Is herpes zoster a marker for occult or subsequent malignancy?

BACKGROUND: It has been suggested that herpes zoster may be a marker for occult malignancy. AIM: To examine the emergence of a subsequent cancer diagnosis in patients with and without herpes zoster. DESIGN OF STUDY: Retrospective cohort study. SETTING: Results were based on the database of Intego, an ongoing Belgian general practice-based morbidity registry, covering 37 general practitioners and including about 311 000 patient years between the years 1994 and 2000. METHOD: Survival analysis comparing the emergence of malignancy in patients with and without herpes zoster. RESULTS: The number of patients below the age of 65 years with herpes zoster, cancer or both was too low to draw any sensible conclusions. Above the age of 65 years we identified a significant increase of cancer emergence in the whole group and in females (hazard ratio = 2.65, 95% confidence interval = 1.43 to 4.90), but not in males. No difference could be identified in the first year after the herpes zoster infection. CONCLUSION: Our results do not justify extensive testing for cancer in herpes zoster patients. The association we identified, however, leaves open a number of questions with respect to the physiopathology behind it.     

Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

Rigid maleimide-alt-vinylpyridine copolymers with pendant chromophores. Synthesis,characterization and monolayer formation

A new series of rigid polymers was synthesized via radical copolymerization of N-phenylmaleimides, bearing pendant chromophores, with 4-vinylpyridine or styrene. Structural characterization was achieved by ¹H NMR and ¹³C NMR spectroscopy, gel permeation chromatography (GPC), elemental analysis and differential scanning calorimetry (DSC). The thermal properties as well as the morphology of the investigated polymers at the air-water interface appear to be related to their rigidity. In spite of the presence of excellent mesogenic units, the polymers do not exhibit liquid crystalline behaviour. The 4-vinylpyridine copolymers form stable monolayers at the air-water interface. The attached chromophores electronically behave as monomers, as shown with in situ UVVIS absorption spectroscopy. Brewster angle microscopy shows a spontaneous aggregation of these polymers into domains on a neutral subphase, whereas on an acidic subphase a more homogeneous monolayer is formed. The monolayers give Z-type transfer onto hydrophilic quartz. However, the chromophores seem to be oriented randomly at the substrate surface. The styrene copolymers do not form stable monolayers as a result of crystallization at the air-water interface.     

Effects of interleukin 4 on CD25+CD4+ regulatory T cell function

CD25+CD4+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance against self and non-self. The modulatory effects of cytokines, such as interleukin 4 (IL-4) on the function of Tregs have not been explored in detail. We here report that IL-4 prevents spontaneous apoptosis and the decline of foxp3 mRNA which were found to occur during culture of isolated Tregs. Tregs exposed to IL-4 were more potent in suppressing the proliferation of na?ve CD4+ T cells and they better inhibited IFN-gamma production by CD4+ T cells as compared to Tregs cultured in medium. IL-4 also enhanced membrane IL-2Ralpha (CD25) expression on Tregs above the levels observed on freshly isolated cells. IL-4-mediated effects on Treg function persisted in Tregs from Stat6-/- mice, pointing to a Stat6-independent intracellular transduction pathway. In conclusion, our data suggest that the anti-inflammatory function of IL-4 could partly be mediated by effects on Tregs function.     

Monte Carlo simulations of a scintillation camera using GATE: validation and application modelling

Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.     

Subtelomeric deletions detected in patients with idiopathic mental retardation using multiplex ligation-dependent probe amplification (MLPA)

Subtelomeric rearrangements are responsible for 5% to 10% of cases of unexplained mental retardation. Despite their clinical relevance, methods to screen for these cytogenetically invisible abnormalities on a routine base are scarce. We screened patients with idiopathic mental retardation for subtelomeric aberrations using multiplex ligation-dependent probe amplification (MLPA). This recently developed technique is based on PCR amplification of ligated probes hybridized to chromosome ends. Currently, 41 telomeres can be screened in just two multiplex reactions. Four subtelomeric rearrangements (5.3%) were detected in a group of 75 patients with mild to severe mental retardation in combination with dysmorphic features and/or a familial history of mental retardation: two terminal 1p deletions, a terminal 1q deletion, and a terminal 3p deletion. Deletions could be verified by FISH and marker analysis. In one case the MLPA indicated a terminal 21q deletion due to a 3-bp deletion at the site of the probe, giving a false-positive rate of 1.3%. This study demonstrates that MLPA is a fast and reliable screening method, potentially suitable for use in routine diagnostics.     

