Cessation of chronic nicotine or amphetamine administration precipitates withdrawal syndromes characterized by affective symptoms, including "diminished interest or pleasure" in rewarding stimuli (i.e., anhedonia) (American Psychiatric Association 1994;Covey et al. 1998;Glassman 1993;Hughes 1992). Interestingly, the symptom of "diminished interest or pleasure" is not only a symptom of drug withdrawal, but also a core symptom of depression and a negative symptom of schizophrenia (American Psychiatric Association 1994;Markou et al. 1998). Brain reward threshold elevation is an operational measure of this symptom because it reflects diminished sensitivity to rewarding electrical stimuli. In rats, withdrawal from drugs of abuse belonging to diverse pharmacological classes, such as nicotine (Epping-Jordan et al. 1998 Watkins et al. 2000b), amphetamine Zacharko 1980a, 1980b;Kokkinidis et al. 1980Kokkinidis et al. , 1986 Barrett 1976, 1980;Lin et al. 1999Lin et al. , 2000Paterson et al. 2000;Wise and Munn 1995), cocaine (Baldo et al. 1999;Kokkinidis and McCarter 1990; Koob 1991, 1992a;Markou et al. 1992) morphine (Schulteis et al. 1994) and ethanol (Schulteis et al. 1995) elevated brain stimulation reward thresholds.In addition to the affective aspects of drug withdrawal reflected in threshold elevations, nicotine, opiate, or ethanol withdrawal also lead to alterations in a set of behaviors termed somatic signs. In the case of nicotine, these somatic signs are primarily gasps, writhes, eye blinks, and ptosis (Epping-Jordan et al. 1998;Hildebrand et al. 1997Hildebrand et al. , 1999Malin et al. 1992). It is unlikely that these somatic signs in the rat reflect the affective component of drug withdrawal. Nevertheless, the study of both threshold elevations and somatic signs permits the investigation of the effects of manipulations on the various aspects of withdrawal.Based on evidence demonstrating the efficacy of serotonergic antidepressant treatments, reduced cerebrospinal fluid levels of serotonin metabolites, endocrine measures reflecting reduced serotonergic neurotransmission and the exacerbation of depressive symptomatology seen after serotonin (5-HT) depletion in depressed individuals, it is hypothesized that reduced serotonergic neurotransmission underlies at least some aspects or some subtypes of non-drug-induced depressions (for reviews, see Caldecott-Hazard et al. 1991; CaldecottHazard and Schneider 1992;Heninger et al. 1996;Markou et al. 1998;Meltzer and Lowy 1988;Willner 1985). The purpose of the present study was to test the hypothesis that reduced serotonergic neurotransmission mediates some of the affective aspects, not only of non-drug-induced depressions, but also of druginduced depressions. Thus, the present study tested the hypothesis that enhancement of serotonergic neurotransmission through acute administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Wong et al. 1995) in combination with a relatively selective 5-HT 1A receptor antagonist would alleviate the symptom of "dimin...

As many drugs in paediatrics are used off-label, prescribers face a lack of evidence-based dosing guidelines. A Dutch framework was developed to provide dosing guidelines based on best available evidence from registration data, investigator-initiated research, professional guidelines, clinical experience and consensus. This has clarified the scientific grounds of drug use for children and encouraged uniformity in prescribing habits in the Netherlands. The developed framework and the current content of the Dutch Paediatric Formulary could be used as basis for similar initiatives worldwide, preferably in a concerted effort to ultimately provide children with effective and safe drug therapy.

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Introduction: While options for treatment strategies for infantile hemangiomas (IH) are numerous, evidence-based information about agents, optimal dosage, adverse effects, treatment modality, pretreatment and treatment strategies remain limited. Areas covered: To evaluate side effects and adverse events of medical treatment in children with infantile hemangioma, a comprehensive review of the literature was performed to provide information for daily practice. In total 254 studies were retrieved from medical databases and comprised 10,022 patients divided into 5 different treatment groups. Information about working mechanism, side effects and adverse events of therapies used as a single agent for IH are discussed and evaluated according to information from pharmacotherapeutic databases. Randomized controlled trials have only scarcely been performed for the many therapeutic options reported for IH. Short-and long-term side effects and adverse events, have not been systematically studied. Subsequently information about the medical treatment options and pharmacotheraputic databases for therapy in children with IH are incomplete. Expert opinion: From the many therapeutic options, propranolol is the first-line approach for IH, predominantly based on clinical observation, efficacy and tolerability in the short-term. The unsolved ravels of possible short and long-term adverse events of propranolol used during early developmental stages of children need thorough review.

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Background: Bordetella pertussis (BP) is a worldwide public health problem, which affects 20 to 40 million people each year.Objective: To describe the clinical and epidemiological pattern of BP infection among children. Methods:We analyzed the clinical files of children with a PCR-confirmed BP in nasopharyngeal aspiration who were hospitalized in a tertiary care hospital between January 2003 and December 2009.Results: There were 36 admissions for whooping cough; 75% of them were infants younger than 2 month-old and 69% had never been vaccinated. The average length of hospitalization was 12.7 days. There was no difference between winter and summer months. The prevalence was higher in 2006 (28% of all cases). Dual infection of BP with other agents occurred in 31% (7 cases of respiratory syncytial virus and 1 case each of metapneumovirus, parainfluenza 3 and adenovirus).Cough was the most frequent symptom (89%; median duration of 12 days). Leukocytosis occurred in 33% and lymphocytosis in 64%.All patients were treated with macrolides (74% erythromycin). Supplemental oxygen was used in 47% (median 8.5 days); bronchodilators in 64%, systemic corticosteroids in 33% and respiratory exercise in 8%.The major complications were apneas (25%) and pneumonia (19%). There were 7 (19%) severe cases that required mechanical ventilation, all in children younger than 3 month-old. One death occurred in a 1 month-old patient.Conclusion: Despite widespread vaccination, the incidence of BP has been rising. New vaccination strategies should be evaluated to protect infants as early in life as possible. COMPARISON OF ANTIBIOTIC DOSING RECOMMENDATIONS FOR NEONATES