P.G. Higgins

Effects of interferon alpha on performance in man: a preliminary report

The effects of three doses of interferon alpha (1.5 Mu, 0.5 Mu and 0.1 Mu) on performance were studied. The injection of 1.5 Mu IFN produced symptoms and performance changes which closely resembled those found in volunteers with influenza. Specifically, volunteers were slower at responding when they were uncertain when a target stimulus would appear, but were not impaired on a pursuit tracking task or syntactic reasoning task. The results suggest that interferon-induced changes in CNS function provide a plausible explanation for the selective effects of influenza on performance.

Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837).

This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds in human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times a day, commencing 28 h before virus challenge; treatment continued for 4 days and one dose (total dose, 25 mg). This regimen suppressed symptoms until 48 h after medication ceased, at which time colds developed. In another trial, medication with R61837 commenced at 4 h before virus challenge and continued for a total of 6 days (total dose, 36 mg). The drug produced substantial reductions in both the mean daily clinical score and the mean daily nasal secretion weight compared with patients given the placebo. These differences reached statistical significance for 2 and 4 days, respectively. In a further trial, intranasal R61837 was not effective in treating colds even when given shortly after the onset of symptoms and in doses of up to 15 mg/day.

Effects of Experimentally Induced Respiratory Virus Infections and Illness on Psychomotor Performance

In two studies experimentally induced colds slowed the speed of response in a serial reaction task. Responding was also slower during the incubation period of the illness, which shows that performance on such a task may be used to predict subsequent illness. Volunteers who had no significant clinical illness, but who had a significant rise in IgG following virus challenge, also showed changes in performance. In contrast to the serial reaction task, neither colds nor subclinical infections impaired performance on a detection task.

The time course of the humoral immune response to rhinovirus infection

The specific humoral immune response of 17 volunteers to infection with human rhinovirus type 2 (HRV-2) has been measured both by neutralization and by ELISA. Six volunteers who had HRV-2-specific antibodies in either serum or nasal secretions before HRV-2 inoculation were resistant to infection and illness. Of the remaining 11 volunteers who had little pre-existing HRV-2-specific antibody, one was immune but 10 became infected and displayed increases in HRV-2-specific antibodies. These antibodies first increased 1-2 weeks after infection and reached a maximum at 5 weeks. All six resistant volunteers who had high pre-existing antibody and eight of the volunteers who became infected maintained their HRV-2-specific antibody for at least 1 year. At this time they were protected against reinfection. Two volunteers showed decreases in HRV-2-specific antibodies from either serum or nasal secretions. They became infected but not ill after HRV-2 inoculation 1 year later.

The efficacy of intranasal interferonα-2a in respiratory syncytial virus infection in volunteers

Abstract In a double-blind, placebo-controlled study, self-administered intranasal interferonα-2a or placebo was given both before and after challenge with respiratory syncytial virus. The incidence of colds and the severity of signs and symptoms were reduced in those receiving interferonα-2a as compared with those given placebo. In a further double-blind, placebo-controlled study, self-administered interferonα-2a or placebo was given only to those volunteers who developed colds following challenge with respiratory syncytial virus. There was no evidence that interferonα-2a reduced the severity of the signs and symptoms or shortened the duration of the illness. The similarity of these results to the effect of interferonα-2a in rhinovirus infections in volunteers is discussed.

A study of the efficacy of the bradykinin antagonist, NPC 567, in rhinovirus infections in human volunteers

Abstract In a double-blind placebo controlled trial intranasal NPC 567, a bradykinin antagonist, failed to alleviate the symptoms of experimental rhinovirus colds. Indeed, there was evidence that the drug enhanced the symptoms although no irritant effect was detected on the uninfected nasal mucosa.

Effects and After-Effects of the Common Cold and Influenza on Human Performance

Volunteers who develop a cold following virus challenge were significantly slower on choice reaction time tasks than those with no illness. This effect was still observed after the clinical symptoms had gone. In contrast to this, influenza illnesses only impaired performance in tasks in which subjects were uncertain where the target stimulus would appear. These results demonstrate that the CNS effects of respiratory virus infections depend on the type of virus, and that performance impairments may remain even after the symptoms of a cold have gone.

The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers.

Two studies involving double‐blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2·6 mg active drug per nostril, q.i.d.) with placebo on clinical symptoms and performance impairment associated with the common cold. In the first study volunteers were challenged with rhinoviruses (RV9 and RV14), and in the second study with respiratory coronavirus. In both studies, active and placebo groups of volunteers were demographically similar. Infection rates in both groups were also similar. There were no withdrawals resulting from unusual symptoms related to either treatment. In the rhinovirus study (19, placebo; 20, nedocromil sodium) daily symptom scores and daily mean nasal secretion weights were significantly lower in the nedocromil sodium‐treated group. In the coronavirus study (26, placebo; 27, nedocromil sodium) there was little difference in the severity of colds between the active and placebo‐treated groups, but trends favoured nedocromil sodium. In both studies the impairment of performance in volunteers who developed a cold was significantly less in those treated with nedocromil sodium than in those treated with placebo.

An appraisal of the efficacy of the antiviral R 61837 in rhinovirus infections in human volunteers

The efficacy of the antiviral R 61837 in experimental colds in three previously reported volunteer trials and one new trial is reviewed here. It was dissolved in a new vehicle, hydroxy-β-cyclodextrin, and used as a nasal spray. A substantial reduction in illness occurred when given prophylactically and during the incubation period but not when used therapeutically.

Failure of intranasally administered 4′, 6-dichloroflavan to protect against rhinovirus infection in man

Summary4′,6-Dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. Dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue culture. A total of 49 volunteers were included in the efficacy analysis.Dichloroflavan did not produce any consistent or significant reduction in clinical or laboratory parameters of infection. Indeed there was some indication that treatment with the drug may have been associated with increased severity of clinical signs and symptoms. Dichloroflavan administered intranasally is not, therefore, of value in the prevention of human rhinovirus infection.