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Same immunologic parameters in the monitoring treatment and prognosis of patients with tuberculosis
16
Tubercle and Lung Disease: Supplement
54 SAME IMMUNOLOGIC PARAMETERS IN THE MONITORING TREATMENT AND PROGNOSIS OF PATIENTS WITH TUBERCULOSIS Kowal, E., Zagdrecka, A., Ossolihka, M., Mrdz, R. Department of Lung Diseases and Tuberculosis, Academy ul. iurawia 14, 14-540 Bialystok, Poland
Medical
PCR provided important information ventional diagnosis was difficult.
whenever the con-
56 RIFAMPICIN-CONTAINING CHEMOPROPHYLAXIS REGIMENS COMPARED IN CORNELL MODEL MURINE TUBERCULOSIS
The aim of this work was to evaluate same immunologic parameters in patients with tuberculosis before the treatment, during the treatment, and in the follow-up period.
Mitchison D.A., Dhillon Jasvir, Sole Kath. Dept of Medical Microbiology, St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
The total number of lymphocytes in the peripheral blood were determined. Monoclonal sera were used to determine particular lymphocyte classes CD4, CDs. Besides the ability of lymphocytes to blast transformation under the influence of PHA was examined. The biologic activity of neutrophiles was also evaluated by means of (spontaneous and stimulated) NBT test. Apart from the immunologic examinations other laboratory and clinical indices showing general biological condition and efficiency of the parenchymal organs were also taken into consideration. The examinations were carried out in 60 subjects, 18-60 years of age, including 16 femals and 44 males. The observation time amounted from several months to two years.
BALB/c mice were infected intravenously with 5.94 log cfu of mouse-passaged M. tuberculosis, strain H37Rv. After 2 weeks, log cfu counts averaged 7.83 in lungs and 7.02 in spleens. Treatment with 25 mg/kg isoniazid and 1.000 mg/kg pyrazinamide (HZ) in the diet was given for 7 weeks when log cfu counts averaged 3.18 in lungs and 2.79 in spleens. The mice were then divided into 4 groups of 43-45 mice and a control group of 10 mice. The controls were continued on dietary HZ for a further 6 weeks (13 weeks in all) when only 4 had positive lungs or spleens. The remaining 4 groups were treated for the 6 weeks with 15 mg/kg rifampicin either (1) alone (R), or (2) with 25 mg/kg isoniazid (RH), or (3) with 150 mg/kg pyrazinamide (RZ) or (4) with isoniazid & pyrazinamide (RHZ). Doses were given by oral gavage 6 x per week, the rifampicin at least 10 min before other drugs. No further chemotherapy was given to the mice until sacrifice of one-third at 26 weeks and two-thirds at 35 weeks. During the previous 3 weeks, they were treated with 0.5 or 0.75 mg di-hydrocortisone IM 3 x weekly. Positive organ cultures were:
The results show marked differentiation of the immunologic reactivity in different patients and different dynamics of the changes during the treatment and during the follow-up period. Resultes of the immunologic examinations were analyzed in relation to other laboratory and clinical parameters. We think that application of chosen immunologic test in clinical practice may be especially useful during monitoring the treatment and prognosing durability of the therapeutical effectiveness.
55 DETECTION OF MYCOBACTERIUM TUBERCULOSIS IN CLINICAL SAMPLES USING THE POLYMERASE CHAIN REACTION Medo, A.M. 1, 2; Ararijo M. F. I, 2; Rodrigues M. F. 1; Pereira M. F. I; Kolk A. H. J. 3. I National Institute of Health, 2 Center for Experimental Cytology, Porto, Portugal and 3 Royal Tropical Institute, Amsterdam, The Netherlands.
A test based on the Polymerase Chain Reaction (PCR), was used for the detection of the Mycobacterium tuberculosis complex in clinical samples. In this test, a 541 bp sequence of the insertion element IS 6110 was amplified and detected by agarose gel electrophoresis in the presence of ethidium bromide. We have tested clinical samples from 66 patients suspected of having tuberculosis. These included, 55 sputa, 81 induced sputa, 22 nose swabs, 21 throat swabs, 2 bronchoaiveolar lavage, 1 sinovial fluid, 8 pleural fluids and 3 pus. Sputum samples were first decontaminated and all samples were treated either with proteinase K or DNA was purified by the guanidinium thiocyanate - diatoms method as described by Boom and coworkers. Part of each sample was spiked with M. tuberculosis DNA to control for the presence of inhibitors of the PCR, causing false negative results and to provide a semiquantitative assay. PCR was positive for all 34 culture positive and Ziehl-Neelsen (ZN)-positive samples and in 30 culture negative ZNnegative samples corresponding to either patients being followed up or to TB patients diagnosed on the basis of clinical findings.
R
RH
RZ
RHZ
“=
43
41
43
45
Spleen %
32 74
2s 61
27 63
23 51
35 81
25 61
28 65
31 69
Spleen %
or lungs
In conclusion, the efficacies of RH, RZ & RHZ were similar though perhaps greater than that of R.
57 RIFABUTIN VS RIFAMPICIN IN THE TREATMENT OF INITIAL PULMONARY TUBERCULOSIS. FOLLOW-UP AT 5 YEARS. Melero, C., Rey, R.,* Ussetti, P., Muiioz, L., Caballero, J., Ortega, A., Ramos, A.; * Centro de Investigacibn Clinica. Institute de Salud Carlos III. Sinesio Delgado 10. 28029 Madrid. Espafia.
Rifabutin (Ansamycin cide power activity studies.
LM-427) had showed higher germithan rifampicin in experimental
Objectives: To analize the efficacy and tolerance of rifabutin versus rifampicin in the classical regimen of nine months in patients with pulmonary tuberculosis. Population:
Patients with pulmonary initial tuberculosis. Inclusion criteria: absence of previous treatment, hepatic diseases, ophtalmologic disorders, renal failure and stable address. Exclusion criteria: terminal illness or neoplasia, suspected pregnancy and white cells counts < 4000 and/or platelets < 150000. Design:
Multicentric controled and randomized study from June 1986 to December of 1987. Follow-up with bacteriologic control of sputum and registration of into-
Tubercle and Lung Disease: Supplement
54 SAME IMMUNOLOGIC PARAMETERS IN THE MONITORING TREATMENT AND PROGNOSIS OF PATIENTS WITH TUBERCULOSIS Kowal, E., Zagdrecka, A., Ossolihka, M., Mrdz, R. Department of Lung Diseases and Tuberculosis, Academy ul. iurawia 14, 14-540 Bialystok, Poland
Medical
PCR provided important information ventional diagnosis was difficult.
whenever the con-
56 RIFAMPICIN-CONTAINING CHEMOPROPHYLAXIS REGIMENS COMPARED IN CORNELL MODEL MURINE TUBERCULOSIS
The aim of this work was to evaluate same immunologic parameters in patients with tuberculosis before the treatment, during the treatment, and in the follow-up period.
Mitchison D.A., Dhillon Jasvir, Sole Kath. Dept of Medical Microbiology, St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
The total number of lymphocytes in the peripheral blood were determined. Monoclonal sera were used to determine particular lymphocyte classes CD4, CDs. Besides the ability of lymphocytes to blast transformation under the influence of PHA was examined. The biologic activity of neutrophiles was also evaluated by means of (spontaneous and stimulated) NBT test. Apart from the immunologic examinations other laboratory and clinical indices showing general biological condition and efficiency of the parenchymal organs were also taken into consideration. The examinations were carried out in 60 subjects, 18-60 years of age, including 16 femals and 44 males. The observation time amounted from several months to two years.
