Advanced waveform analysis of diaphragm surface EMG allows for continuous non-invasive assessment of respiratory effort in critically ill patients at different PEEP levels.

BACKGROUND: Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. METHODS: NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. RESULTS: 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O. CONCLUSION: Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness.

BACKGROUND: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. METHODS: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. RESULTS: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. CONCLUSION: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO- CRD42022301715 . Registered 05 February, 2022.

Background elimination and interferometric capability in optical coherence tomography by a nonlinear optical gating based on type-II second-harmonic generation.

A novel method that uses nonlinear optical gating to control background illumination in optical coherence tomography is presented. With this method, the user can adjust the amount of undesired backscattering or eliminate it completely, which enables dark-field measurements. The interferometric capability of the method in a nonlinear optical regime is demonstrated with the coupling of three overlapping input waves to yield Fizeau fringes. The measurement of a 265 nm step is performed to validate this method, which was originally conceived for 3D MEMS characterization.

A transfer hamiltonian model for devices based on quantum dot arrays.

We present a model of electron transport through a random distribution of interacting quantum dots embedded in a dielectric matrix to simulate realistic devices. The method underlying the model depends only on fundamental parameters of the system and it is based on the Transfer Hamiltonian approach. A set of noncoherent rate equations can be written and the interaction between the quantum dots and between the quantum dots and the electrodes is introduced by transition rates and capacitive couplings. A realistic modelization of the capacitive couplings, the transmission coefficients, the electron/hole tunneling currents, and the density of states of each quantum dot have been taken into account. The effects of the local potential are computed within the self-consistent field regime. While the description of the theoretical framework is kept as general as possible, two specific prototypical devices, an arbitrary array of quantum dots embedded in a matrix insulator and a transistor device based on quantum dots, are used to illustrate the kind of unique insight that numerical simulations based on the theory are able to provide.

Functional characterization of new allelic polymorphisms identified in the promoter region of the human MxA gene.

The Mx proteins are high-molecular-weight dynamin-like proteins whose expression depends strictly on type-I and type-III interferons (IFN). Some isoforms are able to inhibit the life cycle of one or several viruses and are thus components of innate immune response. The human MxA protein displays the broadest antiviral spectrum which makes it appear as a key antiviral effector of innate immunity. Allelic polymorphisms located in the MxA gene promoter can be expected to affect the magnitude of MxA mRNA transcription in response to IFNs and therefore to alter the severity of viral diseases in humans. Here, three single nucleotide polymorphism sites (-309, -101 and +20) were examined for their ability to alter MxA gene promoter-driven reporter expression. We show that, besides the previously reported role of -123A and -88T, the presence of -101G is equally important. Moreover, when a promoter construct carries these three critical nucleotides, a first additional positive effect is conferred by a C at position -309 and, in this latter case, a second additional effect is produced by a A at position +20. This finding is clinically useful to improve prediction of IFN-responsiveness in patients not only with viral diseases for which type-I IFN therapy is used.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Pulmonary effects of red blood cell transfusion in critically ill, non-bleeding patients.

The aim of the study is to evaluate the effects of red blood cell (RBC) transfusions on pulmonary parameters in critically ill, non-bleeding patients. Retrospective chart analysis was performed on critically ill patients without overt bleeding in the intensive care unit (ICU) of a university hospital. In 83 patients in a 5-month period, who had received at least 1 RBC unit and stayed at least 24 h in the ICU, 199 transfusions of median 2 RBCs per transfusion (n = 504) were studied. Pulmonary parameters were retrieved during the period between 24 h before the start of transfusion and 24-48 h after transfusion. Outcome was assessed. The P(a)O(2)/F(I)O(2) dose-dependently decreased from 250 +/- 105 at baseline to 240 +/- 102 mmHg at 24 h after RBC transfusion (P = 0.003), irrespective of acute lung injury at baseline and RBC storage time. The lung injury score (LIS) also increased dose-dependently, whereas, at 48 h, oxygenation and LIS largely returned to baseline. For every seven RBCs transfused, the LIS transiently increased by 1 unit. There were no changes in haemodynamics, lung mechanics or chest radiography. The total number of RBCs given in the ICU did not directly contribute to ICU and 1-year mortality prediction. Transfusion of RBCs decreases oxygenation thereby increasing the LIS, dose-dependently and transiently, in a heterogeneous population of critically ill, non-bleeding patients, independent of prior cardiorespiratory status and RBC storage time. The effects are subtle, may go unseen and unreported and may represent subclinical transfusion-related acute lung injury. They do not adversely affect outcome, even at 1-year follow-up.

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Direct imaging of the visible emission bands from individual ZnO nanowires by near-field optical spectroscopy.

Room-temperature photoluminescence (PL) measurements have been performed on single-crystal ZnO nanowires grown on SiO2/Si and quartz substrates by the vapor transport method using Au as a catalyst. Two emission bands are apparent, one in the UV spectral region around 380 nm (3.26 eV) associated with exciton recombination processes and a much broader structure in the visible range from 420 to 700 nm, which exhibits two distinct peak-like features around 520 and 590 nm (2.38 and 2.10 eV). Spectrally resolved scanning near-field optical microscopy (SNOM) of single ZnO nanowires have been performed for a direct imaging of the PL emission with spatial resolution below 100 nm. SNOM results provide evidence that the yellow emission band observed at 590 nm is a unique property of the ZnO nanowires, being most likely related to radiative recombination processes associated with Au impurities introduced during the catalytic growth.

[Maternal adrenal necrosis in the third trimester of pregnancy: a rare complication of antiphospholipid syndrome]. / Nécrose des surrénales maternelles au troisième trimestre de la grossesse dans le cadre d'un syndrome des antiphospholipides: à propos d'un cas.

Adrenal necrosis, a rare life threatening complication of antiphospholipid syndrome, is difficult to diagnose during pregnancy. We report the case of a 33-year-old woman with bilateral adrenal necrosis which started during the third trimester of her second pregnancy. Antiphospholipid syndrome had been diagnosed few years ago, after a thrombotic event. The pregnancy was uneventful until 36 weeks plus five days, when the patient was admitted for bilateral back ache, initially considered as uterine contractions. Labour was induced because pain persisted and was associated with major thrombocytopenia. A healthy infant was delivered vaginally on the second day, adrenal failure was diagnosed based on intense asthenia, persistent severe lumbar pain, low blood sodium and cortisol. Bilateral adrenal oedema was documented by CT scan and MRI. Symptoms resolved following administration of hydrocortisone and fludrocortisone. This case illustrates the difficulty to diagnose adrenal necrosis in the third trimester of pregnancy.

Synthesis of bio-inspired multilayer polarizers and their application to anti-counterfeiting.

Some insects, such as Papilio blumei and Suneve coronata, are known for exhibiting polarization effects on light such as color contrast or geometrical polarization rotation by reflection on their wing scales. The photonic structures found on these species that show these properties are multilayered spherical cavities or triangular grooves which polarize the light due to multiple inner reflections. These polarization effects, in addition to the intrinsic color-mixing properties of these photonic structures, are of interest in the anti-counterfeiting field due to their invisibility to the naked eye. In this paper, we report micro-fabrication techniques to produce bio-inspired cylindrical grooves (C-grooves) and triangular grooves (V-grooves) that demonstrate the same properties. Theoretical analyses were carried out by using multi-scale simulation (MS) as well as by finite-difference time-domain (FDTD) in order to compare the polarization capability of both structures. The V-grooves show greater polarization contrast than the C-grooves, but the spectrum is specular. The C-grooves exhibit lower polarization effects but have a dispersive spectrum. In both cases, the structures show additional optical properties, such as diffraction, macroscopic color contrast under a polarizer, and contrast inversion due to geometries which contribute to their uniqueness.

Permanently densified SiO2 glasses: a structural approach.

