiography (pCTA) in a prospective randomized clinical trial. METHOD: Three different breathing maneuvers (inspiration, expiration, Mueller) were randomly assigned to 146 patients receiving pCTA for suspected pulmonary embolism (PE). Contrast enhancement of central and peripheral arteries and imaging quality of lung parenchyma were compared and analyzed. Results were compared by using the analysis of variances (ANOVA) and Kruskal-Wallis-Test. RESULTS: Mean enhancement in the pulmonary trunk was highest during breath-hold in inspiration (293 HU, range 195-460 HU) compared to Mueller (259 HU, range 136-429 HU, p = 0022) and expiration (267 HU, range 115-376 HU). This was similar for the right pulmonary artery (inspiration 289 HU, range 173-454 HU; Mueller 250 HU, range 119-378 HU; p = 0.007; expiration 257 HU, range 114-366 HU; p = 0.032) and left pulmonary artery (inspiration 280.3 HU, range 170-462 HU; Mueller 245 HU, range 111-371 HU; p = 0.016; expiration 252 HU, range 110-371 HU).Delineation of peripheral arteries was significantly better in inspiration vs Mueller (p = 0.006) and expiration (p = 0.049). Assessment of the lung parenchyma was significantly better in inspiration vs Mueller (p = 0.013) or expiration (p < 0.001). CONCLUSIONS: Resting inspiratory position achieved the highest enhancement levels in central and peripheral pulmonary arteries and best image quality of the pulmonary parenchyma in comparison to other breathing maneuvers. It is necessary to train the maneuver prior to the examination in order to avoid deep inspiration with the risk of suboptimal opacification of the pulmonary arteries.

Conformational analysis of a mitochondrial presequence derived from the F1-ATPase beta-subunit by CD and NMR spectroscopy.

Previous studies on mitochondrial targeting presequences have indicated that formation of an amphiphillic helix may be required for efficient targeting of the precursor protein into mitochondria, but the structural details are not well understood. We have used CD and NMR spectroscopy to characterize in detail the structure of a synthetic peptide corresponding to the presequence for the beta-subunit of F1-ATPase, a mitochondrial matrix protein. Although this peptide is essentially unstructured in water, alpha-helix formation is induced when the peptide is placed in structure-promoting environments, such as SDS micelles or aqueous trifluoroethanol (TFE). In 50% TFE (by volume), the peptide is in dynamic equilibrium between random coil and alpha-helical conformations, with a significant population of alpha-helix throughout the entire peptide. The helix is somewhat more stable in the N-terminal part of the presequence (residues 4-10), and this result is consistent with the structure proposed previously for the presequence of another mitochondrial matrix protein, yeast cytochrome oxidase subunit IV. Addition of increasing amounts of TFE causes the alpha-helical content to increase even further, and the TFE titration data for the presequence peptide of the F1-ATPase beta-subunit are not consistent with a single, cooperative transition from random coil to alpha-helix. There is evidence that helix formation is initiated in two different regions of the peptide. This result helps to explain the redundancy of the targeting information contained in the presequence for the F1-ATPase beta-subunit.

Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome.

BACKGROUND: This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy (CBGT) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia. METHODS: One hundred thirty-three patients from 2 sites received 12 weeks of CBGT, phenelzine therapy, pill placebo administration, or educational-supportive group therapy (an attention-placebo treatment of equal credibility to CBGT). The "allegiance effect," ie, the tendency for treatments to seem most efficacious in settings of similar theoretical orientation and less efficacious in theoretically divergent settings, was also examined by comparing responses to the treatment conditions at both sites: 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment. RESULTS: After 12 weeks, phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition. However, response to phenelzine therapy was more evident after 6 weeks, and phenelzine therapy was also superior to CBGT after 12 weeks on some measures. There were few differences between sites, suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances. CONCLUSIONS: After 12 weeks, both phenelzine therapy and CBGT were associated with marked positive response. Although phenelzine therapy was superior to CBGT on some measures, both were more efficacious than the control conditions. More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect.

Regulation of topical antimicrobials: history, status and future perspective.

Antimicrobial agents used as disinfectants and antiseptics are increasing in epidemiologic importance. The regulation of topical antiseptics has ranged from nonexistent, lax and confusing to inclusion in the Food and Drug Administration (FDA) over-the-counter (OTC) review of drug ingredients. This article simplifies the complex history, current status and future possibilities for the hospital use of topical antiseptic products.

Polyneuropathy associated with chronic hypoxaemia: prevalence in patients with chronic obstructive pulmonary disease.

The prevalence of clinical and electrophysiological signs of peripheral nerve disease was evaluated in 151 patients with chronic obstructive pulmonary disease. Patients with concomitant disorders affecting the peripheral nervous system were excluded. Thirty patients had clinical signs of a mild sensorimotor and distal neuropathy and 13 additional patients had only electrophysiological abnormalities. The rate and the severity of the neuropathy correlated with the severity of chronic hypoxaemia. Three out of 20 patients with mild hypoxaemia (PaO2 less than 15 mm Hg below normal) had polyneuropathy as compared with 15 out of 36 with severe hypoxaemia (PaO2 more than 30 mm Hg below normal (rates different at the 10% level)). PaO2 and age were the only variables discriminating between patients with and without peripheral neuropathy.

A qualitative study on vanadate effects in the tetrahydrofolate-dependent formate transfer in vitro and in vivo in mice.

Parenteral administration of sodium vanadate (NaVO3, 22 mg/kg b.w., i.p.) to mice depresses the oxidation rate of [14C]formate to [14C]CO2, as determined by radioactive breath analysis. The heavy metal-induced inhibition is relatively fast in onset, fairly intense (up to 80% inhibition), of short duration (about 2 h) and strongly correlated to the presence of vanadate (in the pentavalent state) in plasma. The [14C]CO2 exhalation rate from [14C]bicarbonate is less affected by vanadate in vivo, thereby suggesting a specific interference of vanadium in the intermediate step of formate oxidation to HCO3-. In vitro in mouse liver cytosolic fractions vanadate inhibits the enzymatic transfer of formate to tetrahydrofolic acid. The inhibition is accomplished by a vanadate-dependent oxidative degradation of tetrahydrofolate. In contrast, the concentrations of N5-methyltetrahydrofolate, dihydrofolate and folate remain unchanged upon in vitro-exposure to vanadate. The in vitro studies thus might explain the observed inhibition of formate oxidation to carbon dioxide in vivo by a vanadate-evoked depletion of its biological carrier tetrahydrofolic acid. Whether the interference in tetrahydrofolate metabolism also occurs under in vivo conditions, remains to be elucidated.

Dismantling cognitive-behavioral group therapy for social phobia.

The efficacy of Heimberg's (1991) Cognitive-Behavioral Group Therapy (CBGT) [Unpublished manuscript] for social phobia has been demonstrated in several studies in recent years. However, little is known about the mechanisms underlying the treatment's success. In order to determine whether the cognitive restructuring component of CBGT is essential, this study compared CBGT to an exposure-based treatment without formal cognitive restructuring. A wait-list control was also included. In general, Ss in the active treatment conditions improved and control Ss did not improve on a variety of self-report, clinician, and behavioral measures. Limited evidence indicated that Ss in the non-cognitive treatment may have made somewhat greater gains on some measures. Although CBGT Ss reported more improvement than exposure-alone Ss in subjective anxiety during an individualized behavioral test at posttreatment, this difference disappeared at 6-month follow-up. Surprisingly, CBGT was less effective than in previous controlled trials, and possible reasons for this are discussed. Implications of the results for cognitive theory and cognitive-behavioral therapy for social phobia are addressed.

Microbial accumulation and vitality on different restorative materials.

A new technique using standardized test facings was designed to evaluate interdental plaque accumulation on different restoration materials. In 10 volunteers, a total of 40 samples, including enamel, two different ceramics and a bonding composite, were inserted one by one into a precision attachment in an experimental inlay bordering on either the lower second premolar or the lower first molar. Bacterial accumulation on each approximal specimen was allowed to mature for 3 d. Following microbiological processing of the plaque samples, total bacterial counts, colony forming units and the bacterial vitality were determined. The results revealed different accumulation rate patterns. Both ceramics accumulated less plaque with a reduced vitality compared to enamel, while the bonding composite showed no significant differences compared to the natural tooth substance. No significant differences were detected when comparing the two examined ceramics.

[Is it possible (and desirable) to administer a standard for an effective health policy for the European Union?]. / Est-il possible (et souhaitable) de mener au niveau de l'Union européenne une politique de santé publique efficace?

The European Union has a formal interest in public health under the Article 129 of the Maastricht Treaty. Hitherto, the main contribution of the European Union action in public health has been limited to research, health information and education concerning, in particular major diseases and drug dependence. Unfortunately the European architects did not clearly conceive a plan for the establishment of a common health policy despite the fact that the European health policies are fragmented and are often the indirect results of economic policies. Indeed, the domain of public health is essentially governed by the principle of national sovereignty, onto which the principle of subsidiarity has been grafted. Whereas Article 129 of the Maastricht Treaty applies especially to preventive health policies, the concomitant affirmation of the principle of subsidiarity in this field tends to suspend any establishment of a European health policy. In the same way, the lack of compulsory provisions relating to Community actions, expressed as recommendations, raises the question whether the European Union is willing to move to a European health policy.

Thermodynamics and rheology of cycloolefin copolymers.

Cycloolefin copolymers of ethylene and norbornene, with norbornene content in the range from 36 to 62 mol %, were studied with respect to the thermal, thermodynamic, and rheological properties using differential scanning calorimetry, pressure-volume-temperature, and dynamic mechanical measurements. All copolymers obey the principle of time-temperature superposition, i.e., they can be considered as thermorheologically simple except for a temperature range in the vicinity of T(g). Despite this, the results on (i) the ratio of activation energies E(V)(*)/H(*) used to quantify the origin of the liquid-to-glass transition, (ii) the pressure coefficient of the glass temperature T(g)(P), and (iii) the dynamic fragility m suggest increasing dynamic heterogeneity with increasing norbornene content that is driven by the structural heterogeneity along the backbone.

Kinetic evidence for a two-step mechanism for the binding of chymotrypsin to alpha 1-proteinase inhibitor.

We have used the proflavin displacement method and a stopped-flow apparatus to measure the rate constant for the binding of 2 microM-chymotrypsin to 20-125 microM-alpha 1-proteinase inhibitor. The observed pseudo-first-order constant showed a hyperbolic dependence on alpha 1-proteinase inhibitor concentration, suggesting a reaction mechanism in which a fast pre-equilibrium (K = 0.19 mM) is followed by a first-order formation of the final complex (k = 252 s-1).