Fatores estressores no processo de desenvolvimento de neoplasias malignas em mulheres: uma revisão integrativa / Stressing factors in the development process of malignant neoplasms in women: an integrative review / Factores de estrés en el proceso de desarrollo de las neoplasias malignas en la mujer: una revisión integradora

A relação entre a origem de neoplasias e o estresse vem sendo objeto de estudo na literatura. Desde as primeiras investigações acerca da delimitação do gênero no processo do estresse é revelado ser mulher como uma variável significativa que leva ao adoecimento. O objetivo deste estudo é analisar na literatura se os fatores estressores vivenciados por mulheres influenciam no desenvolvimento de neoplasias malignas e identificar os fatores mais comuns associados a esse desenvolvimento. Trata-se de uma revisão integrativa realizada nas bases de dados SciELO, LILACS, BDENF, MEDLINE, e nas bibliotecas PubMed e BVS. Foram utilizados DeCS e MeSH para auxiliar na busca. Estabeleceram-se 11 artigos como corpus de análise que abordam a relação estresse-câncer em mulheres e sinalizaram estressores associados. Apesar da rede de estudos que apontam a relação do efeito do estresse no organismo e a ativação de componentes neuroendócrinos que impactam o surgimento de quadros neoplásicos, o entendimento da cadeia de reações químicas e resposta do metabolismo aos estímulos estressores ainda é complexo, demonstrando a necessidade da ampliação de estudos. É evidente a importância do acompanhamento ativo da saúde da mulher, além de atentar-se para minimizar fatores estressores e prevenir doenças relacionadas ao estresse.

The relationship between the origin of neoplasms and stress has been studied in the literature. Since the first investigations about the delimitation of gender in the stress process, being a woman has been revealed as a significant variable that leads to illness. The aim of this study is to analyze in the literature whether the stressors experienced by women influence the development of malignant neoplasms and to identify the most common factors associated with this development. This is an integrative review carried out in the SciELO, LILACS, BDENF, MEDLINE databases, and in the PubMed and VHL libraries. DeCS and MeSH were used to assist in the search. A total of 11 articles were established as a corpus of analysis that address the stress-cancer relationship in women and signaled associated stressors. Despite the network of studies that point to the relationship between the effect of stress on the body and the activation of neuroendocrine components that impact the appearance of neoplastic conditions, understanding the chain of chemical reactions and metabolism response to stressful stimuli is still complex, demonstrating the need to expand studies. The importance of actively monitoring women's health is evident, in addition to taking care to minimize stressors and prevent stress-related diseases.

La relación entre el origen de las neoplasias y el estrés ha sido estudiada en la literatura. Desde las primeras investigaciones sobre la delimitación del género en el proceso de estrés, ser mujer se ha revelado como una variable significativa que conduce a la enfermedad. El objetivo de este estudio es analizar en la literatura si los estresores experimentados por las mujeres influyen en el desarrollo de neoplasias malignas e identificar los factores más comunes asociados a este desarrollo. Esta es una revisión integradora, realizada en las bases de datos SciELO, LILACS, BDENF, MEDLINE, y en las bibliotecas PubMed y BVS. Se utilizaron DeCS y MeSH para ayudar en la búsqueda. Se establecieron 11 artículos como corpus de análisis que abordan la relación estrés-cáncer en mujeres y señalan estresores asociados. A pesar de la red de estudios que apuntan a la relación entre el efecto del estrés en el organismo y la activación de componentes neuroendocrinos que impactan en la aparición de condiciones neoplásicas, el conocimiento de la cadena de reacciones químicas y la respuesta del metabolismo a los estímulos estresantes es aún complejo, lo que demuestra que se necesita la ampliación de estudios. Queda evidente la importancia de monitorear activamente la salud de la mujer, además de minimizar los factores estresantes y prevenir enfermedades relacionadas con el estrés.

Secondary infections in a cohort of patients with COVID-19 admitted to an intensive care unit: impact of gram-negative bacterial resistance.

