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Context: Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude. Recent work has established that the effect of hypoxia on pulmonary arterial pressure may depend on iron status, possibly acting through the transcription factor hypoxia-inducible factor, but the pathophysiological and clinical importance of this interaction is unknown.Objective: To determine whether increasing or decreasing iron availability modifies altitude-induced hypoxic pulmonary hypertension.Design, Setting, and Participants: Two randomized, double-blind, placebo-controlled protocols conducted in October-November 2008. In the first protocol, 22 healthy sea-level resident men (aged 19-60 years) were studied over 1 week of hypoxia at Cerro de Pasco, Peru (altitude 4340 m). In the second protocol, 11 high-altitude resident men (aged 30-59 years) diagnosed with chronic mountain sickness were studied over 1 month of hypoxia at Cerro de Pasco, Peru.Intervention: In the first protocol, participants received intravenous infusions of Fe(III)-hydroxide sucrose (200 mg) or placebo on the third day of hypoxia. In the second protocol, patients underwent staged isovolemic venesection of 2 L of blood. Two weeks later, patients received intravenous infusions of Fe(III)-hydroxide sucrose (400 mg) or placebo, which were subsequently crossed over.Main Outcome Measure: Effect of varying iron availability on pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography.Results: In the sea-level resident protocol, approximately 40% of the pulmonary hypertensive response to hypoxia was reversed by infusion of iron, which reduced PASP by 6 mm Hg (95% confidence interval [CI], 4-8 mm Hg), from 37 mm Hg (95% CI, 34-40 mm Hg) to 31 mm Hg (95% CI, 29-33 mm Hg; P = .01). In the chronic mountain sickness protocol, progressive iron deficiency induced by venesection was associated with an approximately 25% increase in PASP of 9 mm Hg (95% CI, 4-14 mm Hg), from 37 mm Hg (95% CI, 30-44 mm Hg) to 46 mm Hg (95% CI, 40-52 mm Hg; P = .003). During the subsequent crossover period, no acute effect of iron replacement on PASP was detected.Conclusion: Hypoxic pulmonary hypertension may be attenuated by iron supplementation and exacerbated by iron depletion.Trial Registration: clinicaltrials.gov Identifier: NCT00952302. [ABSTRACT FROM AUTHOR]

Rationale: Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit. Objectives: Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function. Methods: A two-phase study was performed in patients (hematocrit > or = 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated. Measurements and Main Results: First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O(2) pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance. Conclusions: Acz reduces erythrocytosis and improves pulmonary circulation in Monge's disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether a correlation exists between aortic and renal arterial calcifications detected with spiral CT and significant angiographic renal artery stenosis (RAS).Methods: Forty-two patients (mean age 67 years, range 37-84 years), of whom 24 were hypertensive, prospectively underwent abdominal helical CT and aortic and renal arteriography. The 3-mm thickness CT scans (pitch = 1) were reconstructed each millimeter. A manual outline of the renal artery including its ostial portion was produced. Calcific hyperdensities were defined as areas of density more than 130 HU. CT data were compared with the presence or absence of RAS on angiography (24 cases); hypertension and age were taken into account (Mann-Whitney U-test).Results: CT detection and quantification appeared to be reliable and reproducible. We did not find any correlation between aortic and renal arterial calcifications and RAS, even for the patients above 65 years, with or without hypertension. There was no correlation either between calcifications and hypertension in patients without RAS.Conclusion: In this population, aortic and renal arterial calcifications have no predictive value for RAS. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety of outpatient-based transarterial chemoembolization (TACE) for hepatocellular carcinoma in patients with intermediate (Child-Pugh B) and advanced (Child-Pugh C) liver disease. Materials and Methods: This is a single-center retrospective review of all HCC patients with Child-Pugh B (intermediate) or Child-Pugh C (advanced) cirrhosis who underwent TACE over a 46-month period. Sixty-nine consecutive chemoembolizations in 26 patients with intermediate and advanced liver disease were reviewed. Patients were classified as outpatients if they were discharged on the day of the procedure or as inpatients if they were admitted overnight. A comprehensive database and chart review of post-procedure telephone interviews, clinic visits, and hospital admissions was performed. The end-points of the study were (1) re-admission to the hospital within 48 hours of discharge, or (2) an emergency department visit within 48 hours of discharge. Results: Between July 2009 and October 2011, inpatient TACE treatments were performed in 5 patients with advanced cirrhosis and 9 patients with intermediate disease. Outpatient TACE treatments were performed in 6 patients with intermediate disease. After October 2011, 49 consecutive outpatient TACE treatments were performed in patients with advanced (10) and intermediate (39) cirrhosis. Safety endpoints of an emergency department visit or hospital readmission were identified in a single Child-Pugh B outpatient who returned to the ED within 48 hours for symptoms related to ascites. No patients from either group required readmission. Conclusion: Transarterial chemoembolization can be safely performed in the outpatient setting for patients with intermediate (Child-Pugh B) and advanced (Child-Pugh C) liver disease in an Interventional Radiology practice with close follow-up. [Copyright &y& Elsevier]

