Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-β1 levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-β1 were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide in patients with pulmonary tuberculosis

Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide were studied in healthy controls and patients with active pulmonary tuberculosis. A case-control study of 29 controls and 30 cases attending at the Health Center, July, 2004 to December, 2005 was conducted. The body mass index was significantly reduced in cases compared to controls (p < 0.001). The intestinal paracellular transport of lactulose was significantly (p = 0.019) reduced in cases compared to controls. The transcellular transport of mannitol and the lactulose:mannitol ratio were not significantly (p = 0.0698) reduced in cases compared to controls. Low serum concentrations of rifampin, isoniazid and pyrazinamide were observed in 81 percent (48/59), 92 percent (54/59) and 28 percent (12/59), respectively, in all individuals. The results demonstrated a marked decrease on intestinal paracellular transport in patients with active pulmonary tuberculosis and reduced serum concentrations of rifampin and isoniazid in both groups.

Evaluation of lipid peroxidation product, nitrite and antioxidant levels in newly diagnosed and two months follow-up patients with pulmonary tuberculosis.

This case-control study followed by a longitudinal cohort study was undertaken to evaluate the level of lipid peroxidation product malondialdehyde (MDA) and nitrite as an indirect measurement of nitric oxide vis-à-vis the levels of antioxidants vitamin C and vitamin E in pulmonary tuberculosis. Fifty-six sputum smear-positive cases of pulmonary tuberculosis based on Ziehl-Neelsen (ZN) staining and 50 healthy controls without any systemic disease were included in this study. Thirty-five cases were longitudinally followed up with standard antituberculosis chemotherapy (ATT) for two months. Serum levels of malondiadehyde (MDA), nitrite, and plasma levels of vitamins C and E were measured. The mean serum MDA level was significantly higher (8.1 +/- 1.61 nmoles/ml) in PTB patients before commencement of ATT as compared to healthy controls (3.45 +/- 1.7 nmoles/ml) (p=0.0001) and decreased significantly after 2 months of ATT (3.84 +/- 1.28 nmoles/ml) (p=0.0001). The mean serum nitrite level (47.19 +/- 18.44 micromol/l) was significantly elevated before ATT compared to healthy controls (32.89 +/- 11.94 micromoles/l) and decreased significantly after 2 months of ATT (27.71 +/- 11.97 micromoles/l) (p=0.0001). The mean plasma levels of vitamins C (0.88 +/- 0.33 mg/dl) and E (0.79 +/- 0.24 mg/dl) in PTB patients before commencement of ATT were lower than healthy controls (1.42 +/- 0.38 mg/dl) and (1.35 +/- 0.35 mg/dl), respectively (p=0.001). There was a significant increase in vitamin C levels after 2 months of ATT (1.19 +/- 0.40 mg/dl) compared to before ATT (0.83 +/- 0.31 mg/dl) (p=0.0001), but no significant change in mean plasma vitamin E level before and after 2 months on ATT was found. Elevated malondialdehyde and nitrite levels with concomitant depressed vitamin C and E levels are indicative of lipid peroxidation and oxidative stress. The decrease in levels of malondialdehyde and nitrite with subsequent increase in vitamin C levels after two months of follow-up indicate a good response to treatment with standard ATT. Hence, the extent of oxidative stress in PTB can be evaluated by analyzing lipid peroxidation product, antioxidant and nitric oxide levels.

Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

Caspase 1 and caspase 8 in HIV infected patients with and without tuberculosis.

BACKGROUND: Caspase 8 is involved in apoptosis mediated by Fas and p55 tumor necrosis factor receptor ligation in HIV infection. Apoptosis is partially mediated by interleukin-1beta-converting enzyme (caspase-1). AIMS: We determined apoptosis, using caspase-1 and caspase-8, among patients with HIV infection, with and without tuberculosis (TB), those with TB alone and healthy individuals. SETTING AND DESIGN: Cross-sectional analysis of caspase-1 and caspase-8 among patients with HIV infection, with and without TB, those with TB alone and healthy individuals. MATERIALS AND METHODS: Nineteen HIV infected patients with TB (HIV+/TB+) and 20 with HIV infection without TB (HIV+/TB-) were studied. Fifteen individuals with TB alone were disease controls (HIV-/TB+) and 20 were healthy controls (HIV-/TB-). Caspases were measured by single-step ELISA using commercially available monoclonal antibodies. STATISTICAL ANALYSIS: Two-way ANOVA and Pearson's correlation coefficient. RESULTS: Mean CD4 counts of HIV+/TB+ were lower than HIV+/TB- (p<0.05). OD value of caspase 1 in HIV+/TB+ was 0.295+0.05, while that in HIV+/TB- it was 0.302+0.18. It was 0.293+0.07 in HIV-/TB+ and in HIV-/TB- the values were 0.287+0.06. OD value of caspase 8 in HIV+/TB+ was 0.307+ 0.07, lower than HIV+/TB- (0.927+0.25). It was 0.008+0.03 in HIV-/TB+ and in HIV-/TB-, 0.074+0.004. Values of caspase 8 in patients with HIV infection (with/without TB) were higher than those with TB alone or healthy individuals (p<0.01). Levels of caspase 8 in HIV+/TB- were higher than patients with HIV+/TB+ (p<0.01). CONCLUSION: Levels of caspase-1 are not different irrespective of presence or otherwise of TB and HIV infection. Fas-related apoptosis is higher in HIV infection. With concomitant TB, levels of caspase 8 were lower as compared with those without TB.

