Exploration and management of adrenal incidentalomas. French Society of Endocrinology Consensus.

The French Society of Endocrinology convened a multidisciplinary panel of endocrinologists, radiologists, nuclear physicians and surgeons to address the appropriate evaluation and treatment of adrenal incidentalomas. The panel conducted a systematic review of medical literature on the following issues: epidemiology, natural history, radiological and scintigraphic evaluation, endocrine assessment, surgical management and appropriate follow-up. The following text reports the recommendations of experts on behalf of the French Society of Endocrinology. The authors emphasize the paucity of published scientific data that hampers evidence-based medicine recommendations. The crucial points of the French consensus are: the usefulness of CT-scanning evaluation of adrenal incidentalomas, the systematic screening for pheochromocytoma, the usefulness of the 1mg overnight dexamethasone test to screen for latent hypercortisolism, the difficulty to interpret mild biological abnormalities of the HPA axis, the consensus to remove surgically most of tumours greater than 4cm, the necessity to follow clinically glucorticoid tissular targets in the follow-up of non operated benign adrenocortical incidentalomas.

Changes in type B natriuretic peptide (BNP) concentrations during cardiac valve replacement.

OBJECTIVE: The aim of our study was to investigate the ability of BNP levels to reveal the immediate post-surgery cardiac function improvement. We measured the perioperative variations in BNP concentrations in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB), chronic mitral regurgitation, valvular aortic stenosis, or myocardial ischaemia. METHODS: Three groups were included: patients with coronary artery bypass graft (CABG, group I, n = 14), aortic (AVR, group II, n = 14) or mitral (MVR, group III, n = 7) valve replacement. BNP assay was performed at the induction of anesthesia, immediately after the CPB, at the arrival in the intensive care unit, 4 h, 8 h and 12 h after the arrival in ICU. RESULTS AND CONCLUSION: The occurring variation in BNP levels after the operation is an increase whatever the corrective surgery, underlying the relative lack of specificity of BNP with regard to the cardiac pathology. Besides iatrogenic cardioplegia one can supposes that cardiac surgery involves other major stimuli such as anesthesia, sternotomia, hemodynamics, post-operative that could influence in a non specific way BNP levels.

Characterisation, cloning and sequencing of a conformation-dependent monoclonal antibody to the alphaIIbbeta3 integrin: interest for use in thrombus detection.

The detection of newly formed thrombi is of primary importance in clinical medicine. The activated platelet is a potential target for the localization of thrombotic lesions in arteries. The integrin alpha(IIb)beta(3) membrane changes conformation upon activation. A novel anti-alpha(IIb)beta(3) monoclonal antibody (MAb), XIIF9, is described which recognizes an epitope whose expression was enhanced by activation. Radioiodinated XIIF9 bound to a single class of sites on the beta(3) subunit, with 13600 +/- 2000 molecules bound per unstimulated platelet and a K(d) of 34.5 nM. Platelets stimulated with 0.5 U/ml of thrombin bound 66000 +/- 4000 molecules/cell (K(d) = 51.6 nM). Moreover, XIIF9 binding to unstimulated platelets could be increased 4-fold by treatment of the alpha(IIb)beta(3) complex with 5 mM EDTA. Thus, XIIF9 recognized an epitope on the beta(3) subunit whose accessibility was increased upon thrombin activation or EDTA treatment. Sequence analysis of the gene segment encoding the XIIF9 heavy chain revealed interesting motifs shared with cyclic CX6-7C anti-alpha(IIb)beta(3) peptides or with AC7, a published MAb specific for activated alpha(IIb)beta(3). In vivo experiments in atherosclerotic rabbits followed by immunohistological analysis, revealed a specific binding of XIIF9 on platelets engaged in thrombus formation, demonstrating real clinical potential for such MAbs in imaging.

Assessment of brain natriuretic peptide in patients with suspected heart failure: comparison with radionuclide ventriculography data.

BACKGROUND: The aim of the study was to prospectively evaluate patients with suspected or known heart disease using plasma brain natriuretic peptide (BNP) measurement and radionuclide ventriculography to examine whether left ventricular dysfunction is associated with an abnormal rise of BNP concentration. METHODS: Patients (n=153) and controls (n=14) underwent radionuclide ventriculography to determine Left ventricular Ejection Fraction (LVEF) and measurement of plasma BNP concentration using a commercial kit. RESULTS: Plasma BNP concentration in controls was significantly lower than that in patients whatever the stage of the disease, significantly lower than that of patients with normal LVEF (LVEF>55%); than that of patients with altered LVEF (LVEF< or =40%); and than that of patients with moderately reduced LVEF (40%

Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas.

