[Intima-media thickness and carotidofemoral plaques for cardiovascular risk stratification]. / Épaisseur intima-média et plaques carotido-fémorales pour stratifier le risque cardiovasculaire.

Cardiovascular (CV) diseases are still one of the most important -killers in developed countries. In the last 40 years, great progresses have been achieved in recognizing and treating these diseases and their underlying risk factors. Risk assessment models using tradi-tional risk factors estimate the probability of a cardiovascular event in most cases and drive preventive treatment. However, these risk assessment models have weaknesses, and it is estimated that about 30 % of cardiovascular events are related to undetected risks. Many surrogate parameters have been investigated and have the potential to better predict CV risk beyond classical risk factors. The aim of this article is to assess the value of measuring the intima-media thickness and the detection of atheroma of the carotid and femoral bifurcation by ultrasound.

Dans les pays industrialisés, les maladies cardiovasculaires (CV) sont toujours une cause majeure de mortalité. Au cours des 40 ­dernières années, d'importants progrès ont permis de mieux ­reconnaître et traiter ces maladies et leurs causes. Les scores utilisant des facteurs de risque permettent d'estimer la probabilité d'un événement CV et de gérer la prévention primaire. Cependant, environ 30 % des événements CV échappent aux modèles de prédiction, raison pour laquelle de nombreux paramètres ont été étudiés afin de mieux identifier le risque au-delà des facteurs de risque CV traditionnels. L'objectif de cet article est de décrire la valeur ajoutée de la mesure de l'épaisseur intima-média (EIM) et du dépistage de plaques des bifurcations carotido-fémorales par échographie.

[Patient with lower extremity artery disease†: news in therapeutic approach]. / Artériopathie oblitérante des membres inférieurs†: nouveautés dans la thérapie médicamenteuse.

Prevalence of lower extremity artery disease (LEAD) is increasing with age, and there is a trend over the last decade towards an increase of LEAD patients. These patients are at increased risk of lower limb adverse event (MALE), but also at very high risk of major cardiovascular events (MACE). The best medical treatment, including medications, enable a reduction of this risk. Nevertheless, some patients will continue to develop MACE. New therapeutic molecules have been developed with randomized controlled trials, and showed a reduction of the -cardiovascular risk among these selected patients.

La prévalence de l'artériopathie oblitérante des membres inférieurs augmente avec l'âge, et, sur la dernière décennie, la tendance est à l'augmentation du nombre de patients atteints. Or ces patients sont à risque de développer des complications vasculaires locales, mais aussi des complications cardiovasculaires dans d'autres ­territoires. La prise en charge optimale, qui comporte un volet ­médicamenteux, permet de réduire le risque cardiovasculaire de ces patients. Chez certains, cependant, il persiste un risque résiduel. De nouvelles classes thérapeutiques ont été développées au travers d'essais cliniques contrôlés, randomisés, en double aveugle et ont permis de mettre en évidence une réduction complémentaire du risque cardiovasculaire chez ces patients.

[Deep vein thrombosis in uncommon localisations]. / Thromboses veineuses profondes de localisation inhabituelle.

Venous thromboembolism (VTE) with its two components, deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common disease with an incidence of 0,75­2,69/1000. Deep vein thrombosis is localized in unusual sites in about 10 %, and rare DVT's have specific symptoms and risk factors. Uncommon DVT's are often related to local factors, inflammation, cancer, hematologic diseases and thrombophilia. Their diagnostic workup is less straightforward than in suspected VTE of lower limbs and PE, and rare DVT's are often unexpected findings of imaging studies. By extrapolating evidence of lower limbs VTE, most rare DVT are treated by anticoagulants, except retinal vein thrombosis. However, evidence for the type and duration of anticoagulation is limited.

