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Biomedical subjects

P G Higgins

Publications and source records attributed to P G Higgins.

At least 37 records · Page 2Linked to original sources

Effects of experimentally induced colds on aspects of memory.

Four experiments were carried out to investigate the effects of experimentally-induced colds on various aspects of memory of 27, 47, 39, and 30 adults. Free recall, digit span, and retrieval from semantic memory were unaffected by having a cold. Immediate recognition of important information from a story was impaired in subjects with colds, which suggests they were less able to follow the theme of the story. In contrast to this, volunteers with colds had better recognition of information from a story learned prior to the virus challenge.

Adult↗

von Willebrand factor is an acute phase reactant in man.

Plasma von Willebrand factor antigen (vWfAg) concentrations in 19 patients with acute infectious illnesses of bacterial, viral or parasitic origin were significantly elevated with a mean greater than 3-fold above normal. In individual patients the elevation of vWf correlated strongly with the elevation of serum C-reactive protein (CRP). When patients were studied longitudinally, vWfAg and CRP concentrations both returned to normal values over 3-4 weeks. Similarly, in 14 volunteers infected with cold virus, vWfAg and CRP levels rose significantly and fell together during the course of infection. VWf is thus an acute phase reactant in man.

Acute-Phase Proteins↗

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.

Adult↗

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.

Administration, Intranasal↗

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.

Adult↗

Failure to demonstrate synergy between interferon-alpha and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers.

Marked synergy between the antirhinoviral effect of rHuIFN alpha and enviroxime has been observed in vitro but an attempt to demonstrate it in volunteers was unsuccessful. The sub-optimal intranasal dose of rHuIFN alpha (0.18 Mu four times daily for 4 1/4 days) used prophylactically in the trial did reduce the severity of colds induced by RV9 and 14, but the difference did not reach statistical significance and was not enhanced by the administration of enviroxime (0.28 mg six times daily for six days). The main reason for failure is thought to be the rapid removal of enviroxime from the nose when given intranasally.

Adolescent↗

The effects of experimentally induced respiratory virus infections on performance.

Studies of experimentally induced respiratory infections and illnesses showed that influenza impaired performance on a visual search task but had no effect on a simple motor task, whereas colds impaired the motor task but not the search task. The effect of influenza on the search task was observed in both volunteers with significant clinical symptoms and volunteers who were shown, by virological techniques, to be infected but who had no significant clinical illness. Performance was also impaired during the incubation period of this illness, which confirms that subclinical influenza virus infections can have behavioural effects. In contrast to influenza, the effects of colds were restricted to volunteers who had significant clinical symptoms, and the impairments in performance were observed only when the symptoms were apparent.

Adolescent↗

Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers.

The first evaluation of intranasal (i.n.) recombinant human interferon-gamma (rHuIFN-gamma) as prophylaxis against experimental rhinovirus (RV) infection and illness in volunteers is reported. In two studies, 7 of 27 (26%) of the volunteers who received rHuIFN-gamma (2 Mu i.n. 3 x /day) had either blood stained nasal secretions or nose bleeding which was not observed in any of the 26 placebo recipients. Some volunteers given rHuIFN-gamma showed increased nasal secretion and the majority complained of slight nasal stuffiness, whereas only a few of those receiving placebo complained of these symptoms. In the prophylactic study, 17 volunteers were given the above regimen of rHuIFN-gamma and 17 placebo; after the fourth dose all were challenged with RV9, followed 1 h later with RV14 (100 TCID50 of each virus). Compared with the placebo-treated controls, interferon recipients showed no significant reduction in the proportion who developed colds or became infected, and there was an increase in both their mean clinical scores and mean nasal secretion weights. Thus i.n. rHuIFN-gamma did not prevent rhinovirus infection or illness and may enhance the symptoms.

Administration, Intranasal↗

Biometric outcomes of a geriatric health promotion programme.

A geriatric health promotion programme was conducted to determine biometric changes in cardiovascular, nutritional and musculoskeletal status. Sixty-seven older adults participated in the study. The experimental group of 34 elderly subjects showed statistically significant increases in flexibility and high density lipoprotein with significant decreases in resting pulse rate, blood pressure, total cholesterol, weight and skinfold measures. The overall results of the wellness programme showed significant improvements in the physical health status of older adults.

Aged↗

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

4',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.

Administration, Intranasal↗

Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers.

The antirhinovirus agent chalcone Ro 09-0410 was tested in double-blind place-controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. Fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (TCID50) of human rhinovirus 2 (RV2). There was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase in the nasal secretion produced.

Administration, Intranasal↗

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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.

Common Cold↗

Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).

Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.

Adult↗

Interferon-beta ser as prophylaxis against experimental rhinovirus infection in volunteers.

The first test of intranasal recombinant human interferon-beta ser (IFN-beta ser) as prophylaxis against common colds is reported. IFN-beta ser was cleared from the nose like IFN-alpha. A total of 10 volunteers were each given a total of 2.6 X 10(7) units of IFN-beta ser as 13 doses administered three times daily over 4 days and there were negligible symptoms that were not significantly different from those in 10 given placebo. Twenty-seven volunteers were then given the same regime and challenged after the fourth dose with rhinovirus types 9 and 14. Compared with 27 volunteers given placebo and virus, there were significant reductions in the mean total clinical scores, the amount of nasal secretion, and the frequency of virus excretion. It is concluded that IFN-beta shows antiviral activity in the human respiratory tract and should be tested to determine whether it is tolerated on continued administration.

Adolescent↗

Prevention and treatment of experimental influenza A virus infection in volunteers with a new antiviral ICI 130,685.

The initial prophylactic and therapeutic trials of ICI 130,685 against influenza A virus infection are reported. Prophylaxis with either 200 mg/day (38 volunteers received drug and 40 received placebo) or 100 mg/day (28 volunteers received drug and 28 received placebo) for seven days significantly reduced illness, mean clinical score and nasal secretion weight when volunteers were challenged with 10(4.1) EID50 of influenza virus A/Eng/40/83 (H3N2). Overall, prophylaxis with 200 mg/day and 100 mg/day gave 91% and 72% protection against illness relative to placebo, respectively. In addition, prophylaxis with both regimens for seven days also significantly reduced the number of volunteers who excreted virus. In a therapeutic study, volunteers were inoculated with the same dose of virus and those who developed symptoms which persisted for 6-15 h were treated with 200 mg/day of drug (20 volunteers) or placebo (19 volunteers) for four days. Generally, treatment reduced both the amount of virus excreted and the mean daily clinical score. However, these reductions were only statistically significant (P less than 0.05) on the third day of medication for the amount of virus excreted and on the fourth day of treatment for the mean clinical score. It was concluded that ICI 130,685 is effective in the prevention and treatment of influenza virus infection. An initial tolerance study in 16 volunteers who received either drug (200 mg/day) (8 volunteers) or placebo (8 volunteers) for seven days, indicated that the drug was generally well tolerated. Combining data from all studies, 43% of volunteers who received the drug at the 200 mg/day dosage and 21% who received placebo complained of one or more symptoms. However, symptoms were generally minor and of short duration. At the lower dosage (100 mg/day) the symptoms were qualitatively similar to those reported with placebo.

Adolescent↗