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Serge Goldman

Publications and source records attributed to Serge Goldman.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacoscintigraphic evaluation of lipid dry powder budesonide formulations for inhalation.

Lung deposition of new formulations of budesonide, using solid lipid microparticles (SLmP) as a pharmaceutically acceptable filler and carrier for inhalation aerosols, and administered from a dry powder inhaler (Cyclohaler), were compared with that from Pulmicort Turbuhaler. Six healthy volunteers took part in a three-way randomized cross-over study, and inhaled a nominal dose of 400 microg budesonide, labelled with 99mTc, on each study day. Lung deposition was determined by gamma scintigraphy and by a pharmacokinetic method. The percentage of dose (SD) in the whole lung was 49.9 (3.7)% for the lipidic matricial form (M) and 62.8 (4.9)% for the lipidic physical blend formulation (PB). These results corresponded well with the in vitro fine particle assessment. In comparison with data recorded in literature for in vivo deposition obtained with Pulmicort Turbuhaler, it was estimated that lung deposition was 1.5 and 2.0 times higher for the M and PB formulations, respectively. Furthermore, the relative drug availability obtained from the pharmacokinetic evaluation, expressed as the percentage of pulmonary absorption of the comparator product, was 154% and 220% for M and PB, respectively. The results of the present study indicate that pulmonary administration using SLmP gives a prominent and significant increase in budesonide lung deposition.

Absorption↗
PubMed2006

Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome.

BACKGROUND: A major challenge in the management of severely brain-injured patients with altered states of consciousness is to estimate their residual perception of the environment. OBJECTIVE: To investigate the integrity of detection of one's own name in patients in a behaviorally well-documented vegetative state (VS), patients in a minimally conscious state (MCS), and patients with locked-in syndrome. DESIGN: We recorded the auditory evoked potentials to the patient's own name and to 7 other equiprobable first names in 15 brain-damaged patients. RESULTS: A P3 component was observed in response to the patient's name in all patients with locked-in syndrome, in all MCS patients, and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results suggest that partially preserved semantic processing could be observed in noncommunicative brain-damaged patients, notably for the detection of salient stimuli, such as the subject's own name. This function seems delayed in MCS and (if present) in VS patients. More important, a P3 response does not necessarily reflect conscious perception and cannot be used to differentiate VS from MCS patients.

Acoustic Stimulation↗
PubMed2006

Correlation between dynamic susceptibility contrast perfusion MRI and methionine metabolism in brain gliomas: preliminary results.

PURPOSE: To evaluate in brain gliomas the relationship between tumor vascularity measured by MR-based maximum regional cerebral blood volume (rCBV) and tumor amino-acid metabolism based on maximum carbon-11 methionine (MET) uptake on positron emission tomography (PET). MATERIALS AND METHODS: Eighteen patients with histologically proven primary brain gliomas were included in the study. In addition to conventional MR sequences, dynamic MR images, including a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence and a PET study using MET, were acquired. Eleven patients had low-grade gliomas, and seven had high-grade gliomas. rCBV ratios and MET uptake ratios normalized to the contralateral white matter (WM) corresponding values were measured in each tumor. Both maximum rCBV ratios and maximum MET uptake ratios were correlated to histopathology. The maximum rCBV ratios were correlated to the maximum MET uptake ratios. RESULTS: Both the maximum rCBV ratios and maximum MET uptake ratios of high-grade gliomas were significantly higher than those of low-grade gliomas (P<0.05). There was a significant positive correlation between maximum rCBV ratios and maximum MET uptake ratios (Spearman: r=0.89, P<0.00001). CONCLUSION: The maximum rCBV ratio and maximum MET uptake ratio are significantly correlated in gliomas, reflecting a close link between amino acid uptake and vascularity in these tumors.

Adult↗
PubMed2006

Iodine deficiency mitigates growth retardation and osteopenia in selenium-deficient rats.

