Implantability, Complications, and Follow-Up After Transjugular Intrahepatic Portosystemic Stent-Shunt Creation With the 6F Self-Expanding Sinus-SuperFlex-Visual Stent.

BACKGROUND: The transjugular intrahepatic portosystemic stent-shunt (TIPSS) builds a shortcut between the portal vein and a liver vein, and represents a sophisticated alternative to open surgery in the management of portal hypertension or its complications. OBJECTIVES: To describe clinical experiences with a low-profile nitinol stent system in TIPSS creation, and to assess primary and long-term success. PATIENTS AND METHODS: Twenty-six patients (5 females, 21 males; mean age 54.6 years) were treated using a low-profile 6F self-expanding sinus-SuperFlex-Visual stent system. The indication for TIPSS creation was refractory bleeding in 9 of the 26 patients, refractory ascites in 18 patients, and acute thrombosis of the portal vein confluence in one patient. Portosystemic pressure gradients before and after TIPSS, periprocedural and long-term complications, and the time to orthotopic liver transplantation (OLT) or death were recorded. RESULTS: The portosystemic pressure gradient was significantly reduced, from 20.9 ± 6.3 mmHg before to 8.2 ± 2.3 mmHg after TIPSS creation (P < 0.001). Procedure-related complications included acute tract occlusion (n = 2), liver hematoma (n = 1), hepatic encephalopathy (n = 1), and cardiac failure (n = 1). Three of the 26 patients had late-onset TIPSS occlusion (at 12, 12, and 39 months after TIPSS creation). Three patients died within one week after the procedure due to their poor general condition (multiorgan failure, acute respiratory distress syndrome, necrotizing pancreatitis, and aspiration pneumonia). Another four patients succumbed to their underlying advanced liver disease within one year after TIPSS insertion. Seven patients underwent OLT at a mean time of 9.4 months after TIPSS creation. CONCLUSION: The sinus-SuperFlex-Visual stent system can be safely deployed as a TIPSS device. The pressure gradient reduction was clinically sufficient to treat the patients' symptoms, and periprocedural complications were due to the TIPSS procedure per se rather than to the particular stent system employed in this study.

Labeling Human Melanoma Cells With SPIO: In Vitro Observations.

OBJECTIVES: To use the superparamagnetic iron oxide (SPIO) contrast agent Resovist (±transfection agent) to label human melanoma cells and determine its effects on cellular viability, microstructure, iron quantity, and magnetic resonance imaging (MRI) detectability. MATERIALS AND METHODS: Human SK-Mel28 melanoma cells were incubated with Resovist (±liposomal transfection agent DOSPER). The cellular iron content was measured, and labeled cells were examined at 1.5 T and 3.0 T. The intracellular and extracellular distributions of the contrast agent were assessed by light and electron microscopy. RESULTS: The incubation of melanoma cells with SPIO does not interfere with cell viability or proliferation. The iron is located both intracellularly and extracellularly as iron clusters associated with the exterior of the cell membrane. Despite thorough washing, the extracellular SPIO remained associated with the cell membrane. The liposomal transfection agent does not change the maximum achievable cellular iron content but promotes a faster iron uptake. The MRI detectability persists for at least 7 days. CONCLUSION: The transfection agent DOSPER facilitates the efficient labeling of human metastatic melanoma cells with Resovist. Our findings raise the possibility that other Resovist-labeled cells may collect associated extracellular nanoparticles. The SPIO may be available to other iron-handling cells and not completely compartmentalized during the labeling procedure.

Therapeutic angiographic procedures: differences in dose area product between analog image intensifier and digital flat panel detector.

