Publications

bse and variant creutzfeldt-jakob disease: never say never.		2002	12012095
bovine spongiform encephalopathy update.	bovine spongiform encephalopathy (bse) is a zoonosis being the origin of variant creutzfeldt-jakob disease and an important cattle disease in its own right. countries have been slow to learn the importance of protecting, not only their cattle populations, but also their human populations. since 2000, several additional european countries have reported bse in native-born stock and this has led to a concern about the bse status of countries that have imported cattle and catlle products from infect ...	2002	12014225
prnp contains both intronic and upstream regulatory regions that may influence susceptibility to creutzfeldt-jakob disease.	the prion protein (prp) plays a central role in creutzfeldt-jakob disease (cjd) and other transmissible spongiform encephalopathies (tses). mutations in the protein coding region of the human prp gene (prnp), which have been proposed to alter the stability of the prp protein, have been linked to a number of forms of tse. however, the majority of cjd cases are not associated with mutations in the prnp coding region and alternative mechanisms must therefore underlie susceptibility to these forms o ...	2002	12034503
follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions.	infectious prion diseases initiate infection within lymphoid organs where prion infectivity accumulates during the early stages of peripheral infection. in a mouse-adapted prion infection, an abnormal isoform (prp(sc)) of prion protein (prp) accumulates in follicular dendritic cells within lymphoid organs. human prions, however, did not cause an accumulation of prp(sc) in the wild type mice. here, we report that knock-in mouse expressing humanized chimeric prp demonstrated prp(sc) accumulations ...	2002	12051707
food safety: bovine spongiform encephalopathy (mad cow disease).	bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform enceph ...	2002	11984426
neurological adverse events associated with vaccination.	public tolerance to adverse reactions is minimal. several reporting systems have been established to monitor adverse events following immunization. the present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. these complications include autism (measles vaccine), multiple sclerosis (hepatitis b vaccine), meningoencephalitis (japanese encephalitis vaccine), guillain-barré syndrome ...	2002	12045734
deaths from variant creutzfeldt-jakob disease in the uk.	in 2002, 17 people died from variant cjd (vcjd) in the uk, compared with 20 in 2001 and 28 in 2000. we analysed data for deaths from vcjd since 1995 and estimated the underlying trend in mortality. the trend had a quadratic component (p=0.005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. the death rate peaked in 2000. these findings are encouraging, but mortality might increase again in the future.	2003	12620741
molecular and clinical classification of human prion disease.	while rare in humans, the prion diseases have become an area of intense clinical and scientific interest. the recognition that variant creutzfeldt-jakob disease is caused by the same prion strain as bovine spongiform encephalopathy in cattle has dramatically highlighted the need for a precise understanding of the molecular biology of human prion diseases. detailed clinical, pathological and molecular data from a large number of human prion disease cases have shown that distinct abnormal isoforms ...	2003	14522862
magnetic resonance spectroscopic abnormalities in sporadic and variant creutzfeldt-jakob disease.	to study the proton mr spectroscopic findings in creutzfeldt-jakob disease (cjd) (sporadic and variant).	2003	12623045
organ distribution of prion proteins in variant creutzfeldt-jakob disease.	in this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. the normal prion protein is distributed ubiquitously throughout human body tissues. endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. as exemplified by variant creutzfeldt-jakob disease (vcjd) the abnormal prion protein can accumulate in th ...	2003	12679264
factors determining the pattern of the variant creutzfeldt-jakob disease (vcjd) epidemic in the uk.	following the emergence of a new variant of creutzfeldt-jakob disease (vcjd) 6 years ago, and the gradual rise in clinical cases, there has been increased speculation regarding the overall magnitude of this epidemic in great britain. in this paper, we explore the epidemiological factors and uncertainties determining the scale of this epidemic in light of the most recent data on reported vcjd mortality. our results demonstrate that, while the magnitude of the uncertainty has decreased dramaticall ...	2003	12713742
role of variant creutzfeldt-jakob disease for safety of treatment with blood components: screening of lymphatic tissue is a potential tool for risk assessment.	transmissible spongiform encephalopathies (tses) are neuropathological diseases caused by prions. prions are infectious particles (prpsc) which can induce bovine spongiform encephalopathy and most likely also the related infectious disease, variant of creutzfeldt-jakob disease (vcjd). the exposure of humans to orally ingested bse agent in contaminated meat products presumably led to the emergence of vcjd. in vcjd, prions can be detected immunohistochemically not only in neuronal tissue but also ...	2003	12631254
predicting incidence of variant creutzfeldt-jakob disease from uk dietary exposure to bovine spongiform encephalopathy for the 1940 to 1969 and post-1969 birth cohorts.	to investigate variant creutzfeldt-jakob disease (vcjd) incubation period, transmission barrier, and short-term vcjd predictions for methionine homozygotes in 1940-1969 and post-1969 birth cohorts by use of gender- and age-specific exposure intensities to bovine spongiform encephalopathy (bse), based on consumption of beef mechanically recovered meat (mrm) and head meat.	2003	14559750