Some studies have shown that secondary infections during the COVID-19 pandemic may have contributed to the high mortality. Our objective was to identify the frequency, types and etiology of bacterial infections in patients with COVID-19 admitted to an intensive care unit (ICU) and to evaluate the results of ICU stay, duration of mechanical ventilation (MV) and in-hospital mortality. It was a single-center study with a retrospective cohort of patients admitted consecutively to the ICU for more than 48 h between March and May 2020. Comparisons of groups with and without ICU- acquired infection were performed. A total of 191 patients with laboratory-confirmed COVID-19 were included and 57 patients had 97 secondary infectious events. The most frequent agents were Acinetobacter baumannii (28.9%), Pseudomonas aeruginosa (22.7%) and Klebsiella pneumoniae (14.4%); multi-drug resistance was present in 96% of A. baumannii and in 57% of K. pneumoniae. The most prevalent infection was ventilator-associated pneumonia in 57.9% of patients with bacterial infections, or 17.3% of all COVID-19 patients admitted to the ICU, followed by tracheobronchitis (26.3%). Patients with secondary infections had a longer ICU stay (40.0 vs. 17 days; p < 0.001), as well as a longer duration of MV (24.0 vs 9.0 days; p= 0.003). There were 68 (35.6%) deaths overall, of which 27 (39.7%) patients had bacterial infections. Among the 123 survivors, 30 (24.4%) had a secondary infections (OR 2.041; 95% CI 1.080 - 3.859). A high incidence of secondary infections, mainly caused by gram-negative bacteria has been observed. Secondary infections were associated with longer ICU stay, MV use and higher mortality.

Secondary infections in a cohort of patients with COVID-19 admitted to an intensive care unit: impact of gram-negative bacterial resistance

ABSTRACT Some studies have shown that secondary infections during the COVID-19 pandemic may have contributed to the high mortality. Our objective was to identify the frequency, types and etiology of bacterial infections in patients with COVID-19 admitted to an intensive care unit (ICU) and to evaluate the results of ICU stay, duration of mechanical ventilation (MV) and in-hospital mortality. It was a single-center study with a retrospective cohort of patients admitted consecutively to the ICU for more than 48 h between March and May 2020. Comparisons of groups with and without ICU- acquired infection were performed. A total of 191 patients with laboratory-confirmed COVID-19 were included and 57 patients had 97 secondary infectious events. The most frequent agents were Acinetobacter baumannii (28.9%), Pseudomonas aeruginosa (22.7%) and Klebsiella pneumoniae (14.4%); multi-drug resistance was present in 96% of A. baumannii and in 57% of K. pneumoniae. The most prevalent infection was ventilator-associated pneumonia in 57.9% of patients with bacterial infections, or 17.3% of all COVID-19 patients admitted to the ICU, followed by tracheobronchitis (26.3%). Patients with secondary infections had a longer ICU stay (40.0 vs. 17 days; p < 0.001), as well as a longer duration of MV (24.0 vs 9.0 days; p= 0.003). There were 68 (35.6%) deaths overall, of which 27 (39.7%) patients had bacterial infections. Among the 123 survivors, 30 (24.4%) had a secondary infections (OR 2.041; 95% CI 1.080 - 3.859). A high incidence of secondary infections, mainly caused by gram-negative bacteria has been observed. Secondary infections were associated with longer ICU stay, MV use and higher mortality.

Sampling CASE Application for the Quality Control of Published Natural Product Structures.

Structure elucidation with NMR correlation data is dicey, as there is no way to tell how ambiguous the data set is and how reliably it will define a constitution. Many different software tools for computer assisted structure elucidation (CASE) have become available over the past decades, all of which could ensure a better quality of the elucidation process, but their use is still not common. Since 2011, WebCocon has integrated the possibility to generate theoretical NMR correlation data, starting from an existing structural proposal, allowing this theoretical data then to be used for CASE. Now, WebCocon can also read the recently presented NMReDATA format, allowing for uncomplicated access to CASE with experimental data. With these capabilities, WebCocon presents itself as an easily accessible Web-Tool for the quality control of proposed new natural products. Results of this application to several molecules from literature are shown and demonstrate how CASE can contribute to improve the reliability of Structure elucidation with NMR correlation data.

Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice.