BACKGROUND: Radiation exposure remains an unceasing concern in angiographic procedures. Modern angiography machines such as analog image intensifiers (AII) or the new flat panel detectors (FPD) aim at a further dose reduction. PURPOSE: To present dose area products (DAP) in a broad spectrum of therapeutic angiographic procedures, comparing an AII to an FPD angiography system. MATERIAL AND METHODS: A total of 999 peripheral therapeutic angiography procedures performed with an FPD (n = 562) and an AII system (n = 437) were evaluated. DAP, fluoroscopy time, and patients' body mass index (BMI) were recorded. Interventions were classified into five main groups: percutaneous transluminal angioplasty (PTA); PTA and stent placement; intra-arterial thrombolysis; embolization procedures; and specialized interventions. RESULTS: DAP values in therapeutic angiographic procedures were significantly higher when performed with the FPD compared to the AII system. The increase of the FPD versus AII system was 100.1% for PTA, 39.9% for PTA and stent placement, 187% for intra-arterial thrombolysis, 31.3% for embolization procedures, and 361% for specialized interventions. These differences persisted after standardizing DAP values to the geometric mean fluoroscopy duration of each procedure. Fluoroscopy times were shorter in all interventions performed at the FPD as compared to the AII system. DAPs increased with higher BMI, but the DAP increase of both systems with elevated BMI was variable, depending on the individual intervention. CONCLUSION: In therapeutic angiographic procedures, the FPD system required higher DAPs despite shorter fluoroscopy times as compared to an AII system. Better ergonomics and speediness of the FPD system may be advantageous in the emergency setting.

Cell Cycle Regulation of Smooth Muscle Cells--Searching for Inhibitors of Neointima Formation: Is Combretastatin A4 an Alternative to Sirolimus and Paclitaxel?

PURPOSE: To compare the effects of sirolimus, paclitaxel, and combretastatin A4 (CA4) on regulatory proteins of the cell cycle in proliferating smooth muscle cells (SMCs). MATERIALS AND METHODS: Human aortic SMCs were treated with sirolimus, paclitaxel, and CA4 at 5 × 10(-9) mol/L. After 1 day, half of the cells were harvested (DAY1 group). The treatment medium of the other half was replaced with culture medium on day 4, and those cells were harvested on day 5 (DAY5 group). Cyclins D1, D2, E, and A and cyclin-dependent kinase (CDK) inhibitors p16, p21, and p27 were detected by Western blot technique. Quantification was performed by scanning densitometry of the specific bands. RESULTS: In the DAY1 group, treatment with sirolimus resulted in decreased intracellular levels of cyclins D2 and A (P < .05). Increased D cyclins and reduced levels of cyclins E and A (P < .05) in the DAY5 group indicated a permanent G1/S block by sirolimus. Paclitaxel led to only slight alterations of cyclin and CDK inhibitor expression (P > .05). In the DAY1 group, CA4 decreased intracellular levels of cyclins D2, E, and A (P < .05). Despite recovery effects in the DAY5 group (increase of cyclins D1, D2, and A compared with DAY1 group; P < .05), the upregulation of the CDK inhibitor p21, increased D cyclins, and decreased cyclins E and A (P < .05) are compatible with a G1 arrest. CONCLUSIONS: CA4 is a stronger inhibitor of the SMC cycle than sirolimus or paclitaxel and may represent an alternative for drug-eluting stents in atherosclerotic luminal stenosis. The effect of CA4 on neointima formation should be evaluated further.

Comparison of visibility for four self-expanding nitinol bare stents in vitro.

