PubMed Health⌕ Search

Biomedical subjects

Heiko Alfke

Publications and source records attributed to Heiko Alfke.

At least 19 recordsLinked to original sources

Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.

PURPOSE: There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects. METHODS: Biodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of (131)I and (99m)Tc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, (99m)Tc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration. RESULTS: NIS-expressing neuroendocrine tumors strongly accumulated (131)I and (99m)Tc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of (131)I or (99m)Tc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of (99m)Tc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of (99m)Tc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons. CONCLUSIONS: NIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.

Animals↗

Manifestations of hereditary hemorrhagic telangiectasia in children and adolescents.

The medical literature provides little information on manifestations of hereditary hemorrhagic telangiectasia (HHT) in children. The presented investigation was initiated to analyze early presenting symptoms in HHT, which should help to make the diagnosis at a young age and thus prevent potential complications from occult visceral arteriovenous malformations (AVM), which have commonly been described in HHT. A series of 15 children and adolescents with a suspicious diagnosis of HHT were examined clinically for typical signs and symptoms of the disorder. If the diagnosis of HHT seemed to be likely, recommendations for non-invasive screening procedures were given. Screening was directed at the detection of occult visceral AVMs. Main outcome measures were the definition of principal signs of HHT in children and adolescents. Family history was positive for HHT in 13 persons. The principal sign of recurrent epistaxis was present in 10/15 individuals and the earliest age of onset with regard to epistaxis was 4 years. Cutaneous vascular lesions were present in 5/15 patients. Screening for AVMs was performed in six individuals and revealed vascular lesions of the brain in two patients and vascular lesions of the lung in two patients. Gastrointestinal hemorrhages were present in one infant. Based on these findings, diagnosis of HHT seemed likely in ten individuals and unlikely in five individuals. Signs and symptoms of HHT in children and adolescents may be discrete, but are detectable at an earlier age than previously thought. Clinical examinations in children from HHT families may help identify candidates who will benefit from molecular genetic testing or screening imaging studies.

Adolescent↗

Volumetric analysis of mice lungs in a clinical magnetic resonance imaging scanner.

Small animal models are widely used to study various pathologies. Magnetic resonance imaging (MRI) allows investigation of these animals in a non-invasive way. Therefore, the aim of our study was to develop and evaluate a low-cost approach to measure lung volumes in small animal MRI using a clinical scanner and a specially designed RF coil. Five mice (three of an established emphysema model and two controls) were investigated in a 1.0-T clinical scanner using a specially built small animal saddle coil and three different three-dimensional sequences; overall imaging time was approximately 16 min. Lung volumes were calculated from these images using an interactive watershed transform algorithm for semi-automatic image segmentation. The gold standard for the volume measurement was water displacement after surgical explantation. MRI measured volumes correlated significantly with ex vivo measurements on the explanted lungs (r = 0.99 to 0.89; p < 0.05). Mean lung volume in emphysema model mice was larger than in controls. High-resolution, small animal MRI using a clinical scanner is feasible for volumetric analysis and provides an alternative to a dedicated small animal scanner.

Animals↗

Treatment of benign tracheal stenosis utilizing self-expanding nitinol stents.

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated.

Adult↗

[MR-Imaging of lower leg muscle perfusion].

