Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease.

BACKGROUND: CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES: Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS: The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS: The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS: The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases / O desafio do tratamento da tuberculose extensivamente resistente em um hospital de referência no estado de São Paulo: um relato de três casos

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

RESUMO Relatamos aqui os casos de três pacientes portadores de tuberculose extensivamente resistente, internados em um hospital de referência no estado de São Paulo, e mostramos sua evolução clínica, radiológica e laboratorial pelo período de um ano. O tratamento instituído foi baseado nas diretrizes da Organização Mundial da Saúde, com a inclusão de uma nova proposta de uso de uma associação de drogas antituberculose (linezolida e imipenem). Nos casos estudados, demonstrou-se o desafio de construir um esquema terapêutico aceitável e eficiente com drogas mais tóxicas, mais dispendiosas e que foram utilizadas por períodos mais prolongados. Mostramos também o importante acréscimo nos custos do tratamento desses pacientes, com possíveis impactos no sistema de saúde mesmo após a alta hospitalar. Ressaltamos que, em casos extremos como os apresentados neste estudo, a hospitalização em centros de referência mostrou-se o caminho mais efetivo para oferecer tratamento adequado com possibilidade de cura. Em conclusão, todos os esforços dos profissionais da saúde e do poder público devem ser direcionados a evitar casos de tuberculose multirresistente e extensivamente resistente.

Perspectives of Patients, Doctors and Medical Students at a Public University Hospital in Rio de Janeiro Regarding Tuberculosis and Therapeutic Adherence.

INTRODUCTION: The World Health Organization (WHO) identifies 8.7 million new cases of tuberculosis (TB) annually around the world. The unfavorable outcomes of TB treatment prevent the achievement of the WHO's cure target. GOAL: To evaluate existing intersections in the conceptions relative to the knowledge of TB, the experience of the illness and the treatment. METHODS: Doctors, medical students and patients were selected from a public university in Rio de Janeiro, Brazil, from 2011 to 2013. The data were obtained by semi-structured individual and focus group interviews, participant observation and a field journal. The inclusion of patients was interrupted due to saturation, and the inclusion of doctors and medical students stopped due to exhaustion. The theoretical background included symbolic Interactionism, and the analysis used rounded Theory. The analysis prioritized the actions/interactions axis. RESULTS: Twenty-three patients with pulmonary TB, seven doctors and 15 medical students were included. In the interviews, themes such as stigma, self-segregation, and difficulties in assistance emerged, in addition to defense mechanisms such as denial, rationalization, isolation and other mental mechanisms, including guilt, accountability and concealment of the disease. Aspects related to the assistance strategy, the social support network, bonding with the healthcare staff and the doctor-patient relationship were highlighted as adherence enablers. Doctors and students recommended an expansion of the theoretical and practical instruction on TB during medical students' education. The existence of health programs and policies was mentioned as a potential enabler of adherence. CONCLUSION: The main concepts identified were the stigma, self-segregation, guilt, responsibility, concealment and emotional repercussions. In relation to the facilitation of therapeutic adherence, the concepts identified were the bonds with healthcare staff, the doctor-patient relationship, assistance and educational health strategies.

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases.

Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen can cause drug-induced hepatitis, and we discuss the alternatives in this situation.

Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 2: second line drugs.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid). We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha / Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 1: first-line drugs

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Revisamos sucintamente o novo tratamento farmacológico da tuberculose introduzido pelo Ministério da Saúde do Brasil em 2009 e mostramos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no esquema básico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal. Também descrevemos os mecanismos pelos quais as interações das drogas antituberculose do esquema básico podem causar hepatite medicamentosa e as possíveis alternativas nessa situação.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen can cause druginduced hepatitis, and we discuss the alternatives in this situation.

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha / Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 2: second line drugs

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Descrevemos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no tratamento da tuberculose multidroga resistente (aminoglicosídeos, fluoroquinolonas, cicloserina/terizidona, etionamida, capreomicina e ácido para-aminossalicílico). Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid). We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

Isoniazid-resistant Mycobacterium tuberculosis strains arising from mutations in two different regions of the katG gene.

