BACKGROUND: The primary aim of the study was to investigate the cytokine/chemokine response in the kidney, lung, and liver following acute kidney injury (AKI). The secondary aim was to test whether alpha-melanocyte-stimulating hormone (alpha-MSH) could prevent a reduction in organ function, and attenuate the inflammatory cytokine/chemokine response within the kidney, lung, and liver following AKI in rats with or without preexisting chronic kidney disease (CKD). METHODS: A two-stage animal model, in which AKI was induced in rats with preexisting CKD, induced by 5/6 nephrectomy (Nx), was used. Six weeks later, AKI was induced by intestinal ischemia and reperfusion (IIR). Sham procedures [S(Nx) and S(IIR)] were also performed. RESULTS: Increasing levels of serum creatinine (sCr) demonstrated progressive development of CKD in response to Nx, and following IIR sCr levels increased further significantly, except in the S(Nx) group treated with alpha-MSH. However, no significant differences in the fractional increase in sCr were observed between any of the groups exposed to IIR. In kidney, lung, and liver tissue the levels of interleukin (IL)-1beta were significantly higher in rats undergoing IIR when compared to the S(IIR) and control rats. The same pattern was observed for the chemokine monocyte chemoattractant protein (MCP)-1 in lung and liver tissue. Furthermore, kidney IL-1beta and RANTES levels were significantly increased after IIR in the Nx rats compared to the S(Nx) rats. CONCLUSION: Both the functional parameters and the cytokine/chemokine response are as dramatic when AKI is superimposed onto CKD as onto non-CKD. No convincing protective effect of alpha-MSH was detected.
Acute Kidney Injury* ; alpha-MSH* ; Animals ; Chemokine CCL5 ; Creatinine ; Interleukins ; Ischemia ; Kidney ; Liver ; Lung ; Models, Animal ; Monocytes ; Nephrectomy ; Rats* ; Renal Insufficiency, Chronic* ; Reperfusion

PURPOSE: To develop a novel combination of controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) with integrated SSFP (CAIPI-iSSFP) for accelerated SSFP imaging without banding artifacts at 3T. MATERIALS AND METHODS: CAIPI-iSSFP was developed by adding a dephasing gradient to the balanced SSFP (bSSFP) pulse sequence with a gradient area that results in 2π dephasing across a single pixel. Extended phase graph (EPG) simulations were performed to show the signal behaviors of iSSFP, bSSFP, and RF-spoiled gradient echo (SPGR) sequences. In vivo experiments were performed for brain and abdominal imaging at 3T with simultaneous multi-slice (SMS) acceleration factors of 2, 3 and 4 with CAIPI-iSSFP and CAIPI-bSSFP. The image quality was evaluated by measuring the relative contrast-to-noise ratio (CNR) and by qualitatively assessing banding artifact removal in the brain. RESULTS: Banding artifacts were removed using CAIPI-iSSFP compared to CAIPI-bSSFP up to an SMS factor of 4 and 3 on brain and liver imaging, respectively. The relative CNRs between gray and white matter were on average 18% lower in CAIPI-iSSFP compared to that of CAIPI-bSSFP. CONCLUSION: This study demonstrated that CAIPI-iSSFP provides up to a factor of four acceleration, while minimizing the banding artifacts with up to a 20% decrease in the relative CNR.
Acceleration ; Artifacts ; Brain ; Liver ; White Matter

Management of intestinal strictures associated with Crohn's disease (CD) is clinically challenging despite advanced medical therapy directed toward mucosal healing to positively influence the natural course of CD-associated complications. Although medical therapy is available for inflammatory strictures, therapy of fibrostenotic strictures is the domain of surgery and endoscopy. Endoscopic balloon dilation (EBD) has been recognized as a well-established first-line procedure in terms of safety and efficacy. Although surgery is a valuable treatment modality for the management of CD-related strictures, EBD can help prevent multiple surgical interventions, which might in the long-term lead to a risk of short bowel syndrome. In this review we discuss requirements, techniques, safety, short- and long-term outcomes, as well as combinations of this procedure with surgical and medical treatment in CD-associated intestinal strictures.
Constriction, Pathologic* ; Crohn Disease ; Endoscopy ; Short Bowel Syndrome

OBJECTIVE: To describe a 2010 outbreak of nine cases of measles in Australia possibly linked to an index case who travelled on an international flight from South Africa while infectious.

METHODS: Three Australian state health departments, Victoria, Queensland and New South Wales, were responsible for the investigation and management of this outbreak, following Australian public health guidelines. Results: An outbreak of measles occurred in Australia after an infectious case arrived on a 12-hour flight from South Africa. Only one of four cases in the first generation exposed to the index case en route was sitting within the two rows recommended for contact tracing in Australian and other guidelines. The remaining four cases in subsequent generations, including two health care workers, were acquired in health care settings. Seven cases were young adults. Delays in diagnosis and notification hampered disease control and contact tracing efforts.

