Histologic Comparison of Vibrating Guidewire with Conventional Guidewire Technique in an Experimental Coronary In Vivo Model

Purpose: To compare the damage caused by vibrating guidewire manipulation and conventional guidewire manipulation of soft coronary wires in normal sheep coronary arteries. Methods: Using an intact sheep model the two methods of passing a coronary guidewire down a normal coronary artery under fluoroscopic screening control were studied. The resulting arterial damage caused by the two techniques was studied histologically. The severity of damage was scored from 1 (no damage) to 4 (severe damage) and expressed as: (a) percentage of damaged sections, (b) mean damage score per section and (c) percentage of sections suffering the most severe degree of damage (scores 3 and 4). Results: One hundred and sixty-eight sections were studied. The percentage of damaged sections was lower in the vibrating guidewire group (p = 0.004). The mean damage score and the percentage of sections with a damage score of 3 or 4 were smaller in the vibrating guidewire group than in the conventional guidewire manipulation group (p = 0.001 and p = 0.009, respectively). Conclusions: Both methods of guidewire manipulation cause identifiable vascular damage. The extent and severity of damage appear greater when the guidewire is manipulated manually.     

Buttoned Device Occlusion of Patent Ductus Arteriosus

Buttoned device, consisting of a square-shaped occluder and a rhomboid-shaped counter-occluder can be implanted across patent ductus arteriosus (PDA) via relatively small sheaths. In a large multi-institutional study, successful device implantation was achieved in 98% of patients. Decrease in the pulmonary-to-systemic flow ratio occurred. Effective occlusion was demonstrated in 88% of patients. PDAs could be occluded irrespective of their shape (conical, tubular, or short), length (short or long), or diameter (small or large). During follow-up for 1 to 60 months, 3% of patients required reintervention to treat residual shunts with (1%) or without (2%) hemolysis. There was gradual reduction and disappearance of the residual shunt during follow-up. Despite these encouraging results, patients with residual shunts are at risk for developing bacterial endocarditis. Therefore, the device was modified by incorporating a folding plug over the button loop, which resulted in complete occlusion of PDA at implantation.     

Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 ± 0.0025 μM (31 ± 1 μg; low dose; n = 7), 0.55 ± 0.02 μM (216 ± 8 μg; high dose; n = 6), and 4.55 ± 0.1 μM (1774 ± 39 μg; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.     

Developmental profiles of infants with an <Emphasis Type="Italic">FMR1</Emphasis> premutation

Background

Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known.

Methods

This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period.

Results

The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development.

Conclusions

These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers.

     

Echocardiographic estimation of balloon-stretched diameter of secundum atrial septal defect for transcatheter occlusion.

Stretched diameter of the atrial septal defect (ASD), determined by balloon sizing at cardiac catheterization, is commonly used to select the sizes of the devices used for transcatheter closure of the secundum ASD. We have previously evaluated the utility of pulmonary/systemic flow ratio and angiographic and echocardiographic (echo) sizes of the ASD in estimating stretched ASD diameter in a group of 16 patients and determined that echo diameter had the best correlation with stretched diameter (r = 0.82; p less than 0.001). The stretched diameter can be estimated: 1.05 x echo diameter in millimeters + 5.49. In this study we have prospectively evaluated this formula in estimating the stretched ASD diameter by two-dimensional echo measurements obtained in two (long and short-axis) subcostal views in another group of 21 patients aged 2.5 to 29 years (median 4.5 years). The echo size of the ASD was 9.7 +/- 3.0 mm, whereas the measured stretched diameter was 15.3 +/- 4.0 mm. The predicted stretched ASD diameter was calculated according to the above formula and was 15.7 +/- 3.1 mm, not significantly different (p greater than 0.1) from the measured stretched diameter. The correlation between predicted and measured stretched ASD sizes was excellent (r = 0.9; p less than 0.001). The mean squared error was 2.4. The differences between measured and predicted values were within 2 mm in all but three patients. It is concluded that stretched ASD diameter can be estimated accurately by two-dimensional subcostal echo measurements, which in turn could be used for selection of device size for occlusion of the ASD.     

Analysis of Clinical Applicability of the Breast Cancer Nomogram for Positive Sentinel Lymph Node: The Canadian Experience

Background  A Breast Cancer Nomogram (BCN) for predicting nonsentinel lymph node (NSLN) involvement has been developed and prospectively tested in several series. However, its clinical applicability has never been tested among surgeons. Methods  The BCN was applied to 209 SLN-positive patients. Its performance was assessed by the area under the receiver–operating characteristic (ROC) curve. Surgeons in Quebec were surveyed to determine the predicted NSLN positivity below which they would not dissect the axilla. The accuracy of the BCN was determined in this clinically relevant range. Results  The predictive accuracy of the BCN had an area under the ROC curve of 0.687. Almost half of interviewed surgeons treat over 20 breast cancer per year. Fourteen out of 82 surgeons questioned would never leave the patient without a completion axillary dissection after a positive SLN, regardless of the BCN result. Seventy one percent of them would not complete axillary dissection if the prediction of a positive NSLN was ≤10%. Only 37 of the 209 patients were in this 10% or less category, with a mean observed rate of positive NSLN of 13% (95% confidence interval [CI], 2–24%). Conclusion  The global performance of the BCN was fair. A majority of surgeons in Quebec would omit an axillary lymph node dissection (ALND) if the predicted probability of positive NSLN is 10% or less. Although useful, the BCN data should be used with caution at the low end of the scale. Because of some limitations in the performance in this category, other clinical factors and judgment must accompany its use.     

Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express connexin 36

Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF). Double staining revealed that Cx36 co-localizes with both anti-β-III tubulin, a neuronal marker, and anti-glutamine synthetase, a satellite glial cell (SGC) marker. In neurons, Cx36 staining was mostly uniform in somata and fibers of all sizes and its intensity increased at the cell membranes. This labeling pattern was in contrast with Cx36 IF dots mainly found at junctional membranes in islet beta cells used as a control tissue. Co-staining with anti-Cx43 and anti-Cx36 showed that whereas mostly uniform staining of Cx36 was found throughout neurons and SGCs, Cx43 IF puncta were localized to SGCs. Cx36 mRNA was expressed in normal lumbar DRG, and it was significantly down-regulated in L4 DRG of rats that underwent sciatic nerve injury resulting in persistent hypersensitivity. Collectively, these findings demonstrated that neurons and SGCs express Cx36 protein in normal DRG, and suggested that perturbation of Cx36 levels may contribute to chronic neuropathic pain resulting from a peripheral nerve injury.