RESUMO
INTRODUCTION: The most common early postoperative complication after total laryngectomy (TL) is pharyngocutaneous fistula (PCF). Rates of PCF are higher in patients who undergo salvage TL compared with primary TL. Published meta-analyses include heterogeneous studies making the conclusions difficult to interpret. The objectives of this scoping review were to explore the reconstructive techniques potentially available for primary TL and to clarify which could be the best technique for each clinical scenario. METHODS: A list of available reconstructive techniques for primary TL was built and the potential comparisons between techniques were identified. A PubMed literature search was performed from inception to August 2022. Only case-control, comparative cohort, or randomized controlled trial (RCT) studies were included. RESULTS: A meta-analysis of seven original studies showed a PCF risk difference (RD) of 14% (95% CI 8-20%) favoring stapler closure over manual suture. In a meta-analysis of 12 studies, we could not find statistically significant differences in PCF risk between primary vertical suture and T-shaped suture. Evidence for other pharyngeal closure alternatives is scarce. CONCLUSION: We could not identify differences in the rate of PCF between continuous and T-shape suture configuration. Stapler closure seems to be followed by a lower rate of PCF than manual suture in those patients that are good candidates for this technique.
Assuntos
Fístula Cutânea , Neoplasias Laríngeas , Doenças Faríngeas , Procedimentos de Cirurgia Plástica , Humanos , Fístula Cutânea/prevenção & controle , Fístula Cutânea/complicações , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Doenças Faríngeas/etiologia , Doenças Faríngeas/prevenção & controle , Doenças Faríngeas/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
La Ataxia de Friedreich (AF) es una enfermedad neurodegenerativa autosómica recesiva con compromiso multisistémico. En esta revisión, se actualizan aspectos epidemiológicos, fisiopatológicos y clínico-terapéuticos y se conduce una búsqueda sistemática de casos de AF reportados en Latinoamérica. La prevalencia de AF en poblaciones caucásicas es estimada entre 2 y 5 casos por 100 000 habitantes. En Latinoamérica se han publicado 35 estudios que reúnen 1481 casos en 6 países. Causada por la expansión anormal de repeticiones GAA en el gen FXN, la etiopatogenia está asociada a una reducción en los niveles de la proteína frataxina (que altera el metabolismo energético) y el acúmulo de hierro mitocondrial. El fenotipo clásico de AF suele comenzar antes de los 25 años, aunque hay otros de inicio tardío y retención de reflejos. La sintomatología se caracteriza por ataxia progresiva, alteración sensitiva, arreflexia, disartria, y alteraciones oculomotoras, además de compromiso cardiaco, endocrino y musculoesquelético. El diagnóstico requiere evaluación neurológica detallada, estudios neurofisiológicos, neuroimágenes y pruebas bioquímicas pero el enfoque determinante es el estudio genético que demuestre variantes genéticas bialélicas en el gen FXN. El manejo es multidisciplinario, orientado a aminorar los síntomas, prevenir complicaciones y brindar asesoramiento genético apropiado. Recientemente se ha aprobado el primer tratamiento farmacológico para AF con varios más en fases de experimentación.
SUMMARY Friedreich Ataxia (FA) is an autosomal recessive neurodegenerative disease with multisystemic involvement. This update of epidemiological, pathophysiological, and clinico-therapeutic aspects of FA, includes a systematic review of cases in Latin America. The estimated FA prevalence in Caucasian populations is between 2 to 5 cases per 100 000. In Latin America, 1481 cases have been published in 35 articles from six different countries. Caused by an abnormally repeated expansion of GAA trinucleotide inside the FXN gene, FA's etiopathogenesis is associated with reduced levels of the frataxin protein, which disturb the energy metabolism and result in mitochondrial iron accumulation. The classic phenotype usually shows symptoms before the age of 25, although there are others with a later onset. The main symptoms of AF are progressive ataxia, sensory disturbances, areflexia, dysarthria, and oculomotor alterations, in addition to cardiac, endocrine, and musculoskeletal compromise. Diagnostic workup requires a detailed neurological examination, neuroconduction studies, neuroimaging, and biochemical tests. The definitive diagnosis is provided by genetic testing showing biallelic variants within the FXN gene. The management is multidisciplinary, aimed at reducing symptoms, preventing complications, and providing an appropriate genetic counseling. Recently, the first pharmacological treatment for AF has been approved, with several others in clinical assessment trials.
