A 6-month regimen for EPTB with intermittent treatment in the continuation phase: a study of 679 cases.

BACKGROUND: No large studies have demonstrated the effectiveness of a 6-month regimen for all forms of extra-pulmonary tuberculosis (EPTB). METHODS: Retrospective, observational analysis to evaluate the effectiveness of a 6-month treatment regimen (2HRZE/4H3R3) for all patients diagnosed with EPTB in Caracas, Venezuela, from 1 January 1998 to 31 December 2000, using direct observation. RESULTS: Of 679 patients enrolled, 101 (14.9%) had AIDS. In 83.2% the diagnosis was based on microbiological, histological or genetic amplification information. Of 612 (90.1%) patients who took more than 90% of the doses, treatment had to be altered in six (1%) due to drug side effects. Of the remaining 606 patients who took more than 90% of the doses, 603 (99.5%) were cured and three failed. In the follow-up conducted 2 years after the end of treatment, only 6 relapsed (1%). Cures without relapse were achieved in 24 cases of central nervous system involvement, 27 cases of osteoarticular involvement and in the 42 who had miliary and/or disseminated TB. CONCLUSION: A 6-month treatment regimen for all forms of EPTB, with treatment three times a week during the continuation phase, was highly effective.

A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma.

We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.

Comparative ultrastructure and immunolabeling of MHC-II antigens of alveolar macrophages obtained from patients with paracoccidioidomycosis and other lung diseases.

Samples of alveolar macrophages (AM) obtained by bronchoalveolar lavage from patients with either paracoccidioidomycosis, silicosis, sarcoidosis, or allergic alveolitis were investigated by electron microscopy and immunocytochemistry to compare cellular ultrastructure and expression of MHC-II antigens in the AM cell surface. All samples of AM obtained from patients with these pathologies showed heterogeneous structural features. Although, this morphological diversity is also present in AM of healthy donors, our observations seem to indicate that in the diseases studied this morphofunctional diversity is associated with additional ultrastructural characteristics inherent to each disease. In paracoccidioidomycosis the proportion of vacuolated macrophages is significantly lower than in other diseases; this might indicate that in paracoccidioidomycosis the proportion of activated AM is smaller. We observed significant differences in the expression of MHC-II antigens. Silicosis, sarcoidosis, and allergic alveolitis do not differ significantly in the quantity of immunolabeled AM or in the distribution of the label. The percentage of AM from paracoccidioidomycosis that exhibit the MHC-II molecule is very low with poor immunolabeling. In this disease the low expression of the MHC-II molecule could be related to a decrease of the antigen presenting function by AM.

A double-blind, cross-over study using salbutamol, beclomethasone, and a combination of both in bronchial asthma.

A double-blind, cross-over protocol was applied to 22 asthmatic patients who were previously subjected to provocation tests with methacholine. The baseline FEV1 for mild asthma was 89.6 +/- 13.6% while for moderate asthma it was 73 +/- 6%. The initial provocation tests with methacholine revealed that the mild asthma group needed a greater accumulated dose of methacholine than that required by the moderate asthma group to lower the FEV1 by 20%, stressing the enhanced bronchial hyperreactivity present in the latter group. Significant differences in the PD20 values were obtained in both groups of patients using the combination of salbutamol plus beclomethasone. Salbutamol alone was ineffective to change the PD20 values in mild asthma while beclomethasone alone was able to change significantly the PD20 values in these patients, stressing the importance of the inflammatory component in the pathogenesis of stable asthma. Furthermore, the combination of both drugs was also more effective in the moderate asthma group than either medication alone, confirming the pharmacological control of the obstructive and inflammatory changes that are already established in patients with moderate asthma.

Specific digestive deficiency of phagocytes in paracoccidioidomycosis. Its absence in peripheral blood neutrophils of members of the nuclear family of patients. An initial report.

Paracoccidioidomycosis (PARA) affects only a minority of individuals, who have presumably been exposed to the causative fungus (Paracoccidioides brasiliensis). Neutrophils (PMNs) from patients with PARA show a significant and specific digestive deficiency phagocytosed P. brasiliensis in vitro. It is not known whether the defect is acquired after contact with the fungus, or precedes it. We studied the spouses and offspring of three patients with PARA. Individuals studied stayed in the same house as their husband or father. None of the relatives had evidence of PARA, and their PMNs showed no defect in their ability to digest or kill the fungus. Relatives showed no indication of sensitization against P. brasiliensis. These results are compatible with the view that effective contact with P. brasiliensis may occur only under restricted conditions and that the defect in digestive ability is an infrequent and specific occurrence.