OBJECTIVE: To analyze and compare the mutations in two different regions of the katG gene, which is responsible for isoniazid (INH) resistance. METHODS: We analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the Professor Hélio Fraga Referral Center, in Brasília, Brazil. Another 6 INH-sensitive strains did not present mutations and were included as controls. We used PCR to amplify two regions of the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. RESULTS: Seven strains were resistant to INH and did not contain mutations in either region. Thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4% of the strains. Nine strains had mutations exclusively in region 1, which allowed the proportion of INH-resistant strains identified to be increased to 90.6%. CONCLUSIONS: The number of mutations at codon 315 was high, which is consistent with cases described in Brazil and in other countries, and the analysis of region 1 resulted in a 9.2% increase in the rate at which mutations were identified.

Resistência do Mycobacterium tuberculosis à isoniazida por mutações em duas regiões diferentes do gene katG / Isoniazid-resistant Mycobacterium tuberculosis strains arising from mutations in two different regions of the katG gene

OBJETIVO: Analisar e comparar as mutações em duas regiões diferentes do gene katG, responsáveis pela resistência à isoniazida (INH). MÉTODOS: As análises foram feitas em 97 cepas de Mycobacterium tuberculosis multirresistentes isoladas de culturas de escarro provenientes do Centro de Referência Professor Hélio Fraga. Outras 6 cepas, sensíveis à INH, não apresentaram mutações e foram incluídas como controle. Duas regiões do gene katG (GenBank nº de acesso U06258) - região 1, do códon 1 até o códon 119, e região 2, do códon 267 até o códon 504 - foram amplificadas por PCR e sequenciadas para a identificação das mutações. RESULTADOS: Sete cepas eram resistentes à INH e não mostraram mutação nas duas regiões. Trinta cepas apresentaram mutações na região 1, que se caracterizou por um grande número de deleções, especialmente no códon 4 (24 cepas). A região 2 mostrou 83 mutações pontuais, principalmente no códon 315, com 73 casos de troca de serina (AGC) para treonina (ACC). A análise da região 2 permitiu o diagnóstico de resistência à INH em 81,4 por cento das cepas. Nove cepas tiveram mutações somente na região 1, e isso permitiu o aumento de identificação de cepas resistentes à INH para 90,6 por cento. CONCLUSÕES: O número de mutações do códon 315 foi elevado, compatível com os casos descritos no Brasil e em outros países, e a análise da região 1 aumentou a detecção de mutações em mais 9,2 por cento.

OBJECTIVE: To analyze and compare the mutations in two different regions of the katG gene, which is responsible for isoniazid (INH) resistance. METHODS: We analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the Professor Hélio Fraga Referral Center, in Brasília, Brazil. Another 6 INH-sensitive strains did not present mutations and were included as controls. We used PCR to amplify two regions of the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. RESULTS: Seven strains were resistant to INH and did not contain mutations in either region. Thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4 percent of the strains. Nine strains had mutations exclusively in region 1, which allowed the proportion of INH-resistant strains identified to be increased to 90.6 percent. CONCLUSIONS: The number of mutations at codon 315 was high, which is consistent with cases described in Brazil and in other countries, and the analysis of region 1 resulted in a 9.2 percent increase in the rate at which mutations were identified.

Clinical evolution of a group of patients with multidrug-resistant TB treated at a referral center in the city of Rio de Janeiro, Brazil.

OBJECTIVE: To analyze the clinical characteristics and evolution of a group of patients with positive sputum cultures for multidrug-resistant (MDR) Mycobacterium tuberculosis and treated at a referral center in the city of Rio de Janeiro, Brazil. METHODS: Based on the positive results in sputum cultures for MDR M. tuberculosis, 50 patients were selected, and their clinical data were obtained from the Brazilian Ministry of Health MDR-TB Database. The frequencies of noncompliance, relapses, failures and previous treatments for TB up to diagnosis of MDR-TB were compiled. The radiological patterns were classified as unilateral or bilateral, and with or without cavitation. Two years after the end of the standard treatment for MDR-TB, the outcome (cure, failure, noncompliance or death) for each patient was evaluated and reassessed every two years. The post-treatment follow-up period was eight years. RESULTS: The mean number of previous treatments was 2.3 +/- 0.9. The mean interval between the initial diagnosis and the development of MDR-TB was 2.0 +/- 1.7 years. Two years after the initial treatment for MDR-TB, 2 patients had abandoned treatment, 8 had died, 18 had been cured, and 22 had presented treatment failure. The bivariate analysis showed that bilateral pulmonary involvement and cavitary pattern markedly reduced the chances for cure, with a relative risk of 1-0.6 (40%) and 1-0.7 (30%), respectively. At the end of the follow-up period, 2 patients had abandoned treatment, 9 had presented treatment failure, 17 had been cured, and 22 had died. CONCLUSIONS: Bilateral pulmonary involvement and cavity pattern greatly reduced the chances for cure of the patients with MDR-TB. Most patients who presented treatment failure died within the 8-year follow-up period.

