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Biomedical subjects

N Grenier

Publications and source records attributed to N Grenier.

At least 37 records · Page 2Linked to original sources

[Takayasu's disease: interest in methotrexate treatment].

UNLABELLED: Takayasu's disease is a nonspecific aortic arteritis that affects mostly young women and sometimes children. Usual treatment consists of early and prolonged steroids. Some patients do not respond to this treatment, become steroid-dependent or suffer from side effects. We report a case in which methotrexate proved to be effective. CASE REPORT: A 6-year-old girl presented with Takayasu's disease with elevated blood pressure of renovascular origin. Corticosteroids controlled the inflammatory syndrome but not the renal involvement and stopped the growth. Methotrexate (10 mg/m2/week) resulted in the control of the disease, the reduction of steroids and normal growth. CONCLUSION: In Takayasu's disease, steroids should be given as first-line therapy. In case of failure, side effects or steroid dependency, small doses of methotrexate may facilitate the disease's control and weaning from the steroids.

Child↗

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.

Adenoma↗

[Color Doppler sonography of superficial capillary hemangiomas].

PURPOSE: Retrospective analysis of the morphologic and hemodynamic characteristics of hemangiomas in infants provided by color Doppler sonography. MATERIALS AND METHODS: 94 hemangiomas were studied in 87 children separated into four classes of age (0-3 months, 3-6 months, 6-12 months, > 12 months). Eleven were followed with several examinations. Echogenicity, compared to normal subcutaneous tissues, and degree of vascularization were assessed qualitatively. Resistive index (RI) was measured in 78 cases. RESULTS: All lesions presented as vascularized solid masses: 63% were hypoechoic, 16% hyperechoic and 21% mixed. All hypoechoic and mixed lesions showed higher vascularity than hyperechoic ones. Hyperechoic hemanigomas were more frequent in the fourth class of age. Mean resistive index was significantly higher in the first (0.61 +/- 0.14) and the fourth (0.6 +/- 0.14) classes of age than in the second (0.51 +/- 0.12) (p = 0.01 and < 0.03, respectively), and higher in the hyperechoic group (0.7 +/- 0.13) than in the hypoechoic group (0.53 +/- 0.11), (p < 0.01). Seven of 11 cases moved from hypoechoic to hyperechoic or mixed. Increase of resistive index with age was noted in 9/11 cases. CONCLUSIONS: Superficial hemangiomas have typical but variable gray-scale, spectral and color flow sonographic patterns. These fluctuations are probably related to phases of evolution.

Age Factors↗

Thermal therapies in interventional MR imaging. Focused ultrasound.

MR image-guided focused ultrasound (FUS) provides an entirely noninvasive approach for local thermal therapies. MR imaging allows target definition and continuous temperature mapping. Therefore, the heating procedure can be controlled spatially and temporally based on automatic feedback to the FUS apparatus. Phased-array ultrasound technology will further help the development. MR imaging/FUS may be applied not only for tissue ablation, but also for local drug delivery, gene therapy, and drug activation.

Animals↗

Hyperthermia by MR-guided focused ultrasound: accurate temperature control based on fast MRI and a physical model of local energy deposition and heat conduction.

Temperature regulation in MR-guided focused ultrasound requires rapid MR temperature mapping and automatic feedback control of the ultrasound output. Here, a regulation method is proposed based on a physical model of local energy deposition and heat conduction. The real-time evaluation of local temperature gradients from temperature maps is an essential element of the control system. Each time a new image is available, ultrasound power is adjusted on-the-fly in order to obtain the desired evolution of the focal point temperature. In vitro and in vivo performance indicated fast and accurate control of temperature and a large tolerance of errors in initial estimates of ultrasound absorption and heat conduction. When using correct estimates for the physical parameters of the model, focal point temperature was controlled within the measurement noise limit. Initial errors in absorption and diffusion parameters are compensated for exponentially with a user-defined response time, which is suggested to be on the order of 10 sec.

Animals↗

Local hyperthermia with MR-guided focused ultrasound: spiral trajectory of the focal point optimized for temperature uniformity in the target region.

The objective of hyperthermia treatment is to deliver a similar therapeutic thermal dose throughout the target volume within a minimum amount of time. We describe a noninvasive approach to this goal based on magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) with a spherical transducer that can be moved along two directions inside the bed of a clinical MR imager and that has an adjustable focal length in the third dimension. Absorption of FUS gives rise to a highly localized thermal buildup, which then spreads by heat diffusion and blood perfusion. A uniform temperature within a large target volume can be obtained using a double spiral trajectory of the transducer focal point together with constant and maximum FUS power. Differences between the real and target temperatures during the first spiral are evaluated in real time with temperature MRI and corrected for during the second spiral trajectory employing FUS focal point velocity modulation. Once a uniform temperature distribution is reached within the entire volume, FUS heating is applied only at the region's boundaries to maintain the raised temperature levels. Heat conduction, together with the design and timing of the trajectories, therefore ensures a similar thermal dose for the entire target region. Good agreement is obtained between theory and experimental results in vitro on gel phantoms, ex vivo on meat samples, and in vivo on rabbit thigh muscle. Edema in muscle was visible 1 hour after hyperthermia as a spatially uniform rise of the signal intensity in T(2)-weighted images.

Animals↗

Dilatation of the collecting system during pregnancy: physiologic vs obstructive dilatation.

Dilatation of the collecting system is a classical phenomenon during pregnancy, due to hormonal and extrinsic compressive factors. Imaging has to differentiate a physiological dilatation and a pathological obstruction due to urolithiasis. Presently, sonography, using both, B-mode and color Doppler, has the potential to demonstrate the physiological compression of ureters at the level of the pelvic brim. A pathological obstruction is considered either when a stone is detected above the usual site of compression or when the ureter appears dilated beyond. Color Doppler helps in localizing the site of ureteral compression against the vessels and in differentiating ureters from veins. Magnetic resonance urography, with strongly T2-weighted sequences, also may show the site and type of obstruction without contrast agent administration. These two non-radiating techniques make it possible to avoid the use of X-rays in most cases for management of these patients. The type of treatment is based mostly on the level of pain and the presence or absence of stone.

Female↗

Ex vivo expanded mobilized peripheral blood CD34+ cells accelerate haematological recovery in a baboon model of autologous transplantation.

To address the value of ex vivo expanded haematopoietic cells for shortening cytopenia in autologous haematopoietic transplantation, we designed an ex vivo expansion protocol based on a cocktail of early acting cytokines and short-term culture and tested it in a baboon model. Expansion involved enriched CD34+ peripheral blood haematopoietic cells cultured for 6 d with a combination of FLT3-L, stem cell factor (SCF), thrombopoietin (TPO) and interleukin (IL)-3 (50 ng/ml each); CD34+ cells, granulocyte-macrophage colony-forming units (GM-CFU) and megakaryocytic colony-forming units (MK-CFU) were amplified, respectively, 10.5-, 20.5- and 17.9-fold. Baboons were submitted to a myeloablative regimen consisting of cyclophosphamide plus total body irradiation (TBI; 6 Gy) and were then grafted with either 2 x 106/kg unmanipulated CD34+ cells (control group, n = 4) or cells cultured from 2 x 106/kg CD34+ cells (expansion group, n = 4). No cytokines were administered after transplantation. All the animals engrafted. The mean times to white blood cell (WBC), granulocyte and platelet recovery were significantly shorter in the expansion group than in the control group: WBC (> 1 x 109/l) and neutrophil (> 0.5 x 109/l) recovery occurred on days 8 (range 6-9) and 9 (range 6-11), respectively, compared with days 12 (range 10-15) and 14 (range 11-16); platelets recovered (> 20 x 109/l) on day 9 (range 7-12) compared with day 13 (range 11-15) in the control group (P < 0.05). No toxicity was observed after reinfusion. No secondary hypoplasia was observed during more than 12 months of follow-up. Functions of both neutrophils and platelets produced from expanded cells were normal in terms of oxidative metabolism, chemotaxis and the bleeding time. This study shows that in comparison with unmanipulated cells peripheral blood haematopoietic cells expanded from similar doses of CD34+ cells, under the conditions defined here, accelerated both neutrophil and platelet recovery without impairing long-term haematopoiesis.

Animals↗

Nephrotoxic nephritis and obstructive nephropathy: evaluation with MR imaging enhanced with ultrasmall superparamagnetic iron oxide-preliminary findings in a rat model.

