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Biomedical subjects

M Nowicki

Publications and source records attributed to M Nowicki.

At least 109 records · Page 6Linked to original sources

Contribution of monocyte-macrophage system to serum alpha 1-antitrypsin.

The major serum antiprotease is alpha 1-antitrypsin (A1AT). Deficiency of A1AT can result in infantile cirrhosis and premature emphysema, both of which have a high degree of morbidity and significant mortality. Although synthesized primarily by the liver, A1AT has been histochemically localized in monocytes and macrophages in vitro and has been shown to be produced in tissue culture of monocyte-macrophage origin. This study was planned to quantitatively and qualitatively assess the in vivo monocyte-macrophage system contribution to serum A1AT. We used bone marrow transplantation (BMT) as an experimental method because there is commanding evidence that after engraftment, the monocyte-macrophage system of the recipient is replaced by that of donor origin. Protease inhibitor (Pi) typing was done on 150 potential BMT recipients and on their potential donors before transplantation. From these initial recipients, 92 eventually underwent transplantation, and 11 recipient-donor pairs, in which each donor's Pi type contained a band not in the recipient's Pi type, were chosen for the study. Six recipients survived beyond 100 days after BMT, and in these cases the donor contained either an S or an M2 band in his or her Pi type not present in the recipient. Using a silver stain method on diluted serum of known M1M2 and MS types, we were able to detect a 2% dilution of the S band and a 25% dilution of the M2 band. When the same method was applied to gels used in typing recipient Pi after BMT, we were unable to detect any contribution to serum A1AT by the donor monocyte-macrophage system.

Bone Marrow Transplantation↗

Effect of culture medium on morphology and virulence of Legionella pneumophila serogroup 1.

In a preliminary study, the preparation of a modified charcoal yeast extract by predialysis of yeast extract (CDYE) allowed us to obtain short non filamentous forms of Legionella pneumophila ser 1 (Philadelphia) found to be more virulent in the chick embryo than the long forms grown on conventional media. We confirmed these findings in guinea pigs inoculated by either intraperitoneal injection or aerosol inhalation. LD50s were calculated using the method of Reed and Muench. Survival curves were established using Liddell's method. If for chick embryo the most virulent organisms were those derived from yolk sac culture, organisms grown on CDYE agar were more virulent than those grown on the other media. There was a significant positive correlation between the mean length of the bacilli and the log 10 of the LD50 (r = 0.96; 0.02 less than p less than 0.05). For guinea pigs by either intraperitoneal injection or inhalation we confirmed that the bacteria cultured on CDYE were more virulent than those grown on other solid media. Thus for the guinea pig inoculated intraperitoneally, the LD50s of the CDYE and BCYE cultures were 1.4 X 10(7) and greater than 3 X 10(9) CFU, respectively. The mortality of guinea pigs inoculated by aerosol with CDYE cultures was significantly higher than that of guinea pigs infected with BCYE cultures using suspensions of 10(8) and 10(9) CFU/ml (p less than 0.01) and 10(10) CFU/ml (p less than 0.05).

Aerosols↗

[Doxycycline treatment of experimental legionellosis in guinea pigs infected by aerosol].

The efficacy of curative and preventive treatment by doxycyclin was studied with the same experimental model as during the study of erythromycin [14]. The infectious aerosol was done with a strain of Legionella pneumophila serogroup 1, Philadelphia (ATCC 33152). Male albinos Dunkin-Hartley guinea-pigs were exposed for 30 min to an aerosol dose of 1, 10 or 100 LD 50 (10(3), 10(4) or 10(5) viable organisms). After preliminary assays to find out the efficient posology, doxycyclin was administered intraperitoneally (IP) 18 h after the infection at a dosage of 60 mg/kg/day for 5 days in the animals infected with 1 LD 50, and 75 mg/kg/day in the animals with 10 and 100 LD 50. The preventive treatment (75 mg/kg/day) administered one day before and the day of the infection was tested with animals infected with 10 LD 50. The guinea-pigs were observed 8 days (weight, rectal temperature) and watched over 3 weeks after the end of treatment; serological and bacteriological tests (cardiac blood, lungs, spleen) were performed in every animal; doxycyclin assays (serum, lungs) during treatment were performed by high performance liquid chromatography (HPLC). The treatment of guinea-pigs infected by 1, 10 and 100 LD 50 gave a survival rate of 100%, 75% and 50% respectively. On the other hand the animals which received preventive treatment were all survivors. Seroconversions with antibody titres from 64 to 512 were observed for all the survivors. Bacteriological tests were all negative. The mean doxycyclin concentrations in serum (microgram/ml) and lung (microgram/g) were 1.66 and 11.42 after 24 h of treatment and 5.71 and 18.93 after 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

