Neonatal bacillus Calmette-Guerin vaccination and environmental mycobacteria in sensitizing antimycobacterial activity of macrophages.

An immunoepidemiological study was performed to evaluate the effect of neonatal bacillus Calmette-Guérin (BCG) vaccination and tuberculin response on macrophage killing profile against Mycobacterium tuberculosis. In this epidemiological field work, the study subjects were drawn from in and around Chennai city, South India. The descriptive epidemiological pattern of neonatal BCG vaccination and its impact on tuberculin skin test were studied. The study subjects for the immunologic laboratory experiments were recruited based on the skin test (Mantoux) outcome and were grouped in to 4 natural study groups that include vaccinated reactors, vaccinated nonreactors, nonvaccinated reactors and nonvaccinated nonreactors. In immunologic laboratory work part, the elucidation of macrophage killing profile was studied for all the 4 groups, and appropriate intercomparisons were made. The parameters used for the macrophage killing profile were (1) glutathione assay, (2) measurement of phagocytosis, (3) intracellular growth kinetics of M. tuberculosis H37Rv, (4) tumor necrosis factor-α assay and (5) interferon-γ assay. The results found that in the BCG-vaccinated tuberculin reactors the macrophage responses were significantly higher than the BCG-vaccinated tuberculin nonreactors. There was no significant difference in the responses among the BCG-vaccinated tuberculin reactors when compared with the nonvaccinated tuberculin reactors. The immune responses of nonvaccinated tuberculin reactors were significantly higher than the vaccinated tuberculin nonreactors. These findings show that the immune response among the adolescents/young adults is elicited by exposure to mycobacteria and not by the neonatal BCG vaccination.

Underestimation of impaired kidney function with serum creatinine.

Serum creatinine (SCr) levels are frequently used as a screening test to assess impaired renal function; however, patients can have significantly decreased glomerular filtration rate (GFR) with normal SCr values and making the recognition of kidney dysfunction more difficult. Hence, this study was designed to determine the extent of misclassification of the patients who have significantly reduced GFR as calculated by reexpressed four variable modification of diet in renal disease (MDRD) equation but, normal range of SCr. The study included 1040 in and out patients referred by physicians for serum creatinine measurement. When an exclusion criterion was applied 928 patients were qualified for the study. SCr was measured in 928 patients by a Roche kinetic compensated Jaffe's assay. GFR was calculated using reexpressed four variable MDRD study equation. Of the 928 patients 270 (29.1%) had renal dysfunction on the basis of eGFR (<60 ml/min/1.73 m(2)). However, with SCr only 162 (17.5%) patients had abnormal renal function (>1.5 mg/dl) and SCr values misrepresented (108) 11.6% patients with impaired kidney function. In addition, more females, about 15% were failed to detect by SCr method in contrast to males of 9%. This study documented that, a large proportion of patients with impaired renal function are not diagnosed if clinicians rely solely on normal SCr as evidence of normal renal function. Inclusion of eGFR calculated by re-expressed 4 variable MDRD equation may facilitates the early identification and intervention of patients with renal impairment.

Oxalate-induced and cell-cycle-dependent expression of nuclear pore complex oxalate binding protein gp210.

The effect of oxalate, a constituent of renal stone, on the expression of nuclear pore complex oxalate binding protein (gp210) in Vero monkey kidney cells was examined. The expression of this protein was found to increase more in mitotic phase than in S phase, suggesting cell cycle dependency. Exposure of cells to oxalate-containing growth medium resulted in a relative increase in nuclear pore complex oxalate binding protein in each stage of cell cycle. The concentration of this protein was found to increase six times in the telophase stage of the cells exposed to high concentrations of oxalate in the growth medium, though slight reduction in cell density was observed. Structural analogues of oxalate did not show any stimulatory effect on expression of this oxalate binding protein. Hence, the expression of the nuclear pore complex oxalate binding protein gp210 was specific to oxalate and is cell cycle dependent.

HLA-DR2 phenotype and plasma lysozyme, beta-glucuronidase and acid phosphatase levels in pulmonary tuberculosis.