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.

Stability of brain natriuretic peptide (BNP) in human whole blood and plasma.

Brain natriuretic peptide is proposed as a biochemical marker which could provide a useful screening test to select patients for further cardiac investigations in heart failure. The applicability of such a biochemical test in clinics, hospital wards, and clinical laboratories is dependent on its ease of use and on the complexity of sample handling. The present study was undertaken to evaluate the stability of brain natriuretic peptide under a number of different handling conditions (sample collection, storage temperatures, freezing temperatures) assayed with a commercially available kit. The results clearly demonstrate that brain natriuretic peptide is stable at room temperature for 24 hours, or in up to 30 degrees C for 12 hours in the presence and absence of aprotinin, on the condition that brain natriuretic peptide is assayed within one month (frozen at -20 degrees C) after blood collection. The presence of aprotinin prevents brain natriuretic peptide degradation in samples preserved for more than 1 month at -20 degrees C before assay.

Pulmonary embolism revealed on helical CT angiography: comparison with ventilation-perfusion radionuclide lung scanning.

OBJECTIVE: We compared helical CT angiography and ventilation-perfusion radionuclide lung scanning as initial tests in the diagnosis of acute pulmonary embolism. SUBJECTS AND METHODS: Two hundred sixteen consecutive patients who were clinically suspected of having acute pulmonary embolism underwent helical CT angiography, ventilation-perfusion radionuclide lung scanning, and Doppler sonography of the veins of the legs. On the basis of concordance of the results for ventilation-perfusion radionuclide lung scanning and helical CT angiography and on the degree of clinical suspicion, certain patients underwent pulmonary angiography. Patients without pulmonary embolism at initial evaluation in whom no treatment was instituted were followed up for at least 3 months to determine the potential recurrence of thromboembolic disease. RESULTS: Of the 216 patients, 37 (17%) were excluded because of insufficient data to assess the initial event. Final diagnosis for the 179 remaining patients was pulmonary embolism in 68 (37.9%) and no pulmonary embolism in 111 (62.0%), based on pulmonary angiography in 23 patients (12.8%) and concordant imaging findings and outcome in the remaining patients. Statistically significant differences (p < 0.05) were found between sensitivity, specificity, positive predictive value, and negative predictive value for helical CT angiography and ventilation-perfusion radionuclide lung scanning (94.1% versus 80.8%; 93.6% versus 73.8%; 95.5% versus 82%; and 96.2% versus 75.9%, respectively). Interobserver agreement was excellent for helical CT angiography (kappa = 0.72) and moderate for ventilation-perfusion radionuclide lung scanning (kappa = 0.22). CONCLUSION: Helical CT angiography could replace ventilation-perfusion radionuclide lung scanning as the initial test for screening patients who are clinically suspected of having pulmonary embolism.

Review of 10 years of the clinical use of brain natriuretic peptide in cardiology.

Ten years ago brain natriuretic peptide (BNP), the second compound of a family of polypeptide hormones named natriuretic peptides was identified. This peptide has great pathophysiologic importance as a stress-induced cardiac hormone secreted from ventricles, and it rises in several cardiac diseases. It promotes natriuresis and diuresis, acts as a vasodilator, and antagonizes the vasoconstrictor effects of the renin-angiotensin-aldosterone system. The measurement of this peptide in blood by immunoassay has shown promise over the past decade in clinical diagnosis and prognosis. Because heart failure is a major health problem worldwide, BNP is proposed as a biochemical marker that might provide a useful screening test to select patients for further cardiac investigations. Such a hormone assay is inexpensive and available. The implications of BNP in diagnosis, prognosis, and therapy will be reviewed.

Evaluation of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients with negative radioiodine scintigraphy.

