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Salmeterol and paroxetine: More evidencefor paradoxical medicine Lurie and Wolfe of Public Citizen recently suggested discussions have focused on incomplete disclosure, in the Lancet that Glaxo SmithKline (GSK) bundled we remain intrigued by the possibility that chronic post-trial data with trial data that effectively down- use of these drugs can produce an exacerbation of played the risk of death with use of salmeterol [1].
the underlying condition. In the case of paroxetine, Similar claims were recently levied against GSK only the phenomenon of serotonin withdrawal syndrome last year with respect to studies of paroxetine in has become increasingly recognized, and, as such children and adolescents in which data on suicide may have contributed to an increased risk of morbid- was not initially fully disclosed [2,3]. While these ity and mortality. In the case of salmeterol, although the beta-agonist may have directly produced some [2] Is GSK guilty of fraud? Lancet 2004;363(9425):1919.
of the witnessed sequelae, this putative risk may [3] Hay A. Questions about SSRI antidepressant drug regulation.
actually be less than what has been traditionally pre- [4] Murray JJ. Cardiovascular risks associated with beta-agonist sumed [4]. However, an additional explanation may therapy. Chest 2005;127(6):2283–5.
merit consideration—the idea that paradoxical ef- [5] Doux JD, Bazar KA, Lee PY, Yun AJ. Can chronic use of fects caused from interval withdrawal between anti-inflammatory agents paradoxically promote chronic times of administration may have caused autonomic inflammation through compensatory host response. MedHypotheses 2005;65(2):389–91.
remodeling and patient deaths. If so, beta-agonists [6] Yun AJ, Lee PY, Doux JD. Paradoxical inflammation revis- may potentially represent the fourth class of drugs ited: muraglitazar and cardiovascular risk. Med Hypotheses to show paradoxical responses that did not emerge initially with shorter term trials and that only be- [7] Yun AJ, Lee PY, Bazar KA. Paradoxical strategy for treating came revealed with chronic use. Each of these drug chronic diseases where the therapeutic effect is derivedfrom compensatory response rather than drug effect. Med categories has an entirely independent mechanism of action—we have previously discussed cyclooxygen-ase-2 inhibitors [5] and more recently the PPAR ago- nist muraglitazar [6]. Given such a consistent pattern of behavior for different types of medica- tions, we believe that this phenomenon warrants a more fundamental explanation—namely that we are witnessing paradoxical medicine in action [7], but as a detriment rather than as a benefit.
E-mail address: [email protected] (A.J. Yun) [1] Lurie P, Wolfe SM. Misleading data analyses in salmeterol (SMART) study. Lancet 2005;366(9493):1261–2. discussion Tumor-causing plant bacteria may infect animals Agrobacterium tumefaciens is a well known phytop- potential infectivity and oncogenetic flow between atogen; it is a soil bacterium that causes plant’s tu- Agrobacterium and animals in vivo [13].
mors disease called Crown Galls [1]. The microbe After 120 days of wild Agrobacterium injection contains a DNA plasmid called DNA Ti (tumor induc- on wounded Chrisantemum maximum, galls are ing) [7]. The bacterium is introduced in a wounded evident and pathologically confirmed. Then, we plant and the plasmid is then integrated in to the treated 40 SWISS mice, 8 mice each group, with cell plant genome and overproduces growth regula- A. tumefaciens cultured: Orally, SC and intraperi- tors (auxins and cytokines) that can initiate the toneal injections weekly shaved skin and topicated Crown Gall [6] disease. The growth regulators are with crown galls bacteria and only shaved as con- also present in mammal’s metabolism. Discovered trol. After 11 weeks, skin lesions and regionally by Erwin Smith (1854–1927) [2–5], we know now nodes are evident in 6–8 mice in shaved and topi- that the soil bacterium may jump Kingdoms [8]. In cated group. At optical microscope, H–E · 450, 2001, Vitaly Citovsky from the State University of lymphoid hyperplasia, neoangiogenesis and neofi- New York and colleagues found that the plant bacte- brinogenesis are confirmed. After 18 weeks, multi- rium was able to attach human cells in vitro and in- ple tumors and distant metastasis are seen, due to sert its DNA as it does with plant cells [9]. Recently, hyperplasia and mesenchymal metaplasia.
the soil microbe has been isolated from blood sam- Our observations confirmed in vivo the pathoge- ples of cancer patients [10–12]. We are studying the nicity of A. tumefaciens on mammals and we think

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