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Biomedical subjects

D A Tyrrell

Publications and source records attributed to D A Tyrrell.

At least 109 records · Page 6Linked to original sources
PubMed1983

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

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

Adolescent↗
PubMed1983

An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-alpha 2.

Before the prophylactic effect of human interferon alpha 2 (HuIFN-alpha 2) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.

Administration, Intranasal↗
PubMed1983

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 1. Short-term immunity.

Groups of volunteers were immunized subcutaneously with one of three inactivated influenza virus A/USSR/77 (H1N1) vaccine preparations; a whole virus vaccine, a surface-antigen subunit adsorbed vaccine, or an aqueous surface-antigen subunit vaccine. The reactions to immunization were recorded, and the antibody response was measured 1 month later. A fourth group of volunteers were inoculated intranasally with live attentuated A/USSR/77 (H1N1) influenza virus; the reactions and antibody response of these volunteers were also measured. One month after immunization, the incidence of infection by challenge with homologous live attentuated virus was determined for all groups of volunteers. The results showed that all four vaccines used were relatively non-reactogenic, and that inactivated vaccines induced higher titres of serum antibody than the live attenuated vaccine. All the vaccines induced significant protection against challenge virus infection which was directly related to the level of serum HI antibody response.

Adolescent↗
PubMed1983

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 2. Long-term immunity.

Groups of volunteers were immunized with one of three influenza virus vaccines, and the resistance to challenge infection with attenuated influenza A (H1N1) virus was measured 8 months later. The vaccines were aqueous subunit influenza A/USSR/77 (H1N1) vaccine, aqueous subunit influenza B/Hong Kong/73 vaccine, or attenuated influenza virus A (H1N1) vaccine. The B virus vaccine was included as a control to assess the incidence of natural A virus infection during the study period. A proportion of the B virus vaccinees had pre-existing A (H1N1) virus antibody and were used to study the immunity conferred by natural infection to the live virus challenge. The serum antibody responses were measured at 1 and 8 months after immunization. The results showed that all the vaccines induced serum HI antibody in a proportion of the volunteers; however, after 1 month, higher titres of serum antibody were found in volunteers given inactivated A vaccine than in those given live attenuated A virus vaccine. Eight months post-immunization the titres of serum antibody in volunteers given inactivated vaccine had declined significantly, but there were no changes in the antibody titres of those given live virus vaccine. The incidence of infection by the challenge virus at 8 months post-immunization was directly related to the serum antibody titres 1 month post-immunization; no evidence was obtained to suggest that those given live virus vaccine had a more solid immunity than those given inactivated vaccine.

Adolescent↗
PubMed1983

An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2 1/2 years. Analysis of variance on data obtained from behavioral observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2 1/2 years after injection by automated activity monitoring. There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation. Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.

Animals↗
PubMed1983

Comparative intranasal pharmacokinetics of interferon using two spray systems.

Physician-administered and self-administered interferon (IFN) nasal sprays were compared by measuring residual IFN recovered from the nose at intervals following single doses. Amounts of IFN recovered five minutes after administration and the decay curves of recoverable antiviral and immunoreactive IFN with time were variable between volunteers but similar for both methods. It follows that a self-administered IFN spray would be suitable for future trials of IFN in upper respiratory infections. It was also confirmed that IFN persists in the nose for at least 24 h and is not all recovered by nasal washing, suggesting that it may be bound to, then slowly released from, nasal mucosal cells.

Administration, Intranasal↗
PubMed1983

Therapeutic activity of enviroxime against rhinovirus infection in volunteers.

The therapeutic effect of intranasal 2-amino-1-(isopropylsulphonyl)-6-benzimidazole phenyl ketone oxime (enviroxime) against human rhinovirus type 9 was evaluated in a double-blind, placebo-controlled volunteer trial. Enviroxime given 6 times a day was well tolerated, producing a reduction in clinical evidence of infection which coincided with the start of medication (44 h after virus challenge). Although there was a statistically significant reduction in clinical score in the enviroxime group on day 5 after virus challenge, reductions in total clinical score accumulated during the trial and reductions in the quantity of nasal secretions were not significant. A separate analysis was performed on data from volunteers who did not have symptoms when medication began (and who might have been expected to benefit more from enviroxime therapy). No apparent enhancement of the effects of enviroxime could be demonstrated in this group.

Adult↗
PubMed1983

Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.

Administration, Intranasal↗
PubMed1983

Further studies of the cytopathic effect in tissue cultures inoculated with CSF from patients with schizophrenia and other nervous system diseases.

