Metabolic signature of lung cancer: a metabolomic study of human tissues and biofluids

This thesis reports the application of metabolomics to human tissues and biofluids (blood plasma and urine) to unveil the metabolic signature of primary lung cancer. In Chapter 1, a brief introduction on lung cancer epidemiology and pathogenesis, together with a review of the main metabolic dysregulations known to be associated with cancer, is presented. The metabolomics approach is also described, addressing the analytical and statistical methods employed, as well as the current state of the art on its application to clinical lung cancer studies. Chapter 2 provides the experimental details of this work, in regard to the subjects enrolled, sample collection and analysis, and data processing. In Chapter 3, the metabolic characterization of intact lung tissues (from 56 patients) by proton High Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is described. After careful assessment of acquisition conditions and thorough spectral assignment (over 50 metabolites identified), the metabolic profiles of tumour and adjacent control tissues were compared through multivariate analysis. The two tissue classes could be discriminated with 97% accuracy, with 13 metabolites significantly accounting for this discrimination: glucose and acetate (depleted in tumours), together with lactate, alanine, glutamate, GSH, taurine, creatine, phosphocholine, glycerophosphocholine, phosphoethanolamine, uracil nucleotides and peptides (increased in tumours). Some of these variations corroborated typical features of cancer metabolism (e.g., upregulated glycolysis and glutaminolysis), while others suggested less known pathways (e.g., antioxidant protection, protein degradation) to play important roles. Another major and novel finding described in this chapter was the dependence of this metabolic signature on tumour histological subtype. While main alterations in adenocarcinomas (AdC) related to phospholipid and protein metabolisms, squamous cell carcinomas (SqCC) were found to have stronger glycolytic and glutaminolytic profiles, making it possible to build a valid classification model to discriminate these two subtypes. Chapter 4 reports the NMR metabolomic study of blood plasma from over 100 patients and near 100 healthy controls, the multivariate model built having afforded a classification rate of 87%. The two groups were found to differ significantly in the levels of lactate, pyruvate, acetoacetate, LDL+VLDL lipoproteins and glycoproteins (increased in patients), together with glutamine, histidine, valine, methanol, HDL lipoproteins and two unassigned compounds (decreased in patients). Interestingly, these variations were detected from initial disease stages and the magnitude of some of them depended on the histological type, although not allowing AdC vs. SqCC discrimination. Moreover, it is shown in this chapter that age mismatch between control and cancer groups could not be ruled out as a possible confounding factor, and exploratory external validation afforded a classification rate of 85%. The NMR profiling of urine from lung cancer patients and healthy controls is presented in Chapter 5. Compared to plasma, the classification model built with urinary profiles resulted in a superior classification rate (97%). After careful assessment of possible bias from gender, age and smoking habits, a set of 19 metabolites was proposed to be cancer-related (out of which 3 were unknowns and 6 were partially identified as N-acetylated metabolites). As for plasma, these variations were detected regardless of disease stage and showed some dependency on histological subtype, the AdC vs. SqCC model built showing modest predictive power. In addition, preliminary external validation of the urine-based classification model afforded 100% sensitivity and 90% specificity, which are exciting results in terms of potential for future clinical application. Chapter 6 describes the analysis of urine from a subset of patients by a different profiling technique, namely, Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS). Although the identification of discriminant metabolites was very limited, multivariate models showed high classification rate and predictive power, thus reinforcing the value of urine in the context of lung cancer diagnosis. Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the potential of integrated metabolomics of tissues and biofluids to improve current understanding of lung cancer altered metabolism and to reveal new marker profiles with diagnostic value.

