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Biomedical subjects

W Mazur

Publications and source records attributed to W Mazur.

At least 19 recordsLinked to original sources

Progastrin and its products from patients with chronic viral hepatitis and liver cirrhosis.

BACKGROUND: Gastrin and its precursor, progastrin, are synthesized in the stomach, particularly when infected with Helicobacter pylori, and they are metabolized, at least in part, in the liver. However, little is known about their levels in various hepatic diseases. METHODS: This study was carried out on 147 patients including chronic hepatitis B (n = 35), hepatitis C (n = 52) and liver cirrhosis (n = 60) of class A (n = 38), class B (n = 15) and class C (n = 7) (Child-Pugh classification) and age- and sex-matched healthy controls (n = 65). The diagnosis of chronic hepatitis was confirmed by liver biopsy in all patients, whereas the diagnosis of liver cirrhosis was based on clinical and laboratory findings. Liver biopsy was done in 38 out of 60 patients. Blood samples were collected under basal conditions and separated plasma samples were kept frozen at -70 degrees C until radioimmunoassay of progastrin and its products, including bioactive amidated gastrins. RESULTS: Median (range) plasma concentrations of total progastrin product and amidated gastrin in control subjects were 147.5 (73-345) pM and 33 (15-65), respectively. These concentrations in hepatitis B and C were not significantly different from those in controls. In cirrhosis (classes A, B and C), the concentrations of the progastrin and of gastrin were significantly (P < 0.05) higher than in controls reaching, respectively, 253.5 (135-683 pM) and 47.5 (17-385) pM. Both progastrin and gastrin levels were significantly higher in H. pylori-positive than in negative cirrhotic patients. Antibodies against H. pylori were present in about 50% of controls, 68% of hepatitis B, 57% of hepatitis C and in 83% in cirrhosis patients. The difference in H. pylori prevalence between cirrhosis and controls was statistically significant. CONCLUSIONS: Plasma levels of progastrin and gastrin are significantly increased in cirrhotic patients and this could be attributed to reduced metabolism of these peptides in liver cirrhosis and to their increased release due to H. pylori infection rate in this disease.

Adolescent↗

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

Adult↗

Isoflavone content of the soy based supplements.

A large number of soy isoflavone products with indications of possible health effects are available on the market. Fifteen different soy based products were analyzed using high performance liquid chromatography (HPLC) with coulometric electrode array detector to determine the total amount of isoflavones in aglycones after the hydrolysis and identify the different forms of the isoflavone conjugates. The aim of the study was to evaluate how well the isoflavone content data supplied by the producers correspond to our analysis results. Only one product contained isoflavones measured in aglycones the same amount as was the value given by the producer. The total amount of the isoflavones in aglycones ranged from 0.121 to 201 mg/g. Measured amounts of isoflavones in aglycones after the hydrolysis were in general lower than the values in the product labels. Product data were often confusing and the concrete amount of isoflavones was difficult to find out.

Chromatography, High Pressure Liquid↗

Cardiac hypertrophy after transplantation is associated with persistent expression of tumor necrosis factor-alpha.

BACKGROUND: The mechanisms that contribute to cardiac allograft hypertrophy are not known; however, the rapid progression and severity of hypertrophy suggest that nonhemodynamic factors may play a contributory role. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced in cardiac allografts and capable of producing hypertrophy and fibrosis; therefore, we suggest that TNF-alpha may play a contributory role. Accordingly, the aims of our study were to define the role of systemic hypertension in the development of hypertrophy, characterize the histological determinants of hypertrophy, and characterize the expression of myocardial TNF-alpha after heart transplantation. METHODS AND RESULTS: To separate the effect of hypertension from immune injury in the development of cardiac allograft hypertrophy, we measured the gain in left ventricular mass by 2D echocardiography in heart transplant recipients and lung transplant recipients who developed similar rates of systemic hypertension. The gain in left ventricular mass was 73% in heart transplant recipients and 7% in lung transplant recipients (P<0.0001). By comparing myocardial samples obtained during the first week after transplant and at 1 year, we found that there was a significant increase in total collagen content (P<0.0001), collagen I (P<0.0001), collagen III (P<0.0001), and myocyte size (P<0.0001). These changes were associated with persistent myocardial TNF-alpha expression. CONCLUSIONS: We suggest that the contribution of hypertension to cardiac allograft hypertrophy is minimal and that persistent intracardiac expression of TNF-alpha may contribute to the development of cardiac allograft hypertrophy.

Cardiomegaly↗

Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.

BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

Angioplasty, Balloon↗

Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular hypertrophy (LVH) in the absence of increased external load. Recently, nonsurgical septal reduction therapy (NSRT) with intracoronary ethanol has been introduced to treat severely symptomatic patients with outflow tract obstruction. Its long-term effects on LV mass, however, are unknown. METHODS AND RESULTS: The LV size, function, and outflow tract gradient of 26 HOCM patients (53+/-15 years old) who underwent NSRT were assessed by echocardiography at baseline and 1 and 2 years after the procedure. LVH was evaluated by wall thickness of individual myocardial segments, planimetered myocardial area, and mass. The outflow gradient decreased from 36+/-6 mm Hg before NSRT to 0+/-3 mm Hg at 2 years (P<0.001), with patients experiencing symptomatic improvement (P<0.05). LV end-diastolic and end-systolic dimensions increased significantly at both 1 and 2 years (P<0.001). All parameters of LVH showed evidence of regression. LV mass decreased (301+/-78 g at baseline, 223+/-5 g at 1 year, and 190+/-58 g at 2 years; P<0.01), with the 2-year reduction in mass related to infarct size and the acute reduction in outflow tract gradient (r=0.48, P<0.05 and r=0.63, P<0.01, respectively). CONCLUSIONS: NSRT results in LV remodeling that is characterized by an increase in LV size and a decrease in the extent of LVH.

Analysis of Variance↗

Stress echocardiography in the diagnosis of coronary artery disease.

Stress echocardiography (SE) is currently a widely accepted method for the diagnostic and prognostic assessment of coronary artery disease. This article reviews new concepts in SE, such as new stress techniques, new methods of endocardial border detection, strain, tissue Doppler velocities, and others. Although some of these techniques are in their infancy, we believe that they will become widely accepted.

Adenosine↗

Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study(1-4).

Many plants that are consumed contain phytoestrogens. Only a few published studies have examined the dietary intake of phytoestrogens in the general Western population. The potentially positive health effects of phytoestrogens might be of relevance to postmenopausal women. The aim of the present study was to estimate the intake of dietary isoflavones, coumestans and lignans by healthy Western postmenopausal women. For this purpose, we studied 964 postmenopausal, Caucasian women who participated in the Framingham Offspring Study and completed the Willett food-frequency questionnaire (FFQ). By searching the medical and agricultural literature and contacting experts, we identified food sources of phytoestrogens. The concentrations of the different isoflavones, coumestrol and lignans in each food in the FFQ were scored in seven categories and multiplied by the serving size of the food and the frequency of its consumption. The estimated daily median intake of the isoflavone daidzein was 39 microg (24-57 microg); of genistein, 70 microg (28-120 microg); of formononetin, 31 microg (13-44 microg); and of biochanin A, 6 microg (2-11 microg). Median total intake of isoflavones was 154 microg (99-235 microg). The main sources of isoflavones were beans and peas. The estimated daily intake of coumestans was 0.6 microg (0.2-1.7 microg), with broccoli as the main source. The estimated daily median intake of matairesinol was 19 microg (12-28 microg) and of secoisolariciresinol 560 microg (399-778 microg). The median total intake of lignans was 578 microg (416-796 microg). The main source of the lignans was fruits. The daily dietary intake of phytoestrogens in healthy postmenopausal Caucasian women in the United States is <1 mg.

Diet↗

Echocardiographic evaluation of mitral regurgitation.

Accurate evaluation of mitral regurgitation (MR) severity remains a challenging task in clinical cardiology. The importance of proper quantification of regurgitation cannot be underestimated because a delayed decision to replace or repair a defective valve may lead to worsening ventricular function and increased perioperative and long-term mortality. In this review we discuss both recent developments in the quantification of MR as well as new insights into the pathophysiology and progression of this lesion.

Disease Progression↗

Myocardial viability: recent developments in detection and clinical significance.

The long-term prognosis of patients with ischemic cardiomyopathy is highly variable, depending on the extent of myocardial viability and the success and completeness of the revascularization techniques used. Other important factors include left ventricular function, extent of coronary artery disease (CAD), and patient age. Chronic left ventricular dysfunction in ischemic cardiomyopathy is the result of a mixture of scarred as well as hibernating myocardium. In fact, most patients have both scarring and hibernation in different regions. Transmural biopsies of dysfunctional segments reveals that recovery of function is inversely proportional to the extent of fibrosis and that endocardial fibrosis extending over 30% of the myocardial thickness precludes recovery of function.Nagueh et al. [1] evaluated the relation of contractile reserve and thallium uptake in hibernating myocardium to myocardial structure in humans. The authors found that segments with postoperative functional recovery had more wall thickening at low-dose dobutamine echocardiography (DE), higher thallium uptake, and less fibrosis (2.0 vs 28%) than those segments without recovery. Also, segments with viability on DE had less fibrosis, less vimentin and fibronectin, more glycogen, and higher thallium uptake, than those segments without viability. Importantly, segments viable by single-photon emission computed tomography (SPECT) and DE had significantly less fibrosis (1%) than those viable by only one of the two techniques. In this review, we discuss recent developments in the detection of myocardial viability, including echocardiography, nuclear cardiac imaging, magnetic resonance imaging (MRI), and other techniques.

Cell Survival↗

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)].

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

Antiviral Agents↗

Short-term changes of serum IL-2 and IL-6 induced by interferon alpha-2b in patients with chronic hepatitis C.

BACKGROUND: The standard therapy of chronic hepatitis C with interferon alpha (IFN alpha) and ribavirin has established but limited efficacy. The prognostic factors of treatment are still under investigation. IL-2 and IL-6 are key cytokines involved in activation of B and T lymphocytes and thus in humoral and cellular responses; they are also deeply involved in generation and maintenance of inflammatory processes. The aim of the study was to evaluate the short-term influence of INF alpha-2b on serum IL-2 and IL-6 levels in sustained responders (SR) and non-responders (NR). MATERIAL AND METHODS: Altogether 12 patients (7 males and 5 females) chronically infected with HCV (anti-HCV positive, HCV-RNA positive by PCR) were enrolled to the study. Patients were treated with IFN 3 MU tiw for 6 months and then they were followed for another 6 months. Five patients responded to the treatment (sustained responders-SR)-Group I, seven patients did not respond (non-responders-NR)-Group II. Serum concentrations of IL-2 and IL-6 were assessed by ELISA before ['0'] and at 1st ['1'], 2nd ['2'], 3rd ['3'], 6th ['4'] and 12th ['5'] hour after the first IFN injection. CONCLUSIONS: Interferon alpha-2b induced short-term increase of serum IL-2 concentrations in SR but not in NR. Serum IL-6 level increased both in SR and NR but this effect was more pronounced and persisted longer in sustained responders.

Adult↗

Interferon versus interferon and UDCA combined therapy in chronic hepatitis C.

BACKGROUND: Interferon alpha (IFN) has been shown to have established efficacy in the treatment of chronic hepatitis C but its effectiveness is unsatisfactory. Combined therapies with IFN and other antiviral or immunomodulatory drugs are under evaluation. A combination of interferon alpha and ursodeoxycholic acid UDCA has been reported to give better results than interferon alone. The aim of the study was to assess the efficacy of IFN monotherapy versus IFN and UDCA therapy in patients with chronic hepatitis C. MATERIAL AND METHODS: We studied 38 patients (25 males and 13 females) chronically infected with HCV (anti-HCV positive, HCV-RNA positive by PCR). Seventeen of them were treated with IFN 3 MU tiw for 6 months--Group I. The remaining 21 patients were treated with IFN, at the same dosage, plus UDCA (10 mg/kg/day) also for 6 months--Group II. Patients were followed for 6 months. 6 months after the end of therapy, laboratory biochemical parameters, HCV viremia and proportion as well as time to relapse were assessed. CONCLUSIONS: In contrast to previous reports we did not find any differences neither in proportion of HCV reactivation nor in the time of its appearance among patients treated because of chronic hepatitis B with IFN alone or with IFN plus UDCA combined therapy. We also did not find any difference in initial and late response to the treatments in both groups.

DNA, Complementary↗

Assessment of HBV DNA levels in human plasma and peripheral blood mononuclear cells by TaqMan Q-PCR assay.

Hepatitis B virus DNA (HBV DNA) levels were quantitatively determined by a TaqMan quantitative polymerase chain reaction (TaqMan Q-PCR) in the plasma and in the peripheral blood mononuclear cells (PBMCs) of 120 patients with biopsy proven chronic hepatitis. The number of HBV DNA copies ranged from 10(1) to 10(10)/ml of the blood. There were no significant differences between plasma and PBMCs levels of HBV DNA in neither of HBV infected alone nor HCV co-infected patients. The number of HBV DNA copies was higher in the both compartments in blood of patients infected with HBV only, in comparison to those co-infected with HBV and HCV. In patients chronic hepatitis caused by both viruses (co-infection), decrease of HBV DNA copies in the PBMCs preceded its disappearance from the plasma. Our results suggest that assessment of HBV DNA in PBMCs does not produce important advantage in diagnosis of chronic hepatitis, and it seems to have the prognostic significance of positive outcome among the patients with chronic hepatitis induced by HBV and HCV co-infection. Our results also indirectly indicate that HCV may reciprocally inhibit replication of HBV.

DNA↗

Increased AST and GGT activity as marker of RT-PCR inhibition in RNA extracts from peripheral blood.

The presence of HCV RNA in PMBC, with simultaneous absence of the virus in the plasma (7.8%), suggests that blood is better material for HCV RNA detection than plasma or serum in the diagnostic procedures of patients with chronic hepatitis C as well as in monitoring the antiviral therapy. We studied 111 patients with chronic hepatitis C (anti-HCV+) and elevated level of at least one biochemical marker: AST, ALAT, GGT, AP and bilirubin. Inhibition of amplification was 2% in plasma and 34% in whole blood samples. We applied modification of extraction to reduce the inhibitory effect on PCR, by introducing additional purification of the RNA extract in the Chomczyński method. After our modification of extraction was applied, inhibition was reduced to 1%. In attempt to identify such inhibitory markers that would label the samples, in which additional RNA extract purification should be applied, we analysed the activity of AST and ALAT enzymes, the key markers for parenchymal liver damage; GGT and AP, the markers for cholestatic hepatitis as well as bilirubin. We observed that the increased GGT and AST activities were correlated with the inhibition of RT-PCR. This correlation was statistically significant; for AST (Mann-Whitney test p = 0.09654 and Kolmogorow-Smirnow test p = 0.01543) and for GGT (Mann-Whitney test p = 0.02419 and Kolmogorow-Smirnow test p = 0.01921).

Alanine Transaminase↗

Dynamics of HCV replication in patients with chronic hepatitis C during interferon and ribavirin combined therapy.

Objective of the present study was to determine the effect of combined therapy with interferon alfa-2b (3 MU; thrice weekly s.c.) and ribavirin (1200 mg daily p.o.) on the number of copies of positive and negative strands of the hepatitis C virus RNA (HCV RNA) in patients with biopsy-proven chronic hepatitis C. Number of copies of both strands was determined by a TaqMan reverse transcription quantitative polymerase chain reaction (TaqMan RT Q-PCR) in the whole blood before treatment, and 4, 12 or 24 weeks after introduction of the treatment. Before the treatment positive strand of HCV RNA was more frequently detectable and its level was higher compared to that of the negative strand. In several patients, we observed therapy-induced transient appearance or increase in the number of copies of the negative HCV RNA strand. As a result of 24-week treatment, the negative strand of HCV RNA was eliminated from the blood more effectively than the positive strand. Our results suggest that the assessment of dynamics of changes of the positive and negative strands levels of HCV RNA in interferon-naive patients with chronic hepatitis C may be useful in monitoring short-term effectiveness of combined antiviral therapy. They also indicate that TaqMan RT Q-PCR appears to be a valuable tool in monitoring the therapy in these patients.

Antiviral Agents↗