Evolução clínica de um grupo de pacientes com TB multirresistente atendidos em um centro de referência na cidade do Rio de Janeiro / Clinical evolution of a group of patients with multidrug-resistant TB treated at a referral center in the city of Rio de Janeiro, Brazil

OBJETIVO: Analisar as características clínicas e a evolução de um grupo de pacientes com culturas de escarro positivas para Mycobacterium tuberculosis multirresistente (MR) e tratados em um centro de referência no município do Rio de Janeiro. MÉTODOS: A partir dos resultados de M. tuberculosis MR em culturas de escarro, foram selecionados 50 pacientes cujos dados clínicos foram obtidos através do Banco de Dados TBMR do Ministério da Saúde. Foram considerados a frequência de abandono, as recidivas, as falências e os tratamentos prévios para TB até o diagnóstico de TBMR. O padrão radiológico foi classificado em uni- ou bilateral, e cavitário ou não. Dois anos após o término do tratamento padronizado para TBMR, o desfecho (cura, falência, abandono ou óbito) de cada paciente foi avaliado e repetido a cada dois anos. O período de seguimento foi de oito anos após o tratamento. RESULTADOS: A média do número de tratamentos prévios foi de 2,3 ± 0,9. O tempo médio entre o diagnóstico inicial e o desenvolvimento de TBMR foi de 2 ± 1,7 anos. Após dois anos do tratamento inicial para TBMR houve 2 abandonos, 8 óbitos, 18 curas e 22 falências. A análise bivariada mostrou que o comprometimento pulmonar bilateral e o padrão cavitário reduziram acentuadamente a chance de cura, com risco relativo de 1-0,6 (40 por cento) e 1-0,7 (30 por cento), respectivamente. Ao final do seguimento, houve 2 abandonos, 9 falências, 17 curas e 22 óbitos. CONCLUSÕES: O comprometimento pulmonar bilateral e lesões cavitárias reduziram a possibilidade de cura dos pacientes com TBMR. A maioria dos pacientes com falha de tratamento evoluiu para óbito no período de 8 anos.

OBJECTIVE: To analyze the clinical characteristics and evolution of a group of patients with positive sputum cultures for multidrug-resistant (MDR) Mycobacterium tuberculosis and treated at a referral center in the city of Rio de Janeiro, Brazil. METHODS: Based on the positive results in sputum cultures for MDR M. tuberculosis, 50 patients were selected, and their clinical data were obtained from the Brazilian Ministry of Health MDR-TB Database. The frequencies of noncompliance, relapses, failures and previous treatments for TB up to diagnosis of MDR-TB were compiled. The radiological patterns were classified as unilateral or bilateral, and with or without cavitation. Two years after the end of the standard treatment for MDR-TB, the outcome (cure, failure, noncompliance or death) for each patient was evaluated and reassessed every two years. The post-treatment follow-up period was eight years. RESULTS: The mean number of previous treatments was 2.3 ± 0.9. The mean interval between the initial diagnosis and the development of MDR-TB was 2.0 ± 1.7 years. Two years after the initial treatment for MDR-TB, 2 patients had abandoned treatment, 8 had died, 18 had been cured, and 22 had presented treatment failure. The bivariate analysis showed that bilateral pulmonary involvement and cavitary pattern markedly reduced the chances for cure, with a relative risk of 1-0.6 (40 percent) and 1-0.7 (30 percent), respectively. At the end of the follow-up period, 2 patients had abandoned treatment, 9 had presented treatment failure, 17 had been cured, and 22 had died. CONCLUSIONS: Bilateral pulmonary involvement and cavity pattern greatly reduced the chances for cure of the patients with MDR-TB. Most patients who presented treatment failure died within the 8-year follow-up period.

Tubersulose: da resistência genômica à isoniazida e à rifampicina ao paciente com multirresistência / Tubersulosis: genomic resistance to isoniazid and rifampicin to patient with multiresistance

A tuberculose (TB) é a principal causa de morte no mundo, por um agente infeccioso único. Atualmente, o maior problema global da TB é o aumento gradual de cepas multirresistentes (resistência pelo menos à isoniazida e à rifampicina) do Mycobacterium tuberculosis (Mtb), pela dificuldade do tratamento que produz. Os dois objetivos iniciais deste trabalho foram: 1. Analisar os tipos de mutação que ocorrem em duas regiões iniciais do gene katG do Mtb, locais de maior frequência de mutações que causam resistência à isoniazida (INH) e 2. Determinar os tipos e frequências das mutações no gene rpoB que produzem resistência à rifampicina (RMP). As culturas, na grande maioria multirresistentes (MR), e os respectivos DNAs, foram fornecidos pelo Centre de Referência Professor Helio Fraga (FIOCRUZ). Duas regiões do gene katG, a primeira do códon 1 até o códon 119, e a segunda, do códon 267 até o códon 504, e a região entre os códons 445 e 560 do gene rpoB foram amplificadas por PCR e os produtos sequenciados, para o diagnóstico de mutações, que ocorreram nas cepas resistentes. Para a análise do gene katG foram utilizadas 101 cepas, conforme a disponibilidade. Na região 1 houve 30 casos de mutação, sendo 24 por deleção de um nucleotídeo no códon 4. Na região 2 ocorreram 80 mutações pontuais, sendo 73 no códon 315, a maioria de Serina AGC para Treonina ACC. Considerando as duas regiões o diagnóstico de resistência foi possível em 87,1% das 101 cepas. Na análise do gene rpoB usamos 120 cepas de Mtb e na região delimitada ocorreram 118 mutações em 107 cepas, sendo a maioria nos códons 531 (45.6%), 526 (26%) e 516 (12.5%). Nosso terceiro objetivo foi determinar as características clínicas e a evolução de 50 pacientes do Estado do Rio de Janeiro, com tuberculose pulmonar (pela facilidade de obtenção dos dados), infectados com os bacilos multirresistentes que estudamos anteriormente. A partir das culturas de escarro os doentes foram identificados e os dados clínicos...

Tuberculosis (TB) is the main cause of death in the world due to a single infectious pathogenic agent. Nowadays, one of the most serious global problems related to this disease is the increase in the occurrence of multidrug resistant (MDR) M. tubersulosis strains, resistant to isoniazid and rifampicin, and their treatment. Firstly, there are two early aims to objectives in the first part of this thesis: 1 - To analyze and compare the types kind of mutations in two different regions of the KatG gene, the usual region for responsible for isoniazid resistance; and 2 - To determine and compare the type and frequency of rpoB gene mutations envolved in the rifampicin resistance. The cultures, almost of all MDR, and their respectively DNA, were provided by Centro de Referência Professor Helio Fraga (FIOCRUZ). Two regions of the katG gene (gene bank U06252), the first going from codon 1 up to codon 119 and the second one, from codon 267 to codon 504, were amplified by PCR, and sequenced to identify the mutations. The analyses were done in 101 Mycobacterium tuberculosis sputum cultures from Centro de Referência Prof. Helio Fraga. To analyse of the KatG gene, were considered 101 TB sputum cultures were considered. Thirty cases had mutations in region 1, being 24 cases by deletions at codon 4. Region 2 showed 80 point mutations, especially at codon 315, where, in 73 cases changed Serine AGC was changed to Threonine ACC. Regarding both regions the diagnosis of resistance occurred in 87.1% of the 101 strains. The analyses of the rpoB gene was done with 120 TB strains, and 118 mutations were detected in 107 isolates, being the majority at codons 531 (45.6%), 526 (26%) and 516 (12.5%). The third aim was to determine the clinical features and evolution of 50 patients with multidrug-resistant Mycobacterium tuberculosis in the lung (TBMDR) from State of Rio de Janeiro. The sputum cultures to MDRTB, clinical data were obtained from Braziliam Ministry of Health MDRTB database...

O essencial na orientação do paciente com tuberculose / The essential information for tuberculosis patient

Embora a tuberculose seja doença curável, no Brasil ocorrem cerca de 5.000 mortes por ano. A maioria decorre do alcoolismo, do tratamento irregular ou do abandono do tratamento. Muitos destes casos se devem à falta de conhecimento da gravidade da doença e a possibilidade de cura. O doente não esclarecido mais facilmente liga a cura à ausência de sintomas e, assim que melhora, abandona o tratamento. A maior dificuldade do médico, para esclarecer o doente, é ter que transmitir um grande número de informações, em um tempo exíguo de consulta, pelo número de doentes que tem de atender. O objetivo deste artigo é oferecer ao médico que trata o doente com TB um texto escrito em linguagem coloquial, com os principais tópicos de orientação do paciente e que pode ser lido em casa, com a ajuda de um parente, ou ser usado como modelo para palestra em sala de espera.

Tuberculosis is concerned a curable disease, however in Brazil there are almost 5,000 deaths per year. The majority cases has been associated with alcohol and non-adherence to treatment. The patients have incorrectly correlated the lacking of symptoms with the cure, as consequence they quit the treatment early. This finding has been justified by poor relationship between patients and doctors. One the most difficult issue for doctors is to explain a long list of important points of this disease in an exiguous period of time in consult and their responsibility by attending of a long line of tuberculosis patients inworking time. The aim of this article is to offer for doctors who treat tuberculosis patients a written text in colloquial language, containing the main aspects for understanding of tuberculosis, which could be read at home by patients, together withfamily members, or as a brochure for lecture by health professionals at outside.

Unidades de pressão usadas em pneumologia, terapia intensiva e anestesia / Units of pressure used in pulmonary medicine, intensive care units and anesthesia

Existem mais de oito unidades de pressão, sendo seis de uso mais rotineiro em ambientes hospitalares: pascal (Pa), cmH2O, mmHg, psi, kgf/cm2 e bar. Esta diversidade dificulta o médico quando ele necessita converter unidades para interpretar um resultado. Nosso objetivo é enfocar a atenção do médico pneumologista, intensivista ou anestesista para as várias unidades de pressão, de uso comum em ambientes hospitalares, indicar modos de grafia destas unidades, propor métodos mnemônicos de conversão e demonstrar a importância do uso de apenas uma só unidade internacional de pressão, o pascal (Pa). O CONMETRO, órgão normalizador das unidades de medida sem uso no Brasil, determina e adota o uso do pascal (Pa) - unidade de pressão do Sistema Internacional de Unidades (SI) - e admite temporariamente o uso de outras unidades como atmosfera, bar e mmHg (Torr), embora não cite as unidades psi, kgf/cm2 ou cmH2O amplamente utilizadas em aparelhos hospitalares. Este Órgão legisla também sobre a grafia das unidades de pressão. As unidades depressão podem ser convertidas com o uso de regra de três e o endereço da Internet: http://www.webcalc.com.br pode ser consultado para conversão rápida. Fato importante é que os aparelhos médicos pneumáticos são padronizados para serem conectados em sistema de pressão de 3,45kgf/cm2, o que equivale a ~50psi ou 338kPa. Concluímos que o uso de múltiplas unidades de pressão traz para o médico diversas dificuldades de interpretação. A adoção do pascal (Pa) e seus múltiplos, como única unidade internacional de pressão vai unificar a linguagem médica. Esta adoção tem que ser gradativa considerando-se o grande número de aparelhos médicos em utilização. A única exceção será a permanência da unidade mmHg para medidas de pressão arterial.

Ventilaçäo com suporte pressórico e volume assegurado (VAPSV) em pacientes com DPOC agudizada em falência respiratória aguda / Volume assured pressure support ventilation (VAPSV) in COPD patients underwent acute respiratory failure

Objetivo: comparar o perfil de oxigenaçäo, macânica torácica e de mortalidade entre a ventilaçäo volumétrica com fluxo desacelerado linear (VCV-df) e da ventilaçäo com suporte pressórico com volume assegurado (VAPSV) em pacientes com doença pulmonar obstrutiva crônica durante o seu primeiro episódio de insuficiência respiratória aguda com necessidade de uso da ventilaçäo invasiva. Perfil: análise retrospectiva. Local: unidade de terapia intensiva multidisciplinar de um hospital público terciário. Pacientes: cem pacientes de ambos os sexos com episódios de agudizaçäo da DPOC com gravidade semelhante conforme o Apache II submetidos, respectivamente, à VCV-df e a VAPSV. Resultados: a VAPSV apresentou melhor perfil de oxigenaçäo, mecânica torácica, bem como de adaptaçäo e de adequaçäo de demanda dos pacientes, como demonstrado pelo seu menor tempo de permanência na prótese ventilatória e taxa de mortalidade mais baixa quando comparada à VCV-df. Conclusäo: a VAPSV pode ser cogitada como a primeira opçäo de suporte ventilatório na DPOC agudizada por insuficiência respiratória aguda.(au)