Work of a district ethical committee.
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Biomedical subjects
Publications and source records attributed to D A Tyrrell.
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Cerebrospinal fluid from 13 of 38 patients with schizophrenia had a cytopathic effect in cultures of MRC5 cells. The cytopathic agent passed a 100 nm but not a 50 nm filter and was unaffected by heat at 56 degrees C for 30 min, treatment with chloroform, or the presence in cultures of bromodeoxyuridine. The agent could not be propagated serially in a satisfactory manner but its properties were those of a virus. A similar cytopathic effect was induced by cerebrospinal fluid from 8 of 11 patients with serious or chronic nervous system disease but only 1 of 25 patients with surgical or general medical conditions.
A virus-like agent (V.L.A.) with a cytopathic effect on cultured cells was found in the cerebrospinal fluid of 18 of 47 patients with schizophrenia, of whom 10 had nuclear schizophrenic symptoms. In most patients with V.L.A., blood and C.S.F. protein concentrations were normal. Patients with and without V.L.A. had similar clinical characteristics but serum IgA levels were higher in those with V.L.A. V.L.A. was also detected in the C.S.F. of 8 of 11 patients with serious or chronic neurological disease (Huntington's chorea, multiple sclerosis, and unexplained alterations of consciousness).
Colonies of cells were obtained from human fetal lung tissue and exposed to recently isolated respiratory viruses. There was a considerable variation in the number of rounded cells found in different colonies exposed to rhinovirus types 2 and 9 (RV2 and 9), human coronavirus 229E (HCV), adenovirus type 3 (Ad3) and respiratory syncytial virus (RSV). Smaller colonies had more rounded cells than larger colonies. Clones were established from 9 out of 11 colonies. They varied in their rate of growth and the pattern formed on a plastic surface. They varied also in their virus susceptibility particularly to "difficult" rhinoviruses such as RV9 and SF1340. One cell clone (HL1/77 Clone 8), was highly susceptible to all these viruses. All cultures were more sensitive to RSV when maintained in F12K medium than in MEM, whereas there was no difference for rhinoviruses. Influenza A and B and parainfluenza 3 viruses sometimes produced cytopathic effect, and always produced haemadsorption, but unlike the previous strains could not be passed serially and presumably produced little infectious virus. All clones were rather insusceptible to Ad3; but the virus could be passed, whereas coxsackie virus B3 produced no CPE. Substantial yields of coronavirus and rhinovirus were obtained in gelatin sponge cultures. Two "very difficult" respiratory viruses which had just been adapted to tissue culture; namely, HS rhinovirus and JK coronavirus grew in 7 of 9 and in 6 of 9 clones respectively.
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Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not.
A disseminated viral illness was demonstrated by isolating a virus from the CSF, blood or urine in 27% of 73 children who were admitted to hospital after a first febrile convulsion. However, a viral aetiology could be implicated for 86% of the children after combining results of tissue culture, electron microscopy, mouse inoculation, complement fixation tests, and interferon assay. Parallel bacterial cultures showed a possible pathogen in 29% of children, but in only 4% was the pathogen isolated from the CSF, blood, or urine. No correlation was found between the nature of the pathogen (or evidence of its dissemination) and the severity of the convulsion, degree of fever, CSF protein, CSF white cells, or the WBC. The results suggest that a febrile convulsion could be a response to invasion of the blood stream or central nervous system by a micro-organism which is usually a virus. Invasion may be of such brief duration that successful isolation of the virus from the blood, CSF, or urine in not more commonly achieved.
In a hospital study rotavirus was identified in 51% of 152 children with diarrhoea. These patients showed a clinical pattern that was distinct from patients in whom the diarrhoea was associated with bacteria, other viruses, or no pathogens. A respiratory illness was described in 66% of rotavirus patients and usually preceded the gastrointestinal symptoms. Vomiting lasted between one and 3 days and was curtailed by substituting the normal diet with clear fluids. Watery diarrhoes continued for 4 or 5 days, even when rehydration was by the intravenous rather than the oral route. Prolonged diarrhoea was rare. Most children infected with rotavirus were under 2 years of age, but dehydration was most severe in infants aged between 12 and 18 months. A clinician can thus recognise the rotavirus syndrome and expect spontaneous recovery if adequate rehydration is maintained for a critical few days.
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A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.
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