Trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary changes in pneumocystis-colonized nonhuman primates with SHIV infection.

BACKGROUND: Despite antiretroviral therapy and trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, Pneumocystis pneumonia remains an important serious opportunistic infection in HIV-infected persons. Pneumocystis (Pc) colonization in HIV-infected individuals and in HIV-uninfected smokers is associated with chronic obstructive pulmonary disease (COPD). We previously developed a nonhuman primate model of HIV infection and Pc colonization and demonstrated that Pc colonization correlated with COPD development. In the present study, we examined kinetics of COPD development in non-human primate and tested the effect of Pc burden reduction on pulmonary function by TMP-SMX treatment. METHODS: Cynomolgus macaques (n = 16) were infected with simian/human immunodeficiency virus (SHIV89.6P), and natural Pc colonization was examined by nested polymerase chain reaction of serial bronchoalveolar lavage fluid and anti-Pc serology. RESULTS: Eleven of 16 monkeys became Pc colonized by 16 weeks post simian-human immunodeficiency virus (SHIV) infection. Pc colonization of SHIV-infected monkeys led to progressive declines in pulmonary function as early as 4 weeks after Pc detection. SHIV-infected and Pc-negative monkeys maintained normal lung function. At 25 weeks post-SHIV infection, TMP-SMX treatment was initiated in 7 Pc-positive (Pc+) (TMP: 20 mg/kg and SMX: 100 mg/kg, daily for 48 weeks) and 5 Pc-negative (Pc-) monkeys. Four SHIV+/Pc+ remained untreated for the duration of the experiment. Detection frequency of Pc in serial bronchoalveolar lavage fluid (P < 0.001), as well as plasma Pc antibody titers (P = 0.02) were significantly reduced in TMP-SMX-treated macaques compared with untreated. CONCLUSIONS: Reduction of Pc colonization by TMP-SMX treatment did not improve pulmonary function, supporting the concept that Pc colonization results in early, permanent obstructive changes in the lungs of immunosuppressed macaques.

Qualidade do ar e atendimentos médicos de emergência por sintomas respiratórios em crianças residentes em Jacarepaguá, Rio de Janeiro / Air quality and emergency medical consultations related to respiratory symptoms among children living in Jacarepaguá, Rio de Janeiro

Apesar da cidade do Rio de Janeiro ser uma das mais importantes metrópoles brasileiras são muito pouco conhecidos os efeitos da exposição aos poluentes atmosféricos na saúde da população carioca. Este trabalho foi idealizado para suprir uma parte desta carência. Os poluentes investigados foram PM10, SO2, NO2, CO e O3 e os desfechos envolveram os atendimentos pediátricos de emergência por sintomas respiratórios em três unidades públicas de saúde de Jacarepaguá, entre abril de 2002 e março de 2003. As variáveis de confusão foram a tendência temporal, sazonalidade, temperatura, umidade relativa do ar, precipitação de chuva e infecções respiratórias. Também foram ajustados os efeitos do calendário, isto é, determinados dias do ano que apresentaram comportamentos anormais como feriados e finais de semana. Houve inúmeras falhas no monitoramento de todos os poluentes e devido ao reduzido volume de dados, optou-se por não incluir o SO2 nas análises. Uma vez que os determinantes e as conseqüências clínicas dasexposições aos poluentes atmosféricos são bastante distintos nas vias aérias superiores e nas vias aéreas inferiores, um dos estudos verificou a associação dos poluentes do ar com transtornosnestes dois segmentos. Embora de pequena magnitude, somente o O3 apresentou resultado positivo e estatisticamente significativo, tanto com todos os atendimentos de emergência por queixas respiratórias como com os atendimentos motivados por sintomas nas vias aéreas inferiores. O efeito foi no mesmo dia da exposição (lag 0). No outro estudo, investigou-se a associação dos poluentes do ar com os atendimentos de emergência por sintomas de obstrução brônquica. Neste caso, as crianças foram categorizadads em três faixas etárias. Somente ascrianças com idades menores que 2 anos tiveram um resultado positivo e estatisticamente significativo, de expressiva magnitude com PM10...

