Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

OBJECTIVES/HYPOTHESIS: Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. METHODS: Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. RESULTS: This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. CONCLUSIONS: GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

Usefulness of late enhancement MRI as diagnostic tool to differentiate myocardial infarction from myocarditis

Introduction: Residual pulmonary artery (PA) anomalies are a major concern after surgery for cono-truncal malformations. This study sought to assess residual PA anomalies using MRI/MRA. Methods: 43 MRI/MRA studies were performed in 37 patients after corrective surgery for cono-truncal malformations. MRI/MRA studies comprised spin-echo, cine, velocity-encoded and 3D Gadolinium-enhanced MRA sequences. Residual PA anomalies were searched in ail patients; angiographie data were available in 13 patients and a comparison with MRI/MRA was made. Results: 32/37 patients had postoperative anomalies of the pulmonary arterial tree. Left pulmonary artery stenosis was the most common finding (14/32), followed by stenosis at multiple sites (11/32). Isolated right pulmonary artery stenosis was rare (2/32). The median time interval between MRI/MRA and angiography in the 13 patients undergoing both types of studies was 54 days. The findings between the two examinations were identical regarding stenoses and collateral vessels. In 4 patients, the MRI/MRA study allowed to plan interventional catheterization with balloon dilatation and/or stenting of the obstructed arteries or co il-occlusion of systemic collaterals. Eleven patients had additional surgery based on MRI/MRA findings. Conclusions: Post-operative anomalies of the PA in cono-truncal malformations can reliably be detected with MRI/MRA. This technique allows planning of the intervention al or surgical procedure to correct the residual anomalies and may th us replace or precede catheterization during the follow-up of surgically corrected cono-truncal malformations.

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.

BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Middle and Late Jurassic carbon stable-isotope stratigraphy and radiolarite sedimentation of the Umbria-Marche basin (Central Italy)

A continuous carbon isotope curve from Middle-Upper Jurassic pelagic carbonate rocks was acquired from two sections in the southern part of the Umbria-Marche Apennines in central Italy. At the Colle Bertone section (Terni) and the Terminilletto section (Rieti), the Upper Toarcian to Bajocian Calcari e Marne a Posidonia Formation and the Aalenian to Kimmeridgian Calcari e Marne a Posidonia and Calcari Diasprigni formations were sampled, respectively. Biostratigraphy in both sections is based on rich assemblages of calcareous nannofossils and radiolarians, as well as some ammonites found in the upper Toarcian-Bajocian interval. Both sections revealed a relative minimum of delta(13)C(PDB) close to + 2 parts per thousand in the Aalenian and a maximum around 3.5 parts per thousand in early Bajocian, associated with an increase in visible chert. In basinal sections in Umbria-Marche, this interval includes the very cherry base of the Calcari Diasprigni Formation (e.g. at Valdorbia) or the chert-rich uppermost portion of the Calcari a Posidonia (e.g at Bosso). In the Terminilletto section, the Bajocian-early Barthonian interval shows a gradual decrease in delta(13)C(PDB) values and a low around 2.3 parts per thousand. This part of the section is characterised by more than 40 m of almost chart-free limestones and correlates with a recurrence of limestone-rich facies in basinal sections at Valdorbia. A double peak with values of delta(13)C(PDB) around + 3 parts per thousand was observed in the Callovian and Oxfordian, constrained by well preserved radiolarian faunas. The maxima lie in the Callovian and the middle Oxfordian, and the minimum between the two peaks should be near the Callovian/Oxfordian boundary. In the Terminilletto section, visible chert increases together with delta(13)C(PDB) values from the middle Bathonian and reaches peak values in the Callovian-Oxfordian. In basinal sections in Umbria-Marche, a sharp increase in visible chert is observed at this level within the Calcari Diasprigni. A drop of delta(13)C values towards + 2 parts per thousand occurs in the Kimmeridgian and coincides with a decrease of visible chert in outcrop. The observed delta(13)C positive anomalies during the early Bajocian and the Callovian-Oxfordian may record changes in global climate towards warmer, more humid periods characterised by increased nutrient mobilisation and increased carbon burial. High biosiliceous (radiolarians, siliceous sponges) productivity and preservation appear to coincide with the delta(13)C positive anomalies, when the production of platform carbonates was subdued and ceased in many areas, with a drastic reduction of periplatform ooze input in many Tethyan basins. The carbon and silica cycles appear to be linked through global warming and increased continental weathering. Hydrothermal events related to extensive rifting and/or accelerated oceanic spreading may be the endogenic driving force that created a perturbation of the exogenic system (excess CO2 into the atmosphere and greenhouse conditions) reflected by the positive delta(13)C shifts and biosiliceous episodes.