Assuntos
Humanos , Adulto Jovem , Ataxia , Ataxia de Friedreich , Proteínas de Ligação ao Ferro , Genes Recessivos , América Latina , Relatos de CasosRESUMO
Introducción: la infección por SARS-CoV-2 en niños representa un porcentaje menor en la incidencia global de pacientes infectados por este virus. La prueba de reacción en cadena de polimerasa (PCR) para SARS-CoV-2 en muestra de secreciones nasofaríngeas es considerada como estándar de referencia, con niveles de sensibilidad y especificidad superiores a otras técnicas. Objetivo: describir las características de los pacientes menores de 15 años a los que se realizó PCR para SARS-CoV-2 en un prestador privado de salud del interior del país entre el 1° julio 2020 y el 30 de abril 2021. Analizar posibles factores asociados a la positividad de la prueba. Describir las características de los casos con PCR positiva Metodología: estudio observacional prospectivo con un análisis retrospectivo de tipo caso-control, a partir del seguimiento de una cohorte de menores de 15 años a los que se les realizó una prueba de PCR para SARS-CoV-2 en el período analizado, en un prestador integral de salud privado del interior del país. Se recabaron datos durante el seguimiento de los pacientes de acuerdo a un protocolo institucional que incluye: datos patronímicos, causa de la solicitud de la PCR, características del contacto, resultado de PCR y umbral de ciclo (CT), manifestaciones clínicas y evolución. Resultados: se solicitaron 2.361 PCR a menores de 15 años (15% del total de las PCR de la institución). Promedio de edad: 8,6 años (rango 7 días-14 años y 11 meses); 49% niñas y 51% varones. Motivo de solicitud de la prueba: 78,4% para estudio de contacto, 14,3% por síntomas sin noción de contacto y 7,3% previo a ingreso hospitalario (de urgencia o coordinación). Porcentaje de positividad de todo el período: 14,7%, con una importante variabilidad mensual (5,6% en diciembre y 27% en abril). La PCR fue positiva en 346 casos, con CT promedio de 27, y rango entre 16,8 y 37,3. No se encontraron diferencias estadísticas en relación a la edad y sexo entre casos positivos y negativos. Solo un caso fue PCR positivo previo al ingreso hospitalario (OR 0,03; IC 95% 0,004-0,22) y 20 de las 611 PCR solicitadas por contacto institucional (escolar, deportivo, etc.), siendo la diferencia estadísticamente significativa cuando el caso era mayor de 15 años (p 0,029). Del estudio retrospectivo de casos (PCR positiva) y controles (PCR negativa) surge una asociación estadísticamente significativa (p<0,000001) con la causa de solicitud por contacto en comparación con otra causa (OR 5,2; IC 95% 3,28-8,26), que el caso índice sea mayor de 15 años (OR 4,57 IC 95% 2,95 - 7,10) y que sea conviviente (OR 5,28 IC 95% 3,97 - 7,04). No hubo hospitalizaciones ni fallecimientos por COVID en la población analizada. Conclusiones: el testeo de niños y adolescentes en busca de COVID 19 continúa siendo una estrategia válida cuando existen síntomas sugestivos o contacto con un caso confirmado. En este estudio, los niños con antecedente de contacto con conviviente positivo, y mayor de 15 años, mostraron una mayor proporción de resultados positivos de PCR para SARS-CoV-2.