commentary: predicting the unpredictable: the future incidence of variant creutzfeldt-jakob disease.		2003	14559751
inactivation of tse agents: safety of blood and blood-derived products.	evidence relating to whether the blood of individuals with sporadic creutzfeldt-jakob disease is infectious is discussed. the conclusion is that this is unproven. similar consideration is given to the blood of individuals with variant creutzfeldt-jakob disease; it is concluded that there is no convincing evidence that the blood is infectious but reasons for caution are presented. there is discussion regarding factors that add to the safety of plasma-derived therapeutic products, including the ca ...	2003	12668184
the impact of variant cjd on transfusion practices in the uk.	this article describes the chronology of bse in the uk, and of its transfer as vcjd to humans. the historic and potential future impacts on transfusion medicine and science in the uk--from donor selection to component processing--are summarised, and put in a global setting.	2003	12679113
variant creutzfeldt-jakob disease.	variant cjd is a novel human prion disease that represents the first known occasion in which animal prion diseases have been transmitted to humans. there are many uncertainties concerning vcjd, including the mechanism of transmission between species, the extent of human exposure to the bse agent, the infectious dose for humans, and the future burden of human disease. it is hoped that continuing scientific research may lead to answers to some of these questions and that further understanding of t ...	2003	12733426
the epidemics of bovine spongiform encephalopathy and variant creutzfeldt-jakob disease: current status and future prospects.	the large epidemic of bovine spongiform encephalopathy (bse) in the united kingdom has been in decline since 1992, but has spread to other countries. the extensive control measures that have been put in place across the european union and also in switzerland should have brought the transmission of bse under control in these countries, provided that the measures were properly enforced. postmortem tests on brain tissue enable infected animals to be detected during the late stages of the incubation ...	2003	12751420
prion diseases: from molecular biology to intervention strategies.	prion diseases are fatal neurodegenerative infectious disorders for which no therapeutic or prophylactic regimens exist. understanding the molecular process of conformational conversion of the cellular prion protein (prp(c)) into its pathological isoform (prp(sc)) will be necessary to devise effective antiprion strategies. in recent years, new findings in the cell biology of prp(c), in the molecular pathogenesis of prp(sc), and in the cellular quality control mechanisms involved in these scenari ...	2003	14661267
sporadic creutzfeldt-jakob disease mimicking variant creutzfeldt-jakob disease.	the determination of the form of prion disease and early diagnosis are important for prognostic, public health, and epidemiologic reasons.	2003	12756143
comparison of the neuropathological characteristics of bovine spongiform encephalopathy (bse) and variant creutzfeldt-jakob disease (vcjd) in mice.	bovine spongiform encephalopathy (bse) and variant creutzfeldt-jakob disease (vcjd) belong to a group of diseases called the transmissible spongiform encephalopathies (tses). transmission studies in inbred mice (strain typing) provided overwhelming evidence that vcjd arose from bse. in this study, we compare the patterns of neuropathology in a panel of three inbred mouse strains (riii, c57bl and vm) and one cross (c57bl x vm) infected with either vcjd or bse. for each mouse strain, patterns of a ...	2003	12787323
improved conformation-dependent immunoassay: suitability for human prion detection with enhanced sensitivity.	the presence of pathogenic prion protein (prp(sc)) in lymphoid tissues of variant creutzfeldt-jakob disease (vcjd) patients raises questions as to whether prions may be present in bodily fluids as well. currently, transgenic mice are highly sensitive in vivo tools for the study of prions in tissues or fluids containing high levels of normal prion protein (prp(c)). we report here an in vitro assay with virtually equivalent sensitivity incorporating a capture antibody into a sandwich conformation- ...	2003	12810888
mortality trend from sporadic creutzfeldt-jakob disease (cjd) in italy, 1993-2000.	the objective was to identify any possible cases of variant creutzfeldt-jakob disease (cjd) in italy, and to estimate the trends in mortality from sporadic cjd for 1993-2000. cjd cases were ascertained through direct notification to the registry; 382 definite or probable sporadic cjd patients, but no cases of variant cjd were identified. the average yearly mortality rate was 1.04 cases per million inhabitants, with an increase in deaths in the 60-69 and > or =70 year age groups. survival was sho ...	2003	12812825
variant creutzfeldt-jakob disease and its transmission by blood.	variant creutzfeldt-jakob disease (vcjd) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (bse). vcjd differs from all other human prion diseases in that the disease-associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinica ...	2003	12871283
