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K Lewandowski

Publications and source records attributed to K Lewandowski.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of fibrinolytic and metabolic system parameters in obese patients with polycystic ovary syndrome and women with simple obesity.

The present study aimed to assess the fibrinolytic and metabolic system parameters in obese patients with polycystic ovary syndrome (PCOS) and to compare them in obese PCOS patients and women with simple obesity. We studied 19 obese women with PCOS (age: 25.1 +/- 4.6 years, body mass index (BMI): 34.7 +/- 3.9 kg/m2; mean +/- standard deviation) and 20 age- and BMI-matched ovulatory controls. We measured blood levels of 17beta-estradiol, testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose and insulin. The following fibrinolytic tests were also performed: euglobulin clot lysis time, plasminogen level, alpha2-antiplasmin activity, plasminogen activator inhibitor-1 activity, fibrinogen concentration and estimated fibrinolytic activity. Testosterone and LH levels were significantly higher in obese women with PCOS (p < 0.01 and p < 0.001, respectively). The groups did not differ with regard to 17beta-estradiol, prolactin, FSH, DHEAS, TC, TG, HDL-C, LDL-C, glucose and insulin. All of the fibrinolysis parameters with the exception of plasminogen were comparable between the two groups. Serum plasminogen level was lower in obese PCOS patients than in women with simple obesity (p < 0.05). Euglobulin clot lysis time was positively correlated with insulin (r = 0.88, p < 0.05) in both groups. Our results show that fibrinolysis is not suppressed in women with PCOS and that there is no difference in fibrinolytic activity between obese patients with PCOS and women with simple obesity.

Adult↗
PubMed2006

Epidemiology of ARDS.

For decades the incidence of the acute respiratory distress syndrome (ARDS) has been unclear. A first effort to tackle the problem was undertaken by the National Heart and Lung Task Force who, in 1972, provided the scientific community with an arguable estimate of 75 cases per 100,000 inhabitants/year for the USA. Nearly 20 years later, the first population based studies yielded figures of 1.5-4.5 cases per 100 000 inhabitants/year in Europe. Epidemiologic research became much more focused when in 1992 the new ARDS and acute lung injury (ALI) definitions of the American-European Consensus Conference became available. In subsequent studies in which these refined definitions were used, incidence figures ranging from 13-23 cases per 100,000 inhabitants/year for ARDS and 18 cases per 100,000 inhabitants/year for ALI were reported. Latest results from a high-class epidemiological study conducted in Seattle, suggested ARDS/ALI incidence figures of 59 and 79 cases per 100,000 inhabitants/year, respectively. These new figures, similar to the one proposed in 1972, led to a paradigm shift: ARDS and ALI are no longer viewed as rare syndromes but as widespread diseases with a massive socio-economic impact that is comparable with the burden from breast cancer, AIDS, asthma or myocardial infarction.

Humans↗
PubMed2004

Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukaemia treated with cladribine.

The increased frequency of second malignancies in chronic lymphocytic leukaemia (CLL) is well known. Moreover, antineoplastic therapy additionally increases the risk of secondary cancers. In this study, we analysed whether treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA) during the course of CLL had an impact on the subsequent occurrence of either secondary solid tumours or Richter's syndrome. There were 1487 eligible patients, 251 treated with 2-CdA alone, 913 treated with alkylating agents (AA)-based regimens alone and 323 treated with both 2-CdA and AA. Median time from the start of CLL treatment to the diagnosis of secondary malignancy was 1.9 years (0.5-5.1 years) for the 2-CdA group, 1.8 years (0.3-7.9 years) for the AA group and 3.9 years (0.3-8.4 years) for the 2-CdA+AA group. A total of 68 malignancies were reported in 65 patients. Ten events were non-melanotic skin cancers and were excluded from the analysis, leaving 58 events in 58 patients. In the group of patients treated with 2-CdA alone, there were 15 (6.0%) cases, in the group of patients treated with AA alone there were 26 (2.8%) cases, and in the group treated with 2-CdA+AA there were 17 (5.3%) cases of secondary malignancies. The differences between the frequency of secondary malignancies in the 2-CdA and 2-CdA+AA versus AA alone groups were not significant (P=0.05 and P=0.06, respectively). Only lung cancers occurred significantly more frequently in the 2-CdA (2.8%) and 2-CdA+AA (2.2%) treated groups compared with the AA patients (0.3%) (P<0.001 and P<0.01, respectively). In conclusion, 2-CdA in CLL patients does not seem to increase the risk of secondary malignancies except for lung cancers. However, further studies are necessary to establish the real risk of lung cancer in CLL patients treated with 2-CdA.

Adult↗
PubMed2004

Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study.

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m2 and C 250 mg/m2, days 1-3, intravenously, every 4 weeks, for a maximum of 6 courses, Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5-32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy. The median PFS was 13 (range 8-26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.

Adult↗
PubMed2003

[Scoring systems in the intensive care unit].

Scoring systems represent classification systems or point systems which have been designed for making quantitative statements regarding the severity of a disease, its prognosis, and its course. Furthermore, scores may serve the purposes of assessing therapies, of quality control and of quality assurance, and of an economic evaluation of intensive care. Like all measuring methods, scores are susceptible to failures and systematic mistakes. The clinical user should be well aware of these limitations. Generally, one would recommend only using scores which have been rigorously tested for their reliability, validity, and practicability. These include, but are not limited to, the updated versions of the APACHE, the SAPS, and the MPM. Although great strides have been made concerning development, verification, and clinical applicability, scores still exhibit a level of uncertainty which precludes their use in individual patients. Frequently, it may be of benefit to combine the more general scores with one or several organ dysfunction scores to determine the extent of functional impairment of specific organs. If, however, well-trained medical personnel apply tried and tested scoring systems, intensive care units will definitely gain a lot from it.

APACHE↗
PubMed2003

Transmission of HCV infection among long-term hospitalized onco-haematological patients.

Hepatitis C virus (HCV) infection is becoming a substantial problem in long-term hospitalized patients. Onco-haematological patients undergoing chemotherapy are especially prone to HCV infection. These patients are usually immunosuppressed and therefore antibodies to HCV are not produced despite the presence of HCV RNA in peripheral blood. The aim of the study was to see how often long-term hospitalized patients acquired HCV infection, and what were the possible sources and routes of virus transmission. The study involved 129 children with lymphoproliferative diseases, 36 patients with solid tumours, and 61 healthcare workers from onco-haematological wards. All were HCV RNA and anti-HCV negative at the time of first hospitalization. During a two and a half-year follow-up study among 165 onco-haematological patients, HCV RNA appeared in 87 in subsequent hospitalizations. The majority of infections were (82/87) were 1a genotype, 2 were 1b, 1 was 1a + 1b and 1 was 1a + 3a. In an attempt to establish the origin of HCV infection, healthcare workers were screened for HCV genotyping. All HCV-infected staff working on wards had the same genotype (1a). None of the staff was infected with 1b genotype. As the most prevalent genotype in Polish blood donors is 1b, HCV infection in onco-haematological patients is most likely due to horizontal transmission, probably involving genotype 1a, and potential horizontal transmission of HCV is implied by the presence of 1a genotype of HCV in saliva and urine of selected patients. Spread of hospital HCV infection among children may be facilitated by micro-injury of the skin and mucosa. Early detection of HCV RNA is important in such immunosuppressed patients, as they are not able to produce anti-HCV antibodies. This may enable the introduction of prophylactic steps to prevent the spread of HCV infection by horizontal transmission.

Adolescent↗
PubMed2002

Comparative studies of the Acinetobacter genus and the species identification method based on the recA sequences.