Introduction: the SARS-CoV-2 infection has shown a lower percentage in children compared to the global incidence of patients infected by this virus. The Polymerase Chain Reaction (PCR) test for SARS-CoV-2 in a sample of nasopharyngeal secretions is considered the reference standard test, and it has shown higher sensitivity and specificity levels than other techniques. Objective: describe the characteristics of patients under 15 years of age who underwent PCR for SARS-CoV-2 in a private health provider in the interior of the country between July 1, 2020 and April 30, 2021. Analyze possible factors linked to test positivity. Describe the characteristics of cases with positive PCR Methodology: prospective observational study with a retrospective case-control analysis based on the follow-up of a cohort of children under 15 years of age who underwent a PCR test for SARS-CoV-2 in the period analyzed, at a private health provider in the interior of Uruguay. Data were collected during patients' follow-up according to the institutional protocol that includes: personal data, reason for requesting the PCR, contact data, PCR result and cycle threshold (CT), clinical manifestations and evolution. Results: 2,361 PCRs were performed to children of under 15 years of age (15% of all PCRs in the institution). Average age 8.6 years (range 7 days - 14 years and 11 months); 49% girls and 51% boys. Reason for requesting the test: 78.4% due to previous contact, 14.3% due to symptoms without knowledge of contact and 7.3% prior to hospital admission (emergency or scheduled). Positivity percentage for the entire period 14.7% with significant monthly variability (5.6% in December and 27% in April). The PCR was positive in 346 cases, with a mean CT of 27, and a range between 16.8 and 37.3. No statistical differences were found regarding age and sex between positive and negative cases. Only 1 case was positive PCR prior to hospital admission (OR 0.03 95% CI 0.004 - 0.22) and 20 out of the 611 PCR were requested due to prior institutional contact (school, sports centers, etc.), the difference being statistically significant when the patient was older than 15 years (p 0.029). From the retrospective study of cases (PCR positive) and controls (PCR negative), a statistically significant link (p<0.000001) arose regarding: when the request resulted from a prior contact compared to other causes (OR 5.2 CI 95% 3.28-8.26), when the index case was older than 15 years of age (OR 4.57 95% CI 2.95-7.10) and when the patient and the contact had cohabited (OR 5.28 95% CI 3.97-7.04). There were no hospitalizations or deaths from COVID in the population analyzed. Conclusions: testing children and adolescents for COVID 19 continues to be a valid strategy in case of suggestive symptoms or contact with a confirmed positive case. In this study, children with a history of contact with a positive case, and older than 15 years, showed a higher proportion of positive PCR results for SARS-CoV-2.
Introdução: a infecção por SARS-CoV-2 em crianças representa um percentual menor do que na incidência global de pacientes infectados por esse vírus. O teste de reação em cadeia da polimerase (PCR) para SARS-CoV-2 em uma amostra de secreções nasofaríngeas é considerado o padrão de referência, com níveis de sensibilidade e especificidade mais elevados do que outras técnicas. Objetivo: descrever as características dos pacientes menores de 15 anos de idade que realizaram PCR para SARS-CoV-2 em uma prestadora de saúde privada do interior do país entre 1º de julho de 2020 e 30 de abril de 2021. Analisar possíveis fatores associados à positividade do teste. Descrever as características dos casos com PCR positivo. Metodologia: estudo observacional prospectivo com análise retrospectiva caso-controle a partir do acompanhamento de uma coorte de crianças menores de 15 anos que realizaram teste de PCR para SARS-CoV 2 no período analisado, em uma assistência médica de saúde no interior do país. Os dados foram coletados durante o acompanhamento dos pacientes de acordo com o protocolo institucional e incluíram: informação pessoal, motivo da solicitação do PCR, características do contato, resultado do PCR e limiar de ciclo (CT), manifestações clínicas e evolução. Resultados: foram solicitados 2.361 PCRs de menores de 15 anos (15% do total de PCRs da instituição). Idade média 8,6 anos (variação 7 dias - 14 anos e 11 meses); 49% meninas e 51% meninos. Motivo do pedido do exame: 78,4% por estudo de contato, 14,3% por sintomas sem conhecimento de contato e 7,3% antes da internação (por emergência ou coordenação). Porcentagem de positividade para todo o período 14,7% com significativa variabilidade mensal (5,6% em dezembro e 27% em abril). O PCR foi positivo em 346 casos, com média de TC de 27 e variação entre 16,8 e 37,3. Não foram encontradas diferenças estatísticas em relação à idade e sexo entre os casos positivos e negativos. Apenas 1 caso foi PCR positivo antes da admissão hospitalar (OR 0,03 IC 95% 0,004 - 0,22) e 20 dos 611 PCR solicitados por contato institucional (escola, centros de esportes, etc.), sendo a diferença estatisticamente significativa para os casos que tinham mais de 15 anos de idade (p 0,029). Do estudo retrospectivo de casos (PCR positivo) e controles (PCR negativo), emergiu uma associação estatisticamente significativa (p <0,000001) quando: a causa da solicitação do teste tinha sido um contato positivo prévio em relação a outra causa (OR 5,2 IC 95% 3,28 - 8,26), e quando o caso índice era mais velho do que 15 anos (OR 4,57 IC 95% 2,95 - 7,10) ou coabitava com o paciente (OR 5,28 IC 95% 3,97 - 7,04). Não houve internações ou óbitos por COVID na população analisada. Conclusões: a testagem de crianças e adolescentes em busca de COVID-19 continua sendo uma estratégia válida quando há sintomas sugestivos ou contato com um caso positivo confirmado. Neste estudo, crianças com histórico de contato com casos positivos na mesma casa e mais velhos do que 15 anos de idade apresentaram maior proporção de resultados positivos de PCR para SARS-CoV-2.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Uruguai/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , COVID-19/transmissãoRESUMO
