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Impfungen stellen bei Kindern und Jugendlichen mit rheumatischen Erkrankungen ein besonderes Problem dar. Wirkungen und Nebenwirkungen von Impfungen sind fur dieses Patientenkollektiv leider nur unzureichend untersucht, und spezifische Impfempfehlungen fehlen. Die bei diesen Patienten haufig erforderliche immunsuppressive Therapie schafft zusatzliche Unsicherheit. Hinzu kommen Bedenken bezuglich impfassoziierter Reaktivierungen der Grunderkrankung. Die bestehenden Unsicherheiten im Umgang mit Impfungen fuhren zu einer erheblichen Praxisvariation unter den Kinderarzten und Impflucken bei den betroffenen Kindern und Jugendlichen. So ist jeder dritte Patient mit juveniler idiopathischer Arthritis unzureichend geimpft, was sogar Standardimpfungen mit Totimpfstoffen wie Tetanus/Diphtherie einschliest. Nach aktuellem Stand des Wissens ist der Nutzen vieler Impfungen gerade bei Patienten mit Autoimmunerkrankungen deutlich hoher als deren Risiko zu veranschlagen. Gerade Patienten mit immunsuppressiver Therapie benotigen einen besonderen Schutz vor Infektionen. Kinder und Jugendliche mit rheumatischen Erkrankungen sollten deshalb – soweit moglich – nach den STIKO-Empfehlungen geimpft werden. Dabei muss der Zeitpunkt der anstehenden Impfung sorgfaltig in Abhangigkeit von der Krankheitsaktivitat und Therapie gewahlt werden.

Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy.A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution.A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008).Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies. METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number. DISCUSSION: Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.

The diagnostic biochemical hallmarks of Smith-Lemli-Opitz syndrome (SLOS) are elevated concentrations of the cholesterol precursors 7- and 8-dehydrocholesterol (7- and 8-DHC). We describe a patient with classical SLOS phenotype and oesophageal achalasia, which has not been reported in SLOS patients before. Plasma 7-DHC and 8-DHC were only marginally elevated. The diagnosis was confirmed by sterol analysis in cultured skin fibroblasts and mutation analysis.

The standard oxygen consumption (cone) calorimeter (described in ASTM E 1354 and NASA STD 6001 Test 2) is modified to provide a bench-scale test environment that simulates the low velocity buoyant or ventilation flow generated by or around a burning surface in a spacecraft or extraterrestrial gravity level. The equivalent low stretch apparatus (ELSA) uses an inverted cone geometry with the sample burning in a ceiling fire (stagnation flow) configuration. For a fixed radiant flux, ignition delay times for characterization material PMMA are shown to decrease by a factor of 3 at low stretch, demonstrating that ignition delay times determined from normal cone tests significantly underestimate the risk in microgravity. The critical heat flux for ignition is found to be lowered at low stretch as the convective cooling is reduced. At the limit of no stretch, any heat flux that exceeds the surface radiative loss at the surface ignition temperature is sufficient for ignition. Regression rates for PMMA increase with heat flux and stretch rate, but regression rates are much more sensitive to heat flux at the low stretch rates, where a modest increase in heat flux of 25 kW/m 2 increases the burning rates by an order of magnitude. The global equivalence ratio of these flames is very fuel rich, and the quantity of CO produced in this configuration is significantly higher than standard cone tests. These results demonstrate that the ELSA apparatus allows us to conduct normal gravity experiments that accurately and quantifiably evaluate a materials flammability characteristics in the real-use environment of spacecraft or extraterrestrial gravitational acceleration. These results also demonstrate that current NASA STD 6001 Test 2 (standard cone) is not conservative since it evaluates a materials flammability with a much higher inherent buoyant convective flow. Published by Elsevier Inc. on behalf of The Combustion Institute.

Das autoimmune lymphoproliferative Syndrom (ALPS; Synonym Canale-SmithSyndrom) tritt typischerweise bereits im Kindesalter auf und ist charakterisiert durch chronische nicht-maligne lymphoproliferative Krankheitsbilder (Lymphadenopathie, Hepatosplenomegalie), Autoimmunitat, Hypergammaglobulinamie, und eine erhohte Anzahl von CD3+CD4–CD8– “doppelt-negativer” T-Lymphozyten. Im Erwachsenenalter haben ALPS-Patienten ein erhohtes Risiko fur maligne Lymphome (M. Hodgkin, Bund T-Zell-Lymphome).

