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.

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.

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.

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.

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.

Transferrin receptor upregulation: in vitro labeling of rat mesenchymal stem cells with superparamagnetic iron oxide.

PURPOSE: To prospectively evaluate the influence of superparamagnetic iron oxide (SPIO) or ultrasmall SPIO (USPIO) particles on the surface epitope pattern of adult mesenchymal stem cells (MSCs) by regulating the expression of transferrin receptor and to prospectively evaluate the influence of transfection agents (TAs) on the uptake of SPIO or USPIO particles in MSCs. MATERIALS AND METHODS: The study was approved by the institutional animal care committee of the University of Tübingen. MSCs were isolated from the bone marrow of four rats. To obtain highly homogeneous MSC populations, MSCs from one rat were single-cell cloned. One MSC clone was characterized and selected for the labeling experiments. The MSCs, which were characterized with flow cytometry and in vitro differentiation, were labeled with 200 microg/mL SPIO or USPIO or with 60 microg/mL SPIO or USPIO in combination with TAs. Aggregations of labeled cells were accommodated inside a defined volume in an agar gel matrix. Magnetic resonance (MR) imaging was performed to measure SPIO- or USPIO-induced signal voids. Quantification of cellular total iron load (TIL) (intracellular iron plus iron coating the cellular surface), determination of cellular viability, and electron microscopy were also performed. RESULTS: Labeling of MSCs with SPIO or USPIO was feasible without affecting cell viability (91.1%-94.7%) or differentiation potential. For MR imaging, SPIO plus a TA was most effective, depicting 5000 cells with an average TIL of 76.5 pg per cell. SPIO or USPIO particles in combination with TAs coated the cellular surface but were not incorporated into cells. In nontransfected cells, SPIO or USPIO was taken up. MSCs labeled with SPIO or USPIO but without a TA showed enhanced expression of transferrin receptor, in contrary to both MSCs labeled with SPIO or USPIO and a TA and control cells. CONCLUSION: SPIO or USPIO labeling without TAs has an influence on gene expression of MSCs upregulating transferrin receptor. Furthermore, SPIO labeling with a TA will coat the cellular surface.

Successful coil embolization of a ruptured gastroduodenal artery aneurysm.

Aneurysms of the gastroduodenal artery are rare. Reported here is the case of a 60-year-old woman suffering from the covered rupturing of a twin aneurysm of the gastroduodenal artery. The patient presented herself in the surgical emergency unit with abdominal discomfort. Diagnostics showed free fluid in the abdominal cavity together with anemia of 9.9 g/dL. A computed tomography scan and an angiography revealed the covered rupturing of a twin aneurysm of the gastroduodenal artery, which was treated by endovascular coiling of the gastroduodenal and pancreaticoduodenal arteries. The patient's hemoglobin level remained stable after treatment, and she was released from the hospital after 18 days. Visceral artery aneurysms are rare. Although endovascular therapy is preferred in cases involving active bleeding, surgery remains the primary therapy in those cases in which bleeding becomes uncontrollable.

Peripheral arteries: treatment with antibodies of platelet receptors and reteplase for thrombolysis--APART trial.

PURPOSE: To prospectively compare the safety and efficacy of combination therapy with the glycoprotein IIb/IIIa antagonist abciximab plus the third-generation thrombolytic agent reteplase versus those of therapy with the standard thrombolytic agent urokinase plus abciximab. MATERIALS AND METHODS: The study was approved by the local ethics committee, and patient informed consent was obtained. Patients with peripheral arterial occlusions less than 60 days old (n=120) were enrolled in the study: 50 patients (32 men, 18 women; mean age, 67 years; range, 23-88 years) received reteplase plus abciximab and 70 patients (36 men, 34 women; mean age, 68 years; range, 28-88 years) received urokinase plus abciximab. Study end points were the rate of major complications at 30 days, therapeutic success, and survival without open surgery or major amputation at follow-up. Fisher exact test was used to compare treatment groups with respect to dichotomous variables, and the event-free-survival probabilities were calculated with the Kaplan-Meier method. For the comparison of the lengths of occlusions among the groups, a two-sample t test was used. RESULTS: Therapeutic success (P=.7) did not differ between the groups, whereas the time required for thrombolysis was lower in the urokinase-plus-abciximab group (P=.001). Patients who received reteplase plus abciximab tended to develop more minor complications (mainly bleeding events) (P<.001). During long-term follow-up (2-4 years), no group differences were observed. The reocclusion rate was 48% (22 of 46) in the reteplase-plus-abciximab group and 45% (29 of 64) in the urokinase-plus-abciximab group. Only two of 120 major amputations were counted in the follow-up period. CONCLUSION: The proposed regimen resulted in only a limited number of major complications, and the low amputation rate in both groups may be attributed to abciximab.

