Segmental body composition assessed by bioelectrical impedance analysis and DEXA in humans.

The present study assessed the relative contribution of each body segment to whole body fat-free mass (FFM) and impedance and explored the use of segmental bioelectrical impedance analysis to estimate segmental tissue composition. Multiple frequencies of whole body and segmental impedances were measured in 51 normal and overweight women. Segmental tissue composition was independently assessed by dual-energy X-ray absorptiometry. The sum of the segmental impedance values corresponded to the whole body value (100.5 +/- 1.9% at 50 kHz). The arms and legs contributed to 47.6 and 43.0%, respectively, of whole body impedance at 50 kHz, whereas they represented only 10.6 and 34.8% of total FFM, as determined by dual-energy X-ray absorptiometry. The trunk averaged 10.0% of total impedance but represented 48.2% of FFM. For each segment, there was an excellent correlation between the specific impedance index (length2/impedance) and FFM (r = 0.55, 0.62, and 0.64 for arm, trunk, and leg, respectively). The specific resistivity was in a similar range for the limbs (159 +/- 23 cm for the arm and 193 +/- 39 cm for the leg at 50 kHz) but was higher for the trunk (457 +/- 71 cm). This study shows the potential interest of segmental body composition by bioelectrical impedance analysis and provides specific segmental body composition equations for use in normal and overweight women.

Y-90 Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced Stage Follicular Non Hodgkin's Lymphoma Updated Results After a Median Follow up of 662 Months From the International, Randomized, Phase III First Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

A meta-analysis of the association of fracture risk and body mass index in women.

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.

Environnement et capacités cognitives chez le rat : compétition entre les facteurs qui influencent les stratégies spatiales

RESUME Ce travail se propose de discuter des résultats comportementaux observés chez des rats obtenus dans trois paradigmes expérimentaux différents : le bassin de Morris (Morris Water Maze, Morris, 1984) ; la table à trous (Homing Board, Schenk, 1989) et le labyrinthe radial (Radial Arm Maze, Olton et Samuelson, 1976). Les deux premières tâches sont spatiales et permettent un apprentissage de place en environnements contrôlés, et la troisième est une tâche comportementale qui différencie deux habiletés particulières, celle d'élimination (basée sur la mémoire de travail) et celle de sélection (basée sur la mémoire de référence). La discussion des résultats porte sur les stratégies de navigation utilisées par les animaux pour résoudre les tâches et plus précisément sur les facteurs qui peuvent influencer le choix de ces stratégies. Le facteur environnemental (environnement contrôlé) et le facteur cognitif (vieillissement) représentent les variables étudiées ici. C'est ainsi que certaines hypothèses communément acceptées ont été malmenées par nos résultats. Or si l'espace est habituellement supposé homogène (toutes les positions spatiales présentent le même degré de difficulté lors d'un apprentissage en champ ouvert), ce travail établit qu'une position associée -sans contiguïté - à l'un des trois indices visuels situés dans la périphérie de l'environnement est plus difficile à apprendre qu'une position située entre deux des trois indices. Deuxièmement, alors qu'il est admis que l'apprentissage d'une place dans un environnement riche requiert le même type d'information. dans la bassin de Morris (tâche nagée) que sur la table à trous (tâche marchée), nous avons montré que la discrimination spatiale en bassin ne peut être assurée par les trois indices visuels périphériques et nécessite la présence d'au moins un élément supplémentaire. Enfin, l'étude du vieillissement a souvent montré que l'âge réduit les capacités cognitives nécessaires à la navigation spatiale, conduisant à un déficit général des performances d'un animal sénescent, alors que dans notre travail, nous avons trouvé les animaux âgés plus performants et plus efficaces que les adultes dans une tâche particulière de collecte de nourriture. Ces expériences s'inscrivent dans une étude générale qui met à l'épreuve le modèle théorique proposé pax Schenk et Jacobs (2003), selon lequel l'encodage de la carte cognitive (Tolman, 1948 ; O'Keefe et Nadel, 1978) se ferait dans l'hippocampe par l'activité de deux modules complémentaires :d'une part le CA3 - Gyrus Denté pour le traitement d'une trame spatiale basée sur des éléments directionnels et Jou distribués en gradient (bearing map) et d'autre part le CAl - Subiculum pour le traitement des représentations locales basées sur les positions relatives des éléments fixes de l'environnement (sketch map). SUMMARY This work proposes to talk about behavioural results observed in three different experimental paradigms with rats: the Morris Water Maze (Morris, 1984); the Homing Board (Schenk, 1989) and the Radial Arm Maze (Olton and Samuelson, 1976). The two first tasks are spatial ones and allow place learning in controlled environments. The third one is a behavioural task which contrasts two particular skills, the elimination (based on working memory) and the selection one (based on reference memory). The topic of the discussion will be the navigation strategies used by animals to solve the different tasks, and more precisely the factors which can bias this strategies' choice. The environmental (controlled) and the cognitive (aging) factors are the variables studied here. Thus, some hypotheses usually accepted were manhandled by our results. Indeed, if space is habitually homogenously considered (all spatial positions present the same degree of difficulty in an open field learning), this work establishes that an associated position -without being adjacent - to one of the three visual cues localised in the environmental periphery is more difficult to learn than a configurationnel position (situated between two of the three cues). Secondly, if it is received that place learning in a rich environment requires the same information in the Morris water maze (swimming task) that on the Homing board (walking task), we showed that spatial discrimination in the water maze can't be provided by the three peripheral cue cards and needs the presence of a supplementary cue. At last, aging studies often showed that oldness decreases cognitive skills in spatial navigation, leading to a general deficit in performances. But, in our work, we found that senescent rats were more efficient than adult ones in a special food collecting task. These experiments come within the scope of a general study which tests the theoretical model proposed by Jacobs and Schenk (2003), according to which the cognitive map's encoding (Tolman, 1948, O'Keefe and Nadel, 1978) should take place in the hippocampus by two complementary modules, first the DG-CA3 should encode directional and/or gradients references (the bearing map), and secondly the Subiculum-CAl should process locale elements (the sketch map).

