Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03-adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity of the vaccines in health professionals from a Clinical Research Institute in Rio de Janeiro, Brazil and there were no serious adverse events following immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva-lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI 95%: 2.62-4.48, respectively]; however, there was no difference between the vaccines in the assessments conducted at seven and 21 days post-vaccination. The group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29-6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We concluded that the two types of vaccines caused no serious AEFI in the studied population and the adjuvanted vaccine was more reactogenic, particularly in the 24 h following vaccination. This behaviour must be confirmed and better characterised by longitudinal studies in the general population.

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.

BACKGROUND The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression.

Via a transcription factor, Foxp3, immunoregulatory CD4(+)CD25(+) T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2-IL-2 mAb complexes for a short period of 3 d induces a marked (>10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1-2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2-IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex-incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation.

Difficulties associated with out-patient management of drug abusers by general practitioners. A cross sectional survey of general practitioners with and without methadone patients in Switzerland

Résumé de l'article Contexte : En Suisse, les médecins de premier recours traitent la plupart des patients dépendants aux opiacés méthadone en tant que traitement de substitution. Méthode : Nous avons étudié les difficultés rencontrées dans la prise en charge des patients toxicodépendants en envoyant par poste un questionnaire d'enquête. Nous avons envoyé ce questionnaire à tous les médecins de premier recours de Suisse Romande prescrivant de la méthadone (556 médecins). Nous avons envoyé un autre questionnaire, plus court, à des médecins de premier recours du Canton de Vaud qui ne prescrivent pas de méthadone. Résultats : le taux de réponse global est de 63,3 %. La plus haute dose de méthadone donnée par les médecins de premier recours est de 120,4 mg/j (moyenne). Questionnés au sujet de l'aide qu'ils désireraient recevoir face à ces patients, les médecins de premier recours avec patients substitués par méthadone ont mentionné premièrement l'importance d'un meilleur remboursement des services prodigués. Les autres éléments demandés ont été une meilleure formation, de meilleures connaissances des pathologies psychiatriques et des groupes de discussion de cas cliniques. Les médecins sans patients sous méthadone refusent de traiter ces patients surtout pour des raisons émotionnelles et relationnelles. En conclusion : les médecins acceptant des patients sous méthadone rencontrent des difficultés relationnelles et émotionnelles. Ils désirent un meilleur remboursement pour les services prodigués.

Long-term prognostic value of single-photon emission computed tomography myocardial perfusion imaging in diabetic patients with and without coronary artery disease

Keywords Diabetes mellitus; coronary artery disease; myocardial ischemia; prognostic value; single-photon emission computed tomography myocardial perfusion imaging Summary Aim: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. Methods: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. Results: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65±10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p<.0001), followed by history of CAD (Hazard Ratio (HR)= t 5.9, p=0.0001), diabetic retinopathy (HR=10.0, p=0.001) and inability to exercise (HR=7.7, p=0.02). Patients with normal 1VIPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. Conclusion: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a > 5 fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients. Mots-Clés Diabète; maladie coronarienne; ischémie myocardique; valeur pronostique; tomoscintigraphie myocardique de perfusion par émission monophotonique Résumé Objectifs: Déterminer la valeur pronostique à long terme de la tomoscintigraphie myocardique de perfusion (TSMP) chez les patients diabétiques pour prédire les événements cardiovasculaires (ECV). Méthodes: Etude de 210 diabétiques caucasiens consécutifs référés pour une TSMP. Les courbes de survie ont été déterminées par Kaplan-Meier et les facteurs prédictifs indépendants par analyses multivariées de type Cox. Résultats: Le suivi a été complet chez 200 (95%) patients avec une durée médiane de 3.0 ans (0.8-50). La population était composée de 114 (57%) hommes, âge moyen 65±10 ans, avec 181 (90.5%) diabète de type 2, 50 (25%) antécédents de maladie coronarienne (AMC) et 98 (49%) patients connus pour un angor avant la TSMP. La prévalence de TSMP anormales était de 58%. Aucun décès d'origine cardiaque ou infarctus du myocarde n'est survenu chez les patients avec une TSMP normale, ceci indépendamment de leurs AMC et des douleurs thoraciques. Les facteurs prédictifs indépendants pour les ECV sont une TSMP anormale (p<.0001), les AMC (Hazard Ratio (HR)=15.9, p-0.0001), suivi de la rétinopathie diabétique (HR-10.0, p=0.001) et de l'incapacité à effectuer un exercice (HR=7.7, p=0.02). Les patients avec une TSMP normale ont présenté un taux de revascularisations de 2.4%. La présence de défauts mixtes accroît le risque d'ECV de 20.1 fois, les défauts fixes de 8.5 fois et les défauts réversibles de 5.2 fois comparés aux sujets avec une TSMP normale. Conclusion: Les patients diabétiques, coronariens ou non, avec une tomoscintigraphie myocardique de perfusion normale ont un excellent pronostique. A l'opposé, une TSMP anormale est associée à une augmentation du risque d'ECV de plus de 5 fois. Ceci confirme l'utilité de la TSMP dans la stratification du risque chez les patients diabétiques.

Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel Ca(V)2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3 bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant Ca(V)2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.

Developmental changes in lateralized inhibition of symmetric movements in children with and without Developmental Coordination Disorder.