Crotamine is a polypeptide toxin isolated from rattlesnake venom. Although several studies have been developed identifying many biological effects of isolated crotamine, none of them evaluated its acute toxicity, antinociceptive, and anti-inflammatory activities through oral administration. All in vivo experiments from this study were performed in mice. The up-and-down procedure and hippocratic screening were carried out to evaluate possible pharmacological and toxic effects. Antinociceptive and anti-inflammatory activities of this toxin were evaluated using acetic acid-induced abdominal writhing, formalin-induced pain assays, croton oil-induced ear edema, and carrageenan-induced pleurisy. Crotamine did not cause lethality or signs of intoxication up to the maximum dose tested (10.88 mg/kg). The number of contortions was reduced significantly by 34, 57, and 74% at the oral doses of 0.08, 0.16, and 0.32 mg/kg, respectively. At the dose of 0.16 mg/kg, crotamine decreases pain time-reactivity at neurogenic phase by 45% and at inflammatory phase by 60%. Also, crotamine elicited antiedematogenic activity through the attenuation of the croton oil-induced ear edema by 77%. In the carrageenan-induced pleurisy, the leukocyte, neutrophil, and mononuclear cell migration to the lesion site were reduced by 52%, 46%, and 59%, respectively. Altogether, crotamine demonstrated in vivo antinociceptive and anti-inflammatory effect through acute oral administration, generating an anti-migratory mechanism of action at non-toxic doses.

Relação das alterações vestibulares em indivíduos com disfunção temporomandibular: um estudo piloto / Relationship of vestibular changes in individuals with temporomandibular dysfunction: a pilot study

Objetivo: Objetivou-se investigar as possíveis relações entre as Disfunções Temporomandibulares com alterações do Sistema Vestibular (SV). Métodos: Estudo descritivo com abordagem quantitativa realizado em 09 pacientes com idade média entre 18 e 40 anos. Os participantes foram recrutados no grupo de estudo e pesquisa em Fisioterapia e Odontologia na Dor Orofacial (FISIODOF) da Universidade de Fortaleza. O presente estudo foi aprovado pelo comitê de ética, com parecer N° 1.310.583. Resultados: De acordo com o RDC/TMD, 3 casos são do grupo G1, 1 caso é do grupo G2, 1 casos é do grupo G1 e G2, e os outros 4 casos como grupos G1 e G3. Todos os pacientes apresentaram resultados negativo no teste de Fukuda. Já na Manobra de Dix-Hallpike 3 pacientes apresentaram resultado positivo. Discussão: A hipertonia muscular é descrita como principal responsável pelos sintomas auditivos e vestibulares de pacientes com DTM. Entretanto, não existe uma relação precisa descrita na literatura entre DTM e disfunção do sistema vestibular. Conclusão: A DTM pode causar alterações no sistema vestibular, explicadas pelo fato das estruturas da articulação temporomandibular e sistema vestibular serem anatomicamente próximas. No entanto, outras pesquisas se fazem necessárias para caracterizar os achados vestibulares em portadores de disfunção temporomandibular(AU)

Objective: The objective was to investigate the possible relationships between Temporomandibular Disorders with changes in the Vestibular System (SV). Methods: Descriptive study with a quantitative approach conducted in 09 patients with a mean age between 18 and 40 years. Participants were recruited from the study and research group in Physiotherapy and Dentistry in Orofacial Pain at the University of Fortaleza. This study was approved by the ethics committee, No. 1,310,583. Results: According to the RDC / TMD, 3 cases are from the G1 group, 1 case is from the G2 group, 1 case are from the G1 and G2 group, and the 4 other cases are from the G1 and G3 groups. All patients had a negative Fukuda test result. In the Dix-Hallpike maneuver, 3 patients had a positive result. Discussion: Muscular hypertonia is described as the main responsible for the auditory and vestibular symptoms of patients with TMD. However, there is no precise relationship described in the literature between TMD and vestibular system dysfunction. Conclusion: TMD can cause changes in the vestibular system, explained by the fact that the structures of the temporomandibular joint and the vestibular system are anatomically close. However, further research is necessary to characterize vestibular findings in patients with temporomandibular disorders(AU)

Análise da terapia craniossacral na disfunção temporomandibular associada a cefaleia tensional / Analysis of craniosacral therapy in temporomandibular dysfunction associated with tensional headache

Resumo Introdução Ocorrendo de forma branda e não invasiva, a terapia craniossacral é uma técnica de manipulação na qual o terapeuta exerce leve pressão sobre estrutura óssea, sendo utilizada como tratamento para diversos problemas de saúde, como cefaleias e DTM. Objetivo Analisar os efeitos da terapia craniossacral em indivíduos com disfunção temporomandibular associada a cefaleia do tipo tensional. Material e método Estudo descritivo, intervencionista com abordagem quantitativa, realizado no núcleo de atenção médica integrado, no período de fevereiro a setembro de 2018. Foram inclusos no estudo indivíduos com disfunção temporomandibular e que apresentaram cefaleia dentre os sintomas. Foram exclusos aqueles que não compareceram ao atendimento ou não apresentaram a sintomatologia. Previamente, foi realizada uma avaliação para identificar a dor na crise de cefaleia, a mensuração da amplitude de movimento mandibular e a palpação dos músculos da mastigação, para classificar a dor em leve, moderada ou forte. Após oito atendimentos, sendo duas vezes por semana com duração de 15 minutos cada, todos foram reavaliados. Resultado Participaram do estudo 31 indivíduos, sendo 90,3% do sexo feminino. Na classificação do RDC/TMD, houve prevalência dos grupos G1 e G1G3. Quanto a mobilidade mandibular, houve ganho para os movimentos de abertura, com 45,6 mm (±7,5) antes da terapia e, na reavaliação, 47,4 mm (±8,4); desvios laterais antes da terapia (lado direito - 7,0 ±2,8) e (lado esquerdo - 7,7±3,0), e após a terapia (8,0±3,0) e (8,6±2,9), respectivamente; o movimento de protusão, antes com média 5,03 ±2,5 e, na reavaliação, com 4,8 ±1,9. Na palpação muscular, destacamos redução do quadro álgico no músculo pterigoideo medial com média 2,2 (±1,05) antes da terapia e 1,5 (±1,02) após a terapia. Conclusão Concluímos que a terapia se mostrou eficaz no tratamento de pacientes com disfunção temporomandibular associada a cefaleia do tipo tensional.

Abstract Introduction Occurring in a mild and non-invasive way, craniosacra therapy is a manipulation technique that the therapist exerts light pressure on the bone structure, being used as a treatment for several health problems, such as headaches and TMD. Objective To analyze the effects of craniosacra therapy in individuals with temporomandibular disorders associated with tension-type headache. Material and method Descriptive, interventional study with a quantitative approach, carried out in the integrated medical care center from February to September 2018. Individuals with temporomandibular disorder and who presented headache among the symptoms were included in the study. And those who did not attend the service or did not present symptoms were excluded. Previously, an assessment was carried out to identify pain during headache attacks, measurement of mandibular range of motion and palpation of mastication muscles, to quantify pain as mild, moderate and severe. After 8 consultations, twice a week lasting 15 minutes each, all were reassessed. Result 31 individuals participated in the study, being 90.3% female. In the classification of the RDC/TMD, there was a prevalence of groups G1 and G1G3. Regarding mandibular mobility, there was a gain for opening movements with 45.6mm (±7.5) before therapy and 47.4mm (±8.4) in the reassessment; lateral deviations before therapy (right side - 7.0 ±2.8) and (left side - 7.7±3.0) and after (8.0±3.0) and (8.6±2.9); and the protrusion movement before with an average of 5.03 ± 2.5 and in the reassessment with 4.8 ± 1.9. And in muscle palpation, we highlight a reduction in pain in the medial pterygoid muscle with a mean of 2.2 (±1.05) before therapy and 1.5 (±1.02) after. Conclusion We conclude that the therapy has been shown to be effective in treating patients with temporomandibular disorders associated with tension-type headache.

SOD1 in amyotrophic lateral sclerosis development - in silico analysis and molecular dynamics of A4F and A4V variants.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the selective loss of motor neurons. Approximately 5% to 10% of patients with ALS have a family history of the disease, and approximately 20% of familial amyotrophic lateral sclerosis (fALS) cases are associated with mutations in Cu/Zn superoxide dismutase (SOD1). In this study, we evaluated the structural and functional effects of human A4F and A4V SOD1 protein mutations. We performed an in silico analysis using prediction algorithms of nonsynonymous single-nucleotide polymorphisms (nsSNPs) associated with the fALS development. Our structural conservation results show that the mutations analyzed (A4V and A4F) were in a highly conserved region. Molecular dynamics simulations using the Linux GROMACS package revealed how these mutations affect protein structure, protein stability, and aggregation. These results suggest that there might be an effect on the SOD1 function. Understanding the molecular basis of disease provides new insights useful for rational drug design and advancing our understanding of the ALS development.

