PDT is an effective treatment for EMPD. Recurrence rates are high with topical ALA-PDT, but comparable with standard therapies. Topical ALA-PDT causes little scarring and is preferred for superficial disease and mucosal surfaces. Systemic Photofrin(R)-PDT may be better suited for bulky disease. While further studies are indicated, PDT is well tolerated and appears to be a useful therapy for EMPD.

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Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the In septic shock, a severe underlying infection triggers a cascade of events leading to intractable hypotension, multiple organ system failure, and high mortality rates (1, 2). The infecting organism stimulates the release of cytokines and vasoactive mediators that ultimately results in vascular smooth muscle relaxation and consequent hypotension. Because several bacterial toxins and a redundant series of receptors and cytokines participate in this process, attempts at therapeutic intervention aimed at a single toxin or mediator have failed (2). Nitric oxide (NO), a potent vasodilator synthesized by nitric oxide synthase (NOS) (3-5), is a key mediator generated late in the sepsis pathway leading to hypotension (6-10). Therefore, NO represents a potentially important target for therapy.In two recent studies, MacMicking et al. (11) and Wei et al. (12) generated mice carrying a disrupted inducible NOS (iNOS) gene. The resistance of these mice to endotoxininduced death underscores the importance of NO in septic shock. Since the overabundance of NO produced during septic shock is generated through the inducible NO pathway, it wouldThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. be beneficial to selectively inhibit this pathway. In fact, investigators have suggested that nonselective inhibition of both the inducible and constitutive (endothelial-cell derived) NO pathways in the treatment of septic shock may be detrimental (9, 13).Transforming growth factor (TGF) (31, which is involved in a number of physiologic processes (14,15), antagonizes the effects of interleukin 1( and tumor necrosis factor a (16-18), two cytokines produced early in the septic shock cascade. TGF-(31 inhibits iNOS gene expression in cultured macrophages (by reducing mRNA stability and translation) (19,20) and in cultured vascular smooth muscle cells (by decreasing the rate of transcription) (21). Because of the critical role of vascular smooth muscle cells in the regulation of vascular tone and the ability of TGF-,B1 to inhibit iNOS after its induction by cytokines in vitro (21), we hypothesized (i) that TGF-,B1 could inhibit iNOS gene expression and protein production after its induction in vivo and (ii) that TGF-131 could block the hypotension of septic shock. We found that TGF-,B1 inhibited iNOS production and arrested hypotension, even after its initiation, in a rat model of septic shock produced by endotoxin. TGF-31 did not increase mean arterial pressure in control rats (not receiving endotoxin), and it did not decrease endothelium-derived constitutive NOS (ecNOS) mRNA in rats receiving endotoxin. These studies suggest that TGF-j31 is an inhibitor of iNOS but not ecNOS during endotoxic shock in vivo. They also suggest that TGF-,B1 may be of benefit in the ...

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Histologically, mesothelioma may resemble a primary adnexal neoplasm, metastatic adenocarcinoma, or angiosarcoma. Immunohistochemistry can clarify the diagnosis. Clinicians should be aware of the varied presentations of mesothelioma, as cutaneous presentations are becoming increasingly common.