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Table 6. Hematologic toxicity % ; during subcutaneous first-line treatment with alemtuzumab in 38 patients with B-CLL who received more than 1 week of therapy NCI grading 0-I Anemia Neutropenia Thrombocytopenia 61 26 84 II-III 39 53 11 IV.
Winquist et al. Relaxation of Porcine Cerebral Arteries ies attempting to elucidate the nature of this transmitter, including ours, have only resulted in ruling out likely candidates Lee et al., 1978; Duckies, 1979; Lee, 1980 ; . However, neurogenic dilation in the pig, but not in the cat Lee et al., 1978 ; , sheep, or dog Duckies, 1979 ; , appears to be inhibited by adrenolytic treatment. These findings appeared consistent with the predominant relaxation in the pig but constriction in the other species ; cerebral vessels in response to exogenously applied NE but are difficult to reconcile with the observations that the neurogenic relaxation is not attenuated by -antagonists and that the NE relaxation response is not potentiated by blockade of neuronal uptake. Both propranolol and cocaine have been shown to alter significantly the sympathetic-neurogenic and NE relaxation responses in a myogenically active rabbit vein Winquist and Bevan, 1981b ; . Therefore, our present results may reflect the involvement of either adrenergic and nonadrenergic nerve terminals or multiple transmitters associated with the adrenergic nerve terminal in the relaxation to TNS in porcine cerebral vessels. This latter hypothesis has been proposed for the neurogenic constrictor response in rabbit cerebral vessels Lee et al., 1980.
Nontuberculous mycobacterial infection with interferon gamma. A preliminary report. N Engl J Med 1994, 330: 1348-55. Squires KE, Brown ST, Armstrong D, Murphy WF, Murray HW: Interferon gamma treatment for Mycobacterium aviumintracellulare complex bacillemia in patients with AIDS. J Infect Dis 1992, 166: 686-7. Nathan CF, Kaplan G, Levis WR, Nusrat A, Witmer MD, Sherwin SA, Job CK, Horowitz CR, Steinman RM, Cohn ZA: Local and systemic effects of intradermal recombinant interferon- in patients with lepromatous leprosy. N Engl J Med 1986, 315: 6-15.
8 Wainwright, S.A., Biggs, W.D., Currey, J.D., and Gosline, J.M., Mechanical Design in Organisms, Princeton University Press, Princeton, 1982. 9 Thomson, M.W., "The AstroMesh deployable reflector, " IUTAM-IASS Symposium on Deployable Structures: Theory and Applications, 2000, pp.435-446. 10 Freeland, R.E., "Survey of deployable antenna concepts, " Large Space Antenna Systems Technology vol.1, NASA CP2269, 1982. 11 Guest, S.D., and Pelligrino, S., "A new concept for solid surface deployable antennas, " Acta Astronautica, 38, 2, 1996, pp.103-113. 12 Watanabe, H., Natori, M.C., Okuizumi, N., and Higuchi, K., "Floding of a Circular Membrane Considering the Thickness, " ISAS 14th Workshop on Astrodynamics and Flight Mechanics: A Collection of Technical Papers, 2004, pp.19-24. 13 Miyazaki, Y., and Uchiki, M., "A Numerical Method of Deployment Dynamics of Inflatable Tube, " AIAA-2002-1254, 2002. 14 Miyazaki, Y., "Wrinkle slack model and finite element dynamics of membrane, " International Journal for Numerical Methods in Engineering in press and dandelion.
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Table 4. PNH: clinical heterogeneity and proposed terminology from 40 ; . Predominant Clinical Features Hemolysis thrombosis Hemolysis thrombosis Purpura and or infection Purpura and or infection Thrombosis Size of PNH Clone Large Large Large Small Small and dapsone.