The development of new treatments capable of controlling infections and pain related to burns continues to be a challenge. Antimicrobials are necessary tools, but these can be cytotoxic for regenerating cells. In this study, antibiotic-anesthetic (AA) smart systems obtained by ionic complexation of polyelectrolytes with ciprofloxacin and lidocaine were obtained as films and hydrogels. Ionic complexation with sodium alginate and hyaluronate decreased cytotoxicity of ciprofloxacin above 70% in a primary culture of isolated fibroblasts (p < 0.05). In addition, the relative levels of the proteins involved in cell migration, integrin ß1 and p-FAK, increased above 1.5 times (p < 0.05) with no significant differences in cell mobility. Evaluation of the systems in a deep second-degree burn model revealed that reepithelization rate was AA-films = AA-hydrogels > control films > no treated > reference cream (silver sulfadiazine cream). In addition, appendage conservation and complete dermis organization were achieved in AA-films and AA-hydrogels. Encouragingly, both the films and the hydrogels showed a significantly superior performance compared to the reference treatment. This work highlights the great potential of this smart system as an attractive dressing for burns, which surpasses currently available treatments.
Assuntos
Queimaduras , Sulfadiazina de Prata , Alginatos/farmacologia , Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Ciprofloxacina/farmacologia , Fibroblastos , Humanos , Hidrogéis/farmacologia , Integrina beta1 , Íons , Lidocaína , Polieletrólitos , CicatrizaçãoRESUMO
Introducción: la autoridad sanitaria ha utilizado numerosas estrategias para la detección precoz de casos y control de la transmisión de SARS-CoV-2, entre ellas la vigilancia activa de infección en ingresos hospitalarios. Objetivo: describir la vigilancia activa de infección por SARS-CoV-2 en menores de 15 años con indicación de ingreso hospitalario durante la pandemia de COVID-19 en un prestador integral de salud privado del interior del país. Metodología: estudio observacional, descriptivo, prospectivo, de menores de 15 años con indicación de ingreso hospitalario del 1/4/2020 al 30/4/2021 en CRAMI-IAMPP. Vigilancia activa según pautas del MSP: PCR para SARS-CoV-2 previo al ingreso hospitalario, asociado a interrogatorio de antecedentes de contacto con caso positivo de COVID-19 y síntomas sugestivos de infección. Datos: causa de ingreso (médica o quirúrgica), tipo (coordinado, urgencia o traslado interhospitalario), vigilancia de síntomas. Se calculó incidencia de infección por SARS-CoV-2, frecuencias y porcentajes. Resultados: se indicó ingreso a cuidados moderados a 231 menores de 15 años. 129 varones (56%), promedio de edad 6,5 años. Causa de ingreso: quirúrgica 60% (coordinada 53%); 89 (40%) por patología médica (20% infecciosa, 19% neurológica, 15% respiratoria, etcétera). Ninguno ingresó por sospecha o confirmación de COVID-19. PCR positiva en un niño coordinado para procedimiento que se suspendió. Incidencia de infección por SARS-CoV-2: 0,4/100 ingresos hospitalarios. No hubo casos de infección intrahospitalaria. Conclusiones: la vigilancia activa de la infección por SARS-CoV-2 en menores de 15 años con criterio de ingreso hospitalario fue adecuada. La incidencia de infección fue muy baja y no se constató transmisión intrahospitalaria
Summary: Introduction: various strategies have been carried out by Health Authorities regarding the early detection and control of the transmission of SARS-CoV-2, including active infection surveillance in hospital admissions. Objectives: to describe the active surveillance of the SARS-CoV-2 infection in children of <15 years of age admitted to hospital during the COVID-19 pandemic at a private health provider, in the interior of the country. Methodology: observational, descriptive, prospective study of children of <15 years of age admitted to hospital from 4/1/2020 to 4/30/2021 at CRAMI IAMPP Hospital. Active surveillance according to the guidelines of the Ministry of Public Health: PCR Test for SARS-CoV-2 prior to hospital admission, plus an interview regarding contact history with a positive COVID-19 case and symptoms suggesting infection. Data: cause of admission (medical or surgical), type (coordinated, emergency or interhospital transfer), monitoring of symptoms. Incidence of SARS-CoV-2 infection, frequencies and percentages were calculated. Results: admission to moderate care was indicated for 231 children of <15 years. Males 129 (56%), average age 6.5 years. Cause of admission: surgical 60% (coordinated 53%); 89 (40%) due to medical pathology (20% infectious, 19% neurological, 15% respiratory, etc.). None were admitted due to suspicion or confirmation of COVID 19. Positive PCR was detected in a child coordinated for a procedure that was suspended. Incidence of SARS-CoV-2 infection: 0.4/100 hospital admissions. No cases of nosocomial infection. Conclusions: active surveillance of SARS-CoV-2 infection in children of <15 years of age with hospital admission criteria was adequate. The incidence of infection was very low and no intrahospital transmission was confirmed.
Introdução: as autoridades sanitárias do Uruguai têm implementado várias estratégias para a detecção precoce de casos e controle da transmissão do SARS-CoV-2, incluindo vigilância ativa de infecção em internações hospitalares. Objetivo: descrever a vigilância ativa da infecção por SARS-CoV-2 em crianças menores de 15 anos com indicação de internação durante a pandemia de COVID-19 num prestador de saúde do interior do país. Metodologia: estudo observacional, descritivo, prospectivo realizado a crianças menores de <15 anos com indicação de internação de 01/04/2020 a 30/04/2021 no Hospital CRAMI IAMPP. Vigilância ativa de acordo com as diretrizes do MSP: PCR para SARS-CoV-2 antes da admissão hospitalar, associada ao questionamento de histórico de contato com um caso positivo de COVID-19 e sintomas sugestivos de infecção. Dados: causa de admissão (médica ou cirúrgica), tipo (coordenada, emergência ou transferência inter-hospitalar), monitorização dos sintomas. Incidência de infecção por SARS-CoV-2, frequência e porcentagens foram calculadas. Resultados: a internação em cuidados moderados foi indicada para 231 crianças <15 anos. Meninos 129 (56%), idade média 6,5 anos. Causa de internação: cirúrgica 60% (coordenada 53%); 89 (40%) por patologia médica (20% infecciosa, 19% neurológica, 15% respiratória, etc.). Nenhuma delas foi admitida por suspeita ou confirmação de COVID 19. Houve um Test PCR positivo em criança coordenada para procedimento que foi suspenso. Incidência de infecção por SARS-CoV-2: 0,4/100 internações hospitalares. Nenhum caso de infecção hospitalar. Conclusões: a vigilância ativa da infecção por SARS-CoV-2 em crianças <15 anos com critérios de internação hospitalar foi adequada. A incidência de infecção foi muito baixa e nenhuma transmissão intra-hospitalar foi confirmada.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Criança Hospitalizada/estatística & dados numéricos , Adolescente Hospitalizado/estatística & dados numéricos , Pandemias , Vigilância em Saúde Pública , COVID-19/epidemiologia , Uruguai/epidemiologia , Incidência , Estudos Prospectivos , Distribuição por Sexo , Estudo ObservacionalRESUMO
This study presents a new antibiotic-anesthetic film (AA-film) based on natural polyelectrolytes ionically complexed with lidocaine and ciprofloxacin to manage pain associated with infected wounds. The rational selection of the components resulted in the AA-films being transparent, compatible with wound skin pH and highly water vapor permeable. The drug release properties evaluated in saline solution and water revealed an ionic exchange mechanism for the release of both drugs and showed that ciprofloxacin acts as a cross-linker, as was confirmed by rheological evaluation. The in vitro antimicrobial efficacy against S. aureus and P. aeruginosa was demonstrated. Furthermore, AA-films exhibit a high fluid absorption capacity and act as a physical barrier for microorganisms. This work highlights the great potential of this smart system as an attractive dressing for skin wounds, surpassing currently available treatments.
Assuntos
Alginatos , Ciprofloxacina , Antibacterianos/uso terapêutico , Lidocaína , Staphylococcus aureus , CicatrizaçãoRESUMO
The in vivo release segregation of rifampicin (RIF) and isoniazid (INH) has been proposed as a strategy to avoid RIF acid degradation, which is known as one of the main factors for reduced RIF bioavailability and can result in drug-resistant tuberculosis. So far, this strategy has been scarcely explored. The aims of this study were to investigate the stability and bioavailability of RIF after combination of a very fast release matrix of RIF with a sustained delivery system of INH. A series of INH-alginic acid complexes (AA-INH) was obtained and characterized. Independent and sequential release profile of AA-INH at biorrelevant media of pH 1.20 and 6.80 was explored. In addition, AA-INH was combined with a RIF-carboxymethylcellulose very fast release complex (CMC-RIF) obtained previously and subjected to acid dissolution assays to evaluate RIF acid stability and determine RIF and INH dissolution efficiencies. Finally, a pharmacokinetic study in dogs was carried out. The AA-INH was easily obtained in solid-state. Their characterization revealed its ionic nature, with a loading capacity of around 30%. The dissolution efficiencies (15 min) confirmed release segregation in acid media with 7.8 and 65.6% for AA-INH and CMC-RIF, respectively. INH release rate from the AA-INH system was slow in acid media and increased in simulated intestinal media. The complete release of INH was achieved after 2 h in simulated intestinal media in the sequential release experiments. The acid degradation of RIF was significantly reduced (36.7%) when both systems were combined and oral administration to dogs revealed a 42% increase in RIF bioavailability. In conclusion, CMC-RIF and AA-INH may be useful for the formulation of a site-specific solid dosage form to overcome some of the main obstacles in tuberculosis treatment. Graphical abstract.
Assuntos
Isoniazida , Tuberculose , Animais , Antituberculosos , Disponibilidade Biológica , Cães , Rifampina , Tuberculose/tratamento farmacológicoRESUMO
Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to optimize the therapeutic efficacy of BNCT, contribute towards exploring the role of BNCT in veterinary medicine, put in place technical aspects for an upcoming clinical trial of BNCT for head and neck cancer at the RA-6 Nuclear Reactor, and assess the feasibility of employing the existing B2 beam to treat large, deep-seated tumors. Five dogs with head and neck cancer with no other therapeutic option were treated with two applications of BNCT mediated by boronophenyl-alanine (BPA) separated by 3-5 weeks. Two to three portals per BNCT application were used to achieve a potentially therapeutic dose over the tumor without exceeding normal tissue tolerance. Clinical and Computed Tomography results evidenced partial tumor control in all cases, with slight-moderate mucositis, excellent life quality, and prolongation in the survival time estimated at recruitment. These exploratory studies show the potential value of BNCT in veterinary medicine and contribute towards initiating a clinical BNCT trial for head and neck cancer at the RA-6 clinical facility.
RESUMO
other: Oral and oropharyngeal cancer is considered a public health problem in several countries due to its high incidence and mortality rate. OBJECTIVE: This study aimed to analyze oral and oropharyngeal cancer mortality in Uruguay from 1997 to 2014 by age, sex and country region. METHODOLOGY: A time series ecological study using secondary data was performed. Data on mortality due to oral and oropharyngeal cancers were obtained from the Vital Statistics Department of Uruguay's Ministry of Public Health. RESULTS: The cumulative mortality rate due to oral and oropharyngeal cancer over the study period was of 19.26/100,000 persons in women and 83.61/100.000 in men, with a mean annual rate of 1.75/100,000 in women and 7.60/100,000 in men. Mortality rate from both sites during the study period was 4.34 times higher in men than in women. Malignant neoplasms of other parts of the tongue and base of tongue showed the highest mortality rate. The means of the annual coefficients of deaths were higher for the age groups between 50 and 69 years. Higher mortality rates of oral and oropharyngeal cancer were observed in Artigas (4.63) and Cerro Largo (3.75). CONCLUSIONS: Our study described a high mortality rate for oral and oropharyngeal cancer in Uruguay from 1997 to 2014. According to the country's health department, men, tongue cancer, and oral cavity had higher mortality rates, with some variation. Prevention strategies with control of risk factors and early diagnosis are necessary to improve survival in the Uruguayan population.