Long-term follow-up of follicular lymphoma (FL) patients receiving single agent rituximab at two different schedules in trial SAKK 35/98

Background: In FL, Rituximab as a single agent delivered in the standard schedule (4 times weekly) may induce a response rate of 50−70% with an event-free survival (EFS) of 1−3 years according to patients' characteristics. Prolonged Rituximab exposure seems to improve EFS at least in responding patients and to increase the rate of longterm responders. Here we report long-term results of a clinical trial comparing single agent Rituximab delivered in the standard schedule versus prolonged exposure, with focus on the proportion of long-term responders and their characteristics. Material and Methods: Between 1998 and 2002, chemotherapy na¨ıve (n = 64) or pre-treated (n = 138) FL patients received Rituximab in the standard schedule. Those responding or with stable disease were randomized to no further treatment (observation, n = 78) or 4 additional doses of Rituximab given at 2-month intervals (prolonged exposure, n = 73). EFS was calculated from the first dose of standard schedule until progression, relapse, second tumor or death. Results: At a median follow up of 9.4 years and with all living patients having been followed for at least 5 years, the median EFS is 13 months for the observation and 24 months for the prolonged exposure arm (p = 0.0007). In the observation arm 13% had no event at 5-years and only 4% at 8 years, while in the prolonged exposure arm it was 27% at 5 years and remained 21% at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was the prolonged Rituximab schedule (hazard ratio 0.58, CI 0.39−0.86, p = 0.007), whereas being chemotherapy na¨ıve, presenting with stage

Improved prediction of coronary heart disease with markers of atherosclerosis and of inflammation in older adults?

Background: Several markers of atherosclerosis and of inflammation have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been well established, especially in the elderly. Methods: We studied 2202 men and women, aged 70-79, without baseline cardiovascular disease over 6-year follow-up to assess the risk of incident CHD associated with baseline noninvasive measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were studied as either nonfatal myocardial infarction or coronary death ("hard" events), and "hard" events plus hospitalization for angina, or the need for coronary-revascularization procedures (total CHD events). Results: During the 6-year follow-up, 283 participants had CHD events (including 136 "hard" events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38-2.75, p for trend <0.001), TNF-a of 1.45 (95%CI: 1.04-2.02, p for trend 0.03), of 1.66 (95%CI: 1.19-2.31) for AAI 0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not independently associated with CHD events. Results were similar for "hard" CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction of CHD; C-index for "hard"/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in the highest quartile of IL-6 combined with an AAI 0.90 or >1.40 yielded an HR of 2.51 (1.50-4.19) and 4.55 (1.65-12.50) above FRS, respectively. With use of CHD risk categories, risk prediction at 5 years was more accurate in models that included IL-6, AAI or both, with 8.0, 8.3 and 12.1% correctly reclassified, respectively. Conclusions: Among older adults, markers of atherosclerosis and of inflammation, particularly IL-6 and AAI, are independently associated with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors.

Peut-on exclure l'hypothèse d'une imitation parfaite de signature?

L'expert, en présence d'une signature contestée qu'il juge authentique, peut être confronté à l'argument selon lequel il pourrait s'agir d'une imitation parfaite. Les différents facteurs pouvant avoir un impact sur cette possibilité sont inventoriés et discutés dans cet article. Il s'agit principalement d'éléments liés soit à la signature en tant que telle, par exemple sa complexité et son degré de variation, soit à l'imitateur putatif, en particulier ses compétences. Pour répondre à la question d'un magistrat sur la possibilité de se trouver face à une imitation parfaite, l'expert sera armé pour écarter la simple explication que représente l'imitation parfaite au profit d'une discussion des résultats balancée et cohérente, où l'ensemble de ces facteurs sont discutés dans un cadre d'évaluation probabiliste.

PsyCoLaUS: santé mentale et maladies cardiovasculaires: association fortuite [PsyCoLaus: mental disorders and cardiovascular diseases: spurious association?].

Cardio-vascular diseases (CVD), their well established risk factors (CVRF) and mental disorders are common and co-occur more frequently than would be expected by chance. However, the mechanisms underlying this association are still poorly understood. The main study questions of PsyCoLaus, the psychiatric arm of CoLaus, are: 1) Do mental disorders increase vulnerability to CVRF and CVD? 2) Do CVRF and CVD promote the development of mental disorders? 3) Do CVRF/ CVD and mental disorders share common pathogenetic processes? The longitudinal project adds a comprehensive psychiatric evaluation to the CoLaus investigation. A better understanding of the psychological, physiological and behavioral links underlying CVD/ CVRF and mental disorders will result in the development of more specific and efficient strategies of prevention and treatment for both psychiatric and CVD/CVRF, two major elements of burden of disease.

Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma.

PURPOSE: We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission. PATIENTS AND METHODS: Patients with CD20(+) stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment. RESULTS: A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. (90)Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P &lt; .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P &lt; .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After (90)Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients. CONCLUSION: Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.

Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis.

Viral double-stranded RNA (dsRNA) is a ubiquitous intracellular "alert signal" used by cells to detect viral infection and to mount anti-viral responses. DsRNA triggers a rapid (complete within 2-4 h) apoptosis in the highly-susceptible HeLa cell line. Here, we demonstrate that the apical event in this apoptotic cascade is the activation of procaspase 8. Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. Both arms impinge upon, and activate, procaspase 9 via two different cleavage sites within the procaspase 9 molecule (D330 and D315, respectively). This is the first in vivo demonstration that the "effector" caspase 3 plays an "initiator" role in the regulation of caspase 9. The dsRNA-induced apoptosis is potentiated by the inhibition of protein synthesis, whose role is to accelerate the execution of all apoptosis steps downstream of, and including, the activation of caspase 8. Thus, efficient apoptosis in response to viral dsRNA results from the co-operation of the two major apical caspases (8 and 9) and the dsRNA-activated protein kinase R (PKR)/ribonuclease L (RNase L) system that is essential for the inhibition of protein synthesis in response to viral infection.

Quantitative ultrasound of bone in institutionalized elderly women: a cross-sectional and longitudinal study.

Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85 +/- 7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p < 0.001) with age in BUA, SOS and stiffness index (-0.47%, -0.06%, and -1.01% respectively per year). In the 94 women, (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p < 0.0001) than in the 176 women with no history of fracture (-8.3% for BUA, -1.3% for SOS, -18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4 +/- 0.8 months showed no significant decrease in BUA (-1%) but a significant decrease in SOS (-0.3%, p < 0.0001) and in stiffness index (-3.6%, p < 0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow.

