Biomedical subjects

V Hombach

Publications and source records attributed to V Hombach.

At least 37 records · Page 2Linked to original sources

PubMed2001

Angioscopic predictors of restenosis following coronary angioplasty--the impact of yellow smooth plaques.

Despite angioscopy being used for more than 10 years, data regarding the prognostic significance are still limited. This study evaluated the prognostic relevance of the angioscopic lesion morphology and plaque colour on restenosis rate following coronary angioplasty. Out of 66 patients with coronary angioscopy prior to an angioplasty procedure, 46 patients with successful balloon dilation and 16 patients with stenting were included into the study. Angioscopic plaque morphology and plaque colour were correlated with the anginal status, the angiographic lesion morphology, the procedural result, and the restenosis rate during six months follow-up. Clinical follow-up was obtained from all patients, re-angiography was performed in 61%. Angioscopically complicated lesions were more frequent in patients with unstable versus stable angina (63% versus 28%, p < 0.005) and ACC/AHA type B2/C versus A/B1 stenoses (86% versus 7%, p < 0.03). In addition yellow plaques were more often seen in unstable versus stable angina (80% versus 50%, p < 0.02) and in type B2/C versus A/B1 lesions (81% versus 47%, p < 0.005). There were no deaths or myocardial infarctions during follow-up. Restenosis (n = 11) occurred significantly more frequent in patients with smooth, yellow lesions (37%) compared to all other lesion morphologies (9%, p < 0.02). Logistic regression analysis revealed angioscopically smooth, yellow plaques (p < 0.05) and angiographically type B2/C lesions (p < 0.03) as independent predictors for restenosis. We conclude that angioscopically smooth, yellow plaques covered by an intact inner vessel surface are associated with a higher incidence of restenosis following coronary angioplasty, potentially indicating a higher proliferative response after a mechanical trauma of such lesions.

Aged↗

PubMed2001

Endovascular irradiation with the liquid beta-emitter Rhenium-188 to reduce restenosis after experimental wall injury.

OBJECTIVE: Postinterventional irradiation is a new therapeutic concept in the prevention of restenosis. The liquid beta-emitter Rhenium-188 allows endovascular brachytherapy using a conventional balloon catheter without the problem of centering the radiation source. In an animal model of restenosis the feasibility and the dose dependent effect of intravascular brachytherapy with a Rhenium-188 filled balloon catheter was investigated. METHODS: In 68 male New Zealand White rabbits after endothelial denudation of the right common carotid artery with a Fogarty catheter, endovascular irradiation was performed with a Rhenium-188 filled 3.0-mm balloon catheter using different dosages (0, 7.5, 15, 30, 45 and 60 Gy at the surface of the vessel). Then 4 weeks after the intervention the vessels were excised and histologically analyzed. RESULTS: Whereas at 7.5 Gy the intimal area (median [first quartile; third quartile]) did not differ significantly from the control (0.46 mm(2) [0.33 mm(2), 0.75 mm(2)] vs. 0.49 mm(2) [0.34 mm(2), 0.66 mm(2)]), neointimal hyperplasia was decreased significantly at 15 Gy (0.15 mm(2) [0.04 mm(2), 0.17 mm(2)]) and 30 Gy (0.07 mm(2) [0.04 mm(2), 0. 10 mm(2)]), and completely inhibited at the highest dosages (45 Gy: 0 mm(2) [0 mm(2), 0.04 mm(2)]; 60 Gy: 0 mm(2) [0 mm(2), 0.01 mm(2)]). CONCLUSIONS: Catheter transmitted endovascular irradiation with the liquid beta-emitter Rhenium-188 after vascular injury is feasible and effectively reduced neointimal hyperplasia in hypercholesterolemic rabbits. A significant reduction of the neointimal formation could be found already at a radiation absorbed dose of 15 Gy at the vessel surface. Following a surface dosage of 45 Gy the proliferative response to the vessel injury is almost completely abolished.

Angioplasty, Balloon↗

PubMed2001

17beta-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta.