Selenium deficiency is associated with impaired bone metabolism and osteopenia in rats. However, it is not known how combined selenium and iodine deficiency affects bone metabolism. Therefore, we investigated the effect of selenium and iodine deficiency on bone metabolism in 2nd-generation selenium- and iodine-deficient rats. Selenium-deficient (Se-), iodine-deficient (I-), selenium- and iodine-deficient (Se-/I-), and control rats (Se+/I+), were pair-fed their respective diets until they were 74 d old. Each pair-fed rat was fed a selenium-adequate diet in the same amount as that consumed the day before by its selenium-deficient counterpart, taking food spillage into account. The skeletal phenotype was analyzed by dual energy X-ray absorptiometry, histomorphometry, and bone metabolism markers. Erythrocyte glutathione peroxidase activity (Gpx) and plasma thyroid hormones were measured to assess selenium and iodine status, respectively. In both Se-/I+ and Se-/I- rats, Gpx was reduced by 99% compared with pair-fed Se+/I+ and Se+/I- rats (P < 0.001). Iodine deficiency reduced plasma thyroxine by 64% in the 2 iodine-deficient groups (P < 0.001). Body weight, tail length, plasma insulin-like growth factor, pituitary growth hormone concentration, and femur and tibia bone mineral density were significantly greater in the Se-/I- rats than in the Se-/I+ rats. This study shows that iodine deficiency mitigated growth retardation and osteopenia in 2nd-generation selenium-deficient rats and suggests that adequate selenium status should be ensured before measures are taken to correct iodine deficiency.

Animal Feed↗
PubMed2006

Coexistence of idiopathic rolandic epilepsy and CSWS in two families.

PURPOSE: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike-waves during sleep (CSWS) in first-degree relatives. METHODS: Clinical, EEG, and cerebral imaging data are described. RESULTS: FAMILY 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. FAMILY 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. CONCLUSIONS: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum.

Cerebral Cortex↗
PubMed2006

Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures.

OBJECT: The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. METHODS: Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and L-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning-demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection-the tumor contours were displayed in the microscope's eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. CONCLUSIONS: Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.

Adolescent↗
PubMed2006

Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients.

UNLABELLED: The aim of this study was to assess the feasibility and the potential role of PET/CT with (18)F-FDG-labeled autologous leukocytes in the diagnosis and localization of infectious lesions. METHODS: Twenty-one consecutive patients with suspected or documented infection were prospectively evaluated with whole-body PET/CT 3 h after injection of autologous (18)F-FDG-labeled leukocytes. Two experienced nuclear medicine physicians who were unaware of the clinical end-diagnosis reviewed all PET/CT studies. A visual score (0-3)-according to uptake intensity-was used to assess studies. The results of PET/CT with (18)F-FDG-labeled white blood cell ((18)F-FDG-WBC) assessment were compared with histologic or biologic diagnosis in 15 patients and with clinical end-diagnosis after complete clinical work-up in 6 patients. RESULTS: Nine patients had fever of unknown etiology, 6 patients had documented infection but with unknown extension of the infectious disease, 4 patients had a documented infection with unfavorable evolution, and 2 patients had a documented infection with known extension. The best trade-off between sensitivity and specificity was obtained when a visual score of >or=2 was chosen to identify increased tracer uptake as infection. With this threshold, sensitivity, specificity, and accuracy were each 86% on a patient-per-patient basis and 91%, 85%, and 90% on a lesion-per-lesion basis. In this small group of patients, the absence of areas with increased WBC uptake on WBC PET/CT had a 100% negative predictive value. CONCLUSION: Hybrid (18)F-FDG-WBC PET/CT was found to have a high sensitivity and specificity for the diagnosis of infection. It located infectious lesions with a high precision. In this small series, absence of areas with increased uptake virtually ruled out the presence of infection. (18)F-FDG-WBC PET/CT for infection detection deserves further investigation in a larger prospective series.

