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R G Will

Publications and source records attributed to R G Will.

At least 73 records · Page 4Linked to original sources
PubMed1998

Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD).

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. Genetic and iatrogenic forms have been recognised but most are sporadic and of unknown cause. We have studied risk factors for CJD as part of the 1993-95 European Union collaborative studies of CJD in Europe. METHODS: The 405 patients with definite or probable CJD who took part in our study had taken part in population-based studies done between 1993 and 1995 in Belgium, France, Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from these patients were compared with data from 405 controls. FINDINGS: We found evidence for familial aggregation of CJD with dementia due to causes other than CJD (relative risk [RR] 2.26, 95% CI 1.31-3.90). No significant increased risk of CJD in relation to a history of surgery and blood transfusion was shown. There was no evidence for an association between the risk of CJD and the consumption of beef, veal, lamb, cheese, or milk. No association was found with occupational exposure to animals or leather. The few positive findings of the study include increased risk in relation to consumption of raw meat (RR 1.63 [95% CI 1.18-2.23]) and brain (1.68 [1.18-2.39]), frequent exposure to leather products (1.94 [1.13-3.33]), and exposure to fertiliser consisting of hoofs and horns (2.32 [1.38-2.91]). Additional analyses, for example stratification by country and of exposures pre-1985 and post-1985, suggest that these results should be interpreted with great caution. INTERPRETATION: Within the limits of the retrospective design of the study, our findings suggest that genetic factors other than the known CJD mutations may play an important part in CJD. Iatrogenic transmission of disease seems rare in this large population-based sample of patients with CJD. There is little evidence for an association between the risk of CJD and either animal exposure, or consumption of processed bovine meat or milk products for the period studied.

Adult↗
PubMed1998

Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993-1995. EU Collaborative Study Group for CJD.

After the occurrence of bovine spongiform encephalopathy (BSE), there has been concern that transmission of BSE to the human population might result in a change in the epidemiological characteristics of Creutzfeldt-Jakob disease (CJD). A collaborative study of CJD in the European Union was performed from 1993 to 1995, to compare data from national registries for CJD in France, Germany, Italy, The Netherlands, Slovakia, and the United Kingdom. Five hundred seventy-five patients with definite or probable CJD died in the study period with an overall annual mortality rate of 0.71 cases per million. The incidence rates for CJD were similar in all participating countries despite variations in postmortem rates, and age-specific incidence rates were also relatively consistent, with the exception of an increased incidence of CJD in patients younger than 39 years of age in the United Kingdom. In relation to etiological subtypes of CJD, 87% of cases were sporadic, 8% genetic, and 5% iatrogenic. Genetic forms of CJD comprised 80% of all cases in Slovakia, and iatrogenic forms of CJD occurred most frequently in France and the United Kingdom. The statistical data reported here do not provide evidence of a causal link between BSE and CJD in Europe as a whole. However, the study has established baseline epidemiological parameters for CJD in participating European countries, which may be important in the assessment of any future change in the characteristics of CJD as a result of the epidemic of BSE.

Adult↗
PubMed1998

New variant Creutzfeldt-Jakob disease.

New variant Creutzfeldt-Jakob disease is a novel human spongiform encephalopathy with a consistent clinico-pathological phenotype. Epidemiological evidence indicates that this disease is occurring almost exclusively in the UK, where there has been an epidemic of spongiform encephalopathy in the cattle population. Current evidence strongly supports the hypothesis that there is a causal link between bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease.

Animals↗
PubMed1998

Creutzfeldt-Jakob disease and the risk from blood or blood products.

The occurrence of iatrogenic cases of Creutzfeldt-Jakob disease (CJD) and the isolation of infectivity in some laboratory transmission studies in transmissible spongiform encephalopathies raises the possibility that CJD might be accidentally transmissible through blood or blood products. Epidemiological evidence, although not conclusive, does not suggest that classical CJD is transmitted through this route. However, new variant CJD (nvCJD) might pose greater risks of accidental transmission of infection and mechanisms to reduce the theoretical risk are under consideration. The theoretical risks from CJD and nvCJD must be balanced against the established therapeutic benefits of blood and blood products.

Biological Products↗
PubMed1997

Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent.

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

Animals↗
PubMed1997

New variant Creutzfeldt-Jakob disease: psychiatric features.

