Flavours and design features on tobacco product packaging near schools before and after plain packaging implementation in Montevideo, Uruguay.

INTRODUCTION: Monitoring tobacco industry marketing strategies in countries that have introduced plain packaging helps with documenting variations in the market during the transition period. Uruguay implemented plain packaging in February 2020. We describe changes in the characteristics of tobacco packaging, content and sticks before and after plain packaging implementation. METHODS: Data were collected across 15 neighbourhoods in different socioeconomic areas in Montevideo, Uruguay, before and after implementation (2019 and 2021). A high school or college was selected in each neighbourhood as the walking protocol starting point. Two stores were visited per neighbourhood. Cigarettes and roll-your-own tobacco (RYO) were purchased and coded for the presence of taste or sensation lexical and imagery features. RESULTS: The number of unique products increased between 2019 (n=23) and 2021 (n=40). Prior to implementation, all packs presented design features. After its implementation, 95.7% of cigarette packs complied with regulations. Overall, 34.7% of cigarettes and RYO were flavoured in 2019 versus 50.0% in 2021 (p=0.01). In 2019, all flavoured cigarette packs conveyed taste through language and/or imagery, while cigarettes had designs on the filter suggesting the potential for altering the flavour. In 2021, 44.0% of cigarette packs indicated flavour through lexicon; and 81.0% of cigarette sticks still included a flavour capsule. CONCLUSIONS: After implementation, we noticed an increase in the availability of unique flavoured cigarettes and RYO among surveyed retailers. However, this increase was less pronounced compared with what is reported in the Latin American region. Non-compliance was identified. Greater efforts should be made enforcing current policy.

Prevalencia de tabaquismo y sus características en pacientes hospitalizados en cuidados moderados de un hospital público universitario / Prevalence of smoking and its characteristics in patients hospitalized in moderate care at a public university hospital / Prevalência de tabagismo e suas características em pacientes internados em cuidados moderados em um hospital público universitário

Resumen: Introducción: El tabaquismo es la principal causa de enfermedad y muerte a nivel mundial, siendo una comorbilidad frecuente en los pacientes hospitalizados, con estadías mayores y peores resultados. En el Hospital de Clínicas, no hay estudios que evalúen la prevalencia del tabaquismo en usuarios internados desde el 2005. Objetivo: valorar prevalencia de tabaquistas y sus características en los pacientes que ingresan a sala de cuidados moderados de un Hospital Universitario. Material y métodos: Estudio observacional, analítico, de corte transversal. Resultados: Se incluyeron 100 pacientes, 38% eran tabaquistas, 27% ex tabaquistas y 35% no tenían historia de tabaquismo. La edad media fue de 48.65 años entre los tabaquistas; 63,11 en los ex tabaquistas; 58,68 en los no tabaquistas. Refirieron abstinencia 44,73% de los tabaquistas y pretendían mantener la abstinencia. La media de internación del grupo de tabaquistas fue de 31,07 días, mientras que entre no tabaquistas fue de 20,11 (p=0.1337). Falleció 14% de la población del estudio durante la internación. De este grupo, 14,28% no eran tabaquistas, 28,57% eran ex tabaquistas y 57,14% eran tabaquistas (p=0.0569). La media de edad de fallecimiento en los tabaquistas fue de 49,37 años, en los ex tabaquistas de 70,75 años y de 76 años en los no tabaquistas. Conclusiones e Implicancias: alta prevalencia de tabaquismo en pacientes hospitalizados, con mayor estadía de internación, y mayor mortalidad a menor edad. Muchos fumadores están altamente motivados al cese y se verían beneficiados de equipos interdisciplinarios para su abordaje.