Adolescent↗
PubMed2005

Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection.

Granulocyte--colony-stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral-blood CD34+ cells without mobilization in six patients with AMI. After large-volume cytapheresis and positive CD34+ cell selection, 3.6 to 27.6 million CD34+ cells were obtained. We performed intra-coronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial-labeled CD34+ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34+ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18F]-fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment.

Adult↗
PubMed2005

A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients.

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.

Adult↗
PubMed2005

Semi-quantification of methionine uptake and flair signal for the evaluation of chemotherapy in low-grade oligodendroglioma.

UNLABELLED: 11C-Methionine (MET) is a useful positron emission tomography (PET) tracer for the evaluation of low-grade gliomas. Among these tumors, a high percentage of low-grade oligodendrogliomas (ODG) are sensitive to chemotherapy with procarbazine, CCNU, and vincristine (PCV). We aimed at: (1) objectively assessing ODG response to PCV by a metabolic index (the Activity Volume Index or AVI) generated from an automated semi-quantification of PET with MET (PET-MET); (2) comparing AVI and quantitative magnetic resonance imaging (MRI) measurements of response to PCV. METHODS: seven patients with ODG were followed for a period of 19.9+/-6.6 months after the completion of PCV chemotherapy. Regions of interest (ROI) were generated by covering all voxels with count values above a threshold level set at 120% of the mean cerebellar activity. On each slice, ROI volume and mean count values were calculated. AVI was calculated as the sum over all ROI of tumor volumex(tumor mean count/cerebellum count). Tumor volume measurements on MRI, were based on signal abnormalities visually detected on fluid-attenuated inversion recovery (FLAIR) sequences. RESULTS: PCV therapy was associated with a drastic decrease in AVI (mean+/-SD, cm3): AVI post-PCV=0.80+/-1.45 vs. AVI prior PCV=12.94+/-11.46 (P=0.03). Likewise, we observed a decrease in tumor volume estimated from the FLAIR signal (31.37+/-11.99 post-PCV vs. 67.95+/-39.96 prior PCV, P=0.03) although AVI decrease after PCV was significantly more pronounced (P=0.015). CONCLUSION: This study, based on limited number of patients and follow-up period indicates that AVI may be a sensitive and observer-independent method applicable to the assessment of ODG responsiveness to PCV treatment and may offer a major added value to both clinical assessment and MRI evaluation of chemotherapeutic outcomes.

Adult↗
PubMed2005

Effects of right ventricular pacing on regional myocardial glucose metabolism.

AIMS: Permanent right ventricular apical pacing (RVP) is associated with a wide range of myocardial abnormalities. The purpose of this study was to determine the changes over time of RVP on myocardial blood flow (MBF) and glucose metabolism as assessed by positron emission tomography (PET). METHODS: In eight candidates for permanent pacemaker implantation PET imaging was performed with 13N-ammonia and 18F-Fluorodeoxyglucose (FDG) to assess MBF and glucose metabolism before (PET1) and repeated after 3 months of RVP (PET2). For the analysis, the left ventricle was divided into three parts (apex, mid-ventricular and base) and subdivided into six segments (inferior, posterior, lateral, anterior, antero-septal and infero-septal). RESULTS: After RVP, defects of FDG uptake were found in the left ventricle near the stimulation site, without corresponding changes in MBF. Changes over time in the mean FDG uptake were statistically significant between PET1 and PET2 in the apical inferior, apical-posterior, apical-anterior, apical antero-septal, apical infero-septal, mid-inferior and mid-infero-septal segments. CONCLUSIONS: This study shows that RVP induces major changes in the distribution of FDG uptake in the left ventricular myocardium. FDG uptake significantly decreases in the regions surrounding the pacing site.

Aged↗
PubMed2005

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Consciousness↗
PubMed2005

Voxel-based assessment of spinal tap test-induced regional cerebral blood flow changes in normal pressure hydrocephalus.

