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1. Altura, B.M., Lefer, A.M. and Schumer, W. Handbook of Shock and Trauma. Vol. 1: Basic Science. NY: Raven Press, 1983. 2. Amezcua, J.L., Palmer, R.M., de Souza, B.M. and Moncada, S. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br. J. Pharmacol. 97: 11191124, 1989. Arai, T., Hiromatsu, K., Kobayashi, N., Takano, M., Ishida, H., Nimura, Y. and Yoshikai, Y. IL-10 is involved in the protective effect of dibutyl cyclic adenosine monophosphate on endotoxininduced inflammatory liver injury. J. Immunol. 155: 5743-5749, 1995. Bearn, A.G., Billing, B. and Sherlock, S. The effect of adrenaline and noradrenaline on hepatic blood flow and splanchnic carbohydrate metabolism in man. J. Physiol. 115: 430-441, 1951. Beck, G.C., Oberacker, R., Kapper, S., von Zabern, D., Schulte, J., van Ackern, K., van der Woude, F.J. and Yard, BA. Modulation of chemokine production in lung microvascular endothelial cells by dopamine is mediated via an oxidative mechanism. Am. J. Respir. Cell Mol. Biol. 25: 636-643, 2001. Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A. and Freeman, B.A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 87: 1620-1624, 1990. Beutler, B. and Cerami, A. The biology of cachectin TNF: a primary mediator of the host response. Ann. Rev. Immunol. 7: 625655, 1989. Chu, A., Chambers, D.E., Lin, C.C., Kuehl, W.D., Palmer, R.M. and Moncada, S. Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dog. J. Clin. Invest. 87: 1964-1968, 1991. Deitsch, E.A. Multiple organ failure: pathophysiology and potential future therapy. Ann Surg 216: 117-134, 1992. Hasko, G., Szabo, C., Nemeth, Z.H., Kvetan, V., Pastores, S.M. and Vizi, E.S. Adenosine receptor agonists differentially regulate IL-10 and TNF production in endotoxemic mice. J. Immunol. 157: 46344640, 1996. Hasko, G., Szabo, C., Nemeth, Z.H., Salzman, A.L. and Vizi, E.S. Stimulation of -adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice. J. Neuroimmunol. 88: 57-61, 1998. Hayes, M.A., Timmins, A.C., Yau, E.H., Palazzo, M., Hinds, C.J. and Watson, D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N. Engl. J. Med. 330: 1717-1722 and prazosin. Pharmaceuticals . Vaccines . Total operating income current.
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Decrease the infectious period and thus potentially shorten or simplify the treatment of disease O'Brien, 2003 ; . One of the TBTC's other new projects is Study 26, a Phase III clinical trial that will compare the effectiveness and tolerability of two regimens for treating LTBI. In one regimen in the trial, patients will take INH--currently the most commonly used treatment for latent tuberculosis infection--daily for nine months, self-supervised. Patients treated with the other regimen will take a combination of INH and rifapentine RFP ; once weekly for three months, administered under direct observation. If the RFP INH combination is found to be as good as, or better than, INH alone, the duration of treatment of LTBI could be reduced from nine months to three months and from 270 doses to 12 doses. Because adherence to or completion of the treatment regimen for LTBI is recognized to be the most challenging aspect of this intervention, the newer, shorter, entirely supervised regimen can be expected to overcome this challenge and to be especially effective in highly vulnerable populations, such as children and persons living with HIV infection. A New and Better Vaccine It is far better to prevent TB than to treat it. Prevention is cheaper Sawert, 2000; Marks et al., 2003 ; , and it avoids the terrible human cost of disease. Moreover, vaccines have been effective tools for preventing and controlling many other infectious diseases. The only TB vaccine currently available is BCG, an attenuated strain of M. bovis. Though it has been used since 1921, its effectiveness is still controversial Fine, 2000 ; . There is a lack of consistency in its protection, and it induces a positive skin test for TB, thus complicating the diagnosis of TB, especially LTBI. Meta-analysis of data from 14 prospective trials and separately from 12 case-control studies found that in children BCG vaccination significantly reduces the risk of active TB cases and deaths and protects from serious forms of pediatric TB, i.e., meningeal and disseminated miliary ; TB Colditz et al., 1994 ; . However, the vaccine's efficacy in reducing the risk of pulmonary TB has varied considerably in clinical trials, with some trials showing that the vaccine actually increases the risk of pulmonary TB Colditz, 1994; Fine, 2000 ; . Recent evidence suggests that differences in the efficacy of BCG among trials are likely the result of several factors, including exposure of persons to environmental mycobacteria mycobacteria other than tuberculosis ; , genetic variability in the human populations studied, and genetic variation in the bacterial strains used to produce the BCG vaccine Fine, 2000 ; . This genetic variation has evolved during the 70 + years that BCG has been growing in laboratories around the world Behr et al., 1999; Young and Robertson, 1999; Andersen, 2001; Black et al., 2002 ; . Thus, development of a better TB vaccine is a high priority CDC, 1998; Institute of Medicine, 2000; Ginsberg, 2000; Andersen 2001; Ginsberg, 2002; Wang and Xing, 2002; Britton and Palendira, 2003; McMurray, 2003 ; . The list of potential vaccines includes live attenuated vaccines, subunit vaccines, and naked DNA vaccines for reviews, see Brandt and Orme, 2002; Sacksteder and Nacy!

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