The aim of the present study was to investigate anti-proliferative and anti-atherogenic properties of 17beta-estradiol in balloon injured female and male rabbit aortae. Thirty-two female and 32 male New Zealand White rabbits where gonadectomised. Vascular injury was performed with a balloon catheter in the lower abdominal aorta. Male and female rabbits were randomised into four groups of eight animals each. Only two of four groups received a 0.5% cholesterol-enriched diet. One cholesterol-diet group and one normal-diet group received intramuscular injections of estradiol valerate (1 mg/kg body weight/week). After 28 days, the denuded part of the abdominal aorta was excised and analysed by morphometry and immunohistochemistry. Estrogen treatment did not show an inhibitory effect on neointimal proliferation in normo-cholesterolemic male or female rabbits. A gender independent inhibitory effect of 17beta-estradiol was seen on atheroma development in cholesterol-fed female and male rabbits, while plasma total cholesterol levels were significantly reduced in male rabbits only. The 17beta-estradiol treatment was associated with a significantly decreased number of luminal endothelial cells in normo and hyper-cholesterolemic female rabbits, as evaluated by immunohistochemical staining for 'von Willebrand factor'. Staining for Ki-67-positive proliferating cells after 28 days showed a statistically significant increased proliferative activity in the neointima of hyper-cholesterolemic female rabbits. The neointimal content of macrophages increased significantly in all hyper-cholesterolemic rabbits. Under 17beta-estradiol treatment, the number of macrophages was increased in female and decreased in male rabbits by tendency. Additionally, the 'classical' vascular estrogen receptor was present in both female and male rabbit aortae without statistically significant differences. In conclusion, 17beta-estradiol did not reduce post-injury neointima formation in normo-cholesterolemic rabbits. However, in hyper-cholesterolemic rabbits, 17beta-estradiol reduced atheroma development gender independently. This effect cannot be explained by lowering of plasma cholesterol levels or endothelium-mediated pathways, and requires further investigation on, for example, antioxidative, antiproliferative or estrogen receptor mediated effects.

Actins↗

PubMed2001

Comparison of the heparin coated vs the uncoated Jostent--no influence on restenosis or clinical outcome.

AIMS: Heparin coating of stents is thought to reduce stent thrombosis and restenosis rates. However, clinical data comparing coated and uncoated stents of the same model are lacking. We compared the heparin coated (C) and the uncoated (U) version of the Jostent stent with regard to the clinical and angiographic outcome after 6 months. METHODS AND RESULTS: Provisional stenting was done in 277 patients and 306 lesions; only 40 were Benestent-II like lesions. Delivery success rate was 98.4%. Both groups (C/U: n=156/150 lesions) were comparable in clinical and procedural data. Post stenting, reference diameter (C/U: 2.68+/-0.56/2.66+/-0.53 mm) and minimal lumen diameter did not differ (C/U: 2.48+/-0.47/2.48+/-0.52 mm). During follow-up the rate of subacute stent thrombosis (C/U: 1.9%/1.3%) and myocardial infarction did not differ. Angiography at the 6-month follow-up (79.4%) revealed no difference in restenosis rate (C/U: 33.1%/30.3%). Risk factors for restenosis were a type B2/C lesion (P<0.02), a stented segment longer than 16 mm (P<0.006) and a stent inflation pressure <14 bar (P<0.0063). CONCLUSION: Corline heparin coating of the Jostent has no impact on the in-hospital complication rate, stent thrombosis or restenosis. The Jostent design gives a high procedural success rate and satisfying result at 6 months in an everyday patient population undergoing provisional stenting.

Anticoagulants↗

PubMed2001

Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF).

Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.

Adult↗

PubMed2001

Leukocyte attack in a 3D human coronary in-vitro model.

