Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Repetitive on-demand drug release from polymeric matrices containing a macroscopic spherical iron core

\u3cp\u3eAbstract: A system for multiple on-demand drug release has been prepared that can be activated with an alternating magnetic field as external trigger. The core/shell samples have been developed based on a macroscopic spherical iron core coated with a thermoresponsive polymer, poly(styrene-stat-butyl methacrylate), containing ibuprofen as a model drug. During exposure of the samples to the magnetic field (ON state), the release rate of ibuprofen is significantly increased, up to 35 times the release rate without the magnetic field (OFF state). Using one sample or two samples in line with the magnetic field does not influence the ON/OFF ratio of the system, showing the possibility of using multiple samples to increase and tune the drug dose. Increasing the concentration of ibuprofen in the polymer layer is shown to increase the release rate in both the ON and OFF states. Increasing the size of the iron core and, consequently, decreasing the polymer thickness, was found to only increase the release rate during exposure resulting in higher ON/OFF ratios. The developed on demand drug delivery systems represents a promising development towards on demand drug delivery implants. Graphical abstract: [InlineMediaObject not available: see fulltext.] Reflections on career goals: During my chemical engineering studies, it was only during my master thesis work that I decided to continue with PhD research as I really enjoyed doing original research. When coming to the end of my PhD research under supervision of Prof. Ulrich S. Schubert, I developed the ambition to pursue an academic career. Fortunately, I got the opportunity to stay with Prof. Schubert as project leader for the Dutch Polymer Institute (DPI). Within this position, I supervised ten researchers and was able to start developing my independent research lines. Despite that I now advise students to not stay in the same laboratory, this first position allowed me to gain some initial independence and to publish a large number of papers that has been a great benefit in my further career. After two and a half years I needed a new challenge that I found by taking up a part-time position at a start-up company in Eindhoven, Dolphys Medical BV, while I also continued as part-time group leader for the DPI. As senior product developer, I was in charge of the research and learned to focus on the application rather than scientific curiosity. This experience made me realize that I prefer the freedom to do academic blue sky research and decided to fully go for an academic position. After personal discussions with some prominent professors in the Netherlands, I applied for a postdoc fellowship in the Netherlands with Prof. Roeland Nolte as well as a Humboldt fellowship in Germany with Prof. Martin Möller, which I both got. As a result, I went one year ‘abroad’ to Aachen and returned to Nijmegen where I intended to start my independent career. However, another opportunity came along. Via my personal network I was informed that I would make a good chance if I applied for a new professor scheme in Ghent. So I applied and the rest is history. Picture of the Supramolecular Chemistry Group (2017) [InlineMediaObject not available: see fulltext.].\u3c/p\u3

Influence of distribution on the heating of superparamagnetic iron oxide nanoparticles in poly(methyl methacrylate) in an Alternating Magnetic Field

The effect of distribution on the heating of superparamagnetic iron oxide nanoparticles in a polymer matrix has been investigated in an alternating magnetic field. Commercially available particles have been distributed using 30 and 50 wt % loading in a poly(methyl methacrylate) (p(MMA)) matrix by different preparation methods, resulting in different distributions of the particles. Freeze-drying a mixture of ferrofluid and p(MMA) latex followed by compounding is found to diminish particle aggregation, leading to an optimal distribution. Subsequently, the heating of the particles in the nanocomposites has been investigated in an alternating magnetic field of 2850 A m-1 with a 745 kHz frequency. These heating experiments show significantly higher specific absorption rates (SARs) of the incorporated iron oxide particles in the case of the freeze-drying method due to the improved distribution of the particles when compared to direct compounding or solvent casting. Furthermore, the higher particle loading provides faster heating, although the SAR decreases due to the presence of larger aggregates

Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.

Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk