Experimental evidence of symmetry breaking of transition-path times.

While thermal rates of state transitions in classical systems have been studied for almost a century, associated transition-path times have only recently received attention. Uphill and downhill transition paths between states at different free energies should be statistically indistinguishable. Here, we systematically investigate transition-path-time symmetry and report evidence of its breakdown on the molecular- and meso-scale out of equilibrium. In automated Brownian dynamics experiments, we establish first-passage-time symmetries of colloids driven by femtoNewton forces in holographically-created optical landscapes confined within microchannels. Conversely, we show that transitions which couple in a path-dependent manner to fluctuating forces exhibit asymmetry. We reproduce this asymmetry in folding transitions of DNA-hairpins driven out of equilibrium and suggest a topological mechanism of symmetry breakdown. Our results are relevant to measurements that capture a single coordinate in a multidimensional free energy landscape, as encountered in electrophysiology and single-molecule fluorescence experiments.

Single walled carbon nanotube/Si heterojunctions for high responsivity photodetectors.

Single walled carbon nanotube/n-Si (SWCNT/n-Si) hetero-junctions have been obtained by depositing SWCNT ultra-thin films on the surface of an n-Si substrate by dry transfer method. The as obtained junctions are photo sensitive in the measured wavelength range (300-1000 nm) and show zero bias responsivity and detectivity values of the order of 1 A W-1 and 1014 Jones respectively, which are higher than those previously observed in carbon based devices. Moreover, under on-off light excitation, the junctions show response speed as fast as 1 µs or better and noise equivalent powers comparable to commercial Si photomultipliers. Current-voltage measurements in dark and under illumination suggest that the devices consist of Schottky and semiconductor/semiconductor junctions both contributing to the fast and high responses observed.

Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta-analysis of randomized controlled trials.

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta-analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re-operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events. SUMMARY: Background Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. Objectives To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction. Patients/Methods We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random-effects model. Results Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, -0.65 units; 95% Confidence Interval [CI], -1.16 to -0.13 units), lost less blood (MD, -253.93 mL; 95% CI, -408.01 to -99.85 mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18-0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results Conclusions Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.

Control of force through feedback in small driven systems.

Controlling a time-dependent force applied to single molecules or colloidal particles is crucial for many types of experiments. Since in optical tweezers the primary controlled variable is the position of the trap, imposing a target force requires an active feedback process. We analyze this feedback process for the paradigmatic case of a nonequilibrium steady state generated by a dichotomous force protocol, first theoretically for a colloidal particle in a harmonic trap and then with both simulations and experiments for a long DNA hairpin. For the first setup, we find there is an optimal feedback gain separating monotonic from oscillatory response, whereas a too strong feedback leads to an instability. For the DNA molecule, reaching the target force requires substantial feedback gain since weak feedback cannot overcome the tendency to relax towards the equilibrium force.

Desmopressin after cardiac surgery in bleeding patients. A multicenter randomized trial.

BACKGROUND: Previous studies showed that desmopressin decreases post-operative blood loss in patients undergoing cardiac surgery. These studies were small and never studied the effect of desmopressin in patients with active bleeding. Objective of the study was to determine whether desmopressin reduces red blood cells transfusion requirements in patients with active bleeding after cardiac surgery who had been pre-treated with tranexamic acid. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study randomized elective patients with bleeding after cardiac surgery despite pre-treatment with tranexamic acid, to receive placebo (saline solution) or a single administration of desmopressin (0.3 µg/kg in saline solution). The primary endpoint was the number of patients requiring red blood cells transfusion after randomization and during hospital stay. Secondary end points were: blood loss from chest tubes during the first 24 h after study drug administration, hours of mechanical ventilation, intensive care unit stay, and in-hospital mortality. RESULTS: The study was interrupted after inclusion of 67% of the planned patients for futility. The number of patients requiring red blood cells transfusion after randomization was 37/68 (54%) in desmopressin group and 33/67 (49%) in placebo group (P = 0.34) with no difference in blood loss: 575 (interquartile 422-770) ml in desmopressin group and 590 (476-1013) ml in placebo group (P = 0.42), mechanical ventilation, intensive care unit stay or mortality. CONCLUSIONS: This multicenter randomized trial demonstrated that, in patients pre-treated with tranexamic acid, desmopressin should not be expected to improve treatment of patients who experience bleeding after cardiac surgery.

Steering the efficiency of carbon nanotube-silicon photovoltaic cells by acid vapor exposure: a real-time spectroscopic tracking.

