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Biomedical subjects

D A Tyrrell

Publications and source records attributed to D A Tyrrell.

At least 91 records · Page 5Linked to original sources
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit.

Intranasal sprays of interferons (IFNs) given one day before and for three days after virus challenge can protect human volunteers from infection with rhinoviruses, coronavirus, and influenza. Longer dosage of IFN gives rise to nasal symptoms and signs such as bloodstained nasal discharge. More effective IFNs and regimes are therefore needed. IFN beta is active but the degree to which it will irritate the nose is unknown. Combining IFNs with synthetic antiviral drugs can produce synergistic increases in antiviral activity. It is suggested that these increases may be exploited in future experiments.

Administration, Intranasal↗
PubMed1986

Common colds.

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Capsid↗
PubMed1986

Antibody dependent cellular cytotoxicity against coronavirus 229E-infected cells.

An antibody dependent cellular cytotoxic (ADCC) reaction was elicited using human mixed lymphocyte cultures against coronavirus 229E-infected C-16 cells. The response was assayed in microtitre plates by radioactive chromium release. Optimal killing of target cells was achieved using cells labelled 22 h after infection. A prozone was present and the optimal dilution of sera was invariably 1:200. The majority (70%) of sera tested gave a positive ADCC response. These included all sera judged positive by ELISA, but also some which were judged negative. Two experiments using purified IgG from serum which was ADCC and ELISA positive suggested that the response is mediated by an IgG antibody and that the prozone is due to a separate serum component.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies.

A total of nine normal volunteer subjects were studied with three forms of [99mTc] hexamethylpropyleneamineoxime (HM-PAO), a potential cerebral blood flow imaging agent. One, the d,l isomer, showed 4.1% uptake in the brain which remained constant over 8 hr. There was good differentiation between uptake in gray and white matter on tomographic slices. We propose that this agent may allow regional cerebral blood flow imaging to be performed on a routine basis.

Adult↗
PubMed1985

Experimental parvoviral infection in humans.

Healthy adult volunteers were inoculated intranasally with human parvovirus obtained from an asymptomatic blood donor. One week after inoculation, intense viremia was observed in seronegative volunteers, accompanied by a mild illness with pyrexia, malaise, myalgia, itching, and excretion of virus from the respiratory tract. In the following week hematologic studies revealed reticulocytopenia with an associated slight drop in hemoglobin concentration, lymphopenia, neutropenia, and a drop in platelet counts. At 17-18 days after inoculation a second-phase illness with rash and arthralgia lasting three to four days occurred in three of four infected volunteers. This study confirms the etiologic role of human parvovirus in erythematous rash illness, with the second-phase illness being consistent with adult cases of erythema infectiosum. Moreover, the hematologic changes associated with infection support the hypothesis that the same virus is responsible for the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with chronic hemolytic anemia.

Anemia, Hemolytic↗
PubMed1985

Rhinovirus colds.

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Benzimidazoles↗
PubMed1985

Normal volunteer studies with modified 99Tcm tin colloid.

99Tcm tin colloid, modified by the addition of various amounts of the surfactant Pluronic F68 was evaluated as a new liver imaging agent in normal adult male volunteers. The relative amounts taken up in the liver and spleen were measured by two quantitative methods with a view to establishing the most useful technique. The changes in biodistribution resulting from mechanical shaking during preparation of the colloids and in vitro ageing of the preparations were assessed. The pharmacokinetics of uptake into liver and spleen of the various formulations tested were independent of Pluronic F68 content. However, at low levels of Pluronic F68 the liver:spleen ratio decreased as the colloid preparation was aged before use. At high levels of Pluronic F68 there was increased background activity. An optimum formulation was identified combining low background activity with a stable pattern of biodistribution independent of preparation age.

Adult↗
PubMed1985

Studies on 44 081 R.P., a new antirhinovirus compound, in cell cultures and in volunteers.

A synthetic compound, 2-[(1,5,10,10a-tetrahydro-3H-thiazolo[3,4b]isoquinolin-3-ylidene) amino]-4-thiazoleacetic acid (S), 44 081 R.P., inhibits the multiplication of rhinoviruses in cell cultures. Of the 69 rhinovirus strains and serotypes that have been studied, 39% were inhibited at a concentration of 7 micrograms/ml, far below that which affects cellular metabolism (250 micrograms/ml). Preliminary data indicate that the compound inhibits some early events of virus replication but that some cellular functions are also involved in its mechanism of action. Despite its antiviral activity in vitro, the compound, when self-administered intranasally as a 0.2% solution to volunteers from the day before to 5 days after inoculation with a human rhinovirus strain, had no significant effect on rhinorrhea, clinical score, or laboratory evidence of infection.

Adolescent↗
PubMed1984

Pharmacokinetics of intranasally applied medication during a cold.

