DIURNAL EFFECTS OF FLUOXETINE AND NALOXONE ON THE HUMAN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

1. Central serotonergic pathways are hypothesized to be involved in the stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue release by both circadian- and stress-induced mechanisms. We aimed to investigate this hypothesis by measuring the effect of the highly specific serotonin re-uptake inhibitor fluoxetine (FX) on ACTH and Cortisol release in the morning and in the afternoon in humans, both by itself and in combination with the opioid antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory to hypothalamic corticotropin-releasing hormone (CRH) secretion. Serotonergic agents may act directly or indirectly through these central noradrenergic pathways and, if so, would be expected to be additive to or synergistic with Nal in causing ACTH and Cortisol release. 2. Oral FX (40 mg) was given at approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later, to normal human volunteers. Plasma ACTH and Cortisol levels were measured for 5 h after FX dosing. 3. Fluoxetine produced a small but non-significant increase in Nal-stiimilated ACTH and Cortisol release in both morning and afternoon studies. Naloxone alone did not cause different ACTH and Cortisol responses in the morning and afternoon. 4. These results suggest that serotonergic pathways are not major regulators of the hypothalamic-pituitary-adrenal axis in humans or that FX has counteracting acute inhibitory effects on the axis, such as inhibition of hypothalamic arginine vasopressin secretion, which has been demonstrated in chronic animal studies.     

Differential effects of Ro15-1788 in actions of chlordiazepoxide and ethanol

Three behavioral tests, namely, runway activity, horizontal dowel test and hypothermia, were used to compare the effects of Ro15-1788, a specific benzodiazepine antagonist, on the common neuropharmacological actions of chlordiazepoxide (CDP) and ethanol in C57BL/6J mice. Ro15-1788 completely reversed the CDP-induced inhibition of runway activity and incoordination on a horizontal dowel, but only partially antagonized the hypothermic effects of CDP. The latter phenomenon was likely to be due to the rapid elimination of Ro15-1788, but could also be due to the fact that hypothermia might not be a specific action of CDP. The sedative actions of ethanol were not antagonized at all by Ro15-1788. In fact, Ro15-1788 potentiated the incoordinating effect of ethanol as determined by the horizontal dowel test such that mice injected with Ro15-1788/ethanol had lower brain ethanol levels than mice injected with vehicle/ethanol when they fell off the dowel. In contrast, mice injected with Ro15-1788/CDP took longer to fall off and had significantly higher CDP levels at fall-off than mice injected with vehicle/CDP. The stimulatory effect of a low dose of ethanol on runway activity was reversed by Ro15-1788. These data are discussed in terms of the possible mechanisms of actions for CDP and ethanol.     

A Satiety Quotient: A Formulation to Assess the Satiating Effect of Food

This paper introduces a satiety quotient (SQ) to assess the satiating effect of an eating episode. This procedure constitutes an improvement on previous measures by considering the satiating effects of the eating episode over time. A satiety quotient was calculated from data obtained from several studies involving the presentation of a preload/meal to young lean male and female subjects. Subjects were presented with preloads/meals of varying composition, and motivation to eat immediately prior to, and periodically following, the eating episode were measured. Food and fluids were not consumed whilst motivation to eat was measured in the post preload/meal period. The SQ was calculated by dividing the difference between ratings of motivation to eat before and after the eating episode (pre minus post) by the weight or energy content of intake during the episode. This quotient relates intake to the rate of return of motivation to eat in the post-ingestive period, a relationship which is not apparent on separate examination of the amount consumed or ratings of motivation to eat. Development of this satiety quotient is a further contribution to the evolution of the concept of quantifying satiating effects of foods, and provides additional information on the effects of food attributes on short-term appetite control.     

P20 Red tattoo reactions

Tattoos are becoming increasingly popular, although reactions to tattoos remain relatively uncommon. We describe 4 patients with a variety of red tattoo reactions, one responding well to intralesional steroid therapy. Case 1: A 50‐year‐old man presented with a florid, inflammatory reaction confined to the red area of his forearm tattoo. Biopsy showed a dense lymphocytic and focal macrophage response to tattoo pigment. Mass spectrometry of biopsy tissue revealed high concentrations of titanium and iron. Patch testing was negative. Intralesional steroid injection has produced a marked improvement. Case 2: A 42‐year‐old man presented with an inflammatory reaction affecting the red area of his leg tattoo. Biopsy revealed a florid lymphoid reaction. Case 3: A 30‐year‐old man presented with an eczematous reaction within the red/brown pigmented areas of his tattoos, which was exacerbated by sun exposure. Patch testing showed a (+) positive reaction to cadmium after 96 hours. Photo patch testing was negative. The reaction settled spontaneously within 12 months. Case 4: A 37‐year‐old woman presented with a florid, indurated inflammatory reaction involving the red area of a shoulder tattoo. Patch testing revealed a (++) and (+) positive reaction to nickel and cobalt respectively with a doubtful (?+) reaction to mercury 0.5% in petrolatum after 96 hours. Tattoo reactions, especially red tattoo reactions can present with a spectrum of histological changes, including lichenoid, granulomatous, hypersensitivity, nodular, pseudolymphomatous or sarcoidal reactions. One of our cases responded well to intralesional steroid injection and one case resolved spontaneously.     

Neurologic complications of 2009 influenza-a H1N1 infection in children

Little is known about the neurologic complications of the 2009 Influenza-A H1N1 epidemic in children. We present a retrospective analysis of children evaluated at a tertiary children's hospital who tested positive for H1N1 with neurologic complications. A total of 164 children tested positive for H1N1. Thirty-one of these patients (19%) were evaluated and discharged from the emergency department. Thirty-nine (24%) were treated in the intensive care unit, the remaining 94 (57%) were treated in medical in-patient units. Six subjects died (3.7%). Neurologic complications identified included headache, encephalitis, polyneuropathy, seizures, and malignant hyperthermia. The rate of neurologic complications in this cohort of patients who tested positive for H1N1 was 19%. The incidence of serious neurologic complications was 3%, with another 3% of patients who experienced rapid clinical deterioration and subsequently died. Our observation of neurologic complications associated with 2009 influenza-A H1N1 epidemic suggests the need for clinical vigilance during future influenza epidemics.