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Biomedical subjects

W Markiewicz

Publications and source records attributed to W Markiewicz.

At least 19 recordsLinked to original sources

The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in breast cancer.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play a significant role in the metabolism of many biological substances. ADH participates in the metabolism of ethanol, retinoic acid, lipid peroxidation products, leukotriene and glutathione metabolism. ALDH is responsible for oxidation of acetaldehyde and other aldehydes and metabolism of histamine and retinoic acid. The aim of this study was to compare the metabolism in breast cancer cells and normal breast parenchyma by measuring ADH isoenzymes and ALDH activities in these tissues. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as a substrate. For the measurement of the activity of ALDH and class I and II isoenzymes of ADH we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was detected by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as substrates. The samples were taken surgically during resection of breast carcinoma from 75 women. The activity of the class I ADH isoenzyme was significantly lower in breast cancer cells than in healthy tissues. The other tested classes of ADH had a tendency for higher levels of activity in cancer cells than in normal mammary tissue. The activity of total ADH and ALDH was also not significantly lower in the cancer cells. The decrease of activity of class I ADH isoenzyme in breast cancer tissues may be a factor of some disorders in metabolic pathways with participation of these isoenzymes that can lead to carcinogenesis.

Alcohol Dehydrogenase↗

Influence of nitric oxide on the blood flow in the porcine uterine artery; an in vivo study.

The aim of this study was to investigate the role of nitric oxide (NO) in the regulation of blood flow in the porcine uterine artery during the course of the oestrous cycle. Experiments were carried out on animals on days 1-5, 8-13 and 17-20 of the oestrous cycle. After induction of anesthesia and opening of the abdominal cavity, blood samples were collected from the ovarian and uterine arteries and veins to determine nitrate and nitrite concentrations; on the opposite side to the blood sampling the branch of the uterine artery was prepared and a venous catheter was inserted into the artery. For measuring the changes in the blood pressure the catheter was connected via a polyvinyl cannula to a pressure transducer. Sodium nitroprusside (NP; 2.4 microg, 24 microg and 240 microg; a NO donor) or Nomega-nitro-L-arginine methyl ester (L-NAME; 2.2 microg, 22 microg, 220 microg and 2200 microg; an irreversible inhibitor of neuronal and endothelial NO synthase and reversible inhibitor of macrophage NO synthase) was administered via a bolus into the uterine artery. Nitrite/nitrate concentrations were: higher (P < 0.05) in the uterine vein as compared to the uterine artery on days 1-5 of the oestrous cycle; lower (P < 0.05) in the uterine artery as compared to the ovarian and uterine veins as well as in the ovarian artery as compared to the ovarian vein on days 8-13 of the cycle; lower (P < 0.05) in the uterine artery as compared to the ovarian artery and uterine and ovarian veins on days 17-20. Administration of NP at doses of 2.4 microg and 24 microg and L-NAME at all doses examined did not affect (P > 0.05) the blood pressure in the uterine artery in all periods examined. NP at a dose of 240 microg decreased (P < 0.001) the blood pressure in the arteries in all periods examined as compared to blood pressure before NP treatment. The results obtained indicate that NO is involved in the regulation of blood flow through the porcine reproductive tract. Moreover, our results suggest that the action of NP in the porcine uterine artery is not dependent on the phase of the oestrous cycle.

Animals↗

Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome.

OBJECTIVE: To investigate the relationship between C-reactive protein (CRP) and various characteristics of the metabolic syndrome. DESIGN: Population-based cross-sectional study. SUBJECTS: A total of 1929 subjects undergoing a medical examination in a preventive medicine clinic (age, 50+/-10 y; 63% males). RESULTS: The proportion of subjects with CRP levels above the cut point generally used to indicate an obvious source of infection or inflammation (>10 mg/l) was 3, 7, and 15% in subjects who were normal weight, overweight, and obese, respectively. Subjects with obesity had markedly higher CRP level compared to patients without obesity regardless of whether they had the metabolic syndrome. However, there was no significant difference in CRP levels between nonobese subjects without the metabolic syndrome and subjects in whom the diagnosis of the metabolic syndrome was based on criteria other than obesity (adjusted geometric mean CRP 1.75 vs 2.08 mg/l, P=0.79). Similarly, CRP levels did not differ among obese subjects with and without the metabolic syndrome (adjusted geometric mean CRP 3.22 vs 3.49 mg/l, P=0.99). There was a linear increase in CRP levels with an increase in the number of metabolic disorders (P(trend) <0.0001), which was substantially diminished after controlling for body mass index (BMI) (P(trend)=0.1). Stepwise multivariate linear regression analysis identified BMI, triglyceride levels, HDL cholesterol levels (inversely), and fasting glucose as independently related to CRP levels. However, BMI accounted for 15% of the variability in CRP levels, whereas triglycerides, HDL cholesterol and fasting glucose levels accounted for only approximately 1% of the variability in CRP levels. CONCLUSION: Obesity is the major factor associated with elevated CRP in individuals with the metabolic syndrome. CRP levels in the range suggesting a source of infection or inflammation (>10 mg/l) are more common among obese subjects than in nonobese subjects.

