Gene therapy in a murine model of methylmalonic acidemia using rAAV9-mediated gene delivery.

Methylmalonic acidemia (MMA), an inherited metabolic disorder caused by deficient activity of methylmalonyl-CoA mutase, carries a poor prognosis for long-term survival. While administration of a recombinant adeno-associated virus serotype 8 vector (rAAV8) can rescue Mut(-/-) mice from neonatal lethality and provide sustained phenotypic correction, translation of gene therapy to human subjects will likely require multiple rounds of systemic administration and, ideally, the use of a vector that transduces the kidney. To examine the effectiveness of alternative rAAVs in the treatment of MMA, a serotype 9 rAAV expressing the Mut cDNA was constructed and delivered to newborn Mut(-/-) mice (n=11). rAAV9 gene therapy directed hepatic transgene expression within 24 h and effectively rescued the Mut(-/-) mice from lethality, conferred long-term survival, markedly improved metabolism and resulted in striking preservation of renal function and histology. Systemic readministration of the vector at a dose similar to that used in human clinical trials (2.5 × 10(9) GC of rAAV9 per gram) to older, treated Mut(-/-) mice (n=5) lowered circulating metabolites, increased in vivo propionate oxidative capacity and produced transgene expression in the kidney and liver. Our data support the use of an rAAV9 vector in the acute and chronic treatment of MMA, and highlight the renal tropism afforded by this novel serotype.

[Imaging of the pulmonary arteries: when, how and when?]. / Quand, comment et pourquoi réaliser une imagerie des artères pulmonaires?

For several years, catheter angiography was the standard imaging technique used for evaluating the pulmonary arteries. Technical advances with computed tomography have had a significant impact on chest imaging, especially the increasing availability of multidetector row CT units. CT pulmonary angiography (CTPA) is now the first line imaging technique to evaluate pulmonary arterial diseases, including pulmonary embolus. Pulmonary angiography is now essentially limited to the endovascular management of pulmonary arteriovenous malformations, pulmonary arteriovenous fistulas or pulmonary arterial aneurysms. Gadolinium enhanced MR angiography of the pulmonary arteries may be helpful in patients with contraindications to the use of iodinated contrast material.

Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollens.

BACKGROUND: Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated. AIMS: To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT). METHODS: Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season. Sinus CT-scans were carried out just before a NPT and 24 h later. Nasal lavage was carried out just before a NPT, 30 min after a positive challenge and again 24 h later. Leucotriene C4/D4, intracellular adhesion molecule-1 and eosinophil cationic protein were measured in nasal secretions. RESULTS: Thirteen patients (65%) showed an alteration in their CT-scans after allergen challenge. Ten of them showed sinus changes controlateral to their allergenic provocation. Radiological changes mainly affected the osteomeatal complex and the ethmoid sinuses. Pre-existing abnormalities (13 of 20 cases) mainly concerned the maxillary sinuses. There was no correlation between CT-scan abnormalities and levels of mediators released in nasal secretions. CONCLUSIONS: We have shown that nasal allergen challenge can produce radiological changes in the paranasal sinuses. This mainly concerned the ethmoid sinuses.

[Value of thoracic CT in the management of severe hemoptysis]. / Hémoptysies sévères: apport de la tomodensitométrie thoracique.

PURPOSE: To assess the value of thoracic CT in the management of patients with severe hemoptysis. PATIENTS AND METHODS: Between January 1997 and January 2001, 62 patients were investigated for severe hemoptysis (>300 ml/24H). The protocol, performed before angiography and embolization, included bronchial fiberoptic examination (BFE) followed by thoracic spiral CT-angiography. Data recorded at CT and BFE were the presence and location of bleeding, the etiology of hemoptysis and the therapeutic modality. RESULTS: Nine patients with life-threatening hemoptysis directly underwent bronchial embolization. CT was available in the 53 remaining patients. No abnormality was found in 4 patients. CT assessed the presence (n=49) and the location (n=38) of the bleeding. The etiology was determined in 49 patients. BFE was feasible in 38/53 patients. BFE assessed the presence (n=38) and location (n=15) of the bleeding. The etiology was determined in 12 cases of bronchial tumour. The available findings of CT and BFE for the presence and the location of the bleeding were concordant. Comparing fiberoptic examination and thoracic CT, the percentages of localized bleedings (39% and 72%) and demonstrated etiologies (32% and 92%), were significantly different (p<0,005 and p<0.0001 respectively). CONCLUSION: Although retrospective and limited by the small number of cases, our study provides arguments to perform thoracic CT before bronchial fiberoptic examination for the management of severe hemoptysis.

Reversible amiodarone-induced lung disease: HRCT findings.

The aim of this study was to describe thoracic high-resolution computed tomography (HRCT) findings of reversible amiodarone-induced lung disease (AILD). The thoracic HRCT of 20 symptomatic patients who were considered as having reversible AILD by the medical staff of our institution were retrospectively reviewed. The patient-selection criteria used were the development of new respiratory symptoms while receiving amiodarone, the exclusion of other respiratory and cardiac diseases, and the decrease of both respiratory symptoms and radiological abnormalities after cessation of amiodarone and corticotherapy. The CT data recorded were those usually sought infiltrative lung diseases. The radiological findings using chest film (n=20) and HRCT (n=4) follow-up was noted. All patients had ground-glass opacities, associated with consolidations (n=4), thin intralobular reticulations (n=5), or both (n=11), with a subpleural (n=18) or central (n=2) location. Eight patients had high-density areas and 13 had pleural thickening (n=13). Bronchial abnormalities included dilation (n=16) and wall thickening (n=19). After therapeutic management, the radiological follow-up showed complete (n=17) or incomplete (n=3) improvement. Ground-glass opacities associated with thin intralobular reticulations and/or subpleural consolidations and bronchial abnormalities are common HRCT findings in reversible AILD.

Changes in wall mechanics after endovascular stenting in the rabbit aorta: comparison of three stent designs.

OBJECTIVE: The aim of this study was to evaluate changes in the wall mechanics of small-diameter arteries after endovascular placement of three different stents. SUBJECTS AND METHODS: Five self-expandable stents (Wallstent), five balloon-expandable noncovered Palmaz stents, and three balloon-expandable covered stents (Jostent) were placed in the infrarenal aorta of 13 New Zealand white rabbits. Systolic blood pressure changes, blood-flow velocity, systolic diameter, and diameter changes were measured and used to calculate the diameter compliance, the distensibility coefficient, and the pulsatility index. RESULTS: Compliance (10(-3) mm kPa(-1)) was 75.3 +/- 20.1 before stenting and reached 94.7 +/- 42.2 upstream, 38.8 +/- 14.2 at the stent level (p < 0.05), and 70.8 +/- 23.2 downstream from the stent. Distensibility (10(-3) kPa(-1)) was 24.3 +/- 6.3 before stenting and reached 27.8 +/- 10.3 upstream, 10.5 +/- 4.4 at the stent level (p < 0.001), and 21.9 +/- 8.6 downstream from the stent. Compliance and distensibility were significantly lower at the stent level than upstream and downstream (p < 0.05). Aortic diameter increased significantly at the stent level from 3.11 +/- 0.40 mm before to 3.76 +/- 0.42 mm after stenting. No significant difference was found among the three stent designs for all the studied data. CONCLUSION: Regardless of the three tested stent designs, endovascular stenting produces a significant decrease in arterial wall compliance of the rabbit aorta.

[Dysfunctioning of central venous catheters: role of the radiologist]. / Dysfonctionnement des cathéters veineux centraux: rôle du radiologue.

Malfunctioning long-term central vein catheters are related to malposition, obstruction, mechanical problems and occlusion of the catheters. The diagnosis and the management of these disorders are based upon chest film examination, catheter or venous enhancement with contrast media. Vascular interventional radiology plays a major role in low invasive management of malfunctioning central vein catheters in hemodialysed patients: transfemoral malpositioned catheter manipulations, fibrin sleeve stripping, infusion of urokinase.

Acute changes in aortic wall mechanical properties after stent placement in rabbits.

PURPOSE: To evaluate mechanical property changes after endovascular stent placement in small-diameter arteries. MATERIALS AND METHODS: Self-expanding stents (Wallstent) were placed in the infrarenal aorta of five New Zealand White rabbits via a surgical right femoral approach. Blood pressure changes (deltaP) were monitored in the aorta. Blood flow velocity was measured with a 20-MHz, pulsed Doppler probe (n = 4) to calculate the pulsatility index. Aortic diameter (dA) and diameter changes (delta(d)) were measured with a 20-MHz probe in echo-tracking mode. Diameter compliance (Cd) and distensibility coefficient (DC) were calculated as Cd = 2(delta)d/(delta)P and DC = 2delta(d)/delta(P)/dA. RESULTS: Aortic diameter increased from 3.360 +/- 0.4033 mm to 4.020 +/- 0.3033 mm after stent placement at the stent level only. Compliance decreased from 77.644 +/- 24.306 mm kPa(-1) to 31.150 +/-8.245 x 10(-3) mm kPa(-1) at the stent level, and was then significantly lower than upstream (98.500 +/- 53.196 mm kPa(-1)) and down-stream (59.047 +/- 13.833 mm kPa(-1)). There was no significant change in pulsatility index. CONCLUSIONS: Endovascular stent placement produces a significant decrease in arterial wall compliance of the rabbit abdominal aorta.

[Thoracic ultrasound]. / L'¿echographie thoracique.