The follow-up of patients who underwent thyroidectomy for differentiated thyroid carcinoma is based on the combination of serum thyroglobulin (Tg) measurement and radioiodine total-body scan (ITBS). The diagnostic strategy to be used in patients with elevated serum Tg level but negative ITBS remains debatable. Somatostatin receptor scintigraphy (SRS) has been proposed. Our objective was to compare the results of SRS and conventional radiological imaging (CRI) for the diagnosis of recurrent disease and/or metastases in 15 patients who had had thyroidectomy for differentiated carcinoma (14 papillary, 1 Hurthle cell carcinoma) and who displayed elevated Tg levels (10 to 65000 ng/mL) together with negative ITBS performed after 100 mCi. All patients underwent SRS and CRI within 3 months, allowing comparison of the 2 approaches for the identification of thyroid carcinoma metastases. CRI first included a chest x-ray and ultrasonography of the neck. It was followed by computed tomography (CT) scanning and/or magnetic resonance imaging (MRI) of the neck, chest and occasionally abdomen, and 99mTc bone scintigraphy in case of negative results. In 6 patients with Tg levels ranging from 65 to 65000 ng/mL, CRI detected 12 histologically proven metastases among 9 organs. Among these patients, SRS identified only 6 metastases. SRS identified 1 case of mediastinal recurrence that was not detected by CRI. In another patient with a Tg level of 51 ng/mL, a cervical node was identified using both SRS and CRI but proved to be a false-positive (inflammatory cervical node). In the other 8 patients with Tg levels ranging from 10 to 580 ng/mL, SRS and CRI were negative, and the source of Tg secretion remains unknown. The results of SRS did not correlate with serum Tg level. In conclusion, the diagnostic accuracy of SRS in this study was disappointing and clearly lower than that of CRI. Our results do not support the use of SRS as a guide conventional imaging modalities in patients operated on for differentiated thyroid carcinoma who display elevated Tg levels together with negative ITBS.

Optimized radioiodine therapy of Graves' disease: analysis of the delivered dose and of other possible factors affecting outcome.

The best approach to radioiodine dose selection in the treatment of Graves' hyperthyroidism remains highly controversial. The formula to calculate the individual dose of (131)I to be delivered has been used for half a century and takes into account the thyroid mass, the effective half-life and the maximum uptake of (131)I. The objective of the present study was to evaluate the accuracy of this formula by determining the relationship between the administered dose of (131)I calculated to deliver a target dose of 50Gy to the thyroid and the actual exact organ dose. We further analyzed if therapeutic success, defined by euthyroidism following the individually calculated dose, can be predicted by different pretreatment parameters and particularly by organ dose. One hundred patients with a first episode of Graves' disease and who had received optimal thyroid irradiation after precise dosimetry were retrospectively reviewed. The patients were categorized according to their thyroid function (plasma free thyroxine (T(4)) serum concentration) as eu-, hyper- or hypothyroid during and 1 year after treatment. The relationship between the administered dose and organ dose was assessed by simple regression. We compared free T(4), free tri-iodothyronine, thyroid weight, the number of patients with antithyroperoxidase antibodies and TSH receptor autoantibodies, 24h urinary iodine excretion, (131)I uptake, and the exact dose of (131)I delivered to the thyroid as pretreatment variables. Although we found a correlation between administered dose (mCi) and organ dose (Gy) (r=0.3, P=0.003), the mean coefficient of variation for organ dose was 45%. Individualized radioiodine therapy enabled euthyroidism in 26% of patients and failed in 74% of patients (33% had persistent or recurrent hyperthyroidism and 41% permanent hypothyroidism). (131)I uptake was significantly higher in the hyperthyroidism group in comparison with the euthyroid group. However, organ dose and other pretreatment variables did not differ among the three groups. In conclusion, these results confirm the low performance of individual dosimetry using what are established ratios, since the delivered dose to the gland, although correlated to the intended dose, is highly variable. The finding that other usual pretreatment variables are not different between groups, gives little hope for improving the way of calculating the ideal dose of radioiodine. We suggest to those not yet ready to give a standard or an ablative dose for Graves' hyperthyroidism that they abandon this way to calculate the (131)I dose.

Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome.