Estudo in vitro da influência da técnica de moldeira fechada e diferentes materiais de moldagem no posicionamento tridimensional dos implantes / Estudo in vitro da influência da técnica de moldeira fechada e diferentes materiais de moldagem no posicionamento tridimensional dos implantes

Objetivo: avaliar o comportamento de diferentes materiais de moldagem na transferência de implantes a partir de um modelo padrão, utilizando-se moldeira fechada e transferentes cônicos. Material e métodos: um modelo em alumínio recebeu três implantes paralelos entre si (A, B e C), e os grupos foram divididos em: hidrocoloide irreversível, poliéter, silicone de condensação e silicone de adição. Todas as moldagens foram feitas com transferentes cônicos e moldeira fechada. As distâncias entre os implantes foram medidas com uma máquina tridimensional de medição por coordenadas (Sheffield) e, com o auxílio de um software específico, foram obtidas as medidas. A precisão entre o modelo padrão e os modelos de gesso foi verificada pelos coeficientes de correlação intraclasse, análises de variância e teste de Dunnett (nível de significância de 5%). Resultados: não houve diferença estatística entre os materiais de moldagem para as distâncias horizontais AB e BC. Entretanto, o uso do hidrocoloide irreversível resultou em maior movimentação anteroposterior em relação ao modelo-mestre, embora excelente replicabilidade tenha sido observada em todos os modelos obtidos. As perpendicularidades de A, mensuradas nos modelos obtidos a partir de moldagens realizadas com poliéter, silicone de condensação e de adição, foram significativamente menores em relação ao modelo padrão (p < 0,001). Conclusão: nas condições estudadas, o hidrocoloide irreversível deve ser evitado em moldagens para transferência de implantes.

Objective: to evaluate the behavior of different impression materials on dental implant transferring using a standard model, closed impression trays, and conical transfer copings. Material and methods: an aluminum model received three parallel implants (A, B and C), and groups were divided into: irreversible hydrocolloid, polyether, condensation, and addition silicones. All impressions were made using conical transfer copings with the closed tray technique. The inter-implant distances were measured with a three-dimensional coordinate measuring machine (Sheffield), and data collected with specific software. The accuracy between the standard and gypsum models was verifi ed by intraclass correlation coefficients, Anova, and the Dunnett test (5% level of signifi cance). Results: there was no statistical difference between the impression materials in relation to horizontal distances AB and BC. However, the use of irreversible hydrocolloid resulted in greater anteroposterior movement in relation to the master model, although excellent repeatability was observed in all the models obtained. The A perpendicularity obtained from polyether, condensation, and addition silicone materials was significantly lower in relation to the standard model (p < 0.001). Conclusion: in the studied conditions, the irreversible hydrocolloid teste here should be avoided for dental implant transferring procedures.

A preliminary list of the Herpetofauna from termite mounds of the cerrado in the Upper Tocantins river valley

Termite mounds are known to offer refuge and microhabitats to a great variety of invertebrates and vertebrates. In the valley of the upper Tocantins River, within areas of influence of hydroelectric power plants 4,000 termite mounds were surveyed to evaluate the diversity of amphibians and reptiles using these environments. Surveys in termite mounds from two other areas (Corumbá River and Araguaia River basins) were used for comparative purposes. The results for termitaria in the upper Tocantins river valley revealed nine families, 13 genera, and 25 species of amphibians, and 16 families, 32 genera, and 47 species of squamate reptiles. Compared to a general herpetofaunal list of the region, the data indicate that between 30.6% and 56.8% of the species use termitaria.

Termiteiros são conhecidos por oferecer refúgio e micro habitats para uma grande variedade de invertebrados e vertebrados. Aproveitando trabalhos realizados na área de influência de usinas hidrelétricas no vale do rio Tocantins, inspecionamos avaliamos 4.000 termiteiros visando determinar os anfíbios e répteis que se utilizam desses ambientes. Resultados obtidos em duas outras áreas (bacias dos rios Corumbá e Araguaia) foram utilizadas como comparação. No vale do alto rio Tocantins nove famílias, 13 gêneros e 25 espécies de anfíbios e 15 famílias, 32 gêneros e 47 espécies de Squamata foram encontrados nos termiteiros. Esses dados indicam que entre 30.6% e 56.8% das espécies da herpetofauna utilizam termiteiros.

