Functional reorganization of the auditory pathways following late callosotomy.

Injuries at various levels of the auditory system have been shown to lead to functional reorganization of the auditory pathways. In particular, it has recently been shown that such reorganization can occur in callosal agenesis. The pattern of cortical activity following callosotomy is however still unknown, but behavioral results suggest that it could be significantly different from that observed in callosal agenesis. We aimed to confirm this hypothesis by investigating fMRI responses to complex sounds presented binaurally and monaurally in a callosotomized patient. In the binaural condition, the callosotomized subject showed patterns of auditory cortical activation that were similar to those of neurologically intact individuals. However, in both monaural conditions, the callosotomized individual showed a significant increase of the asymmetries favoring the contralateral pathways. Such patterns of cortical responses are only partially consistent with the results obtained from callosal agenesis subjects using the exact same procedure. Indeed, the latter show differences compared with normals in both binaural and monaural conditions. These findings provide neurological evidence that callosotomy could lead to distinctive functional reorganization of the human auditory pathways.

Functional reorganization of the human auditory pathways following hemispherectomy: an fMRI demonstration.

The present study investigated the functional reorganization of ipsilateral and contralateral auditory pathways in hemispherectomized subjects. Functional reorganization was assessed using functional Magnetic Resonance Imaging (fMRI) and stimulation with complex sounds presented binaurally and monaurally. For neurologically intact control subjects, results showed that binaural stimulations evoked balanced activity in both hemispheres while monaural stimulations induced strong contralateral activity and weak ipsilateral activity. The results obtained from hemispherectomized subjects were substantially different from those obtained from control subjects. Specifically, activity in the intact hemisphere showed a significant decrease in response to contralateral stimulation but, concomitantly, an increase in response to ipsilateral stimulation. The present findings suggest that a substantial functional reorganization takes place in the auditory pathways following an early hemispherectomy. The exact nature of this functional reorganization remains to be specified.

Auditory processing in a patient with a unilateral lesion of the inferior colliculus.

The role of the inferior colliculus (IC) in human auditory processing is still poorly understood. We report here the results obtained with a 12-year-old boy (FX) who suffered a very circumscribed lesion of the right IC without additional neurological damage. The child underwent an extensive battery of psychophysical hearing tests. Results revealed normal peripheral auditory functioning, bilaterally. Furthermore, masking-level differences and frequency-pattern recognition were normal for each ear. When the right ear was stimulated, behavioural tests assessing central auditory processing yielded normal results. However, when the left ear was stimulated, speech recognition in the presence of a competing ipsilateral signal and duration-pattern recognition were impaired. Similarly, performance on two dichotic speech recognition tests was poor when the target stimulus was presented in the left and the competing signal in the right ear. Finally, sound-source localization in space was deficient for speakers located on the side contralateral to the lesion. The pattern of results suggests that auditory functions such as recognition of low-redundancy speech presented monaurally, recognition of tone duration patterns, binaural separation and integration, as well as sound-source localization in space, depend on the integrity of the bilateral auditory pathways at the IC level.

Influence of postangioplasty beta-irradiation on endothelial function in porcine coronary arteries.

BACKGROUND: Postangioplasty (PTCA) intracoronary radiation therapy (ICRT) has been demonstrated to limit restenosis. The consequences of these procedures on coronary reactivity are unknown. METHODS AND RESULTS: Porcine coronary arteries were studied after PTCA immediately (n=5) and 6 weeks (n=5) after ICRT (n=5 and 5, respectively), after combined PTCA+ICRT (n=5 and 7, respectively), and after no intervention (n=11). A 3-cm-long source train of Sr/Y(90) was used in vivo to deliver 16 Gy at a depth of 2 mm from the source center, as used in clinical trials. Arterial rings were mounted on myographs to record isometric tension. After achieving steady-state contraction to depolarizing physiological solution containing 40 mmol/L KCl, measured baseline tension was significantly elevated immediately after all interventions. It returned to normal levels 6 weeks after PTCA and ICRT alone but was significantly reduced if combined. Active contractions induced by 40 mmol/L KCl were maintained after combined therapy both immediately after and at 6 weeks. In these depolarizing conditions, nitric oxide-dependent relaxation to substance P was trivial after PTCA+ICRT and reduced after ICRT, whereas in the presence of physiological solution and N(omega)-nitro-L-arginine, substance P-induced relaxation was reduced after PTCA and abolished after PTCA+ICRT 6 weeks after intervention. In rings without endothelium, the relaxation mediated by sodium nitroprusside (0.1 micromol/L) was reduced immediately after PTCA and at 6 weeks. CONCLUSIONS: PTCA+ICRT altered the passive mechanical properties of porcine coronary arterial wall. Furthermore, at 6 weeks, receptor-operated release of endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor was reduced by ICRT and PTCA alone, respectively, and was prevented by their combination.

Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations--animal and clinical studies in stented and non-stented coronary arteries.

BACKGROUND: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. METHODS: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. RESULTS: Both systems correlated well for areas (r > or = 0.90, p < 0.0001) and diameters (r > or = 0.84. p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: -0.24 and 0.96 mm2, p < 0.055) and diameter (-0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r > or = 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. CONCLUSIONS: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.

Local Delivery of TGF-b Antibodies to Prevent Neointima Formation after Balloon Injury in a Pig Coronary Artery Model.

BACKGROUND: The formation of neointima after vessel injury results from smooth muscle cell proliferation and extracellular matrix secretion. This process is activated by multiple growth factor release. Among these, Transforming Growth Factor-b (TGF-b) has been shown to play an important role. We hypothesized that local delivery of TGF-b antibodies could reduce neointima formation after balloon angioplasty. METHODS AND RESULTS: Using autoperfusion double-balloon catheters (Baxter, Irvine, California), we infused polyclonal TGF-b antibodies in 30 minutes, immediately after oversized balloon angioplasty in pig coronary arteries. Eleven coronary arteries received 100 m anti-TGF-b and thirteen served as controls. Animals were sacrificed 10 weeks later; coronary segments were harvested and processed for histologic quantitative assessment of the neointima. The extent of injury was similar in treated versus control vessels (39% +/- 5% vs. 30% +/- 4%) and there was no difference in intimal thickening (0.63 +/- 0.19 mm for treated vs. 0.52 +/- 0.12 mm for controls). A previously validated restenosis injury index (ratio of neointimal area to total wall area over extent of injury) was also similar in both groups, 1.46 +/- 0.15 for treated versus 1.55 +/- 0.14 for controls. CONCLUSION: Local delivery of a single dose of TGF-b antibodies failed to demonstrate a benefit on neointima formation in a pig coronary artery model.

Swine model of coronary restenosis: effect of a second injury.

Looking for a coronary artery restenosis model closer to human pathology, a protocol of balloon injury/reinjury (plaque of dilatation) in swine coronary artery was designed. Pig coronary arteries (n = 24) were dilated for this study: 12, group 1, once (sacrifice at 10.0 +/- 2.2 weeks); 6, group 2, twice at 2-wk intervals (sacrifice at 5.2 +/- 0.2 wk); 6, group 3, twice at 4-wk intervals (sacrifice at 9.3 +/- 1.9 wk). A single overdilatation resulted in an eccentric neointimal hyperplasia representing half of the wall area (group 1, 45.6 +/- 5.1%). In animals (groups 2 and 3) subjected to redilatation, fracture length, ratio of fracture length to internal elastic lamina (IEL) circumference, and neointimal hyperplasia response were similar to those observed in group 1. In group 3, the shape of the lesion appeared more concentric and the fracture of the IEL more fragmented than in group 1. Although this model of injury/reinjury did not lead to more severe intimal hyperplasia, performing a second angioplasty at the same site did lead to a more concentric intimal response, related to multiple fractures of the IEL.

Coronary restenosis: evaluation of a restenosis injury index in a swine model.

To investigate the mechanisms of restenosis and detect useful interventions to prevent it, reliable quantitative measurements must be evaluated. Coronary arteries of domestic and minipigs (n = 18) were mechanically injured by balloon overstretching and killed at different intervals (2 to 25 weeks) after quantitative angiographic analysis. Morphometric measurements evaluated intimal hyperplasia at 0.59 +/- 0.42 mm without relation to artery size or balloon/artery ratio. Intimal hyperplasia, expressed as the ratio of neointimal area to total wall area (A), is directly related to the injury, assessed by the ratio of internal elastic lamina (IEL) fracture length to IEL circumference (B), r = 0.84, p = 0.002. Restenosis injury index, defined as A/B, provides a useful tool for the quantitative assessment of future angioplasty-related restenosis interventions.

Coronary artery stenting after angioplasty with self-expanding parallel wire metallic stents.

Parallel wire stents were implanted over exchange guide wires at percutaneous transluminal coronary angioplasty sites in 27 canine coronary arteries that were predilated with slightly oversized balloons. Stents were stainless steel, self-expandable, 3.5 to 4.5 mm in diameter, 9 to 12 mm in length, and were made of 10 wires that were longitudinally laser-welded in a zig-zag design. The compressible stent was delivered by the withdrawal of a Teflon outer catheter (4.2 to 4.9F) and the push of a polyethylene inner catheter. Aspirin, 80 mg per day, was given from the day before the study began, and heparin (150 U/kg) was administered during implantation. Quantitative angiography and pathologic examinations were performed at day 0 and at weeks 2, 4, 12, 26 and 52. The coronary angiographic diameter at the stent site immediately after stenting marginally increased from diameter before stenting: 3.22 +/- 0.40 mm versus 3.14 +/- 0.37 mm (p = 0.03), and during a mean of 14 weeks of follow-up, remained unaltered from immediate post-stenting: 3.29 +/- 0.43 mm versus 3.22 +/- 0.40 mm (p = NS) with no stent displacement. Comparisons of patency and thrombosis between heparin-coated and uncoated stents, between left anterior descending and circumflex arteries, and among the three different diameters of stents showed uniformly good results. At microscopy, the wires were oriented perfectly and embedded in the arterial wall, and by 2 weeks they were covered by mucopolysaccharide ground substance, smooth muscle cells, and an almost complete monolayer of neoendothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)