BRAF Mutation Status Concordance Between Primary Cutaneous Melanomas and Corresponding Metastases: A Review of the Latest Evidence. / Concordancia mutacional de BRAF entre melanoma primario cutáneo y sus correspondientes metástasis. Revisión de la evidencia actual.

The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). AIM: To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. METHODS: We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. RESULTS: There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). CONCLUSIONS: The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients.

Ichthyosis vulgaris: the filaggrin mutation disease.

Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.

[Accessory breast on the vulva]. / Mama ectópica vulvar.

We describe a 24-year-old woman with a subcutaneous swelling in the left inferior pubic region. Histology revealed ectopic breast tissue. Vulvar tumors are uncommon and the presence of ectopic breast tissue in this region is extremely rare. In these cases, patients usually consult for a mass that varies in size with hormonal changes, typically during pregnancy or breast-feeding, or that has associated neoplastic changes. In our patient, the mass had grown progressively with no identifiable underlying hormonal association or neoplasm. We therefore classified it as ectopic breast tissue presenting as a subcutaneous mass.

Lead acetate action on anaphylactic response of guinea pig smooth muscle.

Experiments were performed to evaluate lead acetate effects on the anaphylactic contraction in guinea pigs smooth muscles. Aortic rings from guinea pigs exposed to lead acetate developed an anaphylactic contraction significantly lower than the contraction induced by the antigen in controls. In the smooth muscle of the intestine, lead acetate did not modify the anaphylactic response. Lead induced immunosuppression of the anaphylactic response of aortic rings, whereas sodium acetate had no effect on the anaphylactic reaction of the guinea pig smooth muscle. The amplitude of the norepinephrine contraction was not modified by lead nor by sodium acetate.

Effect of stress on the Schultz-Dale reaction in guinea pig aorta.

The smooth muscle of thoracic aorta from guinea pig sensitized with egg albumin (EA) produced an anaphylactic contraction when it was exposed to EA. Experiments were performed to evaluate stress effects on the anaphylactic contraction in guinea pig aortic rings. Two types of stressors were used as immunosuppressor stimuli: physical restraint and shaking of the animals. Both stressors diminished the amplitude of the Schultz-Dale contraction in aortic rings from sensitized guinea pig. The shake stress stimulus interrupted several times during each session induced higher immunosuppression in animals in which the active sensitization and the stress sessions began the same day. Severe restraint stress, prior to active immunization, also suppressed significantly the anaphylactic response. The Schulz-Dale reaction in guinea pig aorta seems to be a valuable technique to study the stress effects on the anaphylactic response.

Vasoconstrictor effect of Cissus sicyoides on guinea-pig aortic rings.

1. The effect of the aqueous extract of Cissus sicyoides (CS) on isolated guinea pig aortic rings was studied. CS contracts the smooth muscle of the aorta in a dose-response relation. 2. The extract of CS increases the norepinephrine contraction in normal calcium and in solutions without calcium. 3. Lanthanum inhibits the contraction induced by CS. 4. The vasoconstrictor effect of CS was increased in solutions without calcium or with low calcium, which is an inverse calcium-dependent contraction. 5. Prolonged exposure to calcium-free solution did not abolish CS contraction. These contractions can be elicited repeatedly even after 6 hr of continuous exposure to calcium-free solutions. 6. Caffeine reduces contractile response induced by CS in normal calcium, as well as in solutions without calcium. 7. Our results support the idea that the aqueous extract of CS acts at the membrane level, increasing the calcium entry through the membrane as well as acting on the internal calcium deposits, possibly on the sarcoplasmic reticulum.

Actions of perezone on rat smooth muscle.

1. Perezone (PZN) on the in vitro intestinal smooth muscle of the rat relaxes the basal tonus of the smooth muscle, interrupts spontaneous activity and also blocks the contractile response induced by ACh, K+, and Ba2+; these actions are dose dependent. 2. Although in presence of small doses of PZN, the isometric contractile response to ACh was increased. 3. In calcium free intestinal smooth muscle preparation, the addition of PZN in low dose before Ca2+ increased the contractile effect of added calcium to the bath, but in presence of high doses of PZN the response to calcium was depressed. 4. PZN in calcium free preparations antagonized the contraction caused by adding barium. 5. These findings suggested that with small doses of PZN more availability of intracellular calcium free exist and/or an increase in excitability and/or an inhibition of AChase could coexist. 6. The responses of the intestine to high doses of PZN were possibly in part by blocking calcium entry. 7. The smooth muscle responses to PZN suggest that it has a membranal effect and/or an action on the internal calcium stores possibly increasing the intracellular calcium concentration. It is likely to be the expression of an increase in the intracellular calcium concentration above the levels normally reached that would be responsible for uncoupling of the smooth muscle, which would occur if the [Ca2+]i rises excessively.

Influence of formamide on the electrical and mechanical properties of the guinea pig ventricle.

1. Guinea pig papillary muscle in vitro upon exposure of Formamide (FMD) exerts a dose dependent positive inotropic effect. 2. The increase in tension developed by papillary muscle is associated with a marked decrease in the duration of the action potential. 3. The increase in extracellular calcium concentration does not modify the positive inotropic effect, but increases the duration of the action potential. 4. FMD markedly potentiate the increase in tension induced by caffeine 3 M suggesting a possible synergetic effect upon the release of Ca2+ ions from the S.R. 5. These experiments suggest that FMD increases the intracellular calcium concentration by exerting a direct action on intracellular calcium stores.