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A growing literature shows an improvement of chronic hepatitis C virus (HCV)-related depression after successful treatment with direct-acting antivirals. However, depression after HCV cure remains insufficiently documented in people living with HIV (PLWH) and HCV, a population with specific mental health challenges. This study aimed to (i) document the prevalence of moderate-to-severe depression (PHQ-9 score ≥10) across different age classes in HCV-cured PLWH; (ii) identify associated socio-behavioral correlates.Descriptive analyses were performed on data collected during a cross-sectional survey (February 2018 - May 2019) nested in a prospective, multicenter cohort of individuals living with HIV and HCV (ANRS CO13 HEPAVIH). Socio-behavioral correlates of moderate-to-severe depression were identified using logistic regression.Among the 398 HCV-cured individuals in the study sample (median age [IQR]: 56 [53-59] years; 73.1% men), 23.9% presented with moderate-to-severe depression (PHQ-9 score ≥10). Depressive symptom prevalence rates were as follows: anhedonia: 52.3%; feeling 'down' or feelings of hopelessness: 48.3%; sleeping problems: 65.7%; lack of energy: 70.3%; eating disorders: 51.2%; lack of self-esteem: 34.3%; difficulty concentrating: 34.9%; sluggishness (in movement and voice) or restlessness: 24.6%; suicidal ideation: 17.1%. No significant difference was detected across age classes. Female sex, unhealthy alcohol use, sedentary lifestyle, and unhealthy eating behaviors were associated with increased odds of moderate-to-severe depression.Depressive symptoms were common in this sample of HCV-cured PLWH. Unlike findings for the French general population, the prevalence of depression did not decrease with age class. Mental health remains a key issue for HIV-HCV-coinfected individuals, even after HCV cure, especially in women and in individuals with unhealthy behaviors.Despite potential improvements in mental health after successful treatment with direct-acting antivirals, many people living with HIV (PLWH) and hepatitis C virus (HCV) - even in older age classes - still face depressive symptoms after HCV cure. In this population, women and people reporting unhealthy alcohol use, sedentary lifestyle, or unhealthy eating behaviors are more prone to report depressive symptoms after HCV cure. Mental health and lifestyle-related issues should be integrated in a global care model for PLWH living with or having a history of hepatitis C.

International audience; No abstract available

Background It is unclear whether HIV infection affects the long‐term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV‐uninfected (HIV−) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV− patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36‐month follow‐up. A total of 103 PLHIV and 195 HIV− patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow‐up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− patients (17.8% and 15.1%, P =0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67–3.82 [ P =0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32–30.21 [ P =0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P =0.01) and had smaller total cholesterol decreases (–22.3 versus –35.0 mg/dL; P =0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT00139958.

International audience; No abstract available

Adenosine and nitric oxide act on the fine-tuning regulation of neural cardiovascular control in the nucleus tractus solitarius (NTS). Although the interaction between adenosine and NO is well known in the periphery, the mechanisms by which adenosine interferes in the dynamics of nitrergic neurotransmission, related to neural control of circulation, are not completely understood and might be relevant for individuals predisposed to hypertension. In this study we evaluate the interaction between adenosinergic and nitrergic systems in cell culture from the dorsomedial medulla oblongata of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Using quantification of nitrite levels, RT-PCR analysis and RNA interference we demonstrate that adenosine A