For the discovery of treatments against synucleinopathies, it is necessary to unravel and fully understand the mechanism of fibrillation of proteins involved. Among them, α-synuclein (αS) plays a key role in the development of these diseases through its aggregation into oligomers found in Lewy bodies. However, its structural disorder as an intrinsically disordered protein (IDP) makes its characterization by experimental techniques arduously difficult. Atomistic simulations aim to provide insights into this blank canvas and, fortunately, some studies have already suggested promising mechanisms. Still, it is urgent to consider the IDP features in simulations, so recently a lot of force fields designed to deal with IDPs have been developed. In this study, we have carried out a total of 12 μs simulations of an αS core fragment using a popular ff14SB AMBER force field and the ff14IDPSFF variation that includes a grid-based energy correction map (CMAP) method. The predicted chemical shifts from the simulations and those measured from the αS protein in the NMR solution indicate that ff14IDPSFF reproduces the experimental data more accurately. Moreover, structural analysis exhibits opposite trends between secondary structure propensities. The ff14SB force field preserves the α-helices found in the micelle-bound αS structure, which is used as an initial conformation, while ff14IDPSFF stands out with increased structural disorder and the formation of β-sheets, which suggests that the IDP-specific force field can capture more suitable conformations representing the possible intermediate states of the fibrillation process.

An accurate description of the protonation state of amino acids is essential to correctly simulate the conformational space and the mechanisms of action of proteins or other biochemical systems. The pH and the electrochemical environments are decisive factors to define the effective pKa of amino acids and, therefore, the protonation state. However, they are poorly considered in Molecular Dynamics (MD) simulations. To deal with this problem, constant pH Molecular Dynamics (cpHMD) methods have been developed in recent decades, demonstrating a great ability to consider the effective pKa of amino acids within complex structures. Nonetheless, there are very few studies that assess the effect of these approaches in the conformational sampling. In a previous work of our research group, we detected strengths and weaknesses of the discrete cpHMD method implemented in AMBER when simulating capped tripeptides in implicit solvent. Now, we progressed this assessment by including explicit solvation in these peptides. To analyze more in depth the scope of the reported limitations, we also carried out simulations of oligopeptides with distinct positions of the titratable amino acids. Our study showed that the explicit solvation model does not improve the previously noted weaknesses and, furthermore, the separation of the titratable amino acids in oligopeptides can minimize them, thus providing guidelines to improve the conformational sampling in the cpHMD simulations.