Antibodies raised against rough mutants of Escherichia coli and Salmonella strains are opsonic only in the presence of complement

The opsonic capacity of antisera raised in rabbits against rough (R) mutants and smooth (S) parent strains of Escherichia coli and Salmonella typhimurium were studied. All specific antibodies in the antisera belonged to the immunoglobulin G (IgG) class. Radioactively labeled bacteria were preincubated in various dilutions of antisera, in which complement was inactivated. Fresh normal rabbit serum, as a standard complement source, was used in some experiments. After preincubation, washed bacteria were added to normal human neutrophils. Opsonization of R mutants for 5 min in 5% fresh normal rabbit serum resulted in effective phagocytosis; S strains needed at least a 30-min opsonization time or 20 to 50% serum. After incubation for 5 min in diluted, homologous antisera, phagocytosis of S strains was optimal, but preincubation of R mutants in diluted, homologous antisera did not lead to amelioration of phagocytosis compared with that of bacteria preincubated in buffer only. However, when fresh normal serum was added to homologous antisera, uptake of R mutants occurred at a faster rate than that of bacteria opsonized in fresh serum alone. Using six clinical isolates of members of the family Enterobacteriaceae, we found that, with or without complement, antisera raised against E. coli J5 or S. typhimurium Re had, with the exception of one strain, no opsonic activity for these strains. Thus, the protective effect of R antisera in gram-negative bacteremia, as shown by several investigators, is unlikely to be mediated through enhanced opsonization of invading bacteria by IgG antibodies directed against these R mutants.     

Urbanization and risk for schizophrenia: does the effect operate before or around the time of illness onset?

BACKGROUND: Higher level of urbanicity of place of birth and of place of residence at the time of illness onset has been shown to increase the risk for adult schizophrenia. However, because urban birth and urban residence are strongly correlated, no conclusions can be drawn about the timing of the risk-increasing effect. The current study discriminated between any effect of urbanization before and around the time of illness onset. METHODS: All individuals born between 1972 and 1978 were followed up through the Dutch National Psychiatric Case Register for first admission for schizophrenia until 1995 (maximum age 23 years). Exposure status was defined by a combination of place of birth and place of residence at the time of illness onset in the three most densely populated provinces of the Netherlands (the 'Randstad', exposed) or in all other areas (the 'non-Randstad', non-exposed). The risk for schizophrenia was examined in four different exposure groups: non-exposed born and non-exposed resident (NbNr, reference category), non-exposed born and exposed resident (NbEr), exposed born and non-exposed resident (EbNr) and exposed born and exposed resident (EbEr). RESULTS: The greatest risk for schizophrenia was found in the EbNR group, without evidence for any additive effect of urban residence (rate ratio (RR) for narrow schizophrenia in EbNr group, 2.05 (95 % CI 1.18-3-57); in EbEr group, 1.96 (95% CI, 1.55-2.46)). Individuals who were not exposed at birth, but became so later in life, were not at increased risk of developing schizophrenia (RR for narrow schizophrenia in NbEr group, 0.79 (0.46-1.36)). CONCLUSION: The results suggest that environmental factors associated with urbanization increase the risk for schizophrenia before rather than around the time of illness onset.     

Limitations and caveats of magnetic cell labeling using transfection agent complexed iron oxide nanoparticles

Cell labeling with various types of nanomaterial, such as FDA‐approved iron oxide nanoparticles (IONPs) has become common practice in biomedical research. The low uptake of IONPs stimulates the use of transfection agents (TA), but the effect on stability of the IONPs and their cellular interactions has received minimal attention. In the present study, we evaluated the use of Lipofectamine as a commonly used TA and tested different ratios of TA and IONPs. While the TA–IONP complexes are stable in saline, at a high ratio of TA over IONP, substantial aggregation occurred in serum‐containing media. Even for the highest ratio, TA was unable to completely cover the IONPs, resulting in a net negative charge of all complexes. At high TA–IONP ratios, more complexes remained surface‐associated without internalization, resulting in cell death, while at lower TA–IONP ratios, complexes were more avidly taken up through fluid‐phase pinocytosis and clathrin‐mediated endocytosis. At later time points, the endocytosed complexes accumulated within the lysosomes and affected the appearance of lysosomal structures. The data indicate that TAs should be used with care as, depending on the ratio of TA and IONP, the complexes may aggregate, inducing cell death and preventing internalization. Copyright © 2012 John Wiley & Sons, Ltd.