[Voiding cystourethrography : Indications, fluoroscopy technique and radiation protection]. / Miktionszysturethrographie : Indikationen, Durchleuchtungstechnik und Strahlenschutz.

BACKGROUND: Voiding cystourethrography continues to be the gold standard in the diagnostics of a wide range of diseases of the urinary tract in children. MATERIAL AND METHODS: Indications, implementation of voiding cystourethrography in terms of preparation, materials used, dealing with the child and the parents as well as the standardized examination technique are presented. In particular, the technical aspects of fluoroscopy devices and criteria for good image quality are discussed. Case studies are used to illustrate the problems of frequent urological diseases. DISCUSSION: The three standard examinations for the detection of vesicoureteral reflux (VUR), radionuclide cystography, contrast-enhanced voiding urosonography and voiding cystourethrography are compared. Their potential for detecting VUR and additional urological pathologies is discussed in detail. Furthermore, the optimized examination technique of voiding cystourethrography is presented. The applicability of the current dose reference values of the German Federal Office for Radiation Protection (BfS) in the daily routine is discussed and the feasibility of the dose reference values is explained.

Nutritional depletion of total mixed rations by European starlings: Projected effects on dairy cow performance and potential intervention strategies to mitigate damage.

European starlings are an invasive bird species in North America that are known to cause damage to commercial dairies through the consumption of total mixed rations (TMR) destined for dairy cows. We hypothesized that large foraging flocks of starlings alter the physical composition of TMR, and that this change may be significant enough to affect milk production. To better determine if production losses could potentially occur in commercial dairies as a consequence of feed consumption by foraging flocks of starlings, we conducted controlled feeding experiments using a TMR sourced from a commercial dairy that is chronically plagued with seasonal starling damage. European starlings selected the high-energy fraction of the TMR and reduced starch and crude fat availability. Using the dairy National Research Council production model equations, the nutritional changes measured in the controlled feeding experiments could potentially reduce the productivity of dairies. Model output suggests that for Holsteins producing 32 kg of milk/d, total required net energy intake (NEI) was 31.5 Mcal/d. Within the reference TMR, NEI supplied was 29.3 Mcal/d, whereas within the starling-consumed TMR NEI supplied was 27.7 Mcal/d. Following our nutrition experiments, we assessed the efficacy of pelleted feed as a deterrent strategy for bird damage management in commercial dairies. Six different pelleted feed treatments of differing diameter were offered to starlings. All pellets of 0.95 cm diameter or larger inhibited starling consumption by ≥79%.

Diagnostic accuracy of contemporary multidetector computed tomography (MDCT) for the detection of lumbar disc herniation.

OBJECTIVES: To evaluate the diagnostic accuracy of multidetector CT (MDCT) for detection of lumbar disc herniation with MRI as standard of reference. METHODS: Patients with low back pain underwent indicated MDCT (128-row MDCT, helical pitch), 60 patients with iterative reconstruction (IR) and 67 patients with filtered back projection (FBP). Lumbar spine MRI (1.5 T) was performed within 1 month. Signal-to-noise ratios (SNR) of cerebrospinal fluid (CSF), annulus fibrosus (AF) and the spinal cord (SC) were determined for all modalities. Two readers independently rated image quality (IQ), diagnostic confidence and accuracy in the diagnosis of lumbar disc herniation using MRI as standard of reference. Inter-reader correlation was assessed with weighted κ. RESULTS: Sensitivity, specificity, precision and accuracy of MDCT for disc protrusion were 98.8%, 96.5%, 97.1%, 97.8% (disc level), 97.7%, 92.9%, 98.6%, 96.9% (patient level). SNR of IR was significantly higher than FBP. IQ was significantly better in IR owing to visually reduced noise and improved delineation of the discs. κ (>0.90) was excellent for both algorithms. CONCLUSION: MDCT of the lumbar spine yields high diagnostic accuracy for detection of lumbar disc herniation. IR improves image quality so that the provided diagnostic accuracy is principally equivalent to MRI. KEY POINTS: • MDCT is an accurate alternative to MRI in disc herniation diagnosis. • By IR enhanced image quality improves MDCT diagnostic confidence similar to MRI. • Advances in CT technology contribute to improved diagnostic performance in lumbar spine imaging.