Tissue cultures were inoculated with CSF from patients with schizophrenia and some other psychiatric and neurological illnesses. The CPE was readily seen in all 13 strains of human skin fibroblasts examined but could not be serially passaged. The results of retesting many specimens, either by the same worker or under full double blind conditions, usually agreed and thus indicate that the CPE was due to the CSF and not to non specific changes in the cultures. CPE was seen in cultures in which mycoplasmas could not be detected. Degenerated cultures show polymorphous nuclei with condensed nuclear chromatin and enlarged mitochondria with few cristae but virus particles were not identified. The physical properties of the agent in the CSF that induced the CPE were the same as those reported earlier for CSF from schizophrenic patients.

Adult↗
PubMed1983

Interferon system in patients with systemic juvenile chronic arthritis: in vivo and in vitro studies.

Eighteen patients with active systemic juvenile chronic arthritis (JCA) were studied for periods of up to 1 year to see whether any relationships existed between the interferon (IFN) response, the course of the underlying disease and intercurrent infections. The control group consisted of 23 children who were each seen on one occasion. IFN-alpha production by mononuclear cells (MNC) cultured in vitro was stimulated with Newcastle disease virus (NDV). Comparison of the mean IFN-alpha responses from all patients with control responses showed that MNC from the JCA group produced significantly more IFN-alpha. Furthermore, MNC obtained from JCA patients at times of systemic flare produced significantly higher titres of IFN-alpha than at times when the patients were clinically stable. IFN-alpha production by MNC from individual patients fluctuated considerably from occasion to occasion whereas IFN-gamma production by MNC induced with phytohaemagglutinin (PHA) remained more stable. There was no significant difference between patients and controls with respect to IFN-gamma responses and no relationship with clinical condition. Serum IFN was not detected either by sensitive bioassays for IFN-alpha and IFN-gamma or by an immunoradiometric assay for IFN-alpha.

Adolescent↗
PubMed1982

Purified interferon as protection against rhinovirus infection.

In a double-blind placebo-controlled study a preparation of human leucocyte interferon purified by affinity chromatography using a monoclonal antibody and applied by repeated nasal sprays reduced the incidence and severity of colds in volunteers challenged with human rhinovirus 9. Although interferon itself caused some symptoms, these were minor compared with the clinical colds. Interferon activity was still detectable in nasal washings as long as 26 hours after the last dose in about half the volunteers on active treatment.

Administration, Intranasal↗
PubMed1982

Selective infection of lower respiratory tract by respiratory viruses in children with recurrent respiratory tract infections.

Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections.

Adenoviridae↗
PubMed1982

The isolation and partial characterisation of a cytomegalovirus from the brown rat, Rattus norvegicus.

This report describes the isolation and partial characterisation of a cytomegalovirus (CMV) from the wild brown rat (Rattus norvegicus). The isolate was sensitive to ether and heat treatment at 56 degrees C/30 minutes, and had a characteristic herpes virus morphology. In rat embryo fibroblast cells, new virus was detectable by 18 hours after inoculation. The cytopathic effect consisted of a focal rounding of cells which developed to involve the entire monolayer. Inoculation of newborn rats produced mortality of 67-75 per cent which was reduced to 33-46 per cent by intra-peritoneal inoculation or tissue culture passage. Highest virus concentrations were found in the liver and spleen 14 days after inoculation. The virus was also pathogenic (to a lesser extent) to newborn BALB/c mice. It was related to the Osborn strain of mouse CMV by fluorescent-antibody testing but distinct by the serum-neutralisation test.

Animals↗
PubMed1982

Evaluation of a human diploid cell strain rabies vaccine: final report of a three year study of pre-exposure immunization.

The antibody responses of 194 volunteers were studied for up to 3 years after primary immunization with one, two or three doses of human diploid cell rabies vaccine, administered either in 0.1 ml volumes intradermally (i.d.) or as 1.0 ml intramuscularly (i.m.). Sero-conversion occurred in 95% of subjects after the first injection and in 100% after the second. The highest titres and most durable antibody responses were induced by three injections of vaccine. Booster doses were administered either by the subcutaneous (s.c.) or i.d. route, after 6, 12 or 24 months to randomly grouped volunteers; these induced responses greater than or equal to 5.0 i.u. per ml in 95% of subjects. The responses were rapid and were neither influenced by the primary regimen nor by the timing and route of the booster dose. Antibody titres after i.d. immunization were only two-fold lower than those induced by the larger volume of vaccine. The findings suggest that the i.d. route is both effective and economic.

Adolescent↗