Background Medication reconciliation has been carried out since 2015 in the internal medicine ward. However, prescription errors at admission still occur, mainly linked to the transcription in the CPOE system by the physician of the medication history (MH) collected by the pharmacy. In order to improve the quality of prescription at admission, we studied the implementation of a pharmacist pre-prescription (PpP) process. Purpose To evaluate the impact of the PpP on the number of unintentional medication discrepancies (UMD) at admission. Material and methods Interventional prospective study before/after in a 24–bed internal medicine unit. Eligibility criteria: age >65 years and/or >three chronic treatments at admission. Pre–intervention phase (2 months): MH provided by the pharmacist and used by the physician to write the admission prescription. Intervention phase (2 months): MH entered by the pharmacist in the CPOE system as a PpP and then used by the physician to electronically generate an admission prescription without any transcription. Data collected: age, sex, number of UMD on the admission prescription, potential of harm for the patient (minor, moderate or severe) evaluated by the prescriber and the pharmacist, prescriber satisfaction (survey). Results Eighty patients (29 males, 51 females; age 68.4±18.6; medications at admission: 8.8±4.0) were included in the pre-intervention phase. 36.2% of patients had at least one UMD (0.53±0.80 UMD/patient). 40.4% of UMDs had a moderate or severe potential of harm for the patient. The main UMDs were dosage errors (38.0%) and omissions (33.3%). In the intervention phase, 47 patients (28 males, 19 females; age 66.3±18.7; medications at admission: 8.0±4.5) were included and PpP was used for 83% of them. Patients with at least one UMD decreased to 8.5% (p=4.2 × 10–5). Among the 39 patients for whom PpP was used, no UMDs were observed. The four physicians of the ward were satisfied with this new process as it allowed a reduction in medication errors and their time spent on admission prescription. Conclusion This study shows that pre-prescription by pharmacists decreases the number of UMD at admission. The main challenge for the future will consist in integrating PpP as part of the clinical pharmacist’s routine. References and/or acknowledgements No acknowledgements. No conflict of interest.

Introduction Les infections invasives a pneumocoque sont frequentes chez les patients atteints de lupus erythemateux systemique (LES). Le vaccin antipneumococcique polysaccharidique (PPS) 23-valent est sur chez les patients atteints de LES, mais des donnees preliminaires suggerent qu’il pourrait etre moins immunogene que dans la population generale. Le vaccin conjugue pneumococcique 7-valent (PnCj) pourrait permettre d’accroitre l’immunogenicite de la vaccination. Materiels et methodes Etude multicentrique randomisee controlee versus placebo comparant deux strategies de vaccination antipneumococcique chez les patients atteints de LES et ayant une maladie stable : vaccination par placebo ou par PnCj suivie 24 semaines plus tard par un rappel vaccinal par PPS. Le critere d’evaluation principal etait la proportion de patients repondeurs a ≥ 5 des 7 serotypes (4, 6B, 9V, 14, 18C, 19F et 23F) partages a la fois par le PPS et le PnCj a la 28e semaine. Pour chaque serotype, la reponse vaccinale etait definie en Elisa comme un titre d’anticorps ≥ 1 μg/mL. L’activite opsonophagocytaire (OPA) des IgG antipneumococciques etait egalement mesuree a l’entree dans l’etude ainsi qu’a la 28e semaine. Pour chaque serotype, la reponse etait definie par l’augmentation ≥ 4 fois de l’indice d’opsonisation (IO, defini par la dilution du serum permettant de lyser 50 % de l’inoculum bacterien) entre l’entree dans l’etude et la 28e semaine, et par un IO ≥ 8 a la 28e semaine. Resultats Vingt-cinq patients ont ete randomises dans le bras placebo-PPS et 17 dans le bras PnCj-PPS. A l’inclusion, 39 (93 %) patients etaient traites par antipaludeens de synthese, 36 (86 %) par glucocorticoides et 16 (38 %) par immunosuppresseurs (mycophenolate mofetil : n = 8 ; azathioprine : n = 5 ; methotrexate : n = 3). Aucun episode infectieux respiratoire n’est survenu pendant la duree de l’etude. A la 28e semaine, le critere de jugement principal etait atteint chez 72 % (18/25) des patients du bras placebo-PPS et chez 77 % (13/17) des patients du bras PnCj-PPS (p = 0,75). Les taux de patients repondeurs en OPA pour ≥ 5 des 7 serotypes partages a la fois par le PPS et le PnCj etaient de 7/25 (28 %) dans le bras placebo-PPS et de 6/17 (35 %) dans le bras PnCj-PPS (p = 0,38). A la 52e semaine, 13/18 (72 %, bras placebo-PPS) et 10/13 (77 %, bras PnCj-PPS) des patients qui etaient repondeurs en Elisa a la 28e semaine a au moins 5 des 7 serotypes partages par les deux vaccins gardaient une immunite protectrice (p = 0,77). Dans l’ensemble, la proportion de patients repondeurs a la 52e semaine etait de 52 % (13/25) dans le bras placebo-PPS et de 59 % (10/17) dans le bras PnCj-PPS (p = 0,66). Au cours du suivi, aucune infection pneumococcique n’a ete rapportee. Neuf poussees de LES sont survenues chez 6 patients (4 dans le bras placebo-PPS et 2 dans le bras PnCj-PPS, p = 0,70). Conclusion L’administration sequentielle du vaccin PnCj puis du vaccin PPS est sure et efficace a court terme chez les patients atteints de LES mais n’est pas superieure a la vaccination par PPS seule.

