Pharmacokinetics of insulin infused intra-peritoneally via portable pumps

Plasma free insulin was measured repeatedly for 4 hours following a standardized breakfast in 20 C-peptide negative chronically pumped type I diabetic patients and 5 normal subjects. In the former group, insulin was given as a 1 u/h basal infusion and a 1h superimposed meal-dose of 6 u via a peritoneal (IP) catheter lying in the low (n = 10), or in the mid-abdomen (n = 10). The results of the IP patients were correlated with glycosylated haemoglobin and home capillary blood glucose. Fasting free insulin of IP patients was lower than those of normals (14.7 +/- 0.5 vs 21.0 +/- 1.3 mU/l, p less than 0.01). Dose-induced peak occurred similarly in IP patients and normals (70 +/- 6 vs 70 +/- 12 min.). Values tended to baseline after 165 +/- 15 and 185 +/- 22 min. in IP patients and normals (NS). Results of the mid--and low peritoneum subgroups differed only for peak values (31.5 +/- 2.9 vs 25.0 +/- 1.6 mU/l respectively) and did not correlate with diabetic control.     

HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms

Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex genes primarily involved are most often those encoding the peptide-presenting HLA class I or II molecules. A probable mechanism is preferential presentation by the disease-associated HLA molecules of peptides from autoantigens to T cells. Recent studies have shown, however, that other genes in the HLA complex also contribute. Taken together, available evidence suggests that the HLA complex harbour both disease predisposing genes which are quite specific for some autoimmune diseases (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for several diseases. This will be briefly reviewed in the following.     

Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases

Autoimmune regulator gene mutations were identified in 3 children with type 2 autoimmune hepatitis and extrahepatic immune diseases, including 1 child with immune hepatitis recurrence after liver transplantation. These findings suggest that autoimmune regulator gene variants might predispose children to systemic autoimmune disease, a recurrence of immune disease, or both.     

Several genes in the extended human MHC contribute to predisposition to autoimmune diseases

Autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, affect approximately 4% of the population in industrialized countries, and are characterized by an immune-mediated destruction of autologous cells and/or tissues. More knowledge is needed to prevent and treat this large group of diseases. Unravelling the genetic predisposing factors is important in this respect, and large research efforts have been initiated to reach this goal. The human MHC, also called the human leukocyte antigen (HLA) complex, is known to harbour major genetic determinants for autoimmune diseases. For several autoimmune diseases certain classical HLA class II and/or class I genes are strongly associated with disease. As a result of recent systematic screening studies additional genes and regions in the MHC, including the extended MHC, are now known to contribute to the predisposition.     

Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients

Chromosome region 2q33 encodes several regulators of the immune system, among these the CD28, CTLA4, and ICOS molecules. Involvement of these genes in multiple sclerosis (MS) is not yet clear. We investigated six microsatellites and three SNPs in a relatively large and clinically well characterised Norwegian MS cohort. No associations were observed for any of the markers analysed in 575 MS patients and 551 controls. Associations were neither found when stratifying the material for the HLA-DRB1*1501, DQB1*0602 haplotype, gender, age at onset, disease course nor familial aggregation. In conclusion, this study could not confirm association with the CD28/CTLA4/ICOS gene region.     

Acute vanishing bile duct syndrome after ibuprofen therapy in a child

We report the case of a 10 year-old girl who had Stevens-Johnson syndrome and cholestasis after ibuprofen therapy. Liver histology was compatible with vanishing bile duct syndrome. She received ursodeoxycholic acid, and liver tests normalized within 7 months. This report confirms that ibuprofen may induce acute vanishing bile duct syndrome.     

Clostridium difficile-associated reactive arthritis in two children

In adults, reactive arthritis (ReA) following Clostridium difficile-enterocolitis has been documented. In children, only one case of C. difficile-associated ReA has been reported. We now describe two other cases of ReA associated with C. difficile in children. The characteristics of ReA due to C. difficile appear to be similar in adults and children. Both children show polyarthritis after an episode of diarrhoea with positive stool cultures for C. difficile. Arthritis is asymmetrical with a self-limiting course. Nonsteroidal antiinflammatory drug (NSAID) therapy is sufficient. One case is remarkable because of its prolonged course of ReA despite NSAID therapy, and its association with the presence of HLA-B27 antigen.