PURPOSE: To evaluate the role of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation and differentiation of different types of nephropathies. MATERIALS AND METHODS: Two experimental rat models of nephropathies were studied: a model of nephrotoxic nephritis induced by means of intravenous injection of sheep anti-rat glomerular basement membrane serum (n = 43) and a model of obstructive nephropathy (n = 6). Imaging sessions were performed with a spectrometer operating at 4.7 T with fast low-angle shot, or FLASH, sequences. Signal intensity was measured in each kidney compartment before and 24 hours after intravenous injection of USPIO (90 micromol of iron per kilogram of body weight). MR findings were compared with histologic data and urine protein levels. RESULTS: In the nephrotoxic nephritis model 24 hours after injection of USPIO, a significant signal intensity decrease (P: <.05) was present only in the cortex where the glomerular lesions were located. In the obstructive nephropathy model, the signal intensity decrease (P: <.05) was located in all kidney compartments in response to diffuse interstitial lesions. The decrease in signal intensity was due to iron uptake by either macrophages or mesangial cells gaining endocytic activity and was correlated, in the nephrotoxic nephritis model, to the degree of proteinuria. CONCLUSION: Twenty-four-hour delayed USPIO-enhanced MR imaging may help identify and differentiate various types of nephropathies.

Animals↗

Rapid ELISA D-dimer testing in the exclusion of venous thromboembolism in hospitalized patients.

The clinical diagnosis of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is known to be unreliable. Until now, no biological marker has been found to confirm thrombosis, but help can be gained from a biological marker ruling out the diagnosis of DVT or PE, i.e., the sensitive measurement of D-dimer (DD) species. This article summarizes our experience in introducing a rapid D-dimer test (ELISA VIDAS D-dimères test, bioMérieux) in a collaborative strategy for thrombosis diagnosis during 9 consecutive months involving 1,131 measurements. The efficacy of the DD test was very different according the type of patient, and departments where the DD test provides a real diagnostic benefit were identified. High clinical probability for thrombosis was encountered in 32 patients and radiology was carried out, although D-dimer was negative: none of these patients was found to have a thrombosis after radiologic examination. However, extensive progress must be made in test prescription to reduce the excessive rate of positive D-dimer tests (78%) and positive measurements that are not followed up by radiology (42%).

Biomarkers↗

Doppler frequency shift and time-domain velocity enhancement induced by an ultrasonographic contrast agent.

The aim of this study was to evaluate in rabbit aorta the effect of three bolus doses of Levovist on velocity values measured with spectral Doppler sonography and with time-domain correlation method (color velocity imaging). At each step, a mean peak systolic velocity was calculated from five measurements. These measurements were taken before injection, at 20 s after, at every 30 s till the third minute, and at every minute until return to peak systolic velocity at baseline value. Total duration of enhancement was noted after each injection. After each injection, once the systolic velocity values return to baseline values, a 3 min delay was observed before the following intravenous contrast agent injection was done. With Doppler spectral analysis, after the first injection, peak systolic velocity enhancement was 15 +/- 8.4% (5 to 28%), with a 6.4 +/- 4.3 min duration. After the second injection, peak systolic velocity enhancement was 15.8 +/- 8.4% (5 to 28%) with an 8.8 +/- 4 min duration. After the third injection, it was 14 +/- 9.8% (5 to 34%) with a 13.6 +/- 7.6 min duration (P = 0.04). Peak systolic velocity measured with color velocity imaging remained unchanged after every injection. Doppler velocities were increased by a bolus injection of a contrast agent. Amplitude was not cumulative with the number of injections but was cumulative on its duration. Velocity measurement with time-domain correlation was not influenced by repeated injections.

Animals↗

[Non-linear ultrasound imaging].

The recent introduction of non-linear imaging in ultrasound diagnosis could improve image quality by resolving some problems in technically difficult patients allowing a better conspicuity in identification of subtle lesions. Tissue harmonics are generated while the transmitted pulse propagates through tissue. The formation of image by utilising the harmonic signals implies the suppression of fundamental frequency in the received signal. This is achieved by two major processes filtering and pulse inversion imaging. The non-linear properties of contrast agents reinforce the intensity of harmonic signals which could be detected in precise conditions of acoustic power for a non-destructive or destructive imaging. The introduction of this new imaging modality opens new way in ultrasound imaging with precise protocols of acquisition or sequences and possibly in therapy in the near future.

Contrast Media↗

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.

Animals↗