Relationship between digestive and killing abilities of neutrophils against Paracoccidioides brasiliensis.

Peripheral blood neutrophils (PMN) from patients with paracoccidioidomycosis killed and digested Paracoccidioides brasiliensis much less than did PMN from normal individuals or from patients with other diseases. However, deficiency in killing ability was less specific than digestive deficiency and correlated poorly with it. We conclude that the capacities of PMN to digest and kill P. brasiliensis are not intimately related phenomena, and that in paracoccidioidomycosis the key deficiency of neutrophil function is that of digestion of P. brasiliensis.

Bronchial challenge of tropical asthmatics with Ascaris lumbricoides.

Despite the fact that helminthic parasites can stimulate strong immediate hypersensitivity reactions, it is uncertain whether these are relevant to the development of allergic disease in infected patients. In order to examine this possibility, we tested 20 informed chronic asthmatic patients from an Ascaris-endemic area by bronchial challenge with a partially purified extract of this parasite. Sequential measurements were made of both the forced expiratory volume in the first second (FEV1) and the peak expiratory flow rate (PEFR) up to 6 h postchallenge, then of PEFR from 6 to 14 h and at 24 h. These were compared to the effect of control inhalations of saline. Extremely low doses of Ascaris antigen that did not exceed 10 PNU (6 x 10(-7) g of protein) induced significant reductions (> 20%) in FEV1 within 30 min in 3 (15%) patients, and in PEFR in 5 cases (25%). By 6 h postchallenge, 5 (25%) subjects showed significant alterations in FEV1, and 10 (50%) in PEFR. Significant changes in PEFR were recorded between 6 and 24 h in 12 (60%) patients. The challenge of nonasthmatic subjects from the same Ascaris-endemic area did not produce notable changes in pulmonary function, and although asthmatics with no evidence of prior contact with the parasite showed a certain degree of immediate bronchial reactivity to the parasite extract, the late responses were significantly less frequent than in the infected patients. No correlations were detected between the bronchial responses and skin test reactivities to the Ascaris extract, or serum levels of specific IgE or IgG antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukocyte immunophenotypes in bronchoalveolar lavage fluid and peripheral blood of paracoccidioidomycosis, sarcoidosis and silicosis.

Leukocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood of patients with paraccoccidioidomycosis, sarcoidosis and silicosis were characterized using monoclonal antibodies and an immunoperoxidase technique. In paraccocidioidomycosis, the number of T-helper/inducer CD4-positive lymphocytes was lower in peripheral blood than in BAL fluid. Additional analysis showed that the expression of HLA-DR was very similar in alveolar macrophages, lung and blood T-cells. In sarcoidosis and silicosis there were higher proportions of T-helper/inducer cells in peripheral blood than in BAL fluid. The alterations in the T-helper/inducer/T-suppressor/cytoxic CD4/CD8 ratio in sarcoidosis and silicosis were more appreciable in peripheral blood than in BAL fluid, contrasting with the results in paracoccidioidomycosis. The expression of HLA-DR by alveolar macrophages in sarcoidosis was the highest of all the disease studied. No statistically significant differences were observed between chronic multifocal and chronic unifocal paracoccidioidomycosis disease, stage II and stage III sarcoidosis, and chronic and accelerated silicosis. The three granulomatous diseases analyzed had a few alveolar macrophages expressing the CD4 molecule on their surface. These findings and the technique of analyzing both peripheral blood and BAL leukocyte subsets may help to understand the pathogenesis of interstitial lung diseases.

Variabilidad en la prevalencia del asma en un país tropical / Variability in asthma prevalence in a tropical country

