To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.
e Mycobacterium tuberculosis is able to synthesize molybdopterin cofactor (MoCo), which is utilized by numerous enzymes that catalyze redox reactions in carbon, nitrogen, and sulfur metabolism. In bacteria, MoCo is further modified through the activity of a guanylyltransferase, MobA, which converts MoCo to bis-molybdopterin guanine dinucleotide (bis-MGD), a form of the cofactor that is required by the dimethylsulfoxide (DMSO) reductase family of enzymes, which includes the nitrate reductase NarGHI. In this study, the functionality of the mobA homolog in M. tuberculosis was confirmed by demonstrating the loss of assimilatory and respiratory nitrate reductase activity in a mobA deletion mutant. This mutant displayed no survival defects in human monocytes or mouse lungs but failed to persist in the lungs of guinea pigs. These results implicate one or more bis-MGDdependent enzymes in the persistence of M. tuberculosis in guinea pig lungs and underscore the applicability of this animal model for assessing the role of molybdoenzymes in this pathogen.
spontaneously in 8 patients, while the remaining patients required revision surgery. Urethral stricture developed in 33 patients (22.4%), and there were 13 strictures in the neophallic segment and 20 cases of bulbar strictures. All strictures required surgical repair, in 22 patients urethroplasty with buccal mucosa graft was performed. Fistula between remnant vaginal cavity and neourethral lumen was noted in 21 patients (14.3%). Vaginal remnant was excised through perineal approach and urethral opening was closed and covered with local vascularized tissue to prevent fistula formation.CONCLUSIONS: The musculocutaneous latissimus dorsi (MLD) phalloplasty combined with urethral lengthening can provide satisfactory esthetic and functional outcomes. Although urethral complication rate is still high, use of vascularized flaps for neourethra has satisfactory outcomes.
He served in the Merchant Marine in the 1930s, was a major in World War II and served as Professor of Urology at Wayne State University. In 1951 Dr. Bicknell got together a small group of seven urologists interested in pediatric urology during the AUA Annual Meeting. Drs. Campbell, Barber, Johnson, Mertz, Hinman Jr. and Spence all met in Dr. Bicknell's Chicago hotel room and would form The Societies for Pediatric Urology. At the time, Dr. Bicknell's brother-in-law had just become president of the American Academy of Pediatrics (AAP). Dr. John Lattimer with the help of Dr. Bicknell's brother-in-law was able to get a room at the AAP meeting which he filled with 2500 people, thought to be the largest collection of urologists in one room at the time. The success of the session led to the organization of the AAP Section of Urology in 1960 (became a permanent section in 1971). It also impressed upon the AUA the magnitude of interest in pediatric urology. This allowed pediatric urologists to secure an exclusive session on the day before the main AUA meeting which has persisted since that time. In 1980, he wrote a text chapter "Pediatric Urology" describing the birth and history of the field and its current areas of study. Dr. Bicknell introduced a History of Urology Club at the 1965 AUA annual meeting. He chaired this popular event during its first decade, after which it was renamed the Forum on the History of Urology. The forum now occupies an entire afternoon during the annual meeting, with papers presented on historic urologic topics. The highlight of this assembly is the annual lecture on the history of medicine. In 2000, this oration was renamed the Frank Bicknell History of Urology Oration to honor the founder of the History Forum.CONCLUSIONS: Dr. Frank Bicknell was an early leader in pediatric urology and urologic history who helped found The Societies of Pediatric Urology and the AUA History Forum.
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