Numerical and analytical evaluations of the sensing sensitivity of waveguide mode in one-dimensional metallic gratings.

We study numerically and analytically the refractive index sensing sensitivities of surface plasmon (S(SP)) and waveguide (S(WG)) modes arising from one-dimensional Au gratings. By using rigorous coupled wave analysis, we find that while S(SP) is mainly controlled by the periodicity of the grating, the shape of the groove governs S(WG). As a result, it is possible to increase S(WG) to 1000 nm/RIU and figure of merit to 24 by tailoring the height and width of the groove. Finally, a simple analytical expression is derived to describe S(WG) and it agrees well with the numerical data. This easy-to-use expression not only reveals the origin of waveguide mode sensitivity, but also provides useful guidance for the theoretical design and experimental realization of high-sensitivity metallic-gratings-based biosensors.

Atomic-scale magnetometry of distant nuclear spin clusters via nitrogen-vacancy spin in diamond.

The detection of single nuclear spins is an important goal in magnetic resonance spectroscopy. Optically detected magnetic resonance can detect single nuclear spins that are strongly coupled to an electron spin, but the detection of distant nuclear spins that are only weakly coupled to the electron spin has not been considered feasible. Here, using the nitrogen-vacancy centre in diamond as a model system, we numerically demonstrate that it is possible to detect two or more distant nuclear spins that are weakly coupled to a centre electron spin if these nuclear spins are strongly bonded to each other in a cluster. This cluster will stand out from other nuclear spins by virtue of characteristic oscillations imprinted onto the electron spin decoherence profile, which become pronounced under dynamical decoupling control. Under many-pulse dynamical decoupling, the centre electron spin coherence can be used to measure nuclear magnetic resonances of single molecules. This atomic-scale magnetometry should improve the performance of magnetic resonance spectroscopy for applications in chemical, biological, medical and materials research, and could also have applications in solid-state quantum computing.

Surface plasmon resonance in two-dimensional nanobottle arrays.

We report our recent work on surface plasmon polaritons manipulation of two-dimensional arrays of subwavelength bottle-shaped cavities on gold surface. By tuning the geometry of such "nanobottle" it is possible to control the resonant frequencies and near field patterns of different surface plasmon resonances. The plasmonic band structures are not sensitive to the sizes and depths of the nano-bottles, but depend strongly on the polarization. In particular, by using different polarizations, it is observed that different types of plasmonic resonances, whether propagating or localized, can be excited independently. Moreover, we find that the local field and field intensity can by fine-tuned by controlling the topology of the bottleneck of the nanobottle. As a result, we believe these nanobottle arrays are useful for making plasmonic devices.

Dendritic architecture of the von Economo neurons.

The von Economo neurons are one of the few known specializations to hominoid cortical microcircuitry. Here, using a Golgi preparation of a human postmortem brain, we describe the dendritic architecture of this unique population of neurons. We have found that, in contrast to layer 5 pyramidal neurons, the von Economo neurons have sparse dendritic trees and symmetric apical and basal components. This result provides the first detailed anatomical description of a neuron type unique to great apes and humans.

Liquid crystal pretilt control by inhomogeneous surfaces.

We consider the pretilt alignment of a nematic liquid crystal (LC) on inhomogeneous surface patterns comprising patches of homeotropic alignment domains in a matrix favoring homogeneous alignment, or vice versa. We found that the resultant LC pretilt generally increases continuously from the homogeneous limit to the homeotropic limit as the area fraction of the homeotropic region increases from 0 to 1. For any given homeotropic area fraction, the variations are qualitatively different depending on how the distance between adjacent patches compares to the extrapolation lengths of the anchoring domains. Our results agree with those previously found in stripe patterns. The present finding provides useful guidelines for designing inhomogeneous alignment surfaces for variable LC pretilt control.

Amplatzer septal occluder closure of secundum atrial septal defects in the presence of persistent left superior vena cava to coronary sinus.