Estudo do metabolismo da glicose na tuberculose pulmonar ativa utilizando a tomografia por emissão de pósitrons (18F-FDG PET) / Evaluation of glucose metabolism in active lung tuberculosis by positron-emission tomography (18F-FDG PET)

Os métodos de imagem utilizados na avaliação da tuberculose pulmonar incluem a radiografia e a tomografia computadorizada do tórax. As imagens obtidas pelos métodos de medicina nuclear permitem estudos funcionais e metabólicos dos órgãos de interesse, através do uso de radiofármacos específicos. Alterações do metabolismo da glicose podem ser detectadas pela tomografia por emissão de pósitrons (PET) utilizando-se o 18F-fluorodesoxiglicose (18F-FDG). Essas alterações estão presentes nas doenças neoplásicas, inflamatórias e infecciosas. A tuberculose é uma doença granulomatosa causada pelo Mycobacterium tuberculosis, que se utiliza de glicose como fonte de energia. Objetivo: O estudo do metabolismo da glicose na tuberculose pulmonar através da PET e sua comparação com a tomografia computadorizada de tórax. Material e métodos: Foram avaliados 20 pacientes portadores de tuberculose pulmonar. Todos foram submetidos à PET e à tomografia computadorizada de tórax, em até 30 dias após o início do tratamento. Resultados: Todos os pacientes apresentaram captação positiva do 18F-FDG na PET. Na tomografia computadorizada do tórax, todos os pacientes apresentaram sinais compatíveis com atividade de tuberculose. A sensibilidade dos dois métodos foi de 100 por cento. Houve concordância entre os achados do 18F-FDG PET e da tomografia computadorizada (K = 0,27 e p < 0,001). Conclusões: Concluiu-se, através do 18F-FDG PET, que o metabolismo da glicose está alterado na tuberculose pulmonar e que há concordância com as alterações anatômicas observadas pela tomografia computadorizada do tórax

Reserva supra-renal na tuberculose pulmonar: resposta do cortisol sérico ao estímulo com ACTH de açäo prolongada / Adrenal reserve in pulmonary tuberculosis: serum cortisol response to stimulation with long-acting ACTH

Propusemo-nos a inveetigar a reserva supra-renal na tuberculose pulmonar utilizando ACTH-DEPOT, intramuscular, que resulta em estímulo mais intenso e prolongado. Estudamos 32 pacientes com tuberculose pulmonar, recém-diagnosticados com baciloscopia positiva, sem tratamento ou com menos de uma semana de tratamento específico. O estímulo adrenal foi feito com colheita de cortisol plasmático em jejum (basal) e após 6 horas de administraçäo do ACTH-DEPOT. Os pacientes apresentavam cortisol basal de 21,4 +/-/- 6,9ng/dl, após estímulo (6 horas) de 54,3+/-/- 19ng/dl (p<0,001), incremento absoluto de 17,4 +/- 31ng/dl (NS)e incremento relativo de 171 +/-/- 92 por cento (p<0,01)em comparaçäo aos normais, respectivamente 13 +/-/- 5,2ng/dl; 52,4 +/-/- 10,4ng/dl; 39,2 +/-/- 21,7ng/dl e 429 +/-/- 478 por cento. Em relaçäo aos valores pós-estímulo e incremento absoluto, näo houve difernça nos dois grupos, mas o nível basal foi maior nos tuberculosos (p<0,001)e o incremento relativo maior nos normais (p<0,001). O menor incremento relativo na tuberculose podera ser explicado pelos níveis de cortisol basal mais elevados, do que pelo comprometimento granulomatoso da glàndula. Em conclusäo, apesar da diferença em relaçäo ao incremento relativo do cortisol nos pacientes tuberculosos, nenhum apresentou resposta compatível com reserva adrenal diminuída, demonstrando que mesmo na fase ativa o comprometimento funcional da glàndula näo é acentuado.

Relationships between pleural fluid pH, PCO2 to pleural fluid PO2, amylase, protein, glucose and white cells in tuberculous and malignant effusions.

The relationships between pleural fluid pH and PO2 to pleural fluid PO2, amylase, protein, glucose, white cell count were examined in 110 cases of tuberculous and 140 cases of malignant pleural effusions. Pleural fluid amylase concentrations of 200 or more units/ml indicated malignant effusions rather than tuberculous effusions with a specificity of 92.7 per cent and sensitivity of 27.1 per cent. There was evidence which suggested that the increasing pleural fluid amylase concentrations were due to the excessive leakage of serum amylase into the pleural cavity secondary to the break-down of capillaries by tuberculosis and malignancy as well as the production of amylase by tumor cells invading the pleura. The decreasing pleural fluid pH and increasing pleural fluid PCO2 had a significant linear relationship with decreasing fluid PO2, increasing pleural fluid protein and decreasing fluid glucose. These indicated a leakage of serum protein into the pleural cavity and the over-utilization of glucose relative to the transport defect of low pleural fluid glucose concentrations in the acidotic fluid of tuberculous and malignant effusions. No relationship between pleural fluid pH and PCO2 to pleural fluid and white cell count was found in the present study.