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2.
Nucleic Acids Res ; 44(D1): D1104-12, 2016 01 04.
Article in English | MEDLINE | ID: mdl-26578581

ABSTRACT

Antimicrobial peptides (AMPs) are anti-infectives that may represent a novel and untapped class of biotherapeutics. Increasing interest in AMPs means that new peptides (natural and synthetic) are discovered faster than ever before. We describe herein a new version of the Database of Antimicrobial Activity and Structure of Peptides (DBAASPv.2, which is freely accessible at http://dbaasp.org). This iteration of the database reports chemical structures and empirically-determined activities (MICs, IC50, etc.) against more than 4200 specific target microbes for more than 2000 ribosomal, 80 non-ribosomal and 5700 synthetic peptides. Of these, the vast majority are monomeric, but nearly 200 of these peptides are found as homo- or heterodimers. More than 6100 of the peptides are linear, but about 515 are cyclic and more than 1300 have other intra-chain covalent bonds. More than half of the entries in the database were added after the resource was initially described, which reflects the recent sharp uptick of interest in AMPs. New features of DBAASPv.2 include: (i) user-friendly utilities and reporting functions, (ii) a 'Ranking Search' function to query the database by target species and return a ranked list of peptides with activity against that target and (iii) structural descriptions of the peptides derived from empirical data or calculated by molecular dynamics (MD) simulations. The three-dimensional structural data are critical components for understanding structure-activity relationships and for design of new antimicrobial drugs. We created more than 300 high-throughput MD simulations specifically for inclusion in DBAASP. The resulting structures are described in the database by novel trajectory analysis plots and movies. Another 200+ DBAASP entries have links to the Protein DataBank. All of the structures are easily visualized directly in the web browser.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Databases, Pharmaceutical , Peptides/chemistry , Peptides/pharmacology , Anti-Infective Agents/toxicity , Cytotoxins/chemistry , Cytotoxins/toxicity , Molecular Dynamics Simulation , Peptides/toxicity
3.
Ann Thorac Surg ; 89(4): 1158-61, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20338324

ABSTRACT

BACKGROUND: Functional mitral regurgitation (FMR) is associated with leaflet displacement and tethering. Little is known about regional coaptation zones, including variations in coaptation length (CL) and contributions of anterior and posterior leaflets. Regional coaptation zones were analyzed in patients with normal mitral valves and with FMR. METHODS: Cardiac surgery patients underwent a three-dimensional transesophageal echocardiography. Four-dimensional volumetric datasets were acquired with Doppler interrogation. Offline analysis was performed. Orthogonal views were extracted in diastole and systole. Leaflet dimensions and coaptation distance and depth were examined for posterior and apical displacement of the coaptation zones. RESULTS: Twenty patients were analyzed (10 normal and 10 with 2 to 4+ FMR). Anterior leaflet CL was greater than posterior leaflet CL: 2.2+/-0.6 mm versus 0.9+/-0.3 mm in region 1, 3.2+/-0.7 mm versus 1.2+/-0.6 mm in region 2, and 1.8+/-0.4 mm versus 0.6+/-0.3 mm in region 3 (p<0.001). The FMR was associated with shorter leaflet CLs, with a mean anterior CL of 1.7+/-0.4 mm versus 3.1+/-0.4 mm (p=0.04), and a mean posterior CL of 0.7+/-0.3 mm versus 1.1+/-0.3 mm (p=0.03). The biggest difference in CLs was in A2-P2. Coaptation distance and depth were higher in the FMR group: 21.7+/-1.0 mm versus 17.9+/-1.0 mm (p=0.01), and 8.6+/-0.7 mm versus 5.0+/-0.7 mm (p<0.01). CONCLUSIONS: Mitral valve leaflet CL is asymmetric in normal valves, with anterior dominance. Functional mitral regurgitation is associated with a relocated coaptation zone, regional changes, and diminished coaptation. These data suggest an "anterior leaflet reserve." Posterior movement of the coaptation line compensates for annular dilation and presumed left ventricular enlargement in order to maintain competency until inadequate anterior leaflet CL occurs.


