A carotid imaging system utilising continuous-wave Doppler-shift ultrasound and real-time spectrum analysis.
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Biomedical subjects
Publications and source records attributed to M G Taylor.
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Border Leicester X Suffolk sheep infected with a strain of S. mattheei maintained in hamsters do not develop the same pathological changes as Romney Marsh sheep infected with the same strain of parasite before hamster passage. To determine the cause of this reduced pathogenicity, five Romney Marsh sheep were each infected with 10 000 cercariae of the hamster-passaged parasite and five with 10 000 cercariae of a S. mattheei strain from Onderstepoort, South Africa, passaged exclusively through sheep. Striking pathological and parasitological differences were found between the two strains. Infection with the "sheep" strain was lethal, whereas infection with the "hamster" strain produced little evidence of clinical disease. By 13 weeks post-infection the mean body weight of the sheep infected with the sheep strain had declined by 15% compared with both the uninfected controls and the sheep infected with the hamster strain, and the mean PCV was lowered to 20% in the sheep strain infected animals. Egg production began at seven weeks with the sheep strain, faecal counts rising to more than 300 e.p.g., whereas only two of the sheep infected with the hamster strain passed eggs in the faeces (at nine weeks) and the maximum egg count was 50 e.p.g. Twice as many adult worms of the sheep strain were recovered, and, although the number of eggs found in the tissues "per worm pair" was not significantly different, overall egg production was higher for the sheep strain; also more of the sheep strain eggs were deposited in the intestines. Similar parasite differences were seen in a supplementary study in mice and it seemed that "attenuation" of the parasite had occurred, presumably due to its maintenance in hamsters. Histopathological observations and faecal egg counts both indicated an inability of hamster strain eggs to penetrate the intestinal lumen; this was probably important in reducing the pathogenicity of the hamster strain.
We have previously described the characteristics of a relatively non-pathogenic laboratory strain of S. mattheei, attenuation of which was apparently caused by passage in hamsters. We now show that chronic infection with this avirulent strain largely protects sheep from the manifestations of acute schistosomiasis when challenged with a virulent strain of S. mattheei. Four sheep were each infected with 10 000 cercariae of the avirulent strain and, together with four wormfree sheep, challenged 63 weeks later with 10 000 S. mattheei cercariae of a pathogenic strain. Four more sheep acted as uninfected controls. Following challenge, the animals were weighed and bled weekly for PCV and serum protein determinations, and egg counts were carried out fortnightly on faeces taken from the rectum. Red cell and albumin turnover were monitored for two weeks immediately before challenge and for a similar period before necropsy, when the adult worms were recovered by perfusion and tissues sampled for histopathology and egg counting. The unvaccinated sheep developed severe disease 6-12 weeks after exposure characterised by marked anaemia, hypoalbuminaemia and hyper-gamma globulinaemia coinciding with the passage of blood-stained faeces and progressive inappetence. In the vaccinated sheep, there was an even earlier rise in gamma globulins, but the other clinico-pathological changes were generally slower to devleop and much milder in severity. The parasitological data showed that although this was partly due to a reduction in the establishment of the challenge worm population the main factor was probably a reduction in the fecundity of these worms.
Anesthetic pollutants in the operating room have been implicated in producing spontaneous abortion in exposed personnel and congenital malformations among their offspring. To test the effects of trace concentrations of enflurane on pregnancy, rats were exposed to two levels (10.7 and 63.7 ppm) of the anesthetic for 8 hr daily from days 1 to 19 of pregnancy. Litter sizes were not affected but birth weights of exposed offspring were slightly higher than controls. During lactation, cross-fostering studies were performed. Exposed offspring were housed with nonexposed mothers and vice versa to determine if exposure during pregnancy affected early development. Weights at 7, 14, and 21 days of age did not differ among the offspring in the lower dose experiment. Weights of the cross-fostered groups in the high dose experiment were decreased at day seven compared to controls. In the same experiment, exposed offspring housed with exposed mothers were heavier than controls on day 21 of lactation. The modest nature of these alterations suggests that enflurane has little or no gross effect on rat pregnancy and postnatal development.
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Six transformation techniques ((1) incubation of cercariae in isotonic medium; (ii) penetration of isolated skin; (iii) stimulation with crude egg lecithin; (iv) mechanical disruption by passage through a syringe and 21 gauge needle; (v) by whorling of cercariae with a vortex mixer; (vi) syringe transformation followed by incubation) were evaluated. The organism produced were assessed for infectivity for mice by 6 different routes of infection (percutaneous, intradermal, subcutaneous, intra-peritoneal, intravenous and intra-muscular). At perfusion the largest numbers of adult worms were recovered from mice injected intramuscularly with organisms produced by the syringe technique and control mice given cercariae percutaneously. The peak for migration of schistosomula (following syringe transformation and intramuscular injection) through the lungs and the appearance of adult worms in the mesenteries was shown to be similar to cercarie administered percutaneously.
In an attempt to develop a non-pathogenic procedure for immunising baboons against S. mansoni, groups of five baboons were exposed to three doses of 5000 6 Kr-irradiated S. mansoni cercariae or to similar numbers of normal S. rodhaini cercariae and challenged at week 15 with 500 normal S. mansoni cercariae. Faecal egg counts, worm and tissue egg counts, and histopathological examination, showed that neither of the immunising schedules had produced significant protection. In the second experiment baboons were injected by the intramuscular route with 31000 schistosomula of S. mansoni in three doses and the irradiation dose was reduced to near the minimum required for worm sterilisation (2-1--2-4 Kr). Challenge with 3500 normal cercariae of S. mansoni 21 weeks after the first immunising dose again showed no significant protection, although reductions of 20--30% were found in egg and worm counts resulting from the challenge. These results indicate that it may be difficult to develop an effective live vaccine for S. mansoni unless the antigenicity of the immunising larvae can be greatly increased.
Irradiated cercariae, irradiated schistosomula, or heterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of 10(4) S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9-11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed schistosomula were administered by intra muscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection.
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Observations were made on the development of immunity to Schistosoma mansoni in baboons using both homologous and heterologous systems. The baboons were immunized by either (a) a single exposure to cercariae of the homologous species S. mansoni, or (b) 1-2 exposures to cercariae of either a S. rodhaini/S. mansoni hybrid or a S. mattheei/S. haematobium hybrid, or (c) repeated exposure to the cercariae of S. rodhaini or S. bovis. Baboons immunized with 500 cercariae of the homologous parasite developed partial immunity to reinfection, as did the baboons immunized with multiple exposures to the heterologous cercariae of S. rodhaini and S. bovis, although these parasites produced neither adult worms nor eggs in the baboons. The hybrids gave rise to well-established adult worm infections, but produced less immunity, even though the S. rodhaini/S. mansoni hybrid was genetically very similar to S. mansoni. These results indicate that adult worms are not essential to produce a considerable degree of immunity to reinfection, which can be engendered by the earlier stages of the parasites. However, none of the immune responses prevented egg deposition in the tissues, and considerable pathological changes resulted from the challenge infection. These observations suggest that although heterologous infections show some promise as immunizing agents, further studies are needed of the pathological changes resulting from their use.
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