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. METHODS: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. RESULTS: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). CONCLUSION: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

Estudo sobre o consumo de tabaco entre os adolescentes da Ilha Terceira

RESUMO - O objetivo deste estudo foi conhecer o comportamento face ao consumo de tabaco reportado pelos adolescentes escolarizados da ilha Terceira e caracterizar alguns fatores associados. O estudo realizado assumiu uma metodologia de investigação observacional, descritiva, quantitativa e de carácter transversal. Os dados foram recolhidos no ano letivo 2012/2013, nos alunos do 9.º ano de escolaridade, através da aplicação de um questionário de autopreenchimento, anónimo e voluntário, em contexto de sala de aula. A amostra foi constituída por 323 adolescentes, 142 do sexo masculino e 181 do sexo feminino, com idade média de 14,71 anos. Verificou-se que cerca de 16,9% dos adolescentes consome tabaco regularmente, 6,6% ocasionalmente e 76,6% não fuma. Mais de metade dos adolescentes já experimentou fumar tabaco (56%), sendo a idade média de experimentação de 12,49 anos. A maioria dos adolescentes que experimentaram fumar referiram tê-lo feito por curiosidade (84,7%) e, sobretudo, na companhia dos amigos (83,1%). As variáveis associadas ao comportamento tabágico foram: o desempenho escolar, os hábitos tabágicos dos amigos, a permissividade dos pais para se fumar em casa, a frequência à exposição ao tabaco em casa, os conhecimentos da “impotência sexual” como consequência do consumo de tabaco, conhecimento dos danos na saúde em frequentar ambientes com fumo e a crença de que os jovens fumadores são mais atraentes. Os resultados mostram a elevada necessidade de serem desenvolvidas estratégias de prevenção e controlo do tabagismo entre os adolescentes da ilha Terceira.

Consumo de álcool nas mães que amamentam durante o 1º ano de vida da criança, prevalência e fatores associados, em Vila Fanca de Xira, em 2014

RESUMO - Introdução: O consumo de álcool durante o aleitamento materno é um tema que tem vindo a ganhar relevo nos últimos anos. Contrariamente ao consumo de álcool durante a gravidez, em que já se conhecem bem as consequências sobre o feto, sobre os efeitos do consumo de álcool durante a amamentação ainda pouco se sabe. Este estudo visa, assim, caracterizar o consumo de álcool e fatores associados nas mães que amamentam, ou amamentaram, durante o 1º ano de vida da criança no concelho de Vila Franca de Xira em 2014. Metodologia: Foi realizado um estudo transversal, com a aplicação de um questionário de auto-preenchimento, a uma amostra estratificada e com alocação proporcional por Unidade Funcional, de mães que estiveram nas consultas de saúde infantil das unidades de saúde do concelho, entre março e maio de 2014. Resultados: A idade mediana das mães foi 31 anos e das crianças foi 3 meses. O tempo total em aleitamento teve uma mediana de 2 meses e somente 16,3% amamentaram mais de 5 meses. A prevalência do consumo de álcool durante a amamentação foi 7,9% e na gestação foi 8,1%. Os fatores que se associaram, com significância estatística, ao consumo de álcool na amamentação foram a maior idade da mãe, os conhecimentos que esta possuía e o consumo anterior de álcool na gestação. Os hábitos tabágicos durante a amamentação tiveram uma prevalência de 13,4% e o consumo de substâncias ilícitas de 0,6%. Conclusões: A prevalência do consumo de álcool durante a amamentação, a nível local, mantém-se semelhante à da gestação, sendo muito inferior à encontrada em outros estudos de outros países. O tempo total em amamentação é baixo considerando as recomendações nacionais e internacionais.

Évaluation comparative de stratégies visant à augmenter les interventions de courte durée en cessation tabagique auprès du personnel infirmier de milieux hospitaliers

