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Biomedical subjects

J Kähler

Publications and source records attributed to J Kähler.

At least 19 recordsLinked to original sources

[Diagnosis and therapy of infectious endocarditis. What measures are required?].

Infectious endocarditis remains a potentially life-threatening disease, the outcome of which can be substantially influenced by rapid diagnosis and initiation of suitable treatment. Leading clinical features are fever, a new sound suggestive of valvular insufficiency and, when the course is subacute, anemia. The main diagnostic procedures are transthoracic and transesophageal echocardiography that reliably identify vegetation, valvular insufficiency and abscess. Of decisive importance for treatment and prognosis is the rapid identification of the pathogen by means of blood culture and, if necessary, serologic and molecular-biologic measures. Antimicrobial treatment is applied in accordance with the recommendations of the American Heart Association. Surgical treatment is indicated in the event of refractory infection, severe valvular insufficiency with heart failure, valve avulsion, recurrent emboli or large floating vegetation with an elevated risk of embolism.

Anti-Bacterial Agents↗

Antibodies to chlamydial lipopolysaccharides in unstable angina pectoris.

Patients with coronary artery disease frequently have elevated antibody titers against Chlamydia pneumoniae, but whether antichlamydial antibody titers are correlated with prognosis in unstable angina remains unclear. We therefore investigated the sera of 1,096 patients with unstable angina regarding immunoglobulin (Ig) IgG, IgA, and IgM antibody titers against chlamydial lipopolysaccharides (LPS) and the concentrations of C-reactive protein (CRP) and troponin T (TnT). Anti-LPS IgG titers were increased in 45% of patients at enrollment and in 48% of patients at discharge (p <0.0001). Anti-LPS IgA titers were increased in 27% of patients at enrollment and in 33% of patients at discharge (p <0.0001). Patients who subsequently died had significantly lower IgM titers at enrollment than patients without events (p = 0.016). IgG, IgA, or IgM titers did not correlate with concentrations of CRP or TnT. In this large-scale study of patients with unstable angina, we frequently found elevated antichlamydial antibody titers. Patients with low IgM anti-LPS titers were at risk for subsequent death. However, there was no correlation between antichlamydial antibody titers and CRP or TnT.

Aged↗

Membrane-covered stents: a new treatment strategy for saphenous vein graft lesions.

The restenosis rate after stenting of lesions in aortocoronary venous bypass grafts still has to be considered unsatisfactorily high. We investigated a new stent design characterized by an expandable polytetrafluorethylene (PTFE) membrane in between two layers of struts. Five consecutive male patients (age 70 +/- 6 years) were followed prospectively who presented with at least two de novo lesions in different grafts 13 +/- 3 years after bypass surgery. A total of 11 lesions were treated located in grafts anastomosed to the circumflex (n = 3), to the LAD (n = 7), and to the right coronary artery (n = 1). Within the same procedure, every patient received membrane-covered stents (n = 6) and conventional stents (n = 5) in either of their lesions. All patients underwent successful interventions. The minimal luminal diameter increased from 1.0 +/- 0.5 to 2.9 +/- 0.6 mm in lesions treated by the membrane-covered stents and from 0.8 +/- 0.4 to 2.4 +/- 0.7 mm in the lesions treated by conventional stents. During follow-up, four out of five patients required angioplasty for in-stent restenosis of lesions covered by a conventional stent, whereas no patient underwent revascularization for a lesion treated by a membrane-covered device. The mean minimal luminal diameter of lesions covered by a conventional stent decreased by 42% to 1.4 +/- 0.6 mm; the mean minimal luminal diameter of the lesions treated by a stent graft declined by 9% to 2.8 +/- 0.6 mm (P < 0.05). This series of intraindividual comparisons suggests that membrane-covered stents may have the power to reduce in-stent restenosis in obstructed aortocoronary venous bypass grafts.

Aged↗

Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth muscle cells.

Endothelins, nitric oxide, and oxygen-derived free radicals decisively regulate vascular tone. An imbalance in the biosynthesis of these substances in pathophysiologic conditions may trigger vasospasm and promote the development of atherosclerosis. Previous studies have shown that oxygen-derived free radicals can increase the synthesis of endothelin-1 in cultured endothelial cells. Interestingly, conditions of increased oxidative stress within smooth muscle cells as induced by angiotensin II infusion or hypercholesterolemia have been shown to be associated with increased autocrine synthesis of endothelin-1. Because endothelin-1 formed in smooth muscle cells can trigger hypersensitivity to vasoconstrictors, we tested whether oxidative stress per se may affect endothelin expression in vascular smooth muscle cells. Cultured human coronary artery smooth muscle cells were exposed to oxidative stress generated by the xanthine/xanthine oxidase reaction or by hydrogen peroxide. Preproendothelin-1 mRNA content was quantitated by means of quantitative polymerase chain reaction and endothelin-1 protein was measured by radioimmunoassay. Incubation with xanthine/xanthine oxidase significantly increased preproendothelin-1 mRNA synthesis, whereas GAPDH remained unchanged. Likewise, xanthine/xanthine oxidase also led to a dose-dependent increase of intracellular endothelin-1. The increase in ET-1 expression induced by xanthine/xanthine oxidase was significantly inhibited by superoxide dismutase but not by catalase. We conclude that oxygen-derived free radicals can stimulate the synthesis of endothelin-1 in endothelial and vascular smooth muscle cells by increasing preproendothelin-1 mRNA content and that this effect is mediated predominantly by superoxide anions. We therefore have identified a new mechanism in the interaction of oxidative stress and endothelin-1 expression in smooth muscle cells that may have important implications in diseases such as atherosclerosis and hypertension.

Cells, Cultured↗

Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis.

BACKGROUND: Coronary in-stent restenosis might be triggered by contact allergy to nickel, chromate, or molybdenum ions released from stainless-steel stents. We investigated the association between allergic reactions to stent components and the occurrence of in-stent restenosis. METHODS: Patients with coronary stainless-steel stents who underwent angiography for suspected restenosis were consecutively included in this study. Quantitative coronary angiography for analysis of percentage diameter stenosis was done on 131 patients (mean age 62 years [SD 9]) with 171 stents 6.1 months (2.7) after stent implantation. All patients underwent epicutaneous patch tests (Finn chamber method) for nickel, chromate, molybdenum, manganese, and small 316L stainless-steel plates. Patch tests were assessed by independent dermatologists after 48 h, 72 h, and when necessary 96 h of contact with the potential allergen. FINDINGS: In-stent restenosis (> or =550% diameter stenosis) occurred in 89 patients. All ten patients with positive patch-test results had restenoses (p=0.03). Four male patients had positive reactions to molybdenum, and seven patients (four male, three female) had reactions to nickel. No patient with an allergic reaction to the standard test substances had a positive reaction to the stainless-steel plates. All patients with positive results had recurrent angina pectoris and needed target-vessel revascularisation. INTERPRETATION: Patients with allergic patch-test reactions to nickel and molybdenum had a higher frequency of in-stent restenoses than patients without hypersensitivity. Allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent restenosis.

Adult↗

Initial experience with a hydrophilic-coated guidewire for recanalization of chronic coronary occlusions.

Chronic coronary occlusions are still a therapeutic challenge to the interventional cardiologist. New techniques such as laser wire have improved recanalization rates, but outcomes are still far from satisfactory. We report the results of a nonrandomized single-center investigation using a hydrophilic-coated guidewire (Terumo Crosswire). Between September 1996 and September 1998, 107 chronic occlusions in 106 patients were approached when previous attempts with conventional guidewires failed. Median occlusion duration in these cases was 4 months (range, 0.5-122); mean occlusion length was 19 +/- 11 mm (range, 5-60). Forty-five (42%) of these attempts were successful. Attempts were successful in 42% in the left anterior descending artery, in 30% in the left circumflex artery, in 48% in the right coronary artery, and in 43% in coronary artery bypass grafts. Success rates ranged from 56% for occlusions of less than 4-month duration to 18% for occlusions of more than 36-month duration. The success rate in TIMI 1-flow lesions was significantly higher than in TIMI 0 flow lesions, 85% vs. 36%. In a multivariate regression analysis, TIMI flow grade and occlusion age were independent predictors of success. There were no deaths or Q-wave myocardial infarctions; two cases of hemopericardium were treated successfully. In five cases, pericardial contrast staining due to vessel perforation occurred. Our results indicate that the Crosswire is an effective tool in the treatment of chronic coronary occlusions, even when recanalization attempts with conventional guidewires fail. Cathet. Cardiovasc. Intervent. 49:45-50, 2000.

Adult↗

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↗

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↗

[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↗

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↗

[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↗

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↗

[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↗

[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↗

A new electrohydraulic energy converter for a left ventricular assist device.

An energy converting system that can function for years without maintenance is required for the drive of a left ventricular assist device (LVAD). To meet the requirements of safety, the energy converter should have a simple design with few moving elements. The design applied herein has only one moving part and thus has greater inherent safety than competing systems. The only moving part is the rotor unit, comprised of the impeller of a centrifugal pump, the rotor of an electric motor, and the rotor of an electric axial actuator. A reversal of flow of the transmitter fluid can be achieved with an axial shift of this rotor unit. This fluid acts on the outer surface of a blood chamber and enables it to draw in blood and to expel it. Valves direct the flow of blood. The energy converter performs a flow of 12 L/min at a motor speed of 6,000 rpm against a pressure head of 115 mm Hg according to an output of the pulsatile blood pump of 5 L/min.

Electric Power Supplies↗