Establishing cost-effectiveness of antipsychotic drugs.
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Biomedical subjects
Publications and source records attributed to D M Taylor.
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Although bovine spongiform encephalopathy (BSE) has occurred in other European countries, the major epidemic has been in the United Kingdom (UK), where there have been more than 163,000 cases so far. BSE has been linked to the practice of feeding meat-and-bone meal (MBM), putatively contaminated with scrapie agent, to cattle. A ban on the feeding of MBM to ruminants in the UK has resulted in a significant decline in the number of reported cases. It is considered that BSE in other European countries probably originated through the use of British MBM in the diets of cattle in these affected countries. Recently, in the UK, a new variant form of Creutzfeldt-Jakob disease in humans has been discovered, which does not appear to have occurred before the advent of BSE. It may have been caused by BSE agent, possibly as a consequence of dietary exposure. The use of MBM in the diets of any livestock species has now been prohibited in the UK.
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The incidence of bovine spongiform encephalopathy (BSE) in the United Kingdom is now declining at a significant rate, indicating that the 1988 ban on feeding ruminant-derived meat and bone meal to cattle is having the anticipated effect. The question now is whether or not BSE can be completely eradicated. At present there is no evidence of lateral or maternal transmission, the occurrence of which would complicate the eradication process. Eradication therefore seems to be achievable, especially now that meat and bone meal has been recently banned from the diets of all farmed animals in the UK. In this review the aetiological role of meat and bone meal in the causation of BSE is discussed together with the epidemiological data and the results of studies on genetic susceptibility. The controversial theories relating to the nature of the causal agent, and strain-typing studies on BSE agent, are described. Current information on pathogenesis and diagnosis is presented. The occurrence of BSE in cattle outside the United Kingdom, and BSE-related disease in species other than cattle is also discussed.
A 13-wk dietary intervention was carried out with 23 members of the 1991 wintering party of an Australian National Antarctic Research Expedition. Canola margarine and canola cooking oil were substituted for usual dietary fats (butter, a margarine containing 28% saturated fat, a polyunsaturated margarine, and vegetable oil). Mean energy intake slowly decreased although body weight slowly increased during the 42-wk wintering-over period. During 13 wk of dietary substitution, mean total cholesterol and low-density-lipoprotein-cholesterol concentrations fell by 7.0% and 10.0%, respectively (P < 0.05, repeated-measures ANOVA). These changes were not found in a second wintering-over group that did not experience this dietary intervention. The data indicate that a relatively simple change to the food supply has the potential to produce significant beneficial changes in lipoprotein lipid profile.
Partial survival of lyophilized scrapie agent has been reported previously following exposure to dry heat at 360 degrees C for 1 h, and led to speculation that scrapie-like agents might not be completely inactivated by incineration. However, it is known that dried infectivity is more difficult to inactivate by heat than that in hydrated samples. In this present study it was shown that the infectivity in macerates of mouse-brain infected with the ME7 strain of scrapie agent was not completely inactivated by exposure to dry heat at temperatures up to 180 degrees C for 1 h but the titre of surviving infectivity reduced progressively as the temperature was increased. No infectivity was recovered after a 1 h exposure at 200 degrees C. These data suggest that scrapie-like agents are unlikely to survive incineration.
An analysis was made of incubation period data from experiments in which samples of brain-tissue infected with the 263K strain of scrapie agent were injected intracerebrally into hamsters following exposure of the tissue to autoclaving or sodium hydroxide. Where there was survival of infectivity, this often produced extended mean incubation periods compared with the maximal incubation periods in controls injected with untreated agent. These results confirmed that, after chemical or physical treatment, infectivity titre should not be calculated by comparing the incubation period from a single dilution-group against a standard dose-response curve for untreated agent.
Scarification of the skin is a possible route of entry for scrapie infectivity in sheep, and for Creutzfeldt-Jakob disease agent in humans within the context of occupational exposure to infected brain in the autopsy room or laboratory. The effectiveness of skin scarification routes as portals of entry for infectivity had not previously been tested experimentally but this study has shown that these are efficient routes for establishing infection in mice using the 139A and ME7 strains of scrapie agent. Scarification had much the same efficiency as inoculation by the intraperitoneal, intravenous or perivenous routes but was not effective in immunocompromised (SCID) mice. It was concluded that replication of infectivity within the lymphoreticular system, which is precluded in SCID mice, is a necessary prerequisite for the development of infection in the central nervous system following inoculation via scarification.