Densified silica can be obtained by different pressure and temperature paths and for different stress conditions, hydrostatic or including shear. The density is usually the macroscopic parameter used to characterize the different compressed silica samples. The aim of our present study is to compare structural modifications for silica glass, densified from several routes. For this, densified silica glasses are prepared from cold and high temperature (up to 1020 °C) compressions. The different densified glasses obtained in our study are characterized by micro-Raman spectroscopy. Intertetrahedral angles from the main band relative to the bending mode decrease and their values are larger for densified samples from high temperature compression than those samples from cold compression. The relative amount of 3-membered rings deduced from the D2 line area increases as a function of density for cold compression. The temperature increase during the compression process induces a decrease of the 3 fold ring population. Moreover, 3 fold rings are more deformed and stressed for densified samples at room temperature at the expense of those densified at high temperature. Temperature plays a main role in the reorganization structure during the densification and leads to obtaining a more relaxed structure with lower stresses than glasses densified from cold compression. The role of hydrostatic or non-hydrostatic applied stresses on the glass structure is discussed. From the Sen and Thorpe central force model, intertetrahedral angle average value and their distribution are estimated.

A novel gene overexpressed in the prostate of castrated rats: hormonal regulation, relationship to apoptosis and to acquired prostatic cell androgen independence.

We have identified a novel complementary DNA (cDNA) corresponding to a gene overexpressed in the rat ventral prostate after castration. This cDNA displays 89.4% identity with 453 bp of a mouse EST and 81.5% identity with 157 bp of a human EST and was named PARM-1 for prostatic androgen-repressed message-1. The complete cDNA is 1187 bp long and codes for a protein of 298 amino acids that contains four potential glycosylation sites and three half cystinyl residues. The PARM-1 gene was found to be expressed at quite low levels in most rat tissues including those of the urogenital tract. The kinetic of induction of PARM-1 gene in the prostate was highly correlated to the development of apoptosis in the whole organ. Supplementation of castrated animals with androgens reversed both the process of apoptosis and the overexpression of PARM-1 gene. Supplementation with estrogens did not result in an increase in the PARM-1 messenger RNA levels when compared with the castration alone. However, the treatment resulted in a more rapid return to intact levels in the castrated plus estrogen group. When apoptosis of testis and prostate was induced in vivo by hypophysectomy, it was found that PARM-1 was only overexpressed in the prostate. Therefore, PARM-1 seems to be regulated by androgens only in the prostate. Using in situ hybridization and immunohistological techniques, we have shown that PARM-1 gene product is found exclusively in the epithelial cells of involuting prostate. Analysis by flow cytometry of MAT LyLu epithelial cells transiently expressing PARM-1 protein did not allow us to demonstrate a direct effect of PARM-1 gene overexpression on the programmed death of the transfected cells. Treatment of MAT LyLu cells by transforming growth factor-beta induced apoptosis but had no effect on PARM-1 production. However PARM-1 protein has been detected by Western blotting in various cell lines such as MAT LyLu, MAT Lu, and PIF, which are androgen independent. This would suggest that PARM-1 gene product would be a marker for acquired androgen-independence of these tumor cells.

A novel messenger ribonucleic acid homologous to human MAGE-D is strongly expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by follitropin, lutropin, and prolactin.

We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92% homology with the human MAGE-D protein. In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D expression was ubiquitous in healthy rat tissues. In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells. Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting. In MLTC-1 cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression. Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole testis most probably through a direct action on Leydig cells. As MAGE-D is present in both the seminiferous compartment and interstitium and hormonally regulated in each, it is possible that it has specific functions in each compartment during the development and the maintenance of the testis.

Role of astrocytes in antigen presentation and naive T-cell activation.

Astrocytes may have a role in antigen presentation in inflammatory diseases of the central nervous system (CNS) such as MS and EAE. In this study, we have assessed whether purified astrocyte cultures could stimulate naive CD4(+) or CD8(+) T-cells from TCR transgenic mice. As previously described, astrocytes sustained antigen-specific CD4(+) T-cell proliferation only in the presence of IFN-gamma, which promotes expression of both MHC class II and B7 molecules on astrocytes. In addition, we show that astrocytes also have the capacity to present antigens to naive CD8(+) T-cell and promote their proliferation. In one system, this CD8(+) T-cell proliferation was dependent on IFN-gamma-induced upregulation of B7 molecules on astrocytes. However, in a second TCR transgenic system, astrocytes could induce naive CD8(+) T-cell proliferation even in the absence of IFN-gamma. The possible implications of these findings for the pathophysiology of CNS inflammatory diseases are discussed.

The experimental (in vitro) and clinical (in vivo) immunosuppressive effects of a rat IgG2b anti-human CD2 mAb, LO-CD2a/BTI-322.

BACKGROUND: CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells, working as a cell adhesion and costimulatory molecule. The aim of this paper is to analyze the mechanism of action of a rat IgG2b anti-human CD2 monoclonal antibody (mAb) (LO-CD2a/BTI-322 mAb), which is a potent immunosuppressive agent and inducer of cell death. In vivo, this mAb is able to prevent or treat kidney allograft rejection. METHODS: The mechanisms by which the LO-CD2a/BTI-322 mAb is able to induce inhibition of cell activation and cell death were analyzed by mixed lymphocyte reactions and by flow cytometry. After in vivo treatment, levels of circulating mAb were measured by ELISA as well as anti-rat immunization and cytokine release. RESULTS: We show that the inhibition of cell activation induced by LO-CD2a/BTI-322 mAb after allogeneic or OKT3 stimulation is due to an Fcgamma receptor-dependent CD2 down-modulation and to T-cell depletion through an antibody-dependent cell-mediated cytotoxicity mechanism mediated by NK cells or activated monocytes. Peripheral T- and NK-cell depletion was observed after in vivo treatment with LO-CD2a/BTI322. Cytokine release (TNFalpha) was correlated with some side effects, but only after the first injection, and the effects were never severe or life threatening. CONCLUSION: The correlation between the in vitro and in vivo data suggests that T-cell depletion, especially of activated cells, and inhibition of cell activation after CD2 down-modulation are the main mechanisms of action of the LO-CD2a/BTI-322 mAb.

Prophylactic immunosuppression with anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 versus OKT3 in liver allografting. A two-year follow-up study.

A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n = 42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n = 44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n = 43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P = 0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P = 0.002; 1 vs. 3, P = 0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P = 0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.

Prophylaxis of graft-versus-host disease in identical sibling donor bone marrow transplant by anti-IL-2 receptor monoclonal antibody LO-Tact-1.

The efficacy of the rat monoclonal IgG2b antibody LO-Tact-1 specific for the human interleukin-2 (IL-2) receptor was evaluated for prophylaxis of graft-versus-host disease (GVHD) in patients who received transplants of marrow from HLA-matched sibling donors. Fifteen patients received cyclosporine (CsA) + antibody LO-Tact-1, 0.2 mg/kg/day from day +7 to day +28. Twelve additional patients were administered methotrexate (MTX) + CsA+antibody LO-Tact-1, 0.4 mg/kg/day from day -1 to day +28. The antibody was well tolerated. Engraftment was not affected. GVHD grade > or = II occurred in six of 15 and eight of 12 patients receiving CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (P = 0.52). GVHD grade > or = II developed in patients at a median of 32 and 34 days with CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (log-rank test, P = 0.57). GVHD contributed to death in four patients who were administered CsA+LO-Tact-1 and in one patient who was administered MTX+CsA+LO-Tact-1. Chronic GVHD occurred in two patients who were treated with CsA+LO-Tact-1 and in two patients treated with MTX+CsA+LO-Tact-1. Throughout therapy, serum levels of LO-Tact-1 ranged from 2 to 10 mg/l. There was no correlation between serum levels of LO-Tact-1 and the occurrence of GVHD. GVHD occurred in 10 patients during LO-Tact-1 prophylaxis. There was no significant difference between relapse or survival rates among the patient groups. We conclude that, while free of adverse effects, monoclonal anti-IL-2 receptor antibody LO-Tact-1 does not improve prophylaxis of GVHD in HLA-matched sibling BMT.