[Endometriosis as an inflammatory disease ?] / L'endométriose est-elle une pathologie inflammatoire ?

Endometriosis is the presence of stromal and epithelial cells outside the uterine cavity. This chronic inflammatory disease affects about 10 % of the female population in reproductive age and is responsible for chronic pelvic pain and infertility. Its pathogenesis is complex, and the treatment will rely on medical treatment or/and surgery. Medical treatment consists in alleviating pain thanks to analgesic and hormonal treatment but none can eradicate the disease. Medical treatment often fails and about 10 % will add nonsteroid anti-inflammatory drugs to their hormonal treatment. Major role of immune/inflammatory cells in the disease makes them a promising tool for targeted therapy.

: L'endométriose est définie par la présence de cellules stromales et épithéliales endométriales en dehors de la cavité utérine. Considérée comme une pathologie inflammatoire chronique, elle touche environ 10 % des femmes en âge de procréer et est responsable de douleur pelvienne et d'infertilité. Sa pathologie est complexe et le traitement sera médical et/ou chirurgical. Le traitement médical consistera à soulager la douleur grâce à des antalgiques et une hormonothérapie, mais aucune des molécules utilisées actuellement ne permet l'éradication de l'endométriose. Le traitement médical échoue fréquemment. Il est estimé que 10 % des patientes ne seront pas soulagées par une hormonothérapie seule et nécessiteront le recours à des anti-inflammatoires. Le rôle prépondérant des cellules et cytokines inflammatoires dans la survenue de la maladie permet d'envisager des thérapies ciblées.

[The amniotic band syndrome : a rare and severe malformative pathology]. / La maladie des brides amniotiques. Une pathologie malformative rare et sévère.

Antenatal diagnosis of the amniotic band syndrome often occurs during the second trimester of pregnancy when complex and asymmetrical limb deformities are observed. As vital prognosis depends on the gravity of malformations, lesion assessment should be as accurate as possible. Color doppler US screening is useful and could unravel limb vascular compression by an amniotic band. A vascular stop predicts in utero limb amputation. We hereby report the case of a 30-year-old patient pregnant with a fœtus presenting 4-limb deformities. One limb was highly suspected of undergoing amputation. Facing those heavy-burden anomalies, the patient asked for a medical termination of her pregnancy.

Le diagnostic anténatal de la maladie des brides amniotiques est le plus souvent réalisé au deuxième trimestre de la grossesse par la mise en évidence de malformations complexes et asymétriques des membres. Comme le pronostic dépend de la gravité des malformations, un bilan lésionnel précis doit être réalisé. L'utilisation du doppler couleur permet d'évaluer la compression vasculaire par la bride au niveau des membres. L'arrêt du flux artériel semble prédictif d'une amputation du membre in utero. Nous rapportons le cas d'une patiente dont le fœtus présentait des anomalies des 4 membres avec un membre en voie d'amputation et qui, devant la gravité des lésions, a souhaité une interruption médicale de grossesse.

Ulcer of Lipschutz, a rare and unknown cause of genital ulceration.

Acute genital ulcers are painful and distressing to women. Lipchutz Ulcer is an uncommon disease that typically occurs in sexually inactive young women. The main differential diagnosis are sexually-transmitted or non-infectious diseases which cause genital or oro-genital ulcerations. This article aims to review the diagnosis of acute genital ulcers and, through a rare case of acute genital ulcerations, to discuss diagnostic procedures.

Use of a depot steroid formulation with CHOP-based protocol in the treatment of mediastinal lymphoma in cats.

The aims of this retrospective study were to evaluate the efficacy of different steroid formulations (depot vs oral) and if the continuous administration of steroids throughout and beyond a CHOP protocol might improve the survival time and rate of cats with mediastinal lymphoma. The medical records of client-owned cats diagnosed with mediastinal lymphoma were reviewed at two veterinary referral hospitals in Spain. Cases were recruited from 2008 to 2016. Those cats with mediastinal lymphoma treated with chemotherapy were used in the collection of data including surgical procedures, chemotherapy protocol, side effects, complete remission (CR), partial remission and survival time were calculated from time of diagnosis. The median survival time (MST) of group with depot steroid was 370.7 days and all cats are still alive. The MST of group with oral steroid was 267.9 days. The survival distributions were found to be significantly different. The use of depot injectable steroids with a CHOP-based protocol seems to result in a longer survival time in patients with mediastinal lymphoma when comparing the survival distribution for those receiving oral steroids with a CHOP-based protocol. Prospective studies with a higher number of cats are warranted to investigate the utility of injectable steroids depot with a CHOP-based protocol in the treatment of mediastinal lymphoma.

Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study.

STUDY OBJECTIVES: To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy. METHODS: This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change. RESULTS: Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%). CONCLUSIONS: At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier NCT01681121.

Vibrationally resolved photoionization of N2 near threshold.

A recently developed velocity map imaging spectrometer has been used to study the photoionization of molecular nitrogen near threshold. The potentialities of the spectrometer have been exploited to measure simultaneously the energy and angular distribution of the photoelectrons corresponding to the residual N(2)(+) X(2)Σ(g) v = 0-3 ion states. In a single experiment all the experimental observables, i.e., the total and partial cross sections, their branching ratios and the asymmetry parameter of the angular distributions have been determined.

A photoelectron velocity map imaging spectrometer for experiments combining synchrotron and laser radiations.

A velocity map imaging/ion time-of-flight spectrometer designed specifically for pump-probe experiments combining synchrotron and laser radiations is described. The in-house built delay line detector can be used in two modes: the high spatial resolution mode and the coincidence mode. In the high spatial resolution mode a kinetic energy resolution of 6% has been achieved. The coincidence mode can be used to improve signal-to-noise ratio for the pump-probe experiments either by using a gate to count electrons only when the laser is present or by recording coincidences with the ion formed in the ionization process.

Cytokine gene polymorphisms support diagnostic monitoring of Romanian multiple myeloma patients.

INTRODUCTION: Cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. MATERIAL AND METHODS: Cytokine genotyping was performed in 80 patients and 100 healthy blood donors using molecular biology methods (SSP-Invitrogen, USA). RESULTS: Analyzing each polymorphic site, there was an increased frequency of the following genotypes in patients compared to control group: Interleukin-1beta (IL-1ß) pos.+3962 TT, IL-12 pos.-1188 CC, gamma-Interferon (γ-IFN) pos.+874 AA, Transforming Growth Factor- beta1 (TGF- ß1) codon10 TT, IL-2 pos.-330 TG and pos.+166 TT, Interleukin-4Receptor alpha (IL-4Rα) pos.-33 TC, IL-10 pos.-1082 GG and pos.-592 CC, IL-6 pos.-174 GG. It should be noted that almost one third of multiple myeloma patients had IL-6 pos.-174 GG genotype and 62% IL-10 GCC haplotype. These identified haplotypes are high interleukins producer, and this fact was confirmed by serum IL-6 and IL-10 levels performed by ELISA and enhanced chemiluminiscence methods. CONCLUSION: These markers could be successfully used, together with other specific clinical and biological parameters, as reliable individualized prognostic factors in multiple myeloma patients.

Hand transplant--a challenge in immunological management of patients.

The concept of composite tissue allotransplantation (CTA) for restoration of congenital or acquired deformities is not new and the recent success of clinical composite tissue allotransplantation (CTA) attests to the fact that composite tissue allografts have tremendous potential in these life-enhancing reconstructions. A hand transplant, unlike a solid organ transplant, involves multiple tissues (skin, muscle, tendon, bone, cartilage, fat, nerves and blood vessels) and can be considered the 'gold standard' in CTA. In this regard, no other organ or tissue transplant matches the hand transplant in its immunogenicity as well as complexity. Development of assays that allow us to monitor the current state of an immune response (rejection/tolerance) is of great interest and requires an in-depth understanding of the complex and rare phenomenon of tolerance.

Monoclonal antibodies to rhamnogalacturonan I backbone.

Monoclonal antibodies were raised against rhamnogalacturonan I backbone, a pectin domain, using Arabidopsis thaliana seed mucilage-derived rhamnogalacturonan I oligosaccharides--BSA conjugates. Two monoclonal antibodies, designated INRA-RU1 and INRA-RU2, selected for further characterization, were specific for the backbone of rhamnogalacturonan I, displaying no binding activity against the other pectin domains i.e. homogalacturonans, galactans or arabinans. A range of oligosaccharides was prepared by enzymatic digestion of rhamnogalacturonan I isolated from Arabidopsis thaliana seed mucilage and from sugar beet pectin, purified by low-pressure chromatography and characterized by high-performance anion-exchange chromatography and mass spectrometry. These rhamnogalacturonan I oligomers were used to characterize the binding site of the two monoclonal antibodies by competitive inhibition. Both INRA-RU1 and INRA-RU2 showed maximal binding to the [-->2)-alpha-L-rhamnosep-(1-->4)-alpha-D-galacturonic acid p-(1-->](7) structural motif but differed in their minimum binding requirement. INRA-RU2 required at least two disaccharide (rhamnose-galacturonic acid) repeats for the antibody to bind, while INRA-RU1 required a minimum of six disaccharide repeats. Furthermore, the binding capacity of INRA-RU1 decreased steeply as the number of disaccharide repeats go beyond seven. Each of these antibodies reacted with hairy regions isolated from sugar beet pectin. Immunofluorescence microscopy indicated that both antibodies can be readily used to detect rhamnogalacturonan I epitopes in various cell wall samples.

Excitation of 1S and 3S metastable helium atoms to doubly excited states.

We present spectra of triplet and singlet metastable helium atoms resonantly photoexcited to doubly excited states. The first members of three dipole-allowed ;{1,3}P;{o} series have been observed and their relative photoionization cross sections determined, both in the triplet (from 1s2s ;{3}S;{e}) and singlet (from 1s2s ;{1}S;{e}) manifolds. The intensity ratios are drastically different with respect to transitions from the ground state. When radiation damping is included the results for the singlets are in agreement with theory, while for triplets spin-orbit interaction must also be taken into account.

State-to-state inelastic scattering of OH by HI: a comparison with OH-HCl and OH-HBr.

Relative state-to-state cross sections and steric asymmetries have been measured for the scattering process: OH (X (2)Pi(32),v=0,J=32,M(J)=32,f)+HI ((1)Sigma,v=0,J<4)-->OH (X (2)Pi,v=0,Omega=12,J=12-52 and Omega=32,J=32-92,ef)+HI, at 690 cm(-1) collision energy. Comparison with the previously studied systems OH-HCl and OH-HBr reveals relevant features of the potential energy surfaces of these molecular systems. Some measured differences concerning the internal energy distribution after collision and the propensities for the impact with one or the other side of the OH molecule in scattering by HCl, HBr, and HI molecules are discussed.

Rotationally inelastic scattering of OH (2Pi 3/2, v=0, J=3/2, f) by HBr (1Sigma, v=0, J<4).

Relative state-to-state cross sections of OH molecules in the (2)Pi(32), v=0, J=32, M(J)=32, f state have been determined for transitions up to (2)Pi(32), v=0, J=112, f and (2)Pi(12), v=0, J=72, e states by collisions with HBr molecules ((1)Sigma, v=0, J<4) at 750 cm(-1) collision energy. In order to investigate features of the anisotropy of the OH-HBr potential energy surface, the steric asymmetries, which account for the effect of the OH orientation with respect to the collision partner, have been measured. A comparison with other systems previously studied shows strong similarities with the OH-HCl system.

Steric effects in state-to-state scattering of OH (2pi(3/2),J=3/2,f) by HCl.

In this paper we address stereo-dynamical issues in the inelastic encounters between OH (chi2pi) radicals and HCl (chi1sigma+). The experiments were performed in a crossed molecular-beam machine at the nominal collision energy of 920 cm(-1). Prior to the collisions, the OH molecules were selected using a hexapole in a well-defined rotational state v=0, omega=32, J=32, M(J)=32, f, and subsequently oriented in a homogeneous electrical field. We have measured rotationally resolved relative cross sections for collisions in which OH is oriented with either the O side or the H side towards HCl, from which we have calculated the corresponding steric asymmetry factors S. The results are presented in comparison with data previously obtained by our group for the inelastic scattering of OH by CO (E(coll)=985 cm(-1)) and N2 (E(coll)=985 cm(-1)) studied under similar experimental conditions. The dissimilarity in the behavior of the OH+HCl system revealed by this comparison is explained on the basis of the difference in the anisotropy of the interaction potential governing the collisions. The interpretation of the data takes into account the specific features of both nonreactive and reactive parts of the potential-energy surface. The results indicate that the scattering dynamics at this collision energy may be influenced by the HO-HCl van der Waals well and by reorientation effects determined by the long-range electrostatic forces and, furthermore, may involve reactive collisions.

Evaluating different radiology workstation interaction techniques with radiologists and laypersons.

This paper presents a new methodology for evaluating radiology workstation interaction features, using lay subjects to perform a radiology look-alike task with artificial stimuli. We validated this methodology by evaluating two different workstation interaction techniques with two groups of subjects: laypersons and radiologists, using a set of artificial targets to simulate the reading of a diagnostic examination. Overall, the results from the two groups of subjects performing the same tasks were very similar. Both groups showed significantly faster response times using a new interaction technique, and the mouse clicks for both groups were very similar, showing that all the subjects mastered the style of interaction in a similar way. The errors made by both groups were comparable. These results show that it is possible to test new workstation interaction features using look-alike radiological tasks and inexperienced laypersons, and that the results do transfer to radiologists performing the same tasks.

Inelastic state-to-state scattering of OH (2Pi3/2, J=3/2,f) by HCl.

Parity resolved state-to-state cross sections for inelastic scattering of OH (X2Pi) by HCl were measured in a crossed molecular beam experiment at the collision energy of 920 cm(-1). The OH (X2Pi) radicals were prepared in a single quantum state, Omega=3/2, J=3/2, MJ=3/2, f, by means of electrostatic state selection in a hexapole field. The rotational distribution of the scattered OH radicals by HCl was probed by saturated LIF spectroscopy of the 0-0 band of the A 2Sigma+ - X 2Pi transition. Relative state-to-state cross sections were measured for rotational excitations up to J=9/2 within the Omega=3/2 spin-orbit manifold and up to J=7/2 within the Omega=1/2 spin-orbit manifold. A propensity for spin-orbit conserving transitions was found, but no propensity for excitation into a particular Lambda-doublet component of the same rotational state was evident. The data are presented and discussed in comparison with results previously obtained for collisions of OH with CO (Ecoll=450 cm(-1)) and N2 (Ecoll=410 cm(-1)) and with new data we have measured for the OH+CO system at a comparable collision energy (Ecoll=985 cm(-1)). This comparison suggests that the potential energy surface (PES) governing the interaction between OH and HCl is more anisotropic than the PES's governing the intermolecular interaction of OH with CO and N2.

Blood pressure variability and cognitive function in older hypertensives.