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Although MM is incurable with conventional and high-dose therapies, novel rationally based treatment strategies both directly targeting MM cells as well as the BM microenvironment offer great promise to improve patient outcome since these approaches have the potential to overcome drug resistance as illustrated in both preclinical and clinical studies.13, 16 In this report, we demonstrate that R-etodolac SDX-101 ; induces cytotoxicity in drug-sensitive and drug-resistant, including dexamethasone-, doxorubicin-, and bortezomib-resistant, MM cell lines and in primary patient MM cells, with IC50 of 0.22 to 1.06 mM. Importantly, we observe no cytotoxicity in PBMCs at drug concentrations of 0 to 2.5 mM, suggesting selective cytotoxicity against MM tumor cells. Since reductions in average lymphocyte counts have been observed in patients with CLL administered R-etodolac at steady-state blood levels of approximately 300 to 600 M, 22 the cytotoxicity observed in vitro against MM cell lines and primary patient samples at concentrations of 1 mM encouraging. Recently, attention has been focused on the antiproliferative activity of NSAIDs and their potential utility as chemopreventive and antitumor agents.60, 61 To date, however, the mechanisms underlying the effects of these drugs on cancer cells are undefined. Although inhibition of COX with subsequent decrease in prostaglandin production may explain part of the antitumor activity of certain NSAIDs, some of these drugs exert anti-inflammatory and antitumor activity in COX-independent manners.62, 63 For example, NSAIDs might inhibit nuclear factor- B NF- B ; signaling64-68 or p42 44 mitogen-activated protein kinase MAPK ; 69 or modulate and daptomycin.
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One cohort study47 reported bleeding in 1.5% 95% confidence interval [CI], 0.0 to 8.3% ; of children treated for deep-vein thrombosis DVT ; pulmonary embolism PE ; . However, many children were treated with suboptimal amounts of heparin compared to the target aPTT ; in this study, 47 and further studies are required to determine the true frequency of heparin-induced bleeding in children. There are only three case reports5254 of pediatric heparin-induced osteoporosis, and in two of them patients received concurrent steroid therapy. The third received high-dose IV heparin therapy for a prolonged period.55 However, given the convincing relationship between heparin and osteoporosis in adults, the long-term use of heparin in children should be avoided when other alternative anticoagulant agents are available. There have been a number of case reports56 60 of pediatric heparin-induced thrombocytopenia HIT ; in the literature, and the patients described in those case reports range in age from 3 months to 15 years. Heparin exposure in these cases ranged from low-dose exposure during heparin flushes used in maintaining the patency of venous access devices, to supratherapeutic doses given during cardiopulmonary bypass and hemodialysis. Some studies30, 61 have suggested that the frequency of HIT may be increased in children in the pediatric ICU PICU ; [2.3%] compared to children in a non-PICU setting. A high index of suspicion is required to diagnose HIT in children, as many patients in the neonatal ICU PICU who are exposed to heparin have multiple potential reasons for thrombocytopenia and or thrombosis. Danaparoid sodium Orgaran; Organon Inc; Roseland, NJ ; , hirudin, and argatroban are alternatives to heparin in the treatment of children with HIT.56, 57, 59, 62.
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Similar remarks apply to operational and quality control. Many of those interviewed reported a higher degree of satisfaction with projects conducted under the `Brusselsoriented' management that was the norm during the early years of Phare activity in this area. This satisfaction reflects several factors. Management is interesting primarily when it does not work. Management structures have caused delays due to confusion over responsibilities within countries, within the EC side and between national and EC organisations. The maturing Phare programme has experienced an inevitable increase in bureaucracy and consequent delays. These delays are taken into account in programme design through drafting of wide and flexible objectives and clear communication about the time required for the various steps between programme and project initiation. As a result, projects can usually be adjusted to reflect current needs, and often differ in specific detail from the early indications of activities planned for a specific programme. Programme management and project oversight require substantial resources, especially in such a complex situation. There does not appear to be a clear policy for providing these support resources at least, they are not usually comprehensively costed and resourced in Financial Memoranda. It is also debatable whether Phare should provide direct support for PMU activities some argue that countries should demonstrate their commitment towards the programme by financing the PMU. Those countries whose national governments provide such support and the close co-operation that goes with it ; have tended to do somewhat better though PMU support could simply be an additional symptom of underlying commitment rather than a direct success factor. On the negative side, however, some Polish projects were less successful precisely because there was no Ministry support for Phare; the PMU was required to function entirely outside the Ministry and deferasirox.
Medicine, Philadelphia, Pa J.A.B. ; . Received November 23, 1992; revision requested January 4, 1993; revision received March 3; accepted March 16. JAB. supported in part by Mental Retardation Research Center Core Grant P30 DH26979 from the National Institute of Child Health and Human Development. Address reprint requests toJ.S.M., Department of Radiology, Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104.
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