Clinical Utility of the Cardiorespiratory Optimal Point in Patients with Heart Failure

Introduction We assessed the cardiorespiratory optimal point (COP)—the minimal V̇E/V̇O2 in a given minute of an incremental cardiopulmonary exercise test—in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes. Methods We studied 277 HF patients (67 (58–74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, 30.7). Results Median COP was 28.2 (24.9–32.1) and was reached at 51% ± 15% of V̇O2peak. Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (−0.8; 95% confidence interval, −1.3 to −0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33–0.84) for adverse clinical outcomes as compared with high COP. Conclusions Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs.Eurostars Grant (E!114585

Serious bacterial infections in patients with rheumatoid arthritis under anti‐TNF‐α therapy

Objective. With rising numbers of anti‐tumour necrosis factor α (TNF‐α) treatments for rheumatoid arthritis (RA), Crohn's disease and other conditions, physicians unaware of potential pitfalls are increasingly likely to encounter associated severe infections. Our purpose was to assess the incidence and nature of severe infections in our RA patients under anti‐TNF‐α therapy. Methods. We reviewed patient charts and records of the Infectious Disease Unit for serious infections in patients with RA in the 2 yr preceding anti‐TNF‐α therapy and during therapy. Results. Serious infections affected 18.3% of patients treated with infliximab or etanercept. The incidence was 0.181 per anti‐TNF‐α treatment year vs 0.008 in the 2 yr preceding anti‐TNF‐α therapy. In several cases, only a few signs or symptoms indicated the severity of developing infections, including sepsis. Conclusions. A high level of suspicion of infection is necessary in patients under anti‐TNF‐α therapy. We suggest additional strategies for the prevention, rapid identification and pre‐emptive therapy of such infection

A supersonic arc jet

In the plasma of a cascaded arc, with arc currents from 40 up to 100 A, arc voltage of about 100 V and an argon pressure of about 0.5 bar, the gas temperature equals the electron temperature of about 12000K. The electron density ranges from 10(21) to 10(23) m/sup -3/, ionization degree is about 10%. The equilibrium of this kind of plasmas is well understood. In the authors' experiment this arc plasma expands into a vacuum system through a hole with a diameter of 4 mm in the anode. To obtain a background pressure of roughly 1 mBar, large pumping speeds are needed. The expansion clearly shows supersonic behaviour and is limited by a shock front (Barrel-shock and Mach-disk). The experiments were done in a mixture of argon (70 cc/sec) and hydrogen (0,7 cc/sec

In situ infrared absorption spectroscopy of dusty plasmas

In situ, time-resolved Fourier transform infrared spectroscopy was used to study particulate formation in rf discharges in mixtures of silane, argon, and nitrogen. The spectra were taken at a maximum rate of 20 Hz. The discharge conditions were chosen such that previous calibrations of the time evolutions of particle size and density could be used. The measurements indicate that the onset of the solid-state vibrational absorptions of the SiH and SiH2 bands only takes place after the nucleation and coagulation phase have finished; it coincides with the previously predicted start of the deposition of amorphous hydrogenated silicon on the particles. The dissociation of the silane feed gas is found to be in the range of 30%, and its time development suggests that also the large-scale dissociation of silane only starts after the coagulation phase. This is in agreement with previously observed trends for the electron temperature. If silicon partilces are grown in the plasma, and the silane flow is stopped, the Si particles stay trapped in the glow. The infrared measurements, however, show that they almost completely oxidize: the SiH/SiH2 vibrations disappear and a strong SiO vibration appears. If nitrogen gas is allowed into the plasma, the SiO vibration is replaced by a SiN vibration. © 1996 American Vacuum Societ

The role of apoptosis in bispecific antibody-mediated T-cell cytotoxicity.

In this report we describe the role of apoptosis in the process of tumour cell killing by bispecific monoclonal antibody (BsMAb)-redirected cytolytic T cells. The BsMAb used, BIS-1, has dual specificity for the CD3 complex on T cells and the pancarcinoma-associated 38 kDa transmembrane antigen EGP-2. BIS-1 allows activated T cells to specifically recognise and kill EGP-2-positive but not EGP-2-negative target cells. An assay was developed to quantify apoptosis in cells by separation of 3H-thymidine-labelled low-molecular, i.e. fragmented, from high-molecular, i.e. non-fragmented DNA. The presence of low molecular weight DNA was measured both within the target cells and in the cell-free supernatant. After exposure to BIS-1-redirected, -activated T cells, apoptosis was observed in EGP-2-positive target cells but not in EGP-2-negative target cells. Also no DNA fragmentation proved to be induced in the activated effector cells during assay. The degree of EGP-2-positive target DNA fragmentation depended on the concentration of BsMAb, the E/T ratio and the incubation time. Using a low E/T ratio (1/1), DNA fragmentation in and 51Cr release from target cells showed similar characteristics and kinetics. At higher E/T ratio (20/1), the 51Cr release from the target cells increased to a greater extent than the percentage fragmented target cell DNA. Inhibitors of DNA fragmentation added to the cytotoxicity assay inhibited not only DNA fragmentation, but also the release of chromium-51 from the target cells, suggesting that apoptosis and cell lysis are closely related in BsMAb-mediated cell killing

Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.co

Immunomodulatory effects of intravenous BIS-1 F(ab')2 administration in renal cell cancer patients.

We report the immunomodulatory effects of an intravenous treatment with F(ab')2 fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the EGP-2 molecule on carcinoma cells and some normal epithelia. The amount of BIS-1 F(ab')2 bound to peripheral blood lymphocytes (PBLs) increased dose-dependently. This occupation degree was highest at the end of the 2 h infusion and rapidly decreased subsequently. During the first hour of BIS-1 F(ab')2 infusion the number of PBLs decreased slowly. This was followed by an increase in serum tumour necrosis factor alpha (TNF-alpha) concentrations and a rapid decrease in the numbers of peripheral blood lymphocytes, monocytes and eosinophils. In our view, the most likely explanation for the observed decrease in occupation degree of BIS-1 F(ab')2 and the rise in TNF-alpha levels is based on the assumption that BIS-1-carrying T cells leave the circulation. The CD3 antigens on these extravasated T cells become cross-linked by EGP-2 antigens, inducing TNF-alpha secretion. This results in an enhanced decrease in the numbers of PBLs, monocytes and eosinophils. These preliminary results suggest that BIS-1 F(ab')2 treatment during IL-2 therapy may induce local T-cell activation

In situ infrared absorption spectroscopy of dusty plasmas

International audienceIn situ, time-resolved Fourier transform infrared spectroscopy was used to study particulate formation in rf discharges in mixtures of silane, argon, and nitrogen. The spectra were taken at a maximum rate of 20 Hz. The discharge conditions were chosen such that previous calibrations of the time evolutions of particle size and density could be used. The measurements indicate that the onset of the solid-state vibrational absorptions of the SiH and SiH 2 bands only takes place after the nucleation and coagulation phase have finished; it coincides with the previously predicted start of the deposition of amorphous hydrogenated silicon on the particles. The dissociation of the silane feed gas is found to be in the range of 30%, and its time development suggests that also the large-scale dissociation of silane only starts after the coagulation phase. This is in agreement with previously observed trends for the electron temperature. If silicon partilces are grown in the plasma, and the silane flow is stopped, the Si particles stay trapped in the glow. The infrared measurements, however, show that they almost completely oxidize: the SiH/SiH 2 vibrations disappear and a strong SiO vibration appears. If nitrogen gas is allowed into the plasma, the SiO vibration is replaced by a SiN vibration

Transport of argon ions in an inductively coupled high-density plasma reactor

The first direct observation of the velocity distribution of the metastable Ar1*~2G9/2! ions in the presheath of an inductively coupled plasma has been achieved by using the Doppler shifted laser induced fluorescence technique. Drift of the ions along the electric field in the presheath is observed and distribution functions of the velocity in both parallel and perpendicular directions, relative to the E field, are deduced at 5 and 40 mTorr. Present results show that in high density plasmas the velocity distribution of the metastable ions is directly related to that of the ground state argon ions. Neutral gas temperature of around 600 K is also measured from the absorption profile of a diode laser beam, set on one of the 772.4 nm argon lines