[nasu hakola disease: a report of the first two cases in bolivia].	nasu hakola disease (nhd) is a progressive dementia that presents accompanied by bone cysts and, at random, epilepsy. it is an autosomal recessive hereditary disease and its genetic defect is located at the 19q13.1 chromosome. the genetic mutation was identified at dap 12. it appears that dap 12 is expressed in the microglial activation and the differentiation of macrophages in the central nervous system and, at the same time, in the osteoclasts in charge of bone remodelling. this double charact ...	2003	12717671
prion diseases: infectious and lethal doses following oral challenge.	a brain homogenate prepared from a terminally ill hamster infected with scrapie strain 263k was serially diluted and administered orally to groups of hamsters. the undiluted brain homogenate led to clinical scrapie in all animals inoculated. the attack rate decreased with dilutions of the homogenate, and subclinical infections were identified among the healthy survivors at 520 days post-infection by western blotting. the number of animals succumbing to disease and the combined number of western ...	2003	12810889
[prion diseases].	prion is an ubiquitous membrane protein in mammals, which is mainly synthesized in central nervous system. prion diseases are the result of an accumulation of prions having acquired a resistance to the physiological degradation and an infectious capacity. human prion diseases are very rare diseases including sporadic creutzfeldt-jakob disease (the most frequent form manifesting as a presenile dementia), familial transmissible spongiform encephalopathies and two juvenile transmissible forms: iatr ...	2003	12818782
diagnosis and prevention of bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.	an outbreak of bovine spongiform encephalopathy (bse) arose in the united kingdom as a result of prions entering and being recycled through the ruminant food chain. humans have since developed a variant form of creutzfeldt-jakob disease (vcjd), also mostly in the united kingdom, that occurs in younger individuals and causes prominent psychiatric and/or behavioral manifestations early in disease. laboratory studies now provide strong evidence that the causative agent of bse in cattle and vcjd in ...	2003	12525677
rapid echoplanar diffusion imaging in a case of variant creutzfeldt-jakob disease; where speed is of the essence.	neuroimaging with magnetic resonance imaging (mri) is important in the diagnosis of creutzfeldt-jakob disease (cjd), but is frequently frustrated by patient movement. diffusion-weighted imaging (dwi) has previously shown markedly restricted diffusion in grey matter structures of patients with cjd, and may add to diagnostic sensitivity. echoplanar imaging (epi) sequences, which are usually used for dwi, are also very rapid, and typically allow imaging of the whole brain in less than 1 min. a case ...	2003	12879327
variant creutzfeldt-jakob disease.	a variant form of creutzfeldt-jakob disease (vcjd) has had major impact in europe during the last decade. in this article, we review the aetiology of vcjd and its relation with bovine spongiform encephalopathy. further, treatment of the disease, the strategies focusing on prevention of transmission, future prospects, and the limitations encountered in epidemiological research of vcjd are discussed.	2003	12908711
assessment of the risk posed by bovine spongiform encephalopathy in cattle in great britain and the impact of potential changes to current control measures.	we extended an existing back-calculation model to analyse data on reported clinical cases of bovine spongiform encephalopathy (bse), data from random testing of healthy animals slaughtered in abattoirs and testing data from animals reported as sick or dying on the farm. extensive analysis of demographic data was also undertaken. we estimated past and current bse infection prevalences in the cattle population and the degree of case under-ascertainment resulting from excess mortality in cattle nea ...	2003	12908978
prion protein accumulation in eyes of patients with sporadic and variant creutzfeldt-jakob disease.	creutzfeldt-jakob disease (cjd) primarily affects the brain. this study was conducted to assess the possible involvement of the eye in sporadic and variant cjd by testing for the presence of the disease-associated, protease-resistant isoform of the prion protein (prp(sc)) in ocular tissue.	2003	12506094
short-term projections for variant creutzfeldt-jakob disease onsets.	projections of both the short- and long-term course of the variant creutzfeldt-jakob disease (vcjd) epidemic in great britain have demonstrated great uncertainty due to the lack of knowledge of key aspects of the biology and epidemiology of this new disease. such projections are sensitive to assumptions made regarding the pattern of exposure to bse-infected animals, the effectiveness of control measures introduced in 1989 and 1996 in reducing this exposure, the functional form of the incubation ...	2003	12828241
does the neuropathology of human patients with variant creutzfeldt-jakob disease reflect haematogenous spread of the disease?	to test the hypothesis that the distribution of the pathology in variant creutzfeldt-jakob disease (vcjd) represents haematogenous spread of the disease, we studied the spatial correlation between the vacuolation, prion protein (prp) deposits, and the blood vessel profiles in the cerebral cortex, hippocampus, dentate gyrus, and cerebellum of 11 cases of the disease. in the majority of areas, there were no significant spatial correlations between either the vacuolation or the diffuse type of prp ...	2003	12893420
proceedings of a consensus conference: blood-borne hiv and hepatitis-optimizing the donor selection process.	over the past several years, concern for the safety of blood transfusion has evolved from a primary focus on bacterial infections such as syphilis to viral infections including hepatitis b, c, and human immunodeficiency virus (hiv), and most recently, the theoretical risk of variant creutzfeldt-jakob disease (vcjd). as a result of these changes, blood bankers have found themselves faced with the dilemma of balancing the rights of transfusion recipients to receive safe blood products, with the ri ...	2003	12522769