Secundum atrial septal defects (ASDs) are routinely closed using transcatheter devices. In patients with left superior vena cava (LSVC) draining to the coronary sinus (CS), the device must not obstruct CS drainage. We report five cases of successful ASD device closure without obstructing flow from the LSVC or dilated CS.

Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinflammatory activity.

A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 microM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.

Outcomes of transcatheter balloon angioplasty of obstruction in the neo-aortic arch after the Norwood operation.

Obstruction of the reconstructed aortic arch, or the neoaortic arch, is now known to be an important factor increasing mortality after the Norwood operation for hypoplastic left heart syndrome. Transcatheter balloon angioplasty has been shown to provide effective relief of both native aortic coarctation and obstructions of the aortic arch occurring subsequent to therapeutic intervention. We sought to determine the outcomes of balloon angioplasty used as an initial treatment for obstruction of the neoaortic arch occurring after the Norwood operation. We gathered the characteristics of 58 patients with such obstruction from 8 institutions, noting procedural factors and outcomes of initial balloon dilation. Obstruction occurred at a median interval of 4 months, with a range from 1.5 months to 6.3 years, after a Norwood operation. Ventricular dysfunction was present before dilation in 13 patients. Mean peak to peak systolic pressure gradients were acutely reduced from 31+/-20 mm Hg to 6+/-9 mmHg (p<0.001), with outcome subjectively judged to be successful in 89%. Three patients with pre-existing ventricular dysfunction died within 48 hours of dilation. There were 10 additional deaths during the period of follow-up, with Kaplan Meier estimates of survival after intervention of 87% at 1 month, 77% at 12 months, and 72% after 15 months. In addition, 9 patients required re-intervention during the period of follow-up, with Kaplan Meier estimates of freedom from re-intervention after dilation of 87% at 6 months, 78% at 12 months and 74% after 18 months. Although transcatheter dilation of neoaortic arch obstructions after Norwood operation is successful, there is a high risk of re-intervention and ongoing mortality in this subgroup of patients. Close follow-up is recommended.

Major coronary artery anomalies in a pediatric population: incidence and clinical importance.

OBJECTIVES: We sought to prospectively determine the incidence and clinical significance of major coronary artery anomalies in asymptomatic children using transthoracic two-dimensional echocardiography. BACKGROUND: Anomalous origins of the left main coronary artery (ALMCA) from the right sinus of Valsalva or anomalous origins the right coronary artery (ARCA) from the left sinus are rarely diagnosed in children and can cause sudden death, especially in young athletes. Because most patients are asymptomatic, the diagnosis is often made post mortem. No study to date has prospectively identified anomalous coronary arteries in asymptomatic children in the general population. METHODS: After serendipitously identifying an index case with ALMCA, we examined proximal coronary artery anatomy in children with otherwise anatomically normal hearts who were referred for echocardiography. In those diagnosed with ALMCA or ARCA, we performed further tests. RESULTS: Within a three-year period, echocardiograms were obtained in 2,388 children and adolescents. Four children (0.17%) were identified with anomalous origin of their coronary arteries, and angiograms, exercise perfusion studies and/or stress tests were then performed. One ARCA patient had decreased perfusion in the right coronary artery (RCA) perfusion area and showed ventricular ectopy on electrocardiogram (ECG) at rest that diminished but did not resolve with exercise. A second patient with ALMCA had atrial tachycardia immediately after exercise, with inferior and lateral ischemic changes on ECG and frequent junctional and/or ventricular premature complexes both at rest and recovery. CONCLUSIONS: This study demonstrates that although anomalous origins of coronary arteries are rare in asymptomatic children, the prevalence is greater than that found in other prospective studies. Ischemia can occur with both ALMCA and ARCA even though patients remain asymptomatic. Because of the high risk of sudden cardiac death, aggressive surgical management and close follow-up are necessary.

First-stage palliation of complex univentricular cardiac anomalies in older infants.

BACKGROUND: Poor outcomes have been reported for children older than 30 days of age with cardiac anomalies treated with first-stage palliation. METHODS: Our institution has offered first-stage palliation for all such patients regardless of age. The results of this policy were reviewed. RESULTS: Nine patients older than 30 days (median age 67 days, range 36 to 108 days) with diagnoses of hypoplastic left heart syndrome (n = 5), double-outlet right ventricle with hypoplastic aortic arch (n = 2), unbalanced atrioventricular septal defect (n = 1), or single left ventricle with subaortic stenosis (n = 1) underwent surgical palliation. Patients underwent a Norwood (n = 7) or Damus-Kaye-Stancel (n = 2) procedure with a 4- or 5-mm modified Blalock-Taussig shunt; all patients survived the operation. Eight patients underwent a subsequent bidirectional Glenn (2 perioperative deaths, both due to pneumonia; 6 survivors). Two of the 6 surviving patients have undergone Fontan reconstruction and 4 are awaiting Fontan. CONCLUSIONS: Surgical palliation for complex univentricular cardiac malformations can be performed in older infants with results comparable to those in neonates. The use of a larger shunt may contribute to these improved outcomes.

Effects of isosteric pyridone replacements in androgen receptor antagonists based on 1,2-dihydro- and 1,2,3,4-tetrahydro-2,2-dimethyl-6-trifluoromethyl-8-pyridono[5,6-g]quin olines.

A series of nonsteroidal human androgen receptor (hAR) antagonists based on 8-substituted 1,2-dihydro- and 1,2,3,4-tetrahydro-2,2-dimethyl-6-trifluoromethylpyrido[3,2-g]quin olines was synthesized. Compounds in this series were tested for the ability to bind to hAR and inhibit hAR-dependent transcription in a mammalian cellular background.

Nonsteroidal progesterone receptor antagonists based on 6-thiophenehydroquinolines.

Synthesis and biological evaluation of 6-thiophene 1,2-dihydro or 1,2,3,4-tetrahydroquinoline derivatives resulted in a number of potent nonsteroidal antiprogestins.

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease.

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.

Transcatheter closure of large PDA using 0.052" gianturco coils: controlled delivery using a bioptome catheter through a 4 French sheath.

For over 30 years, a number of devices have been used for transcatheter vascular occlusion procedures, with varying degrees of success. The most prevalent shortcoming with transcatheter occlusion devices is the lack of device control during implant. In patients with congenital heart defects, transcatheter occlusion is complicated by the wide range of vessel sizes, and various anatomical defects. Gianturco embolization coils are very effective and inexpensive occlusion devices. We report a new procedure for transcatheter vascular occlusion using readily available products (Gianturco coil, bioptome, long sheath) that provides complete control of the coil during implant and excellent results.

The hemodynamic effects of propofol in children with congenital heart disease.

UNLABELLED: We studied the hemodynamic effects of propofol during elective cardiac catheterization in 30 children with congenital heart disease. Sixteen patients were without cardiac shunt (Group I), six had left-to-right cardiac shunt (Group II), and eight had right-to-left cardiac shunt (Group III). The mean (+/-SD) ages were 3.8+/-3.1 yr (Group I), 3.2+/-3.7 yr (Group II), and 1.0+/-0.6 yr (Group III). After sedation and cardiac catheter insertion, hemodynamic data and oxygen consumption were measured before and after the administration of propofol (2-mg/kg bolus, 50- to 200-microg x kg(-1) x min(-1) infusion), and values were compared by using a paired t-test (significance: P < 0.05). After the propofol administration, systemic mean arterial pressure and systemic vascular resistance decreased significantly and systemic blood flow increased significantly in all patient groups; heart rate, pulmonary mean arterial pressure, and pulmonary vascular resistance were unchanged. Pulmonary to systemic resistance ratio increased (Group I, P = 0.005; Group II, P = 0.03; Group III, P = 0.10). In patients with cardiac shunt, propofol resulted in decreased left-to-right flow and increased right-to-left flow; the pulmonary to systemic flow ratio decreased significantly (Group II, P = 0.005; Group III, P = 0.01). Clinically relevant decreases in Pao2 (P = 0.008) and Sao2 (P = 0.01) occurred in Group III patients. We conclude that propofol can result in clinically important changes in cardiac shunt direction and flow. IMPLICATIONS: The principal hemodynamic effect of propofol in children with congenital heart defects is a decrease in systemic vascular resistance. In children with cardiac shunt, this results in a decrease in the ratio of pulmonary to systemic blood flow, and it can lead to arterial desaturation in patients with cyanotic heart disease.

