eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Chromosomal gains and losses in ocular melanoma detected by comparative genomic hybridization in an Australian population-based study

To define the location of potential oncogenes and tumor suppressor genes in ocular melanoma we carried out comparative genomic hybridization (CGH) analysis on a population-based series of 25 formalin-fixed, paraffin-embedded primary tumors comprising 17 choroidal, 2 ciliary body, 4 iris, and 2 conjunctival melanomas. Twelve (48%) of the 25 melanomas showed no chromosomal changes and 13 (52%) had at least one chromosomal gain or loss. The mean number of CGH changes in all tumors was 3.3, with similar mean numbers of chromosomal gains (1.5) and losses (1.8). The highest number of chromosomal changes (i.e., nine) occurred in a conjunctival melanoma and included four changes not observed in tumors at any other ocular site (gains in 22q and 11p and losses in 6p and 17p). The most frequent gains in all primary ocular melanomas were on chromosome arm 8q (69%), 6p (31%) and 8p (23%) and the most frequent losses were on 6q (38%), 10q (23%), and 16q (23%). The most common pairing was gain in 8p and gain in 8q, implying a whole chromosome copy number increase; gains in 8p occurred only in conjunction with gains in 8q. The smallest regions of copy number alteration were mapped to gain of 8q21 and loss of 6q21, 10q21, and 16q22. Sublocalization of these chromosomal changes to single-band resolution should accelerate the identification of genes involved in the genesis of ocular melanoma.

Ecological aspects of American cutaneous leishmaniasis: 4. Observations on the endophilic behavior of the sandfly and the vectorial role of Psychodopygus intermedius in the Ribeira Valley region of the S.Paulo State, Brazil

The invasive tendency of Psychodopygus intermedius in the home environment, observed initially by Forattini et al. (1976), has now been confirmed by the demonstration of its high endophilic ability and by the use of human residences for shelter. Populations such as Lutzomyia migonei and Pintomyia fischeri were also present in that environment, though their low densities registered during this investigation could be an indication of their poor ability to overcome the barriers raised by the artificial environment. An objective epidemiological analysis based on the variables here given showed that human infection takes place in the extraforest environment, and the principal vectorial function falls, without doubt, on P. intermedius.

Risco crescente de melanoma de pele no Brasil

A ocorrência de melonoma maligno de pele no Brasil é analisada a partir dos dados de mortalidade disponíveis no Ministério da Saúde e dos dados de incidência dos seis Registros de Câncer de Base Populacional, localizados em seis capitais brasileiras. Os coeficientes de incidência nessas capitais situam-se em padrões intermediários se comparadas às cifras mundiais. Para o Município de Porto Alegre, uma das capitais estudas, que apresentou os maiores coeficientes de incidência, é feita comparação entre os dados relativos ao período 1979-1982 e 1987, constatando-se que houve aumento relativo de 38% entre homens e de 11% entre mulheres. Concluiu-se pela necessidade de se conduzir estudos no Brasil entre comunidades de indivíduos de pele clara, os quais apresentam risco potencializado para o desenvolvimento de melanoma, para que sejam definidas medidas específicas e eficazes de controle.

Physiological age in Lutzomyia youngi (Diptera: Psychodidae) populations from an endemic area for cutaneous leishmaniasis, Venezuela

Batches of sylvatic females of Lutzomyia youngi (Phlebotominae) captured in a Shannon trap on twelve occasions over one year in a locality where subcutaneous leishmaniasis is endemic, near the city of Trujillo, Venezuela, were used to study: 1) the percentages of parous females according to previously established criteria and 2) the average number of eggs laid spontaneously by isolated females during 7 days after feeding on hamsters. The data on the batches of females captured on nights previous to the rainy period (prepluvial) were compared with those on females captured after the rains (postpluvial) . Significant differences were detected by variation analysis for two variables and different number of N, as also were consistent groupings by Duncan's Test for pre-and postpluvial lots of females. The females captured on nights prior to the rainy periods (January-March and August-September) presented higher rates of nulliparity (86-72%) and contained or laid a greater number of eggs (71-67) than those captured after the rains (March-June and November-December) which presented lower rates of nulliparity (60-24%) and a smaller number of eggs (50-30). The rainfall peaks occurred in April and September-October, respectively. It is considered that these differences can be used by epidemiological studies as a means of estimating the physiological age of female populations of L. youngy.