the predictability of the epidemic of variant creutzfeldt-jakob disease by back-calculation methods.	we present a back-calculation analysis of the variant creutzfeldt-jakob (vcjd) epidemic in the uk to estimate the number of infected individuals and to explore the likely future incidence of the disease. the main features of the model are that the hazard of infection was assumed proportional to the incidence of bse in the uk with allowance for precautionary control measures taken in 1988 and in 1996, and that the incubation period distribution of vcjd follows an offset generalized f distribution ...	2003	12828242
cross-species infections.	animals have always been a major source of human infectious disease. some infections like rabies are recognized as primary zoonoses caused in each case by direct animal-to-human transmission, whereas others like measles become independently sustained within the human population so that the causative virus has diverged from its morbillivirus progenitor in ruminants. recent examples of direct zoonoses are variant creutzfeldt-jakob disease arising from bovine spongiform encephalopathy, and the h5n1 ...	2003	12934941
modelling the epidemic of variant creutzfeldt-jakob disease in the uk based on age characteristics: updated, detailed analysis.	incubation period of the new variant creutzfeldt-jakob disease (vcjd) from infection to clinical onset and the eventual impact of the disease remain major concerns. based on i) epidemiological conceptualization of human exposure to bse contaminated material, ii) exponentially decreasing susceptibility after 15 years of age, and iii) typical incubation period (ip) distributions for time from infection to onset, we have previously estimated mean incubation period and projected number of vcjd cases ...	2003	12828243
the geographical distribution of variant creutzfeldt-jakob disease cases in the uk: what can we learn from it?	the causative agents of variant creutzfeldt-jakob disease (vcjd) and of bovine spongiform encephalopathy (bse) are currently indistinguishable. however, the route(s) by which humans became infected remain unknown. the path by which humans were infected with the bse agent might impact on the geographical distribution of cases and we therefore sought evidence of regional variation and local clustering of vcjd cases. with the notable exception of a group of five cases in leicestershire, the absence ...	2003	12828244
european union's rapid tse testing in adult cattle and sheep: implementation and results in 2001 and 2002.	after the discovery of variant creutzfeldt-jakob disease (vcjd), scientific advances quickly led to post-mortem tests to identify late-stage bovine spongiform encephalopathy (bse) disease. these were first used in switzerland in 1999 for active bse surveillance of a) fallen and emergency-slaughter bovines (risk stock) and b) 5% sample of routinely slaughtered cattle over 30 months of age. in 1999 and 2000, switzerland's estimated 103 bse positives per 1000000 adult cattle put it in the same bse ...	2003	12828246
anti-prion antibodies for prophylaxis following prion exposure in mice.	prion disease is characterized by a conformational change of the normal form of the prion protein (prp(c)) to the scrapie-associated form (prp(sc)). since the emergence of new variant creutzfeldt-jakob disease a potentially large human population is at risk for developing prion disease. currently, no effective treatment or form of post-exposure prophylaxis is available for prion disease. we recently showed that active immunization with recombinant prp prolongs the incubation period of scrapie. h ...	2003	12505623
[the use of disposable instruments of a high performance polymer for tonsillectomy and adenoidectomy].	cases of the new variant creutzfeldt-jakob disease (vcjd) in human beings have to be anticipated in germany. in subclinical vcjd, the accumulation of prions in lymphoid tissue has been identified prior to their manifestation in cerebral tissue. the remarkable resistance of prions to standard methods of sterilisation questions the safety of reusing metallic surgical instruments. the transmission of vcjd via such reusable surgical instruments in tonsillectomies and adenoidectomies cannot be exclud ...	2003	12835857
immunohistochemical localization of 14.3.3 zeta protein in amyloid plaques in human spongiform encephalopathies.	the localization of 14.3.3 proteins was studied in different subtypes of brain amyloid plaques. we examined paraffin-embedded brain sections of sporadic mv2 creutzfeldt-jakob disease (scjd) with kuru plaques, sporadic vv2 cjd with plaque-like prp(sc) (the abnornal form of prion protein) deposits, variant cjd (vcjd) with florid plaques, gerstmann-straüssler-scheinker (gss) with multicentric plaques and of alzheimer's disease (ad) with senile plaques. adjacent immunostaining revealed prp(sc) and 1 ...	2003	12557018
prion diseases and dental treatment: principles and practice of patients with/suspected or at-risk of cjd: case reports.	the emergence of variant cjd (vcjd) in the last decade has heightened awareness of the need for rigorous infection control precautions in all healthcare environments. it has also raised particular problems in relation to the clinical management of patients who are either suffering from prion diseases or who are perceived as being 'at risk'. from the healthcare perspective cjd is of concern because at present it is an incurable, fatal disease and the causative agent, abnormal prion protein, is re ...	2003	14512992
