Single versus multiple primary melanomas: old questions and new answers.

BACKGROUND: In patients with multiple primary melanomas (MPM), mean tumor thickness tends to decrease from the first melanoma to the second melanoma, and prognosis may be improved compared with the prognosis for patients who have a single primary melanoma (SPM). In this study, the authors compared the clinicopathologic features of patients with MPM and SPM to better characterize the differences between these 2 groups and to determine whether or not there is an inherent difference in tumor aggression. METHODS: In total, 788 patients with melanoma who were enrolled prospectively in the Interdisciplinary Melanoma Cooperative Group database from 2002 to 2008 were studied. Patients with SPM and with MPM were compared with regard to clinical and primary melanoma characteristics. RESULTS: Of 788 patients with melanoma, 61 patients (7.7%) had 2 or more primary melanomas. The incidence of developing a second primary melanoma 1 year and 5 years after initial melanoma diagnosis was 4.1% and 8.7%, respectively, and most of the risk accumulated within the first year. The incidence of MPM was greater in patients aged ≥60 years than in those aged ≤60 years. The absence or presence of mitosis and other tumor characteristics did not differ significantly between patients with SPM and patients with MPM (P = .61). CONCLUSIONS: No difference was observed in the presence or absence of mitoses, a marker of tumor proliferation, in SPM and MPM. Because it has been demonstrated that the presence of mitosis is a powerful prognostic marker, the current findings suggested that the tumors behave similarly in patients with SPM and patients with MPM. The authors concluded that differences in tumor thickness and prognosis between SPM and MPM more likely are caused by factors other than tumor biology, such as increased surveillance.

Multiple human papillomavirus-16 associated digital squamous-cell carcinomas in an immunocompetent woman with prior human papillomavirus-related genital carcinoma.

High-risk subtype human papillomavirus (HPV) infection, which is known to contribute to the oncogenesis of anogenital squamous-cell carcinoma (SCC), is detected in the majority of digital SCCs. Evidence suggests a genital-digital route of transmission of high-risk HPV, and most HPV-related digital SCCs occur near the nail unit in immunocompetent adults. As early HPV-related SCC commonly appears as a verrucous periungual papule, a biopsy should be considered if such a lesion persists or occurs in an individual who is likely to inoculate their digits with high-risk HPV from digital-genital contact with themselves or sexual partners. We present a 60-year-old woman, who has a personal history of vulvar and cervical SCC and an appreciable disease burden from SCCs that involved five digits of her hands.

Skin biology.

The development of topical drug delivery systems has recently gained significant interest due to the ease of administration and lesser risks of systemic toxicity. The development of these new technologies utilizes the properties of the structure and function of the skin. The stratum corneum plays the largest role in affecting drug permeation, as the corneocytes and lipid matrix in this layer effectively prevent the diffusion of large molecules. In this review, we introduce the structure and function of the skin as it relates to topical drug delivery.

The history of the capillary wall: doctors, discoveries, and debates.

In 1628, William Harvey provided definitive evidence that blood circulates. The notion that blood travels around the body in a circle raised the important question of how nutrients pass between blood and underlying tissue. Perhaps, Harvey posited, arterial blood pours into the flesh as into a sponge, only then to find its way into the veins. Far from solving this problem, Marcello Malpighi's discovery of the capillaries in 1661 only added to the dilemma: surely, some argued, these entities are little more than channels drilled into tissues around them. As we discuss in this review, it would take over 200 years to arrive at a consensus on the basic structure and function of the capillary wall. A consideration of the history of this period provides interesting insights into not only the central importance of the capillary as a focus of investigation, but also the enormous challenges associated with studying these elusive structures.

Endothelial biomedicine: its status as an interdisciplinary field, its progress as a basic science, and its translational bench-to-bedside gap.

The endothelium, a layer of endothelial cells lining the luminal surface of all blood vessels, functions as a highly metabolically active organ spatially distributed throughout the body. Despite enormous advances in our understanding of endothelial cell biology, little awareness of this organ reaches clinical practice. The present study aims to document the extent and scope of the bench-to-bedside gap in endothelial biomedicine, and to offer hypotheses to explain the gaping chasm. A PubMed search using keywords "endothelial cells" and "endothelium" yielded over 90,000 publications, increasing exponentially over the past decade. A Scirus search without date restriction returned journal results for the endothelium not greatly fewer than for the epithelium. A survey of representative vascular biology meetings revealed a high percentage of talks related to the endothelium. The number of grants awarded by the National Institutes of Health for studies in endothelial cell biology continues to steadily increase. At the bedside, however, few clinicians give consideration to the health of the endothelium. A survey of the major medical textbooks revealed a paucity of index entries for "endothelial cells" or "endothelium." The endothelium does not offer itself for inspection, palpation, percussion, and/or auscultation. No convenient blood tests measure endothelial function. The authors propose to explain the bench-to-bedside gap in endothelial biomedicine as a function of (1) historical constraints, (2) the unseen and diffuse nature of the cell layer, (3) the complexity of the system, and (4) its adaptability. Until the bench-to-bedside gap closes, the enormous potential of the endothelium as a diagnostic, preventive, and therapeutic target will remain largely untapped.

Boron binding with the quorum sensing signal AI-2 and analogues.

[reaction: see text] The unstable bacterial metabolic product, DPD, and the related natural product, laurencione, are shown to have a high affinity for borate complexation, through the hydrated analogue. The boron complex of DPD is Vibrio harveyi AI-2, an interspecies quorum sensing signal in bacteria, and an affinity column with a borate resin is effective in providing the first method for concentrating and purifying V. harveyi AI-2 from the biosynthetic product.