Diverse computational methods to support fragment-based drug discovery (FBDD) are available in the literature. Despite their demonstrated efficacy in supporting FBDD campaigns, they exhibit some drawbacks such as protein denaturation or ligand aggregation that have not yet been clearly overcome in the framework of biomolecular simulations. In the present work, we discuss a systematic semi-automatic novel computational procedure, designed to surpass these difficulties. The method, named fragment dissolved Molecular Dynamics (fdMD), utilizes simulation boxes of solvated small fragments, adding a repulsive Lennard-Jones potential term to avoid aggregation, which can be easily used to solvate the targets of interest. This method has the advantage of solvating the target with a low number of ligands, thus preventing the denaturation of the target, while simultaneously generating a database of ligand-solvated boxes that can be used in further studies. A number of scripts are made available to analyze the results and obtain the descriptors proposed as a means to trustfully discard spurious binding sites. To test our method, four test cases of different complexity have been solvated with ligand boxes and four molecular dynamics runs of 200 ns length have been run for each system, which have been extended up to 1 μs when needed. The reported results point out that the selected number of replicas are enough to identify the correct binding sites irrespective of the initial structure, even in the case of proteins having several close binding sites for the same ligand. We also propose a set of descriptors to analyze the results, among which the average MMGBSA and the average KDEEP energies have emerged as the most robust ones.

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis through the suppression of the iron regulatory hormone hepcidin. Hypoxia also suppresses hepcidin through a mechanism that is unknown. We measured iron indices and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high altitude (4340 m above sea level), with and without prior intravenous iron loading. Without prior iron loading, a rapid reduction in plasma hepcidin was observed that was almost complete by the second day at altitude. This occurred before any index of iron availability had changed. Prior iron loading delayed the decrease in hepcidin until after the transferrin saturation, but not the ferritin concentration, had normalized. We conclude that hepcidin suppression by the hypoxia of high altitude is not driven by a reduction in iron stores.

Acute mountain sickness (AMS) is a common and disabling condition that occurs in healthy individuals ascending to high altitude. Based on the ability of iron to influence cellular oxygen sensing pathways, we hypothesized that iron supplementation would protect against AMS. To examine this hypothesis, 24 healthy sea-level residents were randomized to receive either intravenous iron(III)-hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro de Pasco, Peru (4340 m). The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude. No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude. However, the mean increase in AMS score was 65% smaller in the iron group than in the saline group (p<0.05), and the change in AMS score correlated negatively with the change in ferritin (R=-0.43; p<0.05). Hematocrit and arterial oxygen saturation were unaffected by iron. In conclusion, this preliminary randomized, double-blinded, placebo-controlled trial suggests that intravenous iron supplementation may protect against the symptoms of AMS in healthy volunteers.

Background: Chronic mountain sickness (CMS) is characterized by a loss of adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension (PH), which may lead to cardiac failure, develop in patients. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced PH., Methods: Fifteen healthy men living at sea level (SL) were compared to 15 healthy men living at HA and 55 patients with CMS from Cerro de Pasco, Peru (altitude, 4,300 m). Pulmonary pressures and cardiac function were estimated by echocardiography., Results: None of the subjects had overt cardiac failure symptoms. CMS patients exhibited elevated mean pulmonary pressures as assessed by high-tricuspid pressure gradients (CMS patients, 34 +/- 10 mm Hg; HA subjects, 25 +/- 4 mm Hg [p = 0.002]; and SL subjects, 19 +/- 3 mm Hg [p < 0.001]). They also showed right ventricular (RV) dilation (mean end-diastolic RV area: CMS patients, 17 +/- 2 cm(2); HA subjects, 13 +/- 2 cm(2); SL subjects, 12 +/- 2 cm(2); p < 0.001) but did not display impaired systolic ventricular function. However, the RV Tei index was increased in CMS and HA subjects (CMS patients, 0.56 +/- 0.15; HA subjects, 0.52 +/- 0.12; SL subjects, 0.21 +/- 0.12; p < 0.001)., Conclusion: Despite obvious pulmonary arterial hypertension and right heart dilation, CMS patients did not show any symptom or echocardiographic parameter of heart failure., Trial Registration: ClinicalTrials.gov. Identifier: NCT00424970.