La maladie thromboembolique veineuse avec ses deux facettes, la thrombose veineuse profonde et l'embolie pulmonaire (EP), est fréquente (incidence 0,75­2,69 ‰). Environ 10 % des thromboses ont des localisations inhabituelles et sont caractérisées par des symptômes et étiologies spécifiques. Les thromboses rares sont souvent liées à des facteurs locaux, inflammatoires, des néoplasies, des maladies hématologiques ou une thrombophilie. La démarche diagnostique est moins standardisée par rapport à celle pour les thromboses des membres inférieurs et souvent il s'agit de découvertes fortuites d'imagerie. Avec l'exception de la thrombose rétinienne, une anticoagulation thérapeutique est instaurée dans la majorité des cas, en analogie au traitement des autres thromboses, cependant avec un faible niveau d'évidence quant au choix et à la durée de l'anticoagulation.

[The treatment of venous malformations in adult patients: the role of US-guided sclerotherapy]. / Traitement des malformations veineuses chez l'adulte : rôle de la sclérothérapie échoguidée.

Venous malformations are slow flow dysplastic lesions, constituted by a vascular nest without arterial or capillary connections, more or less independent of the normal venous anatomy and circulation. In certain cases a treatment is required for symptom relief or for natural complications management. The percutaneous sclerotherapy under ultrasound guidance is increasingly used as an effective and mini-invasive option, allowing obtaining very good results with minor side effects. Several substances have been used with different efficacy and side effects rate. We review the literature and present some cases.

Les malformations veineuses sont des lésions à flux lent, constituées d'un nid vasculaire sans connexion artérielle ni capillaire, plus ou moins indépendantes du réseau veineux normal. Dans certains cas, un traitement est indiqué pour en diminuer les symptômes ou pour gérer les éventuelles complications naturelles. Le traitement par sclérothérapie percutanée sous guidage échographique se révèle une option efficace et peu invasive, permettant de diminuer le volume et d'obtenir de très bons résultats avec moins d'effets secondaires. Plusieurs substances ont été utilisées, avec différents résultats en termes d'efficacité et d'effets secondaires. Nous présentons une revue de la littérature et quelques exemples.

[Interventional treatment of venous insufficiency]. / Prise en charge interventionnelle de l'insuffisance veineuse superficielle des membres inférieurs.

Interventional treatment of venous insufficiency has been revolutionized by endovascular techniques. Some of these techniques, and particularly thermal ablation (endovenous laser, radiofrequency) are now recommended as first-line therapy in the latest international guidelines. This is because of less post-operative pain, a shorter leave from employment and similar or lower recurrence rate. Endovenous techniques allow safer and more efficient treatment of certain particular conditions : small saphenous vein, ulcers, and recurrent varicose veins. In addition to clinical history and examination, a duplex sonography of deep and superficial veins, performed by an angiologist, is the most important exam in order to determine proper indication and best treatment strategy for each patient.

La prise en charge de l'insuffisance veineuse des membres inférieurs a été révolutionnée par l'avènement des techniques endoveineuses. En particulier, l'ablation thermique par laser endoveineux, ou radiofréquence des troncs saphéniens, a remplacé la chirurgie comme technique de référence dans les dernières guidelines publiées, notamment en raison d'une diminution des douleurs postinterventionnelles et de la durée d'incapacité de travail avec un taux de récidives identique, voire inférieur. Les techniques endoveineuses permettent, en outre, de traiter certaines indications avec un niveau d'efficacité et de sécurité accru : traitement de la petite veine saphène, ulcères et récidives de varices. Afin de déterminer l'indication et la meilleure stratégie de prise en charge, un bilan veineux par écho-Doppler par un angiologue est une étape obligatoire.

[Relevance of contrast ultrasound with microbubbles in vascular medecine]. / Intérêt de l'échographie de contraste aux microbulles en médecine vasculaire.

Application of ultrasound contrast media has become a standard in diagnostic imaging in cardiology and in the characterization of focal lesions in multiple organs, especially of the liver. In the past years there was a growing body of evidence for their usefulness in vascular medicine. The development of contrast media, microbubbles with a stabilizing envelope and filled with gaz, small enough to pass through pulmonary capillaries made real-time imaging of organ perfusion possible. Ultrasound contrast media are rapidly eliminated by exhalation and can safely be administered to patients with renal failure. The objective of this review is to describe the basic principles of ultrasound contrast imaging and to inform about vascular applications of contrast ultrasound.

