[Prostate gland - what would urologists like to know from radiologists?] / Die Vorsteherdrüse ­ was möchte der Urologe vom Radiologen wissen?

A more than 100-year period, where the prostate was only seen and treated as a whole is coming to an end right now. Finally, high resolution imaging is providing deep insights and detailed information so that new therapeutic procedures can aim for the smallest targets within the gland. The long-standing wish of patients for individual noninvasive diagnostics and treatment of prostate diseases can now be fulfilled by providing new tailored concepts; however, in order to transfer the enormous amount of new information into the specific clinical patient situation, a closely knit interdisciplinary approach is required. In this setting, the traditional outpatient consultation service is overstretched in every aspect. It is now the time for new innovative constructs. The current one-sided service concept for urologists, radiologists and radiation therapists is therefore behind the times and the development of a "prostate management team" with equally cooperating partners from each specialty is the task for the future.

[Successful therapy of metastatic basal cell carcinoma with vismodegib]. / Erfolgreiche Therapie eines metastasierten Basalzellkarzinoms mit Vismodegib.

A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study.

The introduction of clinical genome-wide sequencing raises complex issues regarding the management of incidental findings. However, there is a lack of empirical studies assessing views of providers involved in potential disclosure of such findings. In an anonymous survey of 279 clinical genetics professionals, we found that the vast majority of participants agreed that they were interested in knowing about clinically actionable incidental findings in themselves (96%) and their child (99%), and they reported that these types of findings should be disclosed in adult (96%) and minor (98%) patients. Approximately three-fourths agreed that they were personally interested in knowing about an adult-onset clinically actionable disease (78%) and a childhood-onset non-clinically actionable disease (75%) in their child. A similar percentage of participants (70%) felt that these two types of findings should be disclosed to patients. Forty-four percent of participants wanted to know about an incidental finding that indicates an adult-onset non-clinically actionable condition in themselves and 31% wanted to know about this type of information in their child. Findings from this study revealed participants' views highly dependent on clinical actionability. Further research is needed with a broader population of geneticists to increase generalizability, and with diverse patients to assess their perspectives about results disclosure from clinical sequencing.

Effect of degeneration on gene expression of chondrogenic and inflammatory marker genes of intervertebral disc cells: a preliminary study.

AIM: New techniques for biological repair in the treatment of degenerative disc disease (DDD) have been developed recently. The question arises whether it is possible to find a predictive marker to identify a patient population which could benefit from this new treatment option. Standard magnetic resonance imaging (MRI) fails to differentiate between pathologic painful and asymptomatic aging discs. Neurological symptoms contribute to identifying the pathological level. In this preliminary translational research study we analysed the gene expression of structure proteins and inflammatory mediators as well as histological features of lumbar intervertebral discs in symptomatic patients with various signs of degeneration in the MRI. METHODS: Specimens of intervertebral disc tissue were obtained from 20 patients undergoing lumbar nucleotomy. Preoperatively, a group selection based on four pre-defined MRI-criteria was performed: Group 1 (mild signs of degeneration), group 2 (moderate), group 3 (moderate-severe), group 4 (severe). RESULTS: An increase of the expression of structural proteins and inflammatory markers could be observed in MRI-groups 2 and 3. Gene expression of collagen type I and II and aggrecan went along with levels of cyclooxygenase-2 (COX-2) and (fibroblast growth factor-2) FGF-2 expression. Histological examination showed signs of granulation tissue in only 35% of cases, but no differences between the groups. CONCLUSION: Our findings implicate that the gene expression of structural proteins might correlate with the appearance of inflammatory mediators in symptomatic patients with moderate disc changes in the MRI in this preliminary clinical subset. The assessment of cell activity and protein expression in a larger number of patients could be next step to support and supplement the present data.

A novel temporal filtering strategy for functional MRI using UNFOLD.