The present study investigates developmental changes in selective inhibition of symmetric movements with a lateralized switching task from bimanual to unimanual tapping in typically developing (TD) children and with Developmental Coordination Disorder (DCD) from 7 to 10 years old. Twelve right-handed TD children and twelve gender-matched children with DCD and probable DCD produce a motor switching task in which they have (1) to synchronize with the beat of an auditory metronome to produce bimanual symmetrical tapping and (2) to selectively inhibit their left finger's tapping while continuing their right finger's tapping and conversely. We assess (1) the development of the capacity to inhibit the stopping finger (number of supplementary taps after the stopping instruction) and (2) the development of the capacity to maintain the continuing finger (changes in the mean tempo and its variability for the continuing finger's tapping) and (3) the evolution of performance through trials. Results indicate that (1) TD children present an age-related increase in the capacity to inhibit and to maintain the left finger's tapping, (2) DCD exhibits persistent difficulties to inhibit the left finger's tapping, and (3) both groups improve their capacity to inhibit the left finger's movements through trials. In conclusion, the lateralized switching task provides a simple and fine tool to reveal differences in selective inhibition of symmetric movements in TD children and children with DCD. More theoretically, the specific improvement in selective inhibition of the left finger suggests a progressive development of inter-hemispheric communication during typical development that is absent or delayed in children with DCD.

Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

Validity of the "Drift without pronation" sign in conversion disorder.

BACKGROUND: Conversion disorder (CD) is a psychiatric disorder, yet the diagnosis cannot be established without the expertise of a neurologist, as distinguishing a functional from an organic symptom relies on careful bedside examination. Joseph Babinski considered the absence of pronator drift as a 'positive sign' for hysterical paresis but the validity of this sign has never been evaluated. The aim of this study was to examine the sensitivity and specificity of the "drift without pronation" sign. METHODS: Twenty-six patients with unilateral functional upper limb paresis diagnosed with CD (DSM-IV) and a control group of 28 patients with an organic neurological condition were consecutively included. The arm stabilisation test was performed with arms stretched out in full supination, fingers adducted, eyes closed for 10 seconds. A positive "drift without pronation" sign was defined by the presence of a downward drift without pronation. RESULTS: All CD subjects (100%) displayed a positive sign when only 7.1% of organic subjects did (Fisher's p < 0.001). The sign yielded a sensitivity of 100% (95% CI:84%-100%) and a specificity of 93% (95% CI:76%-98%). CONCLUSION: The observation of a "drift without pronation" sign is specific for Conversion Disorder and can be of help in making a quick distinction between organic and functional paresis at the bedside.

Catalogue des livres portraits, gravures & instruments d'optique. Composant la Bibliothèque et le Cabinet De feu M. Grangeret de Lagrange conservateur-adjoint à la bibliothèque de l'Arsenal, membre du conseil de la Société asiatique, ancien correcteur pour les livres orientaux à l'Imprimerie impériale, etc. : La vente aura lieu ... Les Mardi 19, Mercredi 20, Jeudi 21 et Vendredi 22 Juillet 1859 / [expert] M. Auguste Aubry, Libraire

[Vente. Livres. 1859-07-19 - 1859-07-22]

Increased condom use without other major changes in sexual behavior among the general population in Switzerland.

The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II alpha gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II beta gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II alpha may be a specific marker of cell proliferation, whereas topoisomerase II beta may be implicated in functions of DNA metabolism other than replication.

Catalogue des tableaux modernes dont la vente aura lieu... le lundi 19 février 1872... : collection de feu le bon Michel de Trétaigne / [expert] Francis Petit

[Vente. Art. 1872-02-19. Paris]

Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes

RESUME : La raréfaction des vaisseaux capillaires est une caractéristique de l'hypertension artérielle non traitée. Des données récentes indiquent que cette raréfaction peut être renversée par un traitement antihypertenseur chez les patients hypertendus non diabétiques. Malgré la fréquente association du diabète et de l'hypertension, on ne sait rien de la densité capillaire de patients diabétiques traités, souffrant d'hypertension artérielle. Nous avons dès lors recruté 21 patients normotendus (groupe contrôle), 25 patients souffrant uniquement d'hypertension artérielle , et 21 patients diabétiques (Diabète de type 2) souffrant également d'hypertension artérielle. Tous les patients hypertendus ont été traités avec un inhibiteur du système rénine-angiotensine, et une majorité présentait une tension artérielle moyenne en auto-contrôle à domicile de 135/85 mmHg ou moins. La densité capillaire a été évaluée par vidéomicroscopie sur la peau du dos des doigts et avec laser Doppler sur la peau de l'avant-bras (vasodilatation maximale induite par le chauffage local). Au final, il n'y avait pas de différence entre les groupes de l'étude, que ce soit lors des mesures de la densité capillaire sur le dos du doigt (groupe contrôle 101 ±11 capillaires, groupe des patients non- diabétiques hypertendus 99 ± 16, groupe des patients hypertendus et diabétiques 96 ± 18, p>0,5) ou lors des mesures de débit sanguin maximal sur la peau de l'avant-bras, un témoin indirect de la densité capillaire dans ce territoire (contrôles 666 ±114 unités de perfusion, non diabétique hypertendu 612 ± 126, hypertendus diabétiques 620 ±103, p> 0,5). En conclusion, notre étude est la première à démontrer que indépendamment de la présence ou non d'un diabète de type 2, la densité capillaire est normale chez les patients hypertendus présentant un contrôle raisonnable de la pression artérielle obtenue avec un bloqueur du système rénine-angiotensine.