Abstract: Introduction: Smoking is the main cause of disease and death worldwide, being a frequent comorbidity in hospitalized patients, with longer stays and worse results. At Hospital de Clínicas, there are no studies evaluating the prevalence of smoking in hospitalized users since 2005. Objective: to assess the prevalence of smokers and their characteristics in patients admitted to the moderate care room of a University Hospital. Methods: Observational, analytical, cross-sectional study. Results: 100 patients were included, 38% were smokers, 27% ex-smokers and 35% had no history of smoking. The mean age was 48.65 years among the smokers; 63.11 in former smokers; 58.68 in non-smokers. 44.73% of the smokers reported abstinence and intended to maintain abstinence. The mean hospitalization of the group of smokers was 31.07 days, while among non-smokers it was 20.11 (p = 0.1337). 14% of the study population died during hospitalization. Of this group, 14.28% were not smokers, 28.57% were ex-smokers and 57.14% were smokers (p = 0.0569). The mean age of death in smokers was 49.37 years, in ex-smokers it was 70.75 years and 76 years in non-smokers. Conclusions and Implications: high prevalence of smoking in hospitalized patients, with longer hospital stays, and higher mortality at a younger age. Many smokers are highly motivated to quit and would benefit from interdisciplinary teams to address them.

Resumo: Introdução: O tabagismo é a principal causa de doença e morte em todo o mundo, sendo uma comorbidade frequente em pacientes hospitalizados, com maior tempo de permanência e piores resultados. No Hospital de Clínicas, não há estudos avaliando a prevalência de tabagismo em usuários hospitalizados desde 2005. Objetivo: avaliar a prevalência de fumantes e suas características em pacientes internados na unidade de terapia moderada de um Hospital Universitário. Métodos: Estudo observacional, analítico, transversal. Resultados: 100 pacientes foram incluídos, 38% eram fumantes, 27% ex-fumantes e 35% não tinham história de tabagismo. A média de idade foi de 48,65 anos entre os fumantes; 63,11 em ex-fumantes; 58,68 em não fumantes. 44,73% dos fumantes relataram abstinência e pretendem manter a abstinência. A média de internação do grupo de fumantes foi de 31,07 dias, enquanto entre os não fumantes foi de 20,11 (p = 0,1337). 14% da população do estudo morreu durante a hospitalização. Desse grupo, 14,28% não eram fumantes, 28,57% eram ex-fumantes e 57,14% eram fumantes (p = 0,0569). A idade média de morte em fumantes foi 49,37 anos, em ex-fumantes foi 70,75 anos e 76 anos em não fumantes. Conclusões e implicações: alta prevalência de tabagismo em pacientes hospitalizados, com maior tempo de internação e maior mortalidade em idades mais jovens. Muitos fumantes estão altamente motivados para parar de fumar e se beneficiariam de equipes interdisciplinares para abordá-los.

Evaluación de la personalidad y resultados en cesación tabáquica

Resumen: Introducción: Los resultados en cesación tabáquica son insatisfactorios, menores al 30% al año de finalizado el tratamiento. No existe suficiente evidencia sobre la relación entre el Nivel de Funcionamiento de la Personalidad (NFP) y cesación. La Escala de NFP (ENFP) del Manual Estadístico de los Trastornos Mentales 5ed. que evalúa la personalidad en relación consigo mismo y con los otros a través de cuatro dominios, podría ser útil para predecir y mejorar resultados. Objetivos: Evaluar la asociación entre el NFP y la abstinencia al final del tratamiento y a los 6 meses. Metodología: Estudio longitudinal y analítico de una muestra no probabilística de pacientes que consultaron en una Unidad de Tabaquismo. Se aplicó test de chi2 o test exacto de Fisher para evaluar asociación de variables categóricas. Se evaluó NFP con la ENFP y grado de dependencia física con el Test de Fagerström. Resultados: Participaron 28 pacientes, 57% mujeres, edad promedio 48 años (± 12,3). 16 de los 28 cesaron, de ellos 14 presentaron bajos puntajes en la ENFP, correspondiente a mejor NFP. A menores alteraciones en el NFP, mayor cesación al final del tratamiento. En relación a los dominios, la cesación se asoció con identidad, autodirección y empatía y no así con intimidad. La mayoría de los pacientes con enfermedades tabaco-dependientes que presentaban alteraciones del NFP no logró cesar. Conclusiones: Los pacientes sin alteraciones del NFP, tienen más probabilidad de dejar y mantenerse sin fumar. Esto sugiere la utilidad de evaluar el NFP para predecir resultados en la cesación.