Ultrasound exploration of the thorax is a very useful imaging method in children. For adults, it is useful for pleural effusion, study of the diaphragm and to guide percutaneous puncture of targeted pleuro-parietal, mediastinal or peripheral parenchymal sites. Thoracic ultrasound remains underused, particularly as a bedside exploration technique or in emergency or intensive care situations.

[Interventional radiology of the thorax]. / Radiologie interventionnelle du thorax.

Interventional radiology of the thorax includes a wide variety of diagnostic and/or therapeutic procedures. Transthoracic needle biopsy is a widely used technique. Generall, computed tomography is used to guide the puncture, less commonly fluoroscopy or in exceptional cases ultrasound. Targets include parenchymatous, pleural and mediastinal lesions. The biopsy specimen is used for cytology, histology, bacteriology, mycology and parasitology studies. Needle biopsy is also the first step in more complex procedures: drainage of thoracic collections, inserting harpoons, thoracic sympatholysis, palliative treatment of aspergillomas. Bronchial arteriography with embolization is an effective emergency symptomatic treatment for severe hemoptysis. Endovascular vaso-occlusion procedures can be used for rare arteriovenous pulmonary fistulas. Superior vena cava obstruction can be treated, usually in a palliative procedure, by installing an endovascular endoprosthesis.

[Carney's triad: update and report of one case]. / Triade de Carney.

The Carney's syndrome associates three different tumors on the same subject, a young woman generally: a gastric leiomyosarcoma, a pulmonary chondroma and a non adrenal paraganglioma. The authors report a new case of that unfrequent syndrome of unexplained pathogeny.

[Embolization treatment of a traumatic adrenal hemorrhage]. / Traitement par embolisation d'un traumatisme hémorragique de la surrénale.

We report a case of adrenal hemorrhage in a blunt abdominal trauma after a motor vehicle crash. The patient was treated by a percutaneous embolization without any complication.

Bronchial aneurysms mimicking aortic aneurysms: endovascular treatment in two patients.

Bronchial artery dilatation and aneurysm formation is a potential complication of local inflammation, especially in bronchiectasis. When the bronchial artery has an ectopic origin from the inferior segment of the aortic arch, aneurysms may mimick aortic aneurysms. Despite this particular location, endovascular treatment is possible. We report two such aneurysms that were successfully embolized with steel coils.

[Contribution of high-resolution volume computed tomography (HRVCT) for the exploration of diffuse pulmonary infiltrative disorders]. / Apport de la TDM avec haute résolution volumique (TDM HRV) dans l'exploration des pneumopathies infiltratives diffuses.

AIM: To assess high-resolution volume computed tomography (HRVCT) for the investigation of diffuse pulmonary infiltrative disorders. PATIENTS AND METHODS: Thirty patients with diffuse interstitial disease (idiopathic fibrosis n = 7, silicosis n = 4, asbestosis n = 5, sarcoidosis n = 7, histiocytosis n = 2, lymphangitis carcinomatosa n = 2, tuberculosis n = 1, bronchiolitis obliterans n = 1) were explored using high-resolution computed tomography (HRCT) and HRVCT. All diagnoses were proven by fiberscopy, bronchoalveolar lavage and respiratory function tests and/or lung biopsy. The HRVCT protocol consisted of spiral tomography using 10 mm slices. Data were processed with a Windows Advantage workstation (GE Milwaukee). Two readers compared multiprojection volume reconstruction (MPVR) using maximal intensity projection (MIP) and minimal intensity projection (MINIP) displays with millimetric HRCT slices acquired at the same volume. RESULTS: Micronodules were detected better with HRVCT than with HRCT. MIP mode enabled better distinction between nodules and vessels. MINIP mode enabled better detection of cysts in the pulmonary parenchyma than HRCT. The honeycomb aspect of pulmonary fibrosis was differentiated better than super-infected central-lobar emphysema. MINIP mode enabled detection of ground glass opacities which were not visible on HRCT. Certain anomalies were however detected only on HRCT. HRVCT was very sensitive to movement effects which altered image quality, particularly in the MINIP mode. CONCLUSION: HRVCT is a new and promising approach for investigating diffuse pulmonary infiltrative disorders.

[Lateral view of the thorax: the profile]. / L'incidence latérale du thorax: le profil.

The lateral view of the chest is a complementary incidence performed less frequently nowadays with the great frequency of chest CT. In fact, this lateral radiograph has important potential and can even give some exclusive information. With the 3-dimensional visualization provided by CT, the lateral radiograph of the chest is even easier to understand. Following in the footsteps of our great predecessors (Felson, Heitzman, Proto) we propose the left lateral view and offer our opinion about indications, techniques and results. The left lateral view can be performed with perfect perpendicular orientation or with a slight lateral shift that can be chosen with the right shoulder forwards (shifted right anterior lateral) or the contrary (shifted left anterior lateral). The left lateral view, like the antero-posterior view must be interpreted in a circular-concentric fashion.