PURPOSE: This article describes the potential of dynamic contrast- enhanced magnetic resonance tomography (DCE-MRT) for the visualization and quantification of blood flow of lower leg muscles at rest and after individually adjusted muscular exercise. PATIENTS AND METHODS: Five cases were chosen to exemplify the qualitative and semi-quantitative blood flow evaluation in the lower leg muscles. The crural muscle state was determined with an isometric maximal strength measurement from a female patient with peripheral arterial occlusive disease (pAVK), a male patient with coronary heart disease (KHK) without clinical signs of a pAVK, a volunteer with sufficient physical activity in accordance with the Freiburg Questionnaire of Physical Activity and two professional athletes. After calibration of the plantarflexion ergometer MR-PEDALO (Figures 2a and 2b) for the execution of auxotonic muscle work a 1- minute alternating foot extension and flexion exercise on MRPEDALO was performed in the MR machine. Instead of the lower leg splint shown in Figures 2a and 2b the MR coil fits exactly in MR-PEDALO used for DCE-MRT. Mechanical work performed during the 1-minute exercise ranged from 52 watt seconds (Ws) to 244 Ws (0.65 W to 4.07 W), indicating similar interindividual work loads in relation to the individual maximum isometric strength. DCE-MRT was performed at rest and immediately after auxotonic exercise test (T1w 2DFLASH- GE sequence with TR/TE/alpha: 100 ms/6 ms/70 degrees; field of view: 400; matrix: 81 x 256; slice thickness: 10 mm; acquisitions: 73 at 8.3 s each; total examination time: 9.24 min; bolus application of Magnevist, Schering, 0.02 ml/kg kg, 20 ml bolus NaCl, flow 2 ml/s, 22G cannula in a cubital vein). Signal intensity (SI) curves were analyzed with DynaVision (MeVis gGmbH, Bremen, Germany). RESULTS: Measuring peripheral blood flow needs appropriate muscular stress tests. The SI-curves of the region of interest (ROI) representing the peroneus, tibialis anterior and gastrocnemius muscle run almost parallel at rest. Workloads between 52 Ws and 244 Ws (0.65 W and 4.07 W), similar in relation to the individual maximum isometric strength, induce distinctive changes of the upslope, wash-in, peak and washout of SI-curves preferably for the peroneus muscle and less predominant also for the tibialis anterior muscle and gastrocnemius muscle respectively. The first case, a 55-year-old female patient with peripheral arterial occlusive disease (pAVK) stage Fontaine IIb before (Figure 3a) and after (Figure 3b) percutaneous transluminal angioplasty (PTA) of a right femoral artery stenosis shows after interventional treatment a rapid post-exercise SI-increase in the peroneus muscle. The steeper SI-curve indicates a better contrast medium inflow due to an improved perfusion. The second case, a 65-year-old man suffering from coronary heart disease without clinical signs of pAVK (Figure 4) exercised with a workload of 92 Ws. After stress test the ROI for the peroneus muscle shows a clear intensity increase. After exercise the SI-curve for the tibialis anterior muscle shows a similar, but less predominant change while the shape of the SI-curve of the gastrocnemius muscle remains mainly identical. A 23-year-old male person with average physical activity (Figure 5) performed DCE-MRT of the left lower leg after stress test with 172 Ws demonstrating a rapid signal increase in the peroneus muscle while the synergistic tibialis anterior muscle and antagonistic gastrocnemius muscle show a comparatively slow contrast-medium wash-in. A 26-year-old male athlete (Figure 6) exercised with 196 Ws showing a rapid contrast medium inflow in the peroneus muscle and initially also in the synergistic tibialis anterior muscle. A contrast-medium wash-out appears in both muscles, while the shape of the gastrocnemius muscle SI-curve remains substantially unchanged. A 26-year-old female athlete (Figure 7) exercised with 244 Ws. Post exercise SI-curves show a distinctive and rapid increase of contrast medium wash-in with a sharp peak particularly in the peroneus muscle and similarly in the tibialis anterior and gastrocnemius muscle. After exercise all SI-curves show a wash-out phase. CONCLUSION: SI-curves show relative increase in correlation with Time-to-Peak (TTP) decrease and Mean-Intensity to Time Ratio (MITR) increase indicating blood flow reserve mobilization after exercise. Individual muscle state seems to be linked to muscle recruitment and muscle coordination reflected by post-exercise SI-curves. The gastrocnemius muscle shows comparatively low SI-curve changes after muscular load test. Further methodological standardization and optimization of the stress test is mandatory to assure intra- and interindividual comparisons. Due to direct visualization and quantitative evaluation of the peripheral microcirculation DCE-MRT has a diagnostic potential for monitoring therapeutic response in peripheral circulation disorders and sports medicine.

Adult↗

[Interventional therapy of peripheral arterial disease-potentials and limitations].

The technical success rate of endovascular interventions in order to improve perfusion in peripheral arterial disease in the lower extremities has been markedly improved in the last decade due to clinical application of new recanalization techniques like application of hydrophil-coated guide wires, implantation of stents or stent grafts. If the-even long-segment-obstruction can be recanalized, the interventional radiologist is able to open the arterial vessel sufficiently. The excellent immediate results are limited in the long term by recurrent stenoses, which appear in different rates according to the vascular region. Whereas recurrent stenoses have nearly no clinical significance in the aortoiliac vascular segment due to the size of the treated vessels and the excellent flow, there is a significant amount of restenoses in the femoropopliteal segment and, even more, in the tibial arteries. This leads to a different indication of endovascular therapy according to the segment treated. However, in an interdisciplinary consensus we offer primary endovascular therapy for treatment of aortoiliac obstruction to all patients, whereas lesions at the femoral bifurcation are a clear primary indication for open surgical treatment. In the femoropopliteal segment, we choose a primary endovascular procedure with respect to the length of the occlusion, patient's risk factors and comorbidities. Yet, longer obstructions are a clear indication for primary surgical treatment. In cases of infrapopliteal disease, we recommend an endovascular treatment as the initial option due to the reduced invasiveness of the predominantly old and multimorbid patient cohort. Further clinical research for the evaluation of endovascular therapeutic measures in peripheral arterial disease urgently requires outcome studies, which include clinically relevant endpoints to better define the clinical value of endovascular therapy compared to traditional surgical bypass procedures. Until new clinical trials will be published, the Transatlantic Consensus document (TASC) of a variety of vascularly specialized scientific societies seems to be a helpful guideline.

Angiography↗

Effects of altering infusion parameters on intimal hyperplasia following local catheter-based delivery into the rabbit iliac artery.

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.

Angiography↗

Effects of different application parameters on penetration characteristics and arterial vessel wall integrity after local nanoparticle delivery using a porous balloon catheter.

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.

Animals↗

Encapsulation of gadobutrol in AVE-based liposomal carriers for MR detectability.

Artificial virus-like envelopes (AVEs) are liposomal carriers that may be useful for target-site-specific delivery of contrast agents. We speculated that T(1) relaxation times of a suspension of Gadolinium-filled AVEs might be shortened after internalization and lysosomal breakdown. To test this hypothesis we evaluated the T(1) relaxation times of Gadobutrol-containing AVEs before and after degradation in vitro and after receptor-mediated cellular uptake. AVEs were filled with 1 M Gadobutrol (Gadovist; Schering AG, Berlin, Germany) yielding Gd-chelate-AVEs. T(1)-relaxation times were calculated using an inversion recovery technique for different concentrations of the liposomal suspension. AVEs were degraded in vitro to mimic the release of the encapsulated Gadolinium in cells and to determine a putative increase of the T(1)-effect. Finally, Gd-chelate-AVEs where equipped with integrin-binding RGD ligands and the T1 relaxation times of these Gd-chelate-RDG-AVEs were determined after cellular uptake into endothelial or melanoma cells. Gadobutrol could be encapsulated into AVEs at a high concentration of 1 M (Gd-chelate-AVEs). The Gd-chelate-AVEs could be visualized by MRI. Concentrations down to 1:4 x 10(3) showed a significant T(1)-shortening effect. The degradation of the liposomes with Triton X-100 resulted in a further reduction down to concentrations of 1:10 x 10(3). In addition, cellular uptakes of Gd-chelate-RGD-AVEs also lead to a significant T(1)-shortening. Our study shows that Gadolinium can be efficiently encapsulated into AVEs and that Gd-chelate-AVEs can be detected by MRI T(1)-weighted measurements. The MRI detectability is enhanced by degradation. Gd-chelate-RGD-AVEs can be used to enhance the Gd uptake in cells expressing the alpha(v)beta(3) receptor.

Biological Transport↗

The value of screening for multiple arterio-venous malformations in hereditary hemorrhagic telangiectasia: a diagnostic study.