RORγt expression in Tregs promotes systemic lupus erythematosus via IL-17 secretion, alteration of Treg phenotype and suppression of Th2 responses.

Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immunopathogenesis. However, a pathogenic role for the T helper type 17 (Th17) axis was demonstrated by many studies, while regulatory T cells (Tregs ) were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both the Treg characteristic transcription factor forkhead box protein 3 (FoxP3) and the Th17-defining retinoic acid receptor-related orphan nuclear receptor γt (RORγt). Studies in a model of acute glomerulonephritis unveiled potent regulatory, but also proinflammatory, functions of RORγt+ FoxP3+ Tregs . This bi-functional nature prompted us to suggest the name 'biTregs '. Importantly, the pathogenic biTreg effects were dependent upon expression of RORγt. We thus aimed to evaluate the contribution of RORγt+ FoxP3+ biTregs to pristane-induced SLE and explored the therapeutic potential of interference with RORγt activation. Our analyses revealed expansion of IL-17 producing biTregs in a distinctive time-course and organ-specific pattern, coincident with the development of autoimmunity and tissue injury. Importantly, specific ablation of RORγt activation in endogenous biTregs resulted in significant amelioration of pristane-induced pulmonary vasculitis and lupus nephritis. As potential mechanisms underlying the observed protection, we found that secretion of IL-17 by biTregs was abrogated completely in FoxP3Cre  × RORCfl/fl mice. Furthermore, Tregs showed a more activated phenotype after cell-specific inactivation of RORγt signalling. Finally, and remarkably, biTregs were found to potently suppress anti-inflammatory Th2 immunity in a RORγt-dependent manner. Our study thus identifies biTregs as novel players in SLE and advocates RORγt-directed interventions as promising therapeutic strategies.

[Changing the internal cost allocation (ICA) on DRG shares : Example of computed tomography in a university radiology setting]. / Umstellung der internen Leistungsverrechnung (ILV) auf DRG-Anteile : Beispiel der Computertomographie einer universitären Radiologie.

BACKGROUND: In hospitals, the radiological services provided to non-privately insured in-house patients are mostly distributed to requesting disciplines through internal cost allocation (ICA). In many institutions, computed tomography (CT) is the modality with the largest amount of allocation credits. OBJECTIVES: The aim of this work is to compare the ICA to respective DRG (Diagnosis Related Groups) shares for diagnostic CT services in a university hospital setting. MATERIALS AND METHODS: The data from four CT scanners in a large university hospital were processed for the 2012 fiscal year. For each of the 50 DRG groups with the most case-mix points, all diagnostic CT services were documented including their respective amount of GOÄ allocation credits and invoiced ICA value. As the German Institute for Reimbursement of Hospitals (InEK) database groups the radiation disciplines (radiology, nuclear medicine and radiation therapy) together and also lacks any modality differentiation, the determination of the diagnostic CT component was based on the existing institutional distribution of ICA allocations. RESULTS: Within the included 24,854 cases, 63,062,060 GOÄ-based performance credits were counted. The ICA relieved these diagnostic CT services by € 819,029 (single credit value of 1.30 Eurocent), whereas accounting by using DRG shares would have resulted in € 1,127,591 (single credit value of 1.79 Eurocent). The GOÄ single credit value is 5.62 Eurocent. CONCLUSIONS: The diagnostic CT service was basically rendered as relatively inexpensive. In addition to a better financial result, changing the current ICA to DRG shares might also mean a chance for real revenues. However, the attractiveness considerably depends on how the DRG shares are distributed to the different radiation disciplines of one institution.

Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.

Diffusion tensor imaging of the trigeminal nerve in patients with trigeminal neuralgia due to multiple sclerosis.

INTRODUCTION: Neurovascular compression (NVC) is the most common cause of trigeminal neuralgia (TN), leading to microstructural changes in the affected nerve detectable using diffusion tensor imaging (DTI). But TN may also emerge as a symptom of multiple sclerosis (MS). The aim of this study was to evaluate if patients with MS-related TN feature the same DTI characteristics as patients with TN caused by NVC. METHODS: Twelve patients with MS-related TN, 12 age-matched patients with NVC-related TN, and 12 healthy controls were included. Using 3T-DTI, mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for each affected and contralateral trigeminal nerve in patients with MS and NVC-related TN as well as healthy controls. Furthermore, presence of NVC was evaluated for patients with TN. RESULTS: There was no significant difference concerning FA or ADC when comparing the affected and the non-affected sides in patients with MS. FA was significantly lower and ADC higher in patients with MS on the TN affected as well as on the non-affected side compared to the non-affected side of patients with idiopathic TN or healthy controls. Likewise, FA was significantly lower on the affected side compared to the non-affected side in patients with idiopathic TN or healthy controls. NVC was evident in 41.7/0% on the affected/contralateral side in MS patients and 100/8% in the patients with NVC-related TN. CONCLUSION: In patients with MS-related TN, DTI reveals microstructural changes within the trigeminal nerve not only on the affected side but also on the clinically non-affected side.

UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation.

Podocytes are terminally differentiated cells of the glomerular filtration barrier that react with hypertrophy in the course of injury such as in membranous nephropathy (MGN). The neuronal deubiquitinase ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed and activated in podocytes of human and rodent MGN. UCH-L1 regulates the mono-ubiquitin pool and induces accumulation of poly-ubiquitinated proteins in affected podocytes. Here, we investigated the role of UCH-L1 in podocyte hypertrophy and in the homeostasis of the hypertrophy associated "model protein" p27(Kip1). A better understanding of the basic mechanisms leading to podocyte hypertrophy is crucial for the development of specific therapies in MGN. In human and rat MGN, hypertrophic podocytes exhibited a simultaneous up-regulation of UCH-L1 and of cytoplasmic p27(Kip1) content. Functionally, inhibition of UCH-L1 activity and knockdown or inhibition of UCH-L1 attenuated podocyte hypertrophy by decreasing the total protein content in isolated glomeruli and in cultured podocytes. In contrast, UCH-L1 levels and activity increased podocyte hypertrophy and total protein content in culture, specifically of cytoplasmic p27(Kip1). UCH-L1 enhanced cytoplasmic p27(Kip1) levels by nuclear export and decreased poly-ubiquitination and proteasomal degradation of p27(Kip1). In parallel, UCH-L1 increased podocyte turnover, migration and cytoskeletal rearrangement, which are associated with known oncogenic functions of cytoplasmic p27(Kip1) in cancer. We propose that UCH-L1 induces podocyte hypertrophy in MGN by increasing the total protein content through altered degradation and accumulation of proteins such as p27(Kip1) in the cytoplasm of podocytes. Modification of both UCH-L1 activity and levels could be a new therapeutic avenue to podocyte hypertrophy in MGN.

[MRI for monitoring of high intensity focused ultrasound: current developments]. / MRT zum Monitoring bei hochintensivem fokussiertem Ultraschall: Aktuelle Entwicklungen.