OBJECTIVE: The importance of peripheral blood leukocytes for the development of early atherosclerosis and restenosis has confronted cardiologists with classical hematologic issues. Three-dimensional human coronary in-vitro units of leukocyte attack (3DLA-units) open the field for exact studies of leukocyte attack and its subsequent effects on human medial coronary smooth muscle cells (HCMSMC). METHODS: Central part of 3DLA-units are polycarbonate membranes with a pore size of 5 microm that correspond to the internal elastic membrane. Human coronary endothelial cells (HCAEC) were cultured on one side of the membranes, HCMSMC on the other side. Before leukocyte attack expression of adhesion molecules was up-regulated by tumour necrosis factor-alpha (TNF-alpha). Leukocyte attack was mimicked by selective adding of human monocytes (MC), respectively human CD4+-lymphocytes (CD4+-LC) to the HCAEC side of the 3DLA-units. Three-dimensional leukocyte attack units were fixed and stained after a period of 30 min, 1, 2, 3, 4, 6, and 24 h. Cell divisions of HCMSMC were analysed by measuring the uptake of bromodeoxyuridine (BrdU). RESULTS: Monocytes were able to adhere to the endothelial surface, pass through the filter-pores, and penetrate the HCMSMC side of the 3DLA-units. Human CD4+-lymphocytes (CD4+-LC) only attached to the HCAEC side, and no chemotaxis to the HCMSMC side was detected. Proliferation of HCMSMC was increased 2.9-fold (P< 0.001) after selective MC-attack and 3.5-fold after selective MC-attack and TNF-alpha stimulus. No significant increase was found after selective CD4+-LC attack, a significant increase (2.1-fold; P < 0.001) was seen after selective CD4+-LC attack and TNF-alpha, stimulus. CONCLUSIONS: Within the given limitations of the model the study emphasizes a predominance of MC in comparison to CD4+-LC in the process of adhesion, chemotaxis, and triggered reactive proliferation of co-cultured HCMSMC within the first 24 h after leukocyte attack. 3DLA-units offer an elegant method to study directly the effects of intravascular and intramural treatment strategies.

CD4-Positive T-Lymphocytes↗

PubMed2001

Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.

OBJECTIVE: This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. PATIENTS AND METHODS: The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. RESULTS: The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01). CONCLUSION: The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.

Adult↗

PubMed2001

Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid profile.

Infectious agents may be involved in atherothrombogenesis. The potential pathogenic pathway, however, remains unclear. We investigated the association between various infectious agents and lipoproteins known to have an atherogenic effect. We recruited 470 healthy blood donors and 238 patients with angiographically proven coronary heart disease (CHD), aged 40 to 68 years. Seropositivity to Chlamydia pneumoniae (CP), chlamydial lipopolysaccharide, and cytomegalovirus (CMV) was determined; infection with Helicobacter pylori (HP) was assessed by using the [(13)C]urea breath test. In all subjects, total cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), and various apolipoproteins (apos) were determined. In unadjusted analysis, mean HDL cholesterol concentration was significantly decreased in HP-positive healthy subjects (1.36 vs 1.44 mmol/L, P=0.006) compared with HP-negative subjects. The HDL cholesterol to total cholesterol ratio was significantly decreased in HP-positive (0.259 vs 0.276, P=0.01) and CP-seropositive (0.266 vs 0.280, P=0.04) healthy subjects compared with (sero)negatives. Mean apoAI levels were significantly lower in HP-positive healthy subjects (1.46 vs 1.51 g/L, P=0.03) and in CMV-positive healthy subjects (1.47 vs 1.52 g/L, P=0.01) compared with (sero)negative subjects. After multivariable adjustment by means of linear regression analysis, only the association between HP infection and decreased HDL cholesterol (P=0.002), decreased HDL cholesterol to total cholesterol ratio (P:=0.005), decreased apoAI (P=0.02), and increased apoB (P=0.02) persisted and remained significant. There was no independent association between other lipoproteins and serological markers of CP or CMV infection. Current infection with HP, but not seropositivity to CP or CMV, was associated with an atherogenic, modified lipid profile. These lipid alterations could explain, at least in part, the reported weak association between chronic HP infection and atherosclerotic diseases.

Adult↗

PubMed2000

Diagnostic and prognostic role of myoglobin in patients with suspected acute coronary syndrome. North-Württemberg Infarction Study (NOWIS) Group.