Les produits de contraste échographiques sont utilisés depuis de nombreuses années en imagerie diagnostique et font partie de l'arsenal de l'investigation cardiologique et des lésions focales de multiples organes, surtout hépatiques. Leur emploi dans le domaine vasculaire est plus récent et permet une meilleure imagerie de la vascularisation que l'écho-Doppler natif. Le développement de microbulles de gaz enrobées d'une enveloppe et franchissant les capillaires pulmonaires a permis de visualiser la perfusion des organes en temps réel. Elles sont rapidement éliminées par exhalation et peuvent être utilisées chez des patients souffrant d'insuffisance rénale sévère. Cette revue a pour objectif d'expliquer les principes fondamentaux de l'ultrason au contraste, et de décrire les principales applications vasculaires de celle-ci (CEUS).

Aberration measurement technique based on an analytical linear model of a through-focus aerial image.

We propose an in situ aberration measurement technique based on an analytical linear model of through-focus aerial images. The aberrations are retrieved from aerial images of six isolated space patterns, which have the same width but different orientations. The imaging formulas of the space patterns are investigated and simplified, and then an analytical linear relationship between the aerial image intensity distributions and the Zernike coefficients is established. The linear relationship is composed of linear fitting matrices and rotation matrices, which can be calculated numerically in advance and utilized to retrieve Zernike coefficients. Numerical simulations using the lithography simulators PROLITH and Dr.LiTHO demonstrate that the proposed method can measure wavefront aberrations up to Z(37). Experiments on a real lithography tool confirm that our method can monitor lens aberration offset with an accuracy of 0.7 nm.

Advances in lithography: introduction to the feature.

Optical projection lithography has been the key technology for the ongoing miniaturization in semiconductor devices over the past 40 years. This issue features original research covering mask and image modeling methods and computational techniques for various inverse problems in advanced lithography, including source and mask optimization, wavefront retrieval, and design of Fresnel lenses.

Pixel-based defect detection from high-NA optical projection images.

The reconstruction of subwavelength defects from measured images of high-NA-projection systems is demonstrated. A structure consisting of a few small unknown defects in an otherwise known mask layout is studied. The footprint of the defect, which is the measured or simulated difference between images of masks with and without defects, is used to reconstruct the position, shape, and transmission of defects. The requirement is that the few unknown defects are sparsely located in the known mask layout. The technique relies on the cost function and an appropriate optimizer. The dependency of the reconstruction results on defect sizes and types of defects is presented. Moreover, the sensitivity of the technique to noise is investigated.

Advances in lithography: introduction to the feature.

Optical projection lithography has been the key technology for the ongoing miniaturization in semiconductor devices over the past 40 years. This issue features original research covering mask and image modeling methods and computational techniques for various inverse problems in advanced lithography, including source and mask optimization, wavefront retrieval, and design of Fresnel lenses.

Biomarkers of Neutrophil Activation in Patients with Symptomatic Chronic Peripheral Artery Disease Predict Worse Cardiovascular Outcome.

Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO-DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002-1.015; p = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024-1.066; p < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001-1.024; p = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000-1.020; p = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004-1.051; p = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56-0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO-DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ -0.287; p = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17.

PURPOSE: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab. PATIENTS AND METHODS: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years. RESULTS: Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response

Resonant metamaterials for contrast enhancement in optical lithography.

The transmission through ultra-thin metal films is noticeable and thus limits their potential for the formation of lithographic masks. By sub-wavelength patterning of a metal film with a post structure, a resonant metamaterial is formed, which can effectively suppress the transmission. Measurements as well as calculations identify the width of the metal islands as a critical geometrical feature. Hence, the extraordinarily low transmission effect can be explained by the resonant response of single scatterers known as Localized Surface Plasmon Resonances (LSPR). A potential application of this suppressed transmission effect to thin metal masks in optical lithography is experimentally investigated.

Influence of two typical defects on the near-field optical properties of multilayer dielectric compression gratings.