Occult visceral arterio-venous malformations (AVMs) may be a constant threat to patients suffering from hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome (M. ROW). HHT patients predominantly become symptomatic through chronic, recurrent epistaxis, a symptom that can alert physicians at an early stage of the disease. The purpose of this study was to investigate whether occult, visceral arterio-venous malformations could be detected by screening imaging studies in patients suffering from HHT. In a comprehensive diagnostic study, Rendu-Osler-Weber patients were examined for potential visceral arterio-venous malformations by physical examination and non-invasive imaging techniques. The Department of Otolaryngology of the Philipps University of Marburg is a major referral center and coordinated the screening procedures. Thirty-five individuals with the presumed diagnosis of HHT gave informed consent to the screening investigations. Eighteen of 35 individuals were found to suffer from visceral vascular malformations; most of the AVMs were diagnosed in the lung, but also the liver, spleen, brain and eyes were affected. Six patients could be treated preventively by arterial embolization for AVMs of the lung, liver and brain. Comprehensive screening for occult AVMs in HHT patients seems to be justified to avert potential complications in this group of patients.

Adolescent↗

Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical management of patients with gastrointestinal neuroendocrine tumors: an analysis in 188 patients.

AIM: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. PATIENTS AND METHODS: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). RESULTS: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1-3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. CONCLUSION: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT.

Cross-Over Studies↗

In vitro MR imaging of regulated gene expression.

PURPOSE: To design and evaluate a construct that allows regulated expression of the magnetic resonance (MR) imaging reporter gene human tyrosinase under control of the tetracycline response element. MATERIALS AND METHODS: A breast cancer cell line (MCF-7) was transfected with a plasmid that codes for the tetracycline-controlled transactivator and a new construct. In this construct, the reporter gene human tyrosinase is under control of the tetracycline response element, thus allowing suppression of gene expression by adding doxycycline (tetracycline switched off). A reverse transcription polymerase chain reaction was conducted to evaluate gene expression. Additionally, immunohistochemical investigation of tyrosinase and melanin staining was undertaken to analyze the presence of these molecules. After culture in an iron- and holotransferrin-enriched medium, cells were imaged in a 1.0-T clinical MR imager by using a surface coil and T1-weighted spin-echo and gradient-echo sequences. RESULTS: Two stable transfected cell clones were established. Cells cultured with doxycycline showed no background expression of the human tyrosinase gene, whereas withdrawal of doxycycline resulted in detectable tyrosinase messenger RNA expression. Gene expression results in a detectable tyrosinase protein level and melanin content. Increased signal intensity on T1-weighted MR images in cells that expressed the reporter gene was observed in comparison to genetically identical cells with the reporter gene switched off. CONCLUSION: Our construct enables MR imaging of regulated tyrosinase gene expression in vitro.

Breast Neoplasms↗

Influence of percutaneous transluminal angioplasty on transcutaneous oxygen pressure in patients with peripheral arterial occlusive disease.

PURPOSE: To determine in a prospective controlled trial the effect of percutaneous transluminal angioplasty (PTA) on skin oxygen supply and microcirculation as measured by means of transcutaneous oxygen pressure in patients with disabling lower-limb ischemia compared with that in patients who underwent intraarterial angiography for the assessment of disabling lower-limb ischemia. MATERIALS AND METHODS: Thirty-four patients (17 men, 17 women; mean age, 68.6 years +/- 9.8 [SD]) with peripheral arterial occlusive disease (PAOD) (claudication, n = 15; critical ischemia, n = 19) underwent transcutaneous oxygen pressure measurement at the dorsum of the foot 1 day before PTA, during PTA, 1 day after PTA, and 6 weeks after PTA. Measurements were obtained with the patient in the supine and erect sitting positions, as well as after exercise. Thirty-one patients (21 men, 10 women; mean age, 68.5 years +/- 9.3) with symptomatic PAOD who were undergoing intraarterial angiography served as the control group. RESULTS: Mean pressure before PTA was 31.6 mm Hg +/- 24 in the supine position, 50.8 mm Hg +/- 22 in the sitting position, and 22.2 mm Hg +/- 23 after exercise. Immediately after PTA, a significant increase to 34 mm Hg +/- 20 in the supine position was noted (P <.05). One day after PTA, pressure was 37.3 mm Hg +/- 20 for the supine position and 52 mm Hg +/- 20 for the sitting position. Six weeks after treatment, a further significant increase to 43.9 mm Hg +/- 19 in the supine position, 61 mm Hg +/- 15 in the sitting position, and 44.7 mm Hg +/- 24 after exercise was noted (P <.05). In the control group, a significant pressure decrease immediately after and 1 day after angiography was noted (P <.05). Measurements returned to baseline at 6 weeks follow-up. CONCLUSION: PTA has a positive effect on oxygen supply to the skin in patients with PAOD. Conversely, intraarterial angiography in patients with PAOD deteriorates skin microcirculation temporarily.