BACKGROUND: Sufficient radiopacity of stents is a prerequisite for safe interventions and minimization of the radiation dose for the patient and the interventionist. Modern nitinol stents are considered less radiopaque compared to formerly used stents. PURPOSE: To evaluate the objective detection rate (ODR) and the subjective radiopacity score (SRS) of four self-expanding nitinol stents with their markers on a phantom human pelvis. MATERIAL AND METHODS: We evaluated the ODR (as a percentage of correctly identified stents) and the SRS (on a scale from 0 = not visible to 4 = excellent visibility) for four self-expanding nitinol stents (SinusSuperflex, SMART, Luminexx, Zilver) with 8 mm diameter and 40 mm length. Stents were placed on a phantom human pelvis and images of the stents were taken in four different positions (right and left lumbosacral joint and near the right and left limbus acetabuli) using the following modes: spotfilm, pulsed fluoroscopy (4, 7.5, 15, and 30 pulses/min) and at three different digital magnification modes. Dose area products (DAPs) were assessed. RESULTS: ODR and SRS, respectively, were significantly increased for the SMART stent compared to all other tested stents (P < 0.05): SMART 93.53% and 2.43, SinusSuperflex 90.81% and 2.21, Luminexx 90.39% and 2.20, and Zilver 89.28% and 2.21. ODR was significantly reduced in position 3 where the bone overlap was more pronounced for all stents (detection rates 77.14-79.56%). An increase in magnification significantly improved the ODR and SRS for all stents (70.33-99.25% and 1.07-3.28, respectively, P < 0.05). Increased pulsing frequency did not improve the ODR of the various stents but did increase the DAP. CONCLUSION: The SMART stent had the best overall performance. In the presence of bone overlap, all self-expanding nitinol stents had poor results. Increased pulsing frequency did not improve ODR or SRS but did increase the DAP. Use of digital magnification modes had no effect on DAP increasing ODR and SRS.

Comparison of digital flat-panel detector and conventional angiography machines: evaluation of stent detection rates, visibility scores, and dose-area products.

OBJECTIVE: The objective of this study was to compare the performance and radiation doses of a flat-panel detector (FPD) angiography machine with an image intensifier (II) angiography machine. MATERIALS AND METHODS: Images of four nitinol stents (Sinus-SuperFlex, SMART, Luminexx, and Zilver stents) in a phantom of a human pelvis were acquired on an FPD system (Axiom Artis) and an II system (Fluorospot TOP) using the following modes: spot-film, continuous fluoroscopy (4, 7.5, 15, and 30 pulses/s), and three amplification modes. Objective stent detection rates and subjective radiopacity scores (scale: 0 [not visible] to 4 [excellent visibility]) were calculated. The radiation doses evaluated by the respective machines were compared. RESULTS: Over all modes and stents, the mean objective correct stent detection rates and mean subjective radiopacity scores were 89.49% and 1.81, respectively, for the Axiom Artis and 91.00% and 2.26 for the Fluorospot TOP. The stent detection rates over all modes for the SMART and Luminexx stents were better using the Axiom Artis machine (97.61% vs 93.55% and 98.28% vs 90.41%, respectively) and those for the Sinus-SuperFlex and Zilver stents were better using the Fluorospot TOP machine (90.83% vs 83.56% and 89.29% vs 80.50%). The subjective radiopacity scores of stent visibility were worse for the Axiom Artis than the Fluorospot TOP for all stents except the Luminexx stent (mean score, 2.34 vs 2.21, respectively). The objective stent detection rates and subjective radiopacity scores improved using the spot-film mode and with raising amplification, whereas increases in the fluoroscopy pulsing frequency did not improve stent detection rates or radiopacity scores for either machine. The radiation doses at continuous fluoroscopy were approximately 90% higher for the Axiom Artis than for the Fluorospot TOP (2.60 vs 1.41 µGy/m(2) at 30 pulses/s, respectively). CONCLUSION: The objective correct stent detection rates were similar for both machines with differences in detection for the respective stents. The subjective radiopacity scores were almost always better for the Fluorospot TOP machine. Also, the Axiom Artis machine generated approximately 90% higher radiation doses in fluoroscopy. For both machines, using a higher fluoroscopy pulsing frequency had no positive effect on objective correct stent detection rates or subjective radiopacity scores.

The Automated Breast Volume Scanner (ABVS): initial experiences in lesion detection compared with conventional handheld B-mode ultrasound: a pilot study of 50 cases.

The idea of an automated whole breast ultrasound was developed three decades ago. We present our initial experiences with the latest technical advance in this technique, the automated breast volume scanner (ABVS) ACUSON S2000(™). Volume data sets were collected from 50 patients and a database containing 23 women with no detectable lesions in conventional ultrasound (BI-RADS(®)-US 1), 13 women with clearly benign lesions (BI-RADS(®)-US 2), and 14 women with known breast cancer (BI-RADS(®)-US 5) was created. An independent examiner evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. The diagnostic accuracy for the experimental ABVS was 66.0% (95% confidence interval [CI]: 52.9-79.1). The independent examiner detected all breast cancers in the volume data resulting in a calculated sensitivity of 100% in the described setting (95% CI: 73.2%-100%). After the ABVS examination, there were a high number of requests for second-look ultrasounds in 47% (95% CI: 30.9-63.5) of the healthy women (with either a clearly benign lesion or no breast lesions at all in conventional handheld ultrasound). Therefore, the specificity remained at 52.8% (95% CI: 35.7-69.2). When comparing the concordance of the ABVS with the gold standard (conventional handheld ultrasound), Cohen's Kappa value as an estimation of the inter-rater reliability was κ = 0.37, indicating fair agreement. In conclusion, the ABVS must still be regarded as an experimental technique for breast ultrasound, which definitely needs to undergo further evaluation studies.

Effects of magnetic resonance imaging contrast agents on human umbilical vein endothelial cells and evaluation of magnetic resonance imaging contrast media-triggered transforming growth factor-beta induction in dermal fibroblasts (HSF) as a model for nephrogenic systemic fibrosis.

RATIONALE AND OBJECTIVES: The objective of this study was to evaluate effects of 6 commercially available magnetic resonance contrast media (CM) on human umbilical vein endothelial cells (HUVEC) and the induction of transforming growth factor-beta (TGF-ß) in dermal fibroblasts (HSF) as a possible model for the pathogenesis of nephrogenic systemic fibrosis. METHODS: HUVECs were incubated with 10× and 20× of the molar standard blood concentration achieved with CM applications for magnetic resonance imaging examinations (10× and 20× concentration) for 24 hours using gadolinium-based CM Gadovist, Magnevist, Multihance, and Omniscan, as well as Teslascan (Manganese-based), and Resovist (Iron-based). Proliferation kinetics (PK), colony formation, and viability assays were performed. Additionally, human dermal fibroblasts (HSF) were incubated for 24 hours with 1× and 20× concentration in all 6 CM, and TGF-ß levels were assessed directly after the incubation period as well as on days 3 and 8 postincubation. RESULTS: HUVEC PK data show similar gains in cell numbers for all 6 CM in both concentration groups over the 17-day assessment period. Only cells incubated with Omniscan and Teslascan differed from the other groups on days 3 and 7 postincubation (P < 0.05). After day 7, a cell regain occurred in the Omniscan and Teslascan groups reaching the numbers of the other groups in sequel. Differences in colony formation were consistent with PK results with a statistically significant reduction in clonogenic activity for Teslascan and Omniscan in HUVEC cells, P < 0.05. No reduction in viability was seen for all groups and conditions. TGF-ß expression of HSF cells incubated with 1× concentration and all CM did not differ significantly from control cells for any point in time investigated. At 20× concentration directly after incubation, TGF-ß was significantly reduced for the Teslascan and Resovist group as 3 compared with control and all other CM groups, P < 0.05. On day 3 postincubation, only Resovist-incubated HSF cells showed a significant reduction of TGF-ß (1.614, standard deviations: 89) as compared with the control group (2.883, standard deviations: 30) and the other CM. TGF-ß was slightly reduced for all CM groups 8 days after incubation (not statistically significant, P > 0.05). CONCLUSIONS: After 24 hours of incubation with Omniscan and Teslascan (10× and 20× concentration), considerable short-term antiproliferative effects in HUVECs were observed. HSF cells (20× concentration) showed a reduction of TGF-ß for Resovist and Teslascan directly after incubation, whereas TGF-ß levels in HSF cells were slightly reduced for all CM 8 days after incubation. Therefore, TGF-ß-mediated proliferative effects on fibroblasts or on collagen synthesis potentially leading to nephrogenic systemic fibrosis may mainly be triggered by tissue monocytes and macrophages in the peripheral blood instead of dermal fibroblasts.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact.