A preliminary list of the Herpetofauna from termite mounds of the cerrado in the Upper Tocantins river valley

Termite mounds are known to offer refuge and microhabitats to a great variety of invertebrates and vertebrates. In the valley of the upper Tocantins River, within areas of influence of hydroelectric power plants 4,000 termite mounds were surveyed to evaluate the diversity of amphibians and reptiles using these environments. Surveys in termite mounds from two other areas (Corumbá River and Araguaia River basins) were used for comparative purposes. The results for termitaria in the upper Tocantins river valley revealed nine families, 13 genera, and 25 species of amphibians, and 16 families, 32 genera, and 47 species of squamate reptiles. Compared to a general herpetofaunal list of the region, the data indicate that between 30.6% and 56.8% of the species use termitaria.

Termiteiros são conhecidos por oferecer refúgio e micro habitats para uma grande variedade de invertebrados e vertebrados. Aproveitando trabalhos realizados na área de influência de usinas hidrelétricas no vale do rio Tocantins, inspecionamos avaliamos 4.000 termiteiros visando determinar os anfíbios e répteis que se utilizam desses ambientes. Resultados obtidos em duas outras áreas (bacias dos rios Corumbá e Araguaia) foram utilizadas como comparação. No vale do alto rio Tocantins nove famílias, 13 gêneros e 25 espécies de anfíbios e 15 famílias, 32 gêneros e 47 espécies de Squamata foram encontrados nos termiteiros. Esses dados indicam que entre 30.6% e 56.8% das espécies da herpetofauna utilizam termiteiros.

Immune function in young children with previous pulmonary or miliary/meningeal tuberculosis and impact of BCG vaccination.

OBJECTIVE: Children <5 years old are at increased risk of miliary/meningeal tuberculosis, but the immunologic factors that place them at risk are unknown. BCG vaccine protects against miliary/meningeal tuberculosis, but the mechanism of protection is unknown. We assessed for abnormalities in immune response associated with miliary/meningeal or pulmonary tuberculosis in young children. PATIENTS AND METHODS: We conducted a case-control study among HIV-seronegative Brazilian children who were <5 years old. Case subjects had previous culture-confirmed or clinical miliary/meningeal tuberculosis. There were 2 sets of control subjects: those with culture-confirmed pulmonary tuberculosis and purified protein derivative-positive household contacts. All of the children had completed treatment. Peripheral blood mononuclear cells were stimulated (phytohemagglutinin, phytohemagglutinin + interleukin 12, lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative), and cytokine responses (interleukin 1beta, interleukin-4, interleukin-6, interleukin-8, interleukin 10, interleukin 12, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1) were quantified by bead-based assay. Median cytokine responses were compared by the Kruskal-Wallis test. Multivariate analysis of variance accounted for multiple comparisons. RESULTS: There were 18 case subjects with miliary/meningeal tuberculosis, 28 pulmonary control subjects, and 29 purified protein derivative-positive control subjects. The median age was 4.2 years. There was no difference in case and control subjects by age, gender, race, BMI, or median CD4 count. Twelve (67%) of 18 case subjects, 26 (93%) of 28 pulmonary control subjects, and 28 (97%) of 29 purified protein derivative-positive subjects had received BCG vaccine. No cytokine defects were identified in case subjects with miliary/meningeal tuberculosis compared with either set of control subjects. Pulmonary control subjects had uniformly higher monocyte chemoattractant protein 1 levels than case subjects with miliary/meningeal tuberculosis and purified protein derivative-positive control subjects, both at rest and with lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative stimulation. Pulmonary control subjects did not have a higher frequency of allele G in the -2518 monocyte chemoattractant protein 1 promoter polymorphism. Case subjects with miliary/meningeal tuberculosis who had received BCG vaccine (n = 12) had lower stimulated interleukin 8 production than children who did not receive BCG vaccine (n = 6). CONCLUSIONS: Children with previous miliary/meningeal tuberculosis did not have a major defect in the cytokine pathways studied. Increased monocyte chemoattractant protein 1 levels were associated with pulmonary disease, occurred despite BCG vaccination, and were not associated with a polymorphism in the monocyte chemoattractant protein 1 promoter.