Early effects of rhenium-188 treatment on proliferation, migration, and matrix synthesis of cultured human aortic smooth muscle cells.

BACKGROUND AND PURPOSE: Due to its properties rhenium-188 (188Re) seems to be a promising radionuclide for stent coating to reduce restenosis following percutaneous transluminal angioplasty (PTA). In order to characterize the early effects of local 188Re treatment, human aortic smooth muscle cells (HaSMCs) were incubated with different doses of 188Re. MATERIAL AND METHODS: 2 days after plating, HaSMCs were treated for a period of 5 days with 188Re. The total radiation doses applied were 1 Gy, 4 Gy, 8 Gy, 16 Gy, and 32 Gy. On days 1, 3, 5, and 7 (i.e., 2 days after the end of 188Re incubation), cell growth, clonogenic activity, cell migration, cell-cycle distribution, as well as matrix synthesis were evaluated. RESULTS: From the 1st day on, a dose-dependent growth inhibition was observed. Cumulative doses of > or = 8 Gy completely inhibited colony formation. The results of the migration tests were contradictory; on day 3 the migratory activity of all treated cells was increased compared to the controls, on day 5 it was reduced. Cumulative radiation doses of > or = 8 Gy resulted in an increased fraction of cells in G2/M-phase. The synthesis of the extracellular matrix protein tenascin was not affected by the treatment. CONCLUSION: Incubating human smooth muscle cells with 188Re for a period of 5 days (i.e., seven half-lives) results in an effective inhibition of muscle cell proliferation and colony formation. Partially, this is due to a radiation-induced G2/M-phase block. Cell migration and matrix synthesis were not effectively affected in the presented in vitro system.

Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children.

Recombinant human deoxyribonuclease I (dornase alfa) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis. In a randomized, placebo-controlled, double-blind clinical study in 100 infants, we investigated whether the therapeutic use of dornase alfa can be extended to ventilated, fluid-restricted children to reduce reintubation rate, ventilation duration, pediatric intensive care unit (PICU) stay, and ventilation complications. While reintubation rates were similar for dornase alfa 7% vs. placebo 9% (odds ratio, 0.77; confidence interval, 0.11-4.9), the incidence of atelectasis (6 vs. 17, respectively; P-value 0.051), median ventilation time (2.2 vs. 3.4 days, respectively; P-value 0.043), median length of PICU stay (7 vs. 8 days, respectively; P-value 0.051), and mean costs (4,830 vs. 6,320, respectively) were lower in the dornase alfa group. No adverse effects were observed, even in critically ill patients. We found that dornase alfa was beneficial and safe. Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward, particularly when longer ventilation (>3 days) is expected in fluid-restricted children after cardiac surgery.

Morphological and functional investigations of neuroendocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas are rare neoplasms arising predominantly from the pancreatic islets of Langerhans and are thus known as islet cell tumors. More than the half of all neuroendocrine tumors are called functioning islet cell tumors because they secrete one or more biologically active peptides that may produce clinical symptoms. Clinical diagnosis of non-functioning, i.e., biologically inactive, tumors is often delayed and patients tend to present with advanced tumors (size greater than 5 cm) that are easily localized by using conventional imaging modalities. On the other hand, symptoms of functioning islet cell tumors usually appear early in the clinical course, rendering the preoperative localization of these small hormone-producing tumors (size less than 2 cm) difficult with non-invasive methods. Since functioning islet cell tumors can often be cured by surgical resection, invasive procedures are warranted when necessary for localization diagnosis. Failure to search for, detect, and resect these small tumors will invariably result in persistent symptoms. Regarding the unsatisfactory results of morphological imaging methods, functional studies, especially arterial stimulation with hepatic venous samplings, may provide a preoperative regionalization of the pancreatic adenoma, regardless of its size.

Drug-eluting stents: potential applications for peripheral arterial occlusive disease.

Many different approaches have been evaluated to prevent restenosis in stents after vascular implantation. Currently, drug-eluting stents are extremely promising in suppressing neointimal hyperplasia. Various animal studies and randomized trials in humans have shown excellent results in terms of safety and efficacy during intermediate-term follow-up. This article will give an overview of experimental and clinical data of the different agents in published and ongoing trials.