SLCO1B1 variants as predictors of methotrexate-related toxicity in children with juvenile idiopathic arthritis.

Objectives: Methotrexate (MTX) administered at the dose 10-15 mg/m2 is currently recommended as the first line therapy in most juvenile idiopathic arthritis (JIA) subtypes. Gastrointestinal side effects and hepatotoxicity are the most prevalent manifestations of MTX intolerance, frequently leading to discontinuation of otherwise effective treatment. Genetic variability within solute carrier organic anion transporter family member 1B1 (SLCO1B1), encoding a hepatic MTX membrane transporter, has been associated with high-dose MTX efficacy and toxicity in paediatric patients with acute lymphoblastic leukaemia. The aim of our study was to determine the association between single-nucleotide polymorphisms in the SLCO1B1 gene (rs4149056, rs2306283) on the disease activity and presence of side effects of MTX therapy in patients with JIA.Method: The study recruited 100 children with JIA of all subtypes treated with MTX. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months after starting MTX. Genotyping was performed using genomic DNA isolated from peripheral blood samples.Results: In comparison to wild-type allele, SLCO1B1 rs4149056 CT/CC variant was significantly associated with higher odds ratio of MTX gastrointestinal side effects occurrence (OR=4.55, 95%CI 1.37-15.13; p=0.013). SLCO1B1 rs4149056 TT subjects were more likely than CT/CC individuals to develop hepatotoxicity (17.86% vs 4.76%, p = 0.046).Conclusion: SLCO1B1 rs4149056 may serve as a determinant of MTX treatment toxicity in children with JIA.

[The state of the gastrointestinal tract and glucose metabolism as limiting factors of parenteral-enteral nutrition in patients with intracranial hemorrhages].

A part of patients' arterial hyperglycemia is not accompanied by increases in the content of glucose in brain substance, and aggressive correction of hyperglycemia can lead to reduction in concentration of glucose expressed in "affected", and conditionally "intact" brain substance. At choosing a mixed strategy of parenteral-enteral correction should take into account not only condition of the gastrointestinal tract but especially absorption of glucose (the level of cellular homeostasis).

[Toxicity of mushrooms Paxillus involutus and Paxillus atrotomentosus]. / K voprosu o toksichnosti gribov vida svinushka tonkaia i tolstaia.

Thirty-eight patients with mushroom (Paxillus involutus and Paxillus atrotomentosus) poisoning were treated. Slight poisoning (acute gastroenteritis) was diagnosed in 17 patients, medium-severe in 13, severe in 6, and extremely severe in 2 patients. Changes in the LPO-AOD system correlated with the severity of hepatorenal involvement. The treatment included hepatotropic therapy; patients with acute renal failure were treated by hemodialysis. Paxillus mushrooms induced functional evacuatory disorders in the small intestine. Eleven patients with adhesions in the abdominal cavity developed ileus. Two patients died: a man aged 26 years after eating fried (not boiled) mushrooms and a woman aged 76 years with ileus with symptoms of multiple organ dysfunction. The rest patients were discharged from hospital in satisfactory condition. Clinical course of poisoning with Paxillus mushrooms is discussed.

Attitudes toward abortion, capital punishment, and assisted suicide.

In 51 college students, attitudes toward abortion, capital punishment, and assisted suicide were not consistently anti- or pro-death.