Relationship of epicardial adipose tissue by echocardiography to coronary artery disease.

OBJECTIVE: To study the relationship of echocardiographic epicardial adipose tissue (EAT) with coronary artery disease (CAD) risk factors and the extent of coronary atherosclerosis. METHODS: EAT thickness was measured in 527 patients undergoing their first coronary angiography. EAT was defined as an echo-lucent area on the free wall of the right ventricle on the still image of the two-dimensional echocardiogram at end diastole in the parasternal long-axis and parasternal short-axis views. A CT scan at the umbilicus was acquired to measure abdominal visceral adipose tissue (VAT) from a random sample of 30 patients. The extent of coronary atherosclerosis was assessed using a coronary atherosclerosis score based on the quantitative coronary angiography results. RESULTS: EAT thickness was correlated with abdominal VAT (r(s) = 0.626, p<0.001), age (r(s) = 0.480, p<0.001), waist circumference (r(s) = 0.309, p<0.001), body mass index (r(s) = 0.233, p<0.001), C reactive protein (r(s) = 0.224, p<0.001), and the homoeostasis model assessment score (r(s) = 0.249, p<0.001). EAT was thicker in subjects with CAD than in those without CAD (4.0 vs 1.5 mm, p<0.001). Patients with unstable angina had thicker EAT than those with stable angina or atypical chest pain (4.0, 3.0, and 1.5 mm, respectively, p<0.001). EAT (> or =3.0 mm) was an independent factor of CAD on multiple logistic analysis (odds ratio = 3.357; 95% CI 2.177 to 5.175, p<0.001). CONCLUSIONS: These results suggest that EAT may reflect the amount of visceral fat, which is associated with insulin resistance and inflammation. The echocardiographic measurement of EAT may provide additional information for assessing CAD risk and predicting the extent and activity of CAD.

Determinants of Staphylococcus aureus nasal carriage.

Nasal carriage of Staphylococcus aureus has been identified as a risk factor for community-acquired and nosocomial infections. We screened 230 donors of diverse ethnic and socioeconomic backgrounds and identified 62 (27%) whose nasal secretions were colonized by S. aureus. In 18 donors in whom the various regions of the nasal luminal surface were separately sampled, the predominant region of S. aureus colonization was the moist squamous epithelium on the septum adjacent to the nasal ostium. Nasal fluid from carriers was defective in killing endogenous S. aureus and nasal carrier isolates of S. aureus but not a laboratory S. aureus strain. Transmission electron microscopy revealed that S. aureus isolates incubated in nasal fluid from carriers for 2 h at 37 degrees C were less damaged than those incubated in noncarrier fluid and were coated with an electron-dense layer. Compared with that from healthy donors and patients with acute rhinitis, nasal fluid from carriers contained elevated concentrations of the neutrophil-derived defensins human neutrophil peptides 1 to 3 (47- and 4-fold increases, respectively), indicative of a neutrophil-mediated inflammatory host response to S. aureus colonization. The concentration of the inducible epithelial antimicrobial peptide human beta-defensin 2 was also highly elevated compared to that in healthy donors, in whom the level was below the detection limit, or patients with acute rhinitis (sixfold increase). Thus, nasal carriage of S. aureus takes hold in nasal fluid that is permissive for colonization and induces a local inflammatory response that fails to clear the colonizing bacteria.

Calcitermin, a novel antimicrobial peptide isolated from human airway secretions.

The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules. Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria. We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C. The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2). Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents.

The carboxyl terminus of type VII collagen mediates antiparallel dimer formation and constitutes a new antigenic epitope for epidermolysis Bullosa acquisita autoantibodies.

Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical domain flanked by two noncollagenous domains, NC1 and NC2. The NC2 domain has been implicated in catalyzing the antiparallel dimer formation of type VII procollagen. In this study, we produced the entire 161 amino acids of the NC2 domain plus 186 amino acids of adjacent collagenous domain (NC2/COL) and purified large quantities of the recombinant NC2/COL protein. Recombinant NC2/COL readily formed disulfide-bonded hexamers, each representing one antiparallel dimer of collagen VII. Removal of the collagenous helical domain from NC2/COL by collagenase digestion abolished the antiparallel dimer formation. Using site-directed mutagenesis, we found that mutation of either cysteine 2802 or cysteine 2804 alone within the NC2 domain blocked antiparallel dimer formation. In contrast, a single cysteine mutation, 2634, within the collagenous helical domain had no effect. A generated methionine to lysine substitution, M2798K, that is associated with recessive dystrophic epidermolysis bullosa, was unable to form antiparallel dimers. Furthermore, autoantibodies from epidermolysis bullosa acquisita patients also reacted with NC2/COL. We conclude that NC2 and its adjacent collagenous segment mediate antiparallel dimer formation of collagen VII. Epidermolysis bullosa acquisita autoantibodies bound to this domain may destabilize anchoring fibrils by interfering with antiparallel dimer assembly leading to epidermal-dermal disadherence.