variant creutzfeldt-jakob disease.		2003	14535362
risks of transfusion-transmitted infections: 2003.	while the risks of transfusion-transmitted human immunodeficiency virus, hepatitis c virus, and human t-cell leukemia virus i/ii continue to decrease, additional threats to transfusion safety are posed by emerging "new" infectious diseases.	2003	14564170
variant creutzfeldt-jakob disease: pathology, epidemiology, and public health implications.	prion diseases, or transmissible spongiform encephalopathies, include creutzfeldt-jakob disease (cjd) in humans and scrapie and bovine spongiform encephalopathy (bse) in animals. these neurodegenerative diseases are invariably fatal and can be transmitted by inoculation or dietary exposure. they are associated with the accumulation of an altered, disease-associated form of the normal prion protein. pathologically, prion diseases result in neuronal cell death and a characteristic spongiform appea ...	2003	12936961
creutzfeldt-jakob disease--identifying prions and carriers.	two major obstacles to be overcome in minimizing the possibility of transmitting creutzfeldt-jakob disease or variant creutzfeldt-jakob disease are associated with identifying the prion on disinfected surgical instruments and identifying carriers of the protease-resistant form of the prion. new developments indicate that the means for doing both soon may be available.	2003	12940422
latrogenic creutzfeldt-jakob disease with florid plaques.	florid plaques indistinguishable from those found in vcjd were identified at a postmortem examination in the brain of a 58-year-old clinical suspect case of creutzfeldt-jakob disease (cjd). western blotting of brain tissue revealed an unusual prion protein type. since the patient had received a dura mater graft 20 years prior to death and florid plaques are not only found in new variant cjd, the findings argue in favor of an iatrogenic origin of the disease with the longest incubation time follo ...	2003	12946015
molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl) amino]-2-naphthyl]ethylidene) malononitrile labels prion plaques in vitro.	the study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (fddnp) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed gerstmann-sträussler-scheinker disease, sporadic creutzfeldt-jacob disease (cjd) with kuru plaques, and variant cjd (vcjd). fddnp is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent ...	2003	12954864
structural properties of gerstmann-straussler-scheinker disease amyloid protein.	prion protein (prp) amyloid formation is a central feature of genetic and acquired forms of prion disease such as gerstmann-sträussler-scheinker disease (gss) and variant creutzfeldt-jakob disease. the major component of gss amyloid is a prp fragment spanning residues approximately 82-146. to investigate the determinants of the physicochemical properties of this fragment, we synthesized prp-(82-146) and variants thereof, including entirely and partially scrambled peptides. prp-(82-146) readily f ...	2003	12970341
diagnosing variant creutzfeldt-jakob disease with the pulvinar sign: mr imaging findings in 86 neuropathologically confirmed cases.	variant creutzfeldt-jakob disease (vcjd) is a rare but important cause of dementia and death in young patients and is causally linked to bovine spongiform encephalopathy. symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalamus (pulvinar sign) on brain mr images was described as a specific, noninvasive, diagnostic sign of vcjd in a previous small series. this purpose of this larger study was to evaluate this sign prospectively and further define the mr imaging characteristic ...	2003	13679271
neuronal and astrocytic responses involving the serotonergic system in human spongiform encephalopathies.	the relationships between the degree of cortical prion protein (prp) deposition, tissue vacuolation and astrocytosis were studied in the frontal cortex of 27 cases of human spongiform encephalopathy, encompassing 13 cases of sporadic creutzfeldt-jakob disease (scjd), four cases of familial cjd (fcjd) (one owing to e200k mutation, one owing to 144 bp insertion, one owing to p102l mutation and one owing to a117v mutation), five cases of iatrogenic cjd (icjd) owing to growth hormone therapy and fiv ...	2003	14507340
ethical issues in human prion diseases.	prion diseases or transmissible spongiform encephalopathies are a group of closely related transmissible neurodegenerative conditions of humans and animals, all of which are incurable. in recent years, they have captured public attention with the emergence of the bovine spongiform encephalopathy (bse) epidemic in europe, and more recently with the appearance of variant cjd (vcjd) in humans, a novel form of creutzfeldt-jakob disease (cjd) that is linked to dietary exposure to bse. in this chapter ...	2003	14522867
approaches to prophylaxis and therapy.	despite important progress in experimental treatment of neurodegenerative diseases, no therapeutic strategy has today proven its capability to cure or even to stabilise human tses. pathogenesis experiments performed in rodent tse models have shown that central nervous system damages are detectable long before the appearance of the clinical symptoms. at the time of disease onset, prp(sc) accumulation has almost reached its highest level, and the neuropathological lesions (spongiosis, gliosis) are ...	2003	14522865
caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.	prion diseases are characterized by accumulation of misfolded prion protein (prp(sc)), and neuronal death by apoptosis. here we show that nanomolar concentrations of purified prp(sc) from mouse scrapie brain induce apoptosis of n2a neuroblastoma cells. prp(sc) toxicity was associated with an increase of intracellular calcium released from endoplasmic reticulum (er) and up-regulation of several er chaperones. caspase-12 activation was detected in cells treated with prp(sc), and cellular death was ...	2003	14532116
