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Biomedical subjects

B Nowak

Publications and source records attributed to B Nowak.

At least 127 records · Page 7Linked to original sources

A case of hidden receptacle-adapter incompatibility.

Connection of a universal VS-1 adapter to a VS-1 receptacle resulted in intermittent loss of pacing and of sensing in a pacemaker dependent patient. This was caused by the use of an adapter that only provides stable electric contact if the adapter pin is deformed by the set screw. Since we had implanted a pulse generator with a "side-lock" connector without screws, only a loose connection was achieved. The manufacturers should provide information on such hidden incompatibilities.

Adult↗

[Procollagen III-peptide and angiotensin converting enzyme in bronchoalveolar lavage in sarcoidosis].

In 39 cases with active and 36 cases with inactive sarcoidosis the angiotensin converting enzyme (ACE) and in 56 of them (21 active/35 inactive sarcoidosis) procollagen-III-peptide (P III P) content as well as the total protein content of the broncho-alveolar lavage (BAL) and of the serum were determined. These results were compared with those of a control group of 53 patients (ACE group) resp. 25 patients (P III P-group). Both the relative ACE content (ACE related to 1 g of protein) and the relative P III P content (P III P related to 1 mg of protein) showed significant increase in cases of acute sarcoidosis compared to the other two groups of patients. However, none of the three groups showed statistically significant differences in the other parameters. ACE in the BAL can therefore be regarded as a good indication of the activity of sarcoidosis. This is also true of P III P in the BAL as an indication of fibrogenesis.

Adult↗

A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.

A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.

Adult↗

Occupational exposure in operational radiology.

Measurements of dose-rate on the body surface of workers engaged in operational radiology permit the assessment of average annual effective dose equivalent, and dose equivalents in eye lenses and in hands. Measurements were made in 20 hospitals in the course of different operations in which x-radiation was used. Individual values of annual effective dose equivalent ranged from about 0.1 to about 45 mSv. In the majority of cases this did not exceed 5 mSv at the current workload. For the eye lens, the respective dose equivalent range was from 0.01 to about 70 mSv; only in one case, due to the engagement of a totally inappropriate operating procedure, could the eye dose reach 1.9 Sv per year. The individual values of the dose equivalent to hands ranged from 0.5 to 140 mSv.

General Surgery↗

[Comparison of the effects of the irritant action of different amounts of cooling mineral oil with biocides on the rabbit skin].

Effects of different concentrations of Emulgol EN-BIO C/88 oil on rabbit skin were studied. Experiments were carried out to examine oil irritancy to the skin and the inner surface of the ear skin subjected to a 24-hour closed exposure and repeated open exposure for 10 days, respectively. The data obtained have shown that 5 and 10 per cent emulsions of Emulgol EN-BIO C/88 produce mild skin irritation, while a 50 per cent emulsion and concentrate cause irritation of moderate degree. This means that the irritating potential of Emulgol depends on its concentration in oil-water emulsion. It is concluded that EN-BIO C/88 oil should be used in a 5 per cent concentration in industry.

Animals↗

[Immunomodulating properties of Acnevac vaccine].

The influence of Acnevac vaccine on immune responses of CBA mice was tested. Acnevac, the vaccine used in a treatment of patient with acne vulgaris, was produced by a Cracow Sera and Vaccines Manufacturer from cultures of Propionibacteria-strains. It was shown that Acnevac has strong immunomodulatory properties. It strongly stimulates humoral responses, has moderate effect on cell-mediated immune responses and it also activates peritoneal macrophages to release TNF-alpha.

Acne Vulgaris↗

Experimental balloon valvuloplasty of fibrotic and calcific mitral valves.

