[New therapy approaches, better outcomes? : Results from inception cohorts for patients with juvenile idiopathic arthritis]. / Neue Therapiewege, bessere Outcomes? : Ergebnisse aus Inzeptionskohorten für Patienten mit juveniler idiopathischer Arthritis.

Prospective cohort studies collect demographic and clinical data of newly diagnosed patients using standardized questionnaires and validated measuring instruments. Therefore, they are a valuable data source for evaluating disease progression, outcome parameters and predictors. In this article a selection of results from four inception cohorts on juvenile idiopathic arthritis (JIA) are presented. In all cohorts, one half to three quarters of the patients achieved an inactive disease within the first year under observation but there were relevant differences between the different JIA categories. The time from symptom onset to diagnosis could be identified as an important predictor of this outcome. Data from the German JIA cohort showed that the health-related quality of life of patients and healthy control subjects had largely converged 3 years after inclusion. Young children with JIA and the detection of antinuclear antibodies have an increased risk of developing JIA-associated uveitis. Of these, the uveitis was inactive in approximately 80% after 1 year; however, at the time of diagnosis, almost 30% of patients already had uveitis-related complications. The previous therapy with methotrexate proved to be preventive for the development of uveitis. The early outcome of JIA patients is generally good. The differences in the JIA categories indicate the need to further individualize the therapy and to adapt it better to the risk profile of the individual patient. Data on long-term outcomes will provide information on which factors have a decisive influence on the course of the disease and how the care of children and adolescents with JIA can be further improved.

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis.

OBJECTIVES: To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. METHOD: Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. RESULTS: The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89-0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. CONCLUSIONS: The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.

Survey about tolerance of the AS03-adjuvanted H1N1 influenza vaccine in children with rheumatic diseases.

The objective of this study is to evaluate complications and changes in health status (disease activity and flare) in response to the AS03-adjuvanted H1N1 vaccine in children with rheumatic diseases. We conducted a nationwide survey addressing paediatric rheumatology sites who participated in the national paediatric rheumatology database. Ninety patients were documented-38 % under treatment with biologicals-of whom 18 % suffered from complications (10 % local and 8 % systemic) with no relevant changes in median disease activity or flare rate during 4 weeks following the vaccination. The adjuvanted H1N1 influenza vaccine seems to be adequately tolerated in children with rheumatic diseases.

[Uveitis in conjunction with rheumatological diseases in childhood]. / Uveitis bei rheumatologischen Erkrankungen im Kindesalter.

Children with juvenile chronic arthritis are at risk to develop intraocular inflammation depending on the type of arthritis. The pathogenic mechanisms are unclear; however, an association with antinuclear antibodies is well known. In particular young girls with oligoarticular onset of arthritis are affected most often. Regular ophthalmologic examinations should allow early diagnosis and effective therapy. Complications such as synechiae, cataract, or macula edema are seen especially in uveitis patients with late diagnosis and insufficient anti-inflammatory therapy. Better therapeutic regimens have led to a better overall prognosis of intraocular inflammation in recent years.

Bipallidal haemorrhage after ethylene glycol intoxication.

Acute or subacute bipallidal lesion, an uncommon radiological feature produced by metabolic disorders or poisoning, has never been attributed to ethylene glycol (EG) intoxication. This 50-year-old Afro-Caribbean alcoholic man had unexplained loss of consciousness. Blood tests showed osmolar gap. Drug screening was positive for EG at 6.06 mmol/l. Brain CT revealed bilateral pallidal haemorrhage. Pallidal haematoma, which could be related to deposition of oxalate crystals issued from EG metabolism, should lead to toxicological screening.

Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort.

BACKGROUND: Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. OBJECTIVE: The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. METHODS: Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. RESULTS: CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. CONCLUSION: The CD14-159 SNP might not play a major role in the development of atopy in German children.

Aldicarb poisoning

Aldicarb, 2-methyl-2 (methylthio) propanal o-[(methylamino)-carbonyl] oxime is a pesticide manufactured since 1965. This carbamate ester is sold under the tradename Temik and is used as an insecticide and nematicide. The Environmental Protection Agency has classified aldicarb in the highest toxicity category and has defined a strict control for its delivery and use. In Brazil and the Caribbean island of Guadeloupe, aldicarb is illegally used as a household rodenticide with a widespread risk of poisoning. Our study presents the first review of aldicarb poisoning with clinical and analytical findings and oxime treatment is discussed. Eighteen patients with cholinergic symptoms admitted to the Emergency Unit and two with a history of aldicarb poisoning who died were included in the study. As agricultural workers, only two of them could legally use Temik. Seventy percent of the patients were managed by the Emergency Mobile Unit. Serum cholinesterase activity was always < 30 percent of the normal range and aldicarb was identified by ultraviolet spectra and retention time after liquid chromatography separation. The most common muscarinic effect was diarrhoea (98 percent), the main nicotinic sign was fasciculation (78 percent) and 44 percent of the poisoned patients had central nervous system depression (Glasgow Coma Score < 8). Four patients had serious abnormalities and two of them died. These results suggest that aldicarb intoxication is always severe. Oxime treatment did not produce side effects and should be recommended whenever the pesticide involved is unknown. Effective measures should be implemented to stamp out the illicit use of aldicarb.(Au)

Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES.