Polymorphism in the upstream regulatory region (URR) of the MHC class II DQA1 gene defines 10 different alleles named QAP (DQA1 promoter). In vitro studies have suggested that allelic polymorphism in the HLA-DQA promoter region may result in differences in HLA-DQA1 gene expression. In the present study, we used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify differences in HLA-DQA1 gene expression. After the isolation of total mRNA, reverse transcription into cDNA was carried out using random hexamer priming and moloney murine leukaemia virus (MMLV) reverse transcriptase. Quantification of DQA1 mRNA species using a set of six group-specific primer pairs for the detection of HLA-DQA1*01, *02, *03, *04, *05 and *06 was carried out on an ABI PRISM GeneAmp 7700 Sequence Detection System (Perkin Elmer, Foster City, CA) with real-time detection and quantification taking advantage of the fluorescence TaqMan technology (Perkin Elmer, Foster City, CA). Normalization of cDNA templates was achieved by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) quantification. In addition, the total amount of mRNA produced by HLA-DQA1 and HLA-DRA1 expression was quantified for comparison. Subsequently, this approach was validated using Raji and HUT-78 cell lines and tested with peripheral mononuclear cells (PBMC) of 45 samples taken from healthy volunteers. The sensitivity was determined with > or = 10(2) copies. Comparison of the allele-specific DQA1 expression with the total expression of DQA1 and DRA1 mRNA indicated that DQA1*04 expression was increased compared with the expression of other alleles of the DQA1 gene. Thus, allele-specific quantification of DQA1 gene products could be achieved by real-time RT-PCR suitable for the analysis of differential expression of DQA1 mRNAs in homozygote and heterozygote combinations.

Growth factor deprivation-induced apoptosis plays an important role in several cellular systems. However, knowledge of the molecular mechanisms involved are restricted to a few murine models or tumor cell lines. Therefore, we aimed studying signaling pathways leading to apoptosis in activated human peripheral T cells after IL-2 withdrawal. Lymphoblasts from patients with CD 95 (Fas/APO-1)-deficiency revealed that functional CD95 was not required to induce apoptosis after IL-2 withdrawal. Moreover, apoptosis induction in response to various cytotoxic stimuli was found to be mediated in the absence of functional CD95 but was affirmatorily influenced by IL-2 signaling. Immunoblots showed no downregulation of Bcl-2 or Bcl-xL and no upregulation of Bax, whereas decreased mitochondrial membrane potential was readily measurable 24 h after cytokine deprivation. Tetrapeptide inhibitors showed limited efficacy in preventing apoptosis whereas the caspase inhibitor zVAD-FMK potently blocked induction of apoptosis. Cleavage of different fluorogenic substrates revealed multiple caspase enzyme activities in lymphoblasts, which were not negatively affected by the fas mutation. Starting at 8 h after IL-2 withdrawal, upregulation of active caspase-3 but not of caspase-8 could be detected. Taken together, our data argue for molecular mechanisms of cytokine deprivation-induced apoptosis in activated human lymphocytes independent of CD95.

The expression of m-fas/apo1 (CD95) and its soluble form (s-fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m-fas/s-fas transcripts was calculated by densitometry of fas-specific RT-PCR products. An inverted ratio of m-fas/s-fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m-fas/s-fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m-fas/s-fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA-JCA which is not limited to the affected joints.

Exclusive incoherent electroproduction of the ρ0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q^2>0.4 GeV^2 and positron energy loss ν from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark-antiquark fluctuations with the nuclear medium.

Determination of the efficacy of an early ultrasound examination followed by immediate treatment of hip joint dysplasia as well as measuring the therapeutic success in a population-based cohort study of neonates.The Survey of Neonates in Pomerania (SNiP) study included 4,093 neonates which represents 95.1 % of the total neonatal population. Of these children 2,534 (61.9 %) underwent ultrasound examination of the hip joint during the U2 stage (3-10 days after birth). The mean gestational age was 38.9 weeks. The sonographic classification was performed according to Graf.Initially (U2 stage) 42 (1.66 %) children were reported to be in need of therapy (stage IIc or higher according to Graf). The analysis showed a significantly higher incidence in girls (32 girls vs. 10 boys, p 0.023, χ(2) test) and in children who had a breech birth (116, 4.6 %). A genetic predisposition was ascertained in 180 (7.1 %) children. The children could be subdivided into two groups: 1) children who underwent hip joint ultrasound during both U2 and U3 and 2) children who were first screened at the U3 stage. Of the 49 out of 54 neonates where the ultrasound findings were positive at the U2 examination the hip joint was matured in 32 children at U3 (4-8 weeks), 11 children had to be treated for 8-12 weeks 5 children were treated for over 3 months and1 child needed surgical correction.The early diagnosis of hip maturation disorders and joint dysplasia facilitates early implementation of effective treatment. At our clinic over 60 % of the infants underwent the U2 check up and, given a pathological finding, could undergo early treatment. It was possible to successfully treat 78 % of these children with a Tübingen hip flexion splint in just 4-8 weeks. In contrast, infants who were first examined at the U3 stage needed treatment for 4-12 months. In our opinion, early diagnosis at the age of 3-10 days should be carried out for all newborns.

Chronic anterior uveitis is a common complication of juvenile idiopathic arthritis (JIA). Leflunomide is a frequently used alternative to methotrexate in the treatment of joint manifestations of JIA. However, very little is known on the effect of leflunomide treatment on concurrent chronic uveitis in JIA.

The increasing use of combination therapies, including disease-modifying antirheumatic drugs (DMARD) and biologicals has improved the outcome for children and adolescents in several rheumatic diseases. However, this strategy has increased the risk of drug-specific side-effects, such as an increased risk of infections. Furthermore, the underlying rheumatic disease itself often includes an increased risk of infections and some patients additionally present with immunological or organic comorbidities (e.g. complement deficiency and interstitial pulmonary disease) further increasing the susceptibility to infections. The presented review is based on an analysis of the currently available literature proposing a checklist of diagnostic procedures and immunological laboratory tests specific for the detection of patients prone to infections. The combined stratification of the underlying disease, comorbidities and the immunological mechanisms of the medication enables (1) an individual risk stratification of planned immunosuppressive therapy and (2) a prediction of the risks of infection for the patient.

A Large Acceptance Detector System (LADS) has been designed and built at the Paul Scherrer Institute to study multiparticle final states following pion-nucleus absorption. It consists of a 28-sector cylinder of plastic scintillators of 1.6 m active length and 1.4 m diameter, two cylindrical wire chambers, and two 14-sector plastic scintillator end-caps which close each end. The nearly 4π solid angle coverage of this detector minimizes uncertainties associated with extrapolations over unmeasured regions of phase space. The design and the performance of the LADS detector are presented.

We have measured the analyzing power for elastic scattering of {pi}{sup +} from a target of polarized {sup 1}H. Data were taken for incident pion beam energies of 165 and 240 MeV at several pion scattering angles. The current data generally agree with previously existing measurements of {ital A}{sub {ital y}} for this reaction and also with results of the SAID phase-shift analysis program. In most cases the new data are of higher precision than previously existing data. {copyright} {ital 1996 The American Physical Society.}

Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA 1*0401, *0501, *0601 and DPB1*0201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5′ flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and-200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box-125 to-115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA 1-alleles (DQA 1*0401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.

