Aerosolized interferon-alpha treatment in patients with multi-drug-resistant pulmonary tuberculosis

Multi-drug-resistant tuberculosis (MDR-TB) has emerged as an obstacle to the control of tuberculosis. Recent data however, suggest that interferon-(IFN)-gamma and IFN-alpha may improve disease evolution in subjects affected with pulmonary tuberculosis caused by multi-resistant (IFN-gamma) and sensitive (IFN-alpha) strains. The mechanisms involved are not known, even though it has been reported that IFN-gamma-secreting CD4+ Th cells may possess antitubercular effects. In addition, IFN-alpha can induce IFN-gamma secretion by CD4+ Th cells, and both types of IFN may stimulate macrophage activities. The aim of this study was to explore the possibility that aerosolized IFN-alpha, administered concomitantly with conventional antitubercular chemotherapy, may improve the course of pulmonary tuberculosis. After six months of directly observed therapy (DOT), seven patients who were non-responders to a second line antitubercular therapy were given an IFN-alpha aerosol (3 MU, three times a week) for two months as adjunctive therapy. All strains were resistant to at least two first-line drugs. After IFN-alpha administration, the patients were followed up for a further six months with the same DOT. Sputum samples were collected monthly during the study period, with the exception of the IFN-alpha administration period, when the observations were performed weekly. High resolution computed tomography (HRCT) chest scans were performed before and after IFN-alpha inhalations. The analysis of the results showed that the mean number of Mycobacterium tuberculosis (Mt) had remained statistically unchanged (p = 0.80) during the first 6 months of DOT. During the following 2 months of IFN-alpha administration, 5 patients became negative (p = 0.02). After the end of treatment a progressive increase in Mt number was observed (p = 0. 02). Sputum cultures remained positive for all patients throughout the study period, although a significant decrease (p = 0.02) in the colony number per culture was observed after adjunctive treatment with IFN-alpha. After stopping administration of IFN-alpha, a significant increase (p = 0.03) in the colony number per culture was noted as well as in Mt numbers. HRCT scans were slightly improved in all patients. These preliminary data suggest that aerosolized IFN-alpha may be a promising adjunctive therapy for patients with MDR-TB. Optimal doses and schedules however, require further studies.     

Pulmonary surfactant protein A interacts with gel-like regions in monolayers of pulmonary surfactant lipid extract

Epifluorescence microscopy was used to investigate the interaction of pulmonary surfactant protein A (SP-A) with spread monolayers of porcine surfactant lipid extract (PSLE) containing 1 mol % fluorescent probe (NBD-PC) spread on a saline subphase (145 mM NaCl, 5 mM Tris-HCl, pH 6.9) containing 0, 0.13, or 0.16 microg/ml SP-A and 0, 1.64, or 5 mM CaCl(2). In the absence of SP-A, no differences were noted in PSLE monolayers in the absence or presence of Ca(2+). Circular probe-excluded (dark) domains were observed against a fluorescent background at low surface pressures (pi approximately 5 mN/m) and the domains grew in size with increasing pi. Above 25 mN/m, the domain size decreased with increasing pi. The amount of observable dark phase was maximal at 18% of the total film area at pi approximately 25 mN/m, then decreased to approximately 3% at pi approximately 40 mN/m. The addition of 0.16 microg/ml SP-A with 0 or 1.64 mM Ca(2+) in the subphase caused an aggregation of dark domains into a loose network, and the total amount of dark phase was increased to approximately 25% between pi of 10-28 mN/m. Monolayer features in the presence of 5 mM Ca(2+) and SP-A were not substantially different from those spread in the absence of SP-A, likely due to a self-association and aggregation of SP-A in the presence of higher concentrations of Ca(2+). PSLE films were spread on a subphase containing 0.16 microg/ml SP-A with covalently bound Texas Red (TR-SP-A). In the absence of Ca(2+), TR-SP-A associated with the reorganized dark phase (as seen with the lipid probe). The presence of 5 mM Ca(2+) resulted in an appearance of TR-SP-A in the fluid phase and of aggregates at the fluid/gel phase boundaries of the monolayers. This study suggests that SP-A associates with PSLE monolayers, particularly with condensed or solid phase lipid, and results in some reorganization of rigid phase lipid in surfactant monolayers.     

Epidemiological danger of patients with pulmonary tuberculosis and alcoholism refusing treatment

The comparative evaluation of the epidemiological danger of alcohol-addicted persons with pulmonary tuberculosis who evaded treatment (the test group of 133 persons) and that of tuberculosis patients receiving adequate treatment under hospital conditions (the control group of 162 patients) was made. The morbidity level among relations having contacts with the patients evading treatment exceeded the morbidity level in the families of tuberculosis patients undergoing adequate treatment 4.5-fold for adults and 3.4-fold for children and adolescents, the contamination level in the latter group being twice as high. Although no cases of the disease were registered in the foci of infection where sick persons evading treatment had low bacterial discharge, still the elevated level of infection among children and adolescents in these foci as compared with the foci where tuberculosis patients did not evade treatment (35.0% and 21.7% respectively) indicated that the foci of infection where such aggravating factors as alcohol addiction in the source of infection was present were rightly considered to be epidemiologically most dangerous. Persons suffering with both tuberculosis and alcoholism should be subjected to compulsory hospitalization as early as possible.     

Polyantibiotic therapy in the complex treatment of patients with acute diffuse peritonitis

On the basis of the analysis of 217 records of acute diffuse peritonitis peculiarities of the postoperative process of that complication in persons treated with 2 antibiotics (161) and 4 antibacterial drugs (56) were discussed. 4 risk levels were defined with an account of the inflammation process severity. The use of poly-antibiotic therapy was validated. The technique of its application is described in detail. The technique allowed to lower the frequency of postoperative complications and lethality 5-fold.     

Drug resistance in patients with pulmonary tuberculosis.

A review of the records of 984 patients admitted to hospital from 1970 through 1973 with bacteriologically proven pulmonary tuberculosis showed bacterial resistance to one or more antituberculosis drugs in 103 (10.5%). Among the patients who had had previous drug treatment for tuberculosis the prevalence of drug resistance was 20% in the Canadian-born patients and 69.4% in the recent immigrants. Among the patients who had had no previous drug treatment the prevalence of drug resistance (primary resistance) was 2.7% in Canadian-born patients but 11.4% in recent immigrants. Because of the higher prevalence of drug resistance among recent immigrants and the finding in recent years that increasingly more tuberculosis patients in Ontario are recent immigrants, drug resistance in this group is likely to assume even more importance in the future.