Introduction : Les résultats de recherches ont démontré que la cessation tabagique augmente là où des interventions professionnelles préventives sont appliquées avec constance. On rapporte qu’au Québec, 62 % des infirmières (toutes pratiques confondues) évaluent le statut tabagique de leurs clients et 38 % suggèrent la cessation tabagique. En milieu hospitalier, l’évaluation du statut tabagique diminue à 30 %. Or, le personnel infirmier hospitalier est présent dans les unités de soins 24 heures sur 24, ce qui laisse prévoir une influence potentielle non négligeable dans la décision des patients de cesser de fumer. Objectif : La présente recherche a pour objectif de comparer, avec un groupe contrôle, l’efficacité de stratégies (formation interactive, rappel, multiple) pour augmenter les interventions réalisées en cessation tabagique dans des unités de médecine et de chirurgie. Le choix de ces stratégies repose sur leur efficacité et leur potentiel d’implantation dans d’autres centres. Méthodologie : Un devis expérimental avec randomisation par groupe a été choisi. Le modèle factoriel permet d’évaluer l’effet de chacun des groupes expérimentaux en regard du groupe contrôle. Des mesures préstratégies et poststratégies (à 1 mois et à 3 mois) sont privilégiées. Plusieurs outils permettent de mesurer les effets des stratégies et ce, avec des sources diversifiées (personnel infirmier, patients, dossiers des patients, gestionnaires et responsables des centres d’abandon du tabac). Résultats : Au total, 156 infirmières et infirmières-auxiliaires ont répondu à des questionnaires au temps 1, 78 au temps 2 et 69 au temps 3. Parallèlement au personnel infirmier, 156 patients ont été rejoints au temps 1, 89 au temps 2 et 98 au temps 3. Les résultats démontrent que le personnel infirmier évalue le statut tabagique chez 35,7 % de la clientèle seulement et la motivation à cesser de fumer chez 17,6 % des patients. Au cours de notre recherche, peu d’interventions en cessation tabagique ont été réalisées dans les unités de médecine et de chirurgie; la présence de plusieurs obstacles de même qu’une perception d’inefficacité des interventions de la part du personnel infirmier semblent en être les causes. Les résultats de notre recherche ne nous a pas permis d’appuyer nos hypothèses. Cependant, des analyses complémentaires ont démontré que la stratégie de formation interactive a permis d’augmenter certaines pratiques cliniques à court terme et de diminuer la perception d’obstacles à l’intervention. Le rappel n’a pas fonctionné correctement et n’a pu être évalué. Conclusion : En considérant les résultats modestes des stratégies implantées, la formation interactive a eu un impact à très court terme sur les interventions courtes en cessation tabagique réalisées par le personnel infirmier d’unités de soins en médecine et en chirurgie. Les difficultés rencontrées lors de l’implantation des stratégies ont été expliquées, ce qui permettra une planification plus éclairée de futures recherches dans le domaine.

Características de la conducta de fumar en función de la fase de abandono en una muestra de personal de la Universidad de Girona

Objetivos: Determinar la prevalencia y las características de la conducta de fumar y la distribución por estadios de abandono del tabaquismo entre el personal de la Universidad de Girona. Pacientes y método: Se diseñó un estudio descriptivo transversal. Para ello se realizó una entrevista sobre la conducta de fumar a una muestra representativa de los 941 miembros del personal de la Universidad de Girona en el segundo semestre de 1999. Resultados: De los 281 participantes en el estudio, 77 (27,4%) eran fumadores, 67 (23,9%) exfumadores y 137 (48,7%) no fumadores. Por Facultades, la mayor prevalencia de fumadores se encontró en: Letras: 38,9%; Ciencias de la Educación: 31% y Enfermería: 28,3%. La distribución de los sujetos por etapas de abandono fue la siguiente: precontemplación: 36,8%; contemplación: 13,2%; preparación: 3,5%; acción: 3,5% y mantenimiento: 43%. El consumo de tabaco light fue del 49,1% en precontemplación, 47,1% en contemplación y 33,3% en preparación. Respondieron haber recibido consejo médico para dejar de fumar: precontemplación: 35,8%; contemplación: 52,6%, preparación: 60%, acción: 20% y mantenimiento: 24,2%. Conclusiones: 1. Las Facultades relacionadas con el ámbito de la salud, Ciencias de la Educación y Enfermería son, junto con las de Letras las que presentan mayor consumo de tabaco. 2. Los fumadores en precontemplación, en comparación con los sujetos en contemplación y preparación, informan con mayor frecuencia de consumir tabaco bajo en nicotina y de no haber recibido consejo médico

