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Biomedical subjects

Ulrich Speck

Publications and source records attributed to Ulrich Speck.

14 recordsLinked to original sources
PubMed2006

Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter.

BACKGROUND: Treatment of coronary in-stent restenosis is hampered by a high incidence of recurrent in-stent restenosis. We assessed the efficacy and safety of a paclitaxel-coated balloon in this setting. METHODS: We enrolled 52 patients with in-stent restenosis in a randomized, double-blind, multicenter trial to compare the effects of a balloon catheter coated with paclitaxel (3 microg per square millimeter of balloon surface area) with those of an uncoated balloon catheter in coronary angioplasty. The primary end point was late luminal loss as seen on angiography. Secondary end points included the rates of restenosis (a binary variable) and major adverse cardiac events. RESULTS: Multivessel disease was present in 80% of patients in both groups. Quantitative coronary angiography revealed no significant differences in baseline measures. At 6 months, angiography showed that the mean (+/-SD) in-segment late luminal loss was 0.74+/-0.86 mm in the uncoated-balloon group versus 0.03+/-0.48 mm in the coated-balloon group (P=0.002). A total of 10 of 23 patients (43%) in the uncoated-balloon group had restenosis, as compared with 1 of 22 patients (5%) in the coated-balloon group (P=0.002). At 12 months, the rate of major adverse cardiac events was 31% in the uncoated-balloon group and 4% in the coated-balloon group (P=0.01). This difference was primarily due to the need for target-lesion revascularization in six patients in the uncoated-balloon group (P=0.02). CONCLUSIONS: Treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly reduced the incidence of restenosis. These data suggest that the inhibition of restenosis by local drug delivery may not require stent implantation and sustained drug release at the site of injury. (ClinicalTrials.gov number, NCT00106587 [ClinicalTrials.gov].).

Aged↗
PubMed2006

Adverse events after unenhanced and monomeric and dimeric contrast-enhanced CT: a prospective randomized controlled trial.

PURPOSE: To prospectively evaluate adverse events (AEs) in patients who underwent nonionic monomeric or dimeric contrast media-enhanced computed tomography (CT) and to compare these effects with AEs in patients who underwent unenhanced CT. MATERIALS AND METHODS: Local ethics committee approval and written informed consent were obtained. Patients were randomly assigned to the dimeric group, monomeric group, or concurrent control group. Acute (occurring during or within 1 hour after contrast agent injection) and delayed (occurring between 1 hour and 7 days after contrast agent injection) AEs were evaluated and categorized (mild, not requiring treatment; moderate, self-limiting AE requiring simple treatment; severe, AE requiring extensive treatment or endangering life). The two-sided Fisher exact test and the Mann-Whitney U and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: A total of 895 patients were recruited. Acute AEs were noted significantly (P < .05) more often in the monomeric group (44.8% [133 of 297 patients]) than in the dimeric (23.7% [71 of 300 patients]) or control (9.4% [28 of 298 patients]) groups. Two moderate acute AEs were noted in one patient in each contrast agent group; all other acute AEs were mild. There was no significant difference in the overall incidence of delayed AEs between the dimeric and monomeric groups (53.1% [139 of 262 patients] vs 50.8% [131 of 258 patients]). Delayed cutaneous AEs were noted significantly (P < .05) more often in the dimeric group. A total 16 AEs (2.0%) were moderate; no AE was severe. CONCLUSION: The dimeric contrast agent caused fewer acute AEs than the monomeric contrast agent; however, the dimeric and monomeric agents caused a similar overall number of delayed AEs. Delayed cutaneous symptoms were noted more often with the dimeric contrast agent. Both contrast agents were safe in that no severe AEs and only a few moderate AEs were observed.

Adult↗
PubMed2006

Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries.

PURPOSE: To compare the inhibition of neointimal proliferation by using non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. MATERIALS AND METHODS: Experiments were conducted with permission of the animal protection committee of the local government. Paclitaxel was either dissolved in a nonionic contrast medium or coated on balloons. Stents were crimped on the coated balloons. Effectiveness was tested in 22 pigs. Two coronary stents were placed in each pig, and slight overstretch was applied. The animals were treated as follows: group A (control group), uncoated balloons, bare stents, and "plain" contrast medium; group B, same treatment as group A, but with paclitaxel in the contrast medium; group C, paclitaxel-coated balloons, with premounted bare stents and plain contrast medium; and group D, sirolimus-eluting stents, noncoated balloons, and plain contrast medium. Stenosis was assessed 4 weeks later at angiography and histomorphometry. For exploratory purposes, continuous variables of quantitative coronary angiography and histomorphometry were compared by using analysis of variance. RESULTS: Results at follow-up angiography indicated a mean of 1.00 mm +/- 0.18 (standard deviation) lumen diameter loss in the control group and 0.14 mm +/- 0.18 loss in the group treated with the paclitaxel-coated balloon (group C; P < .001). Findings at histomorphometry confirmed the effectiveness of drug delivery, with the most impressive inhibition of neointimal proliferation from coated balloons-the neointimal area was 2.4 mm2 +/- 0.3 (P < .01 vs all other groups), compared with 5.2 mm2 +/- 0.3 in group A (control group), 4.3 mm2 +/- 0.3 in group B, and 3.8 mm2 +/- 0.3 in group D. CONCLUSION: In spite of the short intima contact time, paclitaxel coated on the balloon inhibits neointimal formation in the porcine model of coronary stent placement.

Analysis of Variance↗
PubMed2005

A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions.

PURPOSE: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. MATERIALS AND METHODS: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. RESULTS: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-FcepsilonRI antibodies) (6763.7 pg/ml+/-1367.3 versus 2299.8 pg/ml+/-399.2; p<0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administration. In vitro iopromide (p<0.0002) and iotrolan (p<0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6h after CM administration (p<0.05). CONCLUSION: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future.

Adult↗
PubMed2004

Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis.

BACKGROUND: Drug-eluting stents have shown promising antirestenotic effects in clinical trials. Non-stent-based local delivery of antiproliferative drugs may offer additional flexibility and also reach vessel areas beyond the immediate stent coverage. The aim of the present study was to evaluate a novel method of local drug delivery based on angioplasty balloons. METHODS AND RESULTS: Stainless steel stents (n=40; diameter, 3.0 to 3.5 mm; length, 18 mm) were implanted in the left anterior descending and circumflex coronary arteries of domestic pigs. Both conventional uncoated and 3 different types of paclitaxel-coated, percutaneous transluminal coronary angioplasty balloons (contact with vessel wall for 1 minute) were used. No difference in short-term tolerance between coated and uncoated balloons and no signs of thrombotic events were observed. Quantitative angiography and histomorphometry of the stented arteries asserted the statistical equality of the baseline parameters between the control and the 3 treatment groups. Paclitaxel balloon coating led to a marked, dose-dependent reduction of parameters characterizing in-stent restenosis (reduction of neointimal area up to 63%). Despite the marked reduction in neointimal proliferation, endothelialization of stent struts was present in all samples. There was no evidence of a significant inflammatory response in the neighborhood of the stent struts. CONCLUSIONS: Paclitaxel balloon coating is safe, and it effectively inhibits restenosis after coronary angioplasty with stent implantation in the porcine model. The degree of reduction in neointimal formation was comparable to that achieved with drug-eluting stents.

Angioplasty, Balloon, Coronary↗
PubMed2004

Inhibition of restenosis in stented porcine coronary arteries: uptake of Paclitaxel from angiographic contrast media.

RATIONALE AND OBJECTIVES: Paclitaxel added to angiographic contrast medium (CM) has been shown to inhibit restenosis in the porcine coronary overstretch model. This study determined early local tissue concentrations after the administration of different paclitaxel doses and preparations. MATERIALS AND METHODS: Fifteen pigs received 2 stents each in the left coronary artery. During and/or after the intervention, paclitaxel-containing CM or diluted Taxol was injected. Fifteen minutes after the last intracoronary injection, paclitaxel concentrations in the arterial wall and myocardium were measured by high-performance liquid chromatography. RESULTS: Mean paclitaxel concentrations in the left coronary arteries reached 3-10 microM. Higher volumes and higher paclitaxel concentrations resulted in higher tissue concentrations. Paclitaxel in CM was better tolerated and led to higher local concentrations than diluted Taxol. Low paclitaxel concentrations in the uninjected right coronary artery and in plasma indicate selectivity. CONCLUSION: When admixed to CM, paclitaxel results in local tissue concentrations proportional to the amount of the drug injected.

Animals↗
PubMed2003

Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation.

OBJECTIVES: The present study was designed to test the efficacy of paclitaxel added to the contrast agent iopromide in the prevention of restenosis. BACKGROUND: Contrast media adhere to the coronary vessel wall for some seconds after injection. Such a layer of contrast agent could serve as a matrix for antiproliferative drugs. METHODS: Thirty-four stents were implanted into the left anterior descending and circumflex coronary arteries of 17 pigs, using a 1.2:1.0 overstretch ratio. The unsupplemented contrast agent iopromide-370 was used as a control; the treatment groups were treated with 80 ml intracoronary iopromide plus either 100 or 200 mumol/l paclitaxel, or 80 ml intravenous iopromide plus 200 mumol/l paclitaxel. Quantitative angiography and histomorphometry were used to assess comparable baseline parameters between the treatment groups. RESULTS: A short time incubation (3 min) almost completely inhibited vascular smooth muscle cell proliferation, sustained for up to 12 days. Whereas intravenous paclitaxel had no effect, intracoronary application of paclitaxel reduced the diameter stenosis from 55 +/- 13% to 29 +/- 18% and 13 +/- 12%. Late lumen loss dropped from 1.94 +/- 0.35 mm under the control condition to 1.19 +/- 0.55 mm with 100 mumol/l paclitaxel and to 0.82 +/- 0.54 mm with 200 mumol/l paclitaxel. Histomorphometry revealed a corresponding dose-dependent reduction of the neointimal area and restenosis by intracoronary iopromide paclitaxel. Assessment of left ventricular function and myocardial histology revealed no adverse effects of intracoronary paclitaxel application. CONCLUSIONS: This study provides evidence that intracoronary application of a taxane dissolved in a contrast medium profoundly inhibits in-stent restenosis. This novel, widely feasible approach may be suited for the prevention of restenosis in a broad spectrum of interventional treatment regimens.

Animals↗
PubMed2003

Laser-induced thermotherapy (LITT) of liver metastases: MR-guided percutaneous insertion of an MRI-compatible irrigated microcatheter system using a closed high-field unit.

PURPOSE: To evaluate the efficacy and safety of a new MRI-compatible irrigated laser microcatheter system for thermal ablation of liver metastases. MATERIAL AND METHODS: The new microcatheter system consists of a titanium needle with a diameter of 1.5 mm and a surrounding Teflon catheter with an outer diameter of 1.8 mm (5.5 F). In vitro laser-induced coagulation of bovine liver tissue was performed to determine the optimal perfusion rate of cooling saline flow, maximum laser energy, and ablation time. Laser-induced thermotherapy using the new microcatheter system, an Nd:YAG laser (Dornier), and a flexible laser light guide (Somatex GmbH, Berlin, Germany) was performed in 28 patients with liver metastases. Percutaneous insertion and positioning of multiple microcatheters in the lesion and monitoring of therapy was performed with a closed high-field MRI scanner using T1-weighted gradient-echo sequences during breath-hold. RESULTS: A perfusion rate of 0.75 mL/minute, a laser energy of 15 W, and an ablation time of 20 minutes were found suitable to achieve safe and sufficient ablation of metastatic tissue. The mean volume of induced coagulation in vitro was 23.9 mL. Ablation of liver metastases in patients was technically and clinically successful. CONCLUSION: The new microcatheter system allows for both catheter placement and monitoring of therapy using a single imaging modality. This shortens the procedure and enables more precise puncture and therapy of liver metastases. Due to the miniaturized design of the catheter and the real-time monitoring, the procedure is minimally invasive and very well tolerated by patients. This new technique seems to be a safe and feasible alternative in treating liver metastases.

Aged↗
PubMed2003

Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.

BACKGROUND: Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting. METHODS AND RESULTS: In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area. CONCLUSIONS: First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.

Animals↗
PubMed2003

No difference among modern contrast media's effect on neointimal proliferation and restenosis after coronary stenting in pigs.

RATIONALE AND OBJECTIVES: Recent clinical trials indicate that the choice of radiographic contrast media (CM) may influence the late outcome of coronary interventions. This might be explained by the different effects of various CM on neointimal proliferation. METHODS: The effect of a 1-hour incubation of bovine aortic smooth muscle cells in ioxaglate or iopromide solution on in vitro cell division was tested. Furthermore, in 12 pigs randomized into 3 groups (iopromide, ioxaglate, and iosimenol; a novel nonionic dimer), coronary angiography was performed followed by implantation of stents. After 28 days, restenosis was assessed by quantitative angiography and histomorphometry. RESULTS: Compared with saline, CM did no change cell counts up to 15 days after incubation. Baseline parameters in the pigs indicated no difference between the test groups. After 28 days, the test groups showed no significant differences in the parameters characterizing in-stent restenosis. CONCLUSIONS: Under the experimental conditions iopromide, ioxaglate, and iosimenol had no or very similar direct or otherwise mediated effect on cell proliferation and restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2003

Cytokine profiles after nonionic dimeric contrast medium injection.

RATIONALE AND OBJECTIVES: Mediators of contrast media (CM)-induced allergic/pseudoallergic side effects are largely unknown. We evaluated the possibility of cytokines released as surrogate markers for allergic/pseudoallergic responses in patients who tolerated CM injection well. MATERIALS AND METHODS: Interleukin-1beta (IL-1beta), -2, -4, -5, -6; tumor necrosis factor-alpha; plasma histamine level; and the anaphylatoxin C5a were measured by enzyme-linked immunosorbent assay technique in 9 patients who received the nonionic dimeric iodinated CM iotrolan under routine computed tomography examination conditions. Serum samples were collected before, 1 hour, 6 hours, and 24 hours after contrast medium injection. RESULTS: The cytokine values did not correlate with the hematocrit. Kinetic studies revealed a trend, although not statistically significant (P>0.05), for an early increase of IL-2 (1 hour after CM), followed by delayed increase of IL-4 and IL-6. Histamine significantly decreased after iotrolan injection and C5a increased 6 hours (P>0.05) after CM administration in parallel to IL-6. IL-1beta decreased (with the lowest value measured 6 hours after CM injection; P>0.05), and tumor necrosis factor-alpha did not show any tendency. Patients with late adverse reactions had a T helper 1 to T helper 2 shift and 24 hours after CM injection had the highest histamine values. CONCLUSION: The results suggest CM-related liberation of cytokines with a sequential T helper type 1 (IL-2 after 1 hour), and T helper type 2-like pattern (IL-4, -5, and -6).

Adult↗
PubMed2002

Acute cardiac tolerance of current contrast media and the new taxane protaxel using iopromide as carrier during porcine coronary angiography and stenting.

RATIONALE AND OBJECTIVES: The systemic tolerance thresholds of modern low-osmolar x-ray contrast media (CM) are similarly high, but their effects on the cardiovascular system and on the coagulation differ. The aim of this study was to comparatively evaluate the cardiovascular tolerability of iopromide, ioxaglate, and iosmin, and of a novel taxane protaxel, dissolved in iopromide, as a carrier, by coronary angiography and stenting. METHODS: Sixteen pigs were randomized into four groups: iosmin (350 mg iodine/mL, n = 4, nonionic dimer), iopromide (370 mg iodine/mL, n = 4, nonionic monomer), ioxaglate (320 mg iodine/mL, n = 4, ionic dimer), and 70-micromol protaxel dissolved in iopromide 370 mg iodine/mL, intended to prevent restenosis. Coronary angiography was performed via the left carotid artery followed by implantation of stents into the left anterior descending and the circumflex arteries. About 80 mL per animal was used in each group. RESULTS: There were no thrombotic complications and no significant adverse events of electrocardiography, blood pressure, or contractility during or after CM injections. There were no differences among the CM tested except that ioxaglate was the only agent showing a significant reduction in dp/dt after 50 seconds compared to iosmin. The values of preinjection parameters were most rapidly regained after iosmin, compared with other CM tested. CONCLUSIONS: The novel iso-osmolar nonionic CM iosmin is well tolerated in porcine coronary angiography and subsequent stenting. The cardiac tolerance of iopromide has not been adversely affected by addition of the cytostatic protaxel.

Animals↗