Hybrid carbon nanotube-silicon (CNT-Si) junctions have been investigated by angle resolved photoemission spectroscopy (AR-XPS) with the aim to clarify the effects of a nonstoichiometric silicon oxide buried interface on the overall cell efficiency. A complex silicon oxide interface has been clearly identified and its origin and role in the heterojunction have been probed by exposing the cells to hydrofluoric (HF) and nitric (HNO3) acid. Real-time monitoring of the cell efficiencies during the steps following acid exposure (up to 1 week after etching) revealed a correlation between the thickness and chemical state of the oxide layer and the cell efficiencies. By matching the AR-XPS and Raman spectroscopy with the electrical response data it has been possible to discriminate the effects on the cell efficiency of the buried SiO(x) interface from those related to CNT acid doping. The overall cell behavior recorded for different thicknesses of the SiO(x) interface indicates that the buried oxide layer is likely acting as a passivating/inversion layer in a metal-insulator-semiconductor junction.

Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study.

BACKGROUND: The effect of anaesthesia on postoperative outcome is unclear. Cardioprotective properties of volatile anaesthetics have been demonstrated experimentally and in haemodynamically stable patients undergoing coronary artery bypass grafting. Their effects in patients undergoing high-risk cardiac surgery have not been reported. METHODS: We performed a multicentre, randomized, parallel group, controlled study among patients undergoing high-risk cardiac surgery (combined valvular and coronary surgery) in 2008-2011. One hundred subjects assigned to the treatment group received sevoflurane for anaesthesia maintenance, while 100 subjects assigned to the control group received propofol-based total i.v. anaesthesia. The primary outcome was a composite of death, prolonged intensive care unit (ICU) stay, or both. Thirty day and 1 yr follow-up, focused on mortality, was performed. RESULTS: All 200 subjects completed the follow-up and were included in efficacy analyses, conducted according to the intention-to-treat principle. Death, prolonged ICU stay, or both occurred in 36 out of 100 subjects (36%) in the propofol group and in 41 out of 100 subjects (41%) in the sevoflurane group; relative risk 1.14, 95% confidence interval 0.8-1.62; P=0.5. No difference was identified in postoperative cardiac troponin release [1.1 (0.7-2) compared with 1.2 (0.6-2.4) ng ml(-1), P=0.6], 1 yr all-cause mortality [11/100 (11%) compared with 11/100 (11%), P=0.9], re-hospitalizations [20/89 (22.5%) compared with 11/89 (12.4%), P=0.075], and adverse cardiac events [10/89 (11.2%) compared with 9/89 (10.1%), P=0.8]. CONCLUSIONS: There was no observed beneficial effect of sevoflurane on the composite endpoint of prolonged ICU stay, mortality, or both in patients undergoing high-risk cardiac surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00821262. Eudra CT (2008-001752-43).

Protein C zymogen in adults with severe sepsis or septic shock

INTRODUCTION: Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen. Design, setting and participants: A prospective study on 23 adult patients with severe sepsisor septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50 IU/kg bolus followed by continuous infusion of 3 IU/kg/h for 72 h).RESULTS: The Z-test evidenced a significant reduction between the expected mortality (53%)and the observed mortality 30% (Z value = 1.99, p = 0.046) in our sample population. Protein Clevels increased from 34 ± 18% to 66 ± 22% at 6 h after PC bolus (p < 0.001), and kept on increasing during 72 h of administration (p < 0.001 to baseline). Sequential Organ Failure Assessment(SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14 ± 2 to 7 ± 4 (p < 0.001). No adverse event drug related was noted. CONCLUSION: Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial

INTRODUCCIÓN: La proteína C activada se asocia a un elevado riesgo de hemorragia, y sus efectos sobre la supervivencia en los pacientes con choque séptico son cuestionables. El zimógeno de proteína C no presenta ningún riesgo de hemorragia, y mejora los resultados en los pacientes con choque séptico. Describimos la serie de casos más amplia publicada de pacientes adultos tratados con zimógeno de proteína C. Diseño, ámbito y participantes: Se ha llevado a cabo un estudio prospectivo en el que han articipado 23 adultos con sepsis grave o choque séptico, 2 o más fallos orgánicos, y un elevado riesgo de hemorragia, tratados con zimógeno de proteína C (dosis en bolo de 50 UI/kg seguida de una infusión continua de 3 UI/kg/h durante 72h). RESULTADOS: La prueba Z puso de manifiesto una disminución significativa entre la mortalidad prevista (53%), y la mortalidad observada 30% (valor Z = 1,99; p = 0,046) en nuestra serie. Las concentraciones de proteína C incrementaron de 34 ±18% a 66 ± 22% a las 6 h de la dosis en bolo (p < 0,001), y siguieron incrementando durante las 72 h siguientes a la administración (p < 0,001 respecto a la situación basal). La puntuación en la evaluación secuencial del fallo orgánico (SOFA) disminuyó entre la situación basal, y 7 días después de la administración de proteína C de 14 ± 2 a 7 ± 4 (p < 0,001). No se registraron reacciones farmacológicas adversas. CONCLUSIÓN: El zimógeno de proteína Z debería investigarse su utilización en los pacientes con sepsis mediante un estudio aleatorizado y controlado

Protein C zymogen in adults with severe sepsis or septic shock.

INTRODUCTION: Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen. DESIGN, SETTING AND PARTICIPANTS: A prospective study on 23 adult patients with severe sepsis or septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50IU/kg bolus followed by continuous infusion of 3IU/kg/h for 72h). RESULTS: The Z-test evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (Z value=1.99, p=0.046) in our sample population. Protein C levels increased from 34±18% to 66±22% at 6h after PC bolus (p<0.001), and kept on increasing during 72h of administration (p<0.001 to baseline). Sequential Organ Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14±2 to 7±4 (p<0.001). No adverse event drug related was noted. CONCLUSION: Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial.

Counter-propagating dual-trap optical tweezers based on linear momentum conservation.

We present a dual-trap optical tweezers setup which directly measures forces using linear momentum conservation. The setup uses a counter-propagating geometry, which allows momentum measurement on each beam separately. The experimental advantages of this setup include low drift due to all-optical manipulation, and a robust calibration (independent of the features of the trapped object or buffer medium) due to the force measurement method. Although this design does not attain the high-resolution of some co-propagating setups, we show that it can be used to perform different single molecule measurements: fluctuation-based molecular stiffness characterization at different forces and hopping experiments on molecular hairpins. Remarkably, in our setup it is possible to manipulate very short tethers (such as molecular hairpins with short handles) down to the limit where beads are almost in contact. The setup is used to illustrate a novel method for measuring the stiffness of optical traps and tethers on the basis of equilibrium force fluctuations, i.e., without the need of measuring the force vs molecular extension curve. This method is of general interest for dual trap optical tweezers setups and can be extended to setups which do not directly measure forces.

Force spectroscopy with dual-trap optical tweezers: molecular stiffness measurements and coupled fluctuations analysis.

Dual-trap optical tweezers are often used in high-resolution measurements in single-molecule biophysics. Such measurements can be hindered by the presence of extraneous noise sources, the most prominent of which is the coupling of fluctuations along different spatial directions, which may affect any optical tweezers setup. In this article, we analyze, both from the theoretical and the experimental points of view, the most common source for these couplings in dual-trap optical-tweezers setups: the misalignment of traps and tether. We give criteria to distinguish different kinds of misalignment, to estimate their quantitative relevance and to include them in the data analysis. The experimental data is obtained in a, to our knowledge, novel dual-trap optical-tweezers setup that directly measures forces. In the case in which misalignment is negligible, we provide a method to measure the stiffness of traps and tether based on variance analysis. This method can be seen as a calibration technique valid beyond the linear trap region. Our analysis is then employed to measure the persistence length of dsDNA tethers of three different lengths spanning two orders of magnitude. The effective persistence length of such tethers is shown to decrease with the contour length, in accordance with previous studies.

Acute renal failure after isolated CABG surgery: six years of experience.

BACKGROUND: A prospective observational study was carried out in a Cardiosurgical Intensive Care Unit (ICU) in order to evaluate the incidence of Acute Renal Failure (ARF) after coronary artery bypass graft surgery and identify its predictors. The effects of ARF on outcome were also investigated. METHODS: The study enrolled 3,013 consecutive patients undergoing coronary artery bypass graft surgery. Baseline variables including age, sex, preoperative renal failure, left-ventricular dysfunction, emergency surgery, neurological adverse events, patient history of chronic obstructive pulmonary disease and diabetes mellitus were collected. Intraoperative variables were: type of surgery (on- or off-pump), intra-aortic balloon pump placement, and cardiopulmonary bypass duration. The measured postoperative variables were: low cardiac output syndrome, hemorrhage, transfusion of blood products, and surgical revision. RESULTS: Preoperative renal dysfunction (creatinine >1.4 mg/dL), blood transfusion, low-output syndrome, emergency surgery, low ejection fraction and age were independently associated with ARF. The median (interquartile range) ICU stay was 5.5 (range 4-11.5) days in patients who did and 1 (range 1-2) day in those who did not develop ARF (P<0.001). The median (interquartile range) hospital length of stay was 10 (range 8-21) days in patients who did and 5 (range 4-7) days in those who did not develop ARF (P<0.001). CONCLUSION: Preoperative renal dysfunction, blood transfusion, low-output syndrome, emergency surgery, low ejection fraction and age were independently associated with ARF. Length of ICU and hospital stay were reduced in patients not developing ARF.

Cardiac protection by volatile anaesthetics: a multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

BACKGROUND AND OBJECTIVES: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. METHODS: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate-based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. RESULTS: There was a significant (P < 0.001) difference in the postoperative median (25th-75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3-9,5) ng dL(-1) when compared to patients receiving desflurane 2,5 (1,1-5,3) ng dL(-1). The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5-104.8) vs. 36.3 (17.9-86.6) h ng dL(-1) (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q-wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Multivessel off-pump coronary artery bypass grafting in a nonagenarian: anesthesiologic management.

A 90-year-old male admitted with history of angina (three-vessel disease) on medical therapy for hypertension and chronic renal failure was scheduled for elective coronary artery bypass grafting (CABG). After standard premedication and monitoring anesthesia was induced with propofol and maintained with isoflurane. Middle dose opioids and atracurium were also given. Multivessel revascularization was done through median sternotomy and anastomoses were performed with the aid of coronary stabilization and shunting. Cerebral and renal perfusion were maintained with high arterial pressure (140/70 mmHg) and continuous infusion of fenoldopam (0.05 microg kg(1) m(-1)). The perioperative period was uneventful. Elderly patients are at increased risk for mortality and morbidity after CABG. The procedure can be performed safely on elderly patients without using cardiopulmonary bypass and preventing cerebral and renal ipoperfusion.

Low perioperative mortality for cardiac surgery in octogenarians.

AIM: The number of cardiac operations in octogenarians is steadily increasing. A review of personal 4 years' experience is made in order to identify which variables are associated to a poor prognosis in this high risk population. METHODS: Perioperative variables and short-term outcome of 109 consecutive octogenarians were prospectively collected in a database. Data were analysed with descriptive statistics. Univariate and multivariate analyses were performed to identify preoperative risk factors for prolonged mechanical ventilation and ICU stay. RESULTS: The 109 octogenarians represented 1.8% of the 4 940 cardiac operations performed at our University Teaching Hospital in the period January 1998-June 2001: 94 patients had comorbidities (86%); 46 underwent valve surgery (42%), 38 had coronary artery bypass grafting surgery (36%), and combined procedures or aortic arch replacement were performed in 25 patients (22%). Two patients died (1.8%). Postoperative complications included: myocardial infarction (10 patients, 9%), stroke (6 patients, 5%), renal replacement therapy (1 patient, 1%). Sixty nine patients (63%) had an uneventful perioperative period (63%). On a multivariate analysis, cardiopulmonary bypass (CPB) time was associated with prolonged intubation and ICU stay; mitral pathology predicted prolonged intubation while previous cardiac surgery was associated with prolonged ICU stay. CONCLUSION: The 109 octogenarians studied had an excellent course in the immediate postoperative period. Therefore, on the basis of personal experience cardiac surgery could be safely performed in octogenarians.

Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from patients with sarcoidosis.

BACKGROUND: Mediators released by alveolar macrophages, as well as by T cells, play an important part in modulating local immune processes in sarcoidosis. Among alveolar macrophage secretory products, arachidonic acid metabolites are known to regulate inflammatory and immune reactions. It has been suggested that cyclo-oxygenase and lipoxygenase pathway metabolites of arachidonic acid modulate the evolution of the granulomatous inflammatory response in the lung differently. METHODS: Alveolar macrophages recovered from the bronchoalveolar lavage (BAL) fluid of 32 patients with sarcoidosis in different states of disease activity and 10 normal subjects were evaluated for their ability to release prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Alveolar macrophages were cultured in the presence or absence of opsonised zymosan (500 micrograms/ml), and PGE2 and LTB4 levels in the culture supernatants were determined by enzyme immunoassay (EIA). RESULTS: Stimulated alveolar macrophages from patients with active sarcoidosis released higher LTB4 levels than those from normal subjects, but no differences in PGE2 release were observed between the two groups. The time course of LTB4 release by activated alveolar macrophages showed that normal cells produced similar levels of the hydroxyacid during the early and late times of culture while LTB4 release by activated cells from patients with sarcoidosis increased markedly after 60 minutes of culture, remaining elevated until 24 hours. Indomethacin (3 x 10(6) M) caused the expected inhibition of PGE2 formation without affecting LTB4 release. CONCLUSIONS: These results suggest that alveolar macrophages from the BAL fluid of patients with active sarcoidosis are primed to release LTB4, which may contribute to the locally heightened immune response.