Aged↗

Imaging lung tumors with peptide-based radioligands.

The somatostatin analogue octreotide was the first radiopeptide to be used for the scintigraphic diagnosis of tumors. Somatostatin receptor scintigraphy (SRS) has proven its value, especially in the detection of gut neuroendocrine tumors. In some tumor types, it is considered the diagnostic gold standard. In carcinoid tumors of the lung, SRS is of major importance in diagnostic workup. Furthermore, the combination of computed tomography scanning and SRS is a reliable and cost-effective approach for the evaluation of single pulmonary nodules. Despite these favorable properties, SRS fails in the detection of metastases of lung cancer. The problem of false-positive results in SRS resulting from inflammatory disease might be overcome by the use of new radiopeptides such as cholecystokinin-B receptor-binding gastrin analogues. This article focuses on the current status of peptide-receptor scintigraphy in the diagnosis of lung tumors and on future developments in this field.

Cost-Benefit Analysis↗

Superselective embolization with coils in high-flow priapism.

Priapism can be divided into "low-flow" veno-occlusive priapism and, especially in children, rare "high-flow" arterial priapism. We report a 5-year-old boy who developed arterial priapism after blunt perineal trauma that was successfully treated by superselective embolization with microcoils.

Angiography↗

X-ray digital subtraction angiography with 1 mol/L gadobutrol: results from a comparative porcine study With iodinated contrast agents.

RATIONALE AND OBJECTIVES: To evaluate prospectively diagnostic accuracy of 1 mol/L gadobutrol as a contrast agent for intraarterial x-ray digital subtraction angiography (DSA) in comparison to iodinated, nonionic contrast media and 0.5 mol/L gadolinium-DTPA. METHODS: Flush arteriograms (ascending, descending, abdominal aorta, iliac, and femoral arteries) and selective angiograms (carotid, renal, and visceral arteries) were obtained from bilateral femoral arterial access (5 F sheaths) in 10 domestic pigs (70 kg body weight). Digital subtracted angiograms were obtained during injection of undiluted 1 mol/L gadobutrol, 300 mg I/mL iopromide, or 0.5 mol/L gadopentetate. Injection parameters (volume and velocity) were similar for all three contrast agents. In paired arteries, two different contrast media were used during the same angiographic run. Diagnostic quality and accuracy of the angiograms were evaluated on a three-step scale by three independent blinded investigators. RESULTS: Sufficient nonselective angiographic images were obtained in 90% of cases using iodinated contrast material. Gadobutrol achieved sufficient nonselective angiograms in 64%. Selective angiograms were sufficient in 98% using iodinated contrast material, 90% using 1 mol/L Gadobutrol and 48% using 0.5 mol/L Gd-DTPA. Adverse reactions to any of the used contrast agents were not noted. CONCLUSION: One mol/L Gadobutrol solution allows x-ray digital subtraction angiography with a diagnostic accuracy equivalent to 300 mg/mL iodinated contrast media, if selective injections are performed. Flush aortograms are of inferior image quality to iodinated contrast material.

Angiography, Digital Subtraction↗

Paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction: possible topical application in malignant bile duct obstructions.

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.

Antineoplastic Agents, Phytogenic↗