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R G Will

Publications and source records attributed to R G Will.

At least 91 records · Page 5Linked to original sources
PubMed1996

[A patient with Creutzfeldt-Jakob disease following treatment with human growth hormone].

In a 39-year old woman Creutzfeldt-Jakob disease was diagnosed. More than twenty years prior to the first clinical symptoms she had been treated with human pituitary growth hormone. After four months of illness she died of Creutzfeldt-Jakob disease, as was shown by the post-mortem finding of spongiform encephalopathy immunochemically positive for abnormal prion protein. The patient represented the first case of Creutzfeldt-Jakob disease associated with the use of human growth hormone in the Netherlands.

Adult↗
PubMed1996

A new variant of Creutzfeldt-Jakob disease in the UK.

BACKGROUND: Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) was reinstituted in the UK in 1990 to identify any changes in the occurrence of this disease after the epidemic of bovine spongiform encephalopathy (BSE) in cattle. METHODS: Case ascertainment of CJD was mostly by direct referral from neurologists and neuropathologists. Death certificates on which CJD was mentioned were also obtained. Clinical details were obtained for all referred cases, and information on potential risk factors for CJD was obtained by a standard questionnaire administered to patients' relatives. Neuropathological examination was carried out on approximately 70% of suspect cases. Epidemiological studies of CJD using similar methodology to the UK study have been carried out in France, Germany, Italy, and the Netherlands between 1993 and 1995. FINDINGS: Ten cases of CJD have been identified in the UK in recent months with a new neuropathological profile. Other consistent features that are unusual include the young age of the cases, clinical findings, and the absence of the electroencephalogram features typical for CJD. Similar cases have not been identified in other countries in the European surveillance system. INTERPRETATION: These cases appear to represent a new variant of CJD, which may be unique to the UK. This raises the possibility that they are causally linked to BSE. Although this may be the most plausible explanation for this cluster of cases, a link with BSE cannot be confirmed on the basis of this evidence alone. It is essential to obtain further information on the current and past clinical and neuropathological profiles of CJD in the UK and elsewhere.

Adolescent↗
PubMed1996

A prion disease with a novel 96-base pair insertional mutation in the prion protein gene.

There are coding mutations in the prion protein gene in familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, and other phenotypes that make up the inherited prion diseases. Insertional mutations consisting of two, five, six, seven, eight, and nine additional octapeptide repeat elements are seen in the inherited prion diseases and usually present as atypical dementias with considerable intrafamilial phenotypic variability. A four-octarepeat insertion was reported previously in an individual without neurodegenerative disease who died of hepatic cirrhosis. Here we report a novel four-octarepeat insertional mutation in a case with classical clinical, electroencephalographic and histopathologic features of CJD with the unusual finding of pronounced prion protein immunoreactivity of the molecular layer of the cerebellum.

Amino Acid Sequence↗
PubMed1996

Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies.

To review the evidence for risk factors of Creutzfeldt-Jakob disease (CJD), we pooled and reanalyzed the raw data of three case-control studies. The pooled data set comprised 178 patients and 333 control subjects. The strength of association between CJD and putative risk factors was assessed by computing the odds ratio as estimate of the relative risk. The risk of CJD was statistically significantly increased for subjects with a family history of CJD (odds ratio = 19.1; 95% CI 1.1 to 348.0). Further, there was a significant association between the risk of CJD and a history of psychotic disease (odds ratio = 9.9; 95% CI 1.1 to 86.1). Although not significantly increased, there was an elevated risk of CJD for subjects with a family history of dementia, a history of poliomyelitis, subjects employed as health professionals, and subjects ever exposed to cows and sheep. No association could be shown with organ meat consumption, including brain. The negative results of this reanalysis reassures the absence of a common risk factor in all CJD patients. However, the ongoing epidemiologic surveillance of CJD in several European countries may provide more evidence to exclude any environmental exposure early in childhood.

Animals↗
PubMed1996

[Consensus report: tissue handling in suspected Creutzfeldt-Jakob disease and other spongiform encephalopathies (prion diseases) in the human. European Union Biomed-1 Concerted Action].

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion diseases) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. The autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for safe performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories experienced in handling tissue from transmissible spongiform encephalopathies. In essence, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potentially infectious material must be adequately decontaminated by specific means. The full English text of this Consensus Report was published in Brain Pathology 5: 319-322 (1995).

Autopsy↗
PubMed1995

Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene.

A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and anti-prion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaining a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed.

Base Sequence↗
PubMed1994

Iatrogenic Creutzfeldt-Jakob disease: an example of the interplay between ancient genes and modern medicine.

We tested DNA from 15 centrally infected cases of iatrogenic Creutzfeldt-Jakob disease (CJD) (dura mater or corneal homografts and stereotactic EEG electrodes), 11 peripherally infected cases (native human growth hormone or gonadotrophin), and 110 control individuals for the presence of mutations in the chromosome 20 amyloid gene. No patient or control had any of the known pathogenic point or insert mutations found in familial disease, but allelic homozygosity at polymorphic codon 129 was present in all but two (92%) of the 26 patients, compared with 54 (50%) of the 110 controls (p < 0.001). Pooled data from all identified and tested cases of iatrogenic disease yielded a worldwide total of 56 patients, of whom all but four were homozygous at codon 129 (p < 0.001). These findings support the thesis that homozygosity at codon 129 enhances susceptibility to iatrogenic infections of both central and peripheral origin, with evident implications for the population of dura mater homograft and pituitary hormone recipients whose lives have been complicated by the possibility of exposure to the infectious agent of CJD.

Amyloid↗
PubMed1993

Creutzfeldt-Jakob disease and blood transfusion.

Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) in the UK identified 21 patients who had received a blood transfusion and 29 who had donated blood, out of a total of 202 definite and probable cases. This frequency of blood transfusion or donation did not differ from that in age and sex matched controls, and the clinical features in patients with a history of blood transfusion were similar to those of classical CJD and clearly distinct from CJD in recipients of human growth hormone. This evidence does not suggest that blood transfusion is a major risk factor for CJD.

Blood Donors↗
PubMed1993

Epidemiology of Creutzfeldt-Jakob disease.

Extensive information on the epidemiology of Creutzfeldt-Jakob Disease (CJD) has accumulated since the original transmission of CJD to primates in 1968. One aim of this research was to discover the mechanism of natural transmission of CJD but the epidemiological evidence virtually precludes case to case transmission as a causative mechanism, except in rare iatrogenic cases, and has provided little evidence to suggest an environmental 'source of infection'. An understanding of the few positive epidemiological findings such as the high incidence in Slovakia has depended on major advances in molecular biology rather than on epidemiological evidence. The occurrence of Bovine Spongiform Encephalopathy (BSE) has however reinforced the importance of having established the epidemiological characteristics of CJD and this information is an important background on which to evaluate the findings from basic scientific research.

Creutzfeldt-Jakob Syndrome↗