Purpose: Both training and chronic hypoxia act on the autonomic nervous system. Because trained Andean high-altitude natives could perform a high-altitude marathon (4220 m above sea level) in 02:27:23 h, we hypothesized that living in chronic hypoxia does not limit the training-induced benefits on the autonomic modulation of the heart., Methods: Trained (N=13) and sedentary (N=11) Andean high-altitude natives performed an active orthostatic test. Eight of the trained subjects repeated the test 6-8 and 20-24 h after the end of a high-altitude marathon. Resting heart rate (HR) and the autonomic modulation of the heart were assessed by time domain and spectral analysis of HR variability (HRV): sympathetic (RR low frequency (LF)) and parasympathetic (RR high frequency (HF)) modulations, and sympathovagal balance (RR-LF:HF ratio)., Results: Trained subjects exhibited a higher total power of HRV and a lower resting HR (+30%, P<0.005) than sedentary subjects secondary to a higher and dominant parasympathetic modulation on sympathetic activity (RR-HF, RR-LF:HF ratio). At 6-8 h after the marathon, total power of HRV decreased (-69%), whereas resting HR increased from basal level (+22%), mainly because of a rise in sympathetic modulation (RR-LF, RR-LF:HF ratio). From 8 to 24 h of recovery, sympathetic modulation fell (RR-LF, RR-LF:HF ratio) and all HRV parameters were restored. Responses to the active standing position did not change between each recording session., Conclusion: Living in chronic hypoxia does not limit the training-induced benefits on the autonomic control of the cardiovascular system in Andean high-altitude natives. The sympathetic predominance on the heart observed 6-8 h after the high-altitude marathon disappeared after 1 d of recovery. Therefore, living at high altitude does not impair the autonomic response to training.

The purpose was to illustrate that single or multirow spiral CT angiography has become the main modality for the examination of the abdominal aorta. Our multidisciplinary group investigates weekly 15 abdominal aortas, with a single slice spiral CT since 1995, and a 4 row detector spiral CT since 1999. CT scans protocols and parameters optimization for the 2 CT systems are described. Indications and results of CT to investigate the various abdominal aortic diseases are illustrated and discussed: aneurisms (pretherapeutic staging, selection of indications of endovascular stent-grafting); obstructive aorto-arteriopathies (pretherapeutic staging, follow up after endovascular revascularization); dissection (diagnosis, pretherapeutic staging, follow up); inflammatory diseases; normal patterns and principal complications after surgery. Situations where multislice CT is superior to single slice CT and compared advantages of MRI are discussed. CT is at the present time the main technique to image abdominal aorta. Multislice CT is especially interesting to explore the whole aorta, poly traumatisms, and to plan and follow up endovascular treatments.

Objective: To compare three methods used to clear the lacrimal canal., Patients and Methods: A total of 32 files (20 for the dacryocysto-rhinostomy by endoscopic way, 5 for the dacryocysto-rhinostomy by external way and 7 cases of percutaneous stenting) were reviewed. For each, costs of performed interventions were reviewed. An average of the total cost per patient was calculated for all three methods and was then correlated to the initial efficiency of the method., Results: Results show that the average cost for stenting is up to 1,366.80 EUR, for the endoscopic way is up to 2 001.53 EUR and for the external way is up to 2,220.46 EUR. ANOVA (Analysis of Variance) gives significant results when comparing stent to endoscopic way (p=0.000007) and to the external way (p =0.02). The analysis of sensitivity concerning the success rate of various treatments shows that the stent was potentially the most cost-effective and that a failure rate of 35.1% is rather acceptable by comparison to the endoscopic method. If the stent is considered as an outpatient intervention, then, a failure rate of 50% is acceptable., Conclusion: If the failure rate stays under 35.1%, the stent may be considered as a short-term cost-effective method.

Fluoroscopic nonsurgical placement of an expandable polyurethane stent is less invasive than surgery for the treatment of epiphora due to obstruction of the nasolacrimal duct. It needs to be performed with the collaboration of an ophthalmologist, using a high resolution digital subtraction imaging unit.

Objectives: Dacryographies and CT dacryographies are usually performed after catheterization of a lacrimal canaliculus. We evaluated the quality of opacification on CT scan after simple instillation of contrast medium, without any catheterization., Patients and Methods: 39 patients (78 nasolacrimal ducts) were examined for lacrimal pathways obstruction by CT scan after instillation of diluted contrast medium. Additional CT scan imaging was performed after catheterization when the first study did not provide adequate opacification., Results: CT dacryography after instillation is a well tolerated technique. In our study, it allowed detection of all pathologic lacrimal ducts; 7 normal lacrimal pathways (after catheterization) were not opacified after instillation (false positives). The sensitivity of the method was 100%, its specificity 84%., Conclusion: CT dacryography after instillation is a physiologic, simple and sensitive method to evaluate lacrimal obstruction. We propose it as a first step, catheterization being used only in the absence of opacification after instillation.

trans-Epsilon-viniferin, the dimer of resveratrol, extracted from Vitis vinifera, has been evaluated for its antioxidant capacity. Its properties have been compared to those of resveratrol and synthetic stilbenic derivatives (4-hydroxystilbene, 4,4'-dihydroxystilbene, 3,5-dihydroxystilbene, and trimethylresveratrol), in regard to their liposolubility using two media with different polarity. The bleaching of beta-carotene by lipoperoxyl (LOO.) radicals in an oil/water (O/W) emulsion and the scavenging of superoxide anions (O(-)(2) in dimethyl sulfoxide (DMSO) using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap were followed using UV-visible and electron paramagnetic resonance, respectively. Epsilon-viniferin exhibits the best antioxidant capacity in the DMSO/O(-)(2) polar system (IC(50) = 0.14 mM) while 4,4'-dihydroxystilbene presents the highest antioxidant capacity in the O/W/LOO. system (inhibition of beta-carotene bleaching, 82%). Partition coefficients and kinetics of partition between 1-octanol and water were measured to discuss the antioxidant efficiency of the compounds in relation with their chemical structure.

The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM. Quinacrine did not modify the dependence of NO release on extracellular L-arginine. Acceleration or deceleration of O2- dismutation, which altered NO release in control cells, did not modify it in quinacrine-treated cells. Quinacrine did not modify NO amperometric signal or reaction with O2- produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg2+ -independent and could not be attributed to an inhibition of phospholipase A2 activity. Quinacrine made NO release insensitive to Cu2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O2- production.

1. Dichlorofluorescein oxidation and electrochemical monitoring of in situ nitric oxide (NO) release from cultured human endothelial cells reveals that agonists such as thrombin and histamine simultaneously stimulate transient superoxide production. 2. The duration of *NO release was increased only in the simultaneous presence of extracellular L-arginine and exogenous superoxide dismutase. In contrast, the inhibition of membrane reduced nicotinamide adenine dinucleotide (phosphate) oxidases, the major source of *O2- in endothelial cells, did not prolong *NO release, although extracellular L-arginine was also present. Comparison of these two experimental conditions suggested that H2O2 was involved in the extension of the *NO signal. 3. The present study demonstrates that, in the absence of external L-arginine, *O2- production does not constitute the major pathway controlling the duration of agonist-induced *NO signal. These results suggest that L-arginine and H2O2 act jointly to maintain nitric oxide synthase in an activated form.

Purpose: Henoch-Schonlein purpura is a rare eventuality in adulthood. Abdominal involvement can worsen the short-term prognosis and justify medical treatment to avoid surgery., Methods: Abdominopelvic computed tomography (CT) was performed in six adult patients (four men and two women; age range, 19-74 years) with Henoch-Schonlein purpura before any treatment. Abdominal symptoms were concomitant with the purpuric rash in two cases and followed it in the other cases., Results: The small bowel was always involved with a parietal thickening, and the target sign was observed in three patients. The lesions were located in the duodenum in two patients, the jejunum in two and the ileum in five. Two segments were involved in one patient and three segments in another patient. A peritoneal effusion was always present. No colonic lesion was discovered on CT. Once the results were known, all patients received steroids with initially intravenous methylprednisolone in five patients at doses ranging from 80 to 1,000 mg/day. On follow-up, none of the patients underwent surgery., Conclusion: Abdominopelvic CT scan demonstrated signs suggestive of intestinal vasculitis. An underlying neoplasia or an eventual other cause of abdominal pain were explored and a steroid therapy was then began with a good outcome. Abdominal CT can be helpful in the diagnosis of abdominal involvement in Henoch-Schonlein purpura.