A major challenge for fMRI at high spatial resolution is the limited temporal resolution. The UNFOLD method increases image acquisition speed and potentially enables high acceleration factors in fMRI. Spatial aliasing artifacts due to interleaved k-space sampling are to be removed from the image time series by temporal filtering before statistical mapping in the time domain can be carried out. So far, low-pass filtering and multi-band filtering have been proposed. Particularly at high UNFOLD factors both methods are non-optimal. Low-pass filtering severely degrades temporal resolution and multi-band filtering leads to temporal autocorrelations affecting statistical modelling of activation. In this work, we present a novel temporal filtering strategy that significantly reduces temporal autocorrelations compared to multi-band filtering. Two datasets (finger-tapping and resting state) were post-processed using the proposed and the multi-band filter with varying set-ups (i.e. transition bands). When the proposed filtering strategy was used, a linear regression analysis revealed that the number of false positives was significantly decreased up to 34% whereas the number of activated voxels was not significantly affected for most filter parameters. In total, this led to an effective increase in the number of activated voxels per false positive for each filter set-up. At a significance level of 5%, the number of activated voxels was increased up to 41% by using the proposed filtering strategy.

[Phytobezoar in the common hepatic duct - rare cause of obstructive jaundice following pancreatoduodenectomy: case report and review of the literature]. / Phytobezoar des Ductus hepaticus communis - seltene Differenzialdiagnose einer Cholestase im Langzeitverlauf nach Kausch-Whipple-Operation: Fallbericht und Literaturübersicht.

Obstruction of bile flow following pancreatoduodenectomy can be caused by stenosis of the hepaticojejunostomy created at the time of surgery, obstruction of the bile-draining jejunal loop, stones or, very rarely, ingested foreign bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or the once popular side-to-side-choledochduodenostomy, the creation of a hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling intestinal content such as ingested foreign bodies or food fibers to migrate into the bile duct. We report on the case of a patient developing biliary tract obstruction due to fibrous material in the common hepatic duct 15 years after pancreatoduodenectomy. In addition, an overview of the literature on the rare phenomenon of foreign body-associated obstructive jaundice is given.

Nitrogen and phosphorus removal using tile-treatment wetlands: A 12-year study from the midwestern United States.

Nutrient enrichment from tile-drained agricultural lands to the Mississippi River is a leading cause of hypoxia in the Gulf of Mexico. Small edge-of-field wetlands can effectively treat nitrate-nitrogen (NO3 -N) export from tiles, although less research exists on their capacity to treat phosphorus (P). Additionally, long-term data are needed to incorporate variability of weather and farming practices into assessments of wetland performance longevity. Research conducted over 12 yr quantified size-effectiveness of wetlands to reduce NO3 -N and dissolved P (orthophosphate [ORP]) loadings from subsurface tile systems. Nitrate-N export was significantly higher during corn (Zea mays L.) than soybean [Glycine max (L.) Merr.] production years, during which 80-84% of mean annual loadings were exported during spring. Wetlands representing 3% (W1) of tile-drained farmland area reduced 15-38% of NO3 -N export, with cumulative reductions of 39-49 and 49-57% observed in wetlands representing 6 (W2) and 9% (W3) areas, respectively. Mass NO3 -N removal ranged from 28 to 52%. Twelve-year total ORP load reductions for W1 ranged from 53 to 81%, with cumulative reductions of 35-91% and 32-95% for W2 and W3 wetlands, respectively. Mass ORP removal ranged from 71 to 85%. Results emphasize how incorporating constructed wetlands into state and watershed-level conservation planning can significantly contribute toward reducing excess N and P export to river systems and ultimately to the Gulf of Mexico.

Evaluating agricultural best management practices in tile-drained subwatersheds of the Mackinaw River, Illinois.

Best management practices (BMPs) are widely promoted in agricultural watersheds as a means of improving water quality and ameliorating altered hydrology. We used a paired watershed approach to evaluate whether focused outreach could increase BMP implementation rates and whether BMPs could induce watershed-scale (4000 ha) changes in nutrients, suspended sediment concentrations, or hydrology in an agricultural watershed in central Illinois. Land use was >90% row crop agriculture with extensive subsurface tile drainage. Outreach successfully increased BMP implementation rates for grassed waterways, stream buffers, and strip-tillage within the treatment watershed, which are designed to reduce surface runoff and soil erosion. No significant changes in nitrate-nitrogen (NO-N), total phosphorus (TP), dissolved reactive phosphorus, total suspended sediment (TSS), or hydrology were observed after implementation of these BMPs over 7 yr of monitoring. Annual NO-N export (39-299 Mg) in the two watersheds was equally exported during baseflow and stormflow. Mean annual TP export was similar between the watersheds (3.8 Mg) and was greater for TSS in the treatment (1626 ± 497 Mg) than in the reference (940 ± 327 Mg) watershed. Export of TP and TSS was primarily due to stormflow (>85%). Results suggest that the BMPs established during this study were not adequate to override nutrient export from subsurface drainage tiles. Conservation planning in tile-drained agricultural watersheds will require a combination of surface-water BMPs and conservation practices that intercept and retain subsurface agricultural runoff. Our study emphasizes the need to measure conservation outcomes and not just implementation rates of conservation practices.

