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Biomedical subjects

R Köster

Publications and source records attributed to R Köster.

At least 37 records · Page 2Linked to original sources
PubMed2000

Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter.

Modulation of the biosynthesis of the vasoconstrictor peptide endothelin-1 by oxygen-derived free radicals generated by xanthine oxidase or hydrogen peroxide was studied in cultured endothelial cells. Endothelin-1 metabolism was investigated at the level of endothelin-1 promoter, preproendothelin-1 mRNA and intracellular big endothelin-1. Endothelin-1 mRNA, as characterized by Northern blotting, was increased both time- and dose-dependently by xanthine oxidase to up to 500% above baseline. Analysis of endothelin-1 promoter activity using a construct containing 1329 bp of the endothelin-1 promoter revealed that promoter activity was increased up to eight-fold by incubation with xanthine oxidase. Specificity was ascertained by co-incubation with superoxide dismutase and catalase leading to inhibition of the effect of xanthine oxidase. A significant contribution of nitric oxide was ruled out, since NOS III-mRNA transcription remained unchanged and l -NAME did not significantly alter endothelin-1 promoter activity. Synthesis of intracellular big endothelin-1 protein was increased dose-dependently by xanthine oxidase. Our results indicate that oxidative stress leads to increased endothelial synthesis of big endothelin-1, which is a previously unknown mechanism and may help to understand the detrimental association of increased oxidative stress and elevated endothelin-1 levels in pathophysiological conditions promoting atherosclerosis.

Animals↗
PubMed2000

Six-month clinical and angiographic outcome after successful excimer laser angioplasty for in-stent restenosis.

OBJECTIVES: This study evaluated the clinical and angiographic six-month follow-up after excimer laser coronary angioplasty (ELCA) for restenosed coronary stents. BACKGROUND: Excimer laser coronary angioplasty has recently been shown to be safe and efficient for the treatment of in-stent restenosis. METHODS: Ninety-six consecutive patients successfully treated with ELCA within 141 stents were included in a six-month clinical and angiographic follow-up. RESULTS: During follow-up there was one sudden death and one patient with documented myocardial infarction. Angina pectoris classified as > or = Canadian Cardiovascular Society II reoccurred in 49 patients. Follow-up angiography was obtained in 89 patients (93%) with 133 stents. Quantitative coronary angiography revealed a mean diameter stenosis of 77 +/- 10% before intervention, 41 +/- 12% after laser treatment and 11% +/- 12% after adjunctive percutaneous transluminal coronary angioplasty (p < 0.001). Six months after ELCA the mean diameter stenosis had increased to 60 +/- 26% (p < 0.001). A > or =50% diameter stenosis was present in 48 patients (54%); in 24 of these patients diameter stenosis was > or =70%. Total occlusions occurred in an additional 10 patients (11%). There was a trend toward an increased recurrent restenosis rate in patients with diabetes mellitus and long lesions or total occlusions (p = 0.059). Forty-eight patients (50%) received medical treatment after six months. Reinterventions were necessary in 30 patients (31%), and coronary artery bypass surgery was performed in 17 patients (18%). Event-free survival was 50%. CONCLUSIONS: Excimer laser angioplasty for in-stent restenosis was associated with a high incidence of recurrent restenosis in this group of patients, suggesting that this technique is unlikely to reduce recurrent in-stent restenosis and that other approaches are necessary.

Adult↗
PubMed1999

[Role of Chlamydia pneumoniae in the pathogenesis of coronary disease].

Several studies have demonstrated an association Chlamydia pneumoniae with coronary artery disease, suggesting that infection with C. pneumoniae increases the risk for coronary artery disease by factor 2 or more. Since atherosclerosis is considered to be a chronic inflammatory process, these data would fit into the response-to-injury hypothesis of atherosclerosis rather than representing a completely novel concept. Several pathomechanisms as increased cytokine synthesis, proliferative and proaggregatory effects could transmit the effects of chronic C. pneumoniae infection. Animal models and first clinical trials using antibiotic therapy seem to support an etiological role of C. pneumoniae in coronary artery disease. In this paper the current knowledge of the role of C. pneumoniae in coronary artery disease is reviewed and possible pathomechanisms are discussed.