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The present investigation was aimed at establishing the distribution of neptunium in blood and liver cells as a function of the mass and chemical form of the radionuclide injected. Four groups of rats received intravenous injections of 237Np(V), 237Np(IV), 239Np(V) or 239Np(IV). Twenty-four hours after injection of the radionuclide, subcellular structures of the liver were separated by ultracentrifugation and serum and liver cytosol were subjected to gel permeation chromatography. The intracellular distribution of neptunium in liver depends on the mass of the radionuclide injected; the relative specific activity for 237Np compared to 239Np was 2 in nuclei and 0.5-0.9 in cytosol. By contrast, the initial chemical form of the radionuclide has no significant effect on its intracellular distribution. In cytosol, neptunium was bound mainly by two proteins of molecular weight 450 and 200 kDa, respectively. The former was identified as ferritin, but the latter remains unidentified. In this compartment, no effect of mass or chemical form was seen. In blood, the bulk of the radionuclide was bound to transferrin whatever the mass and initial chemical form injected.
The 22A strain of scrapie agent was exposed to boiling or microwave irradiation. Subsequent bioassay in IM and VM mice showed that neither treatment had inactivated the agent. Although IM and VM mice are homozygous for the p7 allele of the Sinc gene which controls the incubation period of scrapie in mice, the incubation period for unheated 22A was 22 days longer in IM compared with VM mice. This suggests that other unidentified genes can have a more minor effect on incubation period. The difference between the IM and VM incubation period with microwave-irradiated 22A was much the same as for the unheated control but was increased to 68 days after boiling. The conclusion is that the agent is modified in some way by boiling but not by microwave irradiation such that it is more subject to the influence of genes other than Sinc which affect incubation period.
Bovine brain infected with the bovine spongiform encephalopathy (BSE) agent was used to spike material processed in pilot scale facsimiles of 12 rendering processes which are used within the European Union, and three which are not. The raw materials for experimental rendering represented those used in practice, and consisted of appropriate proportions of BSE-infected brain tissue, bovine or porcine intestine, and bovine bone. Meat and bone meal, and tallow were produced from the rendered tissues. Suspensions of all the meat and bone meal samples were assayed in inbred mice for BSE infectivity, and two of the tallow fractions were tested similarly. Four of the 15 processes produced meat and bone meal with detectable BSE infectivity. Neither of the tallow samples had detectable infectivity.
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Although the current world inventory of plutonium is overwhelmingly man-made, it is important to recognize that 244Pu was a primeval radioelement and that 239Pu is formed continuously by spontaneous fission of 238U; the atom ratio U:Pu being about 10(11):1. It has been calculated that the human body has always carried a base load of, perhaps 10(3)-10(5) atoms (< 0.2 amol) of natural plutonium. Since 1945, the release of 239Pu into the environment from atmospheric nuclear weapons testing has added to this base load a civilization-related load which, at approximately 300 fmol, is at least 5 orders of magnitude greater. Within the human body plutonium is deposited mainly in the liver and skeleton where it appears to be retained tenaciously with half-times of many years. Based on 1970-1980 levels, environmental plutonium may give rise to alpha-particle radiation doses of approximately 3-7 microSv/a in human bone and approximately 10-20 microSv/a in liver, doses which from our present understanding of the radio-and chemical toxicity of plutonium are far too small to cause any recognizable health effects.
The present investigation was aimed at establishing the distribution of 237Np within the different structures of hepatocytes. Rats were contaminated experimentally by intravenous injection of 237Np (V) and the subcellular structures of the liver were separated by ultracentrifugation. Twenty-four hours after contamination, the nuclear and cytosolic fractions bound 54 and 32%, respectively, of the total radionuclide. Purification of the nuclei followed by dissociation of the protein components in medium of increasing ionic strength showed a specific binding of neptunium to the structural proteins of the nuclear matrix.
The study examined the effects of a reduced-fat, oleic acid and carbohydrate-enriched diet on serum lipid profiles and body weight in the setting of an isolated Australian Antarctic station. A 12-week dietary intervention period was provided for 30 healthy, free-living expeditioners against a background diet typical of the Australian population. The diet tested a "modified U.S. Dietary Goals" regimen which increased oleic acid preferentially (29% energy from fat and 46% from carbohydrate, polyunsaturated: monounsaturated: saturated fatty acid ratio [P:M:S] of 0.6:1.3:1.0, 30 g fibre/day, less than 300 mg cholesterol/day). During the intervention period, mean serum HDL-cholesterol (HDL-C) levels remained relatively stable while mean serum total cholesterol (TC) fell significantly (a fall of 0.95 mmol/l, p < 0.05). The mean serum triglyceride (TG) level rose initially (1.44 to 1.64 mmol/l, p < 0.05) but the level returned to baseline (1.41 mmol/l) by the end of the intervention period. The change in TG level was associated with increased dietary carbohydrate but not with changes in body weight, alcohol intake or season. The study demonstrates that a reduced-fat, oleic acid and carbohydrate-enriched diet can result in significant improvements in serum lipid profiles. The diet was acceptable to the subjects and was easily provided in Antarctica with unobtrusive changes to the typical Australian diet.