Purpose: To compare helical CT-angiography (CTA) and two techniques of MR angiography (MRA) to conventional angiography in aorto-iliac occlusive disease., Materials and Methods: The abdominal aorta and iliac arteries in 22 patients (4 for preoperative assessment of abdominal aortic aneurysm and 18 for peripheral vascular disease) were imaged using four techniques: digital subtraction angiography ("gold standard"), 2D TOF MR angiography, 3D Gd-enhanced MR angiography and helical CT angiography. Source (CTA and 2D TOF MRA) and MIPed images (after subtraction measures before and after gadolinium injection for 3D Gd-MRA) were reviewed., Results: Sensitivity, specificity and accuracy for the detection of significant (>50%) stenosis and occlusion of aorto-iliac arteries were respectively: 38%, 89%, 77% for 2D TOF MRA; 75%, 71%, 72% for 3D Gd-MRA and 95%, 90%, 92% for CTA. Excluding the internal iliac arteries, results were 54%, 96%, 88% for 2D TOF MRA; 96%, 80%, 83% for 3D Gd-MRA and 92%, 93%, 95% for CTA., Conclusion: 3D Gd-MRA, a technique with potential for further improvement, is superior to 2D TOF MRA for detecting significant stenosis and occlusion of aorto-iliac arteries. Results at Gd-MRA are nearly similar to those at CTA (after excluding internal iliac arteries). Results at Gd-MRA are not affected by calcified plaque.

A case of chronic hematic cyst of the orbit which caused unilateral globe displacement with painful diplopia is described in a 72-year-old man. CT scans showed an extraconal soft tissue mass located between the orbital roof and the superior rectus muscle with a bone lysis. Characteristic appearance on MRI (benign signs, subperiosteal localization of the hematoma) has been confirmed by removal surgery. Chronic hematic cyst of the orbit is uncommon and MRI is helpful to establish this diagnostic.

Purpose: Evaluate the MR sensibility for detection and localisation of ACTH-secreting microadenomas of the pituitary gland., Patients: and method. The MRI studies of the pituitary gland, performed before transsphenoidal surgical exploration, about 14 patients who present clinical and biological signs of Cushing disease, were reviewed retrospectively. We have always used unenhanced sagittal and coronal spin-echo T1 sequences, and coronal T1 after injection of gadolinium (1 Tesla)., Results: The global sensibility for detection of an adenoma was 100% (84 to 92% when the lesional localisation was considered). The injection of gadolinium increased the sensibility of 38 to 42% according the readers. 7 to 14% of the lesions were isointense after injection. The estimation of lesional size after injection was the nearer to the surgical results. The indirect sign most frequently seen (35.7 to 64.3%) was focal bulging of the sellar diaphragm. The only differences between the different radiologists, statistically significant, concerned the lesional size before injection and location of the lesion in the sagittal plane., Conclusion: This study confirmed the good sensibility of contrast-enhanced MRI in detection of ACTH-secreting microadenomas. The anatomo-radiological correlations are nevertheless incomplete.

Background: Aneurysms of the duodenopancreatic arcades account for 2 to 3% of all aneurysms of the digestive arteries. Mortality is high due to the risk of rupture and the difficult diagnostic situation., Case Reports: The first case involved a short wide collar aneurysm implanted on the first centimeter of the superior mesenteric artery, associated with tight stenosis of the celiac trunk. The patient complained of diffuse abdominal pain and was treated surgically. In the second case, there was a false aneurysm of the gastroduodenal artery which developed a few months after acute biliary pancreatitis. The aneurysm was treated by exclusion using a transcutaneously delivered endovascular coil prosthesis., Conclusion: These cases illustrate the importance of imaging (magnetic resonance angiography) both for diagnosis and treatment monitoring, allowing early care with very limited morbidity and mortality.