This study evaluated the mechanism of valvular area expansion during single- and double-balloon valvuloplasty in fibrotic and calcific mitral valves. Special interest was focused on the morphological features of the valves treated. Mitral valves that appeared unsuitable for commissurotomy were excised in toto at the time of mitral valve replacement in 15 patients. The excised valves were mounted in a fluid-filled chamber with a window for photographic evaluation. The chamber was perfused continuously to ensure maximal valvular opening. The valve was photographed, and the orifice area was measured before and after balloon expansion. In addition, the specimens were examined macroscopically and radiographically with regard to calcium content and degree and localization of fibrosis. These data were correlated with splitting of commissures and with rupture of leaflets. Nine valves were fibrotic, and six were calcific. Dilatation was performed first with a single-balloon catheter (diameter, 2 cm) and then with a double-balloon catheter (diameter, 2 and 1.5 cm). After dilatation with one balloon, the average mitral valve area increased from 0.79 to 1.09 cm2, and with two balloons, average area increased to 1.59 cm2. The single-balloon technique caused commissural splitting in nine valves, stretching in three, partial leaflet rupture in one, and no change in two. After the double-balloon technique, commissural splitting occurred in 12 valves and three leaflets were ruptured where severe fibrosis and calcification were mainly located within the commissures. As a rule, after dilatation with the single-balloon technique, the remaining stenosis was still severe, and after dilatation with the double-balloon technique, the remaining stenosis was moderate.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcinosis↗

Occupational exposure to X-radiation in Poland in the years 1966-1988.

The paper presents the results of measurements of individual doses received by persons occupationally exposed to X-radiation. About 99.5% of the monitored population receives an annual dose equivalent below 0.1 of the limit i.e. below 5 mSv. Doses higher than annual limit occur only very rarely--a few cases each year.

Humans↗

Modulation of arabinosylcytosine metabolism by arabinosyl-2-fluoroadenine in lymphocytes from patients with chronic lymphocytic leukemia: implications for combination therapy.

Our previous studies indicated that K562 cells loaded with arabinosyl-2-fluoroadenine 5'-triphosphate (F-ara-ATP) accumulated arabinosylcytosine 5'-triphosphate (ara-CTP) at a threefold higher rate compared to the control cells. In the present study lymphocytes were obtained from patients with chronic lymphocytic leukemia before and after F-ara-A monophosphate therapy. The rate of ara-CTP accumulation after in vitro ara-C incubation was compared in lymphocytes obtained prior to therapy without any other manipulation, after ex vivo F-ara-ATP (100 mumol/L) treatment, and after in vivo F-ara-A monophosphate therapy. Lymphocytes showed a 2.2-fold (n = 23) and 1.7-fold (n = 23) median increase in the cellular concentration of ara-CTP after an ex vivo incubation with 100 mumol/L F-ara-A and 20 to 24 hours after the first dose (25 or 30 mg/m2) of F-ara-A monophosphate in vivo treatment, respectively. Although the rates of F-ara-ATP and ara-CTP accumulation varied among patients, a relationship was observed in individuals between the cellular concentration of F-ara-ATP at the beginning of the ara-C incubation and ara-CTP accumulation. These studies strongly suggest that a protocol designed to administer F-ara-A monophosphate prior to ara-C infusion will augment ara-CTP accumulation by leukemia cells.

Antineoplastic Combined Chemotherapy Protocols↗

[Detection of calcium in mitral valve diseases using computer-assisted 2-dimensional echocardiography].

In order to detect mitral valve calcification, 31 consecutive patients were examined using two-dimensional echocardiography 1 day before mitral valve replacement. Calcifications of the valve were diagnosed by digital image control (grey-scale manipulation using S-curve and reject control). After the operation, the excised valves were X-rayed to determine the degree of calcification. Calcifications of the mitral valve were found by echocardiography with a sensitivity of 89.5%, a specificity of 91.7% and a predictive accuracy of 90.3%. The degree of calcification, however, was underestimated in 47%. The results show that the described grey-scale manipulations are a reliable method of detecting calcifications of the mitral valve by echocardiography. This enables the preoperative identification of those patients who are suitable for mitral valve commissurotomy.

Calcinosis↗

Saturation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate accumulation in leukemia cells during high-dose 1-beta-D-arabinofuranosylcytosine therapy.