SRIF receptor scintigraphy (SRS) has been proposed for the localization of ectopic ACTH-secreting tumors responsible for Cushing's syndrome. However, in most cases reported, the tumors were also visible using conventional imaging. Therefore, the usefulness of SRS in localizing truly occult ectopic ACTH-secreting tumors remains unknown. We report the results of SRS in 12 patients with ectopic ACTH syndrome (EAS) and in whom the source of ACTH was occult at presentation despite carefully performed conventional imaging. The diagnosis of EAS was made by identification of an ACTH-secreting tumor during follow-up in 5 patients or given a pituitary-to-peripheral ACTH ratio of 1.9 or less during petrosal sinus sampling combined with CRH injection and a negative pituitary magnetic resonance imaging (MRI). Whole-body planar SRS, using (111)In-pentetreotide, was performed 19 times in the 12 patients during initial workup and/or follow-up. Axial tomography imaging (single-photon emission-computed tomography) was performed in 7 of these. Conventional imaging was performed within a month of SRS, allowing comparison of the two approaches for the localization of the ACTH-secreting tumors. In addition, the response of plasma cortisol, after a single injection of 200 microg octreotide, was studied in 6 patients. Five patients had negative SRS and conventional imaging studies. The source of ACTH secretion remains occult despite 10-55 months of follow-up in four of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was found at laparotomy in one patient, 14 months after presentation. SRS was positive in 4 of 12 patients. It was false-positive in 1 patient with follicular thyroid adenoma. Nineteen months after presentation, SRS identified liver metastasis that was also visible using MRI in one patient, but the primary tumor remains occult. SRS identified a 10-mm pancreatic tumor that became detectable, using computed tomography (CT) scanning 9 months later, in 1 patient; and 2 mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient, whereas no tumor was detectable within the parenchymal lung. SRS had little influence on therapeutic options in these 2 patients, in whom no final diagnosis could be made. Repetition of SRS during the follow-up of patients with previously negative scintiscans was useless. Conventional imaging was positive in 6 of 12 patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph nodes, conventional imaging studies were interpreted as positive only after the results of SRS. One patient had liver metastasis that was also visible using SRS. Thin-section CT scanning visualized ACTH-secreting bronchial tumors and metastatic mediastinal lymph nodes of 10-15 mm in diameter in 3 patients after 14-72 months of follow-up, whereas SRS was negative. There was no evident relationship between the endocrine status (hyper- or eucortisolism) and the results of SRS. The in vivo response of plasma cortisol to octreotide correlated to the results of SRS in 4 of 6 cases. In conclusion, both imaging procedures had a low diagnostic yield in this series. However, the sensitivity of SRS for the detection of bronchial carcinoids was lower than that of thin-section CT scanning. We therefore advocate the use of conventional imaging, including thin-section CT scanning of the chest, analyzed by experienced radiologists, as the first-line investigation in patients with occult EAS. SRS should not be repeated during the follow-up in patients with a previously negative scintigram.

Segmented 5 versus nonsegmented flow quantitation: comparison of portal vein flow measurements.

RATIONALE AND OBJECTIVES: Times of acquisition, mean velocities, mean flows, and their respective standard deviations provided by segmented and nonsegmented flow quantifications (FQ) were compared in the main portal veins of ten healthy adults. METHODS: The segmented FQ performed five phase-encoding lines per segment. The authors successively applied the two electrocardiogram-triggered techniques in the same slice perpendicular to the portal flow direction. Their measurements were compared in particular by means of the statistical analysis proposed by Bland and Altman. RESULTS: The segmented 5 FQ reduced the acquisition time by two compared with the nonsegmented FQ. The mean velocity and mean flow values of the two techniques were not significantly different. The standard deviations were similar. CONCLUSIONS: The segmented 5 FQ showed its major advantage in the portal vein: the acquisition time was reduced without any loss of accuracy or any uncertainty enhancement.

Effect of right ventricular pacing in patients with complete left bundle branch block.

The relation between left ventricular electromechanical delay and the acute hemodynamic effect of right ventricular pacing was studied in heart failure patients with and without complete left bundle branch block. Whereas right ventricular pacing provided a shorter electromechanical delay that correlated with an improvement in left ventricular function in patients with left bundle branch block, the converse was observed in patients without left bundle branch block.

In vitro and in situ intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells lining a polyester fabric.

In order to improve long-term patency of vascular grafts, the promising concept of endothelial cell seeding is actually under investigation. Our laboratory tested a polyester coated with albumin and chitosan which permits a rapid colonization by human umbilical vein endothelial cells (HUVEC) and it seems relevant to test in vitro the expression of adhesive molecules expressed by cells with regard to the inflammatory process. We studied intercellular adhesion molecule-1 (ICAM-1) expression and focused our work on the determination of ICAM-1 sites expressed per adherent cell lining the biomaterial, thus in situ, in comparison to control HUVEC on plastic wells: the results obtained by binding experiments were correlated to flow cytometry analyses and showed that the polyester does not induce a proinflammatory state and that HUVEC covering the structure are able to respond to a stimulus.

An in vitro biocompatibility evaluation of double-J stents.