Resume La maladie de Behcet est une maladie systemique d’etiologie inconnue caracterisee par une aphtose bipolaire (buccale et genitale) recidivante associee a des manifestations oculaires, cutanees, vasculaires, digestives ou articulaires. Les gynecologues obstetriciens peuvent etre confrontes a cette maladie a tout moment de la vie de leurs patientes, y compris pendant la grossesse. Les premieres manifestations de la maladie pouvant etre des lesions genitales, ils peuvent etre en premiere ligne pour evoquer ce diagnostic. Ils doivent donc en connaitre les principales caracteristiques afin de penser precocement au diagnostic et assurer une prise en charge multidisciplinaire adaptee. Au cours de la grossesse, le traitement de la maladie est a adapter : traitement de fond a moduler, therapeutiques prophylactiques a introduire, retrait de tout medicament teratogene. Il est important d’avoir le traitement optimal pour eviter toutes rechutes ou poussees au cours de la grossesse, a des doses minimales pour eviter d’exposer le fœtus plus que necessaire.

Introduction There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. Methods A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts’ opinion and level of agreement were evaluated. Results The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3–6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10 mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was “very good” for eleven, and “good” for the remaining three. Conclusion Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.

To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS).A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma.One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence.In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

Angiotensin II (ANG II) causes a systemic pressor effect when injected into the cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG II pressor effect are over 100 times larger than in the systemic circulation. Considering the discrepancy of doses, the possibility that ANG II may reach the systemic circulation and promote pressor effects, following injection into the fourth ventricle, was investigated. The effects on blood pressure of different vasoactive peptides that produce pressor responses when injected into the central nervous system were compared. Dose–response curves were obtained for intravenous or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP), bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP, 0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations, pressor responses occurred in the donor rat following injection into the fourth cerebral ventricle of the recipient animal, showing that effective doses of ANG II, administered to the fourth cerebral, reach the systemic circulation. The same results were obtained for the microinjection of 4 nmol of LVP into the fourth cerebral ventricle of recipient animals. High-performance reverse-phase liquid chromatography analyses of arterial blood showed that approximately 1% of the [125I]ANG II injected into the fourth cerebral ventricle may be recovered from the systemic circulation a few seconds after the microinjection. The systemic administration of the ANG II receptor antagonist losartan blocked the response to ANG II injected into the fourth ventricle whereas antagonist administration in the same ventricle did not. Angiotensin injections into the lateral ventricle produced pressor responses that were reduced by antagonist administration to the same ventricle but not by systemic administration of the antagonist. The data suggest that the pressor effect resulting from ANG II or LVP injections into the fourth cerebral ventricle may be due to the action of this peptide in the systemic circulation. On the other hand, the pressor effect due to ANG II microinjection into the lateral ventricle apparently results from the direct stimulation of central periventricular structures.Key words: angiotensin, cerebral ventricles, pressor effect, systemic action.

The regulation by neuropeptide Y of α 2 -adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l -noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1–36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1–36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l -noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1–36) must be employed to counteract the vasodepressor response to l -noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the α 2A -adrenoceptor messenger RNA levels and the B max value of the α 2 -adrenoceptor agonist [ 3 H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1–36) at 1 nM led to a significant increase in the K d value of [ 3 H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1–36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1–36) to antagonistically modulate α 2 -adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of α 2A -adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the α 2A -adrenoceptor messenger RNA levels and the α 2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1–36) to antagonize α 2 -adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.