Adolescent↗
PubMed1999

Laser angioplasty of restenosed coronary stents: results of a multicenter surveillance trial. The Laser Angioplasty of Restenosed Stents (LARS) Investigators.

OBJECTIVES: This study evaluated safety and efficacy of excimer laser angioplasty for treatment of restenosed or occluded coronary stents. BACKGROUND: Balloon angioplasty of in-stent restenosis is limited by a high recurrence rate. Debulking by laser angioplasty is a novel concept to treat in-stent restenosis. METHODS: A total of 440 patients with restenoses or occlusions in 527 stents were enrolled for treatment with concentric or eccentric laser catheters and adjunctive balloon angioplasty. RESULTS: Laser angioplasty success (< or =50% diameter stenosis after laser treatment or successful passage with a 2.0-mm or 1.7-mm eccentric laser catheter) was achieved in 92% of patients. Adjunctive balloon angioplasty was performed in 99%. Procedural success (laser angioplasty success followed by < or =30% stenosis with or without balloon angioplasty) was 91%. There was neither a significant difference in success with respect to lesion length, nor were there differences between small and large vessels or native vessels and vein grafts. Success was higher and residual stenosis lower using large or eccentric catheters. Serious adverse events included death (1.6%, not directly laser catheter related), Q-wave myocardial infarction (0.5%), non-Q-wave infarction (2.7%), cardiac tamponade (0.5%) and stent damage (0.5%). Perforations after laser treatment occurred in 0.9% of patients and after balloon angioplasty in 0.2%. Dissections were visible in 4.8% of patients after laser treatment and in 9.3% after balloon angioplasty. Reinterventions during hospitalization were necessary in 0.9% of patients; bypass surgery was performed in 0.2%. CONCLUSIONS: Excimer laser angioplasty with adjunctive balloon angioplasty is a safe and efficient technology to treat in-stent restenoses. These data justify a randomized comparison with balloon angioplasty.

Adult↗
PubMed1999

Coronary angioplasty in octogenarians. Quality of life and costs.

BACKGROUND: Improvement in quality of life is the major motivation for angioplasty in very elderly patients. The alleviation of symptoms with this method is therefore of particular interest. However, little is known about the impact of angioplasty in terms of quality of life in octogenarian patients and what the treatment costs are. METHODS AND RESULTS: We prospectively compared patients aged 80 years or above (n=34, 83+/-3 years) with younger patients (n=34, 62+/-8 years) regarding their quality of life following coronary angioplasty. Patients were interviewed immediately following angioplasty and 6 months later using the SF-36 health survey. Key determinants of costs and follow-up for 6 months were documented. The number of diseased vessels, interventions performed and number of lesions treated were comparable in both groups. Success rates were lower in the octogenarian than in the control group (88 vs 97%). In both groups angioplasty significantly improved the ability to fulfil physical role expectations and decreased bodily pain. Both the effects on Role Physical and on Bodily Pain were more pronounced in the octogenarian patients. Determinants of costs did not differ significantly between the two groups. CONCLUSIONS: Our data demonstrate that in octogenarians with symptomatic coronary heart disease, coronary angioplasty significantly increases physical abilities and decreases pain. Further, these effects were more pronounced in octogenarian patients than in younger patients.

Aged↗
PubMed1998

[Acute results of ablation of coronary in-stent restenoses with eccentric excimer laser catheters].

UNLABELLED: Laser catheters which run eccentrically on a guide wire were developed for maximization of luminal gain by excimer laser angioplasty (ELCA). We investigated the safety and efficacy of ELCA with these new catheters plus PTCA in patients with restenoses or occlusions in coronary stents. ELCA was performed in 57 patients (60 +/- 9 years) with stenoses in 75 stents (35 AVE Micro stents, 26 Palmaz-Schatz stents, 7 NIR stents, 7 other stents). In 44 patients eccentric 1.7 mm catheters and in 13 patients 2.0 mm catheters were used. The success of the intervention was analyzed by intravascular ultrasound (IVUS) in a subgroup of 7 patients treated with five 1.7 mm and two 2.0 mm catheters. The laser catheters could be advanced through the in-stent restenoses in 56 patients. A passage inhibition occurred in one patient with an inadequately expanded stent < 2.0 mm in diameter. ELCA reduced the diameter stenoses from 77 +/- 10% before intervention to 44 +/- 8% after treatment with the 1.7 mm catheter (n = 43) or to 34 +/- 9% after passages with the 2.0 mm catheter (P < 0.001). PTCA further reduced the diameter stenosis to 11 +/- 12% (P < 0.001). The IVUS analysis revealed a smooth ablation profile in all patients. In 4 patients creatine kinase elevations > or = 2 times normal value occurred. There was no evidence of a Q-wave infarction. No dissections were observed within the stents. Outside of the stents there were dissections in 5 vessels, which required the implantation of additional stents. CONCLUSIONS: ELCA with eccentric laser catheters for treatment of in-stent restenosis is safe and effective. The incidence of complications is acceptable.

Adult↗
PubMed1997

Treatment of in-stent coronary restenosis by excimer laser angioplasty.

We evaluated the efficacy and safety of excimer laser angioplasty (ELCA) with adjunctive balloon angioplasty in patients with restenotic or occluded coronary stents. ELCA was performed in 70 patients (60 +/- 9 years), who had previously been treated with Micro Stents (n = 65), Palmaz-Schatz (n = 38), Wiktor, NIR, Freedom, and Multi-Link stents (n = 1 each). Restenosis (> or =50% diameter stenosis) was documented in 90 stents, another 17 stents were occluded. Laser energy was delivered to the lesions with catheters 1.4, 1.7 (eccentric), and 2.0 mm in diameter. Procedural success was controlled by intravascular ultrasound in a subgroup. Laser catheters crossed all restenotic or occluded stents and decreased diameter stenosis from 80 +/- 13% to 44 +/- 11% (p <0.001). Adjunctive balloon angioplasty further reduced diameter stenosis to 13 +/- 13% (p <0.001). In 13 patients with 21 stents, serial intravascular ultrasound imaging revealed a reduction of plaque area within the stent by 34 +/- 22% (from 4.2 +/- 1.8 mm2 to 2.7 +/- 1.1 mm2) after ELCA and a reduction by 65 +/- 16% (to 1.5 +/- 0.7 mm2) after balloon angioplasty (p <0.01). There were 4 patients with an increase of creatine kinase levels, 8 patients with major dissections (in 7 patients they were related to adjunctive balloon angioplasty), 1 patient with distal embolization, 2 with minor perforations, and 1 patient with stent dislocation. Reintervention during hospitalization was necessary in 3 patients. ELCA is an efficient and safe technique to debulk tissue in restenotic lesions and total occlusions within stents. The incidence of procedure related complications was low.

Adult↗
PubMed1997

[Worldwide HIV incidence--aspects and dynamics of a tardive epidemic].

The present situation of the HIV pandemic is described on the basis of current data from the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), the United States Center for Disease Control (CDC), and selected papers on the subject. The worldwide situation is unstable and alarming. New regional HIV subepidemics are spreading rapidly on several continents. On the worldwide level, the HIV epidemic has not yet reached its maximum: in the next 3-4 years 10-12 millions HIV-infected persons will be added to the existing 22.6 millions. The epidemiological situation in the industrialized countries is described separately: in contrast to the developing countries, HIV transmission among drug addicts predominates, while heterosexual transmission continues to increase. The findings of molecular epidemiology reflect migration trends and special conditions for spread of the disease. As a consequence of the HIV epidemic, classical epidemic diseases, such as tuberculosis, are on the increase again. The worldwide HIV epidemic is more serious than ever and requires more effective preventive strategies.

Adolescent↗
PubMed1997

[Endothelins in cardiovascular diseases].

Endothelins are peptides with powerful vasoconstrictor and mitogenic properties. It has become evident that endothelins are involved in many regulatory mechanisms of the circulation in which they have a modulating role both in short and in long term. However, in many cases it remains unclear whether the alteration of the endothelin metabolism is a primary pathology or a secondary phenomenon. The synthesis of endothelin receptor antagonists and animal models with altered endothelin metabolism have opened a new era of endothelin research that will allow insight into the mechanisms of endothelin-action and eventually might lead to new therapeutic concepts. This review discusses the evidence both in favor and against pathogenic effects of endothelins in cardiovascular disease.

Animals↗
PubMed1996

[Arthrogenic ear canal tumor].

