PubMed Health⌕ Search

Biomedical subjects

W Koenig

Publications and source records attributed to W Koenig.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression of intercellular adhesion molecule-1 in human coronary endothelial and smooth muscle cells after stimulation with tumor necrosis factor-alpha.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) is one of several human cell adhesion molecules that play a critical role in the early stages of postangioplasty restenosis. In this study, the in-vitro expression of ICAM-1 in human coronary endothelial cells and human coronary smooth muscle cells (SMC) after stimulation with tumor necrosis factor-alpha (TNF-alpha) was investigated. METHODS AND RESULTS: SMC were isolated from the media of normal human coronary arteries (n = 26) up to 10 h post mortem (HCMSMC) and from human atherosclerotic coronary arteries (HCPSMC) that were extracted by thrombendarterectomy (n = 25). Endothelial cells of human coronary arteries (HCAEC) were purchased from Clonetics (Cell System, Remagen, Germany), and endothelial cells from human umbilical cord veins (HUVEC) were isolated after vaginal delivery. For investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the proliferative activity of HUVEC, HCAEC, HCPSMC, and HCMSMC, serum-free media was used. After 24 h cell number and cell size distribution were measured in a cell analyzer system. The proliferation of HCPSMC and HCMSMC was increased by TNF-alpha; however, significant differences compared with controls were not reached. The proliferation of HUVEC and HCAEC was significantly reduced by TNF-alpha. For investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the surface expression of ICAM-1, monoclonal anti-ICAM-1 antibodies (84H10) were used. The expression of ICAM-1 was analyzed using an immunofluorescence microscope. For flow cytometry analysis, 5 x 10(3) cells (100% gated) were analyzed using a fluorescence-activated cell sorter. In control cultures with no stimulation, the expression of ICAM-1 was positive in HCAEC, HCPSMC, HCMSMC, and HUVEC. TNF-alpha stimulated the expression of ICAM-1 in a time- and dose-dependent manner. After maximal stimulation with TNF-alpha (20 ng/ml for 24 h), the expression of ICAM-1 was stronger in HCMSMC than in HCPSMC. CONCLUSIONS: These results suggest that the cytokine TNF-alpha regulates the expression of ICAM-1 in both human coronary endothelial cells and SMC, and could therefore play an important role in the pathophysiology of inflammatory and immune processes in restenosis after angioplasty.

Cell Division↗
PubMed1998

Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992.

Plasma viscosity is determined by various macromolecules, eg, fibrinogen, immunoglobulins, and lipoproteins. It may therefore reflect several aspects involved in cardiovascular diseases, including the effects of classic risk factors, hemostatic disturbances, and inflammation. We examined the association of plasma viscosity with the incidence of a first major coronary heart disease event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in 933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37 to 9.53), and the subjects were followed up for 8 years. All suspected cases of an incident CHD event were classified according to the MONICA protocol. There was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of CHD. The relative risk of CHD events associated with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25 to 2.03). After adjustment for age, total cholesterol, high density lipoprotein cholesterol, smoking, blood pressure, and body mass index, the relative risk was reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD events for men in the highest quintile of the plasma viscosity distribution in comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after adjustment for the aforementioned variables. A large proportion of events (40%) occurred among men in the highest quintile. These findings suggest that plasma viscosity may have considerable potential to identify subjects at risk for CHD events.

Blood Viscosity↗
PubMed1998

C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.

There is increasing evidence that complement activation may play a role in atherogenesis. Complement proteins have been demonstrated to be present in early atherosclerotic lesions of animals and humans, and cholesterol-induced atherosclerotic lesion formation is reduced in complement-deficient animals. Potential complement activators in atherosclerotic lesions are now a subject matter of debate. C-reactive protein (CRP) is an acute-phase protein that is involved in inflammatory processes in numerous ways. It binds to lipoproteins and activates the complement system via the classic pathway. In this study we have investigated early atherosclerotic lesions of human coronary arteries by means of immunohistochemical staining. We demonstrate here that CRP deposits in the arterial wall in early atherosclerotic lesions with 2 predominant manifestations. First, there is a diffuse rather than a focal deposition in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media. In this location, CRP frequently colocalizes with the terminal complement complex. Second, the majority of foam cells below the endothelium show positive staining for CRP. In this location, no colocalization with the terminal complement proteins can be observed. Our data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation.

Animals↗
PubMed1998

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Adult↗
PubMed1998

Haemostatic risk factors for cardiovascular diseases.

Strong evidence from large observational epidemiological studies links haemostatic variables to the future risk of myocardial infarction and stroke. Recent data provide further evidence for an early involvement of haemostatic parameters in atherosclerosis. So far, a variety of markers of a procoagulatory tendency e.g. elevated fibrinogen, coagulation factor VII, factor VIII and von Willebrand factor, platelet hyperaggregation, increased plasma levels of D-dimer, and decreased fibrinolytic capacity, e.g. characterized by increased levels of PAI-1 activity and decreased t-PA concentrations have been identified prospectively. Thus, a complex disturbed haemostatic system plays an important role in the development of atherothrombotic events in several vascular beds. This review discusses the epidemiologic evidence of the association between the haemostatic system and cardiovascular disease.

Blood Coagulation Factors↗
PubMed1997

Increased plasma viscosity during an air pollution episode: a link to mortality?

BACKGROUND: Air pollution episodes have been consistently associated with increased mortality, and most strikingly with mortality due to cardiovascular disease. One hypothesis to explain this association is that inflammation of the peripheral airways caused by pollution might increase blood coagulability. We have tested this hypothesis in a cross-sectional study by comparing measurements of plasma viscosity during a severe episode of air pollution during 1985 with those made on less polluted days. METHODS: Plasma viscosity was measured as part of the MONICA Augsburg survey during the winter of 1984-85 in 3256 randomly selected men and women aged 25-64 years. Daily mean concentrations of air pollutants and meteorological variables were measured in Augsburg as part of the automated Bavarian air-quality network. We compared measurements of plasma viscosity made in 324 people who attended for screening during the pollution episode and in 2932 people screened during the remainder of the survey period. FINDINGS: In January, 1985, high concentrations of sulphur dioxide (mean 200 micrograms/m3) and total suspended particles (mean 98 micrograms/m3) were recorded during a 13-day period in Augsburg. In men, the odds ratio for plasma viscosity above the 95th percentile of the distribution (1.38 mPa s) was 3.6 (95% CI 1.6-8.1) comparing measurements during the air pollution episode with non-episode measurements after adjustment for cardiovascular risk factors and meteorological variables. The corresponding odds ratio for women (95th percentile of plasma viscosity 1.37 mPa s) was 2.3 (1.0-5.3). High concentrations of carbon monoxide were also associated with increased plasma viscosity in women. INTERPRETATION: During the 1985 air pollution episode, an increased risk of extreme values of plasma viscosity was observed in both men and women. Altered blood rheology due to inflammatory processes in the lung that induce an acute-phase reaction might therefore be part of the pathological mechanisms linking air pollution to mortality.

Adult↗
PubMed1997

Leisure-time physical activity but not work-related physical activity is associated with decreased plasma viscosity. Results from a large population sample.

BACKGROUND: Regular leisure-time physical activity (LTPA) is inversely associated with coronary heart disease (CHD). This has been mainly explained by its impact on traditional CHD risk factors, but more recently it was also shown to lower fibrinogen, which largely determines plasma viscosity. No data on the effect of work activity (WA) on plasma viscosity have been published. METHODS AND RESULTS: We studied the relationship between self-reported LTPA or WA and plasma viscosity as well as other CHD risk factors in 3522 men and women age 25 to 64 years. Physical activity was assessed by questionnaire. LTPA was inversely associated with plasma viscosity in both sexes. The unadjusted mean differences in plasma viscosity in men between no activity and the highest activity were 0.024 mPa.s (95% confidence interval [CI], 0.016 to 0.032 mPa.s, P < .001) during winter and 0.024 mPa.s (95% CI, 0.016 to 0.031 mPa.s, P < .001) during summer. After adjustment for age, cholesterol, smoking, blood pressure, body mass index, and years of education, mean differences decreased but still remained substantial and statistically significant (0.010 mPa.s; 95% CI, 0.003 to 0.018 mPa.s [P = .009] for winter activity; and 0.010 mPa.s; 95% CI, 0.002 to 0.017 mPa.s [P = .011] for summer activity). Similar results were found in women. WA showed no appreciable association with plasma viscosity after controlling for the covariates. CONCLUSIONS: LTPA is inversely associated with plasma viscosity, independent of other risk factors, whereas WA shows no material effect in men and women. Decreased plasma viscosity may represent one mechanism through which LTPA confers a decrease of CHD risk.

Adult↗
PubMed1997

Felodipine and amlodipine in stable angina pectoris: results of a randomized double-blind crossover trial.

A randomized, double-blind, crossover study tested the antiischemic and antianginal efficacy of felodipine, extended-release 5-10 mg, versus amlodipine, 5-10 mg once daily. Fifty-two patients with documented exercise-induced angina pectoris and myocardial ischemia during 24-h electrocardiographic monitoring were included in the study. Forty-seven patients completed the 8-week treatment period, whereas five patients withdrew from the study. The mean number of ischemic episodes/24 h was reduced from 19.9 at baseline to 2.3 during amlodipine and to 2.4 during felodipine; the total duration of ischemic episodes decreased from 69.8 min/24 h to 15.2 min and 15.5 min during amlodipine and felodipine, respectively (for both variables, p = 0.83 and p = 0.53 between treatments, and for both treatments, p < 0.001 compared with baseline). Eighteen (38%) patients receiving amlodipine and 19 (40%) patients receiving felodipine showed no ST-segment depression during treatment. Maximal ST-depression was reduced from an average of 2.1 mm to 1.1 and 1.2 mm on amlodipine and felodipine, respectively (p = 0.68 between treatments and p < 0.001 compared with baseline). Mean heart rate remained unchanged compared with baseline. Anginal attacks were reduced from 16.4/week at baseline to 4.7/week with amlodipine and to 4.3/week with felodipine (p = 0.26 between treatments, and p < 0.001 vs. baseline). Accordingly, nitrate consumption was reduced from 14.7 capsules per week to 4.0 and 3.8 with amlodipine and felodipine, respectively (p = 0.40 between treatments, and p < 0.001 compared with baseline). Adverse reactions were infrequent and distributed similarly between the two treatments. It is concluded that both drugs effectively reduced ischemic episodes and anginal attacks and were well tolerated in patients with stable angina pectoris. There was no evidence that the two regimens were different in their antiischemic and antianginal properties.

Adult↗
PubMed1997

Seasonal variations of rheological and hemostatic parameters and acute-phase reactants in young, healthy subjects.

The incidence of cardiovascular diseases is increased in winter months. Recent studies have shown seasonal changes in plasma viscosity, fibrinogen, and factor VII activity with elevated levels during winter. An increase in these factors generates a "hypercoagulable state," which may lead to a rise in cardiovascular morbidity and mortality. It has been suggested that an increase in upper respiratory infections might be the underlying cause for the raised acute-phase reactants, in particular fibrinogen, during the winter season. We investigated seasonal variations of 26 parameters, determining blood rheology and hemostasis in 16 healthy volunteers (8 men and 8 women) aged 20 to 41 years. They were seen at monthly intervals over a period of 1 year. Seasonal variation with peak fitted values in the winter months was found for plasma viscosity (P < .001 for the seasonal difference), red blood cell deformability (P < .001), whole blood viscosity (P < .001), hemoglobin (P < .001), hematocrit (P < .001), mean corpuscular volume (P = .001), platelet count (P = .01), alpha 1-glycoprotein (P < .001), fibrinogen (measured by immunonephelometry; P < .001), plasminogen activator inhibitor-1 (P = .002), LDL cholesterol (P = .003), and triglyceride levels (P < .001). HDL cholesterol (P < .001) and cortisol (P = .001) showed inverse seasonal patterns, with a maximum during summertime. No statistically significant seasonal variations were seen for red blood cell aggregation, complement factor C4, total cholesterol, ceruloplasmin, haptoglobin, white blood cell count, and plasminogen. These data do not support the hypothesis that increased morbidity and mortality from cardiovascular diseases during winter may be mainly attributable to increased synthesis of acute-phase proteins due to infections. The cause for the seasonal variations in rheological and hemostatic parameters remains unclear and should be studied in more detail.

Acute-Phase Proteins↗
PubMed1997

Fibrinogen and cardiovascular risk.

The hypothesis that fibrinogen is closely related to cardiovascular risk has been strengthened through the results of various lines of research, which this review will aim to unravel. Several prospective epidemiological studies convincingly show elevated fibrinogen to represent a major, independent cardiovascular risk factor. Cross-sectional studies strongly associate fibrinogen and conventional cardiovascular risk factors. Clinical cohort studies demonstrate that increased fibrinogen is also a risk factor for the sequelae of cardiovascular disease. Our knowledge about the determinants of the variable plasma level of fibrinogen in health and disease is incomplete. Understanding of the mechanisms that might be involved in the atherothrombogenic action of fibrinogen is also fragmentary. Fibrinogen strongly affects blood coagulation, blood rheology and platelet aggregation. In addition, it has direct effects on the vascular wall and is a prominent acute phase reactant. All of these phenomena might constitute pathophysiological mechanisms involved in the association between fibrinogen and cardiovascular events. Their relative importance is unclear at present. Even though many crucial questions await conclusive answers, little doubt exists that fibrinogen represents a major, independent risk factor.

Arterial Occlusive Diseases↗
PubMed1996

Expression of human decay accelerating factor (hDAF) in transgenic pigs regulates complement activation during ex vivo liver perfusion--immunopathological findings.

Ex vivo perfusions of human decay accelerating factor-expressing transgenic (n = 3), and nontransgenic (n = 6) porcine livers with human blood revealed a higher degree of organ damage in non-transgenic pig livers. Transgenic livers were protected from immunohistologically detectable complement deposition, despite corresponding IgM and IgG deposits in both groups. Complement activation and consumption of C3 and C4 turned out to be lower in transgenic pig livers. In contrast to livers of normal landrace pigs, livers from genetically manipulated pigs showed no morphological alterations after perfusion.

Animals↗
PubMed1996

Imbrication versus excision for fascial healing.

BACKGROUND: The purpose of this study was to determine whether imbrication of native fascia versus excision and closure of new raw fascia forms a stronger union. METHODS: We utilized the anterior rectus sheath fascia of Sprague-Dawley rats as the model. Sixty rats underwent fascial tightening procedures. Each rat had the anterior rectus sheath shortened by 1 cm, 30 by imbrication and 30 by excision and closure. Ten of each group were harvested at 7 days' healing, 10 at 14 days, and 10 of each group at 28 days' healing. The anterior rectus sheath was removed, a "dumbbell" shape constructed, and the cross sectional area at the point of interest determined. The fascia was placed on an Instron tensiometer to determine the breaking strength. Tensile strength was calculated and the data analyzed by ANOVA and the Kruskall-Wallis test. Tissue samples of the closures were histologically analyzed for fibroblast counts, degree of inflammation, and presence of dense fibrous connective tissue. Tissue samples were also analyzed for enzymatic collagen crosslinking. RESULTS: There was a statistically significant difference in tensile strength between the two groups at 7, 14, and 28 days. Results show that at 7 days the mean tensile strength of excision was 0.133 kg/mm2 +/- 0.056 and the mean tensile strength of imbrication was 0.083 kg/mm2 +/- .048 (P < 0.05); at 14 days the mean tensile strength of excision was 0.105 kg/mm2 +/- 0.033 and the mean tensile strength of imbrication was 0.057 kg/mm2 +/- 0.014 (P < 0.002), and at 28 days the mean tensile strength of excision was 0.279 kg/mm2 +/- 0.143 and the mean tensile strength of imbrication was 0.145 kg/mm2 +/- 0.061 (P < 0.03). Histologic findings showed no statistical significance between the two closure methods when comparing degree of inflammation or the number of fibroblasts present. However, at 7 and 14 days there is a significantly greater presence of dense fibrous connective tissue in the excision group (P < 0.03 at 7 days and P < 0.044 at 14 days by ANOVA). Collagen crosslink analysis showed that by day 28 there is a significantly greater amount (P < 0.05 by ANOVA) of the difunctional crosslink dihydroxylysinonorleucine (DHLNL) and a greater ratio between DHLNL and the difunctional crosslink hydroxylysinonorleucine (HLNL) in the excision and closure group. CONCLUSION: We conclude that at 7, 14, and 28 days healing, excision provides a significantly stronger closure than imbrication. According to the crosslinking analysis, it is likely that this strength advantage may continue to increase over time. These findings suggest that excision and closure may be the preferred method for fascial tightening procedures.

Animals↗
PubMed1996

Long-term survival after myocardial infarction: relationship with thrombolysis and discharge medication. Results of the Augsburg Myocardial Infarction Follow-up Study 1985 to 1993.

A large number of randomized clinical trials have shown that thrombolysis, long-term treatment with beta-blockers, antiplatelet drugs, and angiotensin converting enzyme inhibitors improve survival after acute myocardial infarction (AMI). However, for calcium channel blockers (nifedipine, diltiazem, and verapamil) there was either no benefit, or positive effects have been reported in subgroups only. Recent studies have raised concern about the safety of this drug class, especially in patients with coronary heart disease. We studied the long-term survival, for a median follow-up time of 4.4 years, of 1197 non-diabetic patients in the population-based AMI registry in Augsburg, Germany, aged 25-74 years, who had survived a first Q wave acute myocardial infarction for at least 28 days. The impact of thrombolysis and prescribed medication at discharge (beta-blockers, antiplatelet drugs, and calcium channel blockers) on long-term survival was analysed using the Cox-Proportional-Hazard model, controlling for age, sex, and concomitant cardiac drug use. Thrombolysis (risk ratio, RR, 0.72; 95% confidence interval, CI, 0.48-1.08), long-term beta-blockade (RR 0.52; 95% CI 0.36-0.74) and antiplatelet drug use (RR 0.69; 95% CI 0.50-0.94) were associated with considerable reductions in total mortality. The use of calcium channel blockers was not associated with a reduction in total mortality (RR 1.23; 95% CI 0.89-1.69). Separate analyses for nifedipine (RR 1.00; 95% CI 0.68-1.48), and diltiazem (RR 1.55; 95% CI 1.04-2.32) showed an increased risk of death associated with the latter. Using patients on beta-blockers only (RR 1.00) as a reference, the prescription of these calcium channel blockers was consistently associated with an increased total mortality (nifedipine, without beta-blockers RR 1.20; 95% CI 1.12-3.57, diltiazem, without beta-blockers RR 2.87; 95% CI 1.75-4.70). These results from an observational study demonstrate a benefit of thrombolysis, beta-adrenergic blockade and antiplatelet drug use on long-term survival in acute myocardial infarction patients. Calcium channel blocker use appears to be associated with an increased risk of death. These data support the need for controlled trials to address this issue specifically.

Adrenergic beta-Antagonists↗
PubMed1995

[Hyperfibrinogenemia and cardiovascular risk--epiphenomenon or causal relationship?].

During the last decade, a variety of experimental, clinical and epidemiological data have been published, documenting an association between fibrinogen and atherosclerosis as well as with its most frequent clinical complications, myocardial infarction and stroke. Although the design of epidemiological studies was not strictly comparable, and studies were carried out in very different populations, with various methods of fibrinogen measurement, the results are remarkable consistent. Together with clinical and experimental data, they strongly suggest a causal role for fibrinogen in atherogenesis and in the pathophysiology of acute ischemic syndromes. Hence, fibrinogen should be determined in patients at high risk for cardiovascular complications. The clinical benefit of lowering fibrinogen in certain patient groups or alternatively, the inhibition of specific fibrinogen induced effects, should be studied in randomised trials.

Arterial Occlusive Diseases↗
PubMed1995

Recent progress in the clinical aspects of fibrinogen.

This article provides an overview of recently accumulated evidence on the pathogenetic role of fibrinogen in various vascular beds; and tries to elucidate determinants for patients' susceptibility so that subgroups at particular risk of severe clinical complications can be characterized more accurately. Based on the considerably elevated risk of cardiovascular complications associated with increased levels of plasma fibrinogen, the potential value of lowering fibrinogen in the primary or secondary prevention of atherosclerotic disease is now recognized as an important topic for consideration. Recent progress in this field will also be reviewed.

Adult↗