Bovine spongiform encephalopathy and natural scrapie

Scrapie in sheep and Bovine Spongiform Encephalopathy in cattle are neurodegenerative diseases. They belong to the group of transmissible spongiform encephalopathies (prion diseases). Scrapie is a worldwide enzootic disease, first described two centuries ago. It is due to more than 20 different strains of agent and strongly influenced by genetic factors of the host. There is no evidence of a link between this disease and human transmissible spongiform encephalopathies. Bovine Spongiform Encephalopathy is a consequence of oral infection of cattle by meat and bone meal produced in the United Kingdom and contaminated by the agent. The strain is unique and has been selected and massively amplified in the alimentary chain. It is probably linked to a new variant of Creutzfeldt-Jakob disease in man. It is expected that the ban on the incorporation of animal proteins in the alimentation of ruminants will soon eradicate it, although the risk of potential mutants of the disease and its possible transmission to sheep and goats exists.     

Making sense of bovine spongiform encephalopathy

The possibility of animals infected with bovine spongiform encephalopathy (BSE) causing Creutzfeldt-Jakob disease (CJD) in humans has caused public alarm resulting in the banning of the export of British beef. This paper explores the current understanding of BSE and its relationship to CJD. Although there are similarities between the diseases, there is no clear evidence of a causal link between the two.     

Studies on the efficacy of hyperbaric rendering procedures in inactivating bovine spongiform encephalopathy (BSE) and scrapie agents

The efficacy of the procedures in use at the two rendering plants in the Netherlands was assessed on a laboratory-scale using procedures that simulated the pressure cooking part of the rendering process. A pool of bovine spongiform encephalopathy (BSE)-infected brainstem from the United Kingdom and a pool of scrapie-infected brainstem from Dutch sheep were used to spike the rendering materials. The mixtures were subjected to various time-temperature combinations of hyperbaric heat treatment related to the conditions used in Dutch rendering plants in the early 1990s, and to the combination of 20 minutes at 133 degrees C required by the EU Directive on rendering of 1996. The efficacy of the procedures in inactivating BSE or scrapie infectivity was measured by titrating the materials before and after heat treatment in inbred mice, by combined intracerebral and intraperitoneal inoculations at limiting dilutions. Two independent series of experiments were carried out. The design of the study allowed for minimum inactivations of up to 2.2 log (2.0 in the second series) to be measured in the diluted infective material and 3.1 log in the undiluted material. After 20 minutes at 133 degrees C there was a reduction of BSE infectivity of about 2.2 log in the first series (with some residual infectivity detected), and in the second series more than 2.0 log (with no residual infectivity detected). With undiluted brain material there was an inactivation of about 3.0 log (with some residual infectivity detected). With the same procedure, scrapie infectivity was reduced by more than 1.7 log in the first series and by more than 2.2 log in the second series. With undiluted brain material there was an inactivation of more than 3.1 log. In each case no residual scrapie infectivity was detected. The BSE agent consistently appeared to be more resistant to heat inactivation procedures than the scrapie agent, particularly at lower temperatures and shorter times.     

The incidence of bovine spongiform encephalopathy in the progeny of affected sires and dams

Case control study techniques were used to compare the incidence of bovine spongiform encephalopathy (BSE) in the progeny of two affected sires and 110 affected dams with the incidence of BSE in the progeny of animals known to be unaffected at the last record. All the progeny were born before the ban on ruminant-derived protein in feedstuffs issued in July 1988. The results provide little, if any, evidence of differences between the incidence in the progeny of the affected animals and the incidence in the progeny of the presumed unaffected animals. Data from five herds were used in a logistic regression analysis to study the effects of the disease status of the dam and the age of the dam at the birth of the calf on the incidence of BSE. The disease status of the dam did not significantly affect the disease status of its progeny, after allowance had been made for the effects of herd, year and the age at last record of the progeny. The difficulty of establishing maternal transmission if a high proportion of the dams are incubating the disease and transmission can occur early in the incubation period is discussed.     

Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update

Further preliminary observations are reported of an experiment to examine the spread of infectivity and the occurrence of pathological changes in cattle exposed orally to infection with bovine spongiform encephalopathy. Calves were dosed at four months of age and clinically monitored groups were killed sequentially from two to 40 months after inoculation. Tissues were collected for bioassay, for histopathological examinations and for the detection of PrP. Previous reported observations have included the presence of infectivity in the distal ileum of cattle killed after six to 18 months, the earliest onset of clinical signs in an exposed animal after 35 months, and diagnostic histopathological changes in the brain, in association with clinical disease, after 36, 38 and 40 months. In spite of the relative inefficiency of the bioassay of scrapie-like agents across a species barrier the new observations confirm that the onset of clinical signs and pathological changes in the central nervous system (CNS) occur at approximately the same time. The earliest pathological change, the presence of abnormal PrP 32 months after inoculation, coincided with the earliest detected infectivity in the CNS and occurred shortly before there was evidence of typical spongiform changes in the brain 36 months after inoculation. Infectivity has now been demonstrated in the peripheral nervous system, in the cervical and thoracic dorsal root ganglia 32 to 40 months after inoculation and in the trigeminal ganglion 36 and 38 months after inoculation. At the time of writing evidence of infectivity in other tissues is confined to the distal ileum, not only after six to 18 months but also after 38 and 40 months, but these findings may be supplemented by the results of further mouse assays. Nevertheless, they are in general agreement with current knowledge of the pathogenesis of scrapie.     