Enfermedad pulmonar obstructiva crónica: correlación patológica-radiológica / Chronic obstructive pulmonary disease

La enfermedad pulmonar obstructiva crónica (EPOC) se caracteriza por una limitación progresiva en el flujo de aire espirado a través del árbol bronquial. Esta limitación no es reversible completamente. Consideramos la EPOC como un continuo conformado, en un extremo, por pacientes con bronquitis crónica,y en el otro, por pacientes con enfisema. La presente revisión correlaciona los hallazgos radiológicos y patológicos que se observan en la bronquitis crónica, y en los diferentes tipos de enfisema

Criptococosis pulmonar / Pulmonary criptococosis: case report

Se presenta un caso de criptococosis pulmonar en varon de 75 años, fumador, con enfisema pulmonar crónico obstructivo, en fase de enfermedad pulmonar aguda, diseminada a sitema nervioso central. El diagnóstico clínico es dificil, pero los examenes auxiliares de diagnóstico, tienen un alto rendimiento y confiabilidad. Es importante tomar en cuenta, la presencia de enfermedades que producen inmunosupresión como el SIDA y otras enfermedades subyacentes.

Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.

BACKGROUND: A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial. PATIENTS AND MEASUREMENTS: We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects. SETTING: Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics. RESULTS: Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining. CONCLUSION: These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.

Variation of infrarenal aortic diameter: A necropsy study.

PURPOSE: To determine anatomicomorphological changes in the infrarenal portion of the abdominal aorta, we performed 645 dissections of the segment in corpses undergoing necropsy. METHODS: The aortas were removed from the corpses with a surgical technique; by means of a device that we designed, the external diameter of the artery was measured after luminal pressure was reestablished. This way, it was possible to avoid underestimation of the arterial diameter postmortem. The influence of age, sex, body size, arterial hypertension, chronic obstructive pulmonary disease, and coronary disease on the aortic diameter and the influence of different degrees of sclerosis on the infrarenal aorta wall were analyzed. Considering the diameters, aortas were regarded as "normal" when they did not present any ectasia, arteriomegaly, aneurysm, or hypoplasia. RESULTS: The sample involved 645 subjects whose ages ranged from 19 to 97 years (mean age, 55.8 years). Of the 645 subjects, 65.5% (423) were men, 34.5% (222) were women, 81% (523) were white, and 19% (122) were of another race. The diameters of arteries showing no anomalous dilatation (ectasis, arteriomegaly, or aneurysm) varied according to subject age, sex, body length, and the degree of atherosclerosis on the aorta wall (P <.01). Aortic diameters of those subjects with arterial hypertension, coronary disease, and chronic obstructive pulmonary disease were compared with the aortic diameters of control subjects, and significant differences were not shown (P >.05). Twenty-nine aneurysms were found (4.5% prevalence). Four were ruptured aneurysms, and all occurred in aortas with diameters larger than 5.0 cm. CONCLUSION: The infrarenal aortic diameter enlarges with aging, and this enlargement occurs earlier in men than in women. Those subjects who had a longer body length and advanced sclerosis on the aorta wall had larger aortic diameters. There was a high prevalence of infrarenal aneurysms (4.5%), with rupture found solely in aortas with diameters larger than 5.0 cm.

Uso de la lidocaína en pacientes con enfermedad bronco pulmonar obstructiva crónica / Use of the lidocaine in patients with bronchopulmonary obstructive chronic disease

El presente estudio fue realizado en el Departamento de Neumonología y Cirugía de Tórax del Hospital Militar "Dr. Carlos Arvelo" específicamente en el laboratorio para el estudio del "Funcionamiento pulmonar" fundado y dirigido hasta el año 1995 por el Dr. Eduardo Carvallo. El mismo busca demostrar dos hipótesis que se plantean ante un fenómeno observado en un estudio previo donde se administró lidocaína 2 por ciento en forma nebulizada, como premedicación antes de la realización de las broncofibroscópias, en el que se pudo apreciar que aquellos pacientes que recibieron el medicamento presentaban un aumento de la diferencial de la Pa02 arterial posterior a la práctica del mismo. De todo esto surge la posibilidad que el medicamento se comporte como un broncodilatador por su acción indirecta sobre los canales de calcio, o puede tener un efecto directo sobre la superficie de intercambio de gases (alvéolo), logrando así este fenómeno. Nuestro estudio se realiza para el período julio de 1995 a junio de 1996, con una muestra al azar de pacientes con EBPOC leve, moderada y severa; de ambos sexos, para una muestra mínima de 41 pacientes en un estudio a doble ciego. Al llegar el paciente, el técnico le realiza medición de los flujos (espirometría) y toma de muestras para gasometría de sangre arterial, luego se nebuliza el paciente con la droga y después se vuelven a medir los flujos y se toma otra muestra para medición de gases arteriales, para seguidamente proceder a tabular los datos obtenidos de cada paciente y se concluye con el análisis de los resultados, posterior a ruptura de los sellos. Nuestros resultados evidencian el efecto de la lidocaína nebulizada sobre la PaO2 de manera evidente, pero sin demostrar un significativo efecto broncodilatador, los que nos hace pensar en un posible efecto directo sobre el intercambio gaseoso a nivel alvéolar