In vitro inhibition of fungal activity by macrophage-mediated sequestration and release of encapsulated amphotericin B nanosupension in red blood cells.

The efficacy of antifungal treatment has been diminished by the biodistribution limitations of amphotericin B (AmB) due to its pharmacological profile, as well as the severe side effects it causes. A cellular drug-delivery system, which incorporates human erythrocytes (RBCs) loaded with an AmB nanosuspension (AmB-NS), is developed in order to improve antifungal treatment. AmB-NS encapsulation in RBCs is achieved by using hypotonic hemolysis, leading to intracellular AmB amounts of 3.81 +/- 0.47 pg RBC(-1) and an entrapment efficacy of 15-18%. Upon phagocytosis of AmB-NS-RBCs, leukocytes show a slow AmB release over ten days, and no alteration in cell viability. This results in an immediate, permanent inhibition of intra- and extracellular fungal activity. AmB-NS-RBC-leukocyte-mediated delivery of AmB is efficient in amounts 1000 times lower than the toxic dose. This drug-delivery method is effective for the transport of water-insoluble substances, such as AmB, and this warrants consideration for further testing.

HPLC detection of miltefosine using an evaporative light scattering detector.

Miltefosine has recently been introduced as leishmanicidal drug for oral administration (Impavido). Previous communications report about the use of liquid chromatography coupled with mass spectrometry detection to detect miltefosine in pharmaceutical preparations and biological fluids. We report about a new method to detect miltefosine using an evaporative light scattering detector (ELSD). The absolute recovery of the analyte was greater than 98.0%. The limit of quantification for miltefosine in plasma at a signal-to-noise ratio of 7.3 was 0.34 microg/ml. The precision of the assay yielded coefficients of variation ranging from 1.8 to 4.5% and an accuracy of 97-107%. Our method advances the qualitative and quantitative detection of miltefosine by combining rapid and efficient solid phase extraction and analysis with an evaporative light-scattering detector.

Ecological-evolutionary relationships in Passiflora alata from Rio Grande do Sul, Brazil.

The geographical distribution, ecological characteristics, flowering and fruiting times, and pollinating agents of Passiflora alata are considered and related to molecular genetic data gathered simultaneously. The first report on this species in Rio Grande do Sul was made in 1934, only in cultivated gardens. Approximately 20 years later, however, the species was already classified as efferata (wild) in Porto Alegre's suburbs. The data presented here, together with the DNA investigations, indicate that P. alata is actively colonizing previously unoccupied areas of this region.

Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors.

Anticancer drugs reversibly bound to magnetic fluids (ferrofluids) could be concentrated in locally advanced tumors by magnetic fields that are arranged at the tumor surface outside of the organism. If certain requirements are met, systemic toxicity might be minimized, and local tumor efficacy might be increased. We have conducted a Phase I clinical trial using this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas. Nine such patients received two treatment courses, 3 patients received one course, and 2 patients received three courses of magnetic drug targeting consisting of the infusion of epirubicin in increasing doses (from 5 to 100 mg/m2) that had been chemically bound to a magnetic fluid and the application of magnetic fields to the tumors for 60-120 min. In 2 of 14 patients, the same dose of epirubicin not bound to a magnetic fluid was administered systemically 3 weeks after drug targeting for intraindividual comparisons. Magnetic drug targeting with epirubicin was well tolerated. In one case, a planned second treatment was withdrawn, because of an episode of chills 130 min after infusion of the magnetic drug. Two patients received a third treatment because of good responses after the first two therapies. Based on magnetic resonance tomographic techniques, pharmacokinetics, and the histological detection of magnetites, it was shown that the ferrofluid could be successfully directed to the tumors in about one-half of the patients. Organ toxicity did not increase with the treatment, but epirubicin-associated toxicity appeared at doses greater than 50 mg/m2. Although treatment with magnetic drug targeting seems safe, improvements are necessary to make it more effective and independent of patient- or disease-related problems. A study design to compare conventional treatments with the new treatment form within one patient seems crucial to eliminate interindividual differences.

Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice.

During systemic immune responses, plasma blasts are generated in secondary lymphoid organs and migrate to the bone marrow, where they can become long-lived, being responsible for the maintenance of long-term antibody titers. Plasma blasts generated in mucosal immune responses of the small intestine home to the lamina propria (LP), producing mainly immunoglobulin A. The migration of these antibody-secreting cells is well characterized during acute immune responses. Less is known about their lifetime and contribution to the long-lived bone marrow compartment. Here we investigate the lifetime of plasma cells (PCs) and the relationship between the PC compartments of the gut and bone marrow after oral immunization. Our findings indicate that PCs in the LP can survive for extended time periods. PCs specific for orally administered antigens can be detected in the bone marrow for at least 9 months after immunization, indicating that the mucosal PC compartment can contribute to the long-lived PC pool in this organ, independent of the participation of splenic B cells. Our findings suggest that the compartmentalization between mucosal and systemic PC pools is less strict than previously thought. This may have implications for the development of vaccines as well as for autoantibody-mediated diseases.

The impact of nanobiotechnology on the development of new drug delivery systems.

Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently nucleotides. Nanoparticles and other colloidal drug delivery systems modify the kinetics, body distribution and drug release of an associated drug. Other effects are tissue or cell specific targeting of drugs and the reduction of unwanted side effects by a controlled release. Therefore nanoparticles in the pharmaceutical biotechnology sector improve the therapeutic index and provide solutions for future delivery problems for new classes of so called biotech drugs including recombinant proteins and oligonucleotides. This review discusses nanoparticular drug carrier systems with the exception of liposomes used today, and what the potential and limitations of nanoparticles in the field of pharmaceutical biotechnology are.

[Morphometric analysis of the temporomandibular joint with MRI in 320 joints]. / Morphometrische Analyse des Kiefergelenkes anhand von 320 Gelenken mit der MRT.

PURPOSE: To compare several morphometric parameters in MRI with the functional status of the articular disc in a large patient group suffering from internal derangement (ID) of the temporomandibular joint (TMJ). MATERIALS AND METHODS: In a retrospective study, 320 analyzable high resolution MRI examinations of the TMJs obtained in a 1.5 T unit were evaluated in 184 patients with clinically suspected ID. The analysis included the anatomical structures and a number of morphometric parameters previously described in the literature. The parameters were compared with the position of the articular disc. RESULTS: The disc position was categorized as "normal" (NDP, 21.9 %, n = 70), "anterior displacement with reduction on opening" (AMR, 51.6 %, n = 165) and "anterior displacement without reduction on opening" (AOR, 26.6 %, n = 85). With increasing disc displacement, significant configurational changes of the disc were observed. Disc displacement was associated with changes of the condyle consisting of increasing deformity and other degenerative changes. A large tuberculum and marked inclination of the eminence can be seen as predisposition for the development of ID. With increasing severity of the ID, the position of the condyle moved from a centric position of the condylar center to an excentric (dorsal and cranial) position. CONCLUSION: MRI demonstrated that increasing disc displacement is associated with changes of the disc, condyles and condylar position in the fossa.

Extracellular Vesicles from MSC Modulate the Immune Response to Renal Allografts in a MHC Disparate Rat Model.

Application of mesenchymal stromal cells (MSC) has been proposed for solid organ transplantation based on their potent immunomodulatory effects. Since side effects from the injection of large cells cannot be excluded, the hypothesis rises that extracellular vesicles (EV) may cause immunomodulatory effects comparable to MSC without additional side effects. We used MSC-derived EV in a rat renal transplant model for acute rejection. We analysed peripheral blood leukocytes (PBL), kidney function, graft infiltrating cells, cytokines in the graft, and alloantibody development in animals without (allo) and with EV application (allo EV). There was no difference in kidney function and in the PBL subpopulation including Tregs between allo and allo EV. In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo. TNF-α transcription was lower in allo EV grafts compared to allo; there was no difference regarding IL-10 and in the development of alloantibodies. In conclusion, the different cell infiltrates and cytokine transcription suggest distinct immunomodulatory properties of EV in allotransplantation. While the increased T- and B-cells in the allo EV grafts may represent a missing or negative effect on the adaptive immune system, EV seem to influence the innate immune system in a contrary fashion.