We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a major factor of their proliferation. In other lymphomas, the IL-6 gene is expressed only in malignancies where differentiated malignant cells are present. In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells express the IL-6 receptor. In patients with HIV infection, the level of production of IL-6, IL-10, and IL-13 is not higher than those of other conditions with immune activation. However, IL-6 contributes to increased production of IgG and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node germinal centers, partly originating from follicular dendritic cells, which may explain some of the pathogenesis of this disease. In systemic lupus erythematosus, the critical cytokine is IL-10, which is produced in large amounts by B lymphocytes and monocytes and is responsible for autoantibody production. Taken together, these data emphasize the roles of IL-6 and IL-10, usually produced by nonlymphoid cells, on B lymphocytes, either malignant or hyperactivated.

A sixty-year old female was referred to the Internal Medicine Department for the treatment of a diffuse high-grade non Hodgkin's lymphoma. She presented episodes of fever in context of neutropenia (neutrophils 0.35 x 10(9)/1 from 1.6 x 10(9)/1 white blood cells). Hemoglobin level was 8.2 g/dl and platelets 132 x 10(12)/1. A monoclonal IgM-Kappa protein (48 g/l) was detected in her serum. A direct antiglobulin test on the red cells proved positive with anti-C3d but not with anti-IgG antiglobulin, due to the presence of an IgM cold antibody with a serological anti-i specificity. The IgM antibody was found on the patient's neutrophils as well as in her serum. The antibody recognized all neutrophils tested in conventional serological tests whether the neutrophil phenotypes in systems NA, NB, and 5. It was demonstrated that it recognized the i antigen expressed on the neutrophils. These results suggest that a cold agglutinin anti-i might be responsible for neutropenia in some patients.

Resume Les auteurs rapportent l'observation d'un homme de 60 ans atteint d'uveite chronique et invalidante. En l'absence de signes neurologiques et compte tenu de signes articulaires et d'une malabsorption isolee, un diagnostic de maladie de Whipple est evoque et initialement ecarte devant la normalite de la biopsie duodenale. Le diagnostic est rectifie secondairement devant les caracteres evolutifs de l'uveite, l'apparition d'une adenopathie et la presence dans un prelevement vitreen de macrophages contenant des corps PAS+. Sous traitement associant rifampicine et trimethoprime-sulfamethoxazole, l'uveite s'est rapidement et totalement amelioree. Les diverses manifestations oculaires de la maladie de Whipple sont evoquees et les traitements actuels discutes d'apres les donnees de la litterature.

An interaction between angiotensin II (Ang II) receptors and α 2 -adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC 50 value of l -noradrenaline when competing for [ 3 H] p -aminoclonidine ([ 3 H]PAC) binding sites, which reached a maximum of 400% with 10 nM of Ang II and was associated with a small decrease in the B 0 value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC 50 value of about 57%, and no change was observed in the B 0 value. Saturation analysis also showed that Ang II (0.1 nM) increased the K D value of [ 3 H]PAC in the WKY strain but in contrast decreased the K D value of [ 3 H]PAC in the SHR. The B max value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced by l -noradrenaline coinjected in the NTS of the WKY rat. No effect was observed in heart rate. In the SHR no counteraction of the l -noradrenaline-induced vasodepressor effect was found, and in contrast a slight increase of the vasodepressor effect associated with a significant increase in the bradycardiac response was observed. The results give evidence for an antagonistic Ang II/α 2 receptor interaction in the cardiovascular part of the NTS of the WKY rat as previously observed in the Sprague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/α 2 receptor interaction enhances α 2 affinity and possibly α 2 receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.

To evaluate the potential of (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB).Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent (18)F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV(max)) of the most (18)F-FDG avid lesions was recorded.The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. (18)F-FDG PET/CT detected active pulmonary TB (n = 1), extra-pulmonary (n = 10) or both (n = 10). The second (18)F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV(max) of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months.(18)F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB.

The modulation of α 2 -adrenoceptors by neuropeptide Y Y 1 and neuropeptide Y Y 2 receptor subtypes has been studied in the nucleus tractus solitarii of the male rat. The autoradiographical experimennts showed that neuropeptide Y-(1–36), neuropeptide Y-(13–36), a selective neuropeptide Y Y 2 receptor agonist, and [Leu 31 , Pro 34 ]neuropeptide Y, a selective neuropeptide Y Y 1 receptor agonist, in the nanomolar range increased the K d value of the [ 3 H] p -aminoclonidine binding sites in the above rank order of potency without changng the B max values. In contrast, in the competition experiments, the neuropeptide Y Y 1 and the neuropeptide Y Y 2 receptor agonists decreased and increased, respectively, with the same potency the IC 50 value of l -adrenaline and especially of clonidine for the α 2 -adrenoceptor agonist binding sites associated with an increase and a decrease of the B 0 value, respectively. Cardiovascular experiments showed that microinjections of clonidine into the nucleus tractus solitarii induced dose-dependent vasodepressor and bradycardiac responses. Threshold doses for vasodepressor effects of neuropeptide Y-(1–36) and of the neuropeptide Y Y 1 receptor agonist and for vasopressor effects of the neuropeptide Y Y 2 receptor agonist significantly counteracted the vasodepressor action elicited by an ED 50 dose of clonidine in the nucleus tractus solitarii, the bradycardiac action of clonidine also being counteracted by the neuropeptide Y Y 2 but not the neuropeptide Y Y 1 receptor agonist. The present results give indications for the existence of an antagonistic modulation of high affinity α 2 -adrenoceptors by the neuropeptide Y Y 1 and neuropeptide Y Y 2 receptor subtype in the nucleus tractus solitarii which may contribute to a reduction of α 2 -adrenoceptor-mediated cardiovascular depression.

Objective. Interleukin-10 (IL-10) is a potent stimulator of B lymphocytes in vitro. In vivo dysregulation of IL-10 gene expression was therefore analyzed in patients with rheumatoid arthritis (RA), primary Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE). Methods. Spontaneous production of IL-10 by peripheral blood mononuclear cells was measured using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay in untreated patients with either RA (n = 10), SS (n = 10), or SLE (n = 10), and in 15 normal control subjects. Results. IL-10 production was dramatically higher in RA, SS, and SLE patients than in controls. In each group, both B lymphocytes and monocytes, but not T lymphocytes, produced IL-10. Conclusion. IL-10 production is increased in RA, SS, and SLE. It may play a role in B lymphocyte hyperactivity and in the development of autoimmunity.

The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.

The cardiovascular effects of adrenaline microinjected alone or together with neuropeptide Y (NPY) receptor agonists into the nucleus tractus solitarius (Sol) of the anaesthetized rat have been investigated in order to evaluate NPY/adrenergic receptor interactions. In the dose range 0.05-20 nmol, adrenaline microinjected unilaterally into the Sol produced significant dose-related reductions in mean arterial blood pressure and heart rate. The vasodepressor action of a close to ED50 dose of adrenaline (0.5 nmol) was significantly counteracted by a threshold dose of NPY (1-36) (1 pmol) and of the NPY Y1 receptor agonist [Leu31,Pro34]NPY (2.5 pmol) microinjected into the Sol, but not by a threshold dose of NPY(13-36)(50 fmol), a selective Y2 receptor agonist. The present study provides evidence for an antagonistic NPY Y1/adrenergic receptor interaction in the Sol of the rat, involved in cardiovascular regulation.

International audience; OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

This research involves a new approach for the study of the mechanical properties of single living cells. The main idea is to use micro electro mechanical systems (MEMS) to investigate the Young modulus and the morphological modification of cells from the engineering point of view. Many different techniques already exist for a local cell analysis but our goal is to be able to test the properties of a single adherent cell in his complexity. We realized a completely transparent device which is versatile and can be coupled with other analysis tools such as atomic force microscopy (AFM) and patch clamp. Starting from a transparent wafer we developed a system to obtain high transparency suspended structures. All structures are made by using micro fabrication techniques. Our MEMS is composed by 3 main parts: (i) testing, (ii) measurement and (iii) actuation area.

A novel, completely transparent bio-MEMS (bio-Micro Electro Mechanical System) device has been devised and manufactured using finite element analysis (FEA) and micro-fabrication techniques. The device has been designed to be used for testing the mechanical properties of single living cells, it is versatile and suitable for coupling with other analysis techniques. Furthermore, being completely transparent, it can be used with either transmission or reflection microscopes. The transparent bio-MEMS is based on a silicon dioxide–silicon nitride structure and, since the main goal is to test living cells, it is meant to work in a liquid environment and allow for cell stretching. Sensors for cell deformation and for platform displacement are also present and the required sensitivity for single cell analyses is granted. The device will moreover allow the recording of the stress–strain curve for single living cells.

Using angiotensin II (ANG II) to compete with (3-[125I]iodotyrosyl-4, Sar1, Ile8)ANG-II ([125I]Sar1, Ile8)ANG II) for its binding sites in the nucleus of the solitary tract (nTS) and the paraventricular hypothalamic nucleus (PV) bradykinin (10 nM) reduced the IC50 value (48 nM) of ANG II, an action blocked by the bradykinin B2 antagonist HOE-140 (100 nM). In contrast, when analysing the high-affinity site (Kd 3.1 nM) for [125I]ANG II in the nTS bradykinin (10 nM) increased the Kd value. Thus, a central bradykinin/ANG II receptor interaction may exist involving a differential regulation of the high- and low-affinity ANG II receptors in the nTS. This regulation by bradykinin of angiotensin receptors in the nTS may help to explain the central vasopressor effect of bradykinin.

Behçet's disease is a multisystemic disease of unknown origin characterized by a recurrent bipolar aphtosis (oral and genital) associated with vascular, digestive or articular symptoms. Gynecologists can be faced to this disease at any time of the life of their patients, including during the pregnancy. Given that the first demonstrations of the disease can be genital, they are in the front line to evoke this diagnosis. They thus have to know the main characteristics of the disease to make the diagnosis and to organize a multidisciplinary management. During pregnancy, the treatment of the disease is to be adapted to avoid teratogenic drugs, and adapt the doses of the treatment.

Interferon-gamma (IFN-gamma) has been shown to inhibit human immunodeficiency virus (HIV) replication in macrophages. However, the site of its effect on the HIV infectious cycle is unknown. We show here that IFN-gamma inhibits the transactivation of HIV long terminal repeat (LTR) during viral infection and that it antagonizes tat effect in HT4LacZ-1 cells. HT4LacZ-1 is an indicator CD4+ HeLa cell line for HIV infectivity, because it harbors a HIV LTR-LacZ gene susceptible to transactivation by tat. It was used in combination with a computer-assisted image analyzer to quantify: (i) the number of transactivated foci following HIV infection, (ii) their individual level of transactivation, and (iii) the fusion potency of infected cells. IFN-gamma induced a 75% decrease of the number of transactivated foci following infection of HT4LacZ-1 cells by HIV. The remaining 25% foci still susceptible to transactivation were transactivated at a lower level than in control cultures, and the fusion potency of infected cells was strongly decreased. IFN-gamma acted after HIV entry into the cell and independently of reverse transcription. IFN-gamma antagonized tat-induced LTR transactivation: it inhibited transactivation of HT4LacZ-1 cells when tat was provided either from a SV40-based expression vector of tat or by polyethylene glycol-induced cell fusion with HeLa-tat-III cells. These results suggest that IFN-gamma affects the expression or the activity of cellular factors interacting with tat and that the high level of IFN-gamma production associated with HIV infection plays a role in the establishment of HIV latency.

1. Kinin analogues bradykinin (BK), T-kinin, Met-Lys-BK, Lys-Lys-BK, Des-Arg9-BK with agonist activity and D-Arg0-Hyp3-Thi5,8-D-Phe7-BK (DAHTDBK) and Arg9-Leu8-BK with antagonist activity were injected into the posterior portion of the fourth cerebral ventricle of unanaesthetized rats implanted with permanent cannulae and arterial pressure was measured directly from the abdominal aorta. 2. The spontaneously hypertensive rats (SHR) were more sensitive than normotensive Wistar rats (NWR) to the pressor effect of BK and other kinin analogues. The SHR did not differ in sensitivity of the pressor response to centrally administered angiotensin II or endothelin-1. 3. Experiments with selective kinin agonists and antagonists revealed that in the SHR, as in the NWR, the receptors which mediated the central pressor response are of the BK2 subtype. 4. Measurements of the pressor activity of kinins with different degrees of susceptibility to degradation, as well as experiments with kininase inhibitors, enalaprilat and CPP-Ala-Ala-Phe-pAB, suggest that the kininase activity in the central nervous system of SHR is reduced in comparison to that of NWR. 5. The SHR also showed increased sensitivity to BK and Lys-Lys-BK, compared with the NWR, when the kinins were injected following the administration of a mixture of the kininase inhibitors, suggesting that mechanisms other than kininase activity may play a role in the increased sensitivity of the SHR to the central pressor action of kinins. 6. An in vivo characterization of the kinin receptors which mediate the central pressor response showed that the interaction with DAHTDBK was reversible and of competitive nature. The pA2 in vivo estimated for the kinin receptors of the SHR was 0.7 logarithm units larger than that obtained in the NWR. 7. The kinin receptors which mediate the central BK pressor effect in the SHR are of the BK2 subtype and are similar to receptors in the NWR. The increased sensitivity to kinins in the SHR may be explained, at least in part, by their decreased kininase activity. At present it is impossible to conclude whether the difference observed in the pA2 represents an increased affinity of the kinin receptors or can be attributed to differences amongst strains in the enzymatic degradation of the antagonist.

Background Medicines reconciliation (MR) is a critical step for reducing medicines errors (ME) at admission to hospital care. However, because of resource constraints it can be difficult to implement in hospital pharmacists’ everyday practice. The Lean method is used to streamline and optimise processes considering all stakeholders and resources. Purpose To redesign the medicines management process at admission to reduce MEs. Material and methods A Lean approach review was conducted of the current medicines management process at admission (retroactive MR process) in order to define the new process (proactive MR), with all the stakeholders (clinicians, nurses, pharmacists, pharmacy technicians, head nurses). 5 activities were performed: mapping of the current process (retroactive MR process) measure of unintended medicines discrepancies (UMDs) at admission analysis of the collected data and root cause implementation design of a new improved process (proactive MR) implementation and measurement of the new process Only patients more than 65 years old and/or taking at least 3 medicines before admission were included. Results 52 patients were initially included (75 years, 7.4 medicines/patient). 46% had at least 1 UMD (0.75 UMDs/patient) and 28.2% of UMDs had the potential to cause moderate to severe discomfort or clinical deterioration. After implementation of the new MR process, 50 patients were included (70 years, 6.9 medicines/patient). The percentage of patients with at least 1 UMD decreased to 12% (p Conclusion Results demonstrate that proactive MR is effective in reducing ME on admissions orders and suggest that Lean is fully adapted to improve the medicines management process. Other studies are warranted to evaluate the impact of Lean on ME reduction. References and/or acknowledgements No conflict of interest.

Among numerous neurotransmitters involved in central cardiovascular control, glutamate is one of the most studied transmitters that are related to nicotine considering its release and its postsynaptic regulation. However, there are no conclusive studies about nicotine effects on glutamatergic system and its relevance on hypertension development, which can help to understand the role of these two systems in that pathology. In this context, the objective of the present study is to evaluate the effects of systemic chronic nicotine exposure on hypertension development as well as the interaction between nicotine and the glutamatergic system in normotensive and neurogenic hypertensive rats. By means of high performance liquid chromatograph, immunohistochemistry, in situ hybridization and binding techniques, glutamatergic system was evaluated in SHR and Wistar Kyoto (WKY) rats treated with nicotine, delivered subcutaneously through nicotine pellets, for 8 weeks. The most important findings in this study were that (1) moderate doses of nicotine accelerated the onset and increased blood pressure in SHR but not in WKY rats, (2) the nicotine dosage and time of treatment employed did not affect body weight, (3) chronic nicotine treatment differentially affected glutamatergic system in normotensive and hypertensive rats, and (4) spontaneously hypertensive rats seem to be more sensitive to peripherally administered nicotine than Wistar Kyoto rats considering blood pressure and glutamatergic neurotransmission changes. In conclusion, we have demonstrated that a moderate dose of nicotine accelerates the onset and exacerbates hypertension in the SHR and that might be, at least in part, related to the modulation of glutamatergic neurotransmission.