The rate at which interferon is cleared from the nose after local administration was measured in volunteers both before and after challenge with virulent strains of human rhinovirus. Interferon was not cleared more rapidly after virus challenge, and there was no relationship between the amount of nasal secretion produced after challenge, and the rate of interferon clearance. These findings suggest that an inverse relationship between the quantity of a locally applied antirhinovirus drug which is recovered in nasal wash, and clinical and laboratory evidence of rhinovirus infection may be taken as evidence for a beneficial effect of the drug.

Administration, Intranasal↗
PubMed1984

Intranasal lymphoblastoid interferon ("Wellferon") prophylaxis against rhinovirus and influenza virus in volunteers.

Purified lymphoblastoid interferon (HuIFN-alpha) or placebo was self-administered intranasally by volunteers using a spray device three times daily for four and one-third days beginning one day before virus challenge. Each subject received a total dose of 35.1 Mu of interferon (IFN) administered in 13 equal doses of 2.7 Mu. Doses were administered in a volume of 0.2 ml (0.1 ml to each nostril). The first group received human rhinoviruses types 9 and 14. There were no significant colds in 19 volunteers receiving IFN and 7 in 23 volunteers receiving placebo (p less than 0.05). Serological responses and/or recovery of challenge virus were obtained in 14 (74%) recipients of IFN and in all 23 recipients of placebo (p less than 0.05). Mean daily and total clinical scores and mean daily and total nasal secretion weights were significantly greater in those receiving placebo than in those given IFN. The second group received influenza virus A/Eng/40/83. There were 4 significant illnesses in 13 volunteers receiving IFN and 10 in 17 volunteers receiving placebo (p greater than 0.05). Serological responses and/or recovery of challenge virus were obtained in 11 volunteers receiving IFN and 14 volunteers receiving placebo. Mean daily secretion weight and mean clinical scores were lower in those given IFN than in those given placebo - the differences were significant for clinical score on 2 days. The results suggest that IFN prophylaxis was less effective against influenza A than against rhinovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Evaluation of the antirhinovirus chalcone Ro 09-0415 given orally to volunteers.

Ro 09-0415, a phosphorylated 'pro-drug' of the potent antirhinovirus compound, 4' ethoxy-2'-hydroxy-4, 6' dimethoxy-chalcone (Ro 09-0410) was tested in a double-blind placebo-controlled trial for its protective effect against experimental rhinovirus infection. The maximum dose, 1200 mg bd, based on considerations of practicality and tolerance was given orally both before and after challenge with a sensitive rhinovirus, type 9. Plasma concentrations of active compound in excess of those required for the inhibition of rhinovirus type 9 in vitro were achieved, but there was no evidence to suggest that treatment with Ro 09-0415 had a beneficial effect. It is concluded that Ro 09-0415 given orally is unlikely to be of value in the prophylaxis or therapy of human rhinovirus infection.

Administration, Oral↗
PubMed1984

Infection and interferon production in systemic juvenile chronic arthritis: a prospective study.

Twenty-four episodes of disease exacerbation in 19 children suffering from systemic juvenile chronic arthritis were studied. Sixteen of these were preceded by an infection (chi 2 = 20.14, p less than 0.001), mostly of the upper respiratory tract. In the 10 cases seen during an infection causative agents were identified in 5 (herpes simplex, rhinovirus, and on 3 occasions streptococcus). The total number of infections was not increased when compared with infection rates predicted by several reported studies. In the absence of clinical infection, specific antibody titres to a panel of microbial antigens were similar to those of a control group but with a trend toward higher titres in patients with hypergammaglobulinaemia. Interferon (IFN) responses were not defective, though sequential in-vitro IFN production from peripheral blood mononuclear cells (PBM) fluctuated considerably in the same patients, occasionally being absent with no obvious clinical correlate. IFN-alpha was induced by stimulation with Newcastle disease virus (NDV), and the mean responses of the patients were significantly greater than those of controls. IFN-gamma production on phytohaemagglutinin (PHA) stimulation was similar in patients and control groups. IFN was not detected in any of the sera from patients or controls.

Adolescent↗
PubMed1984

Treatment of herpes genitalis with carbenoxolone and cicloxolone creams: a double blind placebo controlled clinical trial.

preliminary results in vitro have indicated that carbenoxolone and analogues possessed activity against herpes viruses. We undertook a double blind clinical study to compare the efficacy of carbenoxolone and cicloxolone creams with placebo in initial and recurrent herpes genitalis. Seventy-nine patients (21 of whom were entered in the trial more than once) received 105 courses of treatment, 83 of which were suitable for life table analysis. There were significant differences in the time to disappearance of pain (p = 0.044) and the healing of lesions (p = 0.023) in favour of cicloxolone compared with placebo. Carbenoxolone showed some beneficial effect compared with placebo, but this was not significant. Results on day 5 were similar. The only adverse reaction was mild erythema with irritation in one patient in each treatment group. We conclude that further trials with more extensive virological investigation are indicated to confirm the beneficial effect of cicloxolone.

Carbenoxolone↗