Several studies have shown that cerebrovascular organ damage can related not only to average blood pressure (BP) levels, but also to BP variability. The aim of this study was to investigate the relationship between 24 hr BP variability and cognitive function in older hypertensives. Forty older, never treated hypertensives were submitted to 24 hr ambulatory BP monitoring (ABPM) and subdivided, according to the variability of the systolic BP (SBP), in two groups: 23 with higher (> PV) and 17 with lower (< PV) SBP variability, defined as the standard deviation (SD) of the mean 24 hr SBP values and as coefficient of variation (CV). They underwent a cognitive assessment by mini mental state examination (MMSE) and a recording of the brain event-related potentials (ERPs). ERPs record neuronal electric activity when the patients are submitted to frequent and rare acoustic stimuli and must recognize and count rare (target) stimuli. The two groups with statistically different 24 hr SBP variability, did not show significant differences in MMSE scores or in N2 and P300 ERP latencies, thus indicating a lack of difference in the cognitive ability between the two groups. Our results show that cognitive function is not related to 24 hr SBP variability in older hypertensives.

Circadian blood pressure pattern and cognitive function in newly diagnosed older hypertensives.

Hypertensive subjects can be subdivided in two groups, dippers and non-dippers, according to the presence or the lack of a nocturnal fall of blood pressure (BP) of over 10%. Several studies have investigated cardiovascular and cerebrovascular organ damage in the two groups with discordant results, but fewer of them analysed the relationship between circadian BP pattern and cognitive function, and none in the early phases of hypertension. To this purpose, we selected 40 older hypertensives, 23 dippers and 17 non-dippers, with newly diagnosed hypertension, never treated, who underwent to 24-h ambulatory BP monitoring (ABPM), Mini-Mental State Examination (MMSE) and recording of event-related potentials (ERPs). No significant differences between dippers and non-dippers were found in the MMSE scores and P300 latency values, as we expected, and not even in N2 wave latency values, showing that the non-dipping pattern is not associated with lower cognitive function in the early phases of hypertension.

Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving.

RATIONALE: Acute cravings, often provoked by exposure to smoking cues, appear to be important triggers for smoking relapse. Relief of acute craving may therefore be an important step in preventing relapse. OBJECTIVES: This study was undertaken to assess the effectiveness of nicotine gum in relieving acute craving. METHODS: A multi-center, randomized, placebo-controlled study was conducted with smokers ( n=296) who quit by using either active or inactive gum for 3 days. On their third day of abstinence, smokers participated in a laboratory session in which they were exposed to a provocative smoking cue, chewed active or inactive gum, and then rated their craving at 5-min intervals for 35 min. RESULTS: Craving initially decreased in both groups. After 15 min, however, the smokers using active nicotine gum experienced significantly greater craving reductions. CONCLUSIONS: These results suggest that nicotine gum can effectively reduce acute craving following exposure to smoking cues.

Influence of aging and other cardiovascular risk factors on baroreflex sensitivity.

OBJECTIVES: To examine the influence of known cardiovascular risk factors (cholesterol, blood glucose levels, arterial pressures, heart rate, and aging) on baroreflex sensitivity. DESIGN: An observational epidemiological study. SETTING: Geriatric Division at the Policlinico Umberto Primo, University of Rome La Sapienza. PARTICIPANTS: Two hundred three subjects whose ages ranged from 9 to 94 years, apparently healthy and free of detectable clinical evidence of atherosclerosis. MEASUREMENTS: All subjects underwent determination of baroreflex sensitivity by phenylephrine infusion (BSphe), and by a noninvasive method derived from spectral analysis of R-R interval and arterial pressure variabilities (alpha index). RESULTS: The population, subdivided into tertiles for each variable studied, had lower BSphe values and lower alpha indexes as a function of age, plasma low-density lipoprotein (LDL) cholesterol, and systolic blood pressure. The alpha index was significantly lower in both groups with elevated LDL cholesterol levels than in those with lower levels (II and III vs I tertile, P <.001), whereas BSphe differed significantly only in the two groups who had extreme levels of LDL (I vs III tertile, P <.001). Multiple regression analysis identified a negative association of the alpha index with age (P <.001), heart rate (P <.01), area under the glucose-response curve (P <.001), and LDL cholesterol (P <.01), but of BSphe only with age (P <.001) and heart rate (P <.01). CONCLUSION: These findings indicate that some risk factors for coronary heart disease adversely influence baroreflex sensitivity.