[The role of new molecular tests in the diagnosis of melanoma in a setting of congenital nævus in an infant]. / Apport des nouveaux tests moléculaires dans le diagnostic d'un mélanome sur nævus congénital chez un nourrisson.

INTRODUCTION: Congenital and infantile melanomas are extremely rare. We report a case of a child presenting at birth with a giant congenital nevus complicated by melanoma and on long-term follow-up with exploration using new immunohistochemistry and molecular biology tools. OBSERVATION: A new-born girl presented at birth with a large congenital cervico-mandibular tumour with para-pharyngeal extension and underlying osteolysis. At 7 months, histology and immunohistochemistry of the operative specimen revealed nodules with atypical features (mitotic figures, necrosis and positive expression of KI67 and P53 in approximatively 50 % of the melanocytic nuclei). A diagnosis was made of infantile melanoma associated with congenital nevi. Repeated surgery and monitoring (clinical and imaging) were performed. At the age of 7 years, as there was no evidence of metastatic lesions, further analyses were performed on the initial operative specimen. Investigation of transcription factor expression using immunohistochemistry, comparative genomic hybridization and histology-guided mass spectrometry, although suspect, did not in itself support a diagnosis of melanoma. Finally, at the age of 7 years, hepatic and pulmonary metastases were reported. Despite combined immunotherapy with ipilimumab and nivolumab, the child died 5 months later. CONCLUSION: This case illustrates the complexity of diagnosis of infantile melanoma and the risk of metastatic involvement long after the initial diagnosis. Diagnosis may be difficult and necessitates expert advice and the application of several recent methods to reach a conclusion and initiate appropriate treatment.

[Multiple hypochromic or achromic macules in children and risk of tuberous sclerosis]. / Macules hypochromiques ou achromiques multiples de l'enfant et risque de sclérose tubéreuse de Bourneville.

AIM: To describe in a large paediatric cohort the characteristics of hypopigmented and depigmented (hypochromatic and achromic) macules with no clear diagnosis but potentially evocative of tuberous sclerosis (TS). PATIENTS AND METHODS: This was a retrospective multicentre study performed between 2010 and 2017 at a reference centre for rare skin diseases; it included all children consulting for hypochromic and achromic macules. A descriptive analysis was made of the characteristics of macules with no clear diagnosis, enabling them to be classified in three secondary groups: TS certain, TS ruled out, TS uncertain. RESULTS: Of the 3300 children seen during this 7-year period 7,265 were consulting for hypochromic or achromic macules, with no clear diagnosis in 18 cases: 7 girls and 11 boys of median age at 7.21 years (range: 4 months to 16 years and 7 months). The lesions were congenital in 7 cases. The number of macules varied, with over 20 in some cases. The majority were in the form of ash-leaf spots, followed by the oval form. Two children were diagnosed at clinical examination, and 16 underwent it is not examinations, resulting in a diagnosis of certain ST in 6 of these cases. No particular characteristics of the macules appeared to guide the clinical examination towards ST or isolated lesions. Café-au-lait spots were more frequent in the group in which ST was ruled out than in the other two groups: 67% vs. 33% and 33%. Neurologic involvement was more common in children with certain or uncertain ST than in children in whom ST was ruled out (83% and 67% vs. 11%). CONCLUSION: No identified characteristics of stains enabled the clinical examination to confirm or rule out tuberous sclerosis. Screening for acute any signs of ST is essential. Diagnostic efficacy is enhanced by additional exams.

Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-programmed cell death-1 (PD-1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17-year-old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at a dose of 2 mg kg-1 , every 3 weeks. Parallel therapeutic efficacy of anti-PD-1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti-PD-1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.

Stay in NICU and infantile haemangioma development.

BACKGROUND: Infantile haemangiomas (IHs) are more frequent in low birth weight babies, especially premature. OBJECTIVE: To compare the characteristics of infants with IHs who stayed in neonatal intensive care unit (NICU) vs. those with IHs who did not. METHODS: Prospective observational multicentric study. Consecutive infants consulting for IHs in two departments of paediatric dermatology were included and a questionnaire specifically designed was filled for each patient. To identify factors associated with hospitalization in NICU vs. no hospitalization in NICU, we conducted univariate logistic regression analyses. RESULTS: A total of 210 infants with 323 IHs were included (56 boys, 154 girls, F/M sex ratio 2.75/1); 27 stayed in NICU, whereas 183 did not. Limbs involvement and multiple IHs were more frequent in NICU infants. Similarly, infants who had stayed in NICU had an earlier onset of their IH. Multiple IH was more frequent in infants with a history of congenital onset of IH. CONCLUSION: Infants staying in NICU and those with congenital lesion are at risk for specific type and involvement of their IH and should be early addressed to a dermatologist in case of suspicion of IH to provide them an early diagnosis and to start a treatment if necessary as soon as possible.

Treatment of port wine stains with pulsed dye laser and topical timolol: a multicenter randomized controlled trial.

BACKGROUND: Neoangiogenesis occurs within days following laser treatment of port wine stains (PWS), and plays a central role in treatment failures. Topical use of timolol can significantly reduce the production of vascular endothelial growth factor in vitro, and in animal models. OBJECTIVES: The aim of this study was to assess the efficacy of topical timolol in combination with pulsed dye laser (PDL) treatment, compared with PDL alone, for treating PWS. METHODS: This was a prospective multicenter controlled trial performed in children with PWS of the face who had not previously received laser treatment. After randomization, one group was treated with PDL alone, and the other with PDL followed by twice daily applications of timolol gel. Three laser sessions were performed at 1-month intervals with fixed parameters. The evaluation was performed on standardized pictures by two independent physicians blinded to the treatment received. The primary endpoint was marked or complete improvement of the PWS [Investigator Global Assessment (IGA) 3 or 4] 1 month after the third session. RESULTS: Twenty-two children were included. Two patients were lost to follow-up. There was no difference in the success rate between the two groups (IGA 3 or 4 observed in one of 10 patients and two of 12 patients, for PDL alone, and for PDL associated with topical timolol, respectively; P = 1·0). No side-effect related to the application of topical timolol was observed. CONCLUSIONS: The addition of timolol gel for preventing neoangiogenesis failed to significantly improve the efficacy of PDL treatment of PWS.

[What's new about infantile hemangiomas?]. / Quoi de neuf dans les hémangiomes infantiles ?

Infantile hemangioma is the most common vascular tumor of childhood. This benign tumor appears during the first weeks of life, grows during the first months (endothelial proliferation) and then involutes slowly and spontaneously until resolution (possibly with sequelae) which is observed after several years. Although they are always benign tumors, infantile hemangiomas can cause complications. Regarding their location or size, infantile hemangiomas can be life or function-threatening. They are also painful when ulcerated and can cause permanent disfigurement or long-term adverse psychological consequences. Since 2008 and the serendipitous discovery of the efficacy of propranolol in the treatment of infantile hemangiomas, systemic propranolol therapy has been widely used, with a very interesting benefits/risks balance. It has progressively superseded general corticosteroid therapy. A Compassionate Use Program (CUP) for systemic propranolol therapy has been developed in France and represents nowadays the first-line use for the vast majority of French prescribers.

[Asymptomatic neonatal neurocutaneous melanosis]. / Mélanose neurocutanée néonatale asymptomatique.

Giant congenital nevi in 1% of cases are associated with anomalies of the central nervous system, which are characteristic of neurocutaneous melanosis. When neurocutaneous melanosis becomes symptomatic, it is associated with a poor prognosis. With recommended neonatal screening, asymptomatic neonatal cases are being discovered more frequently. On the basis of this observation, we consider various aspects of this association.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

Evaluación química y organoléptica del ensilaje de maralfalfa (Pennisetum sp) más yuca fresca (Manihot esculenta) / Chemical and organoleptic evaluation of maralfalfa silage (Pennisetum sp) plus fresh cassava (Manihot esculenta)

Objetivo. Evaluar la composición química y características organolépticas del ensilado de maralfalfa (Pennisetum sp.) más diferentes proporciones de yuca fresca (Manihot esculenta). Materiales y métodos. Se evaluaron 4 tratamientos (T) de ensilaje de maralfalfa más diferentes proporciones de yuca fresca: 0% (Tratamiento 1, Control), 5% (Tratamiento 2), 10% (Tratamiento 3) y 15% (Tratamiento 4). Se determinaron las proporciones de fibra detergente neutro (FDN), fibra detergente ácido (FDA), lignina, fracción de materia seca (MS), extracto etéreo (EE), cenizas y proteína bruta (PB). Además, se evaluaron las características organolépticas. Para evaluar las variables nutricionales del ensilaje, se utilizó un diseño completamente aleatorizado y los datos se analizaron a través de un análisis de varianza y la prueba de polinomios ortogonales. Para la evaluación del consumo y variables organolépticas se utilizaron 20 novillas, a las que se les ofreció 30 kg de ensilaje por cada tratamiento, analizando los resultados a través de estadística descriptiva. Resultados. Las variables nutricionales mostraron diferentes tipos de tendencias polinómicas. La MS y EE tuvieron comportamiento lineal, la lignina cuadrático y la PB, cenizas, FDN, FDA y pH comportamiento cúbico. Las características organolépticas para T3 y T4, fueron excelentes. El consumo promedio de T1, T2, T3 y T4 fue 4.66, 4.42, 4.58 y 4.74 kg, respectivamente. Conclusiones. La inclusión de raíz de yuca contribuyó favorablemente en la calidad nutricional del ensilaje de maralfalfa y sus características organolépticas.

Cytophagic histiocytic panniculitis after H1N1 vaccination: a case report and review of the cutaneous side effects of influenza vaccines.

Cytophagic histiocytic panniculitis (CHP) is a rare disease mostly caused by viral infections and/or lymphoproliferative diseases. We describe a case of CHP associated with H1N1 vaccine during the winter 2009-2010 vaccination campaign and discuss the cutaneous side effects of influenza vaccines. A 6-year-old child presented with inflammatory subcutaneous nodules, which had appeared 1 month after the first injection of H1N1 vaccine and 1 week after the second injection. There was no history of recent infection. The skin lesions spontaneously disappeared without scarring. In CHP the abnormal cytokine secretion from neoplastic or reactive T cells promotes monocyte-macrophage activation and haemophagocytosis. Vaccination is not a common cause of CHP, but it seems possible that, as in infectious diseases, reactive T cells to the vaccine antigen could trigger CHP.

[Evaluation of dermatology consultations in a prospective multicenter study involving a French teaching hospital]. / Evaluation de l'activité hospitalière de consultation liaison en dermatologie à partir d'une enquête prospective multicentrique au sein d'un CHU français.

BACKGROUND: Dermatologic practice occurs mainly in the inpatient setting. This activity is also referred to as consultation-liaison dermatology (DL). STUDY AIMS: To describe and quantify this dermatologic consultation activity in a hospital setting in Marseille; to establish the relationship between presumptive dermatologic diagnosis and the final diagnosis retained by the dermatologist. PATIENTS AND METHODS: This was a prospective study carried out three university teaching hospitals and an army teaching hospital for a period of three months. Of particular note is that services requesting consultation were asked in each case to supply their presumptive dermatologic diagnosis at the time consultation was requested. The statistical analysis was carried out using the SPSS 15.0 software package. A total of 352 notes for dermatology consultations were requested and 336 of these were evaluated, representing 5% of all consultations activities within these dermatology departments over this period. Ninety-three percent of the consultations were established by dermatology interns and 86% of consultations took place within 24 hours following their demand. Thirty-one percent of consultations were for patients aged over 75 years and 61% of the requests emanated from medical departments. The main requests concerned elementary lesions, symptoms or non-specific eruptions (56%), recommendations for treating infectious skin diseases (17%), inflammatory diseases (7%) and skin cancer (5%), recommendations for nursing care (14%) and the remainder for various reasons. No diagnosis was established in the face of of non-specific signs in 26.4% of cases. The diagnosis made by dermatologists differed from that initially evoked by the non-specialists in 56.3% of cases. Initial dermatological diagnosis was least successful regarding drug-induced eruption and skin cancer. The majority of consultations (57%) were considered unrelated to the patients' previous histories or reasons for admission. Twenty-six percent of patients were prescribed systemic therapy and 80% were prescribed topical treatment, of whom a quarter received dressings. Therapeutic acts were prescribed for 40% of the patients. Five percent of the patients were hospitalized after their consultation at the respective dermatology department and 14% were referred for outpatient dermatology consultations. DISCUSSION: This study confirms a number of expected features: common dermatological diseases are often not recognized or is misdiagnosed by non-dermatologists, excessive bedside consultations and very particular profiles of the common diagnoses in this activity (nursing care, drug-induced eruption, fungal infections). Less predictable were the absence of links between the requests and the moderate impact of the activity on hospitalization. CONCLUSION: The study of these dermatologic diagnoses in an in-patient setting suggests a number of approaches to more successful management of these consultations.

[Tubercular fibrosing conjunctivitis associated with facial cutaneous tuberculosis]. / Conjonctivite fibrosante tuberculeuse au cours d'une tuberculose cutanée faciale.

BACKGROUND: Tuberculous conjunctivitis has been described only rarely during the course of lupus vulgaris. We report a case of hemifacial cutaneous tuberculosis, diagnosed as atypical lupus vulgaris, associated with homolateral fibrosing tuberculous conjunctivitis. PATIENTS AND METHODS: An 83-year-old woman presented inflammatory conjunctivitis without bullous involvement in the left eye leading to corneal neovascularisation, symblepharons and ptosis. Erythematous and atrophic papules were seen on the left side of the face. Biopsy of the skin and conjunctiva revealed a tuberculoid granulomatous infiltrate. Bacterial culture and PCR were both positive for Mycobacterium tuberculosis. DISCUSSION: This case illustrates the need to consider tuberculosis when faced with an atypical facial eruption and ocular involvement.

Crecimiento de brachiaria decumbens stapf y cynodon nlemfuensis vanderyst en suelos sulfatados ácidos de córdoba / Growth of brachiaria decumbens stapf and cynodon nlemfuensis vanderyst in acid sulphate soils of cordoba

Objetivo. Evaluar el efecto químico de dosis de cal en suelos sulfatados ácidos (SSA) y las respuestas fisiológicas de Cynodon nlemfuensis Vanderyst y Brachiaria decumbens Stapf. Materiales y métodos. El trabajo se desarrolló durante 2006 en suelos sulfatados ácidos de la finca “El Deseo” (Ciénaga de Oro - Córdoba), donde se aplicaron 3, 6 y 9 toneladas de cal agrícola por hectárea y se establecieron dos especies de pasto, Cynodon nlemfuensis Vanderyst (pasto estrella) y Brachiaria decumbens Stapf (pasto brachiaria). Las respuestas consideradas fueron las propiedades químicas del suelo, peso fresco y seco de genotipos y relación hoja/tallo. Se diseñó un experimento de bloques completamente randomizados con estructura de parcelas divididas, donde las parcelas principales correspondieron a los pastos y las subparcelas a las dosis de encalamiento. Resultados. Los valores del pH del suelo aumentaron y las concentraciones de aluminio decrecieron significativamente con la dosis de cal reduciéndose hasta en un 80%. Las bases intercambiables aumentaron con la aplicación de cal y los microelementos disminuyeron en función del tiempo, aunque no con el encalamiento. Por su parte, independientemente del genotipo, la producción de biomasa fresca mostró una relación lineal con el nivel de encalamiento (y=0.656x + 11.99; r2=0.92); la materia seca y la relación hoja/tallo fueron mayores siempre para B. decumbens respecto a C. nlemfuensis, de manera independiente al nivel de encalamiento. Conclusiones. La aplicación de dosis crecientes de cal en SSA incrementó los valores de pH y la producción de biomasa en la pastura independientemente de la especie forrajera.

Effect of the electrostatic charge on the mechanism inducing liposome solubilization: a kinetic study by synchrotron radiation SAXS.

The anionic surfactant sodium dodecyl sulfate (SDS) was used to induce the initial steps of the solubilization of liposomes. The structural transformations as well as the kinetics associated with this initial period were studied by means of time-resolved small-angle X-ray scattering (SAXS) using a synchrotron radiation source. Neutral and electrically charged (anionic and cationic) liposomes were used to investigate the effect of the electrostatic charges on the kinetics of these initial steps. The mechanism that induces the solubilization process consisted of adsorption of surfactant on the bilayers and desorption of mixed micelles from the liposomes surface to the aqueous medium. In all cases the time needed for desorption of the first mixed micelles was shorter than that for complete adsorption of the surfactant on the liposomes surface. The present work demonstrates that adsorption of the SDS molecules on negatively charged liposomes was slower and release of mixed micelles from the surface of these liposomes was faster than for neutral liposomes. In contrast, in the case of positively charged liposomes, the adsorption and release processes were, respectively, faster and slower than those for neutral vesicles.

[Detection of the cutaneous melanomas, their metastasis and relapses by scintigraphies with 99MTC-HMPAO]. / Detección de melanomas cutáneos, sus metástasis y recidivas mediante gammagrafías con 99mTc-HMPAO.

A pilot study was carried out in the Nuclear Medicine Department of the National Institute of Oncology and Radiobiology to learn the diagnostic efficacy of the 99mTc-HMPAO scintigraphy in the detection of cutaneous melanoma, distant and local metastases, in patients with a confirmed histological diagnosis. The planar and/or SPECT scintigraphy was performed in 17 patients and revealed 90% sensitivity for the detection of the disease. We calculated the tumor/background index in all the images obtained and found a value greater than 1 in every case. Thus, we can affirm that the 99mTc-HMPAO accumulation in tumors was higher than the background in all cases. We recommend that this procedure be considered in the follow up of these patients as a new diagnostic method which is very useful in the determination of the patient stage and prognostic evaluation.

Influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics in rats.

The influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics has been studied on the rat. At different times after partial hepatectomy, theophylline was administered intravenously as a single dose of 6 mg/Kg. Drug plasma levels were determined by HPLC and pharmacokinetic parameters were obtained. Physiological parameters were also measured. Following hepatectomy, an increase in mass liver was observed and 15 days after surgery, liver mass was 78% of nonhepatectomized rats. Initial theophylline concentrations varied during the regeneration period, as well as the distribution volume at steady-estate (Vss). Elimination half-life (t 1/2), notably increased after hepatectomy (7.27+/-1.38 h), decreased with time (6.70+/-1.18 h, 6.47+/-0.69 and 5.17+/-0.87 h after 24 h, 3 days and 15 days post-hepatectomy, respectively) to reach a value close to that of the control group (4.30+/-1.37 h). The increase in elimination half-life led to a decrease in the mean residence time during the period of liver regeneration. However, the intrinsic clearance hardly varied during regeneration period. We could establish the following relationship between liver weight (LW) and the elimination half-life: t 1/2 (h)=-0.358*LW (g)+8.6168 (R2=0.9906). For the mean residence time (MRT) this relationship was: MRT (h) =-0.5173*LW (g)+12.433 (R2=0.991).

Influence of ceramides in the solubilization of stratum corneum lipid liposomes by C(12)-betaine/sodium dodecyl sulfate mixtures.

The solubilization of liposomes modeling the stratum corneum (SC) lipid composition and those obtained varying the proportion of ceramides by means of dodecyl betaine (C(12)-Bet)/sodium dodecyl sulfate (SDS) mixtures was studied. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (K) were determined by monitoring the changes in the static light scattering of the system during solubilization. The fact that the free surfactant concentration was always similar to its critical micelle concentration (CMC) indicates that the liposome solubilization was mainly ruled by the formation of mixed micelles. The mole fraction of the zwitterionic component (X(zwitter)) of 0.4 showed the lowest ability to saturate or solubilize liposomes, although exhibiting the highest degree of partitioning into liposomes. This X(zwitter) corresponded to the highest derivation of the CMCs of these mixtures (negative synergism) and to the highest reduction in the skin irritation with respect to the anionic component. Higher and lower proportion of ceramides in the mixture led to a fall and to a rise in both the activity and the partitioning of a specific surfactant mixture (X(zwitter)=0.4). This finding could be related to the recently reported dependences of the level of ceramides in skin and function barrier abnormalities. Comparison of the present Re and K values with those reported for phosphatidylcholine (PC) liposomes shows that, although SC liposomes were more resistant to the action of surfactant mixtures, the surfactant partitioning into SC bilayers was similar to that reported for PC ones in all cases.

Influence of the level of ceramides on the permeability of stratum corneum lipid liposomes caused by a C12-betaine/sodium dodecyl sulfate mixture.

The sublytic interactions of a mixture of N-dodecyl-N, N-dimethylbetaine dodecyl betaine (C12-Bet)/sodium dodecyl sulfate (SDS) (mole fraction of the zwitterionic surfactant=0.6) with stratum corneum (SC) lipid liposomes varying the proportion of ceramides type III (Cer) were investigated. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (K) were determined by monitoring the changes in the fluorescence intensity of liposomes due to the 5(6) carboxyfluorescein (CF) released from the interior of vesicles. The fact that the free surfactant mixture concentration was always lower than its critical micelle concentration indicates that permeability changes were ruled by the action of surfactant monomers in all cases. Higher and lower Cer proportions than that of the SC lipids led to a fall and to a rise in the activity of the surfactant mixture on these bilayer structures. However, the surfactant partitioning into liposomes (or affinity with these bilayer structures) increased as the proportion of Cer increased up to the highest value was achieved for a Cer proportion similar to that in the SC lipids (about 40-45%). Thus, at low Cer proportions the ability of the surfactant mixture to alter the permeability of these bilayer structures was higher than that for liposomes approximating the SC lipid composition despite their reduced partitioning into liposomes. These findings are in agreement with the recently reported dependencies of the level of ceramides in skin lipids and function barrier abnormalities and could explain in part these dependencies.

[Radionuclide study of cutaneous melanomas with 99m Tc-HMPAO: visualization of metastases and recurrence]. / Estudio gammagráfico de los melanomas cutáneos con 99m Tc-HMPAO: visualización de metástasis y recidivas.

Malignant cutaneous melanoma (MCM) is a very aggressive disease that becomes in a true problem of health because of the increase in the last 5 years. In the present paper, authors report the detection of the tumor, metastases and recurrences mean 99mTc HMPAO. We presented 5 cases of MCM patients and observed the radiopharmaceutical uptake in skin, nodules and recurrent tumor lesions. Because of the number of patients was limited, authors recommended the research with a lot of patients. The gammagraphic studies could be very important for the staging of the disease and early detection of metastases and recurrent lesions.