In patients with suspected acute coronary syndrome, myoglobin is, according to IFCC and NACB guidelines, the marker of choice for early determination of acute infarction, in particular in combination with creatine kinase-MB, 4 hours after admission with a sensitivity of 96%, and correctly excludes Q-wave infarctions. In patients without acute myocardial infarction, a positive troponin T (relative risk 31.5%), but not an elevated myoglobin (relative risk 4.5%), is highly predictive for adverse in-hospital outcome.

Angina, Unstable↗

PubMed2000

Intracoronary beta-irradiation with a liquid (188)re-filled balloon: six-month results from a clinical safety and feasibility study.

BACKGROUND: Coronary irradiation is a new concept to reduce restenosis. We evaluated the feasibility and safety of intracoronary irradiation with a balloon catheter filled with (188)Re, a liquid, high-energy beta-emitter. METHODS AND RESULTS: Irradiation with 15 Gy at 0.5-mm tissue depth was performed in 28 lesions after balloon dilation (n=9) or stenting (n=19). Lesions included 19 de novo stenoses, 4 occlusions, and 5 restenoses. Irradiation time was 515+/-199 seconds in 1 to 4 fractions. There were no procedural complications. One patient died of noncardiac causes at day 23. One asymptomatic patient refused 6-month angiography. Quantitative angiography after intervention showed a reference diameter of 2. 77+/-0.35 mm and a minimal lumen diameter of 2.36+/-0.43 mm. At 6-month follow-up, minimal lumen diameter was 1.45+/-0.88 mm (late loss index 0.57). Target lesion restenosis rate (>50% in diameter) was low (12%; 3 of 26). In addition, we observed 9 stenoses at the proximal or distal end of the irradiation zone, potentially caused by the short irradiation segment and the decreasing irradiation dose at its borders ("edge" stenoses). The total restenosis rate was 46% and was significantly lower (29% vs 70%, P=0.042) when the length of the irradiated segment was more than twice the lesion length. CONCLUSIONS: Coronary irradiation with a (188)Re-filled balloon is technically feasible and safe, requiring only standard percutaneous transluminal coronary angioplasty techniques. The target lesion restenosis rate was low. The observed edge stenoses appear to be avoidable by increasing the length of the irradiated segment.

Adolescent↗

PubMed2000

Different radiosensitivity of smooth muscle cells and endothelial cells in vitro as demonstrated by irradiation from a Re-188 filled balloon catheter.

There is an increasing interest in irradiation to control restenosis after balloon angioplasty by an internal radioactive source. Differences in radiosensitivity of the predominant cells of the human coronary artery (i.e. endothelial cells (HCAEC), smooth muscle cells from the media (HCMSMC) and from plaque material (HCPSMC), are issues of controversal discussion. Therefore, we investigated the graded inhibition of cells by irradiation from a balloon catheter filled with a high-energy beta-emitter (Rhenium-188) in vitro. HCPSMC, HCMSMC and HCAEC were cultured and irradiated with increasing dose from 7.5 to 37.5 Gy at a dose rate of 1.5+/-0.3 Gy/min. After irradiation, bromodeoxyuridine (BrdU) was added and cells were fixed 18 h later. In a limited field opposite to the balloon, the number of BrdU-positive cells were analysed in comparison to non-irradiated controls. Significant inhibition was demonstrated in HCPSMC and HCMSMC at 7.5 Gy while HCAEC needed 22.5 Gy for similar effects. The antiproliferative effect was dose dependent in all cell strains. The effect of irradiation with 22.5 Gy on smooth muscle alpha-actin, vimentin, and alpha-tubulin of HCPSMC and HCMSMC and on von Willebrand factor (vWF), vimentin, and alpha-tubulin of HCAEC was investigated by means of indirect immunofluorescence. Within 18 h after irradiation no effect on cytoskeletal components and vWF was documented. This in vitro study demonstrates that irradiation inhibits HCMSMC and HCPSMC at lower dose rates compared to HCAEC.

Catheterization↗

PubMed2000

Seropositivity to chlamydial lipopolysaccharide and Chlamydia pneumoniae, systemic inflammation and stable coronary artery disease: negative results of a case-control study.

OBJECTIVES: We investigated the association between seropositivity to chlamydial lipopolysaccharide (cLPS) or Chlamydia pneumoniae (CP) and angiographically documented coronary artery disease (CAD), and we examined the relationship between serostatus and markers of systemic inflammation. BACKGROUND: The potential contribution of CP to atherogenesis is still a matter of debate, and inflammation has been suggested to represent the link between infection and atherosclerotic disease. METHODS: Subjects age 40 to 68 years were recruited for this case-control study between October 1996 and November 1997: 312 patients with at least one coronary stenosis >50% and 479 age- and sex-matched blood donors without manifest CAD or history of angina. Antibodies against cLPS and CP, C-reactive protein (CRP), fibrinogen, plasma viscosity, leukocytes and neutrophils were determined. The study had a power of >80% to detect an odds ratio (OR) of 1.55 or above for the prevalence of immunoglobulin (IgG) antibodies against cLPS at a significance level of alpha = 0.05. RESULTS: Prevalence of IgG antibodies against cLPS was not different between cases and controls (61% vs. 62%; p = 0.7). The adjusted OR for the presence of CAD given positive IgG serostatus against cLPS was 0.9 (95% CI; 0.6 to 1.3). Similarly, no difference in the prevalence of IgG antibodies against CP was seen (88% vs. 87%; p = 0.6); the adjusted OR was 1.0 (95% CI; 0.6 to 1.6). Markers of inflammation did not show any statistically significant difference between cLPS seropositives and seronegatives. CONCLUSIONS: Our results indicate no strong association between CP and CAD, and increased systemic inflammation in patients with CAD does not seem to be due to seropositivity to cLPS or CP.

Adult↗

PubMed2000

Influence of the orifice inlet angle on the velocity profile across a flow convergence region by color Doppler in vitro.

The converging flow field proximal to a leaking valve is determined among other things by the orifice inlet angle formed by the leaflets. Thus, the inlet angle affects the determination of regurgitant flow rate by the flow convergence method. Based on the hypothesis of spheric isovelocity surfaces, others had postulated that a local velocity within the flow convergence should change inversely proportional to changes in the three-dimensional inlet angle. This concept would allow correction of the determination of regurgitant flow for nonplanar orifice inlet angles. We tested this concept in vitro. In a flow model, the flow convergence region proximal to different orifice plates was imaged by color Doppler: funnel-shaped, planar and tip-shaped (inverted funnels) orifice plates, with circular orifices of 2- and 7-mm diameter. Velocity profiles across the flow convergence along the flow centerline were read from the color maps. As predicted, the local velocities were inversely related to the inlet angle, but only at the 2-mm funnel orifices, this effect was inversely proportional to the three-dimensional inlet angle (i.e., in agreement with the mentioned concept). However, for any 7-mm orifice and/or inlet angle of > 180 degrees, the effect of the inlet angle was considerably less than predicted by the aforementioned concept. With increasing orifice diameter and with decreasing distance to the orifice, the effect of the orifice inlet angle was reduced. The effect of the orifice inlet angle on the flow convergence region is modulated by orifice size and the distance to the orifice. Therefore, correction of flow estimates in proportion to the three-dimensional inlet angle will lead to considerable errors in most situations of clinical relevance, namely to massive overcorrection when analyzing velocities located close to wide orifices.

Blood Flow Velocity↗

PubMed2000

C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis.

Infiltration of monocytes into the arterial wall is an early cellular event in atherogenesis. Recent evidence shows that C-reactive protein (CRP) is deposited in the arterial intima at sites of atherogenesis. In this study, we demonstrate that CRP deposition precedes the appearance of monocytes in early atherosclerotic lesions. CRP is chemotactic for freshly isolated human blood monocytes. A specific CRP receptor is demonstrated on monocytes in vitro as well as in vivo, and blockage of the receptor by use of a monoclonal anti-receptor antibody completely abolishes CRP-induced chemotaxis. CRP may play a major role in the recruitment of monocytes during atherogenesis.