Delta F508 genotype does not predict disease severity in an ethnically diverse cystic fibrosis population.

OBJECTIVE: As part of a study to determine population-based frequencies of CFTR mutations in an ethnically diverse, midwestern cystic fibrosis (CF) population, clinical histories were studied in 119 CF patients. METHODOLOGY: We sought to examine the association between genotype as characterized by the delta F508 and 11 other commonly occurring mutations and clinical parameters including age at diagnosis, clinical presentation, sweat chloride level, chest roentgenogram score, clinical scores, pulmonary function test results, percent weight for height, and presence of associated CF complications. RESULTS: Age at diagnosis of CF was significantly associated with homozygosity for delta F508 (mean age at diagnosis +/- SE: 1.7 +/- 0.3 years for delta F508/delta F508 vs 3.9 +/- 0.9 years for delta F508/other and other/other; P = .03). No other age-adjusted clinical parameter was significantly associated with delta F508 or any other genotype. CONCLUSION: These data suggest that in this sample of CF patients, delta F508 genotype is not predictive of disease severity. The lack of association between disease severity and genotype in this ethnically diverse sample may reflect the presence of more severe undetected mutations in our sample, or the effects of modifying genes at other, non-CF loci.

Assessment of the vascularization of neuroendocrine tumors by stimulated acoustic emission of SH U 508A ultrasound contrast agent and color or power Doppler sonography.

RATIONALE AND OBJECTIVES: To assess the vascularization of neuroendocrine tumors by stimulated acoustic emission (SAE) of SH U 508A during the blood pool phase in comparison with contrast-enhanced Doppler sonography. METHODS: Thirty-six patients with neuroendocrine tumors received contrast-enhanced Doppler sonography and 21, an additional SAE. To classify tumor perfusion on Doppler sonography, a 4-step rating score was introduced: (1) no vessels (hypoperfusion); (2) one feeding or central vessel (hypoperfusion); (3) some vessels (hyperperfusion); and (4) disseminated vessels (hyperperfusion). In 36 patients, 1 pancreatic primary tumor, 33 liver metastases, 1 splenic metastasis, and 1 lymph node metastasis were examined. Results were correlated with biphasic spiral CT (n = 35) and angiography (n = 2). RESULTS: Arterial-phase CT and digital subtraction angiography revealed 18 hyper- and 18 hypoperfused lesions. Contrast-enhanced Doppler correctly classified 15 of 18 patients (83%) with hyperperfused lesions as well as 16 of 18 (89%) hypoperfused tumors by applying the rating score. SAE correctly identified 4 of 9 hyperperfused lesions (44%), 2 were isoperfused compared with normal liver tissue (22%), and 3 were hypoperfused (33%). Of 12 hypoperfused lesions, 11 were classified correctly (92%), and 1 showed isoperfusion. Hence, the positive and negative predictive values for SAE were 80% and 69%, respectively. For contrast-enhanced Doppler sonography, positive and negative predictive values were 88% and 84%, respectively. CONCLUSIONS: Blood pool SAE failed to determine subtle tumor perfusion correctly. The rating score for contrast-enhanced Doppler sonography characterized tumor perfusion with high accuracy. The use of a contrast agent significantly improved perfusion characterization.

Anomalous origin of the right vertebral artery: review of the literature and case report of right vertebral artery origin distal to the left subclavian artery.

We present the case of a 57-year-old patient who was admitted to the hospital for preoperative cerebral angiography because of an intraspinal mass at the level of C1 and C2. Angiographic examination revealed an abnormal origin of the right vertebral artery, which normally originates from the right subclavian artery. Thus, the right vertebral artery was the last branch of the supraaortic vessels. We also review herein the incidence of the various anomalous origins of the right vertebral artery in the literature and discuss their potential embryologic development and clinical significance.

MR of the eye with retrobulbar anesthesia.

MR imaging with retrobulbar anesthesia was performed in eight patients with uveal melanoma. Injection of 2 mL prilocain hydrochloride in 2% epinephrin into the eye muscle cone resulted in improved image quality in seven patients, without side effects. Ocular MR imaging can be indicated to clarify indeterminate sonographic findings in cases of extrascleral growth or to exclude optic nerve invasion in patients with tumors located at the posterior pole of the globe.