[Treatment with erythromycin of experimental legionellosis in guinea pigs infected by aerosol].

The infectious strain L. pneumophila serogroup 1 Philadelphia (ATCC 33152) was cultured on charcoal dialysed yeast extract agar medium (CDYE agar) which produces more virulent strains than those grown on classical agar media. The aerosol was dispersed in a depression chamber by means of a nebuliser and the density was controlled by a density probe. Male albinos Dunkin-Hartley guinea pigs weighing 250-300 g were exposed for 30 minutes to an aerosol dose of 1 LD50 (10(3) viable organisms) and 10 LD50 (10(4) viable organisms). Erythromycin lactobionate (Abbott) was administered subcutaneously 18 hours after the infection, at dosages of 270 mg/kg/day for 4 days in the animals treated with 1 LD50 and for 6 or 7 days in the animals treated with 10 LD50. The guinea pigs were observed for 9 days (weight, rectal temperature; serological and bacteriological tests (cardiac blood, lungs, spleen) and erythromycin assays (serum, lungs) were performed and compared in the treated animals, the non-treated infected control animals and the control animals which only received erythromycin. The percentage survival in the treated guinea pigs after inhalation of 1 LD50 and 10 LD50 (2 tests) were 100%, 75% and 87.5% respectively. Three weeks after treatment, the survivors had antibody titres from 32 to 1,024; the bacteriological cultures and erythromycin assays were negative. In this study, an improvement in the treatment of experimental Legionnaires' disease was observed in comparison with previous experiments. The increased dosage and duration and the early initiation of treatment resulted in survival rates of 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epidemiological evidence of legionellosis transmission through domestic hot water supply systems and possibilities of control.

The use of epidemiological markers for a survey is essential because of the ubiquity of legionellae, particularly L. pneumophila serogroup (SG) 1. The two settings under study were an administrative building associated with a fatal Legionnaires' Disease (LD) case due to L. pneumophila SG 1, and a hospital with 11 cases due to L. pneumophila SG 1 and 3 cases due to L. anisa. Monoclonal antibody serotyping allowed us to establish a link between the outbreaks of LD and the contamination of the hot water supply systems. Two subtypes of L. pneumophila SG 1 and L. anisa were detected in the hospital water system. However the finding of only one subtype of L. pneumophila SG 1 in the patients raised the problem of the difference in virulence of each Legionella strain. By means of aerosol tests on normal and cyclophosphamide-immunosuppressed guinea pigs, we demonstrated the potential pathogenicity of hospital water in the immunosuppressed animals. Two decontamination methods were applied: chlorination and a rise in hot water temperature. Time-limited control measures in the hospital were inadequate, resulting in only temporary eradication, followed by a rapid recolonization of legionellae and the appearance of new nosocomial cases. Decontamination of the administrative building was found to be effective when a constant concentration of 5 ppm free chlorine was obtained at tap outlets, and the water temperature was maintained at 55 C.

Cross Infection↗

Effect of sodium restriction on urinary excretion of cortisol and its metabolites in humans.