OBJECTIVE: Normal pressure hydrocephalus (NPH) is a cause of dementia that may be amended by medical intervention. Its diagnosis is therefore of major importance and the establishment of response criteria to cerebrospinal fluid (CSF) shunting is essential. One of these criteria is the clinical response to spinal tap. The accuracy of the spinal tap test could potentially be improved by adding neuroimaging of regional cerebral blood flow (rCBF) changes to the response criteria. Statistical parametric mapping (SPM) is a voxel-based method of image analysis that may be used to statistically assess the significance of rCBF changes. The objective of this study was to evaluate, by SPM, spinal tap test-induced rCBF changes in patients with NPH syndrome. METHODS: Forty patients with NPH syndrome underwent hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) before and after a spinal tap test (1-day split-dose protocol). The differences in rCBF between these pairs of scans were analysed by SPM in the whole group and between subgroups divided according to gait improvement at the spinal tap test. RESULTS: In the whole group of patients, there was no statistical difference between pre- and post-spinal tap SPECT images. SPM analysis of patients grouped as a function of their clinical response to the spinal tap test revealed a significant post-spinal tap rCBF increase in the bilateral dorsolateral frontal and left mesiotemporal cortex in clinically responding compared with non-responding patients. CONCLUSION: According to SPM analysis, gait improvement at the spinal tap test in patients with NPH syndrome is associated with an rCBF increase localized in the bilateral dorsolateral frontal and left mesiotemporal cortex.

Adult↗
PubMed2005

Integration of [11C]methionine-positron emission tomographic and magnetic resonance imaging for image-guided surgical resection of infiltrative low-grade brain tumors in children.

OBJECTIVE: To evaluate the interest of integrating positron emission tomography (PET) images with the radiolabeled tracer [(11)C]methionine (Met) into the image-guided navigation planning of infiltrative low-grade brain tumors (LGBTs) in children. METHODS: Twenty-two children underwent combined Met-PET with magnetic resonance imaging (MRI) scans in the planning of a navigation procedure. These children presented an LGBT (astrocytomas, 10; oligodendrogliomas, 4; ependymomas, 4; gangliogliomas, 4) located close to functional areas. Tumor boundaries were ill-defined on MRI (including T2-weighted and fluid-attenuated inversion-recovery scans) and could not be clearly identified for allowing a complete, or at least a large, image-guided resection. The PET tracer Met was chosen because of its higher sensitivity and specificity than MRI to detect tumor tissue. The level and extension of MET uptake were analyzed to define the PET contour, subsequently projected onto MRI scans to define a final target contour for volumetric resection. The quality of tumor resection was assessed by an early postoperative MRI and Met-PET workup. RESULTS: In 20 of the 22 children with ill-defined LGBTs, PET improved tumor delineation and contributed to define a final target contour different from that obtained with MRI alone. Met-PET guidance allowed a total resection of Met uptake in 17 cases that were considered total tumor resections because the operative margin left in place contained nontumor tissue. CONCLUSION: These data suggested that Met-PET guidance could help to improve the number of total resections and the amount of tumor removed in infiltrative LGBTs in children.

Adolescent↗
PubMed2005

Estimation of total-body skeletal muscle mass in children and adolescents.

