Incidence of stent thrombosis and adverse cardiac events 5 years after sirolimus stent implantation in clinical practice.

BACKGROUND: The long-term incidence of stent thrombosis (ST) and complications after sirolimus-eluting stents (SES) implantation is still a matter of debate. METHOD: We conducted a systematic follow-up on the day of their 5-year SES implantation anniversary, in a series of consecutive real-world patients treated with a SES. The use of SES implantation was not restricted to "on-label" indications, and target lesions included in-stent restenosis, vein graft, left main stem locations, bifurcations, and long lesions. The Academic Research Consortium criteria were used for ST classification. RESULTS: Three hundred fifty consecutive patients were treated with SES between April and December 2002 in 3 Swiss hospitals. Mean age was 63 +/- 6 years, 78% were men, 20% presented with acute coronary syndrome, and 19% were patients with diabetes. Five-year follow-up was obtained in 98% of eligible patients. Stent thrombosis had occurred in 12 patients (3.6%) [definite 6 (1.8%), probable 1 (0.3%) and possible 5 (1.5%)]. Eighty-one percent of the population was free of complications. Major adverse cardiac events occurred in 74 (21%) patients and were as follows: cardiac death 3%, noncardiac death 4%, myocardial infarction 2%, target lesion revascularization 8%, non-target lesion revascularization target vessel revascularization 3%, coronary artery bypass graft 2%. Non-TVR was performed in 8%. CONCLUSION: Our data confirm the good long-term outcome of patients treated with SES. The incidence of complications and sub acute thrombosis at 5 years in routine clinical practice reproduces the results of prospective randomized trials.

Mobile gibberellin directly stimulates Arabidopsis hypocotyl xylem expansion.

Secondary growth of the vasculature results in the thickening of plant structures and continuously produces xylem tissue, the major biological carbon sink. Little is known about the developmental control of this quantitative trait, which displays two distinct phases in Arabidopsis thaliana hypocotyls. The later phase of accelerated xylem expansion resembles the secondary growth of trees and is triggered upon flowering by an unknown, shoot-derived signal. We found that flowering-dependent hypocotyl xylem expansion is a general feature of herbaceous plants with a rosette growth habit. Flowering induction is sufficient to trigger xylem expansion in Arabidopsis. By contrast, neither flower formation nor elongation of the main inflorescence is required. Xylem expansion also does not depend on any particular flowering time pathway or absolute age. Through analyses of natural genetic variation, we found that ERECTA acts locally to restrict xylem expansion downstream of the gibberellin (GA) pathway. Investigations of mutant and transgenic plants indicate that GA and its signaling pathway are both necessary and sufficient to directly trigger enhanced xylogenesis. Impaired GA signaling did not affect xylem expansion systemically, suggesting that it acts downstream of the mobile cue. By contrast, the GA effect was graft transmissible, suggesting that GA itself is the mobile shoot-derived signal.

In vivo mechanisms leading to transplantation tolerance induced by regulatory T cells

Purpose: The mechanisms by which CD4+CD25+Foxp3+ T cells (Tregs) regulate effector T cells in a transplantation setting and their in vivo homeostasis still remain to be clarified. Using a mouse adoptive transfer and skin transplantation model, we analyzed the in vivo expansion, effector function and trafficking of effector T cells and donor-specific Tregs, in response to an allograft. Methods and materials: Antigen-specific Tregs were generated and expanded in vitro by culturing freshly isolated Tregs from BALB/c mice (H2d) with syngeneic dendritic cells pulsed with an allopeptide (here the Kb peptide derived from the MHC class I molecule of allogeneic H2b mice). Fluorescent-labelled CD4+CD25- naive T cells and donor-antigen-specific Tregs were transferred alone or coinjected into syngeneic BALB/c-Nude recipients transplanted with allogeneic C57BL/6xBALB/c donor skin. Results: As opposed to their in vitro hyporesponsiveness, Tregs divided in vivo, migrated and accumulated in the allograft draining lymph nodes (drLN) and within the graft. The co-transfer of Tregs did not modify the early proliferation and homing of CD4+CD25- T cells to secondary lymphoid organs. But, in the presence of Tregs, effector T cells produced significantly less IFN- and IL-2 effector cytokines, while higher amounts of IL-10 were detected in the spleen and drLN of these mice. Furthermore, time-course studies showed that Tregs were recruited into the allograft at a very early stage posttransplantation and prevented infiltration by effector T cells. Conclusion: Overall, our results suggest that suppression of graft rejection involves the early recruitment of donor-specific Tregs at the sites of antigenic challenge and that Tregs mainly regulate the effector arm of T cell alloresponses.