Background Biological disease modifying antirheumatic drugs (bDMARD) had great impact on the medical management of patients with juvenile idiopathic arthritis (JIA). Many patients nowadays enter adulthood in clinical remission, with normal function and without long-term sequelae. There is little information to what extent the early use of bDMARDs affects the long-term outcome of patients with JIA. Objectives To investigate if the 10-year outcome after JIA onset is associated with the time lag between JIA disease onset and first bDMARD use. Methods Outcome variables were examined in patients prospectively observed in the national JIA biologic register BiKeR and its follow-up register JuMBO since initiation a bDMARD therapy. Analyses included patients with at least one visit in JuMBO. Assessed parameters were JADAS3–10, C-HAQ, joint surgery (replacements, synovectomies), eye surgery and patient-reported outcomes. To analyze the influence of the time lag between JIA onset and first use of bDMARD, patients were assigned to one of the following three groups (G1: ≤2 year = early therapy, G2: intermediate, G3: ≥5 years = late). A general propensity score was estimated to adjust for baseline differences between the three groups. Mixed models were used to determine the association of the three groups and outcomes. Surgeries were analyzed by Cox regression analyses. Results 609 patients were ever treated with a bDMARD and successfully transferred to JuMBO. Most (91%) patients were enrolled in BiKeR on etanercept followed by adalimumab (6%), 93% had previously received a conventional synthetic (cs) DMARD. 27.9% had RF negative polyarthritis and 19.5% enthesitis-related arthritis. The first csDMARD was started 0.4 years after disease onset in the early bDMARD group (n=142), and 1.2 and 3.1 years after JIA onset in the in-between group and late group (n=274), respectively. At their last follow-up (10.2±6.2 years after JIA onset), the patients9 mean age was 21.2 years. The clinical outcome 10 years after disease onset could be investigated in 478 patients. Patients with early biologic treatment were significantly more often in drug-free JADAS remission (15%) for at least 12 months, had more often an inactive disease (JADAS3–10≤1, 27.6%) and no functional limitations (58.6%) compared to late treatment start. There was no significant difference in the patient-reported outcome measures. Among all 609 patients, 35 (5.8%) patients had undergone joint replacement, 100 (16.4%) synovectomy and 19 (3.2%) eye surgery. Patients on bDMARD in follow-up had a lower likelihood for joint replacement (HR=0.25, p=0.003) or synovectomy (HR=0.26, p Conclusions Patients who started with cs and bDMARDs within the first two years of disease are significantly more often in drug-free remission in adulthood and have less sequelae than those who started later. The data emphasize the importance of a fast disease activity control and may support the idea of a window of opportunity for JIA. Disclosure of Interest None declared

Background Since the approval of first biologics for JIA, such treatments in Germany are monitored prospectively by the BiKER registry. Methods sJIA pts documented in BIKER exposed to Etanercept (ETA), Tocilizumab (TOC) or IL-1inhibitors were identified. A 6-month therapy period was chosen as a meaningful time for early efficacy judgement. Intention to treat analysis (ITT) of JADAS10 was performed. Discontinuation due to inefficacy/intolerance was calculated as non-response. Results 205 sJIA patients (51% male) received 269 treatment courses with biologics (TOC 71, Anakina 36, Canakinumab 19, ETA 143). Median age and disease duration (ETA 3.3;TOC 3.3;IL-1i 3.0) were comparable. The choice of drug was influenced by the availability. ETA was started in 80% of pts before 2008 while in the TOC cohort all pts and in the IL-1i cohort 74% started therapy after 2008. Pre-treatment consisted of steroids in all pts, MTX in the ETA/TOC/IL-1i cohort in 88%/83%/76% and biologics preexposure was used in 2%/66%/86%. Concomitant treatment with systemic steroids was significantly less frequent with TOC (44%, p Systemic manifestations were present at baseline in: 8% ETA, 96% TOC and 38% IL-1i cohort. The mean±SD baseline JADAS was higher in the ETA cohort (20.7±9.1) than in the TOC cohort (16.2±10.6) or IL-1i cohort (7.8±8.9). At month 6, a marked decrease of the JADAS was noted in all cohorts. ITT analysis revealed a significant advantage of TOC and Il-1i over ETA (table). Significantly more pts reached a JADAS-Remission (JADAS≤1) upon TOC (OR/95CI 3.85/1.68–8.83/p Conclusions A high proportion of pts showed a significant response to treatment especially with TOC or with IL-1i. After 6 months on treatment JADAS remission criteria were reached by up to 50% of patients while 60% to 65% reached JADAS minimal disease activity desoite much less steroids and DMARD used with TOC or IL-1i. ETA has been used in earlier times but it is less effective and it9s use in sJIA has markedly decreased in Germany. Disclosure of Interest None declared