Bronzeamento e risco de melanoma cutâneo: revisão da literatura

Estudos epidemiológicos sugerem a relação entre comportamentos relacionados ao bronzeamento e risco elevado de melanoma. Nesse sentido, realizou-se revisão sobre essa temática que abrangeu o período correspondente aos anos de 1977 a 1998. Foram pesquisadas as bases de dados Medline e Embase (Excerpta Medica). A análise mostrou que entre os jovens, apesar do conhecimento sobre os riscos da exposição excessiva à radiação ultravioleta e sobre as práticas visando à proteção da pele, prevalece o hábito de expor-se intencionalmente ao sol. Esse hábito é alimentado por crenças e atitudes em relação ao bronzeado e estimulado por influência do grupo e de pessoas consideradas "referências". As práticas mais freqüentemente adotadas para bronzear a pele apresentam risco elevado para o desenvolvimento de melanoma. Conclui-se que a forma mais eficaz de prevenir o melanoma é divulgar nos meios de comunicação que a pele bronzeada não é saudável, pois foi danificada pela radiação ultravioleta solar; e iniciar campanhas com ações efetivas para mudar comportamentos, naquilo que os motiva e os alimenta.

A perfusão isolada dos membros no melanoma maligno (a experiência do IPO-Porto)

Parte I - O contexto Neste capítulo faz-se a contextualização essencial do tema, dividindo-a em duas secções. A primeira secção apresenta conceitos relativos à patologia principal, o melanoma, apesar desta técnica não se aplicar só em doentes com esta patologia, mas considerando o peso da mesma na casuística da instituição, idêntico ao de outras instituições internacionais. A segunda secção apresenta o enquadramento da técnica e da terapêutica da Perfusão Isolada dos Membros, destacando as principais alterações ocorridas nos protocolos dos centros que a praticam, ao longo das últimas décadas. Parte II - A técnica e a terapêutica no IPOFG-Porto Neste capítulo é explicado passo a passo o procedimento da Perfusão Isolada dos Membros, segundo o protocolo do IPOFG-Porto, ilustrando cada passo com imagens de um caso real. Este procedimento apoia-se na técnica da circulação extracorporal, para aplicar uma terapêutica, a perfusão em dose elevada de uma dose pré-determinada de um ou mais citostáticos. São depois enumeradas as características essenciais de cada um dos citostáticos que foram e são usados na PIM ou associados a ela, terminando com a exposição da casuística da instituição, trabalhada apenas em contexto descritivo. Parte III - O seguimento dos doentes Neste capítulo elencam-se e explicam-se as variáveis em estudo no follow-up destes doentes, quer no pós-operatório imediato, quer no seguimento em ambulatório. O follow-up destes doentes pode ser muito longo, quase sempre dependendo do estadiamento prévio da doença antes da realização da PIM. O tipo de resposta clínica deve obter-se entre os 3 e os 6 meses pós PIM, mas pode obter-se antes ou depois. Todas as variáveis estão perfeitamente definidas internacionalmente e dão um contributo específico para o conhecimento da história natural da doença, mas para os doentes a que assume maior impacto é a necessidade, ou o evitar, da amputação do membro. São apresentados os dados destas variáveis relativos ao IPOFG-Porto. Parte IV - As reflexões Neste capítulo são feitas algumas reflexões sobre o custo, a sobrevivência e a qualidade de vida, e as perspetivas futuras da Perfusão Isolada dos Membros. Apesar da sua inegável eficácia terapêutica, a PIM é um procedimento de custo elevado e restrita a centros especializados, o que provoca assimetrias significativas. Os dados internacionais são claros, até agora não parece ter contribuído para um aumento da esperança média de vida destes doentes, mas o seu contributo para a qualidade de vida e manutenção da funcionalidade dos doentes é enorme. A Infusão Isolada dos Membros aparece como uma técnica standard promissora na quimioterapia regional.

Outbreak of persistent cutaneous abscesses due to Mycobacterium chelonae after mesotherapy sessions, Lima, Peru

Outbreaks of rapidly growing mycobacteria have been occasionally described. The article reports an outbreak of cutaneous abscesses due to Mycobacterium chelonae following mesotherapy in Lima, Peru. From December 2004 through January 2005, 35 subjects who had participated in mesotherapy training sessions presented with persistent cutaneous abscesses. Thirteen (37%) of these suspected cases consented to underwent clinical examination. Skin punch-biopsies were collected from suspicious lesions and substances injected during mesotherapy were analyzed. Suspected cases were mainly young women and lesions included subcutaneous nodules, abscesses and ulcers. Mycobacterium chelonae was isolated from four patients and from a procaine vial. In conclusion, it is important to consider mesotherapy as a potential source of rapidly growing mycobacteria infections.

Histopathology of cutaneous and mucosal lesions in human paracoccidioidomycosis

Biopsies from cutaneous and mucosal lesions from 40 patients with active paracoccidioidomycosis, were studied histopathologically. All cases exhibited chronic granulomatous inflammation and 38 also presented suppuration; this picture corresponded to the mixed mycotic granuloma (MMG). Pseudoepitheliomatous hyperplasia and the transepidermic (or epithelial) elimination of the parasite, were observed in all cases. In paracoccidioidomycosis elimination takes place through formation of progressive edema, accompained by exocytosis. The edema gives rise to spongiosis, microvesicles and microabscesses which not only contain the fungus but also, various cellular elements. Cells in charge of the phagocytic process were essentialy Langhans giant cells; PMN's, epithelioid and foreign body giant cells were poor phagocytes. An additional finding was the presence of fibrosis in most biopsies.

Histological and immunohistochemical aspects of cutaneous leishmaniasis in nicaragua

Sixty skin biopsies of fifty-eight non-treated patients with cutaneous leishmaniasis from Nicaragua were studied. Biopsies were classified according to Ridley's histopathologic groups: 36 (60%) were included in group B (diffuse necrosis), 14 in group C (focal necrosis), 7 (11.6%) in group D (reactive tuberculoid). Only three biopsies remained unclassified. None of our cases could be included in groups A and E. Immunohistochemistry disclosed in 17 cases Russel's bodies secreting IgM and only one IgG positive. There was no correlation between the histopathologic groups and the presence of Russel's bodies. However, we believe the presence of Russel's bodies help the diagnosis of leishmaniasis. Correlation between morphological patterns and the different leishmania species was also considered.

Cutaneous leishmaniasis in germfree, gnotobiotic, and conventional mice

Cutaneous leishmaniasis was much more severe in conventional than in gnotobiotic mice as revealed by macro and microscopic examination. An inoculum of Leishmania mexicana amazonensis was used.

Ecological aspects of American cutaneous leishmaniasis: 6. Man-biting sandfly fauna of a patch of residual forest in the middle and north-eastern region of the São Paulo State, Brazil

This report shows the phlebotomine vectorial role in the endemic cutaneous leishmaniasis situated in the middle and north-eastern region of the São Paulo, Brazil. Analysis of information encloses a sandfly man-biting fauna of four different patches of residual forest. So, using the human-bait and Shannon trap for a period of one year we have caught 16,869 sandflies. The predominance of Lutzomyia intermedia (85,6%) was clear. Moreover, the low density of Lutzomyia whitmani and Lutzomyia pessoai and their epidemiological implications at present and in the past are discussed. Information about the daily activity of some species is given and we emphasize for the first time, the diurnal activity of Lutzomyia firmatoi in the São Paulo State.

Treatment of Cutaneous Larva Migrans with albendazole: preliminary report

Twenty three patients with Cutaneous Larva Migrans syndrome were prospectively treated with 400 mg/day of Albendazole for 3 consecutive days. Clinical response, compliance and tolerance was excellent. Patients were asymptomatic within the first 72 hours of treatment and recurrences did not occurred. Preliminary results with three additional patients suggest that a single oral 400 mg dose may be effective as well.