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Preclinical Phase (preclinical + phase)
Selected AbstractsVariant Creutzfeldt,Jakob disease and its transmission by bloodJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003J. W. Ironside Summary., 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 preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell-associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease-associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease-associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD. [source] Bowel movement frequency in late-life and incidental Lewy bodiesMOVEMENT DISORDERS, Issue 11 2007Robert D. Abbott PhD Abstract It is not known if constipation is associated with the preclinical phase of Parkinson's disease (PD), often characterized by the presence of incidental Lewy bodies (ILB). Such an association could provide evidence that constipation is an early symptom of PD. The purpose of this report is to examine the association between late-life bowel movement frequency and ILB. Bowel movement frequency was assessed from 1991 to 1993 in 245 men aged 71 to 93 years in the Honolulu-Asia Aging Study who later received postmortem examinations. All were without clinical PD and dementia. Brains were examined for ILB in the substantia nigra and locus ceruleus. Among the decedents, 30 men had ILB (12.2%). After age-adjustment, the percent of brains with ILB declined with increasing bowel movement frequency (P = 0.013). For men with <1, 1, and >1 bowel movement/day, corresponding percents were 24.1, 13.5, and 6.5%. Findings persisted after additional adjustment for time to death, mid-life pack-years of smoking and coffee intake, physical activity, and cognitive function. Infrequent bowel movements are associated with ILB. Findings provide evidence that constipation can predate the extrapyramidal signs of PD. Constipation could be one of the earliest markers of the beginning of PD processes. © 2007 Movement Disorder Society [source] Decreased cerebrospinal fluid A,42 correlates with brain atrophy in cognitively normal elderly,ANNALS OF NEUROLOGY, Issue 2 2009Anne M. Fagan PhD Objective For therapies for Alzheimer's disease (AD) to have the greatest impact, it will likely be necessary to treat individuals in the "preclinical" (presymptomatic) stage. Fluid and neuroimaging measures are being explored as possible biomarkers of AD pathology that could aid in identifying individuals in this stage to target them for clinical trials and to direct and monitor therapy. The objective of this study was to determine whether cerebrospinal fluid (CSF) biomarkers for AD suggest the presence of brain damage in the preclinical stage of AD. Methods We investigated the relation between structural neuroimaging measures (whole-brain volume) and levels of CSF amyloid-, (A,)40, A,42, tau, and phosphorylated tau181 (ptau181), and plasma A,40 and A,42 in well-characterized research subjects with very mild and mild dementia of the Alzheimer type (n = 29) and age-matched, cognitively normal control subjects (n = 69). Results Levels of CSF tau and ptau181, but not A,42, correlated inversely with whole-brain volume in very mild and mild dementia of the Alzheimer type, whereas levels of CSF A,42, but not tau or ptau181, were positively correlated with whole-brain volume in nondemented control subjects. Interpretation Reduction in CSF A,42, likely reflecting A, aggregation in the brain, is associated with brain atrophy in the preclinical phase of AD. This suggests that there is toxicity associated with A, aggregation before the onset of clinically detectable disease. Increases in CSF tau (and ptau181) are later events that correlate with further structural damage and occur with clinical onset and progression. Ann Neurol 2009;65:176,183 [source] Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 9 2010Jason R. Kolfenbach Objective To determine whether antibodies against peptidyl arginine deiminase type 4 (PAD-4) are present in the preclinical phase of rheumatoid arthritis (RA) and to compare the timing and extent of their appearance with those of other preclinical autoantibodies. Methods Prediagnosis serum samples from 83 patients with RA were evaluated for the presence of anti,PAD-4 antibody, anti,cyclic citrullinated peptide (anti-CCP) antibody, and rheumatoid factor. In addition, a control cohort (n = 83) matched by age, sex, race, number of serum samples, and duration of serum storage was tested for the presence of anti,PAD-4 antibody to determine its sensitivity and specificity for the subsequent development of RA. Results Fifteen of 83 patients with RA (18.1%) had at least 1 prediagnosis sample positive for anti,PAD-4. One of 83 control subjects (1.2%) had at least 1 positive sample, resulting in a sensitivity and specificity of 18.1% and 98.8%, respectively, of anti,PAD-4 for the future development of RA. The mean duration of anti,PAD-4 positivity prior to clinical diagnosis was 4.67 years. Anti,PAD-4 positivity was associated with anti-CCP positivity (odds ratio 5.13 [95% confidence interval 1.07,24.5]). In subjects with prediagnosis samples that were positive for both antibodies, anti-CCP positivity predated anti,PAD-4 positivity in 9 of 13 cases (69%). Conclusion Autoantibodies to PAD-4 are present during the preclinical phase of RA in a subset of patients and are associated with anti-CCP positivity. Further exploration is needed regarding the timing of appearance and disease-related effects of PAD-4 autoimmunity. [source] Gene expression profiling in autoantibody-positive patients with arthralgia predicts development of arthritis,ARTHRITIS & RHEUMATISM, Issue 3 2010Lisa G. M. van Baarsen Objective To identify molecular features associated with the development of rheumatoid arthritis (RA), to understand the pathophysiology of preclinical development of RA, and to assign predictive biomarkers. Methods The study group comprised 109 anti,citrullinated protein antibody (ACPA), and/or rheumatoid factor,positive patients with arthralgia who did not have arthritis but were at risk of RA, and 25 patients with RA. The gene expression profiles of blood samples obtained from these patients were determined by DNA microarray analysis and quantitative polymerase chain reaction. Results In 20 of the 109 patients with arthralgia who were at risk of RA, arthritis developed after a median of 7 months. Gene expression profiling of blood cells revealed heterogeneity among the at-risk patients, based on differential expression of immune-related genes. This report is the first to describe gene signatures relevant to the development of arthritis. Signatures significantly associated with arthritis development were involved in interferon (IFN),mediated immunity, hematopoiesis, and chemokine/cytokine activity. Logistic regression analysis revealed that the odds ratio (OR) for developing arthritis within 12 months was 21.0 (95% confidence interval [95% CI] 2.8,156.1 [P = 0.003]) for the subgroup characterized by increased expression of genes involved in IFN-mediated immunity and/or cytokine/chemokine-activity. Genes involved in B cell immunology were associated with protection against progression to arthritis (OR 0.38, 95% CI 0.21,0.70 [P = 0.002]). These processes were reminiscent of those in patients with RA, implying that the preclinical phase of disease is associated with features of established disease. Conclusion The results of this study indicate that IFN-mediated immunity, hematopoiesis, and cell trafficking specify processes relevant to the progression of arthritis independent of ACPA positivity. These findings strongly suggest that certain gene signatures have value for predicting the progression to arthritis, which will pave the way to preventive medicine. [source] Can we accurately predict the development of rheumatoid arthritis in the preclinical phase?ARTHRITIS & RHEUMATISM, Issue 10 2003Darcy S. Majka First page of article [source] Pre-clinical Dementia: Does it Exist?AUSTRALASIAN JOURNAL ON AGEING, Issue 1 2001Louise M. Waite Identification of syndromes that will progress to dementia carries immense importance for the management of these diseases when therapies are available and for future research into effective early prevention. Evidence supporting the presence of a preclinical phase for dementia has arisen from a range of different areas. Clinical and epidemiological studies have identified both cognitive and neurological abnormalities which predict the future development of dementia. Similarly, various neuroimaging techniques have identified abnormalities in asymptomatic subjects with significant risk for developing Alzheimer's disease and subjects who show mild cognitive deficits. Neuropathological series are hampered by non-representative study populations and poor antemortem data but in studies where informants have been utilised to provide details of subjects' antemortem cognitive function, evidence indicates that the presence of brain pathology is associated with cognitive deficits. This paper reviews the current literature exploring the presence of a pre-clinical phase for dementia, identifies the weaknesses in this research and provides suggestions for future research. [source] | |||||||||||||||||||