Up-regulation of C-C chemokine expression characterizes allergic inflammation and atopic diseases. A functional mutation in the proximal promoter of the RANTES gene has been identified, which results in a new consensus binding site for the GATA transcription factor family. A higher frequency of this allele was observed in individuals of African descent compared with Caucasian subjects (p < 0.00001). The mutant allele was associated with atopic dermatitis in children of the German Multicenter Allergy Study (MAS-90; p < 0.037), but not with asthma. Transient transfections of the human mast cell line HMC-1 and the T cell line Jurkat with reporter vectors driven by either the mutant or wild-type RANTES promoter showed an up to 8-fold higher constitutive transcriptional activity of the mutant promoter. This is the first report to our knowledge of a functional mutation in a chemokine gene promoter. Our findings suggest that the mutation contributes to the development of atopic dermatitis. Its potential role in other inflammatory and infectious disorders, particularly among individuals of African ancestry, remains to be determined.

Aldicarb poisoning.

Aldicarb (2-methyl-2(methylthio) propanal o-[(methylamino)-carbonyl] oxime) is a pesticide manufactured since 1965. This carbamate ester is sold under the tradename, Temik, and is used as insecticide and nematicide. The Environmental Protection Agency has classified aldicarb in the highest toxicity category and has defined a strict control for its delivery and use. In Brazil and the Caribbean island, aldicarb is illegally used as a household rodenticide with a widespread risk of poisoning. Our study presents the first review of aldicarb poisoning circumstances associated with clinical and analytical findings. Moreover, the oxime treatment is discussed. Eighteen patients with cholinergic symptoms admitted to the Emergency Unit and two deceased with a history of aldicarb poisoning were included in the study. As agricultural workers, only two of them could legally use Temik. Seventy percent of the patients was managed by the Emergency Mobil Unit. Serum cholinesterase activity was always lower than 30% of the normal range and aldicarb was identified by UV spectra and retention time after liquid chromatography separation. The most common muscarinic effect was diarrhea, the main nicotinic sign fasciculation and almost half of the poisoned patients had central nervous system (CNS) depression (Glasgow Coma Score lower than 8). Four patients had serious conduction abnormalities and two of them died. These results suggest that aldicarb intoxication is always severe. Oxime treatment did not produce side effects and should be recommended whenever the pesticide involved is unknown. Effective measures should be implemented to stamp out the illicit use of aldicarb.

Differential modulation of interleukin-4 and interleukin-13 secretion from human peripheral blood mononuclear cells.

Interleukin-4 (IL-4) and IL-13 which have been implicated in the pathogenesis of atopic reactions elicit many of the same biologic responses. Therefore, time- and stimulus-dependent differences in the regulation of IL-4 and IL-13 production could be of relevance to their biological effects. In this study we tested the hypothesis that stimulation of peripheral blood mononuclear cells (PBMCs) with different inducers of cell activation would result in a differential expression of IL-4 and IL-13. For this purpose, PBMCs of nonatopic volunteers were incubated with phytohaemagglutinin (PHA), phorbolester (PMA), calcium ionophore A23187, or IL-3. The effect of these stimuli on IL-4 and IL-13 production were analysed by enzyme-linked immunoassay (ELISA) in supernatants of cultured PBMCs. Incubation of PBMCs with A23167 and PHA induced both a dose- and time-dependent increase in IL-4 and IL-13 release. A23187 induced concentrations of IL-4 were higher than those of IL-13 whereas IL-4 release following stimulation with PHA was considerably higher for IL-13 compared to IL-4. In contrast, there was a selective increase in IL-13 but not IL-4 concentrations following stimulation of PBMCs with PMA and IL-3 in vitro. In conclusion in this study evidence is provided that IL-4 and IL-13 production are regulated differently which might explain their functional redundancy.