Hints for a fast precessing relativistic radio jet in LS I+61·303

Here we discuss two consecutive MERLIN observations of the X-ray binary LS I +61◦303. The first observation shows a double-sided jet extending up to about 200 AU on both sides of a central source. The jet shows a bent S-shaped struct ure similar to the one displayed by the well-known precessing jet of SS 433. The precession suggested in the first MERLIN image becomes evident in the second one, showing a one-sided bent jet significantly rotated with respect to the jet of the day before. We conclude that the derived precession of the relativistic (β=0.6) jet explains puzzling previous VLBI results. Moreover , the fact that the precession is fast could be the explanation of the never understood short term (days) variability of the associated gamma-ray source 2CG 135 + 01 / 3EG J0241 + 6103.

VLA multifrequency observations of RSCVn binaries

We present multiepoch Very Large Array (VLA) observations at 1.4 GHz, 4.9 GHz, 8.5 GHz and 14.9 GHz for a sample of eight RS CVn binary systems. Circular polarization measurements of these systems are also reported. Most of the fluxes observed are consistent with incoherent emission from mildly relativistic electrons. Several systems show an increase of the degree of circular polarization with increasing frequency in the optically thin regime, in conflict with predictions by gyrosynchrotron models. We observed a reversal in the sense of circular polarization with increasing frequency in three non-eclipsing systems: EI Eri, DM Uma and HD 8358. We find clear evidence for coherent plasma emission at 1.4 GHz in the quiescent spectrum of HD 8358 during the helicity reversal. The degrees of polarization of the other two systems could also be accounted for by a coherent emission process. The observations of ER Vul revealed two U-shaped flux spectra at the highest frequencies. The U-shape of the spectra may be accounted for by an optically thin gyrosynchrotron source for the low frequency part whereas the high frequency part is dominated by a thermal emission component.

A search for microquasar candidates at low galactic latitudes

Recent studies of relativistic jet sources in the Galaxy, also known as microquasars, have been very useful in trying to understand the accretion/ejection processes that take place near compact objects. However, the number of sources involved in such studies is still small. In an attempt to increase the number of known microquasars we have carried out a search for new Radio Emitting X-ray Binaries (REXBs). These sources are the ones to be observed later with VLBI techniques to unveil their possible microquasar nature. To this end, we have performed a cross-identification between the X-ray ROSAT all sky survey Bright Source Catalog (RBSC) and the radio NRAO VLA Sky Survey (NVSS) catalogs under very restrictive selection criteria for sources with |b|<5 degrees. We have also conducted a deep observational radio and optical study for six of the selected candidates. At the end of this process two of the candidates appear to be promising, and deserve additional observations aimed to confirm their proposed microquasar nature.

One-sided jet at milliarcsecond scales in LSI+61·303

We present Very Long Baseline Interferometry (VLBI) observations of the high mass X-ray binary LSI+61303, carried out with the European VLBI Network (EVN). Over the 11 hour observing run, performed 10 days after a radio outburst, the radio source showed a constant flux density, which allowed sensitive imaging of the emission distribution. The structure in the map shows a clear extension to the southeast. Comparing our data with previous VLBI observations we interpret the extension as a collimated radio jet as found in several other X-ray binaries. Assuming that the structure is the result of an expansion that started at the onset of the outburst, we derive an apparent expansion velocity of 0.003 c, which, in the context of Doppler boosting, corresponds to an intrinsic velocity of at least 0.4 c for an ejection close to the line of sight. From the apparent velocity in all available epochs we are able to establish variations in the ejection angle which imply a precessing accretion disk. Finally we point out that LSI+61303, like SS433 and Cygnus X-1, shows evidence for an emission region almost orthogonal to the relativistic jet.

Search for very high energy gamma-ray emission from pulsar-pulsar wind nebula systems with the MAGIC telescope

The MAGIC collaboration has searched for high-energy gamma-ray emission of some of the most promising pulsar candidates above an energy threshold of 50 GeV, an energy not reachable up to now by other ground-based instruments. Neither pulsed nor steady gamma-ray emission has been observed at energies of 100 GeV from the classical radio pulsars PSR J0205+6449 and PSR J2229+6114 (and their nebulae 3C58 and Boomerang, respectively) and the millisecond pulsar PSR J0218+4232. Here, we present the flux upper limits for these sources and discuss their implications in the context of current model predictions.