Background High plasticity was described for Th1 and Th17 cells depending on the local cytokine milieu and regulation by Tregs. Pathogen-induced human Th17 cells and Tregs are strongly regulated by IL-1beta. So far, the influence of IL-1beta on FoxP3 methylation and stability of the Treg lineage has not been investigated. Further, whether inhibition of IL-1beta and its receptor is able to promote FoxP3 demethylation and to conserve Treg functions, such as suppression of Th17 and Th1 functions, has not been assessed in healthy humans, as well as in patients with autoimmune arthritis. Objectives Thus, the present study aimed to investigate in vitro nTreg and iTreg functions in lymphocytes obtained from stored routine blood samples of patients with juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) in different disease activity states. Methods Proportions of peripheral nTregs and cultured iTregs from stored routine blood samples taken from JIA, RA patients and healthy, age-matched controls (HC) and intracellular cytokine production were analyzed by flow cytometry. Suppressive function of iTregs under in vitro inhibition of IL-1beta was studied by suppression assays. FOXP3 expression and methylation were analyzed by quantitative PCR and bisulfite pyrosequencing. Results Lower proportions of nTregs were found in samples of JIA patients with acute disease flare (mean 2.3% of CD4+ T cells) compared to HC (4.1%) (p Conclusions Induction of Tregs seems to be different depending on disease activity status in autoimmune arthritis. DNA methylation at the FOXP3 promoter and enhancer regions may influence expression of FoxP3 in Tregs and, thus, modify their phenotype. Although IL-10 was not markedly influenced by IL-1beta-dependent mechanisms, our findings indicate that suppressive iTreg functions may be restored by selective blockade of IL-1beta. Disclosure of Interest None declared

Background Since the approval of first biologics for treatment of JIA, surveillance in Germany is monitored prospectively by the BIKER registry. Objectives To evaluate the safety of Tocilizumab (TOC), IL-1 inhibitors (Anakinra & Canakinumab) and Etanercept (ETA). Methods Safety assessments were based on adverse events reports. Results 205 sJIA pts received 269 treatment courses with biologics (TOC 71, Anakina 36, Canakinumab 19, ETA 143 and 57 pts. received MTX only. Median age was lower In the MTX cohort (4.8y) than with ETA (8.2); TOC (9.6); IL-1i (8.2) as was the disease duration. ETA was started in 80% of pts before 2008 while in the TOC cohort all pts and in the IL-1i cohort 74% started therapy after 2008. Pre-treatment consisted of systemic steroids in 75% starting MTX and in all patients starting biologics. Initial concomitant treatment with systemic steroids was significantly less frequent with TOC (44%, p Conclusions Higher rates of safety signals, especially infections were noted upon treatment with TOC and IL-1i. Beside infections, disease reactivation and MAS, further adverse events were rare and overall tolerability was acceptable. However, steroids were markedly spared upon IL6- and Il-1 inhibitors. Disclosure of Interest G. Horneff Grant/research support from: Abbvie, Roche, Chugai, Pfizer, A. Schultz: None declared, A. Hospach: None declared, G. Ganser: None declared, I. Foeldvari: None declared, A. Thon: None declared, R. Trauzeddel: None declared, F. Weller: None declared, K. Minden: None declared, J. Haas: None declared

Fragen zur Ernahrung von Kindern mit autoimmunologischen Erkrankungen sind haufig und die Publikationen in der Laienpresse irrefuhrend. Erschwerend wirken sich die medizinhistorisch begrundete unscharfe Abgrenzung der rheumatoiden Arthritis von der Arthrose und der Arthritis urica (Gicht ) aus. Validierte wissenschaftliche Untersuchungen, insbesondere bei Kindern und Jugendlichen, bilden die Ausnahme und vermitteln ein oft widerspruchliches Bild. Bei den meisten autoimmunologischen Erkrankungen fehlen kontrollierte diatetische Studien vollig. Bei den verschiedenen Formen kindlicher Arthritis, der juvenilen idiopathischen Arthritis (JIA , Einteilung nach Klassifikation der ILAR; Petty et al. 1998) liegen zwar Untersuchungen vor; hierbei wurden die einzelnen Untergruppen der Erkrankung jedoch haufig nicht differenziert betrachtet. Dennoch zeigte sich bei Kindern und Jugendlichen mit einer JIA oder einem juvenilen systemischen Lupus erythematosus (jSLE) eine signifikant erhohte Zufuhr von Fetten und Eiweis bei verminderter Zufuhr von Eisen, Zink und Vitamin A als vorteilhaft (Caetano et al. 2009). Grundsatzlich mussen bei rheumatischen Erkrankungen 3 diatetische Ansatze betrachtet werden: Eliminationsdiaten und Fastenkuren in der Absicht einer Reduktion entzundungsfordernder Nahrungsstoffe, Substitutionsdiaten mit dem Ziel der Zufuhr entzundungshemmender Nahrungsstoffe, Vitamine oder Spurenelemente und diatetische Pravention von Sekundarschaden der Erkrankung und Therapie.

Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

Measurements have been made of [pi][sup +] absorption on [sup 3]He at [ital T][sub [pi]][sup +]=118, 162, and 239 MeV using the Large Acceptance Detector System. The nearly 4[pi] solid angle coverage of this detector minimizes uncertainties associated with extrapolations over unmeasured regions of phase space. The total absorption cross section is reported. In addition, the total cross section is divided into components in which only two or all three nucleons play a significant role in the process. These are the first direct measurements of the total and three nucleon absorption cross sections.

performed with infrared cameras and the Plug-in-Gait Model. Analyses focused spatio-temporal and kinematic parameters in the sagittal plane. Mann-Whitney-UTests (p

A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (or = 4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (4 years) onset (associated with DR4).

Several genetic factors have recently been observed as having an influence on susceptibility, course and prognosis of juvenile idiopathic arthritis (JIA): 1. Affected sib pairs were observed to have a low concordance in terms of disease incidence, but significant concordance in terms of subtype and course of disease. 2. Each subtype of JIA was observed to have a distinct genetic background. 3. Some JIA patients do not carry any of the defined risk genes. 4. Most subtypes of JIA have a distinct different genetic background to rheumatoid arthritis in adults. 5. Multiple factors have been observed to be involved in pathogenesis implying genetic and environmental factors. 6. Systemic JIA differs from all other subtypes in terms of genetic background and treatment options. It is currently assumed to be an autoinflammatory disease. 7. Genetic factors not only affect the course of the disease, but also response and complication rate. Increasing knowledge on the factors involved in the pathogenesis of JIA as well as analysis of large patient cohorts in consortiums cooperating on an international level have helped define many important polymorphisms; these are currently the subject of further investigation.

It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients. We examined the predictive value of kynurenine pathway activity for ongoing sepsis in patients being admitted to a surgical intensive care unit for different reasons. In addition, we asked whether an accumulation of kynurenines in patients’ plasma depends on reduced renal clearance. We conducted a prospective observational study including 100 consecutive patients and monitored laboratory variables, physiological and adverse events, sepsis and outcome. Using tandem mass spectrometry, we quantified the five indoleamines tryptophan, serotonin (5-HT), kynurenine, quinolinic acid and kynurenic acid at baseline and twice a week during the intensive care unit stay. Among the patients enrolled, 50 did not develop sepsis in the intensive care unit (non-septic), 18 patients did not have sepsis at baseline but developed sepsis later on (preseptic) and 32 patients already fulfilled the criteria of severe sepsis and septic shock at baseline (septic). In general, non-septic critically ill patients showed activation of the kynurenine pathway, but septic shock coincided with an exacerbation of kynurenine pathway activity even in the absence of renal failure. Importantly, plasma concentrations of quinolinic acid (area under the curve 0.832 [95% confidence interval 0.710 to 0.954]) and the Quin/Trp ratio (area under the curve 0.835 [95% confidence interval; 0.719 to 0.952]) showed the best discrimination between non-septic and pre-septic patients at baseline. These findings open new avenues for further investigations on the pathophysiology of sepsis.

TNF inhibitors and other biologicals have greatly expanded the therapeutic options for juvenile idiopathic arthritis (JIA). While the efficacy of etanercept and adalimumab has been proven in randomized controlled clinical trials, their long-term safety remains the subject of ongoing investigations. Reports of leukaemia and tumours in children and adolescents treated with etanercept, infliximab and adalimumab have raised questions about an increased risk for malignancies, with lymphoma accounting for the largest group at 50% of all 48 malignancies reported by the FDA.Consequently, TNF inhibitors should be indicated under careful consideration of individual risk factors, such as increased family occurrence of malignancies, or pre-treatment with carcinogenic substances such as cyclophosphamide. This is particularly true for non-approved substances, and non-approved indications, and for combination therapy of TNF inhibitors with immunosuppressive drugs. On the other hand, however, treatment should not be stopped or started in any patient in whom treatment is necessary due to the current knowledge. Adequate patient information, surveillance and documentation of treatment in the registry of the GKJR is strongly recommended.

The official birth statistics are regarded as a reliable data source on births and birth rate in the German population. However, they show methodological limitations with respect to the identification of first-time mothers and the number of children per mother. The mothers' social and economical background is not assessed. The goal of the present analysis was (a) to describe demographic and socio-economic variables of all births in a defined region over a fixed time-frame and (b) to make a comparison on the basis of parity and gravidity.From 2004-2007 4,982 children were born in the region and data from n=4,788 children were assessed (96%); n=3,505 (73%) of these mothers consented to a more detailed assessment.The fertility rate in the SniP region is low. There are fewer children per 1,000 women and born per women in general. The average age of primiparae was 25 and 26 years. As can be expected there is a significant difference between primiparae and multiparae with respect to age. There is also a difference in occupational status. 17% of the primiparae have been multigravidae.For the first time in Germany, the SNiP collected comprehensive population-based data on the age and socio-demographic variables of children and their mothers in a defined geographical region. A significant discrepancy for average age of primiparae between the study results and the official statistics is discussed in the light of methodological and regional issues. Our results require the continuation of comprehensive population-based data assessment. Furthermore, the SniP region could serve as a model region for future research. In international comparisons Germany's reproductive behaviour has proved to be unfavourable, which is accentuated in the region under examination.

Changes in reproductive behaviour and decreasing fertility rates have recently led to policy actions that attempt to counteract these developments. Evidence on the efficacy of such policy interventions, however, is limited. The present analysis examines fertility rates and demographic variables of a population in Germany in response to new maternity leave regulations, which were introduced in January 2007. As part of a population-based survey of neonates in Pomerania (SNiP), all births in the study region from the period 23 months prior to January 1st, 2007 until 23 months afterwards were examined. Crude Birth Rates (CBR) per month, General Fertility Rates (GFR) per month, parity and sociodemographic variables were compared using bivariate techniques. Logistic regression analysis was performed. No statistically significant difference in the CBR or GFR after Jan. 1st, 2007 was found. There were statistically significant differences in other demographic variables, however. The proportion of mothers who (a) were employed full-time before pregnancy; (b) came from a higher socioeconomic status; and (c) had higher income levels all increased after January 1st, 2007. The magnitude of these effects was higher in multigravid women. Forward stepwise logistic regression found an odds ratio of 1.79 for women with a family income of more than 3000 euro to give birth after the new law was introduced. This is the first analysis of population-based data that examines fertility rates and sociodemographic variables in response to new legal regulations. No short-term effects on birth rates were detected, but there was a differential effect on the subgroup of multigravidae. The focus of this policy was to provide financial support, which is certainly important, but the complexity of having a child suggests that attitudinal and motivational aspects also need to be taken into account. Furthermore, these analyses were only able to evaluate the short-term consequences of the policy; further studies are needed to assess for different, long-term effects.

Polymorphisms in the upstream regulatory region of the HLA class II DQA1 gene are currently defined by 10 different alleles. Two of them carrying a Y-box mutation are associated with susceptibility to oligoarticular juvenile idiopathic arthritis (OA-JIA). We investigated allele-dependent differences in HLA-DQA1 gene expression in OA-JIA patients. In cells from affected joints compared to peripheral blood, gene expression of HLA-DRA as well as total HLA-DQA1 was significantly upregulated. Differential analyses of HLA-DQA1 allelic expression showed DQA1*02 and *04 to be comparatively increased. Intra-articular upregulation of HLA-DQA1 was predominantly observed for the OA-JIA associated allele HLA-DQA1*04. Nevertheless, the Y-box mutation of the disease-associated allele DQA1*0401 was not a common denominator for expression behaviour.

Population-based data on smoking behavior in Germany of women before or during pregnancy have been lacking. Smoking rates of these women have now been recorded over a period of 3 years against the background of growing tobacco control activities in Germany.The study was conducted between 4/2003 and 3/2006 in the context of a prospective population-based survey about perinatal morbidity and mortality (Survey of Neonates in Pomerania - SNiP). This survey registers all newborns and their mothers in one defined region. Of the women eligible for the study 2 297 (68.1%) participated after delivery by giving data about their smoking behavior before and during pregnancy.61.2% of the women had smoked at some time, 46.6% had smoked before, 24.2% into the 4. month and 20.5% into the last 4 weeks of pregnancy. Smoking rates remained unchanged over the 3 years that were studied. The rates of smokers who had quit by the time of delivery varied according to the length of school education: (10 years: 30%; 10 y: 59%;10 y: 84%) and age (24 years: 45%; 25-30 y: 65%;30 y: 77%).This study for the first time provides population-based data about the prevalence of smoking before and during pregnancy among women in Germany. The data show extremely high numbers of smokers, especially younger women and women of only 10 years or less of school education. Despite growing tobacco control activities no changes in smoking rates were observed over three years. These findings underline the need to develop effective interventions to prevent smoking of women before and during pregnancy.