PURPOSE: In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions. METHODS: We retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies. RESULTS: Clinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively. CONCLUSION: PET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions-especially without a distinctive morphological correlate-accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions.

Effects of MRI contrast agents on human embryonic lung fibroblasts.

RATIONALE AND OBJECTIVES: The objective of this investigation was to evaluate 6 magnetic resonance contrast media (CM) with regard to their different effects on human embryonic lung fibroblasts (HEL-299). METHODS: Human embryonic fibroblasts (HEL-299) were incubated with 1x, 5x, 10x, and 20x of the normal molar blood concentration (1x, 5x, 10x, 20x conc.) reached through routine contrast media applications for MRI examinations. Four gadolinium-based CM, ie, Gadovist, Magnevist, Multihance, Omniscan, Teslascan (Manganese-based), and Resovist (Iron-based), with incubation periods over 4 hours and 24 hours were investigated. Proliferation kinetics, colony formation, and viability assays were performed after 4 and 24 hours of treatment. Apoptotic cells were quantified after tetramethylrhodamine ethyl ester staining following 24 hours of CM media incubation (20x conc.) by fluorescence activated cell sorting cytometry. Furthermore, immunofluorescence images with vimentin staining were obtained (20x conc., 24 hours treatment). Cell cycle analysis was performed after 24 hours of incubation and 20x conc. directly after incubation and 24 hours later (fluorescence activated cell sorting cytometry). RESULTS: The proliferation kinetics performed with 20x conc. revealed a persistent increase in cell numbers until day 11 for all CM without significant differences after 4 hours of incubation. A significant reduction in initial cell numbers was recorded in the 24-hours-group after 4 days of CM incubation with Magnevist, Multihance, Omniscan, and Teslascan. Solely cells incubated with Resovist and Gadovist failed to show decreased cell numbers when compared with the control group. However, a considerable cell regain occurred afterward reaching control-group levels on day 21. Colony numbers were significantly reduced (about 20%, respectively) with Magnevist at 10x and 20x conc., as well as Omniscan and Multihance at 20x conc. when compared with all other groups, P < 0.05. Cell-cycle distribution showed a reduction of S-phase cells for Magnevist, Omniscan, and Multihance (2.9%-10.5%) when compared with Gadovist, Resovist and Teslascan (16.7%-21.0%). Twenty-four hours after incubation, the percentiles of cells in S-phase were significantly increased for Magnevist, Omniscan, and Multihance (31.4%-38.5%) when compared with Gadovist, Resovist, and Teslascan (18.6%-26.8%), P < 0.05. Viability was not impaired by administration of any CM and no apoptosis was seen after tetramethylrhodamine ethyl ester staining at 24 hours of incubation. Cell morphology remained unchanged in vimentin-staining for all CM and conditioning regimens. CONCLUSIONS: No toxic effects on embryonic fetal lung fibroblasts were detectable after 4 and 24 hours of incubation in 6 MRI CM and 10x to 20x conc. in our setting. Antiproliferative effects, initially detected with Magnevist, Omniscan and Multihance, were rapidly compensated for.

Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles.