PURPOSE: The estimation of total-body skeletal muscle mass (SMM) has been predicted in healthy adults using anthropometric measurements and urine creatinine excretion. SMM measurement is compulsory to evaluate exercise performance and the influence of physical training on muscle mass. However, there is a lack of information on children and adolescents when quantifying appendicular skeletal muscle mass. METHODS: Thirty-nine Caucasian children and adolescents (male and female, 7-16 yr old) and 20 adults (men and women, 20-24 yr old) were tested for total-body SMM using dual-energy x-ray absorptiometry measurement (DEXA), anthropometric measurements (ANTHR), and urine creatinine (UCrn) determination. Skinfold thickness and circumference were measured at mid-arm (CAG), mid-thigh (CTG), and mid-calf (CCG) and the skin-corrected circumferences (cm), together with height (Ht; m), age (yr), and sex (0 for female, 1 for male). The UCrn excretion (g.24 h(-1)) was also determined in all subjects. The ANTHR and UCrn measurements were then compared with DEXA as reference value. RESULTS: The multiple linear regression from anthropometric measurements gave the following equation to evaluate the total-body skeletal muscle mass (SMM) in children and adolescents: SMM (kg) = Ht x [(0.0064 x CAG) + (0.0032 x CTG) + (0.0015 x CCG)(2)] + (2.56 x sex) + (0.136 x age). The prediction of SMM from a 24-h urine collection was obtained with the following equation: SMM (kg) = (10.62 x Crn) + 6.63. The correlation coefficient (r(2)) was 0.966 and 0.710 for the anthropometric and creatinine methods, respectively (P < 0.001). CONCLUSION: Besides DEXA technique, the determination of total-body skeletal muscle mass in children and adolescents can be highly validated with satisfactory confidence by simple anthropometric measurements or 24-h urine creatinine excretion.

Absorptiometry, Photon↗
PubMed2004

Positron emission tomography for the early postsurgical evaluation of pediatric brain tumors.

OBJECT: The object was to study the value of postoperative positron emission tomography (PET) to assess the extension of brain tumor resection. METHODS: Twenty children operated on for total resection of a glial tumor (18 low-grade, 2 anaplastic) presented a signal on postoperative magnetic resonance (MR) images raising the question of a possible tumor residue. PET was performed early ((18)F-Fluoro-deoxyglucose in 1, (11)C-methionine in 16, both in 3) to further characterize the nature of the abnormal MR signal in order to consider second-look surgery. An increased tracer uptake found in 14 children led to reoperation on 11 of them, confirming the tumor histologically. No (11)C-methionine uptake led to a conservative attitude in 6 children in whom MR imaging follow-up showed no tumor progression. CONCLUSIONS: The early postoperative PET, especially with (11)C-methionine, appears to be a valid basis for complementary therapeutic decisions, especially second-look surgery, in glial tumors for which a radical resection is a key factor for prognosis.

Adolescent↗
PubMed2004

Effect of long-term angiotensin II type I receptor antagonism on peripheral and coronary vasomotion.

Angiotensin II, via AT1 receptors plays a key role in endothelial dysfunction and therefore, in atherogenesis. In order to assess whether long-term blockade of these receptors improve peripheral and coronary endothelial function, 13 patients were treated by candesartan cilexetil (AT2B, 16 mg/d in 10 patients and 8 mg in 3). Flow-mediated dilation (FMD, measured with ultra-sound technique) in the brachial artery and cold pressor testing (CPT)-induced changes in myocardial blood flow (MBF, measured with positron emission tomography) were assessed before and after a 6 month treatment period. AT2B did not alter FMD: 5.0 +/- 1.2% vs. 6.4 +/- 0.9% after treatment. MBF increased significantly during CPT before and after AT2B. Although AT2B did not significantly modify heart rate and blood pressure, MBF normalized to the rate pressure product (MBF/RPP x 10000) was significantly higher and this change remained significant during CPT: it increased from 0.94 +/- 0.05 ml/g/min to 1.14 +/- 0.09 ml/g/min after AT2B (P < .05) and did not decrease during CPT (1.12 +/- 0.08 ml/g/min). Moreover, these AT2B-induced changes in normalized MBF were significantly correlated with the changes in FMD (r = 0.66, P < 0.05). Thus, long-term AT2B improves coronary vasomotion. Although no significant alteration in peripheral conduit endothelial function has been observed, treatment-induced FMD changes seem to be a predictor of coronary circulation improvement.

Administration, Oral↗