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The books and articles devoted to the anatomy of the aortic valvar complex are numerous. Until now, however, little consideration has been given to understanding the anatomy with percutaneous valvar replacement in mind. It is axiomatic that knowledge of the anatomy of the valve is fundamental in understanding key principles involved in valvar replacement. Such an appreciation of the anatomy helps better understand the optimal positioning for the prosthetic valve within the root of the aorta with respect to the coronary arteries, mitral valve, and the conduction system and may circumvent complications that can arise during its implantation. In this review, therefore, we describe the anatomy of the trifoliate aortic valvar complex and its implications for percutaneous valvar replacement.

Background —Intracoronary γ- and β-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of β-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. Methods and Results —A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the β-emitting 32 P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11±36% in radiotherapy patients versus 55±30% in controls ( P <0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (≥50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P =0.012) and at target site plus adjacent segments (22% versus 50%; P =0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P <0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. Conclusions —β-radiotherapy with a centered 32 P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

Push-out tests have been conducted on 18 rectangular concrete-filled steel tubular (CFST) columns with the aim of studying the bond behaviour between the steel tube and the concrete infill. The obtained load-slip response and the distribution of the interface bond stress along the member length and around the cross-section for various load levels, as derived from measured axial strain gradients in the steel tube, are reported. Concrete compressive strength, interface length, cross-sectional dimensions and different interface conditions were varied to assess their effect on the ultimate bond stress. The test results indicate that lubricating the steel-concrete interface always had a significant adverse effect on the interface bond strength. Among the other variables considered, concrete compressive strength and cross-section size were found to have a pronounced effect on the bond strength of non-lubricated specimens for the range of cross-section geometries considered, which is not reflected in the European structural design code for composite structures, EN 1994-1-1 (2004). Finally, based on nonlinear regression of the test data generated in the present study, supplemented by additional data obtained from the literature, an empirical equation has been proposed for predicting the average ultimate bond strength for SHS and RHS filled with normal strength concrete.

BACKGROUND: There is some evidence that the perception of bronchoconstriction may very according to the nature of the provoking stimulus. The aims of this study were, firstly, to develop a method for measuring dyspnoea during induced bronchoconstriction in patients with asthma and, secondly, to apply this method to testing differences between directly and indirectly acting bronchoconstricting stimuli. METHODS: Descriptive terms suitable for quantifying respiratory discomfort due to bronchoconstriction in patients with asthma were identified in a preliminary investigation. The relation between reduction in forced expiratory volume in one second (FEV1) and respiratory discomfort, measured using a visual analogue scale (VAS), was then studied during challenges with three different inhaled stimuli: methacholine (MCH), sodium metabisulphite (MBS), and adenosine monophosphate (AMP). Three indices were calculated to describe the relation: the VAS value associated with a 20% fall in FEV1 (FEV20 VAS); the ratio of the final VAS value to the final percentage fall in FEV1 (VAS-FEV1 ratio); and the regression coefficient for predicting VAS from the percentage fall in FEV1 within each challenge (beta VAS FEV1). RESULTS: "Difficulty in breathing" and "chest tightness" were selected as suitable terms for quantifying respiratory discomfort. There were no differences between the three agonists in the qualitative aspects of the respiratory sensation. In paired challenges with the same agonist the three indices were all found to be reproducible for both sensations measured. MCH induced less intense difficulty in breathing and chest tightness for a given fall in FEV1 than did AMP. There was a trend in the same direction for the comparison between MCH and MBS. There were no differences between AMP and MBS. FEV20 VAS was less powerful in discriminating between agonists than the two slope indices. CONCLUSIONS: The relation between induced reduction in FEV1 and the intensity of respiratory discomfort can be measured reliably. The indirectly acting bronchoconstricting agonists AMP and MBS induced more intense respiratory discomfort for a given fall in FEV1 than the direct agonist MCH. This may be due to differences in unmeasured mechanical changes in the lungs or to an additional action on airway sensory nerves.

Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the respiratory tract. It is of interest to determine which respiratory resident cells express NEP. Trachea and bronchi from seven nonsmoking, nonasthmatic subjects were examined. NEP messenger ribonucleic acid (mRNA) was characterized by Northern blot hybridization of cultured human tracheobronchial epithelial and smooth muscle cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) in trachea and bronchi. In situ hybridization with biotin- and 35S-labelled antisense complementary ribonucleic acid (cRNA) probes was used to determine the distribution of NEP mRNA in human bronchial mucosa. NEP-immunoreactive material was detected using MEK10 murine monoclonal antibodies and the immunogold method with silver enhancement. NEP mRNA was 4.5 kb in size in the cultured human smooth muscle and epithelial cells by Northern blot analysis. No evidence was found by RT-PCR for truncated, alternatively spliced NEP mRNAs, such as del exon 16 or del exons 5-18 in human bronchus. NEP mRNA was detected by in situ hybridization in epithelial cells, submucosal glands, bronchial smooth muscle and endothelium. NEP-immunoreactive material was identified in the epithelium, submucosal glands, bronchial smooth muscle, and endothelium, demonstrating an excellent correlation between the distribution of NEP mRNA and the cell surface protein. NEP mRNA and immunoreactive material were excluded from epithelial goblet cell and submucosal gland mucous cell vacuoles. We conclude that the various sites of NEP protein and mRNA expression correlate with the locations of peptide receptors and NEP enzyme function, and are consistent with the hypothesis that NEP may regulate peptide-induced inflammation in human bronchi.