Adult↗

Association between fasting glucose and C-reactive protein in middle-aged subjects.

AIMS: C-reactive protein (CRP), a marker of subclinical inflammation, predicts the occurrence of coronary heart disease in healthy subjects. Hyperglycaemia is known to stimulate the release of inflammatory cytokines from various cell types and can lead to the induction and secretion of acute-phase reactants by adipocytes. The aim of the present study was to determine the relation between glycaemic status and CRP in healthy subjects. METHODS: We studied the relation of high-sensitivity CRP to fasting glucose and other components of the metabolic syndrome in a population-based cross-sectional study (n = 1000; age 50 +/- 9 years). RESULTS: Plasma CRP levels increased continuously from the lowest quartile of normal fasting glucose level to impaired fasting glucose and to diabetes (ln CRP 0.47 +/- 0.09, 0.95 +/- 0.12, and 1.11 +/- 0.13, respectively; Ptrend < 0.0001). Increasing CRP with higher fasting glucose levels was apparent even among subjects with fasting glucose in the normal range (Ptrend = 0.039), and subjects with fasting glucose level in the upper quartile of normal fasting glucose had higher CRP levels compared with subjects in the lower quartile (P = 0.035). There was a positive crude correlation between CRP and smoking, post-menopausal hormone use, body mass index, fasting glucose, triglycerides, hypertension, and uric acid (r = 0.11-0.36, P = 0.002-0.0001). A negative correlation was found between CRP and HDL-cholesterol (r = 0.12, P < 0.0001) and physical activity (r = 0.11, P = 0.002). After adjustment for potential confounders in a stepwise multivariate linear regression model, fasting glucose remained significantly and independently related to CRP levels (correlation coefficient 0.06; 95% confidence interval 0.014-0.11, P = 0.011). CONCLUSIONS: Fasting glucose is significantly and positively associated with plasma CRP in middle-aged subjects. CRP levels increase continuously across the spectrum of fasting glucose, beginning in the lowest quartile of normal fasting glucose. This finding suggests that a proinflammatory effect may contribute to the adverse cardiovascular outcome associated with diabetes, impaired fasting glucose, and increasing glucose levels within the normal range.

Blood Glucose↗

Chronic total occlusion due to diffuse in-stent restenosis: is brachytherapy the solution?

Percutaneous coronary intervention of chronic total occlusions (CTO) is associated with a significantly higher incidence of reocclusion and restenosis compared with non-total occlusions. Randomized and observational trials have demonstrated the effectiveness of intracoronary brachytherapy (ICBT) for the prevention of recurrent in-stent restenosis. However, limited data are available on the effectiveness of ICBT in patients with totally occluded in-stent restenosis. The authors assessed the long-term outcome of patients treated with intracoronary gamma radiation for totally occluded in-stent restenotic lesions. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 100 patients (103 vessels) with diffuse in-stent restenosis. At baseline, CTO of the target vessel at the site of the stent was present in 15 vessels (14.5%). Follow-up data were collected during follow-up visits and from telephone interviews. Repeat coronary angiography was performed in symptomatic patients with clinical restenosis. Clinical and angiographic characteristics were similar between the two groups, although there was a trend towards more unstable angina at the index procedure in CTO patients (66.7% versus 41.4%; p = 0.12) compared with patients without non-total occlusions. A higher percentage of patients (53.3%) with CTO required longer radiation sources (14 seeds, covering a length of 55 mm), compared with 23.9% of patients with non-total occlusion (p = 0.04). With a mean follow-up period of 47.5 +/- 24.0 months, major adverse cardiac events (MACE) were observed in 10 of 15 patients (66.7%) with CTO compared with 25 out of 88 patients (28.4%) without CTO (p = 0.009). According to multivariate analysis, total occlusion of the target vessel at baseline was the single independent predictor of MACE at one-year follow-up (relative risk 16.2, 95% confidence interval 4.2-62.9; p < 0.0001). This study shows that the use of gamma radiation for the prevention of recurrence of in-stent restenosis in patients with CTO does not seem to be as effective as in patients with non-total occlusions. Furthermore, CTO was an independent predictor of worse outcome at long-term follow-up in this study.