Intermediate-term results in pediatric aortic valve replacement.

BACKGROUND: Aortic valve replacement (AVR) in children is now more commonly performed with human tissue valves. METHODS: The results of 100 consecutive pediatric AVRs (50 mechanical, 50 human) were reviewed. RESULTS: There were five perioperative deaths in the mechanical group and one in the human group (p = 0.2). Late complications in the mechanical group included 4 late deaths, 2 cases of endocarditis, 3 thromboembolic complications, and 10 reoperations on the aortic valve. In the human group, there were no late deaths, 2 reoperations for allograft aortic valve deterioration (both in Marfan's patients), and 1 reoperation for allograft pulmonary valve stenosis. Four-year actuarial survival was 83% in the mechanical group and 98% in the human group (p = 0.02). Four-year actuarial survival free of all valve-related complications was 61% in the mechanical group and 88% in the human group (p = 0.008). CONCLUSIONS: Human valves in children requiring AVR provide superior intermediate-term survival and freedom from valve-related complications compared to mechanical valves. Marfan's syndrome may represent a rare remaining contraindication for human AVR in children.

A case for routine screening of coronary artery origins during echocardiography: fortuitous discovery of a life-threatening coronary anomaly.

Anomalous origin of the left main coronary artery from the right sinus of Valsalva with retropulmonary course is a rare congenital abnormality. It is associated with a high incidence of sudden cardiac death, particularly among young, athletic individuals. Many of these individuals do not have symptoms before sudden death, and the diagnosis is usually made at postmortem examination. We present a case of a 15-year-old boy who was evaluated for a systolic click with routine 2-dimensional echocardiography. The anomalous coronary artery was serendipitously identified, allowing surgical intervention. Coronary artery origin and proximal course should be visualized on routine echocardiography in the pediatric population.

Right aortic arch with isolation of the left subclavian artery, moderate patent ductus arteriosus, and subclavian steal syndrome: A rare aortic arch anomaly treated with the Gianturco-Grifka vascular occlusion device.

We present the first described use of the Gianturco-Grifka Vascular Occlusion Device to close a moderate patent ductus arteriosus associated with the rare congenital condition of right aortic arch with isolation of the left subclavian artery. Left vertebral artery "steal" through the moderate patent ductus arteriosus was eliminated by this transcatheter technique. Cathet. Cardiovasc. Intervent. 47:320-322, 1999.

4-Alkyl- and 3,4-dialkyl-1,2,3,4-tetrahydro-8-pyridono[5,6-g]quinolines: potent, nonsteroidal androgen receptor agonists.

A series of human androgen receptor (hAR) agonists based on 4-alkyl-; 4,4-dialkyl-; and 3,4-dialkyl-1,2,3,4-tetrahydro-8-pyridono[5,6-g]quinoline was synthesized and evaluated in competitive receptor binding assays and an androgen receptor cotransfection assay in a mammalian cell background. A number of compounds in this series demonstrated activity equal to or better than dihydrotestosterone in both assays and represent a novel class of compounds for use in androgen replacement therapy.

Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one.

A series of 2H-pyrano[3,2-g]quinolin-2-ones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one, displayed moderate interaction with hAR, but substituted analogues were potent hAR modulators in vitro as measured by an hAR cotransfection assay in CV-1 cells and bound to hAR with high affinity in a whole cell assay. Several analogues were able to activate hAR-mediated gene transcription more potently and efficaciously than dihydrotestosterone.