On the binary nature of the γ-ray sources AGL J2241+4454 (= MWC 656) and HESS J0632+057 (= MWC 148)

We present optical spectroscopy of MWC 656 and MWC 148, the proposed optical counterparts of the gamma-ray sources AGL J2241+4454 and HESS J0632+0 57, respectively. The main parameters of the Halpha emission line (EW, FWHM and centroid velocity) in these stars are modulated on the proposed orbital periods of 60.37 and 321 days, respectively. These modulations are likely produced by the resonant interaction of the Be discs with compact stars in eccentric orbits. We also present radial velocity curves of the optical stars folded on the above periods and obtain the first orbital elements of the two gamma-ray sources thus confirming their binary nature. Our orbital solution support eccentricities e~0.4 and 0.83+-0.08 for MWC 656 and MWC 148, respectively. Further, our orbital elements imply that the X-ray outbursts in HESS J0632+057/MWC 148 are delayed ~0.3 orbital phases after periastron passage, similarly to the case of LS I +61 303. In addition, the optical photometric light curve maxima in AGL J2241+4454/MWC 656 occur ~0.25 phases passed periastron, similar to what is seen in LS I +61 303. We also find that the orbital eccentricity is correlated with orbital period for the known gamma-ray binaries. This is explained by the fact that small stellar separations are required for the efficient triggering of VHE radiation. Another correlation between the EW of Halpha and orbital period is also observed, similarly to the case of Be/X-ray binaries. These correlations are useful to provide estimates of the key orbital parameters Porb and e from the Halpha line in future Be gamma-ray binary candidates.

Exploring the connection between the stellar wind and the non-thermal emission in LS 5039

Context.LS 5039 has been observed with several X-ray instruments so far showing quite steady emission in the long term and no signatures of accretion disk. The source also presents X-ray variability at orbital timescales in flux and photon index. The system harbors an O-type main sequence star with moderate mass-loss. At present, the link between the X-rays and the stellar wind is unclear. Aims.We study the X-ray fluxes, spectra, and absorption properties of LS 5039 at apastron and periastron passages during an epoch of enhanced stellar mass-loss, and the long term evolution of the latter in connection with the X-ray fluxes. Methods.New XMM-Newton observations were performed around periastron and apastron passages in September 2005, when the stellar wind activity was apparently higher. April 2005 Chandra observations on LS 5039 were revisited. Moreover, a compilation of H EW data obtained since 1992, from which the stellar mass-loss evolution can be approximately inferred, was carried out. Results.XMM-Newton observations show higher and harder emission around apastron than around periastron. No signatures of thermal emission or a reflection iron line indicating the presence of an accretion disk are found in the spectrum, and the hydrogen column density () is compatible with being the same in both observations and consistent with the interstellar value. 2005 Chandra observations show a hard X-ray spectrum, and possibly high fluxes, although pileup effects preclude conclusive results from being obtained. The H EW shows yearly variations of 10%, and does not seem to be correlated with X-ray fluxes obtained at similar phases, unlike what is expected in the wind accretion scenario. Conclusions.2005 XMM-Newton and Chandra observations are consistent with 2003 RXTE/PCA results, namely moderate flux and spectral variability at different orbital phases. The constancy of the seems to imply that either the X-ray emitter is located at 1012 cm from the compact object, or the density in the system is 3 to 27 times smaller than that predicted by a spherical symmetric wind model. We suggest that the multiwavelength non-thermal emission of LS 5039 is related to the observed extended radio jets and is unlikely to be produced inside the binary system.

Variable Very-High-Energy Gamma-Ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Asymptomatic high flow subclavian steal in a patient with hemodialysis access.

Subclavian steal phenomenon due to proximal subclavian artery stenosis or occlusion is not un-common but often remains asymptomatic. We describe the case of a 66-year-old man with end-stage renal disease hemodialysed through a brachio-brachial loop graft of the left forearm. Echo-Doppler precerebral examination showed a high reversed flow of 570 ml/min in the ipsilateral vertebral artery. After successful endovascular recanalization of the subclavian artery, access blood flow increased and vertebral flow decreased to 30 ml/min. Complete neurological examination was normal both before and after endovascular treatment. This case demonstrates how high a subclavian steal can be without causing symptoms and how well precerbral and cerebral circulation can adapt to hemodynamic changes.

Transgenic expression of Ly49A on T cells impairs a specific antitumor response.

Inhibitory MHC receptors determine the reactivity and specificity of NK cells. These receptors can also regulate T cells by modulating TCR-induced effector functions such as cytotoxicity, cytokine production, and proliferation. Here we have assessed the capacity of mouse T cells expressing the inhibitory MHC class I receptor Ly49A to respond to a well-defined tumor Ag in vivo using Ly49A transgenic mice. We find that the presence of Ly49A on the vast majority of lymphocytes prevents the development of a significant Ag-specific CD8+ T cell response and, consequently, the rejection of the tumor. Despite minor alterations in the TCR repertoire of CD8+ T cells in the transgenic lines, precursors of functional tumor-specific CD8+ T cells exist but could not be activated most likely due to a lack of appropriate CD4+ T cell help. Surprisingly, all of these effects are observed in the absence of a known ligand for the Ly49A receptor as defined by its ability to regulate NK cell function. Indeed, we found that the above effects on T cells may be based on a weak interaction of Ly49A with Kb or Db class I molecules. Thus, our data demonstrate that enforced expression of a Ly49A receptor on conventional T cells prevents a specific immune response in vivo and suggest that the functions of T and NK cells are differentially sensitive to the presence of inhibitory MHC class I receptors.