Brachytherapy↗

Preliminary identification of carotenoids in malignant and benign neoplasms of the breast and surrounding fatty tissue.

An attempt has been made to identify the carotenoids present in the tissue of neoplastic tumors and the surrounding fatty tissue taken from women with histologically diagnosed cancer (ca ductale infiltrans, G2,G3; n=20) and those with benign changes (fibroadenoma, n=20). Carotenoid pigments were isolated using column and thin-layer chromatography. Prior to chromatography, the material was homogenized with acetone under nitrogen in dark glass bottles and the extracts kept in a refrigerator until analyzed. In the present study, we isolated 13 carotenoids belonging to provitamin A and nonprovitamin A carotenoids. The total content of carotenoids in microg/g of tissue was slightly lower in cancers and the surrounding fatty tissues in comparison to benign changes, but in general it was higher in the fatty tissue surrounding the tumors, irrespective of their histological structure (the mean values for cancers 20.433+/-10.64 vs fatty tissue 25.361+/-12.025, p<0.01; and the mean values for benign changes 22.889+/-12.011 vs fatty tissue 27.021+/-13.180, p<0.01). Epoxide carotenoids - lutein epoxide and violaxanthin, were predominant in fatty tissue, both in malignant and benign changes; epoxide carotenoids - mutatoxanthin and lutein epoxide and other carotenoids such as zeaxanthin, canthaxanthin, lutein and neoxanthin were predominant in neoplastic material. Beta carotene and lutein epoxide were found in all samples, alpha carotene was found in 50% of them. Antheraxanthin was present in fatty tissue only. Beta carotene, the main provitamin A carotenoid, content in the material examined ranged from 2.43 to 4.33% in tumor tissue and in fatty tissue surrounding the tumors it was twice as higs. Such carotenoids as 3'-lutein, canthaxanthin and astaxanthin were sporadic. No reoccurring carotenoid "sequences" were found despite the same histopathological diagnosis. No relationship was found between the neoplasm histopatological grade, lesion diameter and the occurrence of specific carotenoids.

Adipose Tissue↗

Exercise-induced symptomatic ischaemia predicts a poor long-term prognosis after acute myocardial infarction.

STUDY OBJECTIVES: To evaluate the long-term prognostic significance of symptomatic ischaemia during exercise testing performed 3 weeks after acute myocardial infarction (AMI). DESIGN: A prospective study with long-term follow-up. SETTING: A Cardiac Rehabilitation Clinic in a University Hospital. SUBJECTS: A total of 446 patients were allowed to perform exercise testing 3 weeks after AMI and followed for 72 +/- 20 months. MEASUREMENTS AND RESULTS: Patients were divided into three groups according to whether they had no ECG evidence of ischaemia during exercise testing (334 patients), silent ischaemia (90 patients) or symptomatic ischaemia (22 patients). Cardiac death was significantly more frequent in patients with symptomatic ischaemia when compared with silent ischaemia (31.8% vs. 7.8%, P < 0.01) or when compared with no ischaemia (31.8% vs. 10.2%, P < 0.01). The three groups had a low cardiac mortality during the first 48 months of follow-up. The prognosis of patients with symptomatic ischaemia worsens markedly thereafter. The results of exercise testing did not predict recurrence of myocardial infarction. Coronary revascularization was performed in 34.4% of those without ischaemia, 47.8% of those with silent ischaemia and 45.5% of those with symptomatic ischaemia (P < 0.01). CONCLUSIONS: Patients with symptomatic ischaemia have a good prognosis during the first 4 years of follow-up. Their prognosis worsens thereafter as opposed to patients with or without silent ischaemia. This high-risk group of patients with symptomatic ischaemia deserves optimal management including revascularization when appropriate.

Analysis of Variance↗

Priming effects of GM-CSF, IFN-gamma and TNF-alpha on human neutrophil inflammatory cytokine production.

Identifying and evaluating the priming agents for cytokine release by neutrophils might be helpful in controlling the innate immune response of the host. In the present study we examined the role of granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) as priming agents for interleukin (IL)-1beta, IL-6 and TNF-alpha production by stimulated neutrophils from control subjects and malignant melanoma patients. When the cells from controls and patients were preincubated with primer agents, opsonized zymosan-stimulated inflammatory cytokine production was enhanced. The major neutrophil-priming factor for IL-6 secretion by polymorphonuclear leukocytes (PMNs) in the control and patient groups was TNF-alpha. However, GM-CSF and IFN-gamma are also significant primers. GM-CSF priming was critical for the release of TNF-alpha from PMNs in control and melanoma patients. The ability of GM-CSF, IFN-gamma and TNF-alpha to serve as effective priming agents for inflammatory mediator production by PMNs revealed a new role for these cytokines in the innate immune response of the melanoma-bearing host.

Adult↗

Effect of IL-15 on the secretion of IL-1beta, IL-1Ra and sIL-1RII by PMN from cancer patients.

In the present study, we demonstrate an effect of rhIL-15 on the simultaneous secretion of IL-1beta and its natural inhibitors IL-1Ra and sIL-1RII by human neutrophils isolated from normal and tumour-bearing hosts (oral cavity cancer and melanoma patients) compared with serum IL-15 levels. We found an rhIL-15 influence on IL-beta and IL-1Ra secreted by PMN from healthy controls. In contrast, the PMNs from cancer patients were not sensitive to rhIL-15 stimulation. However, we found a priming effect of rhIL-15 on IL-1beta production by LPS-stimulated cells in oral cavity cancer. We also found no effect on sIL-1RII release by PMN from cancer patients.

Carcinoma, Squamous Cell↗

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty.

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.

Adult↗

Acute symptomatic hyponatremia complicating invasive cardiac procedures: a report of three patients.

Hyponatremic encephalopathy is a well-known complication of surgical procedures. This syndrome has not been described in the cardiology literature. We report three patients who developed acute hyponatremia with life-threatening encephalopathy following an invasive cardiac procedure. Diagnosis and treatment were delayed because of a lack of awareness for the syndrome among the cardiology staff. The diagnosis of hyponatremia should be suspected in any patient who develops behavioral or neurological manifestations following an invasive cardiac procedure. Prompt diagnosis and treatment are essential to avoid permanent neurological damage or death.

Acute Disease↗

TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients.

Simultaneous evaluation of cytokines and their soluble receptor production and the serum levels can be helpful in understanding the local and systemic immune response of a tumor-bearing host. In the present study we examined serum levels of TNF-alpha, IL-6 and their soluble receptors: sTNFRp55, sTNFRp75 and sIL-6R confronted with their production by the polymorphonuclear neutrophils (PMN) from cancer patients. Examinations were carried out in patients with adenocarcinoma breast cancer and squamous cell carcinoma of the oral cavity and related to the clinical course and to different phases of therapy. Secretion of IL-6, sTNFRp55 and sTNFRp75 by PMN appeared to be dependent on tumor type, clinical progression of disease as well as on therapy, suggesting a significant role of these cells at different phases of the immune response to cancer associated with these mediators. Changes in values of TNF-alpha, IL-6 and their soluble receptors in sera of both cancer groups, dependent on tumor type, clinical progression and cancer therapy, could have a diagnostic and prognostic role in cancer disease.

Adenocarcinoma↗

TNFRs and IL-6R transmembrane receptors expression and release of their soluble forms by neutrophils and mononuclear cells from cancer patients.

TNF-alpha and IL-6 are multipotential mediators involved in the control of many host's reactions to tumour. Their biological effects are mediated through the membrane-bound receptors (TNFRp55, TNFRp75 and IL-16R respectively) which can exist in soluble forms. In the present study we compared release of soluble sTNFRp55, sTNFRp75 and sIL-6R with expression of their membrane-bound on PMN and PBMC. Cells were isolated from patients with cancer diseases with a different location and histological classification. We have found that alterations of membrane-bound TNFRp75 expression and in the secretion of soluble TNFRp75 form, as opposed to other receptors examined, are characteristic features of neutrophils and mononuclear cells isolated from cancer patients. The similar changes observed in the expression of TNFRp75 by PMN and PBMC appear to confirm a significant role of PMN in the tumour response mediated by TNF-alpha. Furthermore, the altered membrane-bound TNFRp75 expression and sTNFRp75 secretion appear to depend on the tumour type.

Adult↗

Computerized analysis of myocardial echocardiographic enhancement during coronary revascularization by high-speed rotational atherectomy.

A previous report demonstrated transient myocardial echocardiographic contrast (MEC) enhancement following high-speed rotational atherectomy (HSRA). This phenomenon was found to be correlated to the speed and duration of rotation and related to creation of cavitations. To determine other correlations and the significance of MEC, continuous echocardiographic recording was performed in 10 patients undergoing HSRA. Images were digitized and videointensity-time curves generated. Curve parameters were calculated and correlated with procedural variables, plaque mass, and side effects. Twenty-nine ablation passes in 10 patients were analyzed. Videointensity peaked 9-44 sec from initiation of ablation and decayed to a higher baseline level after each consecutive ablation. Increase in peak contrast intensity (PCI) from baseline and the percentage of the left ventricle undergoing enhancement were highest (33 +/- 31 gray level/pixel and 32% +/- 8%, mean +/- SD, respectively) after the second rotation and were not influenced by the duration of rotation. PCI, side effects, and transient left ventricular wall motion abnormalities were positively correlated with plaque mass, defined by the product of lesion length, diameter, and percent stenosis. HSRA resulted in significant myocardial echocardiographic contrast. PCI is related to ablation sequence and plaque mass. Plaque debris embolization is probably responsible for myocardial echocardiographic contrast and transient wall motion abnormalities. Cathet. Cardiovasc. Intervent. 49:39-44, 2000.

Aged↗

Prospective study of early atropine use in dobutamine stress echocardiography.

AIMS: Dobutamine stress echocardiography is a time-consuming test, often requiring atropine at the end of the protocol to achieve target heart rate (HR). We examined whether earlier administration of atropine in appropriate patients would shorten test time and increase the likelihood of achieving peak HR. METHODS: Two hundred and seventy consecutive patients were randomized prospectively to conventional or early atropine protocols. Of these, 120 patients with an inadequate HR response [mid-30 microg/kg/min HR<100 (age <50) or <90 (age >50); or mid-40 microg/kg/min stage HR<120 (age <50) or <110 (age >50)] were included in the analysis. The remaining patients were used in a model to define which patients are likely to require atropine. RESULTS: The 61 patients receiving early-atropine had decreased test-time relative to the 59 not receiving early-atropine (17:05 vs. 18:24 min:sec, P=0.014) accompanied by a 10% reduction in total dobutamine dose (P=0.008). Their HR at end of 40 microg/kg/min was 123+/-18 vs. 105+/-17 respectively, P<0.0001. Only 7% of the early-atropine group failed to reach target HR vs. 15% not receiving early-atropine. By multivariate analysis, age (P<0.0001), HR at end of 30 microg/kg/min stage (P<0.0001), beta-blocker use (P=0.009) and baseline HR (P=0.04) were predictors of need for atropine. CONCLUSION: Giving atropine early in appropriate patients can reduce test times without an increase in side effects. Our model enables accurate prediction of these patients.

Adrenergic beta-Agonists↗

Echocardiography in nonbacterial thrombotic endocarditis: from autopsy to clinical entity.

Bacteria-free verrucae, frequently termed "non-bacterial thrombotic endocarditis," have been recognized in autoimmune disorders as well as in neo-plastic diseases. The antemortem diagnosis of non-bacterial thrombotic endocarditis is rare, and most existing data result from postmortem examinations. In 3 prospective echocardiographic studies we found typical cardiac valvular lesions in patients with primary antiphospholipid syndrome, myelo-proliferative disorders, and solid malignant tumors. Cardiac lesions associated with these 3 different entities had common echocardiographic appearance and correlated positively with thromboembolic events. The possibility of common pathogenesis is suggested, and clinical significance is discussed.

Antiphospholipid Syndrome↗

Long-term value of exercise testing after acute myocardial infarction: influence of thrombolytic therapy.

OBJECTIVES: To evaluate the long-term predictive value of exercise testing performed early after acute myocardial infarction (AMI) in patients receiving thrombolytic therapy. DESIGN: Nonblinded prospective follow-up study. SETTING: Cardiac rehabilitation unit in a 900-bed university hospital. SUBJECTS: Four hundred forty-three patients allowed to perform exercise testing 3 weeks after AMI were followed for a median of 75 months; 183 received IV thrombolysis and 263 did not. RESULTS: Cardiac death hazard ratios were significantly increased in the presence of reduced physical working capacity on exertion, left ventricular dysfunction, and > or = 1-mm (but < 2-mm) ST-segment depression on exertion. In the group receiving thrombolytic therapy, no patient with > or = 2-mm ST-segment depression on exercise died; this group was characterized by a high rate of revascularization, whereas the group with > or = 1-mm but < 2-mm ST-segment depression was not. No parameter related to clinical or exercise testing predicted recurrent infarction in the group receiving thrombolytic therapy. Among patients not receiving thrombolysis, cardiac death was significantly related to > or = 2-mm ST-segment depression on exertion, to reduced physical working capacity, and to the lack of revascularization during follow-up. CONCLUSION: Exercise test-derived parameters have variable value in predicting long-term survival of patients performing exercise test after AMI depending on the following: (1) whether thrombolytic therapy was given or not; (2) the degree of ST-segment depression during exercise testing; and (3) the rate of revascularization.

Adult↗