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Objectives: While tumour necrosis factor (TNF)-α-inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF-α-inhibitor treatment and an increased risk for malignancies especially lymphoma., Methods: Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail., Results: Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years. 12 cases of suspected malignancies, including 7 lymphoid neoplasms, have been reported in patients treated with methotrexate (MTX) , and /or TNF-α inhibitors. 11 patients had received MTX, two received cyclosporine A, single patients received sulfasalazine, azathioprine or leflunomide. 10 patients were exposed to biologics, 9 etanercept, two adalimumab, one infliximab and one case was consecutively treated with adalimumab, etanercept, infliximab and abatacept. A case of mild myelodysplasia, in which the patient recovered spontaneously, a case of lymphoproliferation without clonality and a case of cervical dysplasia were treated as suspected, but not confirmed malignancies. Cases in which a malignant disease was confirmed included two cases of Hodgkin's lymphoma, one case of non-Hodgkin's lymphoma, two cases of acute lymphatic leukaemia (ALL) and one patient with lymphoproliferative disorder, who recovered after discontinuation of immunosuppressive therapy. Single confirmed cases of thyroid carcinoma, yolk sac carcinoma and anaplastic ependymoma have also been described. One patient not exposed to biologics died of ALL, all other patients recovered., Conclusions: In this large cohort of JIA patients, the occurrence of malignancies was higher than in the general population. Whether JIA patients had an increased risk for malignancies, either through their rheumatic disease, or through treatment remains in debate. Treatment with etanercept seems not to further increase the malignancy risk. Long-term observation of JIA patients treated with TNF-α inhibitors into adulthood remains an important task.

A 9-year-old girl born to healthy parents showed manifestations suggestive of ataxia telangiectasia (AT), such as short stature, sudden short bouts of horizontal and rotary nystagmus, a weak and dysarthric voice, rolling gait, unstable posture, and atactic movements. She did not show several cardinal features typical of AT such as frequent, severe infections of the respiratory tract. In contrast, she showed symptoms not generally related to AT, including microcephaly, profound motor and mental retardation, small hands and feet, severely and progressively reduced muscle tone with slackly protruding abdomen and undue drooling, excess fat on her upper arms, and severe oligoarthritis. A cranial MRI showed no cerebellar hypoplasia and other abnormalities. In peripheral blood samples she carried a de novo duplication of 3.14 Mb in chromosomal region 19q12 containing six annotated genes, UQCRFS1, VSTM2B, POP4, PLEKHF1, CCNE1, and ZNF536, and a de novo mosaic inversion 14q11q32 (96% of metaphases). In a saliva-derived DNA sample only the duplication in 19q12 was detected, suggesting that the rearrangements in blood lymphocytes were acquired. These findings reinforced the suspicion that she had AT. AT was confirmed by strongly elevated serum AFP levels, cellular radiosensitivity and two inherited mutations in the ATM gene (c.510_511delGT; paternal origin and c.2922-50_2940del69; maternal origin). This case suggest that a defective ATM-dependent DNA damage response may entail additional stochastic genomic rearrangements. Screening for genomic rearrangements appears indicated in patients suspected of defective DNA damage responses., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Three-dimensional echocardiography (3DE) improves the accuracy of left ventricle (LV) volumetry compared with the two-dimensional echocardiography (2DE) approach because geometric assumptions in the algorithms may be eliminated. The relationship between accuracy of mode (short- versus long-axis planimetry) and the number of component images versus time required for analysis remains to be determined. Sixteen latex models simulating heterogeneously distorted (aneurysmatic) human LVs (56-303 ml; mean 182+/-82 ml) were scanned from an 'apical' position (simultaneous 2DE and 3DE). For 3DE volumetry, the slice thickness was varied for the short (C-scan) and long axes (B-scan) in 5-mm steps between 1 and 25 mm. The mean differences (true-echocardiographic volumes) were 16.5+/-44.3 ml in the 2DE approach (95% confidence intervals -27.8 to +60.8) and 0.6+/-4.0 ml (short axis; 95% confidence intervals -3.4 to +4.6) as well as 2.1+/-9.9 ml (long axis; 95% confidence intervals -7.8 to +12.0) in the 3DE approach (in both cases, the slice thickness was 1 mm). Above a slice thickness of 15 mm, the 95% confidence intervals increased steeply; in the short versus long axes, these were -6.5 to +8.5 versus -7.0 to +10.6 at 15 mm and -10.1 to +15.7 versus -11.3 to +10.9 at 20 mm. The intra-observer variance differed significantly (p<0.001) only above 15 mm (short axis). Time required for analysis derived by measuring short-axis slice thicknesses of 1, 15, and 25 mm was 58+/-16, 7+/-2 and 3+/-1 min, respectively. The most rational component image analysis for 3DE volumetry in the in vitro model uses short-axis slices with a thickness of 15 mm., (Copyright (c) 2005 S. Karger AG, Basel.)

Insect endoparasitoids are capable of suppressing the immune reaction of their habitual hosts in a specific way. Salt (1968) characterized some of the implications: This seeming contradiction--that defence reactions against all kinds of foreign bodies are available to insects and that endophagous parasitoids are nevertheless able to develop in insect hosts--is resolved by recourse to one of the principles of host specificity. Although insects as a group react to every foreign body in the sense that any organism or substance evokes a reaction in most insects, each species of insect fails to make a reaction (or makes an ineffective reaction) to a small group of organisms, its habitual parasites. It is the common paradox of parasitology that defence reactions are least effective against the most noxious parasites, involving the tautology that the most noxious parasites are those against which defence reactions are least effective. Recently, VLP of hymenopteran wasps have been shown to play a crucial part in suppressing the cellular encapsulation reaction (Stoltz and Vinson, 1979a). In some parasitoid wasps, polydnavirus particles are involved in the phenotypic transformation of hemocytes, reducing the capability of the host to mount an immune reaction towards the parasitoid egg (Stoltz and Guzo, 1986; Davies et al., 1987). However, at least in Venturia, the eggs are effectively protected by VLP that lack significant amounts of nucleic acids, precluding any virus expression in the host. The question was raised whether VLP could have acquired properties of the host immune system, which allows specific suppression of the immune response. The finding of structural similarities between VLP proteins and a host component indicated that a host function is expressed in VLP (Feddersen et al., 1986) and this observation has subsequently permitted the identification and characterization of a protein in caterpillars, which appears to inhibit cellular defense reactions (Berg et al., 1987). On the basis of these results we continue to approach this parasitoid-host interaction, assuming that VLP have evolved in the host organism and eventually acquired the coding sequences of a host protein with properties of an inhibitor of encapsulation. Although there are several ways to explain the emergence of VLP in endophagous parasitoid wasps, a simple proposal would be that such hypothetical viruses, which were able to suppress immune reaction in lepidopteran hosts, were incorporated into a parasitoid wasp to become part of the life cycle of the parasitoid.(ABSTRACT TRUNCATED AT 400 WORDS)