Neuropathological findings in cattle with clinically suspect but histologically unconfirmed bovine spongiform encephalopathy (BSE)

Neuropathological observations were made in 200 clinically suspected cases of bovine spongiform encephalopathy (BSE) in which pathognomonic vacuolar changes were absent. Routine histological and immunocytochemical techniques were applied to formalin-fixed, paraffin-embedded sections of the central nervous system. Significant neuropathological findings were detected in 85 (42.5 per cent) cases. The most frequent lesion, detected in 46 (23 per cent) cases, was a focal white matter vacuolation principally affecting the substantia nigra, but its clinical significance was unclear. Listeriosis was diagnosed in 17 (8.5 per cent) cases. In three of seven cases of non-suppurative encephalitis, lesions suggested sporadic bovine encephalomyelitis, a disease not previously reported in the UK. Suppurative thromboembolic or granulomatous lesions accounted for other inflammatory changes. Neuroectodermal tumours were present in five cases (2.5 per cent); three were identical in form and considered to be atypical ependymoma. Cerebrocortical necrosis, oedema or both were detected in four cases. The remaining cases (4.5 per cent), comprised those in which the changes were minor and of doubtful significance. Incidental pathological findings included occasional degenerating or vacuolated neurones, which occurred in the red nucleus in 105 brains, in the habenular nucleus in 71 brains, and singly at other sites in 17 brains. In sections of 37 brains immunostained with antiserum to prion protein (PrP), no evidence of PrP accumulation was found, providing some evidence that the series did not contain bovine prion disease cases which, based on the histological diagnosis, had given a false negative result. It is suggested that, of 115 cases (57.5 per cent) which lacked significant histological lesions, some were suffering from metabolic disorders. The study identified diseases and lesions which feature in the differential diagnosis of BSE. Their more accurate diagnosis may become particularly important if, as predicted, the BSE epidemic declines.     

182 offspring of cows with bovine spongiform encephalopathy (BSE) in Switzerland. 1. Clinical findings

This study involved 182 calves, heifers and cows that were the first generation progeny of cows with bovine spongiform encephalopathy (BSE). All animals underwent clinical and neurological examinations. Blood, milk, urine, ruminal fluid and cerebrospinal fluid samples were examined. Each cow underwent a specific examination for BSE which included assessment of behaviour, sensitivity and locomotion. This examination was performed twice, and there was very good agreement between the results. The most common symptom was nervousness (14 animals). In the first examination, 68 animals were mildly to moderately sensitive to touching of the head, 44 animals were hypersensitive to a halogen light and 35 animals were hypersensitive to a camera flash. Twenty-four animals reacted by kicking when the hindlimbs were touched with a broom. None of the animals had disturbances in locomotion. Based on the interpretation of all findings and the comparison of the results of the first and second examinations, 173 animals were diagnosed as free of BSE. In 9 animals, the disease could not be ruled out; however, it could not be confirmed in any of them. Histological and immunohistochemical examinations of the brain of all animals were negative for BSE (see Part 2 of the study for details). The results of this study indicate that abnormal clinical findings may occur in clinically healthy cattle. However, none of the progeny of cows with BSE exhibited clinical signs typical of BSE, such as disturbances in behaviour; sensitivity and locomotion.     

Human and animal spongiform encephalopathy. Update on December 17, 1996

Recent papers about bovine spongiform encephalopathy (BSE) and new variant of Creutzfeldt-Jakob disease (nvCJD) are reviewed: new data, maternal transmission of BSE, epidemiology of BSE in British cattle, structure of the PrP(res), biochemical signature of PrP(res), chronic pesticide-initiated modification of the prion protein, protein markers in cerebrospinal fluid.     

Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy

BACKGROUND: Spirituality is receiving greater attention in the medical literature, especially in the family practice journals. A widely applicable instrument to assess spirituality has been lacking, however, and this has hampered research on the relationship between spirituality and health in the clinical setting. METHODS: A new instrument, called the Spiritual Involvement and Beliefs Scale, was designed to be widely applicable across religious traditions, to assess actions as well as beliefs to address key components not assessed in other available measures, and to be easily administered and scored. The instrument is a questionnaire containing 26 items in a modified Likert-type format. Following careful pretesting, the instrument was administered to 50 family practice patients and 33 family practice educators. The validity and reliability of the instrument were then evaluated. RESULTS: By several measures, instrument reliability and validity are very good, with high internal consistency (Cronbach's alpha = .92); strong test-retest reliability (r = .92); a clear four-factor structure; and a high correlation (r = .80) with another established measure of spirituality, the Spiritual Well-Being Scale. CONCLUSIONS: The Spiritual Involvement and Beliefs Scale (SIBS) appears to have good reliability and validity. Compared with other instruments that assess spirituality, the SIBS has several theoretical advantages, including broader scope, use of terms that avoid cultural-religious bias, and assessment of both beliefs and actions. More testing is underway to further assess its usefulness.     

Bovine spongiform encephalopathy (BSE): causes and consequences of a common source epidemic

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) or prion disease of cattle first recognized in 1986 in the United Kingdom, where it produced a common source epidemic that peaked in January 1993 and has subsided markedly since that time. The epidemic began simultaneously at many geographic locations and was traced to contamination of meat and bone meal (MBM), a dietary supplement prepared from rendering of slaughterhouse offal. It appears that the epidemic was initiated by the presence of the agent of scrapie (a long-standing TSE of sheep) that was first transmitted to cattle, beginning in the early 1980s, when most rendering plants abandoned the use of organic solvents in the preparation of MBM. The epidemic was probably accelerated by the recycling of infected bovine tissues prior to the recognition of BSE. To terminate the epidemic, a prohibition on the feeding of ruminant-derived protein to ruminants was introduced in the United Kingdom in July 1988. The ruminant feed ban accounts for the decline of the epidemic after an interval of about 5 years, approximately equivalent to the average incubation period of BSE. Relatively few cases of BSE have occurred in cattle born after 1993, and it is predicted that the epidemic will terminate about the year 2000 based on an extrapolation of the present declining curve. A comparison of data from the United Kingdom with data from relatively low incidence countries, such as Switzerland, indicates that this epidemic has been mainly confined to the United Kingdom because of a unique concatenation of risk factors, including: 1) a high ratio of sheep to cattle; 2) a relatively high rate of endemic scrapie; 3) the heavy feeding of MBM to dairy cattle; and 4) changes in the rendering process used to prepare MBM. Recently, cases of a variant form of Creutzfeldt-Jakob disease (a TSE of humans) have been reported in the United Kingdom. These cases, at least 10 of which had onset in 1994-1995, are distinguished by their occurrence in subjects under age 40 years, by their clinical presentation, and by their neurohistopathologic picture. The appearance of this novel disease and its concentration in the United Kingdom have raised the question that it might represent the transmission of BSE to humans. However, the cases gave no history indicating an unusual exposure to live cattle, to the preparation of beef products, or of dietary exposure to bovine tissues, and it remains to be determined whether they are associated with BSE.     

Bovine spongiform encephalopathy. Review of data collected since the statement of February 6, 1996

The observation in 1995 and 1996 of 10 cases of a new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K. suggested a possible relation between this human cases and bovine spongiform encephalopathy (BSE). Recent papers about this topic are reviewed : hypothesis of a possible genetic link between man and cattle, hypothesis of a acquired resistance against the agent of BSE after a previous infection by a less virulent agent of ovine origin, importance of polymorphism at codon 129 according to the hypothesis of a virus-induced amyloidosis, diagnostic test with cerebrospinal fluid, epidemiology of BSE and prediction of future BSE spread.     

Bovine spongiform encephalopathy (BSE): clinical aspects, duty of notification and consequences of positive findings

Excimer lasers and high technology instrumentation have ushered in a new era of vision improvement surgery in Hawaii, replacing the more traditional forms of refractive surgery: cataract surgery, corneal transplant surgery, and radial keratotomy. Corneal surgery has been enhanced by new techniques of microsurgery and a more effective tissue procurement system for donor corneal tissue. Several laser centers provide the latest in FDA-approved excimer laser procedures including PRK and PTK. Mild to moderate myopia and astigmatism may now be corrected. Off-label use of LASIK, too, may soon be realized.     

Identification of bovine rotaviruses in Venezuela: antigenic and molecular characterization of a bovine rotavirus strain

Digestion by restriction enzymes has been carried out on polymerase chain reaction products of the mitochondrial DNA control region of round sardine (Sardinella aurita) samples coming from the Eastern Atlantic and the Mediterranean Sea. The results show i) that, though the habitat is continuous, there is no gene flow between the two basins where two genetically differentiated groups can be recognized, ii) that each basin is genetically homogeneous and, iii) that the haplotypic diversity in the Mediterranean is between two and three times smaller than that observed in the Atlantic. These results can hardly be explained by a recent colonization from the Eastern Atlantic. This suggests that, for S. aurita and some other species, the Mediterranean Sea is genetically little influenced by the Eastern Atlantic.     

Minisatellite and microsatellite length variation at a complex bovine VNTR locus

A report is made of respiratory complications which occurred following the insertion of Palacos bone cement during Howse total hip replacement under spinal anaesthesia in a 78-year-old female patient. Persistent cough and tachypnoea developed 30 s after the insertion of bone cement into the acetabulum and femur and persisted for 2-3 min producing considerable passive movement of the pelvis and femur. The probable cause, disadvantages and prevention of these complications are discussed.     

Molecular and phenotypic variation in patients with severe Hunter syndrome

A review of the present state of the art of laser hair transplantation highlights recommendations for treatment parameters and discusses the studies published in the literature. An evolving field, laser hair transplantation is maturing to find its place in the armentarium for hair restoration surgery.