SETTING: Tuberculosis Research Centre, Indian Council of Medical Research, Madras, India. OBJECTIVE: To elucidate the role of HLA-Class II genes/gene products on phagocyte enzymes such as lysozyme, beta-glucuronidase and acid phosphatase in the plasma of pulmonary tuberculosis patients. DESIGN: Serological determination of HLA-DR and -DQ antigens was carried out in 54 active and 84 inactive pulmonary tuberculosis (quiescent) patients and 36 healthy control subjects. The levels of lysozyme, beta-glucuronidase and acid phosphatase were measured in the plasma of tuberculosis patients and control subjects. RESULTS: Increased lysozyme levels were observed in active pulmonary tuberculosis patients. beta-glucuronidase activity was higher in inactive-TB than in active-TB patients and control subjects. HLA-DR2 positive patients showed a lower lysozyme level than -DR2 negative patients. CONCLUSION: Increase in the plasma lysozyme level in active TB reveals the active stage of the disease. Further, increase in the activity of beta-glucuronidase in inactive-TB patients reveals the quiescent stage of the disease. The low level of lysozyme in HLA-DR2 positive patients may also be one of the possible factors involved in susceptibility to tuberculosis.

Neopterin as a marker for cell-mediated immunity in patients with pulmonary tuberculosis.

SETTING: Cell-mediated immunity (CMI) involves macrophage activation and T cell proliferation. These two parameters are compared in this study. OBJECTIVE: To ascertain the role of neopterin as a biochemical marker for CMI in patients with pulmonary tuberculosis. DESIGN: We measured neopterin levels in serum and the culture supernatants of peripheral blood mononuclear cells (MNC) after stimulation with purified protein derivative (PPD) in 11 patients with pulmonary tuberculosis and 10 healthy individuals. Lymphocyte proliferative response to PPD was carried out in these two groups. RESULTS: The mean concentration of serum neopterin was significantly higher in patients than in controls (P < 0.01). The spontaneous release of neopterin was significantly higher in culture supernatants of MNC from patients when compared with those of healthy controls (P < 0.05). Release of neopterin from MNC stimulated with PPD, however, was similar in both groups. The neopterin release and the stimulation index (SI) in lymphocyte proliferation assay were not comparable, suggesting that these two parameters do not run in parallel for measuring the status of CMI. However, serum concentration of neopterin was inversely related to the SI in a large proportion of subjects (66%). CONCLUSION: Measurement of neopterin, a soluble product of immune cells (macrophage), may provide information on the state of CMI.

Acute phase proteins in tuberculous patients.

The serum concentrations of some acute phase proteins were determined on admission, during treatment, at the end of treatment and at 12 months after stopping treatment in 20 patients with pulmonary tuberculosis. Measurements were also made, on admission and at the end of treatment, in 19 patients with abdominal tuberculosis, and 11 children with tuberculous meningitis. All 20 patients with pulmonary TB had quiescent disease by the end of treatment and none had a bacteriological relapse during the follow-up period of 12 months. The response to treatment was considered favourable in 18 of the 19 patients with abdominal TB, and the CSF findings had returned to normal in 9 of 11 patients with TB meningitis. There was a significant decrease with treatment in the concentrations of C-reactive protein, ceruloplasmin, haptoglobin and alpha-1-acid glycoprotein in all 3 groups of patients. While there was an increase in the concentrations of transferrin in patients with pulmonary and abdominal TB, there was a significant decrease in those with TB meningitis; alpha 2-macroglobulin did not appear to function as an acute phase reactant in any of the 3 groups. Amalgamating the findings in all 3 groups of tuberculous patients, the proportions of patients with abnormal values on admission and at the end of treatment were 62% and 14% for C-reactive protein, 78% and 50% for ceruloplasmin, 86% and 26% for haptoglobin and 92% and 6% for alpha 1-acid glycoprotein, respectively.

Role of rifampicin in arthralgia induced by pyrazinamide

Arthralgia during daily treatment with chemotherapy regimens containing pyrazinamide was found to be considerably less in patients who received rifampicin concomitantly...