Furchgott et al. demonstrated in 1980 that relaxation of arterial smooth muscle cells in response to acetylcholine is dependent on the integrity of endothelium. They named the factor responsible of this intercellular relationship EDRF (Endothelium Derived Relaxing Factor), which was identified 7 years latter as nitric oxide (NO), a free radical gas. In vessels, NO is generated locally by the endothelial NO synthase and its effect is mainly paracrine (relaxation of the underlying smooth muscle cells, and inhibition of platelet aggregation). The in vivo half-life of NO is short, and the assessment of its production is thus difficult. Invasive and non invasive techniques are now available to explore the variations of arterial diameter or flow. Furchgott's pioneering work anticipated the whole pathophysiology of endothelial-dependent relaxation. Indeed, numerous diseases, in particular atherosclerosis, are accompanied by abnormalities of endothelial-dependent vasodilation ("endothelial dysfunction"). Whereas acetylcholine (or serotonin) infused in a normal artery elicits a vasodilation, in contrast, it promotes a vasoconstriction in an atheromatous artery, as a consequence of a decrease in NO bioavailability. This defect in NO favors arterial spasm, interaction between platelets and arterial wall and thrombosis, and thus probably cardiovascular events. NO cannot be measured directly in humans, except in exhaled NO. In vivo, NO is rapidly oxidized in nitrite (NO2-) and in nitrate (NO3-), the summation being NOx. We shall detail the limitations of this measurement as a biochemical index of NO production from "endothelial" origin.

Purpose: To compare the angulation at the origin of dysplastic renal arteries compared to atherosclerotic renal arteries, in order to improve the technique for percutaneous transluminal angioplasty of FMD., Materials and Methods: Retrospective analysis of 40 aortograms in patients who underwent renal angioplasty for dysplastic stenosis, with comparison with 45 control aortograms (with or without atherosclerotic lesions of the renal arteries). The angle of implantation of the renal arteries was measured relative to the aortic axis in the frontal plane, taking into account only the angulation of its proximal segment. We identified three types of kidneys with regard to their position relative to the renal artery ostium., Results: The angle of implantation of dysplastic renal arteries is significantly sharper compared with the control group (63.8 degrees vs 80.9 degrees, p = 0.0001), irrespective of the side. The angulation did not correlate with the position of the kidney or the direction of the renal artery, suggesting a congenital origin., Conclusion: The angle of implantation of the dysplastic renal arteries relative to the aortic axis in the frontal plane is sharper than the angle measured in non dysplastic renal arteries.

Rationale and Objectives: To evaluate the feasibility of endovascular Doppler recording in renal arteries and to compare the reliability of Doppler parameters for detection of renal artery stenosis., Methods: The authors examined 36 renal arteries in 20 patients with a 0.018" endovascular flow wire. Peak systolic velocity and the renal artery-to-aortic peak were measured in the main renal artery. From intrarenal waveforms, acceleration, acceleration time, and the renal resistive index were obtained. Spectral analysis with consensus scoring of early systolic peak was also performed., Results: Twelve significantly stenosed renal arteries and 26 normal renal arteries were examined with the Doppler guide wire, without complications. Peak systolic velocity was the only parameter significantly different in renal artery stenosis (P = 0.037). Peak systolic velocity also differed significantly between hypertensive and normotensive patients. Tardus parvus was specific for severe renal artery stenosis., Conclusions: Endovascular Doppler is a safe and accurate method for the determination of velocity measurements and may be useful during percutaneous renal artery revascularization.

Gastric diverticula are rare. The retroperitoneal site of subcardial diverticula may be suggestive of a left adrenal mass on CT and MR. The authors report two cases. Radiological demonstration of a communication with the stomach confirms the diagnosis.