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In this article, recent research studies in the field of cocaine addiction are reviewed, with an eye toward emergent options for treatment innovation. Particular attention is paid to the neurobiology and specific neurotransmitter and receptor mechanisms involved in cocaine abuse, dependence, and other unique phenomena of addiction such as sensitization, craving, compulsive drug use, and withdrawal. The vicissitudes in the dopamine theory of brain reward mechanisms, dopaminergic effects of cocaine, and emerging roles of GABA, serotonin, glutamate, and nitric oxide in cocaine addiction and its sequelae are discussed. Neuroanatomic findings elicited with imaging studies using PET and functional MRI are summarized. These findings support the role of specific brain regions within the dopaminergic system such as the ventral tegmentum and nucleus accumbens in the induction of the cocaine "high" and craving, respectively. Research approaches to the problem of developing effective pharmacotherapeutic options to render cocaine ineffective and modalities under study, such as dopamine uptake inhibitors and immunotherapy, are also discussed in the context of a variety of practical problems faced by these experimental therapies. Pharmacotherapeutic strategies and new directions in this research, such as the adaptive changes of the opioid system in cocaine addiction, are reviewed. Potential areas for further study are brought forth for further debate and possible clinical evaluation.
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OBJECTIVE: To evaluate the efficacy of primary in situ extracorporeal shockwave lithotripsy (ESWL) for the treatment of ureteric calculi in children. PATIENTS AND METHODS: The Wolf 2500 Piezolith was used to treat 63 children (aged 4 months to 12 years) with 76 ureteric calculi, including 10 children with impacted calculi. The calculi were located in 14 upper, 13 mid and 44 lower ureters, and the stone burden varied from 4 to 17.8 mm (mean 12.6). All children aged < or = 10 years were treated under general anaesthesia; lithotripsy was attempted under intravenous sedation in the older children. RESULTS: At the 3-month follow-up, there was an overall successful outcome in 55 children (87%), which included 12 of 13, eight of nine (89%) and 35 of 41 (85%) of the children with upper, mid and lower ureteric calculi, respectively, and nine of the 10 with impacted calculi. Re-treatment was required in 20 (36%) patients, while auxiliary procedures after ESWL were required in three (6%). The major complications encountered were ureteric obstruction with sepsis in two children, bacteraemia in another and urinary retention due to a urethral stone fragment in a fourth child. CONCLUSIONS: In situ ESWL was an effective treatment modality for ureteric calculi at all levels in children, even when impacted. In the short term, complications were minimal, but the long-term effects need further assessment.