Aluminium-related osteodystrophy and desferrioxamine treatment: role of phosphorus.

We investigated (1) the prevalence of aluminium overload among 96 patients with symptomatic bone disease haemodialysed from 1987 to 1989 in the Sao Paulo area, Brazil; (2) the effect of 6 months desferrioxamine (DFO) treatment (1-2g/week). All patients underwent a first bone biopsy. Aluminium overload (extent of stainable bone aluminium more than 20% trabecular surface) was observed in 74 of 96 patients. Forty overloaded patients were divided into patients with high bone formation rate (BFR) (group 1; n = 17) and patients with low BFR (group 2; n = 23), and had a second biopsy after DFO therapy. In both groups aluminium surface was reduced after treatment (P < 0.001), osteoblast surface (P < 0.02-P < 0.01) and plasma parathyroid hormone (iPTH) (P < 0.01) increased. In group 1 BFR remained high. In group 2 BFR remained low in 16 patients (2a) and increased in seven (P < 0.02) (2b). In group 2a plasma phosphorus was below that in group 2b patients, before (P < 0.03) and after (P < 0.01) DFO. The histological features of group 2a patients resembled hypophosphataemic osteomalacia, those of group 2b patients aluminium osteodystrophy. These data show a high prevalence of aluminium overload in Brazilian patients. Low-dose DFO therapy was safe, decreased bone pain, prevented fractures, and reduced stainable bone aluminium. Bone lesions only partially improved, suggesting that low phosphorus intake and/or plasma calcitriol concentrations may have prevented improvement of bone formation and mineralization.

Effect of SCH 37224 on anti-IgE-induced formation of sulfidopeptide leukotrienes in human lung parenchyma.

SCH 37224, 1-(1,2-dihydro-4-hydroxy-2-oxo-1-phenyl-1,8-naphthyridin-3-yl) pyrrolidinium, is a structurally novel compound that had been shown to inhibit leukotriene D4 formation in guinea pig lung in vitro. We tested whether SCH 37224 is able to inhibit both the formation of eicosanoids from human lung parenchyma in vitro and the binding of sulfidopeptide leukotrienes to membranes of lung parenchyma and bronchi. SCH 37224, at a concentration of 30 and 100 microM, was able to inhibit antigen-induced formation of sulfidopeptide leukotrienes, measured as leukotriene E4, while it did not significantly affect the formation of prostaglandin D2. At concentrations up to 100 microM, it did not affect either the binding of [3H]leukotriene C4 to membranes of human lung parenchyma or human bronchi, or the binding of [3H]leukotriene D4 to the parenchyma. In conclusion, SCH 37224 is a selective inhibitor of leukotriene formation in human lung in vitro, which might be of potential therapeutic interest in the treatment of asthma.

Eicosanoid release and mepyramine, LTC4 and LTD4 binding in passively sensitized human lung parenchyma in vitro.

In vitro passive sensitization of human lung parenchyma with hyper-immune serum did not affect the release of prostaglandin D2 (PGD2) or leukotriene (LT)-like activity upon challenge with anti-IgE antibody with respect to control lung, despite a marked difference in IgE levels between control (C) and sensitized (S) tissue. Binding studies with [3H]LTC4, [3H]LTD4 and [3H]mepyramine (a histamine H1 antagonist) showed a statistically significant increase in the amount bound in sensitized vs control lung for [3H]mepyramine only. Contractile response to 5 x 10(-5) M histamine (H) in C and S lung parenchymal strips did not correlate with binding data. It is concluded that in vitro elevated IgE levels do not affect the interaction of sulfidopeptide leukotrienes with their putative receptors. As for the observed increase in [3H]mepyramine binding, this might not represent a true increase in histamine receptors on lung smooth muscle cells.