Abstract: Introduction: The smoking cessation results are unsatisfactory, less than 30% a year after the end of treatment. There is insufficient evidence on the relationship between the Level of Personality Functioning (LPF) and cessation. The LPF Scale (LPFS) of the Statistical Manual of Mental Disorders 5ed. that evaluates personality in relation to yourself and others, through four domains, could be useful in predicting and improving outcomes. Objectives: To assess the association between LPF and abstinence at the end of treatment and at 6 months. Methodology: Longitudinal and analytical study of a non-probability sample of patients who consulted in a Cessation Unit. The chi2 test or Fisher's exact test was applied to evaluate the association of categorical variables. LPF was evaluated with the LPFS and degree of nicotine dependence with the Fagerström Test. Results: 28 patients participated, 57% women, average age 48 years (± 12.3). 16 of 28 stopped, of them 14 had low scores in the LPFS, corresponding to better LPF. A less alteration in the LPF, greater cessation at the end of the treatment. Regarding the domains, the association was found with identity, self-direction and empathy with cessation but not with intimacy. Most of the patients with tobacco-dependent diseases who presented LPF disorder did not quit. Conclusions: Patients without LPF disorders are more likely to achieve cessation and remain abstinent. This assumes the utility of evaluating the LPF to predict cessation outcomes.

Resumo: Introdução: Os resultados da cessação do tabaco são insatisfatórios, menos de 30% ao ano após o término do tratamento. Não há suficiente evidência sobre a relação entre o Nível de Funcionamento da Personalidade (NFP) e a cessação. Escala NFP (ENFP) do Manual Estatístico de Transtornos Mentais 5 ed. que avalia a personalidade em relação a si mesmo e os outros, através de quatro domínios poderia ser útil para prever e melhorar os resultados. Objetivos: Avaliar associação entre NFP e abstinência ao final do tratamento e aos 6 meses. Metodologia: Estudo longitudinal, analítico de uma amostra não probabilística de pacientes consultados numa unidade de fumantes. Foram aplicados teste de Chi2 ou teste exato de Fisher para avaliar associação de variáveis categóricas. O NFP foi avaliado com ENFP e o grau de dependência física com Teste de Fagerström. Resultados: 28 pacientes participaram no estudo, 57% mulheres, idade média 48 anos (± 12,3). 16 dos 28 conseguirem cessar, 14 deles tiveram escores baixos do ENFP, correspondendo num melhor NFP. Quanto menos alterações no NFP, maior cessação ao final do tratamento. Em relação aos domínios, foi encontrada associação com identidade, autodireção e empatia com cessação, mas não é assim com intimidade. A maioria das pessoas com doenças dependentes do tabaco, que apresentavam alterações no PFN não conseguiu parar. Conclusões: Pacientes sem alterações no NFP têm maior probabilidade de cessação e permanecem livres de fumo. Isso sugere a utilidade de avaliar o NFP pra prever resultados na cessação.

Saborizantes y caracteres de diseño en cigarrillos y productos de tabaco disponibles próximos a centros educativos en Montevideo, Uruguay / Flavour additives and design lettering in cigarettes and tobacco products available close to educational centers in Montevideo, Uruguay / Sabores e características das embalagens de cigarros e produtos de tabaco disponíveis próximos a de centros educativos em Montevidéu, Uruguai

Resumen: Introducción: los productos de tabaco están diseñados para ser atractivos, introduciéndose últimamente elementos aditivos y saborizantes. En Uruguay existen normativas que evitan la publicidad en cualquiera de sus formas, por esto, la atracción del propio producto de tabaco a través de su sabor y diseño es un factor importante para la elección por parte de los fumadores, en particular, jóvenes. Es relevante conocer qué productos se encuentran disponibles en nuestro medio y cuáles son accesibles cerca de centros educativos. Material y método: se realizó un estudio descriptivo, observacional, prospectivo de corte transversal. El protocolo de trabajo de campo se adaptó del Sistema de Vigilancia de paquetes de Tabaco de la Universidad de Johns Hopkins. Resultados: se identificaron 23 variedades. El 34,78% de los productos fueron saborizados, estando disponibles en 86,67% de los puntos de venta. Todas las cajas de los saborizados tenían alguna referencia que indicaba su condición. En la mitad, la marca sugería la presencia de sabor o su activación. El 87,5% de los filtros se referían a la activación del sabor y 37,5% agregaban caracteres tecnológicos para éste; 75% tenía sabor a menta y 24% doble sabor. Solo 39,1% tenía información de protección al menor. Conclusiones e implicancias: hay una gran disponibilidad de productos de tabaco saborizados, incrementado la variedad en los últimos años, siendo en Uruguay menor que en otros países. En ausencia de regulación específica sobre aditivos y saborizantes, los países podrían disminuir la oferta implementando presentación única por marca y prohibición total de la publicidad.