We determined whether platelet-activating factor (PAF) caused bronchoconstriction through the release of leukotrienes (LT) by studying the effect of a potent LTD4 receptor antagonist, ICI 204,219, on PAF-induced bronchoconstriction in normal subjects. Eight males (age 20 to 36 yr) were given either 40 mg ICI 204,219 orally or matching placebo on 2 study days separated by 2 wk in a double-blind crossover study. Specific airway conductance (SGaw) was measured after inhalation of nebulized PAF (45 µg). ICI 204,219 caused a significant inhibition of PAF-induced bronchoconstriction as assessed by comparison of the maximum fail in SGaw or of the area under the curve of the time course of SGaw. ICI 204,219 did not inhibit PAF-induced neutropenia. PAF-induced bronchoconstriction is mediated largely by the release of sulfidopeptide leukotrienes in normal men.

Objectives This study sought to assess the clinical safety and effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in patients with in-stent restenosis (ISR) from 2 large trials. Background ISR treatment is associated with higher rates of subsequent cardiac events compared with treatment of de novo lesions. Although drug-eluting stents (DES) are an option, second-generation DES are largely untested in the treatment of ISR. Methods A total of 3,489 patients were pooled from the RAC (RESOLUTE All Comers) trial and the RESOLUTE International (RINT) registry. Two-year clinical endpoints included clinically driven target lesion revascularization (TLR), target lesion failure (TLF), cardiac death (CD), target vessel myocardial infarction (TVMI), combined CD or TVMI (CD/TVMI), and Academic Research Consortium definite and probable stent thrombosis (ST). Results Overall, 281 patients (8.1%) received an R-ZES for ISR. Two-year TLR and TLF rates were significantly higher in ISR patients than in non-ISR patients (TLR: 12.7% vs. 4.3%, p = 0.003; TLF: 17.4% vs. 9.4%, p = 0.007); however, the CD/TVMI rate was not (6.9% vs. 6.1%, p = 0.711). Seven ISR patients had ST. Two-year outcomes by ISR stent type were similar: bare-metal stent (BMS)-ISR TLR was 12.5% and TLF was 17.2%; DES-ISR TLR was 13.0% and TLF was 18.8%. CD/TVMI was 7.3% and 7.2% for BMS-ISR and DES-ISR, respectively. Conclusions Using R-ZES to treat ISR appears equally safe in BMS-ISR and DES-ISR, with CD/TVMI rates comparable to 2-year outcomes in other clinical trials. Although revascularization rates are still higher in ISR lesions, the R-ZES offers an effective alternative for treatment of BMS-ISR and DES-ISR. (Randomized, Two-Arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; and RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a ‘Real-World’ Patient Population [RINT]; NCT00752128)

Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non‐cholinergic (NC) neural bronchoconstriction in guinea‐pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea‐pig. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea‐pigs which was reduced by atropine (1 mg kg −1 ), but the NC component was unaffected by hexamethonium (10 mg kg −1 ). NC bronchoconstriction was reduced by morphine in a dose‐dependent manner (ED 50 = 132 μg kg −1 with a maximal inhibition of 79 ± 2.1% at 1 mg kg −1 ). Yohimbine (0.5 mg kg −1 ) did not alter the inhibitory effect of morphine (1 mg kg −1 ). The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg −1 ) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg −1 ) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. The selective μ‐opioid receptor agonist Tyr‐( d ‐Ala)‐Gly‐(N‐Me‐Phe)‐Glyol (DAGOL) was significantly more potent than morphine with an ED 50 of 5.4 μg kg −1 and complete inhibition at 100 μg kg −1 . The δ‐agonist Tyr‐( d ‐Pen)‐Gly‐Phe‐( d ‐Pen) (DPDPE) was less potent than DAGOL with an ED 50 of 28 μg kg −1 and a maximal inhibition of only 50 ± 5% at 100 μg kg −1 . The κ‐receptor agonist, U‐50,488H had no inhibitory effect on the NC bronchoconstrictor response. The bronchoconstrictor responses to exogenous substance P (25 μg kg −1 ) or acetylcholine (25 μg kg −1 ) were unaffected by morphine (500 μg kg −1 ). We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on μ‐opioid receptors localized to sensory nerve endings in the airway.