Prevalencia de síntomas respiratorios en avicultores de una empresa de Bogotá

Este estudio identifico la prevalencia de síntomas respiratorios en avicultores de una empresa de Bogotá, mediante la aplicación del: “CUESTIONARIO EPIDEMIOLOGICO ESTANDARIZADO DE SINTOMAS RESPIRATORIOS. ATS-DLD-78-A (FERRIS 1978)”. Participaron 113 trabajadores del sector avícola comúnmente conocidos como galponeros, quienes son responsables de alimentar y cuidar a las aves (pollos), además de veterinarios. La prevalencia general de síntomas respiratorios fue del 45,1% (n=50), siendo el síntoma de sibilancias, la manifestación más prevalente representando el 34,4% (n=39). Se encontró asociación significativa entre la manifestación clínica de sibilancias y género, siendo mayor la prevalencia en los hombres que en las mujeres (22,8% vs. 5,4%, p=0,008). En el síntoma respiratorio de tos se encontró asociado al género (p=0,012), siendo el género masculino el más afectado (29,8% vs. 10,7%). El tiempo de exposición > 8 años está asociado al síntoma respiratorio de sibilancias (p=0,032). No se encontraron relaciones significativas entre hábito de tabaquismo, edad, raza y nivel de escolaridad. Siendo la prevalencia general de síntomas respiratorios alta es necesario fortalecer el uso de elementos de protección personal adecuados para la protección del tracto respiratorio y de gran importancia incluir a los trabajadores en programas de vigilancia epidemiológica para el control de los síntomas respiratorios de tal forma que se les realice un seguimiento anual que incluya exámenes ocupacionales de ingreso y periódicos al igual que exámenes complementarios dirigidos al factor de riesgo.

Interrelations between ceruloplasmin and Fe status during human pregnancy

It is well established that Fe and ceruloplasmin interact in animals and in in vitro models. However, Fe-mediated regulation of ceruloplasmin has never been investigated in humans. In an observational study, 53 pregnant women aged 19-39 yr (29.8±0.7 yr, mean ± SEM) were recruited at the Aberdeen Antenatal Clinic, Aberdeen Maternity Hospital, UK. All requirements for local ethical committees were followed. Venous blood samples were taken from each woman at 34 wk gestation for measurement of Fe status and ceruloplasmin. Various parameters were used to test for Fe status. The most sensitive one appeared to be soluble transferrin receptor, which increased with parity. In the population studied, there was no relationship between hemoglobin or ferritin and serum ceruloplasmin. However, using soluble transferrin receptor (sTfR) levels, we were able to demonstrate an inverse linear relationship (r=0.37, p=0.021, n=41) between Fe status and ceruloplasmin. Fe supplementation, number of previous pregnancies, and smoking habits did not affect this relationship. Our data support in vitro results showing regulation of ceruloplasmin by Fe and also suggest that the interactions between Fe and ceruloplasmin should be considered when Fe supplementation is given.

Lifestyle factors fail to explain the variation in plasma leptin concentrations in women

To assess the relationship between circulating leptin concentrations, metabolic parameters, and lifestyle factors such as alcohol intake, physical activity level, smoking habits, and reproductive history, a cohort of 359 women was drawn from a population-based study conducted in Victoria, Australia. The parameters measured included body mass index (BMI); waist and hip circumference; blood pressure; and fasting glucose, insulin, triacylglycerol, cholesterol, and leptin concentrations. In addition, a self-administered questionnaire was used to assess reproductive history, physical activity level, alcohol intake, and smoking habits. Our results demonstrated that BMI, body weight, waist circumference, and hip circumference were all strongly correlated with circulating leptin concentrations in this population (r > 0.56, P < 0.001 in all cases). Waist/hip ratio, triacylglycerols, insulin, glucose, and cholesterol were also associated with leptin (P < 0.05), but there was no association between leptin and age, height, or blood pressure. When these associations were adjusted for BMI, age, glucose, and waist circumference were significantly associated with leptin. The lifestyle factors examined did not help to explain the observed variation in leptin concentrations between individuals when results were adjusted for degree of adiposity and age.

Asthma Polymorphic Loci genotyping in Madeira population: identification of potential genetic markers of disease susceptibility, severity and clinical relevance

Asthma is a complex disease, influenced by both environmental and genetic factors. In this study, the analysis of multiple environmental factos assessed by questionnaire and the genotyping of SNPs IL131c.144 G/A, IL41590 C/T, IL41RP2 253183, ADRB21c.16 A/G, ADAM331V4 C/G, ADAM331S1 c.710 G/A, GSDML1236 C/T and STAT6121 C/T were performed in a sample of Madeiran asthmatic patients and their families, and their association to asthma susceptibility and severity was assessed. Family, environmental, social and individual factos such as the presence of rhinitis in one of the parents,the habitation conditions, the family smoking habits, individual food habits and allergen sensitivity, were found to account for asthma severity. IL41590*T and IL41RP2*183$ alleles as well as the combined genotypes IL41590*CT/IL41590*TT and IL41 RP2*253183/IL41RP2*253183 were associated to both asthma susceptibility and severity.GSDML1236*TT was found associated only to asthma severity.Allele ADAM331 V4*C was significantly overM transmitted to asthmatic offspring being linked with the disease by TDT. These findings suggest that in addition to environmental influences, IL41 590 C/T, IL41RP2 253183, ADAM331V4 C/G and GSDML1236 C/T SNPs may constitute important genetic factos contributing to asthmasusceptibility and/or severity in Madeira population.

Efeito imediato e a curto prazo do cigarro sobre o transporte mucociliar nasal de fumadores

Background and objectives: The efficiency of mucociliary transport may vary in different conditions, such as in exposure to harmful particles of the cigarette smoke. The present study evaluated the acute and short term effects of smoking on nasal mucociliary clearance in current smokers by the quantification of the Saccharin Transit Time (STT), and to investigate its correlation with the history of tobacco consumption.Methods: Nineteen current smokers (11 men, 51 +/- 16 years; BMI 23 +/- 9 kg/m(2), 27 +/- 11 cigarettes per day, 44 +/- 25 pack-years), entering a smoking cessation intervention program, responded to a questionnaire concerning smoking history and were submitted to lung function assessment (spirometry) and the STT test. STT was assessed immediately after smoking and 8 hours after smoking. The STT test was also performed in nineteen matched healthy non-smokers' who served as control group.Results: When compared to STT in non-smokers' (10 +/- 4 min; mean +/- standard deviation), smokers presented similar STT immediately after smoking (11 +/- 6 min; p = 0.87) and slower SIT 8 hours after smoking (16 +/- 6 min; p = 0.005 versus non-smokers' and p = 0.003 versus immediately after smoking). STT 8 hours after smoking correlated positively with age (r = 0.59; p = 0.007), cigarettes per day (r = 0.53; p = 0.02) and pack-years index (r = 0.74; p = 0.0003).Conclusions: In smokers, although the mucociliary clearance immediately after smoking is similar to non-smokers', eight hours after smoking it is reduced, and this reduction is closely related to the smoking habits. (C) 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Estudo clínico e níveis de ansiedade em uma série de casos de líquen plano oral

Oral Lichen Planus (OLP) is a relatively common, cronic inflammatory disease. Its etiopathogenesis is no completely understood and several factors have proposed in attempt to explain the appearance, variety of clinical manifestations and periods of exacerbation and remission of the symptons of the lesions. The objective of the present study was to assess the presence of local factors, systemic diseases and levels of anxiety in patients with OLP, investigating their association with the clinical characteristics of the lesions. The sample consisted of 37 patients with histopathologically confirmed OLP that were submitted to a clinical exam to evaluate the presence of smoking habits, consumption of alcoholic beverages, diabetes mellitus, hypertension and hepatitis C virus (HCV) infection. The existence of skin lesions, as well as the time course, clinical form, symptomatology, number and location of the oral lesions were also registered. The trait anxiety was measured by Spielberger s Stai-Trait Anxiety Inventory (STAI), and to associate the variables we used the chi-square or Fisher s exact test. It was observed that females were the most affected (75%) and the mean age of the patients was 53,3 years. Most cases were non-smoker (97,3%) and none was drinker. Diabetes mellitus and hypertension were present in 10,8% e 16,2% of the sample, respectively and only one patient was HCV-seropositive (2,7%). Moderate levels of anxiety were seen in most cases (78,4%) and 21,6% had elevated levels. The oral lesions persisted in 95% of the cases for a period of 6 months to 13 years. The erosive form was the most prevalent (57,1%) and symptons were reported by 45,7% of the patients. Multiple lesions were frequent (60%), affecting mainly the buccal mucosa, followed by gums e tongue. There was no significant association of the presence of diabetes mellitus, hypertension and levels of anxiety with the clinical form or symptomatology of the oral lesions (p>0,005), despite a trend in patients with hypertension to have erosive lesions. It was concluded that, in the sample studied, moderate levels of anxiety were commonly observed, and the HCV infection apparently is not related to the onset of the OLP. In this study, the presence of diabetes mellitus, hypertension and levels of anxiety seem not to be associated with the clinical characteristics of the lesions of OLP