With respect to monitoring of high intensity focused ultrasound (HIFU), synonym focused ultrasound (FUS) treatment, magnetic resonance imaging (MRI) is characterized by several advantageous properties: the precise definition and morphological characterization of the target area (before and after the intervention), the real-time visualization of the treatment effect by thermal imaging (during the intervention) and in the sense of a stereotactic system, the 3-dimensional localization of the target lesion, planning of the target volume and assessment of the achieved ablation volume (before and during the intervention). Non-enhanced T2-weighted multislice MR images are acquired for planning of the intervention. For temperature monitoring (comprising thermometry and thermodosimetry), the temperature-dependent shift of proton resonance frequency (PRFS) is most frequently employed. This method is independent of the treated tissue type or thermally induced tissue changes and facilitates a relative measurement of the temperature change based on a reference value. Future MRI applications include diffusion-weighted MRI (DWI-MRI; for the intrainterventional estimation of treatment efficacy), dynamic contrast-enhanced MRI (DCE-MRI, for the prediction of the potential and assessment of the treatment effect achieved) and motion-corrected temperature monitoring (referenceless and multibaseline thermometry).

The safety and efficacy of dexmedetomidine for postoperative sedation in the cardiac surgery intensive care unit.

INTRODUCTION: The α2-adrenoceptor agonist dexmedetomidine is an effective postoperative sedative without clear advantages over midazolam or propofol. We hypothesized that routine use of dexmedetomidine allows early extubation in cardiac surgery patients. Secondary outcomes included the use of narcotic and non-narcotic analgesics during the first 48 hours, early postoperative functional status, and the incidence of bradycardia or hypotension. METHODS: We retrospectively analyzed patients admitted to a cardiothoracic intensive care unit after cardiac surgery. Patient charts and the Society of Thoracic Surgery National database were reviewed. Patients who received no sedation were compared to those who received dexmedetomidine. RESULTS: Ninety-nine patients (52 receiving no sedation and 47 receiving dexmedetomidine) were included in this study. The median time to extubation was 3.9 (2.8-5.4) hours in the control group versus 4.7 (3.45-6.52) hours in the dexmedetomidine (P=.16). The incidence of bradycardia, hypotension, the ability to ambulate, and Glascow Coma Scores = 15 on postoperative day 0 did not differ significantly. Acetaminophen was used more frequently in the first 48 hours postoperatively in dexmedetomidine patients (P=.02) and a trend toward higher opioid (P=.09) and ketorolac use (P=.30) over the first 48 hours was noted. CONCLUSIONS: The use of dexmedetomidine did not allow earlier extubation or less use of analgesics when compared to no sedation. Bradycardia and hypotension were not a problem with the use of dexmedetomidine.

[MR-guided focused ultrasound. Current and future applications]. / MR-gesteuerter fokussierter Ultraschall. Aktuelle und potenzielle Indikationen.

STANDARD RADIOLOGICAL METHODS: High-intensity focused ultrasound (synonyms FUS and HIFU) under magnetic resonance imaging (MRI) guidance (synonyms MRgFUS and MR-HIFU) is a completely non-invasive technology for accurate thermal ablation of a target tissue while neighboring tissues and organs are preserved. METHODICAL INNOVATIONS: The combination of FUS with MRI for planning, (near) real-time monitoring and outcome assessment of treatment markedly enhances the safety of the procedure. ACHIEVEMENTS: The MRgFUS procedure is clinically established in particular for the treatment of symptomatic uterine fibroids, followed by palliative ablation of painful bone metastases. Furthermore, promising results have been shown for the treatment of adenomyosis, malignant tumors of the prostate, breast and liver and for various intracranial applications, such as thermal ablation of brain tumors, functional neurosurgery and transient disruption of the blood-brain barrier.

[Treatment of typical hemolytic-uremic syndrome. Knowledge gained from analyses of the 2011 E. coli outbreak]. / Therapie des typischen hämolytisch-urämischen Syndroms. Erkenntnisse aus dem E.-coli-Ausbruch 2011.