Summary: Introduction: tobacco products are designed to be attractive, and recently, flavour additives have been introduced in the market. In Uruguay, regulations in force prohibit all forms of publicity for these products. For this reason, attracting consumers to tobacco products by means of flavour and design constitutes an important factor in smokers' choice, in particular the young. Learning about products available in our market and those that are close to educational centers is relevant. Method: descriptive, observational, prospective and transversal study. The field work protocol was adapted from the Johns Hopkins University Tobacco Pack Surveillance System Project. Results: 23 varieties were identified. 34.78% of the products were flavoured, and they were available in 86,67% points of sale. All flavoured products' packs included a reference to its condition. In 50% of them, the brand suggested the presence or activation of flavour. 87.5% of filters referred to flavor activation and 37.5% added technological traits. 75% were mint flavoured and 24% were double-flavoured. Only 39.1% included minor protection information. Conclusions: there is great availability of flavoured tobacco products, the variety being greater in recent years, although lower in Uruguay if compared to other countries. In the absence of specific regulations on additives and flavouring substances, countries could reduce the offer by implementing a single presentation by brand and the complete banning of publicity.

Resumo: Introdução: os produtos do tabaco são projetados para serem atraentes, com aditivos e elementos aromatizantes recentemente introduzidos. No Uruguai, existem normas que proíbem a publicidade em qualquer de suas formas, portanto, a atração do próprio produto do tabaco pelo seu sabor e design é um fator importante na escolha dos fumantes, principalmente dos jovens. É importante saber quais produtos estão disponíveis em nosso ambiente e quais estão disponíveis próximos a centros educativos. Material e métodos: foi realizado um estudo transversal descritivo, observacional e prospectivo. O protocolo de trabalho de campo foi adaptado do Sistema de Vigilância de Pacotes de Tabaco da Universidade Johns Hopkins. Resultados: foram identificadas 23 marcas diferentes. 34,78% dos produtos eram aromatizados, estando disponíveis em 86,67% dos pontos de venda. A embalagem de todas as marcas com sabor tinha alguma referência indicando essa característica. A metade delas indicava a presença do sabor ou sua ativação. 87,5% dos filtros referiram-se à ativação do sabor e 37,5% agregaram sus características tecnológicas. 75% tinham sabor mentolado e 24% dois sabores. Apenas 39,1% possuíam informações de proteção à criança. Conclusões e implicações: há uma grande disponibilidade de produtos de tabaco aromatizados, e a variedade tem aumentado nos últimos anos, sendo menor no Uruguai que em outros países. Na ausência de regulamentação específica sobre aditivos e aromatizantes, os países poderiam reduzir a oferta implementando uma apresentação única por marca e a proibição total da publicidade.

Humo de tabaco en vehículos: medición de partículas de materia 2. 5 micras / Smoking in vehicles: measurement of 2. 5 PM matter particles

Introducción: proteger a la población del humo de segunda mano (HSM) es uno de los principios de la Organización Mundial de la Salud en el marco del control del tabaco. Existen pocos datos acerca de la exposición de HSM en vehículos en América del Sur. Este estudio tuvo como objetivo determinar el nivel de dicha exposición. Materiales y método: se midieron niveles de micropartículas de materia de 2,5 micras de diámetro (PM2,5) que vehiculizan el HSM en la vía aérea, en modelos experimentales en autos de fumadores y no fumadores. Resultados: la media de la concentración de PM2,5 fue de 181 µg/m3 en los autos de fumadores y de 0 µg/m3 en los autos de no fumadores (p <0,001). La máxima concentración fue de 2.900 µg/m3 en un auto de fumador estacionado con la ventanilla del conductor parcialmente abierta. Conclusiones: las concentraciones de PM2,5 en vehículos en los que se fuma alcanzó niveles altos, similares a los que se encuentran en ciertos países con políticas de control de tabaco débiles. Este hecho determina la necesidad de nuevas políticas públicas para eliminar el HSM de los vehículos para proteger la salud pública. (AU)