Donor-site morbidity of the sensate extended lateral arm flap.

The free extended lateral arm flap (ELAF) has gained increasing popularity thank to its slimness and versatility, longer neurovascular pedicle, and greater flap size when compared with the original flap design. The aim of this study was to assess the donor-site morbidity associated with this extended procedure. A retrospective study of 25 consecutive patients analyzing postoperative complications using a visual analogue scale questionnaire revealed high patients satisfaction and negligible donor-site morbidity of the ELAF. Scar visibility was the commonest negative outcome. Impaired mobility of the elbow had the highest correlation with patient dissatisfaction. Sensory deficits or paresthetic disorders did not affect patient satisfaction. The extension of the lateral arm flap and positioning over the lateral humeral epicondyle is a safe and well-accepted procedure with minimal donor-site morbidity. To optimize outcomes, a maximal flap width of 6 or 7 cm and intensive postoperative mobilization therapy is advisable.

Cataractogenesis after total body irradiation.

PURPOSE: To evaluate the prognostic factors and the ophthalmologic follow-up on cataract formation following total body irradiation (TBI) prior to bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1980 and 1992, 494 patients were referred to our department for TBI prior to BMT. The mean age was 32 +/- 11 (median: 32, range: 2-63) years and the male to female ratio was 1.6 (304:190). The majority of patients were treated for acute leukemia (lymphoblastic, n = 177, 36%; or nonlymphoblastic , n = 139, 28%); 80 (16%) for chronic myeloid leukemia, 60 (12%) for non-Hodgkin's lymphoma, 23 (5%) for multiple myeloma, and 15 (3%) for other malignancies. Two hundred and fifty-four (51%) patients were grafted in the first complete remission (CR), 118 (24%) in second CR. Allogenic BMT was performed in 210 (43%) patients, and autologous BMT in 284 (57%). Methotrexate combined to steroids (n = 47, 22%) or to cyclosporine (n = 163, 78%) was administered for graft-versus-host disease (GvHD) prophylaxis. In 188 patients (38%), heparin was used in the prevention of veno-occlusive disease (VOD) of the liver. Furthermore, steroid administration was registered in 223 (45%). The conditioning chemotherapy consisted of cyclophosphamide (Cy) alone in 332 (67%) patients. Total-body irradiation was administered either in single dose (STBI; 10 Gy in 1 day, n = 291) or in six fractions (FTBI; 12 Gy over 3 consecutive days, n = 203) before BMT. The mean instantaneous dose rate was 0.0574 +/- 0.0289 Gy/min (0.024-0.1783). It was < 0.048 Gy/min in 157 patients (LOW group), > or = 0.048 Gy/min and <0.09 Gy/min in 301 patients (MEDIUM group), and > or = 0.09 Gy/min in 36 patients (HIGH group). RESULTS: When considering all patients, 42 (8.5%) patients developed cataracts after 13 to 72 months (median: 42 months) with a 5-year estimated cataract incidence (ECI) of 23%. Thirty-three (11.3%) out of 291 patients in the STBI group, and 9 (4.4%) out of 203 patients in the FTBI group developed cataracts with 5-year estimated incidences of 34 and 11%, respectively (p = 0.0004). Seven (19.4%) out of 36 patients in the HIGH group, 33 (10.9%) out of 301 in the MEDIUM group, and 2 (1.2%) out of 157 in the LOW group developed cataracts with respective 5-year cataract incidences of 54%, 30%, and 3.5% (HIGH vs. MEDIUM, p = 0.07; MEDIUM vs. LOW, p = 0.0001; HIGH vs. LOW, p < 0.0001). On the other hand, patients who received heparin as prophylactic treatment against VOD of the liver had less cataracts than those who did not receive (5-year ECI of 16% vs. 28%, respectively; p = 0.01). There was no statistically significant difference in terms of 5-year ECI according to age, sex, administration of steroids, GvHD prophylaxis, type of BMT, or previous cranial radiotherapy in children. Multivariate analysis revealed that the instantaneous dose rate (p = 0.001), and the administration of heparin against VOD (p = 0.05) were the two independent factors influencing the cataract incidence, while age, fractionation, and use of steroids were not. Among the 42 patients who developed cataracts, 38 had bilateral extracapsular cataract extraction and intraocular lens implantation, and only 4 (10%) developed secondary cataracts in a median follow-up period of 39 months. CONCLUSION: Among the abovementioned TBI parameters, high instantaneous dose rate seems to be the main risk factor of cataract formation, and the administration of heparin appears to have a protective role in cataractogenesis. On the other hand, ionizing radiation seems to have a protective effect on posterior capsule opacification following extracapsular cataract extraction and intraocular lens implantation.