Subject(s)
Echocardiography, Transesophageal , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/pathology , Mitral Valve/anatomy & histology , Mitral Valve/diagnostic imaging , Humans , Imaging, Three-Dimensional , Retrospective Studies
4.
Ann Thorac Surg ; 89(3): 723-9; discussion 729-30, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20172117

ABSTRACT

BACKGROUND: A recent report suggested that a thoracotomy approach for reoperative mitral valve (MV) procedures was associated with an equivalent mortality and an unacceptable risk of stroke. We assessed these outcomes in a single institution's experience. METHODS: From 1992 through 2007, 905 patients underwent reoperative MV procedures. The approach was a median sternotomy in 612 (67.6%), right anterior thoracotomy in 242 (26.7%), and left posterior thoracotomy in 51 (5.6%). Concomitant procedures in 411 patients (67.6%) included aortic procedures in 189, tricuspid procedures in 170, and coronary artery bypass grafting in 90. Hypothermic fibrillation was used in 65 patients. Logistic analysis was used to analyze risk factors and outcomes. RESULTS: Overall mortality was 12.7% (115 of 905), 6.7% (25 of 371) for first time isolated MV reoperations, and 10.1% (50 of 494) for all isolated MV operations. Overall incidence of stroke was 3.8% (34 of 905); 10.9% (9 of 82) with retrograde arterial perfusion and 3.0% (25 of 824) with central aortic cannulation (p < 0.001). For isolated MV reoperations, the incidence of stroke was 4.3% (21 of 494): 2.9% (7 of 241) for antegrade perfusion and 5.5% (14 of 253) for retrograde perfusion (p = 0.15). Risk factors for death were age (p < 0.001), renal failure (p < 0.01), tricuspid valve disease (p < 0.001), chronic obstructive pulmonary disease (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.8 to 4.9; p < 0.001), emergency procedure (OR, 2.9; 95% CI, 1.2 to 6.9; p = 0.02), and ejection fraction less than 0.30 (OR, 1.9; 95% CI, 1.1 to 3.3, p = 0.018). Risk factors for stroke were retrograde perfusion (OR, 4.4; 95% CI, 1.8 to 10.3; p < 0.01) and ejection fraction below 0.30 (OR, 2.1; 95% CI, 0.9 to 5.0; p = 0.09). CONCLUSIONS: The incidence of stroke in reoperative MV operations is associated with perfusion strategies, not with the incisional approach. Reoperative sternotomy and minithoracotomy with central cannulation are both useful for reoperative MV procedures and are associated with low stroke rates.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Mitral Valve/surgery , Stroke/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Cardiac Surgical Procedures/methods , Catheterization, Peripheral , Female , Femoral Artery , Humans , Male , Middle Aged , Reoperation , Risk Factors , Sternotomy/methods , Thoracotomy/methods , Young Adult
5.
Ann Thorac Surg ; 88(4): 1180-4, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19766803

ABSTRACT

BACKGROUND: Short-term results with minimally invasive approaches for mitral valve repair in degenerative disease have been encouraging, with potential for diminishing blood loss and hospital length of stay. Little is known, however, about the long-term efficacy of this approach. This report analyzes a single institution's results over 12 years with minimally invasive mitral repair. METHODS: Since 1986, 3,057 patients have undergone mitral valve repair; 1,601 patients had degenerative disease and are the subject of this report. Minimally invasive mitral repair was done in 1071 patients with a right anterior minithoracotomy and direct vision. Clinical and echocardiographic variables were entered prospectively into a database. RESULTS: Hospital mortality was 2.2% for all patients (36 of 1601); 1.3% for isolated minimally invasive (9 of 712) and 1.3% (3 of 223) for isolated sternotomy mitral valve repair; and 3.6% (24 of 666) for valve repair plus a concomitant cardiac procedure. For isolated valve repair, 8-year freedom from reoperation was 91% +/- 2% for sternotomy and 95% +/- 1% for minimally invasive (p = 0.24), and 8-year freedom from reoperation or severe recurrent insufficiency was 90% +/- 2% for sternotomy and 93% +/- 1% for minimally invasive (p = 0.30). Eight-year freedom from all valve-related complications was 86% +/- 3% for sternotomy and 90% +/- 2% for minimally invasive (p = 0.14). CONCLUSIONS: These data indicate that long-term outcomes after minimally invasive mitral repair are excellent and equivalent to results achieved with sternotomy. In view of previously published advantages of short-term morbidity, minimally invasive approaches to mitral valve surgery deserve expanded use.


Subject(s)
Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Minimally Invasive Surgical Procedures/methods , Mitral Valve/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Echocardiography , Female , Follow-Up Studies , Heart Valve Diseases/diagnosis , Heart Valve Prosthesis Implantation/statistics & numerical data , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/statistics & numerical data , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
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