Interobserver reproducibility of histopathologic prognostic variables in primary cutaneous melanomas

Background: The prognosis for patients with localized primary cutaneous melanoma is known to depend principally on tumor thickness, and to a lesser extent on ulcerative state and Clark level. We have recently found in an analysis of 3661 patients that tumor mitotic rate (TMR) is also an important prognostic parameter, ranking second only to tumor thickness. However, few studies have assessed the accuracy and reproducibility with which these features of a melanoma are recorded by histopathologists.
Aim: To assess interobserver reproducibility of major pathologic prognostic parameters in cutaneous melanoma.
Methods: Single hematoxylin and eosin-stained slides of 69 dermally invasive primary cutaneous melanomas were circulated among six pathologists with differing experience in the assessment of melanocytic tumors. The observers independently determined the tumor thickness, Clark level of invasion, ulcerative state, and TMR for each lesion. Intraclass correlation coefficients and kappa scores for multiple ratings per subject were calculated.
Results: The intraclass correlation coefficients were 0.96 for tumor thickness and 0.76 for TMR. The kappa scores were 0.83 for ulcerative state and 0.60 for Clark level. These results indicated excellent agreement among the pathologists for measurements of tumor thickness, ulcerative state, and TMR and fair to good agreement for Clark level.
Conclusions: Appropriately trained and experienced histopathologists can assess prognostically important features of melanomas accurately and reproducibly. Given our recent finding of the significance of TMR in determining prognosis, it is important that this feature be assessed by a standardized method and documented for all primary cutaneous melanomas.

Neurally-derived nitric oxide regulates vascular tone in pulmonary and cutaneous arteries of the toad, Bufo marinus

In this study, the role of nitric oxide (NO) in regulation of the pulmocutaneous vasculature of the toad, Bufo marinus was investigated. In vitro myography demonstrated the presence of a neural NO signaling mechanism in both arteries. Vasodilation induced by nicotine was inhibited by the soluble guanylyl cyclase (GC) inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, and the NO synthase (NOS) inhibitor, N^ω-nitro-_L-arginine (_L-NNA). Removal of the endothelium had no significant effect on the vasodilation. Furthermore, pretreatment with N⁵-(1-imino-3-butenyl)-_L-ornithine (vinyl-_L-NIO), a more specific inhibitor of neural NOS, caused a significant decrease in the nicotine-induced dilation. In the pulmonary artery only, a combination of _L-NNA and the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(_8-37), completely blocked the nicotine-induced dilation. In both arteries, the vasodilation was also significantly decreased by glibenclamide, an ATP-sensitive K⁺ (K⁺_ATP) channel inhibitor. Levcromakalim, a K⁺_ATP channel opener, caused a dilation that was blocked by glibenclamide in both arteries. In the pulmonary artery, NO donor-mediated dilation was significantly decreased by pretreatment with glibenclamide. The physiological data were supported by NADPH-diaphorase histochemistry and immunohistochemistry, which demonstrated NOS in perivascular nerve fibers but not the endothelium of the arteries. These results indicate that the pulmonary and cutaneous arteries of B. marinus are regulated by NO from nitrergic nerves rather than NO released from the endothelium. The nitrergic vasodilation in the arteries appears to be caused, in part, via activation of K⁺_ATP channels. Thus, NO could play an important role in determining pulmocutaneous blood flow and the magnitude of cardiac shunting.

Influence of temperature on evaporative water loss and cutaneous resistance to water vapour diffusion in the orange-thighed frog (Litoria xanthomera)

We evaluated the effect of ambient temperatures between 25 and 43°C on the rate of evaporative water loss (EWL) in eight adult Litoria xanthomera (average body mass = 7.3 ± 0.6 g). Frogs were placed in a cylindrical chamber that permitted them to fully conceal their ventral surfaces using a water-conserving posture. Their EWL was 7.1 ± 0.7 mg g^–1 h^–1 at 25°C and reached 28.0 ± 2.5 mg g^–1 h^–1 at 43°C. Agar replicas of the frogs were used to evaluate boundary-layer resistances associated with the EWL measurements and, thus, to permit evaluation of cutaneous resistance to vapour diffusion (r_c) in live frogs. The r_c of L. xanthomera was stable over the temperature range of 25–35°C, averaging about 28 s cm^–1, and then declined stepwise with ambient temperatures above 37°C. The highest r_c recorded for each individual over the range of temperatures studied averaged 32.0 ± 1.2 s cm^–1. The thermolabile nature of r_c demonstrates a well developed thermoregulatory control of EWL in this species, a trait very similar in pattern and extent to that previously measured in the closely related Litoria chloris.

Postauricular cutaneous mastoid fistula

Postauricular cutaneous mastoid fistula is a rare condition. The cutaneous mastoid fistula is a very rare complication of chronic suppurative otitis media. The fistula tracts are typically difficult to manage because of the surrounding necrotic skin edges. We describe an unusual case of a postauricular cutaneous mastoid fistula and outline the surgical technique used for closure.

Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction

Background: Contact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed-type hypersensitivity (DTH) reactions, affords immunity against tumor cells and microbes. CS response is a self-limiting reaction, and interleukin (IL)-10 is considered to be a natural suppressant of cutaneous inflammatory response. Recently, it has been demonstrated that major depression is related to activation of the inflammatory response and elevation of some parameters of cell-mediated immunity. It has been suggested that such activation of the immune system may play a role in etiology of depression. If this immunoactivation is involved in etiology of depression, one would expect that antidepressant agents may have negative immunoregulatory effects. To the best of our knowledge, the effect of antidepressants on contact hypersensitivity has not been studied.

Methods: The aim of the present study was to establish the effect of prolonged desipramine or fluoxetine treatment on CS reaction to picryl chloride.

Results: Antidepressants significantly suppressed CS reaction, fluoxetine by 53% whereas desipramine by 47% compared to positive control. Moreover, desipramine and fluoxetine decreased relative weight of auxillary lymph nodes. Desipramine decreased also relative weight of inguinal lymph nodes and spleens whereas desipramine and fluoxetine increased production of IL-10 in comparison to positive control.

Conclusion: The observed effect of antidepressant drugs on CS reaction is consistent with the hypothesis that T-cell mediated immunity is targeted by antidepressants.

Mortality and use of the auxiliary score in extensive toxic epidermal necrolysis patients admitted to an adult burns referral centre

 Background: Toxic epidermal necrolysis (TEN) is a rare but fatal condition characterised by cutaneous exfoliation of the dermoepidermal layer and mucosal surfaces. Extensive TEN with epidermal detachment >30% of the total body surface area has been associated with a high mortality. Objective: This study aims to evaluate factors associated with mortality in extensive TEN. In the absence of data to qualify scoring systems such as SCORTEN, this study also aims to evaluate the use of the auxiliary score as a tool for calculating expected mortality. Methods: A retrospective chart review of all patients presenting to our burns service with extensive TEN was undertaken. Application and evaluation of the auxiliary score was also undertaken for this patient population. Results: In extensive TEN, age and delay in admission to a burns centre were factors associated with mortality. Applying the auxiliary score to our patient population, there were no significant differences between expected mortality and observed mortality. Conclusion: Mortality was associated with age and delay in definitive treatment in extensive TEN. Whilst SCORTEN is the gold standard prognostic tool for patients with TEN, in the absence of SCORTEN values, the auxiliary score provides an alternative scoring system to evaluate expected mortality.

Diagnosis and management of oral leishmaniasis--case series and literature review

The worldwide prevalence of leishmaniasis is increasing because of ecologic changes and increased medical profession awareness. Furthermore, solitary cases have been recently reported in Western countries. The authors describe the epidemiology, mode of transmission, and diagnosis of leishmaniasis and present 4 oral cases treated with systemic, localized, or combined therapy. The authors suggest that clinicians should maintain a high index of suspicion for atypical, resistant, oral and perioral lesions in individuals with a history of traveling in certain geographic regions. After diagnosis, treatment should be determined jointly by experts from the fields of oral and maxillofacial surgery, oral medicine, and dermatology based on leishmaniasis species and clinical presentation.

Flight altitude of trans-Sahara migrants in autumn: a comparison of radar observations with predictions from meteorological conditions and water and energy balance models

Radar observations on the altitude of bird migration and altitudinal profiles of meteorological conditions over the Sahara desert are presented for the autumn migratory period. Migratory birds fly at an average altitude of 1016 m (a.s.l.) during the day and 571 m during the night. Weather data served to calculate flight range using two models: an energy model (EM) and an energy-and-water model (EWM). The EM assumes that fuel supply limits flight range whereas the EWM assumes that both fuel and water may limit flight range. Flight ranges estimated with the EM were generally longer than those with the EWM. This indicates that trans-Sahara migrants might have more problems balancing their water than their energy budget. However, if we assume fuel stores to consist of 70% instead of 100% fat (the remainder consisting of 9% protein and 21% water), predicted flight ranges of the EM and EWM largely overlap. Increased oxygen extraction, reduced flight costs, reduced exhaled air temperature, reduced cutaneous water loss and increased tolerance to water loss are potential physiological adaptations that would improve the water budget in migrants. Both the EM and EWM predict optimal flight altitudes in agreement with radar observations in autumn. Optimal flight altitudes are differently predicted by the EM and EWM for nocturnal spring migration. During spring, the EWM predicts moderately higher and the EM substantially higher flight altitudes than during autumn. EWM predictions are therefore in better agreement with radar observations on flight altitude of migrants over the Negev desert in spring than EM predictions.