BACKGROUND: For clinical applications of mesenchymal stem cells (MSCs), labeling and tracking is crucial to evaluate cell distribution and homing. Magnetic resonance imaging (MRI) has been successfully established detecting MSCs labeled with superparamagnetic particles of iron oxide (SPIO). Despite initial reports that labeling of MSCs with SPIO is safe without affecting the MSC's biology, recent studies report on influences of SPIO-labeling on metabolism and function of MSCs. Exposition of cells and tissues to high magnetic fields is the functional principle of MRI. In this study we established innovative labeling protocols for human MSCs using clinically established SPIO in combination with magnetic fields and investigated on functional effects (migration assays, quantification of colony forming units, analyses of gene and protein expression and analyses on the proliferation capacity, the viability and the differentiation potential) of magnetic fields on unlabeled and labeled human MSCs. To evaluate the imaging properties, quantification of the total iron load per cell (TIL), electron microscopy, and MRI at 3.0 T were performed. RESULTS: Human MSCs labeled with SPIO permanently exposed to magnetic fields arranged and grew according to the magnetic flux lines. Exposure of MSCs to magnetic fields after labeling with SPIO significantly enhanced the TIL compared to SPIO labeled MSCs without exposure to magnetic fields resulting in optimized imaging properties (detection limit: 1,000 MSCs). Concerning the TIL and the imaging properties, immediate exposition to magnetic fields after labeling was superior to exposition after 24 h. On functional level, exposition to magnetic fields inhibited the ability of colony formation of labeled MSCs and led to an enhanced expression of lipoprotein lipase and peroxisome proliferator-activated receptor-gamma in labeled MSCs under adipogenic differentiation, and to a reduced expression of alkaline phosphatase in unlabeled MSCs under osteogenic differentiation as detected by qRT-PCR. Moreover, microarray analyses revealed that exposition of labeled MSCs to magnetic fields led to an up regulation of CD93 mRNA and cadherin 7 mRNA and to a down regulation of Zinc finger FYVE domain mRNA. Exposition of unlabeled MSCs to magnetic fields led to an up regulation of CD93 mRNA, lipocalin 6 mRNA, sialic acid acetylesterase mRNA, and olfactory receptor mRNA and to a down regulation of ubiquilin 1 mRNA. No influence of the exposition to magnetic fields could be observed on the migration capacity, the viability, the proliferation rate and the chondrogenic differentiation capacity of labeled or unlabeled MSCs. CONCLUSIONS: In our study an innovative labeling protocol for tracking MSCs by MRI using SPIO in combination with magnetic fields was established. Both, SPIO and the static magnetic field were identified as independent factors which affect the functional biology of human MSCs. Further in vivo investigations are needed to elucidate the molecular mechanisms of the interaction of magnetic fields with stem cell biology.

Impact of rhenium-188, gemcitabine, and 5-fluorouracil on cholangiocellular carcinoma cells: an in vitro study.

The purpose of this study was to compare the beneficial effects of radioactive stents and radioactive stents plus additional chemotherapy in the palliative treatment of cholangiocellular carcinomas. Cholangiocellular carcinoma cells (TFK-1 cells) were treated either with 8 Gy (RTB group) or 16 Gy (RTA group) (188)Re or with (188)Re irradiation (8 Gy) combined with either gemcitabine (8 Gy/Gem) or 5-fluorouracil (8 Gy/5-FU) at a dosage of 20 microg/ml medium for 4 days and subsequently compared with an untreated control group. Proliferation kinetics were assessed on days 4, 7, 11, 18, 25, and 32. Colony formation assays were performed on days 7, 18, and 32 and cell cycle distribution was examined on days 4, 7, 11, 15, 25, and 39. Cell proliferation kinetics showed the lowest cell numbers in the 8 Gy/5-FU group (control, 15,390,000; RTA group, 8,394,000; RTB group, 5,609,000; 8 Gy/Gem group, 423,000; and 8 Gy/5-FU group, 297,667). In contrast, clonogenic activity on day 32 was lower in the 8 Gy/Gem group (control, 29.3 colonies; RTB group, 23.1 colonies; 8 Gy/5-FU group, 21.5 colonies; 8 Gy/Gem, 3.3 colonies; and even augmented in the RTA group, with 37.7 colonies). Cell cycle distribution showed similar curves for all groups on slightly different levels except for the 8 Gy/5-FU group, which showed a relatively augmented percentage of cells on day 7 in the G2 M cycle phase and on day 4 in the S phase. In conclusion, irradiation (8 Gy) with (188)Re administered, e.g., via coated stents, combined with Gem could be a valid option for the treatment of CCCs.

Clinical and in vitro effect of dornase alfa in mechanically ventilated pediatric non-cystic fibrosis patients with atelectases.

INTRODUCTION: At present no evidence-based medical treatment for persistent atelectasis in pediatric non-cystic fibrosis (CF) patients is available. METHOD: To evaluate the use of intratracheally instilled recombinant human deoxyribonuclease (rhDNase) in intubated and ventilated pediatric patients, we performed a single-center observational study on 46 pediatric intensive care patients who had received intratracheal DNase. Patients were classified, according to radiologic findings of atelectasis (group 1) or infiltrates. As controls we examined a historical control group of 17 patients with atelectasis after cardiac surgery, who had been treated with NaCl 0.9% and matched for age and diagnosis with 21 patients from group 1 (subgroup 1a). Radiologic improvement and inflammatory markers in both serum and tracheal aspirates were measured. RESULTS: In group 1, 35 patients had 51 atelectases/dystelectases episodes at baseline. 67 % of patients showed radiologic signs of improvement after 24h treatment with rhDNase. In subgroup 1a, 16 patients had complete resolution of atelectases and minimal change in dystelectases after a treatment of 24 hours rhDNase, compared with the control group of 17 patients, who had 7 atelectases and 10 dystelectases at baseline and an improvement in only 1 out of 17 (6 %) patients after 24h. CONCLUSION: Intratracheal instillation of rhDNase is an effective adjunct to conservative therapy of atelectases in children. Further randomized controlled prospective studies are necessary.

Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability.

BACKGROUND AIMS: Labeling of stem cells is crucial to allow tracking of stem cell homing and engraftment after transplantation. In this study we evaluated the influence of cell labeling procedures using clinically approved small particles of iron oxide (SPIO) with or without transfection reagents (TA) on functional parameters of human mesenchymal stem cells (MSC). METHODS: The study was approved by the institutional review board of the University of Tubingen, Germany. Seven populations of bone marrow (BM)-derived human mesenchymal stem cells (MSC) were labeled with SPIO alone or in combination with various TA. Directly after labeling and two passages after labeling migration assays, quantification of colony-forming units and quantitative evaluation of the differentiation potential were performed. Quantification of the cellular total iron load (TIL), determination of the cellular viability and electron microscopy were also performed. RESULTS: Labeling of mesenchymal stem cells with SPIO with or without TA did not affect cell viability and differentiation potential significantly. SPIO in combination with TA coated the cellular surface directly after labeling but was incorporated into the cells after two passages. Labeling of mesenchymal stem cells with TA led to a significant decrease of migration capacity. This effect was abolished after two passages. Labeling with and without TA led to a significant decrease in colony formation ability. This effect could also be observed after two passages. CONCLUSIONS: The observed decrease of migration capacity and colony-formation ability was not associated with either TIL or localization of particles of iron oxide. SPIO labeling with and without TA had functional effects on human mesenchymal stem cells by decreasing the migration capacity and colony-formation ability of the stem cells.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences.

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

Endovascular treatment of venous graft stenosis in the inferior vena cava and the left hepatic vein after complex liver tumor resection.

Endovascular treatment has been reported for a variety of conditions that result in venous obstruction in the iliocaval territory. The present report describes a patient who underwent a complex resection of a tumor that infiltrated the retrohepatic segment of the inferior vena cava (IVC), necessitating replacement of the IVC with a polytetrafluoroethylene (PTFE) graft. Postoperatively, symptomatic venous obstruction occurred in the graft and the left hepatic vein. Treatment required stent placement bridging native veins and the graft. The patient underwent placement of a self-expanding stent within the IVC and the PTFE graft with treatment of the hepatic vein stenosis via jugular vein access.

The use of clinically approved small particles of iron oxide (SPIO) for labeling of mesenchymal stem cells aggravates clinical symptoms in experimental autoimmune encephalomyelitis and influences their in vivo distribution.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Mesenchymal stem cells (MSC) have been shown to ameliorate symptoms in experimental autoimmune encephalomyelitis (EAE), a model of MS. Using cloned MSC labeled with clinically approved small particles of iron oxide (SPIO) for treatment of EAE we analyzed the tissue localization of transferred cells. Treatment with unlabeled MSC led to disease amelioration compared to controls. In contrast, treatment with SPIO-labeled MSC lead to increase in disease severity. Treatment with SPIO alone did not alter disease course. After transplantation labeled and nonlabeled MSC were detected in the CNS and the liver with significantly more SPIO-labeled cells present in the CNS. Iron deposition was present in the group treated with SPIO-labeled MSC, indicating that in vivo the initially cell surface-bound iron detached from the MSC. These results could be of great importance for imaging of patients in the clinical setting, indicating that in vivo application of SPIO-labeled MSC needs to be performed with caution because the cell-derived exposure of iron can lead to disease aggravation.

Isotropic high-spatial-resolution contrast-enhanced 3.0-T MR angiography in patients suspected of having renal artery stenosis.

The purpose of this study was to prospectively evaluate the diagnostic performance of contrast material-enhanced magnetic resonance (MR) angiography performed at 3 T for assessment of renal artery stenosis (RAS) by using parallel acquisition techniques with high acceleration factors and with digital subtraction angiography (DSA) as the reference standard. The study was institutional review board approved, and written informed consent was obtained from all patients. Twenty-nine patients (18 men, 11 women; mean age, 57.1 years +/- 14.3 [standard deviation]) suspected of having RAS underwent MR angiography. Images were evaluated qualitatively and quantitatively. The interobserver variability, sensitivity, specificity, and positive and negative predictive values of 3-T MR angiography, as compared with DSA (performed in 15 patients), were calculated. All examinations yielded good or excellent image quality. The sensitivity and specificity of MR angiography in grading significant (>75%) stenosis were 94% and 96%, respectively. Owing to its high sensitivity, contrast-enhanced 3-T MR angiography can be used reliably to exclude RAS and can serve as a useful screening method in the diagnostic work-up of patients with arterial hypertension.

GP IIb/IIIa blockade during peripheral artery interventions.

The activation of the platelet GP IIb/IIIa receptor is the final and common pathway in platelet aggregation. By blocking this receptor, platelet aggregation can be inhibited independently of the stimulus prompted the targeting of this receptor. Several years ago, three drugs have been approved for coronary artery indications. Since that time, there is increasing evidence that GP IIb/IIIa receptor blockade might have also an important role in peripheral arterial intervention. This article summarizes the action and differences of GP Ilb/IIIa receptor inhibitors and its possible indication in peripheral arteries.

Management of chronic low back pain: rationales, principles, and targets of imaging-guided spinal injections.

If low back pain does not improve with conservative management, the cause of the pain must be determined before further therapy is initiated. Information obtained from the patient's medical history, physical examination, and imaging may suffice to rule out many common causes of chronic pain (eg, fracture, malignancy, visceral or metabolic abnormality, deformity, inflammation, and infection). However, in most cases, the initial clinical and imaging findings have a low predictive value for the identification of specific pain-producing spinal structures. Diagnostic spinal injections performed in conjunction with imaging may be necessary to test the hypothesis that a particular structure is the source of pain. To ensure a valid test result, diagnostic injection procedures should be monitored with fluoroscopy, computed tomography, or magnetic resonance imaging. The use of controlled and comparative injections helps maximize the reliability of the test results. After a symptomatic structure has been identified, therapeutic spinal injections may be administered as an adjunct to conservative management, especially in patients with inoperable conditions. Therapeutic injections also may help hasten the recovery of patients with persistent or recurrent pain after spinal surgery.