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1.
J Magn Reson Imaging ; 37(6): 1427-35, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23188773

ABSTRACT

PURPOSE: To compare diagnostic accuracy of multi-station, high-spatial resolution contrast-enhanced MR angiography (CE-MRA) of the lower extremities with digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial occlusive disease. MATERIALS AND METHODS: Of 485 consecutive patients undergoing a run-off CE-MRA, 152 patients (86 male, 66 female; mean age, 71.6 years) with suspected peripheral arterial occlusive disease were included into our Institutional Review Board approved study. All patients underwent MRA and DSA of the lower extremities within 30 days. MRA was performed at 1.5 Tesla with a single bolus of 0.1 mmol/kg body weight of gadobutrol administered at a rate of 2.0 mL/s at three stations. Two readers evaluated the MRA images independently for stenosis grade and image quality. Sensitivity and specificity were derived. RESULTS: Sensitivity and specificity ranged from 73% to 93% and 64% to 89% and were highest in the thigh area. Both readers showed comparable results. Evaluation of good and better quality MRAs resulted in a considerable improvement in diagnostic accuracy. CONCLUSION: Contrast-enhanced MRA demonstrates good sensitivity and specificity in the investigation of the vasculature of the lower extremities. While a minor investigator experience dependence remains, it is standardizable and shows good inter-observer agreement. Our results confirm that the administration of Gadobutrol at a standard dose of 0.1 mmol/kg for contrast-enhanced runoff MRA is able to detect hemodynamically relevant stenoses. Use of contrast-enhanced MRA as an alternative to intra-arterial DSA in the evaluation and therapeutic planning of patients with suspected peripheral arterial occlusive disease is well justified.


Subject(s)
Angiography, Digital Subtraction/statistics & numerical data , Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/epidemiology , Lower Extremity/blood supply , Magnetic Resonance Angiography/statistics & numerical data , Organometallic Compounds , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/epidemiology , Aged , Contrast Media , Female , Humans , Lower Extremity/diagnostic imaging , Lower Extremity/pathology , Male , Prevalence , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Switzerland/epidemiology
2.
Eur J Pharm Biopharm ; 80(3): 562-70, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22209978

ABSTRACT

First generation drug eluting stents (DES) show a fivefold higher risk of late stent thrombosis compared to bare metal stents. Therefore, new biodegradable and biocompatible polymers for stent coating are needed to reduce late stent thrombosis. In this study, a reproducible spray-coating process for stents coated with Poly(ethylene carbonate), PEC, and Paclitaxel was investigated. PEC is a biocompatible, thermoelastic polymer of high molecular weight. The surface degradation of PEC is triggered by superoxide anions produced by polymorphonuclear leukocytes and macrophages during inflammatory processes. Stents with different drug loading were reproducibly produced by a spray-coating apparatus. Confocal laser scanning micrographs of fluorescent dye loaded stents were made to investigate the film homogeneity. The abluminal stent site was loaded more than the luminal site, which is superior for DES. The deposition of the layers was confirmed by TOF-SIMS investigations. Referring to the stent surface, the drug loading is 0.32 µg (± 0.05) (once coated), 0.53 µg (± 0.11) (twice coated), or 0.73 µg (± 0.06) (three times coated) Paclitaxel per mm(2) stent surface. The in vitro release mechanism during non-degradation conditions can be explained by diffusion-controlled drug release slightly influenced by swelling of PEC, revealing that 100% of the loaded Paclitaxel will be released via diffusion within 2 months. So, the in vivo release kinetic is a combination of diffusion-controlled drug release and degradation-controlled drug release depending on the presence or absence of superoxide anions and accordingly depending on the presence or absence of macrophages. We conclude that the specific release kinetics of PEC, its biocompatibility, and the favorable mechanical properties will be beneficial for a next generation drug eluting stent meriting further investigations under in vivo conditions.


Subject(s)
Coated Materials, Biocompatible/chemistry , Drug-Eluting Stents , Polyethylenes/chemistry , Polymers/chemistry , Absorbable Implants , Delayed-Action Preparations , Diffusion , Drug Carriers/chemistry , Ethylene Oxide/chemistry , Excipients/chemistry , Kinetics , Paclitaxel/chemistry , Thrombosis/chemically induced
3.
Herz ; 34(6): 485-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19784568

ABSTRACT

In patients with arrhythmogenic right ventricular dysplasia (ARVD), the right ventricular myocardium histologically discloses atrophy paralleled by fibrofatty or fatty replacement. Apoptosis is believed to be a putative major pathogenetic mechanism. Altogether, our knowledge of genetics, etiology and pathophysiology of ARVD has increased impressively in the last few years, and effective genetic tests now principally would be possible. Nevertheless, due to often uncharacteristic or even lacking symptoms, clinical diagnosis may be very difficult and could not be made during lifetime of patient presented here, partly due to additional, independent cardiac problems. The question of an effective preoperative diagnostic regimen for cardiosurgical interventions remains and seems to be currently open.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Arrhythmogenic Right Ventricular Dysplasia/etiology , Cardiac Surgical Procedures/adverse effects , Arrhythmogenic Right Ventricular Dysplasia/prevention & control , Fatal Outcome , Humans , Male , Middle Aged
5.
Digestion ; 79(3): 137-42, 2009.
Article in English | MEDLINE | ID: mdl-19307736

ABSTRACT

BACKGROUND: To assess prospectively the safety and efficacy of Yttrium-90 microspheres in patients with unresectable liver metastases from neuroendocrine tumors. MATERIALS AND METHODS: Microspheres were administered via a temporarily placed hepatic catheter. Patients were monitored prospectively. All patients were followed with laboratory and imaging studies at regular intervals to determine response rates. Toxicity and quality of life scores were measured. RESULTS: Nine patients (7 female) with a mean age of 58.8 years were enrolled in this prospective trial. The mean tumor load was 58.8%. The estimated percentage shunting to the lungs on MAA scans was 5.04 +/- 2.4%. Visceral artery embolization of extrahepatic arteries before treatment was performed in 6 patients. The median dose of microspheres was 2.1 +/- 0.4 GBq. A total of 12 therapy sessions was performed. The mean follow-up was 21.7 months. Technical success was 100%. No major complications occurred. Survival rates were 100, 57 and 57% for 1, 2 and 3 years, respectively. Three months after SIRT therapy partial response (PR) was seen in 6 patients (66%). Calculated reduction of liver metastasis volume was 49%. In 3 patients (33%) stable disease was seen with a calculated tumor reduction of 13%. The estimated time to progression was 11.1 months. CONCLUSION: Radioembolization with (90)Y microspheres is safe and produces high response rates even with extensive tumor replacement for up to 1 year. Acute and late toxicity was very low. Further investigations compared with other local ablative techniques is warranted.


Subject(s)
Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/radiotherapy , Yttrium Radioisotopes/administration & dosage , Adult , Aged , Citrates/administration & dosage , Embolization, Therapeutic/methods , Female , Humans , Male , Microspheres , Middle Aged , Organometallic Compounds/administration & dosage , Quality of Life , Treatment Outcome
6.
Radiology ; 248(3): 852-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18710979

ABSTRACT

PURPOSE: To determine exemplarily the amount of DNA damage and the repair kinetics after interventional radiologic procedures by using visualization of foci of the phosphorylated form of the H2AX histone variant (gammaH2AX) to quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty (PTA) of the lower limb arteries. MATERIALS AND METHODS: After local ethics committee approval and written informed consent were obtained, five patients (two women, three men; mean age, 64.4 years; age range, 45-76 years) scheduled for computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5 years; age range, 53-85 years) scheduled for PTA of lower limb arteries were prospectively entered into the study. Blood samples were taken before the first exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after the last exposure. Additional samples were taken from the irradiated limb (femoral vein) of three patients who underwent PTA--before the first radiation exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last exposure. Lymphocytes were isolated, fixed, and stained with anti-gammaH2AX antibody, and gammaH2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests. RESULTS: Mean increase in number of gammaH2AX foci after CT (7.78 per 1 Gy x cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of gammaH2AX foci per cell increased by factors of 4.08-20.67 in blood samples taken 5 minutes after PTA compared with mean numbers of foci before PTA. Mean radiation dose increase, 6.56/(10 Gy x cm(2)), depended linearly on dose-area product (r = 0.993). Maximal focus yield in cells taken directly from the irradiated limb was higher than that in cells from the systemic circulation (by mean factor of 1.46). Data showed compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24 hours (0.07 focus per cell) was significantly higher than mean number of foci in cell background (0.04 focus per cell, P < .05). CONCLUSION: GammaH2AX focus formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB repair capacity is compromised in patients who undergo PTA of lower limb arteries.


Subject(s)
Angiography/adverse effects , Angioplasty, Balloon/adverse effects , Arteries/radiation effects , Arteries/surgery , DNA Damage , DNA Repair/radiation effects , Radiography, Interventional/adverse effects , Aged , Female , Humans , Lower Extremity/blood supply , Lower Extremity/diagnostic imaging , Lower Extremity/surgery , Male , Middle Aged , Tomography, X-Ray Computed/adverse effects
8.
Cardiovasc Intervent Radiol ; 31(3): 629-32, 2008.
Article in English | MEDLINE | ID: mdl-18060456

ABSTRACT

This report describes a technique for advanced endoluminal reconstruction of complex bifurcational arterial obstructions located within the mesenteric arcade deploying applications from percutaneous transluminal coronary artery angioplasty. A patient was treated for persistent mesenteric ischemia during prolonged recovery after initial small bowel resection due to acute mesenteric ischemia. Following endovascular reconstruction of a complex arterial obstruction within the mesenteric arcade, ischemic symptoms subsided quickly and the patient recovered well. According to the literature, this seems to be the first case where such distal reconstruction of the mesenteric arcade has successfully been achieved percutaneously.


Subject(s)
Angioplasty/instrumentation , Intestines/blood supply , Ischemia/etiology , Mesenteric Vascular Occlusion/diagnostic imaging , Mesenteric Vascular Occlusion/surgery , Stents , Aged , Angioplasty/methods , Follow-Up Studies , Humans , Ischemia/diagnostic imaging , Ischemia/surgery , Male , Mesenteric Arteries , Mesenteric Vascular Occlusion/complications , Prosthesis Design , Radiography, Interventional , Risk Assessment , Severity of Illness Index , Treatment Outcome , Vascular Patency/physiology
9.
J Vasc Interv Radiol ; 18(7): 909-13, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17609453

ABSTRACT

Percutaneous computed tomographic (CT) fluoroscopy-guided biopsy was performed to evaluate an intracardiac tumor located within the left atrium of a 72-year-old woman. Postinterventional follow-up was unproblematic and free of complications. Histopathologic examination revealed a high-grade cardiac sarcoma, and the patient underwent consecutive resection and radiation therapy. In general, percutaneous puncture of the heart must be considered hazardous. Under certain conditions (eg, broad-based tumor, advanced luminal mass, myocardial and/or pericardial infiltration), however, percutaneous CT-guided biopsy may be an appropriate alternative to transluminal catheter biopsy for the minimally invasive investigation of cardiac tumors.


Subject(s)
Biopsy/methods , Heart Atria/diagnostic imaging , Heart Atria/pathology , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/pathology , Radiography, Interventional , Sarcoma/diagnostic imaging , Sarcoma/pathology , Aged , Combined Modality Therapy , Contrast Media , Diagnosis, Differential , Female , Fluoroscopy , Heart Neoplasms/therapy , Humans , Punctures , Sarcoma/therapy , Tomography, X-Ray Computed
10.
Radiology ; 244(2): 457-63, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17562809

ABSTRACT

PURPOSE: To prospectively evaluate the safety and effectiveness of high doses of 1 mol/L gadobutrol as a contrast agent for computed tomography (CT). MATERIALS AND METHODS: Experiments were performed according to guidelines for care of laboratory animals. The local animal care committee approved the study protocol. Unenhanced and contrast material-enhanced CT images of the chest and abdomen were obtained randomly in nine domestic pigs. Gadobutrol was injected (1, 2, or 3 mL per kilogram of body weight; three pigs for each dose). Attenuation was measured in different vascular and parenchymal structures. Changes in blood chemistry and hematologic parameters were monitored before and 1, 2, 3, and 7 days after gadobutrol administration. Urine samples were evaluated before and 7 days after gadobutrol administration. Technetium 99m mertiatide renal scintigraphy was performed before and 7 days after contrast medium injection. Animals were sacrificed 7 days after contrast medium administration, and one kidney was removed from each animal for examination with light microscopy. No serious adverse events occurred. A mixed-model nested analysis of variance was used for statistical evaluation. RESULTS: Mean attenuations for the 1, 2, and 3 mL/kg gadobutrol doses, respectively, were 148 HU +/- 20 (standard deviation), 282 HU +/- 18, and 289 HU +/- 20 in the thoracic aorta; 99 HU +/- 11, 166 HU +/- 9, and 153 HU +/- 18 in the kidneys; and 106 HU +/- 7, 186 HU +/- 18, and 224 HU +/- 24 in the inferior vena cava. No clinically relevant changes in hematologic, blood chemistry, or urine analysis results were detected. Markers for glomerular filtration and tubular function were unaffected in all groups. Scintigraphy revealed no differences between unenhanced and contrast-enhanced results. No morphologic changes of the renal parenchyma were found at histologic analysis. CONCLUSION: Contrast-enhanced CT with a 2 or 3 mmol/kg dose of 1 mol/L gadobutrol resulted in excellent vascular and parenchymal enhancement. A gadobutrol dose of up to 3 mL/kg did not affect renal function.


Subject(s)
Contrast Media/pharmacokinetics , Kidney/metabolism , Organometallic Compounds/pharmacokinetics , Renal Circulation , Tomography, Spiral Computed , Analysis of Variance , Animals , Contrast Media/administration & dosage , Injections , Kidney/diagnostic imaging , Organometallic Compounds/administration & dosage , Prospective Studies , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Random Allocation , Swine , Technetium Tc 99m Mertiatide/administration & dosage
11.
J Control Release ; 119(1): 41-51, 2007 May 14.
Article in English | MEDLINE | ID: mdl-17346845

ABSTRACT

Catheter-based local delivery of biodegradable nanoparticles (NP) with sustained release characteristics represents a therapeutic approach to reduce restenosis. Paclitaxel-loaded NP consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) (PVA-g-PLGA) with varying PLGA chain length as well as poly(lactide-co-glycolide) (PLGA), were prepared by a solvent evaporation technique. NP of <180 nm in diameter characterized by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) are spherical and show smooth surfaces. Yields typically range from 80 to 95% with encapsulation efficiencies between 77 and 87%. The extent of initial in vitro paclitaxel release was affected by the PVA-g-PLGA composition. Blank nanoparticles from PVA(300)-g-PLGA(30) and PVA(300)-g-PLGA(15) showed excellent biocompatibility in rabbit vascular smooth muscle cells (RbVSMC) at polymer concentrations of 0.37 mg/ml. Paclitaxel-loaded NP have an increased antiproliferative effect on cells in comparison to free drug. Confocal laser scanning microscopy of RbVSMC confirmed cellular uptake of nanoparticles composed of fluorescently labeled PVA(300)-g-PLGA(15) loaded with Oregon Green labeled paclitaxel. Cells showed a clearly increased fluorescence activity with a co-localization of paclitaxel and polymer nanoparticles during incubation with particle suspension. To evaluate the antirestenotic effect in vivo, paclitaxel-loaded nanoparticles were administered locally to the wall of balloon-injured rabbit iliac arteries using a porous balloon catheter. As a result a 50% reduction in neointimal area in vessel segments treated with paclitaxel-loaded nanoparticles compared to control vessel segments could be observed (local paclitaxel nanoparticle treated segments 0.80+/-0.19 mm(2), control segments 1.58+/-0.6 mm(2); p<0.05).


Subject(s)
Constriction, Pathologic/drug therapy , Drug Delivery Systems/methods , Lactic Acid/administration & dosage , Nanoparticles/administration & dosage , Paclitaxel/administration & dosage , Polyglycolic Acid/administration & dosage , Polymers/administration & dosage , Animals , Cells, Cultured , Constriction, Pathologic/metabolism , Graft Occlusion, Vascular/drug therapy , Graft Occlusion, Vascular/metabolism , Iliac Artery/drug effects , Iliac Artery/metabolism , Lactic Acid/pharmacokinetics , Male , Paclitaxel/pharmacokinetics , Polyglycolic Acid/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/pharmacokinetics , Rabbits
12.
Endocr Relat Cancer ; 13(4): 1203-11, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17158765

ABSTRACT

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.


Subject(s)
Carcinoid Tumor/diagnostic imaging , Neuroendocrine Tumors/diagnostic imaging , Receptor, Cholecystokinin B/metabolism , Receptors, Somatostatin/metabolism , Adult , Aged , Diagnosis, Differential , Female , Glucagonoma/diagnostic imaging , Humans , Indium Radioisotopes , Insulinoma/diagnostic imaging , Male , Middle Aged , Neuroendocrine Tumors/metabolism , Octreotide/analogs & derivatives , Paraganglioma/diagnostic imaging , Pentetic Acid/analogs & derivatives , Prognosis , Radionuclide Imaging , Radiopharmaceuticals
13.
Vet Anaesth Analg ; 32(5): 308-13, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16135212

ABSTRACT

OBJECTIVE: Evaluation of the LMA-ProSeal for positive pressure ventilation (PPV) in the pig. STUDY DESIGN: Prospective observational study. ANIMALS: Twelve German country pigs, weighing 25-62 kg. METHOD: Lungs of pigs were mechanically ventilated under general anaesthesia using the LMA-ProSeal. The ease of insertion, number of attempts and total time until placement of the LMA-ProSeal and gastric tube were recorded. Bronchoscopy was performed to determine the position of the LMA-ProSeal and to detect signs of aspiration. Ventilation variables and the leak airway pressure (P(leak)) were measured. An arterial blood gas sample was taken to determine the adequacy of ventilation. RESULTS: The airway was secured in all pigs within 39 +/- 19 seconds (27-51). Different sizes of LMA-ProSeal were used; up to 30 kg: size 3, up to 43 kg: size 4; and above 43 kg: size 5. In all but one animal the P-LMA and gastric tube were inserted at the first attempt. In nine animals gastric fluid was drained through the gastric tube. There was no evidence of aspiration in any animal. The mean [+/-SD (95%CI)]P(leak) was 28.8 +/- 7.5 cm H(2)O (24.06-33.60) and normal ventilation was achieved in all animals. CONCLUSIONS: The results of this study indicate that the airway of pigs weighing 25-62 kg can be secured safely and reliably with the sizes 3, 4 and 5 LMA-ProSeal. CLINICAL RELEVANCE: Endotracheal intubation in pigs can be difficult so there is a risk of hypoxemia in the apnoeic animal. With the LMA-ProSeal the airway can be secured rapidly, safely and reliably. Use of the Standard-LMA under PPV can be associated with gas leakage into the stomach and the subsequent risk of gastric distension and regurgitation. Both the ability to drain the stomach and the high P(leak) of the LMA-ProSeal could contribute to improved protection against aspiration under PPV.


Subject(s)
Anesthesia, General/veterinary , Animals, Laboratory/physiology , Laryngeal Masks/veterinary , Respiration, Artificial/veterinary , Swine/physiology , Animals , Equipment Design , Male , Pilot Projects , Prospective Studies , Respiration, Artificial/instrumentation
14.
Cardiovasc Intervent Radiol ; 28(3): 331-7, 2005.
Article in English | MEDLINE | ID: mdl-15886949

ABSTRACT

PURPOSE: To evaluate the efficacy of NF-kappa B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. MATERIALS AND METHODS: In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-kappa B in two different concentrations (1 mug: n = 14; 10 mug: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. RESULTS: NF-kappa B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF-kappa B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm(2) using 1 mug NF-kappa B ODN compared to 0.98 mm(2) in the control group. The higher dose resulted in a neointimal area of 0.97 mm(2) compared to 1.07 mm(2) at the control side. CONCLUSIONS: Local drug delivery of NF-kappa B ODN using the "channeled balloon" catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.