The expression of adhesion molecules in cigarette smoke-induced airways obstruction.

Cigarette smoking produces peripheral airway inflammation in all smokers, and chronic airways obstruction in approximately 20% of heavy smokers. The present study was designed to test the hypothesis that airways obstruction is related to changes in the expression of adhesion molecules involved in the recruitment of cells to sites of inflammation in the lung. Freshly resected lungs from heavy smokers with airways obstruction (n = 10) and from heavy smokers with normal lung function (n = 10) were collected in the operating room, inflated with optimal cutting temperature (OCT) medium and frozen over liquid nitrogen. Six micrometres thick cryostat sections cut from random samples of this tissue were stained, using immunohistochemistry, with monoclonal antibodies to the adhesion molecules on leucocytes: L-selectin, very late activation antigen-4 (VLA-4), CD11a/CD18, CD11b/CD18, CD11c/CD18; and on endothelial and epithelial surfaces: E-selectin, P-selectin, vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM)-1 and ICAM-2 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The slides were coded and the expression of each molecule scored by three observers using a semiquantitative grading system. Two inducible adhesion molecules, E-selectin on endothelium and CD11b on leucocytes, were also evaluated using quantitative morphometric analysis. The results showed a distribution of adhesion molecules that was consistent with the inflammatory response in the airways and parenchyma of all subjects but failed to show any differences between those with or without airways obstruction. We conclude that development of airways obstruction in heavy smokers cannot be explained by differences in the expression of adhesion molecules known to be involved in the control of cell traffic in the lung.

Etiopatogenia na DBPOC / Etiopathogenesis in COPD

A obstruçao crônica do fluxo aéreo se deve normalmente a duas patologias: bronquite crônica e enfisema, embora possam ocorrer separadamente, com manifestaçoes clínicas diferentes, têm em suas lesoes associadas a principal causa de DBPOC (Doença Broncopulmonar Obstrutiva Crônica). A partir disso, os autores fazem uma revisao bibliográfica sobre aspectos do enfisema e da bronquite crônica, a fim de estabelecer dados etiopatogênicos e epidemiológicos da DBPOC.

Cutaneous Nocardia asteroides infection of nontraumatic origin

E relatado um caso de infeccao cutanea de origem nao traumatica por Nocardia asteroides em paciente hospitalizado com doenca broncopulmonar obstrutiva cronica. O diagnostico foi feito pelo exame direto e histologico e culturas do exsudato e fragmento de biopsia. E discutida a classificacao das formas clinicas das infeccoes por Nocardia que afetam a pele.

Chronic obstructive airways disease after bone marrow transplantation.

The clinical course, serial pulmonary function studies, lung histopathologic findings, and treatment in two patients after bone marrow transplantation for acute monoblastic leukemia or aplastic anemia are presented. The course in one patient has been slowly progressive for 2 years and characterized by chronic obstructive airways disease and recurrent pneumothoraces. Histopathologic changes were nonspecific, characterized by chronic interstitial pneumonitis and interstitial fibrosis. In the second patient there was insidious onset of disease with increasing dyspnea on exertion and rapid clinical deterioration; he died within 4 months of severe obstructive airways disease. Necrotizing bronchitis and bronchiolitis characterized the lung findings. Neither patient responded to conventional bronchodilator therapy, and prednisone was the only agent to produce subjective, though transient, improvement. Symptomatic obstructive airways disease associated with chronic graft-versus-host disease is emerging as a potentially major cause of morbidity and mortality after marrow transplantation.