Arthroscopic evaluation of potential structure-modifying drug in osteoarthritis of the knee. A multicenter, randomized, double-blind comparison of tenidap sodium vs piroxicam.

Objective: To test the hypothesis that tenidap has a structure-modifying effect in human knee osteoarthritis.

Study: multicenter, prospective, randomized, double blind, 1 year duration.

Patients: primary painful knee osteoarthritis (ACR criteria) of the medial tibiofemoral compartment, medial joint space width > or =2mm, at least 10% of one cartilage surface of the medial compartment affected by superficial fibrillation or worse at baseline arthroscopy.

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.

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 between MHC type and age of onset or duration of vCJD disease.

Candidate genes for cross-resistance against DNA-damaging drugs.

Drug resistance of tumor cells leads to major drawbacks in the treatment of cancer. To identify candidate genes for drug resistance, we compared the expression patterns of the drug-sensitive human malignant melanoma cell line MeWo and three derived sublines with acquired resistance to the DNA-damaging agents cisplatin, etoposide, and fotemustine. Subarray analyses confirmed 57 candidate genes recovered from a genome-wide scan for differential expression.

Variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease is caused by the transmission of bovine spongiform encephalopathy to humans. The clinical and investigative features of variant CJD are relatively distinct from sporadic CJD. The number of cases of vCJD are increasing with time in the UK, but the total future number of cases of vCJD is uncertain.

A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.

Objective: Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.

Variant Creutzfeldt-Jakob disease: costs borne by families.

The objectives of this study were: (1) to estimate the costs borne by families caring for patients with variant Creutzfeldt-Jakob disease (vCJD); (2) to contextualise results to recent policy initiatives, and (3) to consider the methodological problems of estimating costs of care. Semi-structured interviews and a follow-up postal questionnaire, eliciting costs to families both before and after the patient's death, were carried out. Participants included 19 families of patients with vCJD.

Sensory features of variant Creutzfeldt-Jakob disease.

Objective: Sensory symptoms are a prominent feature of variant Creutzfeldt-Jakob disease (vCJD), occurring at an early stage of the illness. They are persistent and can be troublesome. Here, they are described in detail and a possible anatomical basis is discussed.

First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features.

Objective: To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease.

Design: Cohort study.

Setting: National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom.

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 of CJD.

Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis.

Objective: To determine whether interleukin-1 alpha and 1 beta gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1 beta and rheumatoid arthritis (RA) motif gene.

Methods: IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1 alpha-889 and IL-1 beta + 3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP.

Predicting the size of the vCJD epidemic in France.

More than 5 years after the description of the first cases of variant Creutzfeldt-Jakob disease (vCJD), there is still great uncertainty about the size of the vCJD epidemic in the United Kingdom (UK), although the most recent predictions based on statistical modelling are more optimistic than the previous ones. The number of vCJD cases in France is far too small to attempt any direct modelling of the vCJD epidemic in the French population. Comparative assessment of the level of exposure to the bovine spongiform encephalopathy (BSE) agent in the UK and France could help to estimate the size of the vCJD epidemic in France.

Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom.

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.

MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol.

Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle.

A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels in human rheumatic diseases.

Objective: To develop a sensitive assay to quantitate serum 3B3(-) levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) as well as levels in control sera.

Methods: An enzyme-linked immunosorbent assay (ELISA) was developed using the monoclonal antibody (MAb) 3B3 to detect a chondroitin sulfate (CS) epitope in the sera and synovial fluid (SF) of RA and OA patients. Keratan sulfate levels were measured in the same biological fluids using the 5D4 monoclonal antibody.

Changing a single amino acid in the N-terminus of murine PrP alters TSE incubation time across three species barriers.

The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood. We have introduced a specific mutation into the endogenous murine PrP gene using gene targeting to produce transgenic mice with a single amino acid alteration (proline to leucine) at amino acid position 101 in their PrP protein (P101L). The effect of this alteration on incubation time, targeting and PrP(Sc) formation has been studied in TSE-infected animals.

Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues.

Abnormal accumulations of prion protein (PrP) can be detected in the spleen, lymph nodes, and tonsils of patients with variant Creutzfeldt-Jakob disease (vCJD). Therefore, it has been assumed, but not shown, that these tissues harbour infectivity, which in turn presents the potential for iatrogenic spread through surgery. Here, we show and measure levels of infectivity in spleen and tonsil from two patients with vCJD, by bioassay in intracerebrally inoculated RIII mice.