The adrenal gland is involved in the control of urinary sodium excretion mainly via the secretion of the mineralocorticoid aldosterone. Although under certain conditions glucocorticoid seem to be also involved in the regulation of sodium homeostasis, there are contradictory reports on the relationship between cortisol secretion and sodium intake. Given recent findings linking regulation of physiological activity of steroids to the activity of specific enzymatic pathways, we have examined changes in urinary excretion of cortisol and its metabolites in eight healthy volunteers on a low sodium diet. Urinary steroids were measured with specific radioimmunoassays after extraction and chromatography (F and E) or after dilution (THF and THE). Excretion of cortisol (124 +/-41 nmol/day) was significantly lower on Day 2 (86 +/- 27 nmol/day, p < 0.01) and Day 7 (85 +/- 25 nmol/day, p < 0.01) of sodium restriction. On the same samples calculated ratios of THF/F (55 +/- 15; 61 +/- 22; 68 +/- 21) and E/F (2.5 +/- 0.6; 2.8 +/- 1.4; 3.0 +/- 1.3) reflecting the activity of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase, respectively, showed significant increases in the former on both Days 2 and 7 and for the latter only on Day 7. This study supports the notion that sodium restriction decreases urinary cortisol excretion and provides evidence that increased activity of 5 beta-reductase and lowered metabolism by 11 beta-HSD are presumably the mechanisms of this decrease.

Adult↗

[The effect of treatment with enalapril versus losartan on levels of insulin resistance in patients with essential hypertension].

Insulin resistance and hyperinsulinaemia are presumed to participate in the pathogenesis of essential hypertension (EH). Insulin resistance is characterised by an impaired insulin-mediated glucose uptake. Participation of the renin-angiotensin system in the development of hyperinsulinaemia in EH patients has not been unanimously proven. The present study aimed to asses the influence of antihypertensive therapy with angiotensin converting enzyme inhibitor (ACEI, enalapril = 10 mg/day) (9 male patients) or angiotensin II AT-1 receptor blocker (A II RB = losartan 50 mg/day) (9 male patients) respectively on insulin sensitivity in patients with EH. 3-hours euglycaemic clamp test with constant infusion of insulin (50 mU/m2/min) was performed twice: before and after 8 weeks of therapy with ACEI or A II RB respectively. The control group (CG) consisted of 12 healthy males (clamp test was performed once). Serum insulin concentration (I) was estimated by radioimmunoassay. Glucose disposal rate (M-value = mg/kg/min) and tissue insulin sensitivity (M/I value = mg/kg/min per mU/l) were calculated in subjects of the CG and in patients with EH before and after antihypertensive therapy with ACEI or A II RB, respectively. In CG the M-value (7.38 +/- 0.13) and tissue insulin sensitivity (M/I = = 6.76 +/- 0.19) were significantly higher than in EH before treatment with ACEI (M-value = 5.44 +/- 0.16; M/I = = 4.57 +/- 0.18) or A II RB (M-value = 5.75 +/- 0.21; M/I = 4.77 +/- 0.31), respectively. ACEI therapy was followed by a significant increase of both M (6.82 +/- 0.25) and M/I (5.68 +/- 0.25) values. In contrast to ACEI, treatment with A II RB did not influence neither M (5.75 +/- 0.21) nor M/I (4.79 +/- 0.21) values respectively. In contrast to A II RB, ACEI shows a beneficial effect on insulin sensitivity in EH patients. This effect does not seem to be mediated by an influence on the AT-1 receptor.

Adult↗

[QT/QS2 index in patients with arterial hypertension, mitral valve prolapse and hyperthyroidism].

QT/QS2 ratio has been assessed in 26 patients with both borderline and mild hypertension and mitral valve prolapse syndrome (19 patients), and hyperthyroidism (16 patients) in comparison with method control groups. The following polycardiographic parameters have been analyzed: QT, QTp, QS2, QT/QS2, and QTp/QS2. Higher values of QT/QS2 ratio have been noted in patients with mitral valve prolapse syndrome and hyperthyroidism than that in the control group. There has been no difference in patients with mild hypertension while the values of the analyzed parameter have been significantly lower in patients with borderline hypertension. QT has been longer than QS2 (QT)QS2 1/in 9 (56%) patients with hyperthyroidism. A positive correlation between QT/QS2 ratio and ++thyroxine levels have been noted in these patients. QT values have been higher than QS2 values only in 1 patient with mild hypertension. It seems that QT/QS2 value has limited value as an indirect index of the adrenergic activity in the dysfunction of the autonomic nervous system.

Adrenergic Fibers↗