ABSTRACT
Incidence of sudden death in Rett syndrome is greater than that of the general population, and cardiac electrical instability is a prime suspect cause. The objective of the present study was the evaluation of heart rate variability, a marker of autonomic activity, in females affected by classic Rett syndrome and atypical variants for a possible explanation of the higher risk for sudden death observed in these subjects. Our study showed that girls with classic Rett syndrome had significantly lower heart rate variability and longer corrected QT intervals than in atypical Rett syndrome and age-matched healthy girls. Reduction of heart rate variability progresses with age and with the clinical stage of the syndrome. These results suggest the possible role of the progressive cardiac dysfunction in the sudden death associated with Rett syndrome.
Subject(s)
Heart/physiopathology , Long QT Syndrome/complications , Long QT Syndrome/physiopathology , Rett Syndrome/complications , Verbal Behavior , Child , Death, Sudden/epidemiology , Disease Progression , Electrocardiography , Female , Heart Rate/physiology , Humans , Long QT Syndrome/diagnosisABSTRACT
In 6 normal volunteers given single oral doses of 250,500 and 1000 mg ticlopidine (T), the peak plasma level of unchanged drug was reached after about 2 h. There was no correlation between the plasma T level and its inhibitory effect on platelet function, expressed as % inhibition of ADP-induced aggregation. By means of HPLC and GC/MS significant concentrations of T were demonstrated in washed red cells, platelets and neutrophils, with a marked difference in the time course of the appearance of cell-associated drug. The time course of platelet-associated T very accurately fitted that of the antiaggregatory activity. After subacute oral administration (250 mg b.d. for 7 days), the maximum effect on platelet function was observed after 3 to 4 days, when a significant concentration of platelet-associated T had been reached. The pharmacological effect persisted as long as drug was detectable in platelet. An in vitro study strongly suggested that the antiaggregating effect was retained by treated washed platelets but not by treated plasma. It is suggested that the platelet compartment represents the pharmacological target of T via a specific uptake system.
Subject(s)
Platelet Aggregation Inhibitors/pharmacology , Ticlopidine/pharmacology , Adult , Blood Platelets/metabolism , Dose-Response Relationship, Drug , Erythrocytes/metabolism , Female , Humans , Male , Middle Aged , Neutrophils/metabolism , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/blood , Platelet Aggregation Inhibitors/pharmacokinetics , Ticlopidine/blood , Ticlopidine/pharmacokineticsABSTRACT
In a 24-week multicenter double-blind clinical trial, efficacy and safety of the novel nonsteroidal anti-inflammatory drug imidazole salicylate (750 mg t.i.d. per os) and ibuprofen (600 mg t.i.d. per os) were compared in 60 patients with classical or definite rheumatoid arthritis, randomly assigned to one of the two treatment groups. The patients improved significantly with both treatments in all the clinical parameters examined such as the duration of morning stiffness, grip strength of both hands, Ritchie's articular index and severity of joint pain. The systemic tolerability, assessed by hematological, liver and kidney function tests was excellent with both treatments. The incidence of side effects was overall fairly low with both drugs, and lower in the group treated with imidazole salicylate (23% vs. 33%).