Subject(s)
Angioplasty, Balloon , Arterial Occlusive Diseases/prevention & control , Catheterization , Iliac Artery/drug effects , Oligodeoxyribonucleotides/administration & dosage , Animals , Arterial Occlusive Diseases/pathology , Arterial Occlusive Diseases/therapy , Catheterization/instrumentation , Cell Proliferation/drug effects , Cells, Cultured , Constriction, Pathologic/pathology , Constriction, Pathologic/prevention & control , Drug Delivery Systems , Hyperplasia , Iliac Artery/pathology , Male , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Rabbits , Random Allocation , Tunica Intima/drug effects , Tunica Intima/pathology
15.
Eur J Pharm Biopharm ; 58(1): 161-8, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15207550

ABSTRACT

Catheter-based local delivery of drug loaded nanoparticles agents offers a potential therapeutic approach to reducing restenosis. However, high delivery pressures and large volumes of infusates may cause severe vascular damage and increase intimal thickening. Therefore, we investigated the penetration pattern and vessel wall integrity of fluorescence-labelled nanoparticles (217 nm in diameter) into the non-atherosclerotic aorta abdominalis of New Zealand white rabbits in dependence of the volume (2.5 and 5 ml) and concentration (0.5 and 1 mg/ml) of the nanoparticle suspension, as well as the infusion pressure (2 and 4 atm) using a channelled balloon catheter (SCIMED REMEDY model RC 20/2.5). The location and penetration characteristics of nanoparticles in the arterial vessel wall were visualized using confocal laser scanning microscopy and transmission electron microscopy (TEM). Catheter design and infusion pressure form a radial particle stream through intima and media into the adventitial layer of the aorta abdominalis. Infusion pressures of 4 atm in combination with high particle concentrations lead to effective nanoparticle delivery without severe vessel wall disruptions. Endothelium of the treated vessel segments was slightly affected during catheter insertion showing partly denudation of the innermost cell layer. TEM micrographs underlines transport functional properties of the vasa vasorum inside the vessel wall. Consequently, local delivery efficiency of nanoparticulate carriers is critically affected by infusion pressure, and concentration of carrier suspensions. These factors need to be taken into consideration for the design of in vivo experiments.


Subject(s)
Aorta, Abdominal/drug effects , Catheterization/methods , Drug Delivery Systems/methods , Nanostructures , Animals , Aorta, Abdominal/metabolism , Aorta, Abdominal/ultrastructure , Catheterization/instrumentation , Drug Delivery Systems/instrumentation , Male , Rabbits
16.
Atherosclerosis ; 172(1): 71-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14709359

ABSTRACT

BACKGROUND: Efficient local gene or drug therapy requires optimized application modalities to avoid vessel damage, which might lead to increased neointimal hyperplasia. Aim of the study was to evaluate different application parameters for local delivery using the channeled balloon catheter in order to minimize vessel trauma induced by local application. METHODS AND RESULTS: Sixty cholesterol fed rabbits were randomly enrolled into twelve groups of different local application parameters: group I, application pressure 2atm/application volume 1ml physiologic saline; group II, 2atm/2ml; group III, 2atm/5ml; group IV, 4atm/1ml; group V, 4atm/2ml; group VI, 4atm/5ml. The other six groups received Ringer's solution instead of saline. Administration of the solution was randomly performed in one iliac artery using the channeled balloon catheter with simultaneous balloon angioplasty (8atm). The contralateral iliac artery served as a control and was treated with balloon angioplasty only. Four weeks after local therapy, calibrated angiography was performed; the animals were sacrificed, vessel segments were excised and quantitative morphometric measurements were obtained. In none of the animals acute complications, e.g. dissection, thrombosis or perforation of the vessel, was noted. Up to an application pressure of 4atm and an application volume of 5ml, no significant neointima formation was seen compared to arteries which underwent angioplasty only. Additionally, no significant differences between saline and Ringer's solution were detected. In a multivariate analysis, neither application pressure nor volume were found to have a statistically significant influence on the amount of neointimal hyperplasia. CONCLUSIONS: Local application of "drugs" using the channeled balloon catheter is safe and feasible without significant induction of neointimal hyperplasia compared to angioplasty, if an application volume of 5ml and a pressure of 4atm is not exceeded.


Subject(s)
Drug Delivery Systems/methods , Tunica Intima/pathology , Angiography , Angioplasty, Balloon , Animals , Catheterization , Drug Delivery Systems/adverse effects , Hypercholesterolemia/pathology , Hyperplasia , Iliac Artery , Male , Multivariate Analysis , Rabbits , Random Allocation
17.
Tech Vasc Interv Radiol ; 6(1): 6-13, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12772124

ABSTRACT

Percutaneous mechanical thrombectomy is an established method in interventional radiology and refers to the removal of acute embolic or thrombotic occlusive material in arteries, veins, or vascular grafts using percutaneous transluminal methods. However, initial complete removal of occlusive material can be achieved only in a minority of patients. The amount of removed material varies with the age and composition of the occlusive material. To achieve sufficient revascularization, adjunctive use of a variety of percutaneous endovascular recanalization techniques is necessitated. Additional treatment with local intra-arterial fibrinolysis, balloon angioplasty, stent implantation, endoluminal atherectomy, and other measures results in primary technical success rates of 70% to 100% for revascularization of acutely occluded vessels. The above-mentioned different techniques should not be viewed as competitive treatment modalities, rather a synergistic approach should be offered. The aim of this report is to review different adjunctive techniques in percutaneous mechanical thrombectomy with emphasis on techniques, mechanisms of action, experimental and clinical results, potential complications, and their potential role in view of clinical pathways to treat acute limb ischemia.


Subject(s)
Ischemia/therapy , Thrombectomy/methods , Venous Thrombosis/therapy , Algorithms , Angioplasty, Balloon , Atherectomy , Combined Modality Therapy , Fibrinolytic Agents , Humans , Leg/blood supply , Radiology, Interventional , Stents , Thrombectomy/instrumentation , Ultrasonic Therapy
18.
Invest Radiol ; 38(4): 193-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12649642

ABSTRACT

RATIONALE AND OBJECTIVES: To evaluate prospectively the efficacy of gadobutrol as contrast agent for computed tomography (CT) compared with iodinated contrast media in a porcine animal model. METHODS: In 8 domestic pigs (35 +/- 4 kg body weight [BW]), continuous spiral CTs of the chest and abdomen were performed using either 2 mmol/kg BW Gadovist 1.0 (1 mol/L gadobutrol) intravenously or Ultravist (300 mg I/mL iopromide) (slice 5 mm, table feed 7.5 mm, reconstruction increment 5 mm). One week later, the same animals were examined using the same protocol with the other contrast agent. In 2 additional animals, serial CTs were performed at the same level using gadobutrol or iopromide on day 1 and the alternate agent on day 8 inches order to determine contrast media kinetics, peak enhancement, and time enhancement-product in important vascular regions and parenchymal organs (abdominal aorta, inferior vena cava, liver, and renal parenchyma). Peak enhancement (net increase compared with nonenhanced baseline values) was measured in Hounsfield units (HU) in defined regions of interest. RESULTS: In vivo, the mean peak enhancement 5, 15, 30, and 120 seconds in the abdominal aorta after injection of 2 mL/kg BW gadobutrol and iopromide was 200 +/- 11, 224 +/- 10, 261 +/- 13, and 95 +/- 9 HU versus 232 +/- 10, 298 +/- 10, 152 +/- 11, and 123 +/- 10 HU, respectively. Differences in enhancement of vascular structures was statistically significant (P < 0.05) in carotid arteries (235 +/- 20 HU for gadobutrol and 264 +/- 19 HU for iopromide) and the aortic arch (261 +/- 14 HU for gadobutrol and 279 HU +/- 13 HU for iopromide). No statistical significance was seen in all other measured vascular structures and parenchymal organs. CONCLUSION: Contrast-enhanced CT with 1 mol/L gadobutrol in a dose of 2 mmol/kg BW resulted in an excellent vascular and parenchymal enhancement in most vascular regions and parenchymal organs similar to an equivalent volume of 300 mg/mL iodinated contrast media.


