The present study evaluated, using a well-controlled dehydration protocol, the effects of 24 h fluid deprivation (FD) on selected mood and physiological parameters. In the present cross-over study, twenty healthy women (age 25 (se 0·78) years) participated in two randomised sessions: FD-induced dehydration v. a fully hydrated control condition. In the FD period, the last water intake was between 18.00 and 19.00 hours and no beverages were allowed until 18.00 hours on the next day (23–24 h). Water intake was only permitted at fixed periods during the control condition. Physiological parameters in the urine, blood and saliva (osmolality) as well as mood and sensations (headache and thirst) were compared across the experimental conditions. Safety was monitored throughout the study. The FD protocol was effective as indicated by a significant reduction in urine output. No clinical abnormalities of biological parameters or vital signs were observed, although heart rate was increased by FD. Increased urine specific gravity, darker urine colour and increased thirst were early markers of dehydration. Interestingly, dehydration also induced a significant increase in saliva osmolality at the end of the 24 h FD period but plasma osmolality remained unchanged. The significant effects of FD on mood included decreased alertness and increased sleepiness, fatigue and confusion. The most consistent effects of mild dehydration on mood are on sleep/wake parameters. Urine specific gravity appears to be the best physiological measure of hydration status in subjects with a normal level of activity; saliva osmolality is another reliable and non-invasive method for assessing hydration status.

Disturbances in integrative function have been consistentLy described in psychotic disorder; for instance, prepulse inhibition of the startle reflex (startle-PPI) which is a marker of sensory gating, is deficient in persons with schizophrenia. The N-methyl-D-aspartate antagonist ketamine produces in control subjects a spectrum of neurobehavioural symptoms like encountered in schizophrenia, and disrupts startle-PPI in animals. In the present study, we investigated in 12 healthy subjects whether ketamine would reduce sensory-gating in auditory responses at doses which produce psychotic symptoms. In a double-blind, crossover design loading doses of 0.024, 0.081 and 0.27 mg/kg or saline were employed, followed by maintenance infusion for 120 min. A passive paradigm has been developed which consisted in tone bursts, preceded or not by a (near-threshold) click at intervals of 100 ms or 500 ms. Brain electromagnetic activity imaging of the responses to sound stimuli has been carried out by way of a 148-channel magnetoencephalography-system. Actual evoked response amplitudes and underlying equivalent current dipole strengths have been compared to multi-electrode evoked potentials from the scalp. A click stimulus is capable to inhibit test responses under placebo at the 100 ms interval. During maintenance infusion of ketamine at steady-state (for >30 min) after 0.27 mg/kg, no such amplitude changes were observed anymore (p <0.05) and under these circumstances significant increases in Brief Psychiatric Rating scale and Scale for the Assessment of Negative Symptoms scores were evidenced (p < 0.001). Intermediate effects have been observed when the dose was lowered to 0.081 mg/kg. The present results have shown that ketamine may induce a psychotic-like clinical state associated with gating deficits in healthy subjects.

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Clinical and hormonal findings have been collected from 14 patients affected by carcinoma of the prostate observed over a 5-year period following orchidectomy. Plasma testosterone decreased significantly after surgery (62 ng +/- 21 SD/100 ml), remaining below 100 ng/100 ml even in cases showing only a partial regression or increase of the tumour. Gonadotropin FSH increased 1 year after orchidectomy to 28 mIU +/- 5/ml and remained constantly elevated up to the 5th year, whilst LH increased progressively up to the 5th year (30 mIU +/- 12/ml). Finally, plasma cortisol increased progressively up to 23.2 microng +/- 17.4/100 ml at the 5th year post-orchidectomy, especially in those cases showing partial regression or increase of the tumoral mass, indicating an adrenal hyperfunction which is probably responsible for increased production of weak androgens that can be transformed in the prostate into more active compounds. These results suggest therefore that after orchidectomy, cortisol and adrenal androgen determination may be of value in detecting the potential activation of prostatic adenocarcinoma.

The role of opioid peptides in the secretion of gonadotropins in man was studied by means of three different experimental models: a patient with congenital indifference to pain, morphine addicts and healthy volunteers, representing respectively spontaneous pathology, a pharmacological model and normal conditions. The patient with congenital indifference to pain fully investigated from a neurological point of view, was considered for the high levels of central opioid peptides. Morphine addicts, selected on the basis of a two year drug addiction, were considered as having high pharmacological opiate activity in the brain. Healthy volunteers, given 0.1 mg/kg/h of naloxone i.v., were used as a model with low central opioid activity. FSH, LH and testosterone were evaluated in all subjects by means of a sensitive and specific RIA. Morphine addicts received their usual dose of morphine and blood was collected every 20 minutes for 120 minutes before and after GnRH administration. Blood samples were collected in normal subjects every 20 minutes for 120 minutes in basal conditions and thereafter during naloxone infusion for 240 minutes. GnRH was given in a single i.v. bolus at 120 minutes after the start of the infusion. The same procedure was used in the case of congenital indifference to pain.The patient with congenital indifference to pain showed no detectable FSH and LH in basal conditions and low levels of testosterone; in the GnRH test a response in LH was observed but FSH failed to rise. Morphine addicts showed low gonadotropin levels in basal conditions and the GnRH profile was similar to that described above. In normal subjects naloxone infusion stimulated LH release and GnRH produced a further rise in LH.These data indicate an inhibitory control mechanism of opioids in the release of gonadotropins and suggest that this inhibition may be exerted at a suprahypophyseal level.