La prevalencia de enfermedades alérgicas en el trópico, ha sido reportada frecuentemente como baja y la infección helmíntica ha sido considerada como un factor determinante en este aspecto. En el presente estudio, diferentes poblaciones rurales del país fueron evaluadas encontrándose una prevalencia alta de asma en la isla de Coche (20,4%) del total de la población, aún más elevada en niños (33,0%) en 2531 personas encuestadas que conviven en un caluroso, húmedo, costero y semi árido. En contraste, la prevalencia de asma (55%) era baja en un grupo de 1040 pobladores de una región del Amazonas (San Juan de Manapiare) que sufrían de un menor grado de helmintiasis que en Coche, pero dicha prevalencia era inferior (27%) en 291 indígenas que demostraron una intensa infección helmíntica en otro poblado amazónico (Maroa). La enfermedad asmática en la región amazónica mostró una distribución etaria poco usual, porque fue mayor en adultos. Estos patrones tan contrastantes sobre prevalencia en Coche y Manapiare, fueron confirmados por estudios de la función pulmonar basal y posterior a la inhalación de broncodilatadores. Los niveles de IgE se encontraron bien elevados en Coche y Manapiare y excepcionalmente superiores en Maroa. En los tres grupos estimados la mayor positividad de la IgE específica fue para el Ascaris lumbricoides, aunque en la isla de Coche encontramos cierta positividad para el ácaro del polvo (Dermatofagoides sp), especialmente en los asmáticos. Estos resultados demuestran la amplia variabilidad en la prevalencia de asma y sugieren la multifactorialidad que influye en esta enfermedad en el medio tropical

Influence of serum on in vitro digestion of Paracoccidioides brasiliensis by neutrophils.

Serum from patients with paracoccidioidomycosis (PARA) did not block digestive abilities of neutrophils (PMNs) from healthy individuals against Paracoccidioides brasiliensis. Conversely, serum from healthy donors did not enhance digestive capacities of PMNs from patients with PARA vis á vis the causative organism. We conclude that the specific digestive defect present in PMNs from patients with PARA is not mediated by serum factors.

Digestion of killed Paracoccidioides brasiliensis by neutrophils.

We previously described an in vitro assay showing that neutrophils (PMNs) from patients with paracoccidioidomycosis (PARA) have a specific digestive deficiency against suspensions of live Paracoccidioides brasiliensis. We now report that this defect is equally detectable against autoclaved, but not Amphotericin B-killed P. brasiliensis. The use of autoclaved suspensions facilitates the use of our in vitro assay. It might allow the development of an in vitro intradermal test for digestion of fungi. Differential digestive ability of phagocytes against live (or autoclaved) and Amphotericin-B killed fungi is of conceptual interest. It may be relevant in understanding therapeutic effect of Amphotericin B.

Allergic reactivity and helminthic infection in Amerindians of the Amazon Basin.

Various aspects of the allergic reactivity of Amerindians in the Venezuelan sector of the Amazon basin were examined. The frequency of positivity in immediate hypersensitivity skin tests with extracts of common local environmental allergens was found to be extremely low (6.7%). As sera from significantly higher proportions of the study group contained specific IgE antibody against the test allergens, and their histamine-induced skin responses were normal, these results support previous suggestions of an inhibited expression of allergic reactivity in such populations. Indeed, the intense helminthic infections detected, and the extremely high total serum IgE levels measured (geometric mean 13,088 IU/ml) indicate the possible occurrence of mast cell saturation by parasite-induced IgE. However, despite a similar lack of agreement between the in vivo and in vitro tests for allergic reactivity against Ascaris lumbricoides in these subjects (43.5 and 97.9% positive, respectively), their extremely high responsiveness to the helminth allergens presents a marked contrast to that against the other environmental materials. Factors other than helminthiasis (e.g. racial, cultural, nutritional) might, therefore, also modulate the expression of allergic reactivity in such populations.

[Bird breeder's lung in children]. / Pulmón del criador de pájaros en la infancia.

A case of hypersensitivity pneumonitis due to pigeon-dropping antigens is reported in a 9 year old girl, and compared with other seven previous reports in children. The insidious nature of this disease, as well as the importance of detailed environmental information in children with unexplained respiratory disease are emphasized. In this case, lung function tests showed a classic restrictive ventilatory defect, and a serious obstructive ventilatory defect evidenced in the narrowing of the smaller airways, and a reduction in the forced expiratory flow at small lung volumes. Hypersensitivity pneumonitis is a lung disease that results from sensitization by inhalation of a variety of organic dusts. Patients usually have circulating antibodies against the etiologic agents. Most patients with this disease also have sensitized T-cells to these agents. Long-term exposure can lead to irreversible lung disease. The histopathologic features are chronic interstitial and alveolar inflammation frequently accompanied by a granulomatous response. The most common symptomatic features are fever, chills and dyspnea 4 to 8 hours after exposure. Antibody activity to antigens is detected in the serum of both symptomatic and asymptomatic breeder's lung. Cellular hypersensitivity to antigens is demonstrated "in vitro" with peripheral lymphocyte populations in almost all symptomatic patients.