Shiga toxin-associated hemolytic uremic syndrome (HUS) is an entity of thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, central nervous symptoms, and renal insufficiency. In May 2011, an outbreak of enterohemorrhagic Escherichia coli (EHEC; O104:H4) occurred in Northern Germany. By the end of July 2011, the outbreak was over but nearly 4000 patients had an EHEC infection, 855 cases of hemolytic-uraemic syndrome were reported to the Robert Koch Institute, and there were 35 (4.1%) deaths. Shiga toxin-induced HUS is a rare disease and no controlled clinical trials on therapeutic options are available. First analyses of this outbreak suggest that therapeutic plasma exchange, which was used in the majority of patients, had no benefit and might even be harmful. The role of eculizumab, a monoclonal antibody which inhibits the complement system, is being examined in a multicenter study: the results have not been published yet. Promising is the use of some antibiotics. This would change a paradigm that antibiotics should be avoided. Ongoing and future analyses of the epidemic should be awaited before a final recommendation regarding the different treatment strategies can be made.

Conversion from cyclosporine to everolimus at 4.5 months posttransplant: 3-year results from the randomized ZEUS study.

The long-term effect of conversion from calcineurin inhibitor (CNI) therapy to an mTOR inhibitor requires clarification. Following completion of the 12-month, open-label, multicenter ZEUS study, in which 300 kidney transplant recipients were randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy was reintroduced in 28.4% of everolimus patients by month 36. The primary efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was significantly higher with everolimus versus the CsA group at month 24 (7.6 mL/min/1.73 m(2) , 95%CI 4.3, 11.0 mL/min/1.73 m(2) ; p < 0.001) and month 36 (7.5 mL/min/1.73 m(2) , 95%CI 3.6, 11.4 mL/min/1.73 m(2) ; p < 0.001). The incidence of biopsy-proven acute rejection from randomization to month 36 was 13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and graft survival, as well as incidences of malignancy, severe infections and hospitalization, were similar between groups. Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years. There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant.

[Membranous glomerulonephritis: better therapy with autoantibody monitoring?]. / Membranöse Glomerulonephritis: Differenziertere Therapien durch Autoantikörperbestimmung?

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. Binding of circulating autoantibodies to the glomerular filtration barrier leads to the development of this autoimmune disease. The clinical symptoms range from small proteinuria to severe nephrotic syndrome with enormous oedema, not controllable hyperlipidaemia and increased disposition for infection. One third of patients reach complete or partial remission of proteinuria under symptomatic treatment, which includes ACE-inhibitors and AT-I-blockers, loop diuretics and statins. Untreated the disease leads to loss of renal function over 5-10 years in 20-30% of patients. A risk score based on proteinuria and renal function is used to guide the decision when to start with an immunosuppressive therapy. A better adapted diagnostic and therapy of membranous nephropathy may be possible through measurement of circulating autoantibodies directed against a podocytic phospholipase-A(2) receptor.

Rituximab in adult patients with immunosuppressive-dependent minimal change disease.

BACKGROUND: Minimal change disease (MCD) is one of the leading causes of nephrotic syndrome. Steroid therapy is effective in achieving remission, but relapses, steroid dependence, and steroid resistance are therapeutic challenges. The use of second-line agents such as cyclophosphamide is associated with toxicity and adverse effects. Therefore, we studied the effect of rituximab (RTX) on proteinuria in adult patients with immunosuppressive (IS)-dependent MCD. METHODS: In this single-center, prospective, open series study, 6 consecutive patients with IS-dependent MCD and frequent relapses on different IS regimens - one of them after previous RTX treatment - were included. Patients were treated with a single dose of RTX (375 mg/m²). An additional dose of RTX was administered depending on B-cell count and proteinuria. RESULTS: 5 out of 6 patients achieved complete remission at the end of the follow-up; the other patient had a partial remission. All patients are free of additional IS agents and other medications were remarkably reduced. Three patients had a relapse, which was successfully treated with a further RTX treatment. CONCLUSIONS: RTX could be an alternative in the therapy of patients with IS-dependent MCD, leading to successful cessation of other IS treatment.

Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin.

Phenylbutazone (PBZ) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro-intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono-substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin-permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady-state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin-penetration enhancer in the liposomal gel of PBZ for deer.