Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

The platelet function analyzer (PFA-100) may not be suitable for monitoring the therapeutic efficiency of von willebrand concentrate in type III von willebrand disease.

We describe a type-III von Willebrand patient who was admitted to the hospital with severe deformity and functional deficit of the left knee joint due to recurrent hemarthrosis. Orthopedic intervention was necessary. To prevent bleeding episodes, von Willebrand factor (vWF) replacement therapy was given during and after surgery. APTT, plasma FVIII activity (FVIIIc), vWF antigen (vWF Ag), and vWF ristocetin cofactor (vWF Rco) were measured. Primary hemostasis was monitored using the PFA-100. This "Platelet Function Analyzer" is designed to measure platelet adhesion and aggregation capacities. Whole blood is aspirated through a capillary and is forced to flow through the central hole of a membrane coated with collagen and epinephrine (COL/EPI) or ADP (COL/ADP) as platelet activators. Irreversible platelet aggregation results in the formation of a stable platelet plug, closing the central hole. The result is expressed as "closure time" (CT), i.e., time necessary to stop the blood flow, and is a measure of platelet hemostasis capacity. Laboratory investigations during substitution therapy revealed no shortening of closure times with both COL/EPI and COL/ADP cartridges despite normalization of plasma vWF Ag, vWF Rco, and FVIIIc levels. These observations suggest that intraplatelet vWF, which is totally absent in type-III von Willebrand disease, plays an important function in the adhesion of platelets to the collagen-coated membrane of the PFA-100 system, simulating an injured vessel wall. Consequently, we conclude that the PFA-100 may not be suitable for monitoring the therapeutic efficacy of von Willebrand concentrate in type-III von Willebrand patients during substitution therapy.