We report our findings in two female patients (aged 56 and 64 years) who complained about slight hearing loss that varied during jaw movements. In both cases a polypoid tumor of the external auditory meatus was found that almost completely disappeared with mouth opening. CT showed a bony defect of the anterior wall of the external auditory canal in both patients. Biopsies from the tumor-like lesions were done, revealing a chronic inflammatory hyperplasia of the connective tissue in one case and a rheumatic granuloma in the other. Review of medical histories showed that the first patient suffered from a recurrent neurodermatitis and the second had experienced a chronic polyarthritis for many years. From these findings and on the basis of a literature review, we conclude that these pseudotumors represent a chronic inflammatory hyperplasia of the periarticular tissue which herniated through a persistent "foramen of Huschke." This foramen is formed during embryological development of the two tympanic tubercles, but normally closes before the age of 5 years. However, in a few rare cases is may persist to allow herniation of synovial tissue.

Arthritis, Rheumatoid↗
PubMed1996

Ectopic lens induction in fish in response to the murine homeobox gene Six3.

Recent findings show an unexpected conservation of genes involved in vertebrate and insect eye development. The Drosophila homeobox gene sine oculis is crucial for eye development. Its murine homologue, Six3 is expressed in the anterior neural plate, a region which is involved in lens induction in Xenopus. To examine whether Six3 participates in the process of eye formation, mouse Six3 was ectopically expressed in fish embryos. The results show that Six3 is sufficient to promote ectopic lens formation in the area of the otic vesicle and that retinal tissue is not a prerequisite for ectopic lens differentiation. Our findings suggest a conserved function for Six3 in metazoan eye development.

Animals↗
PubMed1996

Consensus-interferon and platelet-derived growth factor adversely regulate proliferation and migration of Kaposi's sarcoma cells by control of c-myc expression.

Platelet-derived growth factor-B (PDGF-B) is a potent paracrine-acting mitogen in Kaposi's sarcoma (KS) lesions. Interferon-alpha is widely used for clinical treatment of KS. Here we show that platelet-derived growth factor-B activates proliferation and migration of cultivated AIDS-KS spindle cells whereas interferon-alpha acts as an inhibitor. At the molecular level, these opposite activities of platelet-derived growth factor-B and interferon-alpha converged onto the adverse regulation of the c-myc gene expression. Platelet-derived growth factor-B induced c-myc mRNA and protein synthesis in cultivated AIDS-KS spindle cells whereas interferon-alpha inhibited these processes. Using c-myc-specific phoshothioate antisense oligodeoxynucleotides, we demonstrated that down-regulation of c-myc expression is sufficient to inhibit proliferation and migration of KS spindle cells in vitro. This indicated that c-Myc protein may be an important regulatory molecule of KS spindle cell proliferation and migration. High amounts of the c-Myc protein were detected in the nuclei of KS spindle cells in histological sections of AIDS-KS biopsies. This suggested that the c-myc gene may also regulate proliferation and migration of AIDS-KS spindle cells in vivo. In this case, c-myc may play an important role in the focus of major pathogenic and therapeutic pathways of KS.

Cell Division↗
PubMed1996

[Initial clinical and angiographic results with the AVE Micro-Stent].

UNLABELLED: The AVE Micro Stent is a flexible stent with a small surface. Aim of this study was to investigate safety and efficacy of this stent. 105 AVE Micro Stents were deployed in 78 lesions in 64 patients. The implantation was performed electively (19%), after unsatisfactory PTCA (59%), and as "bailout" (23%) into left main (1), LAD (23), LCX (15), RCA (19) or CABG (6). Minimal lumen diameter and percent diameter stenosis were measured by quantitative coronary angiography before and after interventions and, in 21 patients, after 3 months. Stent-implantation was successful in 62 of 64 patients. The passage of the AVE Micro Stents through deployed stents (46) was successful in all of 28 cases. There were no deaths or myocardial infarctions. In two patients, subacute thromboses with subsequent increase of CK occurred, which were successfully treated. The minimal lumen diameter was 0.77 +/- 0.62 mm before intervention, 2.98 +/- 0.48 mm after implantation (p < 0.001), and 2.03 +/- 1.21 after 3 months (p < 0.001). The percent diameter stenosis was 75 +/- 20% before intervention, 39 +/- 20% after PTCA and 0 +/- 12% after implantation (p < 0.001). After 3 months, six of 21 patients (29%) with follow-up angiography had a restenosis, defined as > 50% diameter stenosis compared with the reference vessel. CONCLUSIONS: 1) The AVE Micro Stent is a flexible stent, which can be safely and efficiently deployed even through implanted stents. 2) The AVE Micro Stent appears to be particularly suitable for "bailout" therapy of dissections. 3) The rate of subacute thrombosis was low with this stent.

Adult↗
PubMed1995

[Preliminary clinical results with intracoronary ultrasound angioplasty].

UNLABELLED: BASIS AND AIM OF STUDY: Low-frequency, high-intensity ultrasound has been shown, both in vivo and in vitro, selectively to remove arteriosclerotic plaques and thrombi. This study was undertaken to investigate the safety and effectiveness of intracoronary ultrasound angioplasty. PATIENTS AND METHODS: Ultrasound coronary angioplasty (UCA) with highly flexible ultrasound catheters (1.2 mm or 1.7 mm probe tip) was performed in 50 patients (36 men, 14 women; mean age 64.7 [33-79] years) with coronary heart disease involving one (n = 26 or several (n = 24) vessels. Indications for treatment were exercise-induced (n = 35) or unstable (n = 14) angina or acute myocardial infarction (n = 11). Treated lesions were in the anterior interventricular branch (n = 25), circumflex branch of the left coronary artery (n = 3) and right coronary artery (n = 22). 19 vessels were occluded, 24 lesions were partially thrombosed, 19 were calcified. 22 stenoses were longer than 20 mm. According to AHA/ACC criteria, 10 type A, 17 type B1, 6 type B2 and 17 type C lesions were treated. RESULTS: Total ultrasound time was 336 +/- 308 s; mean passing time through the stenosis was 233 +/- 289 (10-556) s. 17 of 19 occlusions were recanalised after 285 +/- 224 s. Percutaneous transluminal angioplasty (PTCA) was subsequently performed in 49 patients. The mean stenosis grade was reduced by UCA from initially 82 +/- 3 to 64 +/- 2% and by subsequent PTCA to 38 +/- 1%. Average flow grade rose from 1.5 to 1.9 after UCA and to 2.8 after PTCA. No vasospasm, atrioventricular block or perforation was caused by UCA. Angiography demonstrated dissection after PTCA in seven patients, treated in two with a stent. Both UCA and PTCA failed to achieve recanalization in one patient with a thrombotic occluded coronary artery after acute myocardial infarction. In all other patients there were no complications. CONCLUSION: The results show UCA to be a safe method for removing high-degree coronary artery stenosis or recanalize thrombotic occlusions.

Adult↗
PubMed1995

Enhanced migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B.

UNLABELLED: Proliferation and migration of vascular smooth muscle cells (SMCs) are major events in atherogenesis. It is known that platelet-derived growth factor (PDGF) stimulates both of these processes in a paracrine fashion, whereas autocrine stimulation has been shown only for proliferation. The aim of this study was to investigate the influence of PDGF expression in SMCs on migratory activity of these cells. SMCs were cultivated from the vascular tissue of 23 patients. Cellular motility was analyzed by a computer-assisted motion analysis system; 54 images per sample, obtained during an observation period of eighteen hours, were analyzed. PDGF-A and PDGF-B mRNA levels were determined by quantitative polymerase chain reaction (PCR) following reverse transcription. To quantitate mRNA content of SMCs, the authors coamplified cDNA copies of mRNA from cells and from a synthetic reference RNA in the same reaction vessel. Cells derived from atherosclerotic lesions produced a 1.6-fold increase of PDGF-A (P < 0.05) and a 5-fold increase of PDGF-B mRNA (P < 0.05) as compared with those from normal vessels. The migratory velocity (range 11.1-49.2 microns/hr) was independent of PDGF-A and PDGF-B mRNA expression. A significant correlation between levels of PDGF-A mRNA and PDGF-B mRNA and the degree of directional changes of SMCs on the covered track (klinokinesis) was found (P < 0.05). CONCLUSION: PDGF-A and PDGF-B mRNA expression is significantly correlated with positive klinokinesis without affecting migratory velocity. This finding reflects enhanced migratory activity of SMCs. Besides its known mitogenic effects, the authors present evidence that PDGF may act as an autocrine motogen* in SMCs.

Adolescent↗