Multi-clinic cross-over comparison of triazolam (Halcion) and placebo in the treatment of co-existing insomnia and anxiety in anxious out-patients.

In this multi-clinic double-blind cross-over designed study, forty-five anxious and insomniac out-patients received either triazolam (Halcion) 0.25 mg or placebo at bedtime. After seven days the medications were crossed over. The dosage was doubled after nights 2 and 9 if good sleep was not produced. Three patients dropped out, two on placebo (one for side effects and one for lack of efficacy) and one on triazolam (due to misunderstanding instructions). Analysis of sleep questionnaire data showed superiority of triazolam to placebo (p less .001) in all parameters. The incidence of dreams was not affected. Analysis of antianxiety efficacy showed that triazolam was superior to placebo (p less than .001) in all parameters, both physician's and self ratings. Thus, either triazolam or a good night's sleep significantly relieved the patient's anxiety. No side effects or abnormal laboratory values of significance were attributable to triazolam.     

Estrogen receptor-alpha immunoreactive neurons in the ventrolateral periaqueductal gray receive monosynaptic input from the lumbosacral cord in the rhesus monkey.

Estrogen affects female sexual behavior, analgesia, and micturition in mammals. One of the possible sites at which estrogen might exert its effect on these functions is the periaqueductal gray (PAG). The PAG is involved in each of these functions, it receives sensory input relevant to these functions from the lumbosacral cord, and contains estrogen receptor-alpha immunoreactive (ER-alpha IR) neurons. The present light (LM) and electron microscopic (EM) study seeks to determine whether there are monosynaptic projections from the lumbosacral cord to ER-alpha IR neurons in the PAG of the female rhesus monkey. Tracer was injected into the lumbosacral cord to visualize the lumbosacral-PAG projection, and the distribution of ER-alpha IR neurons in the PAG was studied immunohistochemically. The medial part of the ventrolateral caudal PAG received the densest projection from the lumbosacral cord. Another prominent projection was found in the lateral PAG at the intercollicular level. Although ER-alpha IR neurons were widely distributed throughout the PAG, approximately 40% of ER-alpha IR PAG neurons were located as a distinct cluster in the medial portion of the ventrolateral, caudal PAG. Double labeling experiments showed that the location of this cluster precisely overlapped with the densest lumbosacral-PAG projection. EM revealed that axons from the lumbosacral cord made asymmetrical synaptic contacts with unlabeled dendrites and ER-alpha IR neuronal somata in the ventrolateral PAG. It is concluded that there exists a specific, monosynaptic pathway from lumbosacral neurons to ER-alpha expressing PAG neurons in the rhesus monkey. This pathway might be involved in the mechanisms of analgesia, blood pressure, mating behavior, and micturition.     

Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa.

A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy. The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment. Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection. The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers. The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion. The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h. A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg. Mean total body clearance was 23.3 +/- 10.1 liters/h. The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake. The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43). After 6 to 12 days of i.v. treatment, four patients were switched to oral ciprofloxacin. We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v. infusion and oral dosing. The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin.