OBJECTIVESAlveolar haemorrhage (AH) can be a mild or life-threatening manifestation of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), but its prognostic impact and specific characteristics remain controversial. Our objective was to determine the prognostic value of AH in this context.METHODSAH episodes that occurred, between 1991 and 2010, in AAV patients entered in the FVSG database were retrospectively analysed. Data on AH characteristics and outcome measures were collected on a specific form.RESULTSAmong the 80 cases analysed, AAV were 61.25% granulomatosis with polyangiitis (GPA) (Wegener), 26.25% microscopic polyangiitis (MPA), 10% Churg-Strauss syndrome and 2 (2.5%) unclassified. Mild or severe haemoptysis alone, or together with other clinical symptoms was present in 77 (96.2%) patients before AAV diagnosis. Among 10 (12.5%) patients requiring mechanical ventilation, 4 had prior minor haemoptysis before abundant AH. Sixty-one (76.3%) patients had concomitant active rapid crescentic glomerulonephritis causing renal insufficiency (pulmo-renal syndrome): 37/49 GPA (Wegener) (75.5% of all GPA (Wegener)), 19/21 MPA (90.4% of all MPA), 3/8 had CSS and 2/2 had unclassified vasculitis. The mean AH-to-treatment-onset interval was 5.9 days. Mean follow-up was 7.3 years. Forty-seven (58.8%) patients relapsed: 23 with AH and with (13) or without (10) other organ involvement, 24 with non-AH manifestation(s). Three patients underwent kidney transplantation. Sixteen (20%, 8 GPA (Wegener) and 8 MPA) patients died. No death resulted directly from the initial AH; 14 (87.5%) patients with pulmo-renal syndrome died.CONCLUSIONSAs previously demonstrated by the Five-Factor Score, AH alone is not predictive of poor prognosis, unlike kidney involvement, which dictates a poor outcome.

Die rapid progrediente Glomerulonephritis (RPGN) ist als klinisches Syndrom durch die zeitliche Veränderung der Nierenfunktion definiert. Frühes Erkennen und sofortige immunsuppressive Behandlung verbessern die Prognose. Die Nierenbiopsie und die Autoantikörperserologie ermöglichen die genaue diagnostische Zuordnung der RPGN. Es werden ihre Einteilung aufgrund der Immunhistologie, der antineutrophil zytoplasmatische Antikörper (ANCA) und der antiglomerulären Basalmembran-Antikörper (anti-GBM) diskutiert. Anhand von Ergebnissen randomisiert kontrollierter Studien werden die Möglichkeiten der differenzierten Behandlung erläutert.

The biophysical aspects of stereotaxic treatment are summarized, emphasizing the complex interplay between time-dose-fractionation, partial volume effect, physical dose distribution, and set-up uncertainties in influencing treatment outcome. The radiobiological advantage of dose-fractionation for normal tissue sparing is estimated using the linear-quadratic model and viewed in the context of clinical situations and results. Counterbalancing this benefit is the larger geometrical uncertainty associated with multiple fraction treatment, which would require increased treatment volume and an associated decrease in treatment dose. This last consideration requires knowledge of volume-dose relation of radiation-induced normal brain toxicity, the current status of which is also outlined.

We report 6H-SiC samples implanted with hydrogen at a dose of 1x10(17) H+ atom/cm(2), using a 1.0 MeV proton beam. Implantation-induced changes in vibration modes were investigated by backscattering Raman spectroscopy, Results have been discussed in the light of the extended zone scheme and some of the forbidden Br modes tentatively assigned. After 950 degreesC annealing during 1 hr, incomplete crystal recovery is found.

Diffusion behaviour of aluminium in silicon at temperatures up to T=900°C was investigated by nuclear reaction analysis (NRA). Previously published results predict diffusion coefficients ranging from 3×10−15 to 1.3×10−13cm2s−1 at T=900°C. In a first series aluminium films were vapour deposited onto Si〈100〉 substrates, followed by isochronal annealing. The diffusion coefficient was found to be less than 10−15cm2s−1 at 900°C. In a second series Si〈100〉 and Si〈111〉 samples were implanted at room temperature and at 250°C with a fluence of 5×1016 Al+ cm−2. For the samples implanted at 250°C and subsequently annealed at 900°C, the diffusion coefficient was again found to be less than 10−15cm2s−1, while diffusion coefficients of the order of 10−13cm2s−1 were observed for the room-temperature implanted samples. Channeling analyses revealed extensive radiation damage in the latter samples, which was still present after annealing for 1 h at 900°C. In contrast to this, the samples implanted at 250°C were virtually defect-free. From this it is concluded that the high values observed for the room-temperature implants are due to defect-assisted diffusion.

Nuclear reaction analysis was used to determine the range profiles of 150 keV aluminium ions implanted into a variety of metal targets in the atomic number region of 23⩽Z2⩽78. Implantations were performed at room temperature with fluences of 5×1016 Al+ cm−2 and dose rates below 1013 Al+ cm−2 s−1 to prevent excessive target heating. Profiles were determined by detecting the 10.76 MeV photons from the 27Al(p,γ)28Si resonance reaction at 992 keV as a function of proton energy. Range profiles were extracted from the excitation curve after correcting for proton straggling. The experimental profiles and range moments are compared with TRIM predictions, taking target sputtering effects into account.

Range parameters for aluminium ions implanted at 150 keV into metals with atomic numbers in the 12 less than or equal to Z(2) less than or equal to 42 region were analysed using a nuclear resonance reaction technique. Depth profiles were determined by detecting the 10.76 MeV photons from the 12.54 MeV to 1.78 MeV exited level transition at the 0.992 MeV resonance of the Al-27(p,gamma)Si-28 reaction. The results of a four moment analysis are compared with TRIM-calculations using the 1991 and 1995 codes after correcting for proton energy straggling and beam width. The experimental projected ranges are in all cases slightly smaller than expected, while the higher moments indicate an almost gaussian shape in reasonable agreement with computed distributions.

Undoped (100) GaAs crystals were implanted with 0.5, 1.0 and 2.0 MeV protons at high fluences of about 5 x 10(17) ions cm(-2). After implantation the samples were subjected to pulse electron beam annealing (PEBA) at variable energy densities.The samples were analysed with alpha particle channeling as well as with electron channeling patterns (ECP), in order to evaluate the damage introduced during implantation. Surface and compositional studies were performed by means of scanning electron microscopy (SEM) and energy dispersive X-rays (EDX) respectively.Unimplanted samples exhibit a peculiar surface structure after pulsed electron beam annealing at energy densities above 0.9 J cm(-2), consisting of regular rectangles with variable side lengths in the range of 10 to 200 mu m. After high dose proton implantation the PEBA threshold energy density for observing these structures could be reduced to 0.4 J cm(-2).Cross sectional SEM samples reveal a cracked subsurface region at the position where these rectangular blocks separate from the bulk crystal. Deeper into the crystal the ion implanted damage distribution, which correlated well with TRIM calculations, was also observed.

Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that possess a wide spectrum of biological effects. Two natural antagonists of IL-1 action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1 alpha have also been detected in sera of healthy individuals and patients with autoimmune or inflammatory diseases. To characterize such antibodies molecularly, we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40-activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We describe herein the generation and properties of a natural IgG4/kappa anti-IL-1 alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1 alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(-10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized biological activities of both recombinant and natural forms of IL-1 alpha. A recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha antagonism. The presence of somatic mutations within X3 variable regions suggests an antigen-driven affinity maturation. This study extends the demonstration of the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that can function as a third type of IL-1 antagonist.

Channeling of 2.0 MeV α-particles, in conjunction with transmission electron microscopy (TEM), was used to study the radiation damage produced in InP due to the implantation of Bi + and Xe + ions. The 150 keV ions were implanted at room temperature with doses between 1 × 10 12 and 1 × 10 14 ions cm -2 . An amorphous layer was formed at a dose ≥ 5 × 10 13 cm -2 and the recrystallization of this layer was studied as a function of pulsed electron beam annealing (PEBA) at energy densities up to 0.85 J cm -2 . Recrystallization occurs in a sharp energy density range around ∼ 0.4 J cm -2 , but higher energy densities lead to the formation of an In enriched surface.

The lattice site occupation of iodine ions implanted into aluminium single crystals at 5 and 293 K was determined by in situ MeV He+ ion channeling. After implantation at 5 K the iodine atoms occupy substitutional and other regular interstitial positions. Upon annealing to 293 K most of the iodine atoms shift to near-octahedral sites. The relocation is attributed to the formation of iodine-hexavacancy configurations. This complex is also formed during implantation at 293 K. The near-octahedral fraction at 293 K was measured as a function of iodine concentrations. At concentrations of about 0.003% I in Al 〈110〉 the peak height in the center of the channel was about 2.4 + 0.3. Increasing the concentration, the peak height decreases to 1.3 at 0.1% I and to 1.0 at 1.5% I.