Therapeutic effect of a pig-derived peptide antibiotic on porcine wound infections.

PURPOSE: We investigated the therapeutic potential of the pig-derived antimicrobial peptide protegrin-1 (PG-1) against porcine skin wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: Using a porcine skin wound model, PG-1 was added to the wound fluid either at the time of P. aeruginosa inoculation, four hours after inoculation or 24 hours after inoculation. Wound fluids were analyzed 20-24 hours later by use of colony-forming unit (CFU) assays, semiquantitative immunoblot analysis for PG-1, and radial diffusion assays (RDA) for residual in vitro activity. RESULTS: Results of the CFU assays indicated a 10,000-fold decrease in the number of bacteria when PG-1 was added at the time of inoculation, a 120-fold decrease when added 4 hours after inoculation and a 10-fold decrease when added 24 hours after inoculation. Results of immunoblot analysis and RDA indicated that PG-1 concentrations for each of the three conditions remained increased in wound fluid 20 to 24 hours after treatment, and correlated with increased residual in vitro antimicrobial activity. CONCLUSIONS: These results document that the endogenous antibiotic PG-1 significantly prevented the colonization of P. aeruginosa in wounds and reduced the in vivo bacterial concentration in established wound infections. Therapeutics used in the same animal species from which they were derived are a promising means for preventing and treating localized infections.

Effect of transcatheter endovascular radiation with holmium-166 on neointimal formation after balloon injury in porcine coronary artery.

BACKGROUND: Neointimal formation in response to arterial injury is a major contributing element in restenosis after coronary balloon angioplasty and stenting. Endovascular irradiation has been reported to be effective in reducing restenosis. The purpose of this study was to investigate the effect of beta-emitting holmium-166 for the inhibition of neointimal formation in porcine coronary artery. METHODS AND RESULTS: A total of 34 pigs weighing 25 to 30 kg underwent oversized balloon injury (balloon/artery ratio, 1.3:1.4) at the proximal portion of the left anterior descending and circumflex arteries. One artery was randomly assigned to receive radiation after injury. Ho-166 was left in the balloon within the delivery catheter for a period sufficient to deliver 9 Gy and 18 Gy to a depth of 1 mm from the surface of the balloon. Four weeks later, pigs were sacrificed and hearts were perfusion-fixed, followed by histopathologic analysis and planimetry for measurement of maximal intimal thickness, intimal area, and fracture length. The coronary segment of the pigs in the control group had neointimal area of 1.18+/-0.55 mm2; the pigs in the 9-Gy group had neointimal area of 0.68+/-0.40 mm2 (P<.05 vs. control); and the pigs in the 18-Gy group had neointimal area of 0.29+/-0.12 mm2 (P<.01 vs. control). The maximal intimal thickness in the 18-Gy group (0.14+/-0.11 mm) was significantly reduced compared with the maximal intimal thickness in the control group (0.48+/-0.13 mm) (P<.01). CONCLUSIONS: Intracoronary radiation with liquid Ho-166 contained in a perfusion balloon catheter is feasible and effective in reducing neointimal formation after coronary overstretch injury in pigs. Therefore intracoronary irradiation on the injured segment may further reduce restenosis after balloon injury.

Comparison of ablation efficacy of excimer, pulsed-dye, and holmium-YAG lasers relevant to shock waves.

