Mutação do Gene p53 induzindo predisposição hereditária ao câncer: relato de um caso da síndrome de Li-Fraumeni

Li-Fraumeni syndrome is a familiar cancer predisposition syndrome characterized by the appearance of various types of tumors, such as sarcomas, breast carcinomas, brain tumors and leukemia. We present the case of a 37-year-old female who had a strong family history of cancer and herself had a history of six different primary tumors (one colon, one displasic nevus, one ovary and three breast tumors). P53 gene sequencing of her peripheral blood lymphocytes revealed an amino acid change of tryptofan (TGG) to a stop-codon (TAG) in the nucleotide 437 of codon 146 of exon 5 of this gene. Clinical, preventive and ethical implications of this molecular finding are also discussed.A Síndrome de Li-Fraumeni é uma síndrome de predisposição familiar ao câncer, caracterizada pela presença de múltiplos tumores, tais como sarcomas, carcinomas de mama, tumores cerebrais e leucemia. O caso relatado é de uma paciente feminina de 37 anos, que apresenta uma significativa história familiar de câncer, bem como história pessoal de seis diferentes tumores primários (um de cólon, um nevus displásico, um de ovário e três de mama). O seqüenciamento do gene supressor de tumor p53 em seus linfócitos presentes no sangue periférico revelou uma mutação do aminoácido triptofano (TGG) para um códon de parada prematuro (TAG), no nucleotídeo 437 do códon 146 do exon 5 deste gene. As implicações clínicas, preventivas e éticas deste caso são também abordadas

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC

CONTEXT AND OBJECTIVE: Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. DESIGN AND SETTING: Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. METHODS: From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. RESULTS: The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. CONCLUSIONS: Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug

Estudo da atitude e do conhecimento dos médicos não oncologistas em relação às medidas de prevenção e rastreamento do câncer Evaluation of non-oncologist physician's knowledge and attitude towards cancer screening and preventive actions

OBJETIVO: Avaliar o nível de informação e as atitudes preventivas em uso corrente pelos médicos ligados à FMABC. MÉTODOS: Foram entregues questionários para 120 médicos não oncologistas que lidam diretamente com pacientes adultos. RESULTADOS: A taxa de resposta foi de 58,3%. A idade média dos médicos foi de 33,9 anos, sendo 57,1% mulheres e 10% tabagistas. As práticas preventivas para os cânceres mais comuns (mama, colo de útero, próstata, colorretal e pele não-melanoma) foram analisadas e comparadas com as recomendadas pelos consensos adotados (INCA, Sociedade Americana de Cancerologia e Força-Tarefa Canadense). Observou-se que a maioria das práticas (45,72% a 100%) não se adequou a nenhum deles. Sobre possíveis barreiras para o adequado exercício da prevenção do câncer, 82,86% considerou falta de agentes educadores em saúde para a população, 77,14% poucos conhecimento ou treinamento e 70,15% falta de verba para custear exames. Houve uma tendência ao excesso de pedidos de exames de rastreamento. CONCLUSÕES: As práticas preventivas utilizadas pelos médicos entrevistados são heterogêneas e, em sua maioria, não preconizadas pelos consensos de condutas preventivas consultados, o que pode ser relacionado tanto à sua falta de conhecimento em relação a estes consensos como às divergências entre eles. Dessa forma, faz-se necessário um esforço educativo enfatizando a importância da prevenção do câncer no aprendizado e na prática médica.<br>BACKGOUND: New cancer cases are most often diagnosed by non-oncologist physicians. It is therefore essential for all physicians to be aware of cancer preventive practices and use them appropriately with their patients. METHODS: Questionnaires were administered to 120 non-oncologist physicians of various specialties attending the "Faculdade de Medicina do ABC" who deal directly with adult patients. Replies were collected and classified as appropriate or not according to one of these three cancer prevention guidelines: INCA, American Cancer Society and Canadian Task Force. RESULTS: The percentage of replied questionnaires was 58.3% (70 questionnaires). Mean age of physicians was 33.9 years; 57.1% were women and 10% smokers. Most of the current preventive practices adopted by the participating physicians (45.72% to 100%) regarding the most common and preventable tumors (breast, cervix, prostate, colon and rectum and non-melanoma skin cancer) did not agree with any of the guidelines mentioned above. When questioned about possible impediments for the appropriate practice of cancer prevention, 82.86% reported absence of health education agents working with the population, 77.14% scarceness of knowledge or training concerning prevention, and 70.15% lack of financial support for ordering tests. Frequently, whenever there was disagreement between the guidelines and the physician's current practices, preventive tests were ordered in excess of those recommended by the guidelines. CONCLUSIONS: Physicians had a tendency to order excessive laboratory tests, an action which can be related to lack of knowledge and to divergence among guidelines. A more intensive educational effort regarding cancer prevention, directed towards teaching physicians in training, seems to be warranted

Comparison of the antifungal susceptibility patterns (μg/mL) among VNI populations of <i>Cryptococcus neoformans</i> found in this study for the antifungals tested.

<p>Statistically significant differences (p <0.05) are marked with *, Kruskal-Wallis test followed by Dunn's test. The internal horizontal lines represent the median, the bars 25–75% percentiles and the horizontal lines percentiles 10–90%. Larger statistical data available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193237#pone.0193237.s003" target="_blank">S3 Table</a>.</p

DNA polymorphisms in different groups and populations analysed based on the ISHAM-MLST concatenated sequences of 102 <i>Cryptococcus neoformans</i> isolates studied.

<p>DNA polymorphisms in different groups and populations analysed based on the ISHAM-MLST concatenated sequences of 102 <i>Cryptococcus neoformans</i> isolates studied.</p

Genotypic analysis of clinical and environmental <i>Cryptococcus neoformans</i> isolates from Brazil reveals the presence of VNB isolates and a correlation with biological factors

<div><p>Cryptococcal infections are mainly caused by members of the <i>Cryptococcus neoformans</i> species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) <i>C</i>. <i>neoformans</i> isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha. MLST identified 12 known and five new sequence types (ST). Fourteen STs were identified within the VNI isolates, with ST93 (57/102, 56%) and ST77 (19/102, 19%) being the most prevalent. From the nine VNII isolates previously identify by <i>URA5</i>-RFLP only four (ST40) were confirmed by MLST. The remaining five grouped within the VNB clade in the phylogenetic analysis corresponding to the sequence type ST504. Other two environmental isolates also grouped within VNB clade with the new sequence type ST527. The four VNII/ST40 isolates were isolated from CSF. The two VNIV sequence types (ST11 and ST160) were isolated from blood cultures. Two of six patients evaluated with more than one isolates had mixed infections. Amongst the VNI isolates 4 populations were identified, which showed differences in their susceptibility profiles, clinical outcome and virulence factors. These results reinforce that ST93 is the most prevalent ST in HIV-infected patients in the Southeastern region of Brazil. The finding of the VNB molecular type amongst environmental Brazilian isolates highlights that this genotype is not restricted to the African continent.</p></div