Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.

The coordinator attrition problem in the United States: myth or reality?

Excessive attrition among organ procurement coordinators has been suspected problem for many years. In 1994 the United Network for Organ Sharing undertook a procurement coordinator attrition study. Initially, focus groups were conducted in conjunction with the 1994 North American Transplant Coordinators Organization's annual meeting. In 1996, 69 executive directors from organ procurement organizations were surveyed on the subject of procurement coordinator attrition. Thirty-five executive directors responded, resulting in a 51% response rate. The UNOS procurement coordinator attrition study explored actual attrition rates, relationships of certain demographic factors to attrition rates, economic impact of attrition on the organizations, and various job tenure issues. The period under study was January 1, 1990 through December 31, 1993. Results did not demonstrate an industry-wide attrition problem. Additionally, the study revealed no enduring attrition problem in any single organization, and some organizations were found to have no attrition during the entire study period.

Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies.

The Lung Cancer Study Group recently completed a double-blind adjuvant immunotherapy study, in which 473 patients with resected stage I non-small-cell lung cancer were randomized to either intrapleural BCG or placebo. The study showed no significant difference in time to first recurrence for the two treatment arms. The present report analyzes the distribution of the anatomic site of first relapse and relates this to TN staging, histology, and other appropriate risk factors. The overall rate of recurrence is significantly higher for increasing TN status and for nonsquamous as compared to squamous-cell type. However, the distribution of site of recurrence does not, in general, change with increasing TN status or with histology. Approximately 65% to 75% of the first recurrences involve distant sites, with the brain being by far the most common, regardless of TN staging or histology. The implications of this for planning future studies is discussed.