| 1. |
- Björkman, Sven, et al.
(författare)
-
Cerebral uptake of morphine in the pig calculated from arterio-venous plasma concentration gradients: an alternative to tissue microdialysis
- 1995
-
Ingår i: Life Sciences. - 1879-0631 .- 0024-3205. ; 57:25, s. 2335-2345
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to characterize the reversible cerebral uptake of morphine in the pig by measuring the changing arterio-venous plasma concentration gradient over the brain. Seven pigs were anaesthetized by continuous infusions of ketamine and pancuronium and ventilated with oxygen in nitrous oxide. During and after 5-min intravenous infusions of morphine hydrochloride, blood samples were drawn from a central artery and from the internal jugular vein. Concomitantly, cerebral blood flow (CBF) was repeatedly measured as clearance of 133Xe from the brain after intracarotid injection. Plasma concentrations of morphine and, in samples from two animals, morphine glucuronides were assayed by high-performance liquid chromatography. Drug flux (Jnet) from arterial blood to brain was calculated from the arterio-venous plasma concentration gradients, the blood:plasma concentration ratio and CBF. Uptake of morphine from arterial blood to brain was very rapid, with a maximal Jnet typically at 3 min after the beginning of the infusion. The initial cerebral extraction of morphine was close to 50%. When the arterial and jugular venous concentration curves crossed, 1-5 min after the end of the infusion, the initially rapid uptake of morphine changed into a slow and steady release. The cerebral extraction of morphine glucuronides was comparable to that of morphine, however, Jnet was lower due to lower plasma concentrations at time of maximal extraction. The findings demonstrate how the cerebral uptake and release of morphine and its metabolites can be studied with a method that is entirely non-invasive to the brain and permits very flexible sampling. Uptake and release of drug is observed directly and need not be inferred from cerebral concentration curves.
|
|
| 2. |
- Gillberg, Christopher, 1950, et al.
(författare)
-
Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial.
- 1997
-
Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 54, s. 857-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. Methods: Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with "pure" ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. Results: Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children—Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. Conclusion: The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.
|
|