Anliegen: Im Rahmen des Survey of Neonates in Pommerania (SNiP) fand eine Untersuchung der Lebensqualitat (LQ) der Mutter im Zusammenhang mit der Geburt eines Kindes statt. Erhoben wurden die Einschatzung der LQ der befragten Mutter vor Geburt sowie die der erwarteten LQ danach. Einzeldimensionen waren Arbeit, Finanzen, familiare Situation und Wohnsituation, Beziehung zu Freunden, Bekannten und Nachbarn, Gesundheit und Freizeit. Das besondere Augenmerk galt der sozialen Eingebundenheit der Mutter. Methode: Wahrend des Krankenhausaufenthaltes nach der Geburt schatzten die Frauen mittels Selbstausfullerfragebogen ihre LQ ein. Die Befragung fand bevolkerungsbezogen in Ost-Vorpommern im Zuge der Datenerhebung des SNiP statt. Erhebungszeitraum waren die Monate 01.04.2004 bis 30.06.2005. Ergebnis: Von den 1553 Gebarenden konnten 1122 Fragebogen (72,3%) ausgewertet werden. 92,1% der Frauen schatzten ihre allgemeine derzeitige LQ als positiv ein, keine erwartete eine deutliche Verschlechterung. In den Einzeldimensionen fanden sich negative Angaben i.S. von Unzufriedenheit fur die aktuelle Arbeits- (23,3%) und Finanzsituation (26,3%). In 34% erwarteten die Mutter eine Verschlechterung der Arbeits-, in 52,1% der Finanzsituation. In 39,6% befurchteten sie eine Einschrankung ihrer Freizeit. Sonst fanden sich gleich bleibende Einschatzungen oder eine Verbesserungserwartung. Als wichtiger Faktor fur die Einschatzung der gesamten LQ erwies sich die soziale Eingebundenheit (Nachbarn, Freunde, Bekannte, das Vorhandensein von Personen, auf die sich in Notsituationen verlassen werden konnte). Es zeigte sich, dass diese sozialen Faktoren einen deutlich positiven Einfluss auf die Einschatzung haben. Fazit: Der uberwiegende Anteil der Befragten schatzte seine LQ positiv ein und erwartete keine Verschlechterung nach der Geburt des Kindes. Eine starkere soziale Einbindung ging einher mit einer positiveren Einschatzung. Materielle Konsequenzen und deren Wahrnehmung hatten absolut gesehen einen geringeren Einfluss auf die Selbsteinschatzung der allgemeinen LQ als soziale Faktoren. Die finanzielle Situation scheint also fur die Einschatzung der LQ und der Entscheidung zum Kind keine alleinige ausschlaggebende Rolle zu spielen. Die Erwartungshaltung nach der Geburt des Kindes war beim weit uberwiegenden Anteil der Befragten positiv, negative Konsequenzen wurden nur fur wenige Dimensionen angegeben.

Vaccinations represent a special problem in children and adolescents with inflammatory rheumatic diseases. There are very limited data on the safety and efficacy of vaccines in these patients, and guidelines for immunization are missing. The immunosuppressive therapy often necessary for these patients gives rise to additional uncertainty. In addition, many colleagues consider vaccination to increase the risk of relapse of the rheumatic illness. As a consequence, there are substantial variations in practicing vaccination in these patients, resulting in insufficient vaccination coverage rates. For example, every third patient with juvenile idiopathic arthritis is incompletely vaccinated; this even includes toxoid vaccines for tetanus and diphtheria. The benefit of vaccinations, which far outweighs their potential risks, is well recognized even in patients with autoimmune diseases. These patients in particular require a special protection from infections due to their immunosuppressive therapies. Therefore, children and adolescents with rheumatic diseases should be immunized according to the Standing Immunization Commission of the Robert Koch Institute recommendations whenever possible. However, the time of vaccination must be carefully selected, taking disease activity and treatment into account.