Prevalência de fatores de risco para doenças crônicas: inquérito populacional mediante entrevistas telefônicas em Botucatu, São Paulo, 2004

OBJETIVO: Descrever resultados da aplicação de um sistema de monitoramento de fatores de risco para doenças crônicas não transmissíveis (DCNT) por meio de entrevistas telefônicas (SIMTEL) no município de Botucatu/SP. MÉTODOS: Entrevistou-se amostra probabilística (n = 1.410) da população de indivíduos com 18 ou mais anos de idade residente em domicílios do município de Botucatu/SP, conectados à rede de telefonia fixa. A amostragem foi realizada em três etapas: sorteio de linhas do cadastro da companhia telefônica; seleção de linhas residenciais ativas; sorteio para entrevista de um morador com 18 ou mais anos de idade por linha elegível. A taxa de sucesso (entrevistas realizadas: linhas elegíveis sorteadas) foi de 86,9%, sendo de 5,8% a proporção de recusas. Foi aplicado um questionário com 74 questões sobre consumo alimentar, atividade física, tabagismo, consumo de bebidas alcoólicas, peso e estatura recordados e auto-referência a diagnósticos médicos de hipertensão arterial e diabetes. Apresentam-se estimativas brutas da prevalência de fatores de risco/proteção para DCNT e estimativas ajustadas que levam em conta a distribuição segundo idade, sexo e escolaridade da população adulta total do município no Censo Demográfico de 2000. RESULTADOS: Foram observadas altas prevalências de excesso de peso (46.7%) e sedentarismo (57.9%). Houve desvantagem para os homens quanto ao consumo excessivo de bebidas alcoólicas e vantagem no que se refere à prática de atividade física em 1 ou mais dias da semana. Nas mulheres, observou-se associação inversa entre escolaridade e os seguintes fatores de risco: obesidade, excesso de peso, sedentarismo, consumo de carnes com gordura e hábito de fumar. Resultado semelhante foi observado para homens, exceto com relação a obesidade e excesso de peso. CONCLUSÕES: A segunda experiência de aplicação do SIMTEL confirmou o desempenho satisfatório e a utilidade do sistema em nosso meio.

Tabagismo, abandono do fumo e os otorrinolaringologistas do estado de São Paulo

Os otorrinolaringologistas estão diretamente envolvidos no diagnóstico e tratamento de doenças provocadas pelo cigarro, incluindo o câncer das vias aéreas superiores. É importante que os especialistas estejam capacitados a tratar o tabagismo e a dependência da nicotina. Também se sabe que há fumantes entre os próprios médicos. OBJETIVO: Pesquisar as opiniões e condutas de otorrinolaringologistas do Estado de São Paulo frente ao tabagismo e à dependência química da nicotina, e avaliar o hábito tabagístico dos especialistas. FORMA DE ESTUDO: Corte transversal. MATERIAL E MÉTODOS: Foram selecionados aleatoriamente 600 otorrinolaringologistas do Estado de São Paulo. A esses especialistas foi enviado, em março de 2005, por correio, um questionário padrão. Foram analisadas as respostas recebidas no período de março a maio de 2005. RESULTADOS: Foram recebidas 209 respostas. Nestas, 97 profissionais (46,4%) avaliaram sua familiaridade com os meios de tratamento da dependência de nicotina como regular e 60 (28,7%) como insatisfatória. Dos participantes do estudo, 144 (68,9%) nunca fumaram, 50 (23,9%) são ex-fumantes, nove (4,3%) são fumantes ocasionais e seis (2,9%) são fumantes. CONCLUSÃO: A prevalência de tabagistas na amostra de 209 otorrinolaringologistas do Estado de São Paulo foi de 7,1%.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy.MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 C, healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4cm.In conclusion, the data show that radiotherapy has a potent clastogenic effect in Circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm.