Surgery for severe mitral regurgitation and left ventricular failure: what do we really know?

In ischemic and nonischemic cardiomyopathy, functional mitral regurgitation (MR) results from geometric abnormalities of the ventricle, which result in dysfunction of a morphologically normal mitral valve. Enlargement of the left ventricle causes geometric MR through annular dilation, increase in the interpapillary muscle distance, amplified leaflet tethering (elongation and stretch on the chordae tendinae), and decreased closing forces because of muscle weakness and asynchrony of papillary muscle contractile timing. The final common pathway of MR is a failure of coaptation of the morphologically normal leaflets and resultant central MR. These abnormalities can be favorably influenced by antiremodeling pharmacologic therapy and in selected cases by cardiac resynchronization therapy. Surgical repair of functional geometric MR with an undersized complete rigid annuloplasty ring can abolish MR and is associated with improved functional status and left ventricular remodeling. It is unclear if surgery is associated with improved survival in this setting. There is a pressing need for well-conducted prospective randomized clinical trials to quantify the benefits of surgical repair of functional geometric MR.     

Colonic motility diagnosis based on colonic pressure

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.     

Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance

In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the K_m(MCN), less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants tet(X2)_T280A and tet(X2)_N371I. The structure of the most efficient variant, TetX2_T280A, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection.     

Early diagnosis of regional odontodysplasia in an infant

Regional odontodysplasia is a rare and significant dental malformation. It is a dental alteration of unknown etiology, involving both mesodermal and ectodermal dental components, which present clinical, radiographic, and histologic features. This article reports a clinical case of a 10-month-old child who was diagnosed with regional odontodysplasia in the maxilla, confirmed by radiographic examination, with a follow-up of 5 years. The clinical, radiographic, and histologic features were reviewed.     

术中大剂量放疗治疗局部复发头颈癌

该文旨在介绍Beth Israel医疗中心采用大剂量术中放疗(HDR-IORT)治疗复发头颈癌的经验。对2001-2010年间头颈癌局部复发接受大剂量HDR-IORT的患者进行回顾分析。结果,76例患者的87个部位在肿瘤切除后接受了治疗。术后2年控制率为62%。平均总生存期为19个月,其中42%的患