Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

High-performance liquid chromatographic analysis of nadolol and bendroflumethiazide combination tablet formulations.

A reverse-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous assay of nadolol and bendroflumethiazide in tablet formulations. The tablets were extracted with methanol and, after centrifugation, were chromatographed. A phenyl column was used with a mobile phase of aqueous acetate buffer with sodium chloride-methanol (60:40); detection was at 270 nm. Linearity of both drugs was satisfactory. The procedure can be automated and also applied to bendroflumethiazide formulations and bulk material.

Cerebral ventricular volume during hyponatraemia.

In order to determine if the neurologic manifestations in chronic hyponatraemia result partly from brain oedema, we measured the cerebral ventricular volume before and after correction of hyponatraemia in eight patients with central nervous system manifestations. Only the three patients with seizures showed a clear change in the ventricular size and probably had brain oedema.

Prolactin secretion in Cushing's disease.

PRL secretion was evaluated in 11 patients with Cushing's disease (7 women, 4 men). Basal morning levels were elevated when compared to normal subjects. PRL reactivity to TRH and hypoglycemia was normal in most patients. The 24-h mean PRL levels were elevated, with partial or total alteration of the nyctohemeral rhythm. Cure of Cushing's disease by selective pituitary adenomectomy restored a normal PRL secretion.

Central nervous system complications of Mycoplasma pneumoniae.

Three cases of central nervous system complications of Mycoplasma pneumoniae infections are reported. There were several atypical findings: the first patient presented with an acute disseminated encephalitis with normal cerebrospinal fluid and hypogammaglobulinaemia. The second patient presented with a left sixth nerve palsy followed six weeks later by choreoathetoid movements and an acute psychosis. The third patient presented with an acute encephalitis associated with acute renal failure secondary to rhabdomyolysis and was the only patient who did not completely recover; he was discharged akinetic and mute, but with normal renal function. The diagnosis of complications of Mycoplasma pneumoniae may be difficult. In two of the three cases a raised red blood cell volume secondary to a high titre of cold agglutinins rapidly led to the correct diagnosis.