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

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.

Molecular and physiological characterisation of lonotropic receptors in the sacculus in drosophila

Chemosensation is the detection of chemical signals in the environment that enable an animal to make informed decisions about food choice, mate preference or predator detection. Dissecting the molecular and neural mechanisms by which animals detect chemical cues is an important goal towards understanding how they interact with the environment. An attractive system to dissect the mechanisms of chemosensation is the olfactory system. One of the most-investigated olfactory systems is that of Drosophila melanogaster, a model organism that is amenable to a powerful combination of genetic and physiological analyses. Embedded within the antennal olfactory organ of Drosophila is an unusual sensory structure called the sacculus. The sacculus is comprised of three distinct chambers, each lined with several sensilla housing two to three neurons. Previous morphological, anatomical and surgical studies of sacculus neurons have implicated sacculus neurons in chemosensation, hygrosensation and/or thermosensation. While a subset of sacculus neurons have been physiologically characterised as temperature sensors, the role of this organ has remained largely mysterious, due to its inaccessibility to peripheral electrophysiological analysis. Recently a new family of olfactory receptors, the lonotropic Receptors (IRs), was identified. Five IRs are expressed in sacculus neurons providing the first selective molecular markers for these cells. In this thesis I describe the molecular, physiological and anatomical characterisation of these neurons. Genetic labelling of specific populations of sacculus neurons with anatomical (CD8:GFP) reporters has identified neurons in sacculus chambers I and II express IR40a+IR93a together with their co- receptor IR25a, while neurons in chamber III express IR64a with its co-receptor IR8a. Both these sets of neurons project to two distinct glomeruli in the antennal lobe; IR40a neurons project to the column and arm, IR64a neurons project to DC4 and DP1m. Through a live optical imaging screen I showed that these neurons are indeed olfactory and IR64a neurons recognise acidic ligands, while IR40a neurons recognise amine ligands. IR40a and IR64a neurons are in fact composed of anatomically and physiologically distinct subpopulations, strongly implying the existence of other factors that define their functional properties. My thesis identifies the sacculus as a specialised olfactory organ capable of detecting acids and bases, which are of widespread importance to insects. The data from my thesis along with data from other labs show the sacculus is composed of different populations of olfactory sensory neurons and thermosensory neurons. Comparative genomic analysis of sacculus IRs across insects reveals them to be among the most conserved of this receptor repertoire, suggesting that the sacculus represents an evolutionarily ancient insect olfactory acid-base sensor. - La détection des produits chimiques se trouvant dans l'environnement (perception chimiosensorielle) permet à un animal de choisir sa nourriture, son partenaire ou encore d'identifier ses prédateurs. Décortiquer les mécanismes moléculaires et neuronaux grâce auxquels les animaux détectent ces signaux chimiques permet de comprendre comment ces animaux interagissent avec leur environnement. Un système intéressant pour décortiquer ces mécanismes de perception chimiosensorielle est le système olfactif, de la drosophile (Drosophila melanogaster), aussi appelée mouche du vinaigre. C'est un animal modèle très utile grâce à la combinaison d'outils génétiques puissants et d'analyses physiologiques facilement réalisables. Dans l'antenne de la drosophile, qui est l'organe olfactif principal de cet animal, se trouve une structure appelée sacculus. Celui-ci est composé de trois chambres distinctes, chacune comprenant plusieurs sensilles à l'intérieur desquelles se trouvent deux à trois neurones. De précédentes études morphologiques et anatomiques des ces neurones ont déterminé qu'ils sont impliqués dans la perception des odeurs, de l'humidité et de la température. Malgré ceci, la fonction principale de cet organe reste largement inconnue, principalement car il est inaccessible aux analyses électrophysiologiques. Récemment, une nouvelle famille de soixante-six récepteurs olfactifs, nommés Récepteurs lonotropiques (IRs), a été découverte chez la drosophile. Cinq IRs sont exprimés dans les neurones