CONCLUSION: Review of current contact tracing guidelines following in-flight exposure to an infectious measles case is required. Alternative strategies could include expanding routine contact tracing beyond the two rows on either side of the case’s row or expansion on a case-by-case basis depending on cabin layout and case and contact movements in flight. Releasing information about the incident by press release or providing generic information to everyone on the flight using e-mail or text messaging information obtained from the relevant airline, may also be worthy of consideration. Disease importation, inadequately vaccinated young adults and health care-related transmission remain challenges for measles control in an elimination era.

Melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin alpha5 and abolishing its activity. Active ERK signaling is known to block chondrogenic differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified cartilage layer of the articular cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes cartilage differentiation and inhibits differentiation into bone potentially by regulating signaling processes during differentiation.
Animals ; Bone Morphogenetic Proteins/metabolism ; Cartilage/*cytology/metabolism ; *Cell Differentiation ; Chondrocytes/cytology/enzymology ; Extracellular Matrix Proteins/deficiency/*metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Integrin alpha5/metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Mice ; Neoplasm Proteins/deficiency/*metabolism ; Osteogenesis ; Protein Binding ; Signal Transduction ; Smad Proteins/metabolism

Concomitant Loeys-Dietz syndrome (LDS) and hematologic malignancies are exceptionally rare. This is the first report of a patient operated on for aortic root dilation who had been previously diagnosed with LDS and B-cell-lymphoma. After completion of chemotherapy and complete remission, an elective valve-sparing aortic root replacement (using the David-V method) was performed. Due to the positive family history, pre-operative genetic counseling was conducted, and revealed LDS with a TGFBR1 (transforming growth factor beta receptor type I) mutation in 6 probands of the family, albeit in 1 of them posthumously. This missense mutation has been previously described in relation to aortic dissection, but a causative relationship to malignancy has so far neither been proposed nor proven.
Aortic Aneurysm, Thoracic ; Drug Therapy ; Genetic Counseling ; Hematologic Neoplasms ; Humans ; Loeys-Dietz Syndrome ; Lymphoma, B-Cell ; Mutation, Missense

BACKGROUND: The Occupational Safety and Health Monitoring and Assessment Tool (OSH-MAT) is a practical instrument that is currently used in the German woodworking and metalworking industries to monitor safety conditions at workplaces. The 12-item scoring system has three subscales rating technical, organizational, and personnel-related conditions in a company. Each item has a rating value ranging from 1 to 9, with higher values indicating higher standard of safety conditions. METHODS: The reliability of this instrument was evaluated in a cross-sectional survey among 128 companies and its validity among 30,514 companies. The inter-rater reliability of the instrument was examined independently and simultaneously by two well-trained safety engineers. Agreement between the double ratings was quantified by the intraclass correlation coefficient and absolute agreement of the rating values. The content validity of the OSH-MAT was evaluated by quantifying the association between OSH-MAT values and 5-year average injury rates by Poisson regression analysis adjusted for the size of the companies and industrial sectors. The construct validity of OSH-MAT was examined by principle component factor analysis. RESULTS: Our analysis indicated good to very good inter-rater reliability (intraclass correlation coefficient = 0.64–0.74) of OSH-MAT values with an absolute agreement of between 72% and 81%. Factor analysis identified three component subscales that met exactly the structure theory of this instrument. The Poisson regression analysis demonstrated a statistically significant exposure–response relationship between OSH-MAT values and the 5-year average injury rates. CONCLUSION: These analyses indicate that OSH-MAT is a valid and reliable instrument that can be used effectively to monitor safety conditions at workplaces.
Cross-Sectional Studies ; Occupational Health*

BACKGROUND/AIMS: Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average “real world” patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes. METHODS: Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed. RESULTS: The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies. CONCLUSIONS: Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort.
Biological Therapy ; Cohort Studies ; Crohn Disease ; Humans ; Necrosis ; Patient Selection ; Retrospective Studies ; Ustekinumab ; Weather

Concomitant Loeys-Dietz syndrome (LDS) and hematologic malignancies are exceptionally rare. This is the first report of a patient operated on for aortic root dilation who had been previously diagnosed with LDS and B-cell-lymphoma. After completion of chemotherapy and complete remission, an elective valve-sparing aortic root replacement (using the David-V method) was performed. Due to the positive family history, pre-operative genetic counseling was conducted, and revealed LDS with a TGFBR1 (transforming growth factor beta receptor type I) mutation in 6 probands of the family, albeit in 1 of them posthumously. This missense mutation has been previously described in relation to aortic dissection, but a causative relationship to malignancy has so far neither been proposed nor proven.

A 65-year-old woman was addressed for clinical and biological suspicion of ovarian cancer relapse. 18F-FDG PET/CT revealed massive peritoneal carcinomatosis. Post-chemotherapy PET/CT showed complete metabolic response in initial localizations albeit three new 18F-FDG uptakes appeared in the mesentery and in the retro-hepatic space. Close follow-up (including PET/ CT scan) and surgical examination of the abdominal cavity confirmed the absence of malignancy and the benign nature of these lesions, which appeared to be peritoneal fibrosis mimicking persistent carcinomatosis.