The recA gene is indispensable for a maintaining and diversification of the bacterial genetic material. Given its important role in ensuring cell viability, it is not surprising that the RecA protein is both ubiquitous and well conserved among a range of prokaryotes. Previously, we reported Acinetobacter genomic species identification method based on PCR amplification of an internal fragment of the recA gene with subsequent restriction analysis (RFLP) with HinfI and MboI enzymes. In present study, the PCR products containing the internal fragment of the recA gene, for 25 Acinetobacter strains belonging to all genomic species, were sequenced. Based on the nucleotide sequences the restriction maps and phylogenetic tree were prepared. The restriction maps revealed that Tsp509I restriction enzyme is the most discriminating for RFLP. To verify the computer analysis, the amplified DNAs from all reference genomic species available (43 strains) and 34 clinical strains were digested with each of the three restriction endonucleases mentioned. The results of digestion confirmed the computer analysis. The reconstructed phylogenetic tree showed linkages between genomic species 1 (Acinetobacter calcoaceticus), 2 (Acinetobacter baumannii), 3, 'between 1 and 3', TU13 and 'close to TU13'; genomic species 4, 6, BJ13, BJ14, BJ15, BJ16 and BJ17; genomic species 7 (Acinetobacter johnsonii) and TU14; genomic species 10 and 11; genomic species 8 (Acinetobacter Iwoffii), 9, 12 (Acinetobacter radioresistens) and TU15; and genomic species 5 (Acinetobacter junii). It is interesting that one branch in the phylogenetic tree contains haemolytic species-genomic species 4 (A. haemolyticus), BJ13, BJ14, BJ15, BJ16 and BJ17. The proposed genotypic method clearly revealed that the RFLP profiles obtained with Tsp509I enzyme might be useful for species identification of Acinetobacter strains. In this context, recA/RFLP genotypic method should be seen as an ideal preliminary screening method for large numbers of isolates, with the ultimate confirmatory role reserved for DNA hybridization analysis.

Acinetobacter↗
PubMed2002

[Can lung protective ventilation methods modify outcome?--A critical review].

A large body of experimental and clinical work leaves no room for doubt that mechanical ventilation can contribute to the progression of a lung disease or, in the worst case, produce acute pulmonary damage. The pathophysiological processes involved have been described as barotrauma, volutrauma, atelectrauma and biotrauma. In response, a socalled lung-protective ventilation strategy has been proposed, especially for patients with acute respiratory distress syndrome (ARDS). Such an approach seeks to apply limited airway pressures, small tidal volumes and appropriate levels of positive end-expiratory pressures even if, as a consequence, non-physiological gas exchange values (i.e. elevated PaCO2-levels) need to be tolerated. A recent large prospective randomized trial demonstrated reduced mortality rates using such a strategy. To support lung-protective ventilation in ARDS patients, an array of therapeutic measures has been proposed, including meticulous attention to fluid and transfusion management, prone position, extracorporeal membrane oxygenation (ECMO), inhalation of nitric oxide, implementation of spontaneous breathing, partial liquid ventilation and tracheal gas insufflation. Of these, only prone positioning has become part of routine clinical management, while ECMO is applied in selected cases only. Unfortunately, thus far, none of these measures has passed the litmus test of a randomized controlled trial. Recent large prospective observational studies, however, suggest that only an optimized concert of therapeutic interventions, but not a single measure alone, may improve the outcome of ARDS patients.

Animals↗
PubMed2001

Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin.

OBJECTIVE: Insulin and glucocorticoids are known to increase total leptin levels. However, the effects of insulin and glucocorticoids on the components of the leptin system - free leptin (FL), bound leptin (BL) and soluble leptin receptor (SR) - have not been elucidated. The aim of this study was to determine if there is a differential effect of insulin and glucocorticoids on the leptin system. MATERIAL AND METHODS: In the first of two studies (study 1), we measured free leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insulin, by specific RIA methods, in six healthy subjects on a control day, and subsequently during a hyperinsulinaemic euglycaemic clamp study. In the second study (study 2) we measured the same parameters in six healthy subjects, before (day 1) and during administration of dexamethasone over 3 consecutive days. RESULTS: In study 1, on the control day FL levels rose over the 16 h monitoring period (P = 0.057) and SR levels declined (P < 0.001), but there was no change of BL levels. Even after accounting for diurnal variation, FL levels increased even more substantially over 12 h of insulin infusion than observed on the control day (P < 0.001). In study 2, mean FL concentration doubled from day 1 to day 2 (P = 0.01) and remained elevated subsequently. In contrast to FL, BL and SR levels remained unchanged during the study. Fasting insulin levels (pmol/l) increased from day 1 to day 2, but this rise only approached significance on day 4 (P = 0.05). CONCLUSION: We conclude that insulin and dexamethasone increase free leptin levels, but do not change the concentrations of bound leptin and soluble leptin receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at least partially) independent of the effects of glucocorticoid-induced hyperinsulinaemia.

Adult↗
PubMed2001

Creation of an additional glycosylation site as a mechanism for type I antithrombin deficiency.

We report the identification of a new mutation resulting in type I antithrombin (AT) deficiency and the mechanism by which the deficiency arose. The single base substitution of G to A at nucleotide 2709 was identified in a proband with a family history of venous thrombosis. The mutation results in a substitution of 82 Ser by Asn, creating a new glycosylation site. Expression studies were then carried out, to confirm Asn-linked glycosylation occurred at this consensus site and that this resulted in the AT deficient phenotype. Cell-free translations using rabbit reticulocyte lysate in the presence of microsomes demonstrated that the 82 Asn variant was post-translationally processed efficiently. The 82 Asn variant protein was of a higher molecular weight than normal AT. consistent with the addition of a fifth glycan chain. Incubation of translation product with endoglycosidase H, confirmed that the higher molecular weight product had resulted from additional carbohydrate. Expression of the 82 Asn variant in COS-7 cells resulted in intracellular accumulation, with a low level of secretion of the protein into culture supernatant, consistent with type I AT deficiency. The addition of an extra carbohydrate side chain to residue 82 of antithrombin may block post-translational folding. trapping the variant intracellulary.

Adolescent↗
PubMed2001

Significance of molecular identification of hepatitis C virus RNA in diagnosis of cryptogenic hepatitis in children.

Viral etiology of hepatitis is routinely proved by standard immunological tests detecting specific antibodies. However, identification of specific antibodies cannot always be conclusive. Since specific hepatitis C virus (HCV) antibodies may appear after some months of the infection, identification of HCV RNA and/or hepatitis G virus (HGV) RNA should clarify the etiology of hepatitis. The aim of this study was to diagnose etiologically unknown hepatitis by a reverse transcription-polymerase chain reaction (RT-PCR) testing of the presence of HCV RNA and HGV RNA. The study involved 33 children with histologically proved hepatitis. The presence of HCV and any signs of autoimmune disease were not observed at the beginning of the follow-up study. During 2.5 years of the follow-up HCV-RNA was found in the blood and liver biopsies in 17 patients. Eight of them became HCV antibodies-positive during the follow-up. None of them eliminated the virus from the blood during the follow-up. In two other patients HCV-RNA was found only in the liver. HGV infection in all cryptogenic patients was excluded by PCR testing. Identification of HCV RNA RT-PCR allowed to diagnose 19 out of 33 (57.6%) patients with cryptogenic hepatitis. The etiology of the hepatitis in remaining 12 patients has to be established.

Child↗
PubMed2001

Hepatitis G virus co-infection may affect the elimination of hepatitis C virus RNA from the peripheral blood of hemodialysis patients.

Hemodialysis patients are at risk for hepatitis C virus (HCV) and hepatitis G virus (HGV) infection. The aim of this study was to investigate the possible influence of HGV co-infection on HCV RNA elimination from the peripheral blood of hemodialysis patients. The study involved 144 persons, all with HCV antibodies and HCV RNA. Among 144 patients 24 (16.7%) were positive for HGV RNA. After 2.5 years of observation 80 patients (55.6%) were still HCV RNA-positive. In the latter group 18 patients were co-infected with HGV and 62 were HGV RNA-negative. During 2.5 years of the follow-up study 64 patients eliminated HCV RNA from the serum. In this group only 6 patients were HGV co-infected. None of the HGV-positive patients eliminated HGV RNA from the serum. The higher incidence of HGV co-infection in the group of patients who remained HCV RNA-positive (18/80, 22.5%), in comparison to the group of HCV antibodies-positive patients who lost HCV in the blood (6/64, 9.4%, P < 0.0001) suggests, that the co-infection with HGV may delay the spontaneous elimination of HCV RNA from the blood.

Adult↗
PubMed2001

Limited pattern of TCR delta chain gene rearrangement on the RNA level in multiple sclerosis.

Susceptibility to multiple sclerosis (MS) is most likely affected by a number of genes, including HLA and T-cell receptor (TCR) genes. T cells expressing gamma/delta receptors seem to contribute to autoagression in MS, as evidenced by their localization in the MS plaques in the brain. The aim of this study was to analyse the TCRdelta chain gene rearrangement at the RNA (cDNA) level and compare to the DNA pattern rearrangement. TCRdelta gene rearrangement was analysed in MS patients and healthy individuals with the use of primers specific for Vdelta1-6 and Jdelta1 genes (at the DNA level) and specific for Vdelta1-6 and Cdelta1 genes (at the cDNA level). The size of PCR products was analysed on agarose gel and by ALF-Express (Pharmacia). Additionally, the lymphocyte surface immunophenotype was studied with specific monoclonal antibodies. At the DNA level a restricted pattern of Vdelta3-Jdelta1 and Vdelta5-Jdelta1 was found only in MS patients. Contrary to DNA, mono-, oligoclonal RNA (cDNA) rearrangements were limited to Vdelta1-Cdelta1, Vdelta2-Cdelta1 and Vdelta3-Cdelta1 only in MS patients as well. Surface immunophenotype analysis revealed in MS a much higher frequency of activated gamma/delta T lymphocytes, i.e. expressing HLA-DR and CD25. An elevated level of CD56 positive cells in MS was recorded. Mono-oligoclonal pattern of TCRdelta gene rearrangement at the RNA level, along with increase in activated gamma/delta T cells, strongly argue for a significant role of gamma/delta T lymphocytes in the pathogenesis of MS.

Journal Article↗
PubMed2000

Extracorporeal membrane oxygenation for severe acute respiratory failure.

Extracorporeal membrane oxygenation (ECMO) is a technique for providing life support, in case the natural lungs are failing and are not able to maintain a sufficient oxygenation of the body's organ systems. ECMO technique was an adaptation of conventional cardiopulmonary bypass techniques and introduced into treatment of severe acute respiratory distress syndrome (ARDS) in the 1970s. The initial reports of the use of ECMO in ARDS patients were quite enthusiastic, however, in the following years it became clear that ECMO was only of benefit in newborns with acute respiratory failure. In neonates treated with ECMO, survival rates of 80% could be achieved. In adult patients with ARDS, two large randomized controlled trials (RCTs) published in 1979 and 1994 failed to show an advantage of ECMO over conventional treatment; survival rates were only 10% and 33%, respectively, in the ECMO groups. Since then, ECMO technology as well as conventional treatment of adult ARDS have undergone further improvements. In conventional treatment lung-protective ventilation strategies were introduced and ECMO was made safer by applying heparin-coated equipment, membranes and tubings. Many ECMO centres now use these advanced ECMO technology and report survival rates in excess of 50% in uncontrolled data collections. The question, however, of whether the improved ECMO can really challenge the advanced conventional treatment of adult ARDS is unanswered and will need evaluation by a future RCT.

Acute Disease↗
PubMed2000

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise.

OBJECTIVE: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers. DESIGN: Prospective observational study. SETTING: University laboratory. PARTICIPANTS: Fourteen healthy adult volunteers. INTERVENTIONS: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min. MEASUREMENT AND RESULTS: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 +/- 89 nl/min for non-smokers and 261 +/- 142 nl/min for smokers (mean +/- SD, n.s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 +/- 21 nl/min versus 23 +/- 14 nl/min, p < 0.05; smokers: 41 +/- 8 nl/min versus 22 +/- 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 +/- 3.1 ppb at rest and this decreased to 9.3 +/- 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 +/- 2 to 21 +/- 3 l/min. CONCLUSION: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.

Adult↗
PubMed2000

Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia - updated results of the multicentre study of 378 patients.

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

2-Chloroadenosine↗