du sacculus. Pour la première fois, une sélection de marqueurs moléculaires est disponible pour l'étude de ces cellules. Dans cette thèse, les caractéristiques moléculaires, physiologiques et anatomiques des neurones du sacculus sont décrites. Ces populations de neurones situés dans le sacculus ont été marquées avec des gènes rapporteurs (CD8:GFP). Ceci a montré que les récepteurs IR40a et IR93a sont exprimés ensemble avec le co-récepteur IR25a dans les chambres I et II, tandis que les neurones de la chambre III expriment IR64a avec son co-récepteur IR8a. Ces deux groupes de neurones projettent vers deux glomérules distincts du lobe antennaire : les neurones IR40a projettent vers la column et le arm, alors que les neurones IR64a projettent vers DC4 et DP1m. Un screen d'imagerie optique a démontré que ces neurones sont en effet des neurones olfactifs, et que les neurones IR64a reconnaissent des ligands acides, tandis que les neurones IR40a reconnaissent des ligands aminés. De plus, les neurones IR40a et IR64a sont séparés en sous-populations distinctes anatomiquement et physiologiquement, et d'autres facteurs permettant de définir leurs propriétés fonctionnelles sont probablement impliqués. Cette thèse identifie ainsi le sacculus comme un organe olfactif spécialisé capable de détecter des acides et amines, lesquels sont très importants pour les insectes. Toutes les données collectées durant cette thèse, combinées aux données d'autres laboratoires, montrent que le sacculus est composé de différentes populations de neurones olfactifs et thermosenseurs. Ces IRs sont très conservés parmi les insectes, suggérant que le sacculus représente révolution d'un ancien détecteur olfactif d'acides et de bases chez l'insecte. - Tous les animaux sont capables de percevoir les signaux chimiques dans leur environnement, comme les odeurs ou le goût, via différents organes. L'odorat est le sens qui permet de percevoir les odeurs, et il est implique des neurones olfactifs qui se trouvent dans le nez des mammifères ou les antennes des insectes. La capacité d'un neurone olfactif à détecter une molécule odorante dépend des types de récepteurs olfactifs qu'il exprime. Il existe deux grandes familles de récepteurs qui perçoivent les odeurs : les Récepteurs Olfactifs, ORs, et Récepteurs lonotropiques IRs, qui détectent différents types d'odeurs avec différents mécanismes. Lorsqu'un récepteur reconnaît une molécule odorante, il convertit ce signal en un signal électrique qui est ensuite transmis au centre olfactif dans le cerveau. La drosophile (Drosophila melanogaster), aussi appelée mouche du vinaigre, est utilisée comme animal modèle pour étudier l'odorat, parce que son génome entier a été séquencé et que ses gènes sont facilement manipulables. De plus, l'anatomie du système olfactif de la mouche est similaire à celui des mammifères, malgré qu'il possède moins de neurones, ce qui le rend moins complexe. Ma thèse a pour objectif d'étudier les Récepteurs lonotropiques dans un organe spécifique, appelé le sacculus, situé dans les antennes. Les neurones du sacculus exprimant des IRs envoient leurs projections au centre olfactif du cerveau, suggérant que ces neurones perçoivent les odeurs. Une technique d'imagerie optique a été utilisée sur le cerveau de mouches vivantes afin de mesurer la réponse des neurones du le sacculus à différentes odeurs. J'ai démontré que ces récepteurs détectent des acides et des amines, qui sont très importants pour les insectes. Par exemple, les acides se retrouvent dans les fruits mûrs sur lesquels les mouches vont se nourrir, s'accoupler et poser leurs oeufs, et les amines sont souvent produites par des bactéries pouvant être nuisible pour la mouche. La principale découverte de ma thèse est donc l'identification du sacculus comme un organe capable de détecter deux des principales odeurs importantes pour la mouche. Ces récepteurs sont aussi présents dans d'autres insectes où ils jouent peut-être des rôles différents. Les acides et les amines se retrouvent aussi dans les excrétions (comme la sueur ou l'urine) de beaucoup de mammifères, qui pourraient potentiellement être dangereux pour la mouche, mais qui attirent les moustiques se nourrissant de leur sang.

Chest physiotherapy using passive expiratory techniques does not reduce bronchiolitis severity: a randomised controlled trial.

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children <1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties (P = 0.044). Complications were rare but occurred more frequently, although not significantly (P = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients.