[Psychological impact of out-of-hospital cardiopulmonary resuscitation (CPR) on the witness engaged in gestures of survival]. / Impact psychologique de la réanimation cardio-pulmonaire en extra-hospitalier (ACREH) chez le témoin pratiquant les gestes de survie.

The occurrence of an unexpected sudden death puts the witnesses of this event in a situation of high emotional impact. The benefit to allow the families of victims to dispense the first resuscitation techniques has been emphasized. However, little data exist on the emotional impact of a cardio-respiratory arrest outside the hospital on the witness, who is often a close family member. Recently, we investigated the presence of psychological distress and the factors influencing it, in the active practice of basic resuscitation gestures by the witnesses guided by the operator 112. Resuscitation by a person not belonging to the medical corps seems not to be devoid of psychological impact. Indeed, the presence of psychological distress is observed for most of witnesses questioned 6 to 10 days after the call but also 3 months later. This work highlights therefore the importance of identifying the coping strategies involved, in order to promote potentially beneficial strategies and limit the trauma associated with this type of event.

La survenue d'une mort subite plonge les témoins directs de cet événement dans une situation à haut impact émotionnel. Le bénéfice de laisser les familles des victimes assister aux manœuvres de réanimation a été souligné. Cependant, peu de données existent sur l'impact émotionnel d'un arrêt cardio-respiratoire en dehors de l'hôpital sur le témoin, qui est principalement un proche de la famille. Récemment, nous nous sommes interrogés sur l'induction potentielle d'une détresse psychologique, et les facteurs influençant celle-ci, dans la pratique active des gestes de réanimation de base par le témoin direct, guidé par l'opérateur 112. L'application des gestes de réanimation par une personne n'appartenant pas au corps médical semble ne pas être dénué d'impact. En effet, la présence d'une détresse psychologique chez la plupart des témoins, questionnés 6 à 10 jours après l'appel et 3 mois plus tard, est observée. Ce travail objective donc l'importance d'identifier les stratégies d'adaptation en jeu, afin de favoriser les stratégies potentiellement bénéfiques et de limiter le traumatisme lié à ce type d'événement.

Direct and indirect injuries of the pharynx and larynx.

Direct and indirect injuries of the pharynx and larynx. The neck is characterized by a relatively complex anatomy and a very compact content. It therefore forms an extremely vulnerable part of the human body. Although uncommon, aero-digestive tract injuries caused by trauma present a challenging situation for both the emergency doctor and the head and neck surgeon. Clinical presentations may vary from severe acute distress with immediate life-threatening airway obstruction to apparently more reassuring situations. However, the latter turn out to be frequently misleading, since patients may deteriorate suddenly as the result of unrecognized injuries. In such cases, delayed diagnosis is often associated with increased morbidity and mortality. Due to its role in phonation, breathing and alimentation, injuries to the aero-digestive tract also expose the patient to severe later impairment and a poorer quality of life. Comprehensive airway control remains the highest and often most challenging priority for the emergency physician. Careful clinical examination combined with endoscopy and computed tomography imaging form the key elements in diagnosis and early recognition of patients who may require surgical management.

Efficacy and cost-effectiveness: A study of different treatment approaches in a tertiary pain centre.

BACKGROUND: Chronic pain is considered to be a complex phenomenon, involving an interrelation of biological, psychosocial and sociocultural factors. Currently, no single treatment or therapy can address all aspects of this pathology. In our expert tertiary pain centre, we decide to assess the effectiveness of four treatments for chronic pain classically proposed in our daily clinical work: physiotherapy; psycho-education; physiotherapy combined with psycho-education; and self-hypnosis/self-care learning. METHODS: This study included 527 chronic pain patients, with a mean duration of pain of 10 years. Patients were allocated either to one of the four pre-cited treatment groups or to the control group. Pain intensity, quality of life, pain interference, anxiety and depression were assessed before and after treatment. RESULTS: This study revealed a significant positive effect on pain interference and anxiety in patients included in the physiotherapy combined with psycho-education group, after 20 sessions spread over 9 months of treatment. The most prominent results were obtained for patients allocated to the self-hypnosis/self-care group, although they received only six sessions over a 9-month period. These patients showed significant benefits in the areas of pain intensity, pain interference, anxiety, depression and quality of life. CONCLUSIONS: This clinical report demonstrates the relevance of biopsychosocial approaches in the improvement of pain and psychological factors in chronic pain patients. The study further reveals the larger impact of self-hypnosis/self-care learning treatment, in addition to a cost-effectiveness benefit of this treatment comparative to other interventions.

Gastric leak after laparoscopic sleeve gastrectomy: early covered self-expandable stent reduces healing time.

BACKGROUND: Laparoscopic sleeve gastrectomy has become a very frequent procedure in bariatric surgery due to its efficacy and simplicity compared to gastric bypass. Gastric staple line leak (1 to 7 % of cases) is a severe complication with a long nonstandardized treatment. The aim of this retrospective study was to examine the success and tolerance of covered stents in its management. METHODS: From January 2009 to December 2011, nine patients with gastric staple line leaks after sleeve gastrectomy were treated with covered stents in our department (seven referred from other institutions). The leaks were diagnosed by CT scan and visualized during the endoscopy. Among the studied variables were operative technique, post-operative fistula diagnosis delay, stent treatment delay, and stent tolerance. In our institution, Hanarostent® (length 17 cm, diameter 18 mm; M.I. Tech, Seoul, Korea) was used and inserted under direct endoscopic control. RESULTS: Stent treatment was successful in seven cases (78 %). Two other cases had total gastrectomy (405 and 185 days after leak diagnosis). Early stent removal (due to migration or poor tolerance) was necessary in three cases. The average stent treatment duration was of 6.4 weeks, and the average healing time was 141 days. The five patients with an early stent treatment (≤ 3 weeks after leak diagnosis) had an average healing time of 99 days versus 224 for the four others. CONCLUSIONS: Covered self-expandable stent is an effective treatment of gastric leaks after sleeve gastrectomy. Early stent treatment seems to be associated with shorter healing time.

FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3.

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide-platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide-platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide-platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide-platinum combination, 19 (49%; 12 women, median age 53 (29-78) years) received the FOLFIRI regimen with a median number of 6 (1-16) courses. Six patients (31%) had at least one episode of grades 3-4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide-platinum combination. These results should be confirmed in a future prospective study.

[Prescription of ergot derivatives for lactation inhibition in France: Current practices]. / Pratiques de prescription des dérivés de l'ergot de seigle dans l'inhibition de la lactation en France.

OBJECTIVES: To provide an overview of ergot derivatives prescription for lactation inhibition in France, either label (bromocriptine 2.5mg and lisuride 0.2mg) or off-label prescription (dihydroergocryptine and cabergoline). PATIENTS AND METHODS: Analysis based on a questionnaire sent to all 618 French maternity wards in 2009, and prescription modalities from social security reimbursement data in the Rhône-Alpes region. RESULTS: The mean response rate to the questionnaire was 43% and main characteristics of respondents in this sample were very close to those found at the national level. The use of bromocriptine (89%) was the most frequently proposed. Dihydroergocryptine and cabergoline were mentioned as first or second alternatives in 39 and 24% of cases, respectively. Lisuride, homeopathy and phytotherapy were very rarely mentioned. The analysis of social security reimbursement data in the Rhône-Alpes region between 2008 and 2009 evidenced an increase in the rate of dihydroergocryptine prescriptions (from 37 to 46%), which were more frequent in women also treated with cardiovascular or psychotropic drugs, while that of bromocriptine decreased. CONCLUSION: This study shows that, in France, the main alternative to bromocriptine for lactation inhibition is the off-label use of dihydroergocryptine followed by cabergoline, which seems to be safer.

Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: benefits over classical vesicles.

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells.

Liposome surface charge influence on skin penetration behaviour.

Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

Skin penetration behaviour of liposomes as a function of their composition.

Deformable liposomes have been developed and evaluated as a novel topical and transdermal delivery system. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. The present study concerns ex vivo diffusion experiments using pig ear skin in order to explain the penetration mechanism of classical and deformable liposomes. Classical and deformable vesicles containing betamethasone in the aqueous compartment through the use of cyclodextrin inclusion complexes were compared to vesicles encapsulating betamethasone in their lipid bilayer. Deformable liposomes contained sodium deoxycholate as the edge activator. Liposomes were characterised by their diameter, encapsulation efficiency, deformability, stability (in terms of change in diameter) and release of encapsulated drug. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed that liposomes do not stay intact when they penetrate the deepest layers of the skin. Betamethasone is released from the vesicles after which free drug molecules can diffuse through the stratum corneum and partition into the viable skin tissue.

Development of a new topical system: drug-in-cyclodextrin-in-deformable liposome.