vcjd screening and its implications for transfusion--strategies for the future?	it remains unclear whether creutzfeldt jakob disease (cjd) can be transmitted by blood products. peripheral blood infectivity is demonstrable in experimental animal transmissible spongiform encephalopathy models and has been transmitted via blood transfusion. however, in man, epidemiological case control, lookback and surveillance studies have failed to demonstrate any evidence of sporadic cjd transmission by blood transfusion. it cannot be assumed that variant cjd is not transmissible in this w ...	2003	14567540
similar levels of infectivity in the blood of mice infected with human-derived vcjd and gss strains of transmissible spongiform encephalopathy.	the possible transmission of variant cjd (vcjd) through blood transfusion or use of plasma-derived products prompted this study comparing infectivity in murine models of vcjd and gerstmann-sträussler-scheinker (gss) disease, a non-vcjd form of transmissible spongiform encephalopathy (tse).	2003	14641865
variant cjd: the present position and future possibilities.	variant creutzfeldt-jakob disease (cjd) is one of the transmissible spongiform encephalopathies (tses), or prion diseases, and is thought to be due to transmission of bse from cattle to man via diet. these are characterized by the tissue deposition of an abnormal isoform of the normal cellular prion protein, a progressive, fatal neurological course and having the potential for infectivity. infectivity is difficult to inactivate, and instances of iatrogenic cjd have been reported. the involvement ...	2003	14662173
prion disease: possible implications for oral health care.	prion diseases are a group of rare fatal neurodegenerative disorders in humans and animals that are histopathologically characterized by spongiform change within the central nervous system.	2003	14664268
the spectrum of safety: variant creutzfeldt-jakob disease in the united kingdom.	beginning in the mid 1980s, an epidemic of bovine spongiform encephalopathy (bse) was seen among cattle in the united kingdom. the cause was recognized as a prion agent transmitted in the meat and bone meal products used as animal feed, a practice that was banned in 1988. unfortunately, by that time, infected cattle had already entered the human food supply, and by 1996, several individuals were identified with a variant form of creutzfeldt-jakob disease (cjd), caused by the same infectious agen ...	2003	14690064
a vital fluid: risk, controversy and the politics of blood donation in the era of "mad cow disease".	this article examines the reasons for, and likely impact of, the decision by the us and other countries to permanently defer blood donors who have spent time in britain or europe, for fear they may transmit new variant creutzfeldt-jakob disease (vcjd), the human form of "mad cow disease". it begins by discussing how vcjd and blood transfusion are linked, and how these have been translated into policy. first, maintaining a safe and stable supply of blood entails not only maintaining the trust of ...	2003	14971395
variant creutzfeldt-jakob disease: need for mental health and palliative care team collaboration.	people with a dementia syndrome and a superimposed terminal illness are increasingly being referred to palliative care services. creutzfeldt-jakob disease (cjd) is a dementia syndrome in the early stages of which people experience a variety of psychological symptoms that may lead to them being admitted to psychiatric services. people with cjd have died in psychiatric units. there is clearly a need for collaboration between mental health and palliative care services in providing care for people w ...	2003	14765007
the fundamentals of variant creutzfeldt-jakob disease.	since the discovery of a variant form of creutzfeldt-jakob disease (vcjd), the human form of bovine spongiform encephalopathy, researchers have been persistent in their search for the way in which this disease manifests itself in humans. like all other forms of cjd, vcjd is a prion disease, or transmissible spongiform encephalopathy. the differences from other forms of cid are its manifestation and the population at risk. diagnosing the disease remains a problem because true diagnosis can be det ...	2003	14713099
human prion diseases: epidemiology and integrated risk assessment.	human prion diseases are devastating and incurable, but are very rare. fears that the bovine spongiform encephalopathy epizootic would lead to a large epidemic of its presumed human counterpart, variant creutzfeldt-jakob disease (vcjd), have not been realised. yet a feeling of uncertainty prevails in the general public and in the biomedical world. the lack of data on the prevalence of asymptomatic carriers of vcjd compounds this uncertainty. in addition to this problem, switzerland is currently ...	2003	14636781
new variant creutzfeldt-jakob disease: a controversial but potential blood transfusion risk.		2003	16583978
chorea as a presenting feature of variant creutzfeldt-jakob disease.	we report on a patient with pathologically proven variant creutzfeld-jakob disease in whom chorea was a presenting feature of the disease, and was unaccompanied by the typical prodrome of psychiatric disturbance or sensory symptoms.	2003	12815669
fibreoptic equipment and variant creutzfeldt-jakob disease.		2003	12790824
screening for variant creutzfeldt-jakob disease.		2003	12754373
the application of the precautionary principle to the blood system: the canadian blood system's vcjd donor deferral policy.	the precautionary principle is an influential concept that has been widely used in international treaties and declarations involving the protection of the environment. the principle is now being applied to the development of transfusion policy. in this article, we examine the application of the precautionary principle in the policy process leading to canada's decision to defer donations from individuals who had traveled to the united kingdom because of concerns over variant creutzfeldt-jakob dis ...	2003	12733102
post-tonsillectomy haemorrhage: a 7-year retrospective study.	amongst fears about iatrogenic transmission of new variant creutzfeldt-jakob disease (vcjd), last year the department of health of the u.k. advised that all adenotonsillectomies be performed using disposable instruments. following implementation of these guidelines, many consultants reported an increase in post-tonsillectomy haemorrhage in association with the use of disposable instruments. we have undertaken a retrospective study of tonsillectomy and have confirmed a significant increase in the ...	2003	12732932
risk of variant creutzfeldt-jakob disease and tonsillectomy.		2003	12720005
retention of corneal epithelial cells following goldmann tonometry: implications for cjd risk.	to assess the adequacy of current decontamination methods for the goldmann tonometer in the context of variant creutzfeldt-jakob disease (vcjd).	2003	12714400
adverse events in the prophylaxis of haemophilia.	whilst prophylaxis undoubtedly offers many advantages, the potential for adverse effects must also be borne in mind. modern plasma-derived products have an extremely good safety record with regard to transmission of pathogens, although continuous vigilance is required as new pathogens continue to emerge, eg new variant creutzfeldt-jakob disease. there is no evidence that prophylactic treatment is associated with an increased incidence of inhibitors, and it is now recognized that genetic factors ...	2003	12709038
the biology and epidemiology of variant creutzfeldt-jakob disease.		2003	15025265
spatial correlation between the vacuolation, prion protein, deposition and surviving neurons in patients with creutzfeldt-jakob disease (vcjd).	the histological features of cases of variant creutzfeldt-jakob disease (vcjd) are often distributed in the brain in clusters. this study investigated the spatial associations between the clusters of the vacuoles, surviving neurons, and prion protein (prp) deposits in various brain areas in 11 cases of vcjd. clusters of vacuoles and surviving neurons were positively correlated in the cerebral cortex but negatively correlated in dentate gyrus. clusters of the florid and diffuse type of prp deposi ...	2003	14628194
prions and disposable surgical instruments.	single-use surgical instruments have been used in the uk's ent departments. this is in response to guidelines issued by the department of health and the british association of otolaryngologists and head and neck surgeons, in order to prevent the spread of new variant creutzfeldt-jakob disease (vcjd) in a young population of patients undergoing routine adenotonsillectomy. in one institution we found that the new single-use instruments were inferior to previous standard kits and that postoperative ...	2003	14627177
minimising the risk of prion transmission by contact tonometry.	the unknown prevalence of variant creutzfeldt-jakob disease (vcjd) in the uk population has led to fears of horizontal transmission through routine medical procedures. the potential risk of transmission via contact tonometry was examined.	2003	14609834
[progress in the epidemiologic study of variant creutzfeldt-jakob disease].		2003	15481134
variant creutzfeldt-jakob disease and disposable anaesthetic equipment-balancing the risks.		2003	12488368
hla in french patients with variant creutzfeldt-jakob disease.		2003	12583973
mhc typing in variant creutzfeldt-jakob disease.	identification of factors that cause susceptibility to, and clinical expression of, variant creutzfeldt-jakob disease (vcjd) is essential for future management of the disease. we established mhc genotypes of 76 individuals with vcjd and 131 controls, and analysed mhc phenotypes in relation to age of onset of vcjd and its duration from presentation to death. there were no significant differences between vcjd and control populations in frequencies of any mhc types, nor were there associations betw ...	2003	12583949
genetic susceptibility to variant creutzfeldt-jakob disease.		2003	12583940
detection of residual donor leucocytes in leucoreduced red blood cell components using a fluorescence microplate assay.	in november 1999, universal leucoreduction of blood components was introduced in the uk to minimise the risk of variant creutzfeldt-jakob disease (vcjd) transmission by blood transfusion. the uk specifications for leucodepletion processes state that 99% of leucodepleted components should contain < 5 x 10(6) leucocytes/unit, within 95% confidence limits. however, this leucocyte concentration is below the detection limits of standard haematology analysers. the development of a fluorometric immunoa ...	2003	12609529
pathogen inactivation of platelet concentrates and fresh frozen plasma.	transfusion of blood products carries the risk of pathogen transmission, despite careful donor selection and screening tests. this is due to viral transmission from window-period donations, the emergence of new pathogens such as variant creutzfeldt-jakob disease, for which routine screening tests are not yet available, and to bacterial contamination. techniques have been developed to inactivate pathogens in both fresh frozen plasma and platelet concentrates. the relative benefits to the recipien ...	2003	14725341
