Safety of recombinant vaccinia vaccines.
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Biomedical subjects
Publications and source records attributed to L H Collier.
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In a prospective study of cryoprecipitate administration to patients who had never received large pool concentrates, no evidence of hepatitis or HIV infection was detected in a follow up period of one year. Following the introduction of screening of blood donors for anti-HIV in the UK in October 1985 the use of cryoprecipitate in selected cases should be reconsidered.
By several criteria, replication of herpes simplex virus type 1 (HSV-1) in primary cell cultures from inbred strains of mice resistant (R) to this virus was less than in cultures from susceptible (S) strains. The difference was not obviously related to less efficient adsorption, to more efficient production of interferon or to a larger number of lysosomes. Except at high multiplicities of infection, cells from the F1 progeny of a cross between an R and an S strain replicated virus as well as cells from the S parent; this contrasts with strain-related resistance to intraperitoneal inoculation in vivo, which is inherited as a dominant characteristic. It is suggested that diminished ability of structural cells to replicate HSV-1 may contribute to resistance in the intact animal.
Inbred strains of mice varying in susceptibility to intraperitoneal (i.p.) inoculation of HSV-1 were tested by inoculating 10(5) p.f.u. of the SC 16 strain into the ear pinna. Increase in ear thickness was less in resistant than in susceptible strains. In the resistant C57BL/6 strain, local replication of virus, spread to cervical ganglia and development of latent infections of the ganglia were all less than in susceptible DBA/2 mice; there was also less cellular infiltration of the inoculation site. Like resistance to i.p. inoculation, resistance to ear inoculation appears to be inherited as a dominant characteristic. The test provides a non-lethal method of distinguishing between resistance and susceptibility of inbred strains of mice to HSV-1 and may also be useful in defining resistance factors.
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In children aged 15--16 years receiving routine reinforcement tetanus immunisation, adsorbed vaccine caused more severe and more frequent local reactions than did plain formol toxoid, and a higher incidence of pyrexia. The incidence of swelling and erythema at the inoculation site increased with serum antitoxin titre at the time of inoculation, whereas pain and tenderness were related to the presence of the aluminium hydroxide adjuvant. Both vaccines gave satisfactory antibody responses over a 5-month observation period; plain formol toxoid induced higher mean titres than did the adsorbed vaccine. It is recommended that plain and not adsorbed vaccine be used when reinforcement of immunity to tetanus alone is desired.
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Of 60 TRIC agents isolated from Gambian children with trachoma, 25 were serotype 1 and the remainder type 2. There was a pronounced difference in the proportions of these types in the two villages studied. In the village with a predominance of type 2 strains, TRIC agents remained confined to 2 adjacent compounds over a 14 month observation period. All 19 type 1 strains examined were characterized by the appearance in yolk sac smears of compact aggregates of elementary bodies; such aggregates were seen in only 2 of 35 type 2 strains, and may reflect a chemical difference in the surface of the elementary bodies or in a substance elaborated during their replication.
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Ninety-nine young Gambian children were studied for 61 weeks. About half of them had trachoma at the outset, and 80% of the remainder acquired the disease while under observation. IgG trachoma antibody in the serum and IgG and IgA antibodies in the conjunctival secretions (CS) were titrated by an indirect immunofluorescence method. In serum samples obtained in capillary tubes the mean titre was slightly higher than in samples collected on filter paper. Serum antibody at titres >/= 1/10 was invariably associated with a clinical diagnosis of trachoma; it increased both in frequency and titre as the disease progressed, and was present in about half of those with Tr II. In CS, IgG antibody was present less often and at lower titres than in serum, and IgA antibody was detected even less frequently. There was some evidence of correlation between the titres of IgG and IgA antibodies in CS, but none for a relationship between the titres of the antibodies in serum and those in CS. Antibodies were almost never present in the absence of conjunctival follicles, but their titres were unrelated to the degree of follicular hyperplasia; there was no obvious relationship between the serological findings and corneal lesions. In children diagnosed clinically as trachoma, serum antibody was present in almost all those with conjunctival inclusions, and in a proportion of inclusion-negative subjects; the mean titre was much higher in the inclusion-positive group.These findings do not settle whether CS antibodies are made locally, or are derived partly or wholly from the blood. They suggest that the indirect immunofluorescence test may be a useful diagnostic aid in trachoma, particularly in view of the rarity of false positive reactions; but there is at present little to choose between it and complement-fixation tests in terms of sensitivity.
In terms of the rate of positive diagnoses the indirect fluorescent antibody (FA) test was rather more effective than iodine for demonstrating trachoma (TRIC) inclusions in conjunctival scrapings, but the degree of advantage was not statistically significant. In duplicate scrapings stained at random by one or the other method, FA staining yielded the higher inclusion count significantly more often than did iodine. Some inclusions that failed to stain with FA were found on subsequent staining with Giemsa. A method is described for improving the post-FA Giemsa staining of conjunctival smears stored at subzero temperatures. Given adequate facilities, the FA stain is preferable to iodine for demonstrating TRIC inclusions in the conjunctiva; but the iodine method, properly used, holds advantages for field use.
Trachoma vaccines are usually assayed by testing their ability to protect monkeys or baboons against subsequent challenge of the conjunctiva with a pathogenic strain of trachoma/inclusion conjunctivitis (TRIC) agent. In such experiments the course of infection in vaccinated baboons was compared in terms of arbitrary scores assigned to a range of clinical signs, and of counts of TRIC inclusions in conjunctival scrapings. Analysis of many such scores indicated that after a large challenge dose of strain MRC-4s, the scores for signs of inflammation reached their maximum earlier than the follicle score; the inflammation score was closely related to the number of inclusions, whereas the follicle score was not. With this system, the optimum periods for eliciting differences between vaccinated and control measures varied according to the sign used; it was later for follicles than for inflammation or inclusions. For assessing the influence of vaccination, the mean of the inflammation scores read weekly for the first 3 weeks after challenge and the mean inclusion score over the same period were equally satisfactory, and either was rather better than the mean of three follicle scores taken over the period 3-6 weeks.For assessing the influence of vaccines or therapeutic agents on experimental trachoma it is important to determine which signs discriminate best between treated and control animals, and the optimum times for measuring them.
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