Preparticipation cardiovascular screening for US collegiate student-athletes

Context  Sudden death in young competitive athletes due to unsuspected cardiovascular disease has heightened interest in preparticipation screening. Objective  To assess screening practices for detecting potentially lethal cardiovascular diseases in college-aged student-athletes. Design, Setting, and Participants  A total of 1110 National Collegiate Athletic Association member colleges and universities were surveyed between 1995 and 1997, with 879 (79%) responding to the questionnaire. Main Outcome Measures  Information on the administration and scope of the preparticipation screening process was obtained from the team physician or athletic director; preparticipation screening forms were evaluated for content and compared with 12 items recommended by the 1996 American Heart Association (AHA) consensus panel screening guidelines. Results  Preparticipation screening was a requirement at 855 (97%) of 879 schools, was performed on campus at 713 schools (81%), and was required annually by 446 schools (51%). Team physicians were responsible for examinations at 603 (85%) of 713 schools with on-campus screening, although 135 of these schools (19%) also approved nurse practitioners and 244 schools (34%) allowed athletic trainers to perform examinations. Of the history and physical examination screening forms analyzed from 625 institutions, only 163 schools (26%) had forms that contained at least 9 of the recommended 12 AHA screening guidelines and were judged to be adequate, whereas 150 (24%) contained 4 or fewer of these parameters and were considered to be inadequate. Smaller Division III schools were more likely than larger Division I schools to have inadequate screening forms (30% vs 14%; P<.001). Relevant items that were omitted from more than 40% of the screening forms included history of exertional chest pain, dyspnea, or fatigue; familial heart disease or premature sudden death; and physical stigmata or family history of Marfan syndrome. Conclusion  The preparticipation screening process used by many US colleges and universities may have limited potential to detect (or raise the suspicion of) cardiovascular abnormalities capable of causing sudden death in competitive student-athletes.      

The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes

The thymus plays distinct roles in the pathogenesis of the different Myasthenia gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late onset MG, respectively. By contrast, the thymus is presumably not related to MG that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has not been their standard treatment. This review aims to give an update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal T cell selection and activation, the role of thymic myoid cells, the autoimmune regulator (AIRE) and regulatory T cells.     

Results of single‐center screening for chronic hepatitis E in children after liver transplantation and report on successful treatment with ribavirin

RNA screening for HEV in 22 liver‐transplanted children with chronic graft hepatitis out of a cohort of 267 liver‐transplanted children detected a single patient with chronic HEV infection. Although this patient remained viremic for 33 months, anti‐HEV‐IgG was not detectable with MP assay but with Wantai assay. We present the first case of successful ribavirin therapy in an immunosuppressed child with chronic HEV infection. In conclusion, chronic HEV infection in immunosuppressed children may not be detectable employing serological assays. Therefore, the most reliably screening method is screening for HEV‐RNA. Chronic HEV infection in children can successfully be treated with ribavirin.     

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.     

Synthesis and Ring‐Opening Polymerization of Cyclic Butylene 2,5‐Furandicarboxylate

A new synthetic pathway for the polymerization of furan based polyesters is reported in this work. First, poly(butylene 2,5‐furandicarboxylate) cyclic oligoesters (COEs) are chemically synthesized by semi‐batch esterification. The structure of the COEs is confirmed by infrared spectroscopy, ¹H, and ¹³C‐NMR, while the molecular weight distribution of the COEs is determined by matrix‐assisted laser desorption/ionization time of flight mass spectroscopy. The cyclic oligoesters are then successfully polymerized via ring‐opening polymerization using tetrakis(2‐ethylhexyl)‐titanate as catalyst. Differential scanning calorimetry and ¹H‐NMR analysis unambiguously proves the formation of polymeric species. Both end‐group analysis from ¹H‐NMR spectrum and calculation through Flory–Fox equation give comparable estimates of the number average molecular weight: 5.8 × 10³ g mol^?1 and 7.8 × 10³ g mol^?1, respectively.