The implementation of amplitude-integrated electroencephalography (aEEG) has enhanced the neurological monitoring of critically ill infants. Limited channel leads are applied to the patient and data are displayed in a semilogarithmic, time-compressed scale. Several classifications are currently in use to describe patient tracings, incorporating voltage criteria, pattern recognition, cyclicity, and the presence or absence of seizures. In term neonates, aEEG has been used to determine the prognosis and treatment for those affected by hypoxic-ischemic encephalopathy, seizures, meningitis and even congenital heart disease. Its application as inclusion criteria for therapeutic hypothermia remains controversial. In preterm infants, normative values and patterns corresponding to gestational age are being established. As these standards emerge, the predictive value of aEEG increases, especially in the setting of preterm brain injury and intraventricular hemorrhage. The sensitivity and specificity of aEEG are enhanced by the display of a simultaneous raw EEG, which aids interpretation. Caution must be taken when using and interpreting this tool in conjunction with certain medications and in the setting of less experienced staff. Continuing efforts at developing software that can aid seizure detection and background classification will enhance the bedside utility of this tool.
Caspases play a key role in the apoptotic pathway by virtue of their ability to cleave key protein substrates within the dying cell. Caspases are produced as inactive zymogens, and need to become proteolytically processed in order to become active. A key executioner caspase, caspase-3, has previously been found to exist in both the cytosol and the mitochondria. At the mitochondria, caspase-3 is associated with both the inner and outer mitochondrial membranes, where it interacts with heat shock proteins Hsp60 and Hsp10. Like caspase-3, a small portion of the p53 tumor suppressor protein is localized to mitochondria, particularly after genotoxic stress. p53 interacts with various members of the Bcl2 family at the mitochondria, and this interaction is key to its ability to induce apoptosis. In this study, we sought to determine the identity of other mitochondrial p53-interacting proteins. Using immunoprecipitation from purified mitochondria followed by mass spectrometry we identified caspase-3 as a mitochondrial p53-interacting protein. Interestingly, we find that tumor-derived mutant forms of p53 retain the ability to interact with mitochondrial caspase-3. Further, we find evidence that these mutant forms of p53 may interfere with the ability of procaspase-3 to become proteolytically activated by caspase-9. The combined data suggest that tumor-derived mutants of p53 may be selected for in tumor cells due to their ability to bind and inhibit the activation of caspase-3.
Differentiating melanocytic hyperplasia (MH) on photodamaged skin from junctional lentiginous melanocytic proliferations (JLMP), early evolving melanoma in situ (MIS), or the periphery of a lesion of MIS on staged excision can be challenging. Although previous cross-sectional studies have elucidated important criteria for distinguishing MH on photodamaged skin from more concerning lesions, this study highlights a technique to treat JLMP and MIS with staged mapped excision and baseline scouting biopsies of adjacent nonlesional photodamaged skin to assist in determination of surgical margin clearance. Additionally, we compare the lesional and photodamaged control biopsies from the same patient to evaluate relevant histologic criteria that may be used to distinguish MH in photodamaged skin from JLMP/MIS, while minimizing confounding factors. There was a statistically significant difference (P ≤ 0.05) found for melanocyte density, irregular melanocyte distribution, melanocyte clustering, follicular infundibulum involvement, and nesting. However, criteria such as nesting, epithelioid cells and melanocyte clustering were seen in both photodamaged skin and MIS. These findings underscore the fact that histologic features of photodamaged skin can overlap with the histopathological features of MIS. Of all of the criteria evaluated, melanocytic density was the most objective histologic criterion and did not show overlap between the sun-damaged and JLMP/MIS groups. K E Y W O R D S atypical junctional melanocytic hyperplasia, lentigo maligna, melanoma in situ, scouting biopsy, slow Mohs, staged excision How to cite this article: Speiser J, Tao J, Champlain A, et al. Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies.
Introduction:Burn scars cause cosmetic disfigurement and psychosocial distress. We present two Fitzpatrick phototype (FP) III patients with burn scars successfully treated with combination pulsed dye laser (PDL) and non-ablative fractional lasers (NAFL).Case 1:A 30-year-old, FP III woman with a history of a second-degree burn injury to the bilateral arms and legs affecting 30% body surface area (BSA) presented for cosmetic treatment. The patient received three treatments with 595 nm PDL (7 mm, 8 J, 6 ms), six with the 1550 nm erbium:glass laser (30 mJ, 14% density, 4–8 passes) and five with the 1927 nm thulium laser (10 mJ, 30% density, 4–8 passes). Treated burn scars improved significantly in thickness, texture and colour.Case 2:A 33-year-old, FP III man with a history of a second-degree burn injury of the left neck and arm affecting 7% BSA presented for cosmetic treatment. The patient received two treatments with 595 nm PDL (5 mm, 7.5 J, 6 ms), four with the 1550 nm erbium:glass laser (30 mJ, 14% density, 4–8 passes) and two with the 1927 nm thulium laser (10 mJ, 30% density, 4–8 passes). The burn scars became thinner, smoother and more normal in pigmentation and appearance.Discussion:Our patients’ burn scars were treated with a combination of PDL and NAFL (two wavelengths). The PDL targets scar hypervascularity, the 1550 nm erbium:glass stimulates collagen remodelling and the 1927 nm thulium targets epidermal processes, particularly hyperpigmentation. This combination addresses scar thickness, texture and colour with a low side effect profile and is particularly advantageous in patients at higher risk of post-procedure hyperpigmentation.Conclusion:Our cases suggest the combination of 595nm PDL plus NAFL 1550 nm erbium:glass/1927 nm thulium device is effective and well-tolerated for burn scar treatment in skin of colour.
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