Intra-vascular lymphoma is usually reported as a rare and fatal disorder. We describe here the first case of an intra-vascular lymphoma revealed by a nephrotic syndrome for which a durable remission has been obtained by 8 cycles of bi-mensual CHOP and Rituximab therapy. In this report, 18 fluorodesoxyglucose tomoscintigraphy is discussed as a tool for intra-vascular lymphoma extension and follow-up.

Excisional biopsy for lymphadenopathy is sometimes necessary to confirm the diagnosis of lymphoma or metastatic disease from an unknown primary site. Lymph node excision should be preceded by less invasive approaches which may confirm a benign pathology. Collaboration with medical and hematologic specialists will allow a well-reasoned diagnostic approach with complementary studies; excisional biopsy, if necessary, will then be done under the best conditions and in the most cost-efficient manner.

In vitro thyroid function tests are among the most frequently prescribed laboratory procedures. Serum triiodothyronine (T3) tests are seldom necessary as a first-level measurement. Our objectives were to measure the proportion of T3 measurements relative to all in vitro thyroid function tests in a large hospital network and to investigate the contributions of various interventions to change prescribers'behavior. We performed two cross-sectional surveys in 1995 and 1998 in the 50 Paris University hospitals. Questionnaires were mailed to the heads of the 30 laboratories performing thyroid function tests. One-month orders of free and total thyroxine, free and total T3 and thyrotropin were recorded; changes in T3 measurement orders between the two periods were estimated and association with interventions were expressed as odds ratios and 95% confidence intervals. Twenty-five heads of laboratory responded to both surveys. In 1995, T3 measurements constituted 21% of in vitro thyroid function test ordering, which seems to us exceedingly high. The decrease in T3 measurement ordering observed in 1998 (15% of thyroid function test ordering) was independently associated with multiple behavioral changes: educational interventions, structured test form use and year of prescription.

To determine the distribution of orders for hormonal tests assessing thyroid function in a hospital setting. To collect the opinion of physicians specialized in endocrinology concerning free triodothyronine (FT3) assessment.Using a cross-sectional survey numbers of free thyroxine (FT4), total T4 (TT4), FT3, total T3 (TT3), and TSH tests were collected from the heads of laboratory assessing thyroid function in June 95 at the Assistance Publique-Hôpitaux de Paris (AP-HP). Cost for these tests was estimated. The physicians of the AP-HP specialized in endocrinology were asked through a questionnaire for circumstances justifying FT3 test ordering.Twenty-eight laboratories (93%) responded: 28455 measurements (TSH: 43%, FT4: 33%, TT4: 2%, FT3: 20%, TT3: 2%) were performed and were valued at 3.4 million French Francs. Proportions of T4 (36%) and T3 (20%) tests were lower in hospitals with an inpatient department of endocrinology than in hospitals with an outpatient clinic with specialists in endocrinology (T4: 36%; T3: 27%) or with no endocrinology unit (T4: 33%, T3: 27%); proportion of TSH tests was higher in hospitals with an inpatient endocrinology unit (respectively 44%, 40%, 32%). Forty-two endocrinologists (76%) from 21 departments answered. Follow-up of treatment with amiodarone and euthyroid sick syndrome were considered the only conditions justifying FT3 test ordering.Though the opinion of physicians specialized in endocrinology was not uniform regarding recommendations for TT3 or FT3 tests as a first-line measurement, the cost of these tests has been estimated at 650 thousand Francs for a month at the AP-HP.