BACKGROUND: An apparently new variant of Creutzfeldt-Jakob disease (CJD), new variant CJD (nvCJD), was identified in the UK in 1996. There have now been 21 cases of nvCJD in the UK and one in France. Psychiatric symptoms are prominent in the initial presentation in these cases. METHODS: Cases of nvCJD are identified mainly by direct referral from neurologists and neuropathologists. Detailed clinical information was obtained by review of case notes and interviewing patients' relatives. We report the psychiatric features of the first 14 cases on nvCJD in the UK. Psychiatric notes were examined in all 13 of these cases who were seen by a psychiatrist. RESULTS: Eight cases were women. All 14 cases had early psychiatric features and in nine, the first symptom was psychiatric. 13 cases were seen by a psychiatrist and the majority were diagnosed as suffering from depression or depression secondary to organic disease. Two cases suffered from first-rank symptoms suggestive of psychotic illness and transient delusions and auditory or visual hallucinations occurred in the majority. All cases were referred to a neurologist as the illness evolved and neurological signs developed. INTERPRETATION: Psychiatric symptoms are a consistent early clinical feature in nvCJD. Analysis of the psychiatric symptoms does not suggest specific features that readily allow distinction from more common psychiatric disorders, although the occurrence of associated persistent sensory symptoms may raise the possibility of this diagnosis. Neurological signs, including ataxia, involuntary movements and cognitive impairment developed in all cases and the evolution of increasing neurological deficits is likely to remain critical to the clinical diagnosis of nvCJD.

Adult↗
PubMed1997

New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests.

BACKGROUND: In April, 1996, ten cases of Creutzfeldt-Jakob disease (CJD) with an apparently new clinicopathological phenotype were published and it was suggested that these new variant cases (nvCJD) might be causally linked to bovine spongiform encephalopathy (BSE). There have now been 21 cases of nvCJD in the UK and one case in France. We report clinical features and diagnostic test results of the first 14 cases of nvCJD in the UK. METHODS: Case ascertainment of CJD was mainly by direct referral from neurologists and neuropathologists. Clinical and investigate details were obtained by interview with patients' relatives and by examination of case notes. Ten cases in this report were examined while alive. Prion protein (PrP) gene analysis was carried out with informed consent from the patient or from a relative. The diagnosis of nvCJD was established histologically. FINDINGS: Eight cases were women. Mean age at onset of symptoms was 29 (16-48) years and the median duration of illness was 14 (9-35) months. All patients had early psychiatric symptoms, most often depression, and 13 were seen by a psychiatrist early in the clinical course. Eight patients developed early sensory symptoms which were persistent and often painful. Neurological signs, including ataxia and involuntary movements, developed in all cases and towards the end of the illness, most had akinetic mutism. The electroencephalogram was abnormal in most patients but typical periodic complexes of CJD were not seen in any case. Cerebral imaging was usually normal or showed non-specific abnormalities; in two cases magnetic-resonance imaging scans showed high signal in the thalamus. INTERPRETATION: Clinical features in these cases are similar and relatively distinct from other forms of CJD, suggesting that this is a new clinical phenotype consistent with a single strain of infectious agent. There is, however, some overlap with atypical cases of sporadic CJD, and the diagnosis of nvCJD remains dependent on neuropathological confirmation.

Adolescent↗
PubMed1997

Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96.

OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN: Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING: England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS: During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.

Adolescent↗
PubMed1997

Molecular assessment of the potential transmissibilities of BSE and scrapie to humans.

More than a million cattle infected with bovine spongiform encephalopathy (BSE) may have entered the human food chain. Fears that BSE might transmit to man were raised when atypical cases of Creutzfeldt-Jakob disease (CJD), a human transmissible spongiform encephalopathy (TSE), emerged in the UK. In BSE and other TSE diseases, the conversion of the protease-sensitive host prion protein (PrP-sen) to a protease-resistant isoform (PrP-res) is an important event in pathogenesis. Biological aspects of TSE diseases are reflected in the specificities of in vitro PrP conversion reactions. Here we show that there is a correlation between in vitro conversion efficiencies and known transmissibilities of BSE, sheep scrapie and CJD. On this basis, we used an in vitro system to gauge the potential transmissibility of scrapie and BSE to humans. We found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both scrapie (PrP[Sc]) and BSE (PrP[BSE]). The efficiencies of these heterologous conversion reactions were similar but much lower than those of relevant homologous conversions. Thus the inherent ability of these infectious agents of BSE and scrapie to affect humans following equivalent exposure may be finite but similarly low.

Animals↗