Ablation efficacy of pulsed lasers on human arterial tissue and associated shock waves have been investigated by means of excimer laser at 308 nm, pulsed-dye laser at 480 nm, and holmium-YAG laser at 2.1 microns. A multifiber catheter was used for lasing at 420 mjoules/pulse with holmium-YAG, 18.9 mjoules/pulse with excimer, and 100 mjoules/pulse with pulsed-dye laser. Ablation efficiency (ablated volume/energy) was greatest with pulsed-dye laser in blood and excimer laser in saline solution. There was selectivity for atheroma with pulsed-dye laser (ablation efficiency in atheroma versus normal tissue, 58 versus 27 x 10(-2) mm3/joule in blood; p less than 0.005) and holmium-YAG laser (12.6 versus 5.6 x 10(-2) mm3/joule in blood; p less than 0.001). Ablation efficiency of pulsed-dye laser was enhanced by blood (0.58 in blood versus 0.17 mm3/joules in saline for atheroma; p less than 0.005). Shock waves were correlated with ablation efficiency (r = 0.63 and 0.74 for pulsed-dye laser and holmium-YAG laser, respectively). There was neither selectivity for atheroma nor influence of blood medium with excimer laser. Only holmium-YAG laser could ablate tissue at a distance from the target in the blood medium. Histologic findings showed that all lasers could create smooth-edged craters with minimal coagulation necrosis. In conclusion, laser irradiation with holmium-YAG and pulsed-dye lasers could selectively ablate atheromatous tissue with minimal thermal injury, whereas excimer laser could not. Ablation efficiency was correlated with shock waves. Efficiency of pulsed-dye laser was enhanced by blood.

Characteristics of shock waves induced by pulsed lasers and their effects on arterial tissue: comparison of excimer, pulse dye, and holmium YAG lasers.

Shock waves were investigated using an excimer laser at 308 nm with 18.9 mjoules/pulse, a pulsed dye laser at 480 nm with 100 mjoules/pulse, and a holmium YAG (yttrium-aluminum-garnet) laser at 2.1 microns with 420 mjoules/pulse. At a distance from the target tissue, excimer lasing resulted in no shock waves in saline, while the other lasers produced smaller shock waves than those recorded when the laser was in contact with tissue (0.22 versus 2.0 mm Hg with the pulsed dye laser, 0 versus 0.23 mm Hg with the excimer laser, and 0.44 versus 6.9 mm Hg with the holmium YAG laser; p less than 0.001, respectively). In blood, excimer laser irradiation at a distance from the tissue produced shock waves as great as those produced when the laser was in contact with the tissue (0.19 versus 0.24 mm Hg with the excimer laser, 1.8 versus 3.0 mm Hg with the pulsed dye laser, and 3.1 versus 5.9 mm Hg with the holmium YAG laser; p less than 0.001 with the pulsed dye and holmium YAG lasers, respectively). When lasing was done at 60 mjoules/mm2, the pulsed dye and excimer lasers produced similar shock waves when the lasers were in contact with tissue; however, the holmium YAG laser did not produce shock waves. Thus pulsed lasers can produce shock waves of different characteristics according to the laser source.

Percutaneous mitral valvuloplasty using the double balloon technique: immediate results and determinant factors of increasing mitral regurgitation.

Percutaneous mitral valvuloplasty (PMV) was successfully performed in 112 (95%) out of 118 patients (32 M, 80 F, mean age: 38 +/- 11 years) with mitral stenosis. There was a significant increase in the mitral valve area (MVA) from 0.9 +/- 0.2 to 2.0 +/- 0.7 cm2 p less than 0.0001, a decrease in the mean mitral gradient from 17 +/- 6 to 6 +/- 3 mmHg, p less than 0.001, and a rise in cardiac output from 4.3 +/- 0.8 to 4.8 +/- 1.2 L/min, p less than 0.001. The morphologic features of the mitral stenosis was evaluated using echocardiographic score. Patients with a low-score (less than or equal to 8) had more effective dilation of mitral stenosis compared to patients with a high-score over 8 (0.9 to 2.2 vs 0.8 to 1.6 cm2, p less than 0.001), despite the similar EBDA/BSA (effective balloon dilating area/body surface area). The patients with good results after PMV (MVA greater than or equal to 1.5 cm2) were more likely to be in normal sinus rhythm (p less than 0.0001), younger age (p less than 0.001), smaller left atrial size (p less than 0.05), and lower total echoscore (p less than 0.002), especially in leaflet mobility (p less than 0.02) and degree of calcification (p less than 0.002), compared to patients with relatively poor result after PMV (MVA less than 1.5 cm2). There were no differences in EBDA/BSA, calcification on fluoroscopy, and history of previous surgical commissurotomy between the 2 groups. Mitral regurgitation (MR) developed or increased in severity in 41 (37%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)