Modified EMIT Dau Immunossay to allow cocaine metabolites determination in urine of crack cocaine smokers - abstract

Alkaloidal cocaine (COPC) is widely sold in the West Indies in a form suitable for smoking. These little rocks called "crack", addictive in high doses (typically 120 mg), produce a rapid, intense, high and a very compelling type of COC dependence. The bioavailability and the metabolism of the smoked form (half-life of 56 min versus 78 and 80 min, respectively, after IV and IN COC administration) conduce to low levels of metabolites in serum and in urine. Clinical and forensic toxicology laboratories are more and more solicited for testing major cocaine metabolite: benzoylecgonine (BZE). The Enzyme Multiplied Immunossay Technique (EMIT) is a fast, simple and reliable technology. However, the assay cut off concentration for BZE of the commercially available kit: (EMIT dau Cocaine Metabolite Immunoassay) is too high (300ng/ml) for serum or urine detectable levels of BZE in cocaine smokers. We proposed a modified EMIT assay to make this technique suitable for level of detection. The immunoassay was applied to ROCHE COBAS MIRA Plus analyser. The increase of the sample volume up to 25 ul and the use of calibration standards 0 to 300 ng/ml conduce to a lower detection limit of 50ng/ml. The within run precision of the assay was less than 10 percent. The results were confirmed by gas chromatography mass spectrometry. The increase of sensitivity was near 30 percent. No false positive results were observed. The presented modification demonstrates the application of currently available EMIT Immunoassay to rapid and reliable testing for BZE in cocaine smokers. (AU)

Evidence of crack use by anhydroecgonine methylester identification.

A method using gas chromatography coupled to mass spectrometry for the determination of cocaine (COC) pyrolysis product, anhydroecgonine methylester (AEME), in plasma, saliva, urine, sweat and hair is described. The same procedure allows the simultaneous determination of COC, benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE). After suitable sample preparation (desorption of the sweat patch, acid hydrolysis of the hair) the target drugs were extracted using a 3-steps liquid-liquid extraction (pH 8.4) in presence of deuterated internal standards in chloroform-isopropanol-n-heptane (50 : 17 : 33, v/v). Derivatization was achieved using BSTFA+1% TMCS. Ions for AEME monitoring were m/z 82, 166, 152 and 181. Artifact formation from COC or EME of AEME during the injection was less than 0.5%. AEME was never detected in blood sample although the corresponding urine tested positive. Urine concentrations, in about 90 positive AEME samples, were in the range 5 to 1477 ng/ml. In one case of crack overdose, AEME in sweat was 53 ng/patch with a COC concentration of 1231 ng/patch. AEME in saliva ranged from 5 to 18 ng/ml in the same case. Finally, AEME was identified in 32 hair specimens of crack abusers including fetal hair, with concentrations in the range 0.20 to 21.56 ng/mg. These results suggest that AEME can be a useful marker for the detection of COC smoking in clinical and forensic cases.

Survival after paraquat poisoning in a HIV positive patient.

From 1987 to 1994, 31 cases of acute paraquat poisoning were managed in the CHRU of Pointe à Pitre (FWI). Eighteen patients died, 13 survived. Biological indexes accurately predicted patient's outcome in all cases out of one. In the last case biological parameters were misleading: the corresponding patient survived despite consistent clinical and biological prognosis of death. The unexpected survivor was West Indian, male, agricultural worker of 26 years who alleged drunk about 300 ml of gramoxone (20% v/v paraquat) in a suicide attempt. The patient was HIV-infected (Elisa+, Western-Blot+) and presented an AIDS syndrome (CD4 count inferior to 200 cells/mm2) established since 10 months and treated by AZT. We could not identify any other distinguishing features among the unexpected survivor and the rest of the patients. This observation suggests that the immunological status of the patient could explain this protection from paraquat toxicity.

A biological index to predict patient outcome in paraquat poisoning.

1. In humans, the accidental or voluntary ingestion of paraquat, a non selective contact herbicide, is often lethal. Paraquat induces renal failure amongst other effects. 2. In this study we test the value of an index of the rate of increase in plasma creatinine over a 5 h period (dCreat/dt) to predict the outcome in intoxicated patients. These results are compared to previously published indices of severity of the paraquat poisoning. The proposed index is reliable, within the capability of any laboratory and will indicate the prognosis for poisoned patients within 6 h of admission to hospital.

Testing human hair and urine for anhydroecgonine methyl ester, a pyrolysis product of cocaine.

A method using gas chromatography coupled to mass spectrometry for the determination of the cocaine (COC) pyrolysis product, anhydroecgonine methyl ester (AEME), in urine and hair is described. The same procedure allows the simultaneous determination of COC, benzoylecgonine (BZE), ecgonine methyl ester, and cocaethylene. The assay involves acid hydrolysis for hair, deuterated internal standards, a three-step liquid-liquid extraction, and derivatization with N,O-bis(trimethylsilyl) trifluoroacetamide plus 1% trimethylchlorosilane. Detector responses for analytes were linear over the concentration ranges of 0.2-50 ng/mg and 10-2000 ng/mL for hair and urine, respectively. Artifact formation of AEME during the injection was less than 1%. AEME was tested in 65 and 81 cases for hair and urine, respectively, where COC or BZE or both tested positive. Concentrations of AEME ranged from 0.2 to 2.4 ng/mg (n = 7) and from 4 to 226 ng/mL (n = 12) in hair and urine, respectively. Its presence was observed in few cases, clearly indicating that COC smoking is not frequent in France.