A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis.

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.

Flunisolide nasal spray compared to beclomethasone dipropionate in the treatment of seasonal rhinitis.

Forty-seven informed out-patients with the diagnosis seasonal rhinitis of at least two years' duration took part in a controlled single blind, double observer, parallel four-center study for the purpose to compare efficacy and tolerance of two local corticosteroid nasal sprays: flunisolide 25 micrograms/dose and beclomethasone 50 micrograms/dose. The patients received for four weeks one of the two treatments; flunisolide 50 micrograms in each nostril twice daily or beclomethasone dipropionate 50 micrograms in each nostril four times daily. The study was conducted under the Declaration of Helsinki. Patients were assessed on admission and after two and four weeks. All patients completed the trial. The results showed that both drugs are highly effective in controlling nasal rhinitis symptoms, 21 out of 24 flunisolide treated patients and 21 out of 23 beclomethasone treated stated good to total control after four weeks' treatment during the pollen season. No statistical difference between the two could be discovered in any of the parameters measured. The only side effect recorded was mild transistory stinging in connection with application of the two different sprays. This occurred in a few patients in both groups. The results from the study indicate that the new corticosteroid flunisolide in a dose of 100 micrograms X 2 is comparable to beclomethasone dipropionate 100 micrograms X 4 concerning efficacy and tolerance in prophylactic treatment of seasonal rhinitis.

Size and duration of inhibition in the medial geniculate body in unanesthetized cats.

A method which allows repeated micro-electrode recordings from subcortical structures without using any drugs is described. This method was adopted in combination with convential implantation techniques to study click-evoked potentials and inhibitory processes in the auditory system of the cat. The click-evoked potentials in MG were hardly affected by moderate doses of barbiturate and only to a minor degree in the auditory cortex. In the unanaesthetized animal the most significant contribution to the click-evoked inhibition in the auditory system was due to mechanisms in the MG. The inhibition was diminished both in size and duration as compared with the situation in anaesthetized cats. The MG cells showed a tendency to cyclic inhibition in the unanaesthetized cat, but not so regularly as following administration of sodium pentobarbital. The action of barbiturates on the auditory system is discussed.

Activity of single medial geniculate units in response to single and double clicks.

The discharge pattern to clicks and the time course and pattern of the click-induced inhibition in the medial geniculate body have been studied by single unit recording technique. The medial geniculate neurones showed a tendency to fire at preferred latencies after a click. A conditioning click caused a reduced number and increased latency of the discharges to a subsequent test click. Provided conditioning click of a certain strength was employed, the inhibition was often cyclic, each period lasting for about 100-150 ms. Clicks could also trigger barbiturate spindles with synchrony between the activity of the medial geniculate body and the primary auditory cortex. Interaction experiments suggest that the triggered and spontaneous spindle activity operate with the same neurones.

Inhibitory processes in the medial geniculate body.

Inhibition in the medial geniculate body was studied with a double click technique. A conditioning click caused a marked inhibition of field potentials and unit discharges to a subsequent test click. Cyclic inhibition with a period of about 150 ms was seen in the medial geniculate body and the auditory cortex, but not in the inferior colliculus. The postsynaptic excitability was tested by recording from the killed ends of the thalamocortical fibres. A preceding click reduced the direct response to a test stimulus delivered to the medial geniculate body indicating the presence of postsynaptic inhibition. The excitability of the fibres from the inferior colliculus terminating in the medial geniculate body was tested with a modified Wall (1958) method. The results suggest the presence of a presynaptic inhibitory mechanism in the medial geniculate body. The techniques employed do not allow an estimation of the relative contribution of the two inhibitory mechanisms to the inhibition at the medial geniculate level.

Presynaptic and post-synaptic inhibition elicited in the cat's dorsal column nuclei by mechanical stimulation of skin.

1. Primary afferent depolarization (PAD), with a time course comparable with that of the PAD following limb nerve stimulation, was produced in the cuneate nucleus by mechanical stimulation of the skin of the ipsilateral forepaw. Brushing or blowing on hairs was as effective as any other form of stimulation and there was a rapid adaptation to a sustained stimulus. Up to 55% increase in excitability was produced by blowing on hairs.2. The P-wave and the PAD produced by mechanical stimulation were at a minimum in the rostral part of the cuneate nucleus and at a maximum 2-6 mm caudal to the obex.3. The distribution of the PAD produced in the gracile nucleus by blowing on the skin of the hind foot was studied by a technique allowing measurement of excitability changes near the terminals of single fibres. Minimal values were obtained rostral to the obex and maximal values 1-4 mm caudal to the obex, a distribution matching that previously determined for single cells subject to surround inhibition.4. Post-synaptic inhibition was produced in the cuneate nucleus by gentle blowing on the ipsilateral forepaw. Up to 20% fall in excitability occurred in populations of cells tested by direct electrical stimulation. IPSPs lasting up to 160 msec were observed in single cells following light mechanical stimulation in the immediate neighbourhood of these cells' receptive fields. Blocking of antidromic invasion of single cells was occasionally produced by mechanical skin stimulation.5. It is concluded that both pre- and post-synaptic inhibition must be concerned in the phenomenon of afferent surround inhibition, though there was no evidence to indicate their relative roles, qualitatively or quantitatively.6. It is shown that up to 20% reduction in transmission through the gracile or cuneate nucleus could be produced by blowing on the ipsilateral hind paw or forepaw respectively, measured as reduction in the area of the monophasically recorded lemniscal response. A single electrical stimulus to the skin of the contralateral forepaw reduced transmission through the cuneate nucleus by less than 5%.