Internal electric-field enhancement is critical for the laser-induced damage properties of multilayer dielectric compression gratings (MDG) in high-energy laser systems. Due to the complex fabrication processes of MDGs, such as coating, interference lithography, etching, and cleaning, different kinds of defects in multilayers or profiles on MDG surfaces can't be practically avoided. Combined with a scanning electron microscope of some MDG samples, line-absence and added node seem to be two typical defects, according to which two defective MDG models are established, and numerical calculations are performed. From simulation results, the defect period and defect depth has little effect on the spectral response of the optical elements. However, they may produce large changes of internal electric-field distribution on the grating surface and even in multilayer structures, thus decreasing the damage threshold of MDG. To obtain a better understanding of the dependence of the internal electric-field enhancement on these defects, this work is focused on the near-field distributions of defective MDGs using the Fourier model method.

Learned sensing: jointly optimized microscope hardware for accurate image classification.

Since its invention, the microscope has been optimized for interpretation by a human observer. With the recent development of deep learning algorithms for automated image analysis, there is now a clear need to re-design the microscope's hardware for specific interpretation tasks. To increase the speed and accuracy of automated image classification, this work presents a method to co-optimize how a sample is illuminated in a microscope, along with a pipeline to automatically classify the resulting image, using a deep neural network. By adding a "physical layer" to a deep classification network, we are able to jointly optimize for specific illumination patterns that highlight the most important sample features for the particular learning task at hand, which may not be obvious under standard illumination. We demonstrate how our learned sensing approach for illumination design can automatically identify malaria-infected cells with up to 5-10% greater accuracy than standard and alternative microscope lighting designs. We show that this joint hardware-software design procedure generalizes to offer accurate diagnoses for two different blood smear types, and experimentally show how our new procedure can translate across different experimental setups while maintaining high accuracy.

Focused use of drug screening in overdose patients increases impact on management.

UNLABELLED: Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. STUDY OBJECTIVES: Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. METHODS: Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. RESULTS: A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. CONCLUSIONS: In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED.

Differential allosteric modulation by amiloride analogues of agonist and antagonist binding at A(1) and A(3) adenosine receptors.

The diuretic drug amiloride and its analogues were found previously to be allosteric modulators of antagonist binding to A(2A) adenosine receptors. In this study, the possibility of the allosteric modulation by amiloride analogues of antagonist binding at A(1) and A(3) receptors, as well as agonist binding at A(1), A(2A), and A(3) receptors, was explored. Amiloride analogues increased the dissociation rates of two antagonist radioligands, [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and [3H]8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one ([3H]PSB-11), from A(1) and A(3) receptors, respectively. Amiloride and 5-(N,N-dimethyl)amiloride (DMA) were more potent at A(1) receptors than at A(3) receptors, while 5-(N,N-hexamethylene)amiloride (HMA) was more potent at A(3) receptors. Thus, amiloride analogues are allosteric inhibitors of antagonist binding at A(1), A(2A), and A(3) adenosine receptor subtypes. In contrast to their effects on antagonist-occupied receptors, amiloride analogues did not affect the dissociation rates of the A(1) agonist [3H]N(6)-[(R)-phenylisopropyl]adenosine ([3H]R-PIA) from A(1) receptors or the A(2A) agonist [3H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine ([3H]CGS21680) from A(2A) receptors. The dissociation rate of the A(3) agonist radioligand [125I]N(6)-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide ([125I]I-AB-MECA) from A(3) receptors was decreased significantly by amiloride analogues. The binding modes of amiloride analogues at agonist-occupied and antagonist-occupied receptors differed markedly, which was demonstrated in all three subtypes of adenosine receptors tested in this study. The effects of the amiloride analogues on the action of the A(3) receptor agonist were explored further using a cyclic AMP functional assay in intact CHO cells expressing the human A(3) receptor. Both binding and functional assays support the allosteric interactions of amiloride analogues with A(3) receptors.

Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive-stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK 15/08).

INTRODUCTION: Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. METHODS: Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. RESULTS: Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. CONCLUSIONS: This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404.

Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 Effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy.

Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BMT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BMT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets.

Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo.

To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A(2A) receptor agonism by CGS21680 (CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) secretion, with nominal effect on interferon gamma (IFN-gamma) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF-alpha secretion occurred via A(2A) receptors, with no involvement of A(1), A(2B), or A(3) receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4(+)Th1 and CD8(+)Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4(+) Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells.