Synthesis and some reactions of 2-acetylimidazo[4,5-b]pyridine. Antituberculotic activity of the obtained compounds.

2-Acetylimidazo[4,5-b]pyridine was prepared and its reactions with some aromatic amines and sulfur (Willgerodt-Kindler reaction), some aromatic aldehydes, some carboxylic acid hydrazides as well as thiourea were investigated. New imidazo[4,5-b]pyridine derivatives with different substituents in 2-position (N-arylthioamides, imines, alpha, beta-unsaturated ketones, hydrazido-hydrazones and aminothiazole) were obtained. Most of the synthesized compounds were tested in vitro for their antituberculotic activity.

Some reactions of 2-cyanomethylimidazo[4,5-b]pyridine with isothiocyanates. Antituberculotic activity of the obtained compounds.

Some reactions of 2-cyanomethylimidazo[4,5-b]pyridine with isothiocyanates were carried out. New derivatives of imidazo[4,5-b]pyridine with different substituents in 2-position and derivatives of the new thiazolo-pyrido-imidazo-pyrimidine ring system were synthesized. Most of the obtained compounds were tested in vitro for their antituberculotic activity.

Tuberculosis in the autopsy material: analysis of 1500 autopsies performed between 1972 and 1991 in the Institute of Tuberculosis and Chest Diseases, Warsaw, Poland.

SETTING: The present study is based on 1500 autopsies done in the Institute of Tuberculosis and Chest Diseases Warsaw, Poland during the years 1972-81 and 1982-91. OBJECTIVE: To assess the correctness of tuberculosis diagnosis before death in the above mentioned time periods. DESIGN: The autopsy reports were examined for the diagnosis of active tuberculosis proved by microscopy. The form and localisation of tuberculosis was assessed. The postmortem diagnosis was compared with clinical diagnosis. In those cases in which tuberculosis was not recognised before death the possible causes of this failure were analyzed. RESULTS: Active tuberculosis was found in 119 cases, 7.9% of all autopsies. It was localised in the lungs exclusively in 72 cases, in lungs and in extrapulmonary sites in 45 and in extrapulmonary sites only in 2. The frequency of active tuberculosis was the same for the two periods under evaluation. Tuberculosis was however not recognised before death in a much higher proportion of cases in 1982-92 (54%) than in 1972-81 (24%). The main cause of diagnostic failure was connected with atypical localisation of lesions on chest X-ray and with dissemination outside the lungs. Previous tuberculosis was a factor which facilitated the diagnosis of tuberculosis. CONCLUSIONS: In parallel with the decline of tuberculosis incidence in Poland, many doctors lack experience in diagnosing this disease, especially in cases with atypical X-ray presentation and with extrapulmonary localisation. This may lead to late or even very late diagnosis and have a significant impact on the epidemiological situation.

[Pneumonia in patients after extracorporeal circulation]. / Zapalenia pluc u chorych po operacjach w krazeniu pozaustrojowym.

Hospital infections are still an important problem of to-days medicine. The most common and dangerous one is pneumonia. The purpose of this study was to determine the cause of pneumonia in patients operated on under extracorporeal circulation. It was proved that micro-organisms responsible for pneumonia in our patients were Pseudomonas sp. and Staphylococcus aureus. No correlation between the bacterial flora cultured from the air in operating theatre and post-op. ward and bacterial flora responsible for pneumonia was found. It can be infer that pulmonary infections were rather caused by hospital cross-infections or endogenic infections in colonized patients.

[Drug sensitivity of bacillus strains M. avium-intracellulare (MAIC), M. kansasii cultured from patients with mycobacteriosis before treatment]. / Wrazliwosc na leki szczepów pratków M. avium-intracellulare (MAIC), M. xenopi i M. kansasii, wyhodowanych od chorych z mykobakteriozami przed rozpoczeciem leczenia.

The aim of study was to evaluate a drug sensitivity of M. avium-intracellulare, M. xenopi and M. kansasii cultured from 55 patients with mycobacterioses. The identification of strains was performed with morphological and biochemical tests and thin-layer chromatography. Resistance tests were done on egg L-J and agar media for selected drugs. It was documented that MAIC strains were non-sensitive on isoniazid and rifampicin, and other ones. The most active drug was cycloserine inhibiting growth of 80% but rifabutine--50% of strains. M. xenopi strains were sensitive for tested drugs including isoniazid and rifampicin (about 30%). M. kansasii strains were in 100% sensitive for cyclosporine, rifabutine, Davercin and ofloxacin and partly for isoniazid, streptomycin and Augmentin.

[Tuberculosis as a cause of death in patients treated in the institute of tuberculosis in 1976-1991]. / Gruzlica jako przyczyna zgonu u chorych leczonych w instytucie gruzlicy w latach 1976-1991.

This study aimed at assessing the reasons why tuberculosis-which can be successfully treated today-is still the cause of death in some patients treated at the Institute of Tuberculosis in the last 15 years. The material consisted of clinical documentation and the results of autopsy of 30 patients who died of tuberculosis between 1976-1991. It was found that 19 out of 30 patients were not treated with antituberculous drugs or were treated only during few days because tuberculosis was diagnosed too late (in 15 patients after death). In 6 patients the treatment failed due to side effects of drugs and in 5 immunosuppressed patients, disease progressed despite the treatment. Difficulties in tuberculosis diagnosis were caused by atypical appearance of the disease in the chest X-ray (localization in the middle and lower lobes in 15 cases, absence of cavities in 22 cases) and in the extrapulmonary regions (11 cases). The main obstacle was the failure to cultivate tubercle bacilli from numerous specimens of the sputum in 10 out of 23 patients in whom the cultures were done.

[Investigations of pyrazine derivatives. Part XXVII. Synthesis and tuberculostatic activity of some 6-alkoxypyrazine-2-carbotioamids]. / Badania nad pochodnymi pirazyny. XXVII. Synteza i dzialanie tuberkulostatyczne 6-alkoksypirazyno-2-karbotioamidów.

It was found that reaction of sodium alcoholates and cyanopyrazine yields alkoxypyrazine-nitriles. In heterogenic reaction both 2-alkylimidesters-6-chloropyrazine or 2-alkylimidoesters-6-alkoxypyrazine can be obtained dependent. This is dependent on quantity of alcohol used for reaction. Final products, alkoxypyrazinethioamides were tested for tuberculostatic activity (MIC within 31-500 mcg/cm3).

[Sensitivity to cefoperazone (CEFOBID) of microorganisms isolated from diagnostic specimens]. / Wrazliwosc na cefoperazon (CEFOBID) drobnoustrojów izolowanych z materialów diagnostycznych uzyskanych od chorych.

Sensitivity of cephaperasone (CEFOBID) of 966 straits of microorganisms, isolated from 661 patients was assessed. The study was carried out according to the trial described by Bauer et al, using the Mueller-Hinton medium and original cephaperasone tests (Pfizer). Full sensitivity was found in 87.1% of the organisms. The following conclusions were made: 1. Most isolated organisms were sensitivite to cephaperasone (87.1%); E. coli (98.5%), Kl. Pneumoniae (94.8%), Atrobacter (93.1%), Enterobacter (92.8%), Klebsiella sp (92.5%). Lowered sensitivity was seen in Pseudomonas sp. (70.9%), Acinobacter (70.8%) and Alcaligenes (58.3%). 2. Cross-resistance with other cephalosporines was found in 27.8% of the cases. In 52.4% full sensitivity to cephaperasone was found, and resistance to other clinically used cephalosporines.

[Studies on pyrazine derivatives. XXVI. Synthesis and tuberculostatic activity of N-pyrazinylthiourea]. / Badania nad pochodnymi pirazyny. XXVI. Synteza i aktywnosc tuberkulostatyczna N-pirazynylotiomoczników.

2-Amino-3-chloropyrazine and 2-amino-6-chloropyrazine were reacted with appropriate sodium alkoxides to give 2-aminopyrazine derivatives with the methoxy, benzyloxy, chlorobenzyloxy, dichlorobenzyloxy, bromobenzyloxy or dibromobenzyloxy group at positions 3 and 6 (I-XIV). The obtained compounds were converted into N-pyrazinyl-N'-benzoylthioureas (XV-XXXI) by reacting with benzoyl isothiocyanate. Their hydrolysis yielded N-pyrazinylthioureas XXXII-XLVII. Analogical reactions of alkoxyaminopyrazines with p-chlorophenyl isothiocyanate or 2,6-dichlorophenyl isothiocyanate afforded corresponding N-pyrazinyl-N'-(p-chlorophenyl)thioureas and N-pyrazinyl-N'- (2,6-dichlorophenyl)thioureas (XLVIII-LVIII). The obtained compounds were found to display tuberculostatic in vitro activity with MIC values from 8 meg/cm3 to 1000 mu meg/cm3.