Twenty-seven patients with refractory leukemia were treated with 1-beta-D-arabinofuranosylcytosine (ara-C), 0.3 to 3.0 g/m2 as i.v. infusions over 1, 2, 4, or 24 h. The pharmacokinetics of ara-C in plasma and its 5'-triphosphate (ara-CTP) in leukemic cells from peripheral blood were studied after a single infusion of 3 g/m2 over 2 h in 13 patients. Accumulation of ara-CTP in leukemic cells remained linear until 1 to 2 h after the infusion. At the time when the rate of ara-CTP accumulation deviated from linearity, the plasma concentration of ara-C was 5- to 20-fold lower [8.1 +/- 4.4 (SD) microM] than the steady-state level during the infusion. Plasma ara-C and cellular ara-CTP pharmacokinetics were studied after two serial infusions in 14 additional patients. Varying the duration of infusion of an ara-C dose between 1, 2, and 4 h (corresponding to infusion rates of 3000, 1500, and 750 mg/m2/h) did not substantially change the rate of ara-CTP accumulation by leukemic cells. The peak ara-CTP concentration and the area under the concentration times time curve (AUC) of ara-CTP in leukemic cells increased with prolongation of the infusion. Although steady-state concentration of ara-C and AUC of ara-C in plasma were proportionally reduced by 1.0 or 0.5 g/m2 infusion over 2 h, ara-CTP accumulation rate and AUC in leukemic cells did not change compared with administration of 3 g/m2 over 2 h. However, when the infusion rate was further reduced to 0.4 or 0.3 g/m2 over 2 h, resulting in steady-state plasma ara-C concentrations of less than 7 microM, the accumulation rate of ara-CTP was substantially reduced as was the ara-CTP intracellular AUC. The cellular elimination rate of ara-CTP remained constant under all infusion conditions. These findings support the conclusion that high-dose ara-C therapy, as currently administered, results in plasma ara-C concentrations that saturate the accumulation of ara-CTP by circulating leukemic cells. We recommend that intermediate dose rates, 200 to 250 mg/m2/h, be evaluated in future studies as an alternative to the substantially higher ara-C dose rates currently in use.

Arabinofuranosylcytosine Triphosphate↗

Effect of amsacrine on ara-CTP cellular pharmacology in human leukemia cells during high-dose cytarabine therapy.

The combination of high-dose cytarabine (ara-C) and amsacrine (m-AMSA) is effective treatment for relapsed adult acute leukemia. Studies were performed to determine if m-AMSA affected the pharmacokinetics of the active triphosphate ara-CTP in HL-60 and K562 cells in culture. No significant differences were observed in accumulation, rate of elimination, or total intracellular exposure to ara-CTP in cultures treated with 100 microM ara-C alone or in combination with 1 microM m-AMSA. In clinical investigations, the accumulation and retention of ara-CTP in circulating leukemic cells were studied in five patients after two serial doses of ara-C (3 g/m2 infused over 2 hours) and in six additional patients in whom the second dose of ara-C was accompanied by an infusion of m-AMSA (30 mg/m2 infused over 1 hour). While substantial differences were observed in the cellular pharmacokinetics of ara-CTP among patients, the rate of ara-CTP elimination and the total intracellular exposure to ara-CTP in individuals were remarkably similar after each ara-C infusion. Infusion of m-AMSA with the second dose of ara-C did not significantly affect the cellular pharmacokinetics of ara-CTP. These studies demonstrate the feasibility and utility of conducting investigations of the cellular pharmacology of drug-drug interactions in human leukemic cells during therapy.

Acute Disease↗

[Two-dimensional echocardiography in the quantification of severe mitral stenosis].

The aim of the study was to evaluate the accuracy of echocardiographic quantification of mitral valve opening area in severe mitral stenosis. 31 consecutive patients with severe mitral stenosis were studied with two-dimensional echocardiography before they had complete resection of the mitral valve. The valves were examined for calcifications by x-ray. Each specimen was tensionlessly suspended in a glass cylinder, with 10 to 15 l of warm water (37 degrees C) running through it until maximal opening of the valve. Then the valvular orifice was photographed for planimetry. Now the echocardiographic results were checked again to analyse the errors of the initial assessment. In 6 out of 31 patients the size of the valvular opening area could not be assessed echocardiographically due to poor echo quality. The mean mitral opening area of the specimens was 0.92 +/- 0.32 cm2. With 1.27 +/- 0.52 cm2, the results achieved by echocardiography reached a correlation of only r = 0.44. In 9 out of 25 patients the area was assessed precisely in terms of size and anatomy. The difference between the values calculated from the specimens and echocardiograms was below 0.5 cm2 in 19 out of 25 (76%) patients and below 1 cm2 in another 4 (16%) patients. A larger difference in two patients was due to incorrect beam direction. Otherwise, false results in 10 out of 25 patients were caused by multiple inner echoes and in 2 out of 25 patients by bright reflections due to calcifications. Although the echocardiographically assessed mitral valve opening area does not correlate with the real opening area, it is possible to distinguish in most patients between severe and mild stenosis. Furthermore the valvular opening area can be exactly determined up to 0.5 cm2 in 90 percent of patients, provided that the echo beam is correctly positioned.

Adult↗

[In vitro study of transvenous commissurotomy in severe mitral valve stenoses using the balloon catheter].

To answer the question whether mitral commissurotomy with a balloon catheter is possible, the following in vitro study was performed. In 12 patients who were operated due to severe mitral stenosis the fibrotic (n = 8) or calcified (n = 4) valves were excised and mounted in a glass cylinder. In a first step a valvuloplasty was performed with a balloon catheter (size 20 mm). Mitral valve area increased by about 40%. With simultaneous inflation of a second balloon catheter (size 15 mm) valve area increased more than 100% and reached 1.63 cm2 in the mean. Valvuloplasty was successful (increase of at least 0.5 cm2) in 11/12 cases. In 9 valves the rupture occurred within the commissures, twice within the leaflets and once the opening area increased due to dilatation. Commissurotomy with a balloon catheter seems to be possible even in calcified mitral valves although in most cases a mild to moderate stenosis will remain.

Adult↗

Physical mapping of human cytomegalovirus genes: identification of DNA sequences coding for a virion phosphoprotein of 71 kDa and a viral 65-kDa polypeptide.

Polyadenylated RNA was isolated from fibroblast cultures infected with human cytomegalovirus (HCMV) strain AD169 during the late phase of viral replication. The RNA was selected by hybridization to a series of cosmid clones containing the entire viral genome in partially overlapping segments. Translation of this RNA in a reticulocyte cell-free system allowed the mapping of virus specific polypeptides. Nine polypeptides synthesized in vitro comigrated with major virion structural proteins. An in vitro-translated protein of 71 kDa was precipitated by a monoclonal antibody directed against the phosphorylated internal envelope protein of 71 kDa. The map coordinates of viral DNA coding for this phosphoprotein were localized by hybrid selection with subcloned DNA fragments, and the direction of transcription was determined by hybrid selection with single-stranded DNA cloned in bacteriophage vector M13mp9. An in vitro translation with size-fractionated RNA, combined with immunoprecipitation and Northern blot analyses, indicated that an mRNA of 4 kb encodes the 71-kDa phosphoprotein. An mRNA of the same size, map coordinates, and orientation was translated into an abundant 65-kDa polypeptide which had the same size as the major structural phosphoprotein of HCMV.

Base Sequence↗

Characterization of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins.

Four classes of monoclonal antibody-producing cell lines have been obtained that detect human cytomegalovirus virion structural proteins. These antibodies react with (1) a major outer membrane virion glycoprotein(s) gp58-gp130, whose molecular weight varies between strains of cytomegalovirus, (2) a phosphoprotein, pp71, localized inside the virion membrane, (3) a phosphorylated nucleocapsid protein, pp155, and (4) a virion-associated phosphoprotein, pp29. Polyclonal immune human sera react with a large number of virion proteins including those detected by these monoclonal antibodies. These monoclonal antibodies were employed in a radioimmune assay to detect low levels (6 X 10(3) PFU/ml) of human cytomegalovirus in solution and human urine. These antibodies were also employed in a fluorescent antibody format to identify cytomegalovirus-infected cells obtained from human urine and nasopharyngeal aspirates. These reagents provide useful tools for studying the molecular biology of virus replication, for diagnosing cytomegalovirus infections, and for studying virus latency and activation.

Animals↗