Lack of association between beta 2-adrenergic receptor polymorphisms and juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune arthropathy. Beta 2-adrenergic receptors are a link between the sympathetic nervous system and the immune system. Associations between variants in the gene encoding the beta 2-adrenergic receptor (ADRB2) and autoimmune disorders such as rheumatoid arthritis (RA) have been demonstrated. We aimed to investigate ADRB2 variants for association with JIA. METHODS: Genotypes and haplotypes of two ADRB2 variants (G16R and Q27E) were determined in 348 children with JIA and 448 healthy controls by direct molecular haplotyping using melting-curve analysis of a fluorescently labelled loci-spanning probe. Case-control analysis was performed to investigate whether ADRB2 variants were associated with JIA. RESULTS: No association was found between JIA and alleles, genotypes, or haplotypes of ADRB2. Specifically, the haplotype that demonstrated a strong association with RA (R16/Q27) was not associated with JIA. None of the variants demonstrated association after stratification by JIA subtypes or gender. CONCLUSIONS: Our results indicate that ADRB2 variants are not associated with JIA or any of the major JIA subtypes. These observations suggest that, although they share several clinical and pathological features, JIA and RA have unique genetic associations.

Enteral metronidazole for the prevention of graft versus host disease in pediatric marrow transplant recipients: results of a pilot study.

The use of enteral antibiotics to prevent acute graft versus host disease (GvHD) has not been studied prospectively in children. We hypothesized the risk of GvHD in pediatric bone marrow transplant (BMT) recipients would be decreased with enteral metronidazole. Eligible subjects included pediatric patients referred to one center for first allogeneic BMT. Enteral metronidazole 20 mg/kg/day divided thrice daily (maximum 750 mg/day) was administered from day -14 to day +35. The risk of GvHD grade II or more severe among subjects treated with metronidazole was compared to historical controls. There were no significant differences between treated (n=19) and historical controls (n=83) with respect to age, gender, prophylaxis, or conditioning regimens, proportion receiving unrelated donor marrow, proportion receiving umbilical cord blood, or transplantation indication. The probability of remaining free of GvHD at day +100 was lower in the treated group (P=0.047). The adjusted relative risk of developing GvHD among subjects treated with metronidazole was 0.36 (95% CI: 0.13-0.997; P=0.05). Five patients were unable to complete the study; two were likely related to study medication. We conclude that enteral metronidazole appears effective in the prevention of GvHD. These results suggest that a randomized trial is justifiable in children, especially recipients of alternative donor BMT.

Liver involvement in childhood histiocytic syndromes.

The histiocytic syndromes of childhood are disorders of the reticuloendothelial system with variable clinical manifestations. Included among them are Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis. This discussion will be restricted to these two disorders. Liver disease in these conditions is common. Langerhans cell histiocytosis is characterized by the abnormal clonal proliferation of the macrophage-derived Langerhans cell. Liver involvement at diagnosis has management and prognostic significance. In a subgroup of patients, sclerosing cholangitis develops, which may lead to end-stage liver disease requiring liver transplantation. Hemophagocytic lymphohistiocytosis is a disease of abnormally activated macrophages that can involve multiple organ systems, including the liver. Differentiation between this disorder and other causes of pediatric liver disease is critical, because treatment strategies include chemotherapy, immunosuppression, and frequently bone marrow transplantation.

THE USE AND UTILITY OF THE MONOTONE CRITERION IN MULTIDIMENSIONAL SCALING.

The monotone criterion as a multidimensional scaling technique is theoret- ically and empirically evaluated using the algorithms of Kruskal (MDSCAL) and Guttman-Lingoes (SSA-1). Geometric configurations are used to test the recovery capabaty and other aspects of MDSCAL and SSA-1. In addition to theoretical shortcomings, the monotone criterion permits results which do not correspond to the shape of the input data. Because of its deficiencies, alterna- tive goodness-of-fit criteria are suggested in preference to the monotone criterion.