Introduction: Protection from second-hand smoke (SHS) is one of the main principles of the World Health Organization Framework Convention for Tobacco Control. Limited data is available on SHS exposure in vehicles in South America. This study aimed to assess the levels of exposure. Methods: Levels of respirable and fine suspended particles with 2.5 micrometres or less (PM2.5) diameter were measured in different models in smokers' and non-smoker´s vehicles. Results: Median PM2.5 concentration was 181 µg/m3 in "smoking vehicles" and 0 µg/m3 in "non-smoking vehicles" (p<0.001). The highest concentration reached 2.900 µg/m3 in a parked car with the driver's window partially open. Conclusions: Concentration of PM2.5 in vehicles reached high levels, similar to those at certain sites in countries with weak tobacco control policies. These facts underscore a need for new public policies to eliminate SHS in vehicles to protect public health.

Introdução: um dos princípios da Organização Mundial da Saúde no contexto do controle do tabaquismo é proteger a população da fumaça de segunda-mão (HSM). Existem poucos dados sobre a exposição de HSM em veículos na América do Sul. O objetivo deste estudo foi identificar um mecanismo para determinar o nível desta exposição. Materiais e métodos: utilizando modelos experimentais em veículos de fumantes e não fumantes foram medidos os níveis de micropartículas de matéria de 2,5 micras de diâmetro (PM2,5) transportados pela HSM na via aérea. Resultados: á concentração média de PM2,5 foi 181 µg/m3 nos automóveis de fumantes e 0 µg/m3 nos automóveis de não fumantes (p<0.001). A concentração máxima de 2.900 µg/m3 foi encontrada no automóvel estacionado de um fumante com a janela do motorista parcialmente aberta. Conclusões: as concentrações de PM2,5 em veículos de fumantes alcançou níveis altos, similares aos encontrados em alguns países com políticas de controle de tabaco débeis. Este fato determina a necessidade de novas políticas públicas para eliminar a HSM dos veículos para proteger a saúde pública.

Prevalence of invehicle smoking and secondhand smoke exposure in Uruguay.

INTRODUCTION: Protection from secondhand smoke (SHS) is one of the fundamental principles of the WHO Framework Convention for Tobacco Control. Objective data on SHS exposure in vehicles in South America is scarce. This study aimed to estimate prevalence of smoking inside vehicles. METHODS: The point prevalence of smoking in vehicles was observed, and a method for estimating smoking prevalence was piloted. RESULTS: We observed 10 011 vehicles. In 219 (2.2%; 95% CI 1.91 to 2.49) of them, smoking was observed, and in 29.2% of these, another person was exposed to SHS. According to the 'expansion factor' we constructed, direct observation detected one of six to one to nine vehicles in which smoking occurred. The observed prevalence of smoking in vehicles (2.2%) could reflect a real prevalence between 12% and 19%. In 29.2% (95% CI 23.6 to 35.5) and 4.6% (95% CI 2.2 to 8.3) of vehicles in which smoking was observed, another adult or a child, respectively, was exposed to SHS. CONCLUSIONS: Smoking was estimated to occur in 12%-19% of vehicles, with involuntary exposure in one of three of vehicles observed. These data underscore a need for new public policies to eliminate SHS in vehicles to protect public health.

The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms.

CONTEXT AND OBJECTIVE: By using molecular markers, it is possible to gain information on both the classification and etiopathogenesis of chronic myeloproliferative neoplasias (MPN). METHODS: In a group of 27 Mexican mestizo patients with MPNs, we studied seven molecular markers: the BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation, the MPL W515K mutation, and the calreticulin (CALR) exon 9 deletion or insertion. Patients with the BCR/ABL1 fusion gene were excluded. We studied 14 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary myelofibrosis (MF), and one with undifferentiated MPN. RESULTS: We found twelve individuals with the JAK2 V617F mutation; five of them had been clinically classified as PV, five as ET, and one as MF. One patient with the MPL W515L was identified with a clinical picture of ET. Five patients with the CALR mutation were identified, four ET and one MF. No individuals with either the MPL W515K mutation or the JAK2 exon 12 mutations were identified. The most consistent relationship was that between PV and the JAK2 V617F mutation (p=.01). CONCLUSIONS: Despite its small size, the study shows much less prevalence of JAK2 mutation in PV, ET and MF, which does not match international data.

Pharmacogenetic selection of volunteers increases stringency of bioequivalence studies; the case of clopidogrel.

Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers.

Primary thrombophilia in Mexico IX: the glycoprotein IIIa PLA1/A2 polymorphism is not associated with the sticky platelet syndrome phenotype.

INTRODUCTION: The sticky platelet syndrome (SPS) seems to be a common cause of thrombosis, although no molecular substrate to explain platelet hyperaggregability has been found. OBJECTIVE: To analyze an association between the SPS phenotype and the platelet glycoprotein (GP) IIIa PL(A1/A2) (human platelet antigen [HPA]-1a/b) gene polymorphism. METHODS: Along an 18-month period, Mexican mestizo thrombophilic patients were prospectively accrued. The SPS phenotype was assessed by aggregometry, whereas a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction analysis was used to detect the PLA1 and PLA2 alleles. RESULTS: A total of 95 individuals with SPS and 127 healthy donors were studied; in 11 of the donors and 16 of the patients with SPS the A2 allele of the GP IIb/IIIA was found, yielding a weak and nonsignificant association (odds ratio 2.14, 95% CI 0.94-4.85). CONCLUSION: In Mexican mestizo patients, the platelet GP IIIa PL(A1/A2) gene polymorphism does not lead to the SPS phenotype.

Primary thrombophilia in México VII: the V617F mutation of JAK2 is not a frequent cause of thrombosis.

The study of the V617F JAK2 gene mutation has been used to identify the presence of an underlying myeloproliferative disorder (MPD) as the cause of unexplained thrombosis. In a group of 77 consecutive Mexican patients with a clinical marker of a primary thrombophilic condition, we looked for this JAK2 mutation and did not find any individual displaying it. Given these results, we conclude that an undetected MPD is a very improbable cause of thromboses in Mexican mestizos, a population where the prevalence of these disorders has been found to be lower than that found in Caucasian populations. Accordingly, it seems that the investigation for the V617F mutation of the JAK2 gene is not mandatory in all Mexican mestizo patients with unexplained thrombophilia and that this genetic study should be reserved for special cases, such as patients with thrombosis in uncommon sites or patients with cell counts suggesting the presence of an underlying MPD.

Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico.

Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.

t(8;21) (q22;q22) acute myelogenous leukemia in Mexico: a single institution experience.

We analyze the prevalence and clinical features of a group of patients with t(8;21) (q22;q22) acute myeloblastic leukemia, identified in a single institution in México over a 10-year period. Fifteen patients presented at the Centro de Hematología y Medicina Interna de Puebla from February 1995 to August 2005; only nine were treated and followed in the institution. Median age was 24 years, (range 7-49); there was only one male. According to the French-American-British (FAB) morphological classification of leukemia, the morphology was M2 in four cases, M4 in three cases, M3 in one case and M0 in one. In addition to the myeloid markers, lymphoid markers were identified in 6 patients. Patients were induced to remission with combined chemotherapy and three subsequently underwent bone marrow transplantation (BMT). The median overall and disease-free survival has not been reached, being above 3390 days, the probability of survival at this time was 73%. In this single-center experience in México, we found that the t(8;21) (q22;q22) variant of leukemia was more frequent than in Caucasian populations, that the co-expression of lymphoid markers in the blast cells is very frequent and that this malignancy is associated with a relatively good prognosis.

The Janus Kinase 2 (JAK2) V617F mutation in hematological malignancies in México / La mutación V617F del gen de la cinasa JAK2 en padecimientos hematológicos malignos en México

A new mutation (V617F) affecting the JAK2 gene has been recently described as acquired in patients with myeloproliferative disorders and other myeloid malignancies. Using an amplification refractory mutation system, we investigated this mutation in 70 Mexican mestizo patients with hematological malignancies: 28 cases of acute lymphoblastic leukemia, 17 cases of Phi-positive chronic myelogenous leukemia, 8 patients with acute myelogenous leukemia, 6 patients with chronic lymphocytic leukemia, 6 patients with polycythemia vera (PV), two patients with essential thrombocythemia (ET), one patient with hypereosinophilic syndrome one patient with primary myelofibrosis (MF) and one patient with chronic myelomonocytic leukemia. The mutation was identified in 4 of 6 patients with PV, in one of 2 patients with ET and in the patient with MF. Our data add to the observation that the JAK2 V617F mutation seems to be rather uncommon in myeloid malignancies other than the classic BCR/ABL negative MPD.

Se ha descrito una nueva mutación (V617F) que afecta al gen de la cinasa JAK2 en pacientes con padecimientos mieloproliferativos y otras neoplasias mieloides. Empleando un sistema de amplificación de mutaciones refractarias y reacción en cadena de la polimerasa, investigamos esta mutación en 70 pacientes mestizos mexicanos con neoplasias hematológicas malignas: 28 casos de leucemia aguda linfoblástica, 17 casos de leucemia granulocítica crónica BCR/ABL (+), ocho casos de leucemia aguda mieloblástica, seis casos de leucemia linfocítica crónica, seis casos de policitemia vera (PV), dos casos de trombocitosis primaria (TP), un caso de síndrome hipereosinofílico primario y un caso de mielofibrosis primaria (MF) y un caso de leucemia mielomonocítica crónica. La mutación se identificó en cuatro de seis pacientes con PV, en uno de dos pacientes con TP y en el paciente con MF. Estos datos confirman que esta mutación es infrecuente en neoplasias hematológicas mieloides diferentes a los síndromes mieloproliferativos malignos negativos al BCR/ABL; es probable que esta mutación se convierta en el marcador molecular de la PV.

Molecular characterization of alpha-thalassemia in the Mexican population.

BACKGROUND: alpha-Thalassemia (alpha-Thal) has been poorly characterized at the molecular level in Mexico. METHODS: 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period. alpha and beta-Thal were looked for, the former were characterized at the molecular level. RESULTS: Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of betaThal and 11 cases of alphaThal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the alpha-Thal cases, 8 were heterozygous and two were homozygous for the -alpha3.7 deletion, whereas one case was heterozygous for the alpha2Hph allele. CONCLUSIONS: Only few of the alpha-Thal alleles tested were found, thus the alpha-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Molecular characterization of alpha-thalassemia in the Mexican population / Caracterización molecular de talasemia alfa en una población mexicana

Background. α-Thalassemia (α-Thal) has been poorly characterized at the molecular level in Mexico. Methods. 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period, α and β-Thal were looked for, the former were characterized at the molecular level. Results. Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of β-Thal and 11 cases of α-Thal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the α-Thal cases, 8 were heterozygous and two were homozygous for the -α3.7 deletion, whereas one case was heterozygous for the α2Hph allele. Conclusions. Only few of the α-Thal alleles tested were found, thus the α-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Antecedentes. En México, la α-talasemia (α-Thal) ha sido pobremente caracterizada a nivel molecular. Mátodos. Se estudiaron 106 individuos consecutivos identificados en los Laboratorios Clínicos de Puebla, con hipocromia (CMH < 24 pg) y lo microcitosis (VCM < 75 fl en mujeres o 80 fl en hombres), sin deficiencia de hierro, con o sin anemia, durante un periodo de 16 meses. Se investigaron α y β-Thal; las primeras fueron caracterizadas a nivel molecular. Resultados. De los 106 casos consecutivos estudiados con hipocromia y/o microcitosis, y niveles normales del complejo de protoporfirina-cinc, 48 casos (45.3%) tenían talasemias (37 de ellos β-Thal y 11 α-Thal), mientras que en 58 casos (54.7%) no pudo establecerse un diagnóstico definitivo. De las talasemias α, ocho casos eran heterocigotos y dos homocigotos para la deleción -α3.7, mientras que sólo un caso resultó heterocigoto para el alelo α2Hph. Conclusiones. De los alelos α-Thal estudiados sólo se encontraron algunos, de lo que se infiere que en la población estudiada esas mutaciones parecen ser bastante heterogáneas.