Subject(s)
Contrast Media , Iohexol/analogs & derivatives , Organometallic Compounds , Tomography, X-Ray Computed , Animals , Gadolinium , Image Enhancement , Male , Swine
19.
AJNR Am J Neuroradiol ; 23(9): 1485-92, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12372736

ABSTRACT

BACKGROUND AND PURPOSE: MR sialography has become an alternative imaging technique for ductal salivary gland diseases. We compared the diagnostic accuracies of MR sialography and digital subtraction sialography in patients with successful completion of both examinations and benign salivary gland disorders. METHODS: In a prospective study, we attempted to examine salivary glands in 80 patients with clinically suspected diagnoses of sialadenitis and/or sialolithiasis. Each patient underwent digital subtraction sialography and MR sialography. MR sialography was obtained with a T2-weighted single-shot turbo spin-echo sequence (TR/TE 2800/1100 msec, acquisition time 7 seconds), with use of a quadrature head coil. Final diagnoses were confirmed by clinical follow-up and results of biopsy (n = 9) or surgery (n = 19). RESULTS: Failure rate was 5% (four of 80) for MR sialography and 14% (11 of 80) for digital subtraction sialography. Eighty-one salivary glands (48 parotid, 33 submandibular) in 65 patients were successfully visualized with both modalities. MR sialography depicted the main ductal system and first- and second-order branches, whereas digital subtraction sialography was able to depict third-order branches. Sensitivity and specificity to diagnose chronic sialadenitis were 70% and 98% with MR and 96% and 100% with digital subtraction sialography. MR sialography enabled diagnosis of sialolithiasis with a sensitivity of 80% and a specificity of 98% versus 90% and 98% for each with digital subtraction sialography. CONCLUSION: MR sialography with a heavily T2-weighted sequence is highly successful in the noninvasive visualization of the ductal system of major salivary glands. It is useful for diagnosing sialolithiasis and sialadenitis. Digital subtraction sialography, an invasive technique, had a substantial procedural failure rate, particularly for the submandibular duct. However, because of its higher spatial resolution, successfully completed digital subtraction sialography achieved superior diagnostic information compared with that of MR sialography.


Subject(s)
Magnetic Resonance Imaging , Radiographic Image Enhancement , Salivary Gland Diseases/diagnosis , Sialography , Subtraction Technique , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Parotid Gland/diagnostic imaging , Parotid Gland/pathology , Predictive Value of Tests , Prospective Studies , Salivary Gland Calculi/diagnosis , Salivary Gland Calculi/diagnostic imaging , Salivary Gland Diseases/diagnostic imaging , Sensitivity and Specificity , Sialadenitis/diagnosis , Sialadenitis/diagnostic imaging , Submandibular Gland/diagnostic imaging , Submandibular Gland/pathology
20.
Invest Radiol ; 37(7): 399-404, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12068162

ABSTRACT

RATIONALE AND OBJECTIVES: To evaluate a dose dependent inhibitory effect of paclitaxel to assess a possible local application for biliary tract malignancies in conjunction with stent placement. METHODS: Cell cultures of the three different cell types (human epithelial gallbladder cells [HEGC], human fibroblasts [HF; PA 314 wt] and pancreatic carcinoma cells [PC; P181]) were incubated for 20 minutes at 37 degrees C with increasing doses of paclitaxel (1.0 x 10(-4) - 1.0 x 10(2) micromol). Half of the cultures were then incubated without paclitaxel, the other half with paclitaxel for 20 minutes, 24 hours, or 72 hours. Cell proliferation was detected by photometric measurements of mitochondrial dehydrogenase activity (MTT assay). RESULTS: Incubation of cell cultures with paclitaxel resulted in a dose dependent and cell specific inhibition of cell proliferation. Concentrations of 1.0 x 10(-4) (and higher) paclitaxel for 20 minutes resulted in a inhibition of cell proliferation of HEGC (28%), PA (26%), and HF (17%). A prolonged paclitaxel incubation (up to 72 hours) resulted in an inhibitory effect on cell proliferation of HEGC (40%), PA (45%), and HF (39%). Cytotoxic effects, manifested by development of vacuoles and damage of cell integrity were seen at concentrations above 1.0 x 10(1) for both the short and long term incubation. CONCLUSIONS: Paclitaxel incubation resulted in a dose dependent inhibition of cell proliferation of human epithelial gallbladder cells, human fibroblasts and pancreatic carcinoma cells. This inhibitory effect of paclitaxel on the cell lines could serve as the basis to develop drug coated or drug eluting stents for malignant biliary strictures.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Paclitaxel/pharmacology , Stents , Bile Duct Neoplasms/drug therapy , Cell Division/drug effects , Cell Line , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Humans , In Vitro Techniques , Tumor Cells, Cultured/drug effects
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