BALB/c mice were infected intravenously with 5.94 log cfu of mouse-passaged M. tuberculosis, strain H37Rv. After 2 weeks, log cfu counts averaged 7.83 in lungs and 7.02 in spleens. Treatment with 25 mg/kg isoniazid and 1.000 mg/kg pyrazinamide (HZ) in the diet was given for 7 weeks when log cfu counts averaged 3.18 in lungs and 2.79 in spleens. The mice were then divided into 4 groups of 43-45 mice and a control group of 10 mice. The controls were continued on dietary HZ for a further 6 weeks (13 weeks in all) when only 4 had positive lungs or spleens. The remaining 4 groups were treated for the 6 weeks with 15 mg/kg rifampicin either (1) alone (R), or (2) with 25 mg/kg isoniazid (RH), or (3) with 150 mg/kg pyrazinamide (RZ) or (4) with isoniazid & pyrazinamide (RHZ). Doses were given by oral gavage 6 x per week, the rifampicin at least 10 min before other drugs. No further chemotherapy was given to the mice until sacrifice of one-third at 26 weeks and two-thirds at 35 weeks. During the previous 3 weeks, they were treated with 0.5 or 0.75 mg di-hydrocortisone IM 3 x weekly. Positive organ cultures were:
The results show marked differentiation of the immunologic reactivity in different patients and different dynamics of the changes during the treatment and during the follow-up period. Resultes of the immunologic examinations were analyzed in relation to other laboratory and clinical parameters. We think that application of chosen immunologic test in clinical practice may be especially useful during monitoring the treatment and prognosing durability of the therapeutical effectiveness.
55 DETECTION OF MYCOBACTERIUM TUBERCULOSIS IN CLINICAL SAMPLES USING THE POLYMERASE CHAIN REACTION Medo, A.M. 1, 2; Ararijo M. F. I, 2; Rodrigues M. F. 1; Pereira M. F. I; Kolk A. H. J. 3. I National Institute of Health, 2 Center for Experimental Cytology, Porto, Portugal and 3 Royal Tropical Institute, Amsterdam, The Netherlands.
A test based on the Polymerase Chain Reaction (PCR), was used for the detection of the Mycobacterium tuberculosis complex in clinical samples. In this test, a 541 bp sequence of the insertion element IS 6110 was amplified and detected by agarose gel electrophoresis in the presence of ethidium bromide. We have tested clinical samples from 66 patients suspected of having tuberculosis. These included, 55 sputa, 81 induced sputa, 22 nose swabs, 21 throat swabs, 2 bronchoaiveolar lavage, 1 sinovial fluid, 8 pleural fluids and 3 pus. Sputum samples were first decontaminated and all samples were treated either with proteinase K or DNA was purified by the guanidinium thiocyanate - diatoms method as described by Boom and coworkers. Part of each sample was spiked with M. tuberculosis DNA to control for the presence of inhibitors of the PCR, causing false negative results and to provide a semiquantitative assay. PCR was positive for all 34 culture positive and Ziehl-Neelsen (ZN)-positive samples and in 30 culture negative ZNnegative samples corresponding to either patients being followed up or to TB patients diagnosed on the basis of clinical findings.
R
RH
RZ
RHZ
“=
43
41
43
45
Spleen %
32 74
2s 61
27 63
23 51
35 81
25 61
28 65
31 69
Spleen %
or lungs
In conclusion, the efficacies of RH, RZ & RHZ were similar though perhaps greater than that of R.
57 RIFABUTIN VS RIFAMPICIN IN THE TREATMENT OF INITIAL PULMONARY TUBERCULOSIS. FOLLOW-UP AT 5 YEARS. Melero, C., Rey, R.,* Ussetti, P., Muiioz, L., Caballero, J., Ortega, A., Ramos, A.; * Centro de Investigacibn Clinica. Institute de Salud Carlos III. Sinesio Delgado 10. 28029 Madrid. Espafia.
Rifabutin (Ansamycin cide power activity studies.
LM-427) had showed higher germithan rifampicin in experimental
Objectives: To analize the efficacy and tolerance of rifabutin versus rifampicin in the classical regimen of nine months in patients with pulmonary tuberculosis. Population:
Patients with pulmonary initial tuberculosis. Inclusion criteria: absence of previous treatment, hepatic diseases, ophtalmologic disorders, renal failure and stable address. Exclusion criteria: terminal illness or neoplasia, suspected pregnancy and white cells counts < 4000 and/or platelets < 150000. Design:
Multicentric controled and randomized study from June 1986 to December of 1987. Follow-up with bacteriologic control of sputum and registration of into-