A new delivery system for cutaneous administration combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes was developed, leading to a new concept: drug-in-cyclodextrin-in-deformable liposomes. Deformable liposomes made of soybean phosphatidylcholine (PC) or dimyristoylphosphatidylcholine (DMPC) and sodium deoxycholate as edge activator were compared to classical non-deformable liposomes. Liposomes were prepared by the film evaporation method. Betamethasone, chosen as the model drug, was encapsulated in the aqueous cavity of liposomes by the use of cyclodextrins. Cyclodextrins allow an increase in the aqueous solubility of betamethasone and thus, the encapsulation efficiency in liposome vesicles. Liposome size, deformability and encapsulation efficiency were calculated. The best results were obtained with deformable liposomes made of PC in comparison with DMPC. The stability of PC vesicles was evaluated by measuring the leakage of encapsulated calcein on the one hand and the leakage of encapsulated betamethasone on the other hand. In vitro diffusion studies were carried out on Franz type diffusion cells through polycarbonate membranes. In comparison with non-deformable liposomes, these new vesicles showed improved encapsulation efficiency, good stability and higher in vitro diffusion percentages of encapsulated drug. They are therefore promising for future use in ex vivo and in vivo experiments.

[Allergy to ragweed in the Rhone-Alpes and consumption of anti-allergics]. / Allergie a l'ambroisie en Rhône-Alpes et consommation des anti-allergiques.

AIMS: To measure evolution and cost consumption of anti-allergic medicines during ragweed pollen-period, geographic trend in the locations of anti-allergic consumers. Ragweed is highly spread in Rhone Alps. METHODS: We measured the ratio: number of boxes of anti-allergic medicines per one thousand patients between 6 and 64 years, refunded by twelve local health offices in the Rhone Alps area. We obtained statistical mapping for consumers of triamcinolone, we analysed in the relation to weakly ragweed pollen figures. RESULTS: Four geographic areas showed high increases of antihistaminic consumption from the middle of august to the end of september during the four years studied. A threefold increase of consumption of antihistaminic medicines, anti-allergic eye-drops and anti-allergic nasals topics was observed during ragweed pollen-period (week 33 to week 40). Antihistaminic consumption ratios increased in relation with ragweed pollen-period This study demonstrated that the anti-allergic medicines consumption reflected the image of ragweed allergy. This sanitary feature is easily obtained from the refunded databases of Medical Insurance.

Comparison of two methods of cervical cerclage by ultrasound cervical measurement.

OBJECTIVE: To compare the effects of cerclage performed with a modified Shirodkar procedure or with McDonald's technique using transvaginal ultrasound measurement of the distance between the external os and the suture. MATERIALS AND METHODS: We performed a retrospective study of all patients who underwent a prophylactic cerclage with either the modified Shirodkar procedure or the McDonald's technique over a 3-year period. Physicians chose the cerclage technique according to their own preferences. Transvaginal ultrasound examination of the cervix was performed 2 weeks after the cerclage to measure its functional length and the distance between the external os and the cerclage. RESULTS: During the study period, 14 patients had a cerclage with the modified Shirodkar procedure and 19 patients with the McDonald's technique. Twelve of these 33 patients (36.4%) delivered before 37 weeks. The obstetric characteristics of the patients in both groups were similar. There were no significant differences between the Shirodkar and McDonald groups as to the functional cervical length before (31.3 +/- 8.7 vs. 35.6 +/- 9.7 mm, respectively) or after (37.0 +/- 7.3 vs. 36.1 +/- 7.9 mm) cerclage, the distance between the external os and cerclage (16.7 +/- 3.8 vs. 14.0 +/- 5.2 mm), or the number of deliveries before 32 (0 vs. 2) and 34 (1 vs. 3) weeks. CONCLUSION: The anterior colpotomy of the Shirodkar procedure increased the distance between the external os and the cerclage by a mean of 2.7 mm. This slight gain does not justify exposing the patient to the risks related to this procedure. When cerclage is necessary, McDonald's technique seems preferable.

[Consumption of allergy medicines in 2000 and 2001: data from 12 Primary Medical Insurance Offices (CPAM) in the Rhône-Alpes region]. / Consommation de médicaments allergiques en 2000 et en 2001: données des douze CPAM de la région Rhône-Alpes.