OBJECTIVES: For several years, studies performed to estimate in vitro biocompatibility of urinary catheters have been carried out using permanent cell lines. However, for a rational design of the testing procedure, the cell culture model should depend on the material application. We assess the biocompatibility of 13 double-J stents using an in vitro model of normal human urothelial cells (HUC). This article aims to mimic in vitro, on HUC monolayers, the close contact existing in vivo between the urothelium and double-J stents and to evaluate the subsequent effect on these cells. METHODS: Fragments of each stent were deposited into the wells containing confluent HUC, with close contact maintained between the material and the cells. The same procedure with either no material or fragments of latex catheter was undertaken to provide the negative and positive controls, respectively. The contact was maintained for 1, 3, and 8 days. At the end of the incubation period, fragments of stent were removed and cell activity tests were performed (neutral red assay, MTT assay, and cell proliferation). RESULTS: One of the silicone stents is significantly deleterious on HUC as determined by three tests after 8 days of contact. For two copolymers, a tendency to increase cell proliferation was noted. Concerning polyurethanes, we observed significant decreases in HUC viability and cell metabolic activity for five stents after 8 days of contact. All seven polyurethane stents significantly inhibited cell proliferation. CONCLUSIONS: The HUC culture model may be of relevance for the screening of materials intended for use as double-J stents.

A validation of a flow quantification by MR phase mapping software.

AIM: We evaluated a Siemens software of flow quantification (FQ) by MR phase mapping, in the framework of a common practical use. METHODS: Experiments with a laminar flow phantom and in vivo pulsatile flow were performed. In particular, FQ in ascending aorta was investigated in healthy volunteers. RESULTS AND CONCLUSION: Flow phantom experiments reveal that the FQ slightly underestimates (8% on the average) actual velocities (mean velocities over a vessel area), and also that velocity uncertainties are related to the encoding velocity value, whatever the measured velocity. Furthermore, using well characterized working criteria, we found low intraobserver variability and negligible interobserver variability in ascending aorta FQs. The role played by the choice of reference area in FQ accuracy is emphasized. When recording several cardiac cycles during the same acquisition, it is shown that the FQ software may provide erroneous results. Several comments for FQ software use in the ascending aorta are added.

[Alteration of myocardial viability and systemic ventricular dysfunction after Senning procedure]. / Altération de la viabilité myocardique et dysfonction ventriculaire systémique après intervention de Senning.

After a Senning procedure for transposition of the great arteries (TGA), systolic dysfunction of the right ventricle (RV) is common. Pre and peroperative chronicale hypoxia may be the cause of this ventricular myocardial alteration. In order to detect abnormalities of myocardial viability and to study their relationship to RV function, the authors studied 41 patients (pts), 11.3 +/- 3 years after a Senning procedure. All patients underwent myocardial scintigraphy of the RV under basal conditions. 1 hour after injection of 1.5 mCi of Thallium 201. The RV ejection fraction (n = 41) and at peak effort (n = 25). Exercise ability and aerobic capacity were assessed by exercise testing (Bruce) with gas exchange measurement and compared with 41 normal matched subjects. The cardiorespiratory response to exercise was altered in the Senning group : duration of effort (10.5 +/- 2 vs 13.2 +/- 2 min; p < 0.0001), peak VO2 (33 +/- 5 vs 44.4 +/- 6 ml/min/kg; p < 0.0001), anaerobic threshold (6 +/- 1 vs 8.4 +/- 1.9 min; p < 0.05) were lower compared to controls. Abnormalities of RV viability were observed in 18/41 pts (44%), moderate in 12 cases and severe in 6 cases. Resting and exercise RVEF were significantly lower in patients with myocardial defects (45 +/- 5 vs 51 +/- 7%; p < 0.0005, and 49 +/- 9 vs 58 +/- 9%; p < 0.05 respectively). In conclusion, after the Senning procedure for TGA, scintigraphic abnormalities of the systemic ventricule are common and associated with an alteration of systolic function at rest and on exercise.

Up-regulation of thrombomodulin is inducible on an endothelialized polyester.

The concept of endothelial cell seeding of vascular prostheses is designed as a method for improving long-term patency substitutes because endothelium is considered as the haemocompatible surface of reference. The assessment of the functionality of cells lining a biomaterial is thus of crucial importance. We have reported encouraging results concerning the ability of a polyester coated with albumin and chitosan (M 11) to be lined by a confluent monolayer of cultured human endothelial cells (EC). The aim of the present work was to study the expression of thrombomodulin (membrane glycoprotein responsible for anticoagulant activity) in EC lying on M.11 by anticoagulant activity and mRNA level with and without stimulation. Results obtained in basal conditions showed that EC on M.11 have a comparable expression of TM mRNA when compared to control (EC on tissue culture plates) despite a lower TM surface activity for EC on the biomaterial. In terms of ratio (stimulated cells to unstimulated ones) the response in activity for EC on M.11 is comparable to that of the control. These results indicate that cells lying on M.11 are able to respond to physiological-like stimuli, despite a tendency for these cells to express a procoagulant phenotype when compared with control EC.