S100A8/A9 drives monocytes towards M2-like macrophage differentiation and associates with M2-like macrophages in osteoarthritic synovium.

OBJECTIVES: Macrophages are key orchestrators of the osteoarthritis (OA)-associated inflammatory response. Macrophage phenotype is dependent on environmental cues like the inflammatory factor S100A8/A9. Here, we investigated how S100A9 exposure during monocyte-to-macrophage differentiation affects macrophage phenotype and function. METHODS: OA synovium cellular composition was determined using flow cytometry and multiplex immunohistochemistry. Healthy donor monocytes were differentiated towards M1- and M2-like macrophages in presence of S100A9. Macrophage markers were measured using flow cytometry and phagocytic activity was determined using pHrodo Red Zymosan A BioParticles. Gene expression was determined using qPCR. Protein secretion was measured using Luminex and ELISA. RESULTS: Macrophages were the dominant leucocyte subpopulation in OA synovium. They mainly presented with a M2-like phenotype, although the majority also expressed M1-like macrophage markers. Long-term exposure to S100A9 during monocyte-to-macrophage differentiation increased M2-like macrophage markers CD163 and CD206 in M1-like and M2-like differentiated cells. In addition, M1-like macrophage markers were increased in M1-like, but decreased in M2-like differentiated macrophages. In agreement with this mixed phenotype, S100A9 stimulation modestly increased expression and secretion of pro-inflammatory markers and catabolic enzymes, but also increased expression and secretion of anti-inflammatory/anabolic markers. In accordance with the upregulation of M2-like macrophage markers, S100A9 increased phagocytic activity. Finally, we indeed observed a strong association between S100A8 and S100A9 expression and the M2-like/M1-like macrophage ratio in end-stage OA synovium. CONCLUSION: Chronic S100A8/A9 exposure during monocyte-to-macrophage differentiation favours differentiation towards a M2-like macrophage phenotype. The properties of these cells could help explain the catabolic/anabolic dualism in established OA joints with low-grade inflammation.

Identification of CD64 as a marker for the destructive potential of synovitis in osteoarthritis.

OBJECTIVES: OA is characterized by cartilage degeneration and persistent pain. The majority of OA patients present with synovitis, which is associated with increased cartilage damage. Activated synovial macrophages are key contributors to joint destruction. Therefore, a marker that reflects the activation of these cells could be a valuable tool to characterize the destructive potential of synovitis and benefit monitoring of OA. Here, we aimed to investigate the use of CD64 (FcγRI) as a marker to characterize the damaging potential of synovitis in OA. METHODS: Synovial biopsies were obtained from end-stage OA patients that underwent joint replacement surgery. CD64 protein expression and localization was evaluated using immunohistochemistry and immunofluorescence and quantified using flow cytometry. qPCR was performed to measure the expression of FCGR1 and OA-related genes in synovial biopsies, and in primary chondrocytes and primary fibroblasts stimulated with OA conditioned medium (OAS-CM). RESULTS: Our data exposed a wide range of CD64 expression in OA synovium and showed positive correlations between FCGR1 and S100A8, S100A9, IL1B, IL6 and MMP1/2/3/9/13 expression. CD64 protein correlated with MMP1, MMP3, MMP9, MMP13 and S100A9. Furthermore, we observed that synovial CD64 protein levels in source tissue for OAS-CM significantly associated with the OAS-CM-induced expression of MMP1, MMP3 and especially ADAMTS4 in cultured fibroblasts, but not chondrocytes. CONCLUSION: Together, these results indicate that synovial CD64 expression is associated with the expression of proteolytic enzymes and inflammatory markers related to structural damage in OA. CD64 therefore holds promise as marker to characterize the damaging potential of synovitis.

CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. OBJECTIVES: We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. METHODS: First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. RESULTS: We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. CONCLUSION: Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo.

Measurement of 2D density profiles using a second-harmonic, dispersion interferometer.

A second-harmonic, dispersion interferometer is used to image large-area (≃5 cm2) plasma-jet and gas-jet density profiles. Achromatic telescopes magnify the diameters of the primary-laser beam (1064 nm) and its second-harmonic (532 nm) before probing the sample and de-magnify the beam diameters after the sample, where the primary beam transfers its phase change to a second, second-harmonic beam, allowing the sample's dispersive-phase change to be measured between two, orthogonally polarized second harmonic beams. The telescopes produce an azimuthally symmetric, dispersive-phase shift in the sample + background phase-change image and in the background phase-change image, which is removed by digital subtraction. The interferometer's performance was verified using standard-optical components as dispersive elements (BK7 lenses and wedge plates), resolving a minimum, phase-change sensitivity of Δϕmin ≳ 15 mrad and spatial resolution of Δxres ≃ 100 µm. The phase change produced by unknown-density objects (a pulsed-plasma-jet and a pulsed-gas-jet) was measured, and their data were used to recover the original, 2D density profiles using an inverse Abel transform: peak-number density, Ngas ≃ 6 × 1020 cm-3 and Ne ≃ 5 × 1016 cm-3; line-integrated density, ∫Ngasdl ∼ 2 × 1019cm-2 and ∫Nedl ∼ 1 × 1016cm-2. The techniques and methods developed here are scalable to even larger probe-beam diameters and frame-capture rates, leading to a diagnostic capability that is well-suited for applications involving the real-time measurement of density.

Bowel function and quality of life following surgery for deep endometriosis.

OBJECTIVE: To assess the influence of surgical approach, complications and patient characteristics and their postoperative functional outcomes on (sexual) quality of life (QoL) in patients with deep endometriosis (DE) with bowel involvement. METHODS: Retrospective cohort study on patients surgically treated for DE in a Dutch tertiary referral hospital. Data are based on surgical records and questionnaires covering current postoperative bowel function and (sexual) QoL. RESULTS: Postoperative functional score outcomes: constipation, fecal incontinence and Low Anterior Resection Syndrome (LARS) did not differ between patients treated with rectal shaving or segmental resection. Thirty percent of women treated with rectal shaving experienced LARS-like symptoms as well. Women who underwent segmental resection had a worse sexual QoL compared to patients managed by shaving. Patients who suffered from complications had a worse postoperative QoL. A higher postoperative constipation score was correlated with a significantly higher pain score and a lower overall and sexual QoL. LARS-score was correlated with a worsened sexual QoL. CONCLUSION: Women who underwent surgery for deep endometriosis rated their overall QoL as lower when a complication occurred. Segmental resection resulted in a lower sexual QoL compared to shaving. We showed that a higher LARS-score correlates with a lower sexual QOL, and postoperative constipation with more pain and a lower overall and sexual QoL. Interestingly, after using the shaving technique one-third of the patients experienced LARS-like symptoms as well.

The role of inflammation in mesenchymal stromal cell therapy in osteoarthritis, perspectives for post-traumatic osteoarthritis: a review.

OA is a complex and highly prevalent degenerative disease affecting the whole joint, in which factors like genetic predisposition, gender, age, obesity and traumas contribute to joint destruction. ∼50-80% of OA patients develop synovitis. OA-associated risk factors contribute to joint instability and the release of cartilage matrix fragments, activating the synovium to release pro-inflammatory factors and catabolic enzymes in turn damaging the cartilage and creating a vicious circle. Currently, no cure is available for OA. Mesenchymal stromal cells (MSCs) have been tested in OA for their chondrogenic and anti-inflammatory properties. Interestingly, MSCs are most effective when administered during synovitis. This review focusses on the interplay between joint inflammation and the immunomodulation by MSCs in OA. We discuss the potential of MSCs to break the vicious circle of inflammation and describe current perspectives and challenges for clinical application of MSCs in treatment and prevention of OA, focussing on preventing post-traumatic OA.

Recovery of muscle mass and muscle oxidative phenotype following disuse does not require GSK-3 inactivation.

BACKGROUND: Physical inactivity contributes to muscle wasting and reductions in mitochondrial oxidative phenotype (OXPHEN), reducing physical performance and quality of life during aging and in chronic disease. Previously, it was shown that inactivation of glycogen synthase kinase (GSK)-3ß stimulates muscle protein accretion, myogenesis, and mitochondrial biogenesis. Additionally, GSK-3ß is inactivated during recovery of disuse-induced muscle atrophy. AIM: Therefore, we hypothesize that GSK-3 inhibition is required for reloading-induced recovery of skeletal muscle mass and OXPHEN. METHODS: Wild-type (WT) and whole-body constitutively active (C.A.) Ser21/9 GSK-3α/ß knock-in mice were subjected to a 14-day hind-limb suspension/14-day reloading protocol. Soleus muscle mass, fiber cross-sectional area (CSA), OXPHEN (abundance of sub-units of oxidative phosphorylation (OXPHOS) complexes and fiber-type composition), as well as expression levels of their main regulators (respectively protein synthesis/degradation, myogenesis and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) signaling) were monitored. RESULTS: Subtle but consistent differences suggesting suppression of protein turnover signaling and decreased expression of several OXPHOS sub-units and PGC-1α signaling constituents were observed at baseline in C.A. GSK-3 versus WT mice. Although soleus mass recovery during reloading occurred more rapidly in C.A. GSK-3 mice, this was not accompanied by a parallel increased CSA. The OXPHEN response to reloading was not distinct between C.A. GSK-3 and WT mice. No consistent or significant differences in reloading-induced changes in the regulatory steps of protein turnover, myogenesis or muscle OXPHEN were observed in C.A. GSK-3 compared to WT muscle. CONCLUSION: This study indicates that GSK-3 inactivation is dispensable for reloading-induced recovery of muscle mass and OXPHEN.

Prognostic Factors for the Failure of Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide an overview of prognostic factors predicting failure of second-generation endometrial ablation. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from 1988 until February 2019. The search was conducted without language restrictions using the following search terms: "endometrial ablation," "prognosis," "predict," "long term," "late onset," "outcome." METHODS OF STUDY SELECTION: The literature search provided a total of 990 studies. All types of studies reporting about prognostic factors of second-generation endometrial ablation failure were included. TABULATION, INTEGRATION, AND RESULTS: After screening for eligibility, 56 studies were included in this review, of which 21 were included in the meta-analysis. In these 56 studies, 157,830 women were included. We evaluated 10 prognostic factors: age, myomas, history of tubal ligation, body mass index, parity, preexisting dysmenorrhea, caesarean delivery, bleeding pattern, uterus position, and uterus length. Meta-analysis was performed for the primary outcome (surgical reintervention) to estimate summary treatment effects. Younger age (aged 35 years or younger, odds ratio [OR] 1.68, 95% CI 1.19-2.36; aged 40 years or younger, OR 1.58, 95% CI 1.30-1.93; aged 45 years or younger OR 1.63, 95% CI 1.28-2.07), prior tubal ligation (OR 1.46, 95% CI 1.23-1.73), and preexisting dysmenorrhea (OR 2.12, 95% CI 1.41-3.19) were associated with an increased risk of surgical reintervention. Studies investigating the prognostic factors myomas and obesity showed conflicting results. CONCLUSION: Younger age, prior tubal ligation and preexisting dysmenorrhea were found to be associated with failure of endometrial ablation. Obesity and the presence of large submucous myomas may be associated with failure, as well, though more research is necessary to estimate the influence of these factors. It is important to take the results of this review into account when counselling women with heavy menstrual bleeding. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019126247.

Gated liquid scintillator detector for neutron time of flight measurements in a gas-puff Z-pinch experiment.

Detection of secondary D(t, n)4He neutrons produced when thin argon or krypton gas shells implode on a deuterium gas target is a very challenging task because the secondary neutron yield is a small fraction of the primary neutron yield and because the implosion is often accompanied by an intense hard X-ray burst. We built a large volume neutron time of flight (nTOF) detector using liquid scintillator (xylene solvent with small quantities of wavelength shifting PPO + bis-MSB fluors) in an attempt to increase the detection probability for secondary neutrons in our staged Z-pinch experiments at the 1 MA Zebra pulsed-power generator. Two fast, gated microchannel plate photomultiplier tubes detect the light created in 21 liters of liquid. The hard X-rays were successfully suppressed in the recorded nTOF traces, but we found no evidence of secondary neutrons. The signal quality from the primary D(d, n)3He neutrons was higher compared to the signal quality from a plastic scintillator nTOF, thus providing a more reliable estimate of the deuterium ion temperature at the pinch stagnation time. Cross-calibration with a silver activation detector enables standalone neutron yield measurement.

Injector design for liner-on-target gas-puff experiments.

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ∼1 cm radius gas profile that satisfies the theoretical requirement for best performance on ∼1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.

Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.

Devil's Claw to suppress appetite--ghrelin receptor modulation potential of a Harpagophytum procumbens root extract.

Ghrelin is a stomach-derived peptide that has been identified as the only circulating hunger hormone that exerts a potent orexigenic effect via activation of its receptor, the growth hormone secretagogue receptor (GHS-R1a). Hence, the ghrelinergic system represents a promising target to treat obesity and obesity-related diseases. In this study we analysed the GHS-R1a receptor activating potential of Harpagophytum procumbens, popularly known as Devil's Claw, and its effect on food intake in vivo. H. procumbens is an important traditional medicinal plant from Southern Africa with potent anti-inflammatory and analgesic effects. This plant has been also used as an appetite modulator but most evidences are anecdotal and to our knowledge, no clear scientific studies relating to appetite modulation have been done to this date. The ghrelin receptor activation potential of an extract derived from the dried tuberous roots of H. procumbens was analysed by calcium mobilization and receptor internalization assays in human embryonic kidney cells (Hek) stably expressing the GHS-R1a receptor. Food intake was investigated in male C57BL/6 mice following intraperitoneal administration of H. procumbens root extract in ad libitum and food restricted conditions. Exposure to H. procumbens extract demonstrated a significant increased cellular calcium influx but did not induce subsequent GHS-R1a receptor internalization, which is a characteristic for full receptor activation. A significant anorexigenic effect was observed in male C57BL/6 mice following peripheral administration of H. procumbens extract. We conclude that H. procumbens root extract is a potential novel source for potent anti-obesity bioactives. These results reinforce the promising potential of natural bioactives to be developed into functional foods with weight-loss and weight maintenance benefits.

A direct comparison of efficacy between desloratadine and rupatadine in seasonal allergic rhinoconjunctivitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: H1-antihistamines are recommended as the first-line symptomatic treatment of allergic rhinitis. The objective of this study was to evaluate the effects of rupatadine (RUP) versus desloratadine (DES) in subjects with seasonal allergic rhinitis (SAR). METHOD: To assess the efficacy and safety of RUP in SAR in comparison with placebo (PL) and DES. A randomized, double-blind, multicenter, international, and PL-controlled study was carried out. The main selection criteria included SAR patients over 12 years old with a positive prick test to a relevant seasonal allergen for the geographic area. Symptomatic patients at screening with a nasal symptom sum score of ≥6 points (nasal discharge, nasal obstruction, sneezing, and nasal pruritus), a non-nasal score of ≥3 points (ocular pruritus, ocular redness, and tearing eyes), and a rhinorrhea score of ≥2 points with laboratory test results and electrocardiography within acceptable limits were included in the study. Change from baseline in the total symptom-score (T7SS) over the 4-week treatment period (reflective evaluation) was considered the primary efficacy variable. Secondary efficacy measures included total nasal symptom score (T4NSS) and conjunctival symptom score (T3NNSS), both of which are reflective and instantaneous evaluations. Furthermore questions related to quality of life (eg, sleep disturbances or impairment of daily activities) have also been evaluated. Safety was assessed according to adverse events reported, as well as laboratory and electrocardiography controls. RESULTS: A total of 379 patients were randomized, of which 356 were included and allocated to PL (n = 122), RUP (n = 117), or DES (n = 117). Mean change of T7SS over the 4-week treatment period was significantly reduced in the RUP (-46.1%, P = 0.03) and DES (-48.9%, P = 0.01) groups, compared with PL. Similarly, RUP and DES were comparable and significantly superior to PL for all secondary endpoints, including nasal and conjunctival symptoms and patients' and investigator's overall clinical opinions. Symptom score evaluation (both reflective and instantaneous evaluations) throughout the treatment period showed a progressive and maintained significant improvement with both treatments at day 7 (P = 0.01), day 14 (P = 0.007), and day 21 (P = 0.01) in comparison with PL. Adverse events were scarce and were similar in both treatment groups. Electrocardiography (QTc) and lab test results did not show any relevant findings. CONCLUSION: RUP is a very good choice for SAR due to its contribution to the improvement of nasal (including obstruction) and non-nasal symptoms to a similar degree as DES.

Tomographic imaging system for measuring impurity line emission in a field-reversed configuration.

A 16 chord optical tomography system has been developed and implemented in the flux coil generated-field reversed configuration (FRC). The chords are arranged in two fans of eight, which cover ~35% of the vessel area at the midplane. Each illuminate separate photomultiplier tubes (PMTs) which are fitted with narrow band-pass filters. In this case, filters are centered at 434.8 nm to measure emission from singly ionized argon. PMT crosstalk is negligible. Background noise due to electron radiation and H(γ) line radiation is <10% of argon emission. The spatial resolution of the reconstruction is 1.5 cm. Argon is introduced using a puff valve and tube designed to impart the gas into the system as the FRC is forming. Reconstruction of experimental data results in time-dependent, 2D emissivity profiles of the impurity ions. Analysis of these data show radial, cross-field diffusion to be in the range of 10-10(3) m(2)∕s during FRC equilibrium.

A statement on cefazolin immediate hypersensitivity: data from a large database, and focus on the cross-reactivities.

BACKGROUND: More perioperative cefazolin use has resulted in an increased risk of cefazolin-associated reactions. OBJECTIVE: The aim of this article is to study immediate reactions to cefazolin and attempt to determine possible allergic cross-reactivity with other ß-lactams using data from the Drug Allergy and Hypersensitivity Database (DAHD). METHODS: All 25 cefazolin-associated reactions in the DAHD were reviewed. The cases identified were then investigated according to the European Network for Drug Allergy (ENDA) recommendations by skin testing and challenges. RESULTS: A total of 10 individuals with proven IgE-mediated cefazolin hypersensitivity were identified between January 1999 and July 2009. All the index reactions were compatible with an acute IgE-mediated process, six with anaphylaxis, two with systemic allergic reactions without hypotension, and two with urticaria/angioedema. Cefazolin skin tests were positive in seven individuals and cefazolin challenges were positive in three more individuals. In the eight cefazolin allergic patients who had challenges with other ß-lactams, there was no positive reaction noted. CONCLUSION AND CLINICAL RELEVANCE: In this cohort of patients with IgE-mediated reactions to cefazolin, a majority tolerated amoxicillin and several patients tolerated other cephalosporins. This implies that the R1 side-chain may play an essential role in IgE-mediated reactions to cefazolin. No clear rule to predict cross-reactivity with other ß-lactams could be determined. More research on IgE-mediated hypersensitivity to cefazolin and other cephalosporins is needed.

Two-chord interferometry using 3.39 µm He-Ne laser on a flux-coil-generated FRC.

A two-chord λ(IR)∼3.39 µm He-Ne laser interferometer system was developed for a flux-coil-generated field-reversed configuration to estimate the electron density and the total temperature of the field-reversed configuration (FRC) plasma. This two-chord heterodyne interferometer system consists of a single ∼2 mW infrared He-Ne laser, a visible (λ(vis)∼632.8 nm) He-Ne laser for the alignment, a 40 MHz acousto-optic modulator, photodetectors, and quadrature phase detectors. Initial measurement was performed and the measured average electron densities were 2-10×10(19) m(-3) at two different radial positions in the midplane. A time shift in density was observed as the FRC expands radially. The time evolution of the line-averaged density agrees with the density estimated from the in situ internal magnetic probes, based on a rigid-rotor profile model.

Spectroscopic measurement of ion temperature and ion velocity distributions in the flux-coil generated FRC.

One aim of the flux-coil generated field reversed configuration at Tri Alpha Energy (TAE) is to establish the plasma where the ion rotational energy is greater than the ion thermal energy. To verify this, an optical diagnostic was developed to simultaneously measure the Doppler velocity-shift and line-broadening using a 0.75 m, 1800 groves/mm, spectrometer. The output spectrum is magnified and imaged onto a 16-channel photomultiplier tube (PMT) array. The individual PMT outputs are coupled to high-gain, high-frequency, transimpedance amplifiers, providing fast-time response. The Doppler spectroscopy measurements, along with a survey spectrometer and photodiode-light detector, form a suite of diagnostics that provide insights into the time evolution of the plasma-ion distribution and current when accelerated by an azimuthal-electric field.

Electron density measurements of a field-reversed configuration plasma using a novel compact ultrastable second-harmonic interferometer.

A compact high-sensitivity second-harmonic interferometer for line-integrated electron density measurements on a large plasma machine is presented. The device is based on a fiber coupled near-infrared continuous-wave Nd:YAG laser and is remotely controlled. The performances of the instrument are tested on the Irvine field-reversed configuration machine, and a sensitivity of few 10(14) cm(-2) in measuring line integrated electron density is demonstrated with a time resolution of a few microseconds. The interferometer is self calibrated, has an impressive stability, and it does not require any further alignment after proper installation. These features make this device a real turn-key system suitable for electron density measurement in large plasma machines.

Systematic follow-up increases incidence of anaphylaxis during adverse reactions in anesthetized patients.

BACKGROUND: The incidence of hypersensitivity reactions during anesthesia is underestimated because clinical symptoms may vary and diagnosis is not obvious. Our aim was to investigate the consequences of a systematic follow-up of patients on the estimated incidence of allergic reactions during anesthesia. METHODS: We conducted a prospective study over a 2-year period (70,000 anesthesias). When patients were suspected with hypersensitivity reactions or with unexplained adverse reactions during anesthesia, blood was sampled to measure histamine and tryptase, and then skin tests were performed 4-6 weeks later. RESULTS: During the studied period, 39 patients were enrolled in the database. Eight were excluded because of lack of skin tests. Twenty-two patients had clinical features compatible with immediate hypersensitivity reaction, and nine had reactions rated as 'unexplained' by the attending physician. Following systematic investigation, we found 22 hypersensitivity reactions (15 patients with obvious and seven with unexplained reactions) during anesthesia. This increases the estimated incidence of hypersensitivity reactions from 1 : 4667 to 1 : 3180 anesthesias. Tryptase concentrations were increased in only 50% of these patients. In our series, positive and negative predictive values of tryptase at T(0) for the diagnosis of anaphylaxis were 100% and 60%, respectively. Latex was the major causative agent, followed by neuromuscular blocking agents and antibiotics. CONCLUSIONS: Systematic follow-up of patients with unexplained reactions during anesthesia increases the estimated incidence of IgE-mediated hypersensitivity reactions during anesthesia by 50%.