OBJECTIVES: Comparison of the annual consumption of different classes of antiallergy medicines in the Rhône-Alpes region and as a function of the pollen calendar. MATERIAL AND METHODS: Exhaustive review, over all the beneficiaries of the general system of social security aged from 6 to 65 years, of the number of weekly supplies: non-cholinergic oral antihistamines (antiH1), anti-allergy nasal sprays, anti-allergy eye lotions, delayed release injectable orticosteroids. In the twelve Primary Offices of Medical Assurance of the Rhône-Alpes region for the years 2000 and 2001. The results are expressed as the number of units (boxes)/100 beneficiaries. RESULTS: The principal reports are: Consumptions vary in a parallel way between the different regions with a south > north and plain > mountain gradient between the different therapeutic classes (per os > local administration); a fluctuation closely linked to the presence of allergizing pollens: ragweed is responsible for high consumption in all the departments except the two Savoie. The observed peak of pollinization of birch in 2001 was associated with a peak of deliveries. These data confirm the value of data of medicines consumption both economically and medically.

Transvaginal sonographic examination of the cervix in asymptomatic pregnant women: review of the literature.

Different strategies have been developed to refine the prediction of the risk of preterm delivery in asymptomatic patients. Transvaginal sonography has been used for this reason to measure and examine the length and shape of the cervix. In this review, we focus on clinical studies involving transvaginal sonographic assessment of the cervix in asymptomatic women at high risk of preterm delivery and in the general pregnant population. Three ultrasound signs are suggestive of cervical incompetence, namely, dilatation of the internal os, sacculation or prolapse of the membranes into the cervix (with shortening of the functional cervical length) either spontaneously or induced by transfundal pressure, and short cervix in the absence of uterine contractions. Transvaginal sonography has clearly demonstrated that cerclage leads to a measurable increase in cervical length which may contribute to the success of this procedure in reducing the risk of preterm delivery. Several non-randomized interventional studies among patients with cervical incompetence have been published. They have defined a new group of patients requiring cerclage when the women show progressive cervical modifications on transvaginal sonography, while in other studies, cerclage performed on the basis of cervical changes on transvaginal sonography did not prevent premature delivery. One prospective randomized trial in asymptomatic high-risk women has shown two benefits of cerclage following indications for transvaginal sonography: (1) it would generate fewer prophylactic cerclages in high-risk women; (2) therapeutic cerclage before 27 weeks may reduce the incidence of premature delivery before 34 weeks. The risk of preterm delivery is inversely correlated with cervical length. Routine transvaginal sonography of the cervix performed between 18 and 22 weeks can help identify patients at risk of preterm delivery. However, given the low prevalence of preterm births, screening would generate either a high false-positive rate or a low sensitivity. One non-randomized interventional study among patients with a short cervix on routine ultrasound examination found a lower risk of delivery before 32 weeks in the cerclage group than in the expectant management group. However, to date, there have been no prospective randomized trials in a general population. Although evidence is still lacking, there does appear to be a benefit in performing a cerclage rather than continuing with expectant management in cases with sonographic appearance of cervical incompetence in asymptomatic women at high risk of preterm delivery. Ultrasound can be offered to reduce the indications of cerclage for cases in which the situation is uncertain. Within the general obstetric population, transvaginal sonography might help in the selection of asymptomatic but high-risk women. However, the benefit associated with cerclage for sonographic indication has not been demonstrated.

T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase.

After stimulation of the T cell receptor (TCR), the tyrosine residues 292 and 315 in interdomain B of the protein tyrosine kinase ZAP-70 become phosphorylated and plausibly function as docking sites for Cbl and Vav1, respectively. The two latter proteins have been suggested to serve as substrates for ZAP-70 and to fine-tune its function. To address the role of these residues in T cell development and in the function of primary T cells, we have generated mice that express ZAP-70 molecules with Tyr to Phe substitution at position 292 (Y292F) or 315 (Y315F). When analyzed in a sensitized TCR transgenic background, the ZAP-70 Y315F mutation reduced the rate of positive selection and delayed the occurrence of negative selection. Furthermore, this mutation unexpectedly affected the constitutive levels of the CD3-zeta p21 phosphoisoform. Conversely, the ZAP-70 Y292F mutation upregulated proximal events in TCR signaling and allowed more T cells to produce interleukin 2 and interferon gamma in response to a given dose of antigen. The observation that ZAP-70 Y292F T cells have a slower rate of ligand-induced TCR downmodulation suggests that Y292 is likely involved in regulating the duration activated TCR reside at the cell surface. Furthermore, we showed that Y292 and Y315 are dispensable for the TCR-induced tyrosine phosphorylation of Cbl and Vav1, respectively. Therefore, other molecules present in the TCR signaling cassette act as additional adaptors for Cbl and Vav1. The present in vivo analyses extend previous data based on transformed T cell lines and suggest that residue Y292 plays a role in attenuation of TCR signaling, whereas residue Y315 enhances ZAP-70 function.