age and variant creutzfeldt-jakob disease.	the young and stable median age of those who die of variant creutzfeldt-jakob disease has been attributed to age-dependent infection rates. this analysis shows that an influence of age on risk for death after infection better explains age patterns, suggesting that biologic factors peaking in the third decade of life may hasten disease.	2003	14720404
reusable versus disposable instruments in tonsillectomy: a comparative study of outcomes.	tonsillectomy, traditionally performed using reusable instruments (ris), has recently been performed using disposable instruments (dis), to prevent the theoretical risk of spreading new variant creutzfeldt-jakob disease. following this, there have been concerns of increased risk of complications, especially haemorrhage. we audited our hospital's complication rates of 100 tonsillectomies performed using ri and 100 using dis. we analysed the overall complication rates and the postoperative haemorr ...	2003	14529057
the sympathetic nervous system is involved in variant creutzfeldt-jakob disease.	prion epizoonoses spread from animals consumed by humans raise the question of which pathways lead to prion neuroinvasion after oral exposure of humans. here we show that neurons of sympathetic ganglia of patients with variant creutzfeldt-jakob disease (vcjd) accumulate the abnormal isoform of the protein prion. this observation shows the involvement of the sympathetic nervous system in the pathogenesis of vcjd and suggests a role for gut-associated sympathetic neurons in prion propagation in hu ...	2003	12937415
the neuropsychological profile associated with variant creutzfeldt-jakob disease.	we report the neuropsychological profile associated with variant creutzfeldt-jakob disease (vcjd). a retrospective study was carried out of data from neuropsychological reports prepared on 24 patients with vcjd. while there was some variability in neuropsychological profiles, the overall pattern was one of a combined cortical and subcortical dementia, with impaired performance being particularly prominent on tests of memory, executive function, speed of attention, and visuoperceptual reasoning. ...	2003	12937072
variant creutzfeldt-jakob disease and the potential for its accidental transmission following surgery with contaminated instruments: the risk of transmission in australia.	we present a simple model for the quantitative risk assessment of vcjd transmission following surgery. factors that affect the transmission of the disease are prevalence of the disease, concentration of prions in tissues, genetic susceptibility, the number and type of surgical procedures and the effectiveness of decontamination procedures. the main sources of uncertainty are the number of people currently incubating vcjd in australia and the effectiveness of the decontamination processes for sur ...	2003	12862389
first case of variant creutzfeldt-jakob disease in canada.		2003	12861661
variations in neurodegenerative disease across the uk: findings from the national study of progressive intellectual and neurological deterioration (pind).	to identify any uk children with variant creutzfeldt-jakob disease (vcjd) and obtain information about the causes of progressive intellectual and neurological deterioration (pind) and the geographical distribution of cases.	2004	14709491
the success of precaution? managing the risk of transfusion transmission of variant creutzfeldt-jakob disease.	the precautionary principle has emerged as an important new paradigm influencing decision making in the blood system. the principle has influenced decision making in several nations leading to the institution of policies to protect their blood supplies form variant creutzfeldt-jakob disease (vcjd). increasingly evidence has emerged to support the institution of these policies, which were introduced in advance of clear evidence of risk. these vcjd decisions serve as an example of the successful a ...	2004	15383021
quantifying losses to the donated blood supply due to donor deferral and miscollection.	donors are deferred for multiple reasons. losses related to disease marker rates are well established. donor and donation losses for other reasons, however, have not been extensively quantified.	2004	15383013
improved infection control in the prevention of variant creutzfeldt-jakob disease in australia: costs and benefits.	to evaluate the costs and benefits of infection control strategies to prevent the transmission of variant creutzfeldt-jakob disease (vcjd) in ophthalmic surgery in australia.	2004	15707207
[informing the transfused patient of the possible transmission of variant creutzfeldt-jakob disease by blood transfusion].	true risks and theoretical risks: the texts ruling the obligation of the physician to inform the patient appears not to include theoretical risks in their application. in france however, the field of blood transfusions extends this obligation to the theoretical risk of potential transmission through the blood of the infectious agent responsible for creutzfeldt-jakob's disease.	2004	15637795
variant creutzfeldt-jakob disease and prions in the blood supply.		2004	16163166
the pulvinar sign in variant creutzfeldt-jakob disease.		2004	15023827
mimicry of variant creutzfeldt-jakob disease by sporadic creutzfeldt-jakob disease: importance of the pulvinar sign.		2004	15023826
surveillance for progressive intellectual and neurological deterioration in the canadian paediatric population.	to conduct active surveillance of the canadian paediatric population for children who have a progressive intellectual and neurological deterioration to detect the occurrence of cases of creutzfeldt-jakob disease or variant creutzfeldt-jakob disease.	2004	15198447