Assuntos
Neoplasias Orofaríngeas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Fatores de Risco , Distribuição por Sexo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fatores de Tempo , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Uruguai/epidemiologia , Adulto JovemRESUMO
Abstract Oral and oropharyngeal cancer is considered a public health problem in several countries due to its high incidence and mortality rate. Objective: This study aimed to analyze oral and oropharyngeal cancer mortality in Uruguay from 1997 to 2014 by age, sex and country region. Methodology: A time series ecological study using secondary data was performed. Data on mortality due to oral and oropharyngeal cancers were obtained from the Vital Statistics Department of Uruguay's Ministry of Public Health. Results: The cumulative mortality rate due to oral and oropharyngeal cancer over the study period was of 19.26/100,000 persons in women and 83.61/100.000 in men, with a mean annual rate of 1.75/100,000 in women and 7.60/100,000 in men. Mortality rate from both sites during the study period was 4.34 times higher in men than in women. Malignant neoplasms of other parts of the tongue and base of tongue showed the highest mortality rate. The means of the annual coefficients of deaths were higher for the age groups between 50 and 69 years. Higher mortality rates of oral and oropharyngeal cancer were observed in Artigas (4.63) and Cerro Largo (3.75). Conclusions: Our study described a high mortality rate for oral and oropharyngeal cancer in Uruguay from 1997 to 2014. According to the country's health department, men, tongue cancer, and oral cavity had higher mortality rates, with some variation. Prevention strategies with control of risk factors and early diagnosis are necessary to improve survival in the Uruguayan population.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Orofaríngeas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Fatores de Tempo , Uruguai/epidemiologia , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias Orofaríngeas/patologia , Incidência , Fatores de Risco , Distribuição por Sexo , Distribuição por Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
HLA-DRB1 alleles has been found implicated in susceptibility to autoimmune hepatitis (AIH) in populations from different genetic backgrounds. In Mexicans, HLA-DRB1*04:04 is recognized as a risk allele for AIH but, to date, there is no high-resolution data supporting this association. Also, the association of other nonclassical HLA genes, such as TNF-LTA locus, have not, to our knowledge, been evaluated in this population. The association of HLA-DRB1 alleles determined by sequence-based typing and two polymorphisms in the TNF locus with AIH in a sample of Mexican patients was evaluated. Fifty-six patients from Guadalajara, Mexico, diagnosed with AIH and 115 age-gender matched healthy volunteer blood donors, were genotyped for HLA-DRB1 by the sequencing exon 2 and for TNFA-308G>A and LTA + 252A>G polymorphisms. Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients. However, after corrections for multiple comparisons, associations were not significant. In conclusion, our study does not support the association of HLA-DRB1*04:04:01 with the susceptibility to AIH in Mexican population. More studies including patients from other Mexican regions and considering other genetic, immunological, and environmental factors should be performed.
Assuntos
Cadeias HLA-DRB1/genética , Hepatite Autoimune/genética , Fator de Necrose Tumoral alfa/genética , Feminino , Humanos , Masculino , México , Razão de ChancesRESUMO
Our group has reported the imprint formation of biological material on polycarbonate nuclear track detectors by UV-C exposure, which is used as an approach to simultaneously visualize cell imprints and nuclear tracks coming from the boron neutron capture reaction. Considering that the cell nucleus has a higher UV-C absorption than the cytoplasm and that hematoxylin preferentially stains the nucleus, we proposed to enhance the contrast between these two main cell structures by hematoxylin staining before UV-C sensitization. In this study, several experiments were performed in order to optimize UV-C exposure parameters and chemical etching conditions for cell imprint formation using the SK-BR-3 breast cancer cell line. The proposed method improves significantly the resolution of the cell imprints. It allows clear differentiation of the nucleus from the rest of the cell, together with nuclear tracks pits. Moreover, it reduces considerably the UV-C exposure time, an important experimental issue. The proposed methodology can be applied to study the boron distribution independently from the chosen cell line and/or boron compounds.
Assuntos
Autorradiografia/métodos , Análise de Ativação de Nêutrons/métodos , Coloração e Rotulagem/métodos , Raios Ultravioleta , Boro/efeitos da radiação , Linhagem Celular Tumoral , Hematoxilina/metabolismo , Humanos , Oligoelementos/efeitos da radiaçãoRESUMO
Osteosarcoma is the most common primary malignant tumour of bone in young patients. The survival of these patients has largely been improved due to adjuvant and neo-adjuvant chemotherapy in addition to surgery. Boron neutron capture therapy (BNCT) is proposed as a complementary therapy, due to its ability to inactivate tumour cells that may survive the standard treatment and that may be responsible for recurrences and/or metastases. BNCT is based on neutron irradiation of a tumour enriched in 10B with a boron-loaded drug. Low-energy neutron capture in 10B creates charged particles that impart a high dose to tumour cells, which can be calculated only knowing the boron concentration. Charged particle spectrometry is a method that can be used to quantify boron concentration. This method requires acquisition of the energy spectra of charged particles such as alpha particles produced by neutron capture reactions in thin tissue sections irradiated with low-energy neutrons. Boron concentration is then determined knowing the stopping power of the alpha particles in the sample material. This paper describes the adaptation of this method for bone, with emphasis on sample preparation, experimental set-up and stopping power assessment of the involved alpha particles. The knowledge of boron concentration in healthy bones is important, because it allows for any dose limitation that might be necessary to avoid adverse effects such as bone fragility. The measurement process was studied through Monte Carlo simulations and analytical calculations. Finally, the boron content of bone samples was measured by alpha spectrometry at the TRIGA reactor in Pavia, Italy, and compared to that obtained by neutron autoradiography. The agreement between the results obtained with these techniques confirms the suitability of alpha spectrometry to measure boron in bone.
Assuntos
Boro/análise , Fêmur/química , Adulto , Partículas alfa , Animais , Humanos , Método de Monte Carlo , OvinosRESUMO
The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.
Assuntos
Queimaduras/tratamento farmacológico , Ciprofloxacina/administração & dosagem , Hidrogéis/química , Lidocaína/administração & dosagem , Administração Tópica , Animais , Ciprofloxacina/farmacologia , Modelos Animais de Doenças , Hidrogéis/farmacocinética , Lidocaína/farmacologia , Masculino , Coelhos , Reologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacosRESUMO
This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.
Assuntos
Antibacterianos , Ciprofloxacina , Polieletrólitos , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/urina , Ciprofloxacina/administração & dosagem , Ciprofloxacina/química , Ciprofloxacina/farmacocinética , Ciprofloxacina/urina , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Método Duplo-Cego , Liberação Controlada de Fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Polieletrólitos/administração & dosagem , Polieletrólitos/química , Polieletrólitos/farmacocinética , Comprimidos , Adulto JovemRESUMO
The detailed knowledge of the solid forms of a drug is a key element in pharmaceutical development. Morphine (MOR) is an opiate alkaloid widely used to treat severe acute and chronic pain. Much of the available information on its solid state dates from several decades ago. In order to obtain updated and reliable information, 1-dimensional (1D) and 2-dimensional solid-state nuclear magnetic resonance spectroscopy were used and complemented with powder X-ray diffraction, FTIR, and Raman spectroscopy and thermal analysis. 13C cross-polarization with magic angle spinning 1D spectra accomplish a complete identification of the related forms of MOR. Remarkably, 1H-13C heteronuclear correlation spectra together with FTIR results gave clear evidence that neither MOR nor its hydrate crystallizes as a zwitterion. Our results indicate that the hydrogen bonds in the anhydrate forms have a different nature or strength than in their respective hydrates. The unique information obtained would be useful for the characterization of MOR as a bulk drug, dosage forms, and future developments.
Assuntos
Morfina/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Cristalização/métodos , Cristalografia por Raios X/métodos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodos , Água/química , Difração de Raios X/métodosRESUMO
Irregular antibodies are produced by alloimmunization because of pregnancies or blood transfusions. They are called "irregular" due to target erythrocyte antigens from "rare blood systems," those different from the ABO system. Irregular antibodies have been widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood cross-matching, or to induce hemolytic transfusion reactions. Nevertheless, their incidence and participation in the physiopathology of autoimmune diseases have not been thoroughly studied. In this work, we analyzed the presence and pro-hemolytic capabilities of irregular antibodies in patients with different autoimmune diseases lacking signs of hemolytic anemia, in comparison with healthy multiparous women. Five of 141 autoimmune patients (3.5 %) and two of 77 multiparous women (2.6 %) were positive. Although frequency was relatively low and similar in both populations, the targeted antigens were Kell (k, Kpb, Jsb) and Luth (Lub) in multiparous women, and the same plus Duffy (Fya), Kidd (Jka) and MNS (M, s) in autoimmune patients. Irregular antibodies from autoimmune patients did not induce complement-mediated hemolysis (intravascular), but they were able to induce macrophages-mediated phagocytosis (extravascular hemolysis) in vitro. It is the first approach exploring the presence of irregular antibodies associated with the loss of immune tolerance and demonstrating their hemolytic potential in autoimmune patients without hemolytic manifestations. The presence of irregular antibodies targeted to Duffy (Fya), Kidd (Jka) and MNS (M, s) antigens only in autoimmune patients suggests a loss of immune tolerance to these erythrocyte antigens.