HFE-codon 63/282 (H63D/C282Y) gene variants in Mexican Mestizos are not risk factors for leukemia.

BACKGROUND: In some Caucasian populations it has been found that the C282Y hemochromatosis (HFE) gene mutation is a risk factor for the development of leukemia and other malignancies. METHODS: In a group of 50 Mexican mestizo patients and 153 normal controls, the HFE gene mutations H63D and C282Y were studied by means of ARMS-PCR. RESULTS: In the group of patients with leukemia we found a heterozygote for the C282Y mutation, seven heterozygotes for the H63D mutation, a double heterozygote for the H63D / C282Y mutation and 41 normal homozygotes. These data are not different from those observed in normal controls, where the allele frequencies were 0.062 and 0.013 for the H63D and C282Y HFE gene mutations, respectively. CONCLUSIONS: These HFE gene mutations are not risk factors for the development of leukemia in Mexican mestizos.

The Janus Kinase 2 (JAK2) V617F mutation in hematological malignancies in México.

A new mutation (V617F) affecting the JAK2 gene has been recently described as acquired in patients with myeloproliferative disorders and other myeloid malignancies. Using an amplification refractory mutation system, we investigated this mutation in 70 Mexican mestizo patients with hematological malignancies: 28 cases of acute lymphoblastic leukemia, 17 cases of Ph1-positive chronic myelogenous leukemia, 8 patients with acute myelogenous leukemia, 6 patients with chronic lymphocytic leukemia, 6 patients with polycythemia vera (PV), two patients with essential thrombocythemia (ET), one patient with hypereosinophilic syndrome one patient with primary myelofibrosis (MF) and one patient with chronic myelomonocytic leukemia. The mutation was identified in 4 of 6 patients with PV, in one of 2 patients with ET and in the patient with MF. Our data add to the observation that the JAK2 V617F mutation seems to be rather uncommon in myeloid malignancies other than the classic BCR/ABL negative MPD.

Treatment of acute promyelocytic leukemia: a single institution experience.

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

Treatment of acute promyelocytic leukemia: A single institution experience / Tratamiento de la leucemia promielocítica aguda: Experiencia de una sola institución

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

Se informan los resultados del tratamiento en una sola institución de 14 pacientes con leucemia aguda promielocítica (LAPM) en quienes se empleó la combinación de ácido holotrans-retinoico (ATRA) quimioterapia combinada y prednisona profiláctica. La mediana de edad fue de 30 años (rango 7-49). Se obtuvo remisión completa (hematológica y molecular) (RC) en 13 pacientes (93%); a todos los pacientes se les administró el ATRA de manera ambulatoria. La RC se obtuvo con el ATRA en cinco pacientes; en los demás la RC se obtuvo después de habérseles administrado la quimioterapia con citarabina/adriamicina. No hubo ningún caso de síndrome de ATRA. Un paciente recayó con una LAPM PML/ RAR-a negativa, 575 días después de haber logrado la RC y falleció. Otro paciente recayó 20 meses después de haber logrado la RC y fue rescatado con el mismo esquema de tratamiento; permanece en segunda remisión molecular por más de seis años. La mediana de supervivencia (SV), tanto global como libre de recaídas de todo el grupo, no se ha alcanzado y es mayor de 4,000 días, en tanto que la SV a 12 meses fue de 93% y a tres y cinco años de 85%. El esquema de tratamiento usado difiere de otros en que se usa prednisona oral, se administra el ATRA de manera ambulatoria y se usa adriamicina y no otras antracidinas; los resultados son similares a los obtenidos con otros esquemas parecidos en otros sitios del mundo; es posible que el uso profiláctico de prednisona haya eliminado la ocurrencia del síndrome de ATRA.