Antibodies, Monoclonal↗

PubMed2000

[Risk stratification after myocardial infarct].

In industrialized countries the rate of sudden cardiac death remains unchanged. The most frequently encountered structural heart disease in these patients is coronary artery disease. Despite the era of thrombolytic therapy of acute myocardial infarction patients carry an increased risk of sudden cardiac arrhythmogenic death within a time period of one to two years following the acute event. Therefore, risk stratification post-MI before patient discharge is furthermore mandatory. The spectrum of non-invasive techniques for risk stratification includes the clinical risk profile, measurement of left ventricular global function (LV ejection fraction), the resting ECG (QT dispersion), an ECG stress test (detection and severity of myocardial ischemia), ambulatory ECG monitoring (number and type of ventricular arrhythmias), surface high resolution ECG (detection of ventricular late potentials), measurement of T wave alternans (TWA, alternans ratio), and measurements of the activity and balance of the autonomous nervous system (heart rate variability, baroreflex sensitivity = BRS). Programmed ventricular stimulation (PVS) serves as an invasive risk stratification technique (detection of an arrhythmogenic substrate). The prognostic power of the non-invasive techniques is limited; in general, the prognostic value of a negative test is reasonably high (90 to 100% depending on the test used), whereas the prognostic value of a positive test is rather low (4 to 42% depending on the test used). Combining several non-invasive tests may significantly improve the positive predictive value above 50%, but this goes along with a significant decreases of sensitivity below 50%. Therefore, a combination of several non-invasive tests (detection and exclusion of a large number of low-risk individuals) with the invasive method of PVS (detection of an arrhythmogenic substrate, i.e. a high-risk patient) seems reasonable, as has been convincingly shown by several smaller prognostic studies.

Arrhythmias, Cardiac↗

PubMed1999

Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response.

BACKGROUND: There is controversy about the association between Helicobacter pylori infection and manifestations of coronary heart disease (CHD), the potential role of the more virulent H pylori strains, and whether or not a positive serostatus is related to increased levels of markers of systemic inflammation. METHODS AND RESULTS: We assessed the prevalence of an infection with H pylori and in particular the anti-cytotoxin-associated protein A (CagA) antibody response of the more virulent strains expressing CagA in 312 patients with stable CHD and in 479 control subjects. Serological prevalence of H pylori infection (IgG titer) was significantly higher in patients than in control subjects after adjustment for age and sex (44.2% versus 31.3%, P<0.001). After adjustment for various covariates in multiple logistic regression, the odds ratio (OR) for CHD was 1.3 (95% CI, 0.9 to 1.9) given a positive IgG serostatus. The prevalence of CagA-positive strains was 27.9% in patients and 21.7% in control subjects (P=0.076 adjusted for age and sex). The OR for CHD in the fully adjusted model was 1.1 (95% CI, 0.7 to 1.7). None of the inflammatory markers (C-reactive protein, fibrinogen, plasma viscosity, or leukocytes) was significantly different according to serostatus. CONCLUSIONS: In this large case-control study, the association of H pylori infection with stable CHD was strongly reduced and was no longer statistically significant after controlling for potential confounders. We also found no independent association between the more virulent strains and CHD. In addition, a positive serostatus was not associated with a systemic inflammatory response. Thus, these data do not support the hypothesis that infection with H pylori might be a major risk factor for stable CHD.

Aged↗

PubMed1999

Effect of 17-beta estradiol on pre-existing atherosclerotic lesions: role of the endothelium.

The atheroprotective effects of estrogen during the process of atherogenesis is well documented, whereas limited information is available about the effect of estrogen on pre-existing atherosclerotic lesions. After bilateral ovariectomy, 24 New Zealand White rabbits were randomized into three groups of eight animals each and subsequently fed a 0.5% cholesterol diet. In group I, the vessels were excised at day 84, whereas in group II, the cholesterol diet was continued for a total of 168 days. In group III, the animals were first fed with a cholesterol diet for 84 days; in the second phase of the experiment, the cholesterol diet was continued for a further 84 days with a combined estrogen treatment (1 mg estradiol valerate per kg body weight per week intramuscularly). At the end of the experiment, the proximal aortic arch, right carotid artery, thoracical aorta and abdominal aorta of each animal were excised and prepared for histological and immunohistological examination. By day 168, morphometrical analysis displayed a significantly lower plaque development under estrogen therapy in the carotid artery (0.08+/-0.18 mm(2) vs. 0.60+/-0.39 mm(2)), the thoracic aorta (0.56+/-0.94 mm(2) vs. 3.63+/-2.06 mm(2)), and in the abdominal aorta (0.55+/-0.70 mm(2) vs. 1.71+/-1.05 mm(2)) in comparison with the corresponding 168 day control group. However, estrogen treatment has failed to reduce further atherosclerotic plaque development in the aortic arch (9.42+/-1.79 mm(2) vs. 11. 64+/-3.29 mm(2)). Immunohistological detection of the 'anti-human factor VIII related antigen', i.e. the 'von Willebrand factor' (vWF), showed a significantly lower number of luminal cells positive for vWF in the aortic arch in the 84-day cholesterol group, compared with the corresponding controls of normocholesterolemic rabbits (65. 9+/-12.4% vs. 83.1+/-6.2%; P<0.05). Estradiol was able to inhibit the further progression of atherosclerosis when moderate vessel wall alterations were present, whereas pre-existing severe atherosclerosis was associated with a failure of the anti-atherosclerotic estrogen action. As suggested by the in situ detection of vWF as a morphological marker for endothelial cells, an intact endothelial layer might play an important role in mediating the beneficial effect of estrogen in the process of atherosclerosis.

Animals↗

PubMed1999

A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling.

PP1 has previously been described as an inhibitor of the Src-family kinases p56(Lck) and FynT. We have therefore decided to use PP1 to determine the functional role of Src in platelet-derived growth factor (PDGF)-induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs). A synthetic protocol for PP1/AGL1872 has been developed, and the inhibitory activity of PP1/AGL1872 against Src was examined. PP1/AGL1872 potently inhibited recombinant p60(c-src) in vitro and Src-dependent tyrosine phosphorylation in p60(c-srcF572)-transformed NIH3T3 cells. PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs, as determined in the modified Boyden chamber, as well as PDGF-stimulated proliferation of HCASMCs. Surprisingly, in addition to inhibition of Src kinase, PP1/AGL1872 was found to inhibit PDGF receptor kinase in cell-free assays and in various types of intact cells, including HCASMCs. PP1/AGL1872 did not inhibit phosphorylation of the vascular endothelial growth factor receptor KDR (VEGF receptor-2; kinase-insert domain containing receptor) in cell-free assays as well as in intact human coronary artery endothelial cells. In line with the insensitivity of KDR, PP1/AGL1872 had only a weak effect on vascular endothelial growth factor-stimulated migration of human coronary artery endothelial cells. On treatment of cells expressing different receptor tyrosine kinases, the activities of the epidermal growth factor receptor, fibroblast growth factor receptor-1, and insulin-like growth factor-1 receptor were resistant to PP1/AGL1872, whereas PDGF alpha-receptor was susceptible, albeit to a lesser extent than PDGF beta-receptor. These data suggest that the previously described tyrosine kinase inhibitor PP1/AGL1872 is not selective for the Src family of tyrosine kinases. It is also a potent inhibitor of the PDGF beta-receptor kinase but is not a ubiquitous tyrosine kinase inhibitor. PP1/AGL1872 inhibits migration and proliferation of HCASMCs probably by interference with 2 distinct tyrosine phosphorylation events, creating a novel and potent inhibitory principle with possible relevance for the treatment of pathological HCASMC activity, such as vascular remodeling and restenosis.

3T3 Cells↗