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At least 1,135 records · Page 63Linked to original sources
PubMed2005

Alterations of self-reactive antibody repertoires in HIV disease: an insight into the role of T cells in the selection of autoreactive B cells.

Infection with human immunodeficiency virus (HIV) is characterized by a progressive depletion of CD4(+) T cells that parallels a dysfunction of the B cell compartment and a disturbed recognition of self-antigens. The relationship between T lymphocyte homeostasis and abnormalities in the selection of self-reactive B cells is not clear as yet. We have therefore compared repertoires of natural antibodies of healthy donors and of patients at various stages of HIV infection. The reactivity of IgM and IgG antibodies in plasma of healthy blood donors and of HIV-positive patients with high and low CD4(+) T cell counts was assessed by semi-quantitative immunoblotting using self-antigens extracted from normal human tissues. Repertoires of reactivites were compared between groups of individuals by means of multiparametric statistical analysis. We observed that repertoires of self-reactive IgM and IgG from HIV-seropositive patients exhibited significantly altered patterns of reactivity, as compared to those of healthy controls. Further, self-reactive repertoires of IgM and IgG of patients with high CD4(+) T cell counts differed significantly from those of patients with low CD4(+) T cell counts. A longitudinal analysis of self-reactive antibody repertoires of progressor and non-progressor patients suggested an influence of CD4(+) T cell counts on immunoglobulin reactivity toward self-antigens. These observations support the hypothesis that altered T cell/B cell interactions due to altered CD4(+) T cell help severely impact on the selection of self-reactive antibody repertoires and may contribute to the onset of pathological autoimmunity in HIV disease.

Autoantibodies↗
PubMed1998

Decline in lung function related to exposure and selection processes among workers in the grain processing and animal feed industry.

OBJECTIVES: To follow up workers in the grain processing and animal feed industry five years after an initial survey, and to monitor exposures to organic dust and endotoxin and changes in prevalence of respiratory symptoms and lung function. METHODS: Outcome measures in the present survey were decline in lung function over five years, rapid annual decline in forced expiratory volume in one second (FEV1) above 90 ml.s-1, and loss to follow up. RESULTS: Among 140 workers included in the longitudinal analysis, annual decline in FEV1 and maximal mid-expiratory flow (MMEF) were significantly related to occupational exposure to dust and endotoxin in the grain processing and animal feed industry. Assuming a cumulative exposure over a working life of 40 years with an exposure of 5 mg.m-3, the estimated effect on the FEV1 would be a decline of 157 ml.s-1 (95% CI 13 to 300)--that is, about 4% of the group mean FEV1 and 473 ml.s-1 (95% CI 127 to 800) of the MMEF (about 12%). Workers with a dust exposure > 4 mg.m-3 or endotoxin concentrations > 20 ng.m-3 at the 1986-8 survey had significantly higher risk of rapid decline in FEV1 (odds ratio (OR) 3.3, 95% CI 1.02 to 10.3). The relations between occupational exposure and decline in lung function in this study occurred, despite the selection through the healthy worker effect that occurred as well. Increasing working years was related to decreasing annual decline in FEV1 and fewer people with rapid decline in FEV1 (OR 0.04, 95% CI 0 to 0.61 for over 20 v < 5 working years in the grain processing and animal feed industry). The presence of respiratory symptoms at baseline was a strong predictor of subsequent loss to follow up. Baseline lung function was not found to be predictive of subsequent loss to follow up. However, among workers lost to follow up the number of working years was more strongly negatively related to baseline lung function than among the workers who were studied longitudinally. CONCLUSIONS: The existence of the healthy worker effect implies that an exposure-response relation in the grain processing and animal feed industry may well be underestimated. This should be taken into account when health based recommended limit values are to be developed.

Adult↗
PubMed2005

Physical activity and sedentary behavior: a review of longitudinal studies of weight and adiposity in youth.

AIM: To review the published prospective observational studies of the relationship of physical activity and sedentary behavior with the development of overweight and adiposity, with an emphasis on methodologic issues. METHODS: Sample size, population studied, length of follow-up, assessment of exposure (physical activity, inactivity, or sedentary behavior), assessment of outcome (relative weight, overweight, % body fatness, adiposity), statistical approach, and main findings were extracted, summarized, and key methodological issues highlighted. RESULTS: In total, 17 studies of physical activity and 15 studies of inactivity/sedentary behavior were identified; as these were not mutually exclusive, 20 unique studies were reviewed. Results were mixed, with most studies showing an inverse association of physical activity with weight or fatness outcomes and/or a direct association of inactivity/sedentary behavior with weight or fatness outcomes. The effects identified were generally of small magnitude. Imprecise measurement of activity exposures likely weakens the observed relationships. Most studies used a pre-post design and had limited duration of follow-up (< or = 2y). Studies with longer and more frequent follow-up did not always use the most advantageous statistical approach. CONCLUSIONS: On balance, the available evidence from prospective observational studies suggests that increased physical activity and decreased sedentary behavior are protective against relative weight and fatness gains over childhood and adolescence. In addition to improved measurement methods, longer and more frequent follow-up as well as truly longitudinal analysis methods would help establish these important prevention and intervention targets, and identify subgroups or development periods where interventions would likely be effective.

Adolescent↗
PubMed1998

[Gompertzian analysis of ischemic cardiopathy mortality in Spain, 1951-1992].

INTRODUCTION AND OBJECTIVES: In Spain ischemic heart disease mortality was increasing prior to 1975 and has decreased since 1975. This trend is common to both genders. The goal of this paper is to separate the genetic, environmental and competitive risk factors influencing this evolution. METHODS: The Gompertz function was adjusted cross-sectionally to age-specific mortality due to ischemic heart disease for each year from 1951 to 1992. The Gompertzian longitudinal analysis was applied to the coefficients obtained to estimate the effect due to environmental and competitive factors. RESULTS: Ischemic heart disease in Spain is a Gompertzian disease with an intersection point at 67 years for men and 40 years for women. Environmental factors were increasing before 1975 and have decreased since then. However, the competitive factors decreased in men since 1980 and in women since 1951 on. CONCLUSION: The evolution of risk factors (smoking, hypercholesterolemia and hypertension) is responsible for the major proportion of ischemic disease mortality changes. Treatment of instaured ischemic disease has a low influence.

Adult↗
PubMed1997

Serum angiotensin-converting enzyme in multiple sclerosis.

OBJECTIVE: To determine the extent and significance of serum angiotensin-converting enzyme (ACE) elevation in multiple sclerosis (MS) and the correlation between serum ACE activity and clinical and magnetic resonance imaging (MRI) indicators of disease activity. DESIGN: A retrospective cross-sectional study of 45 consecutive patients with clinically definite MS and a longitudinal study of 30 additional patients with clinically definite MS involved in a long-term study of neurologic function and MRI in MS. SETTING: Comprehensive MS center of a tertiary care university hospital. SUBJECTS: A total of 75 patients with clinically definite MS and 31 healthy controls. METHODS: Serum ACE activity was measured using a spectrophotometric assay and correlated with clinical indicators of disease activity and with total cerebral MS lesion volume measured by MRI. RESULTS: An elevated ACE activity was found in 17 (23%) of 75 patients with MS as compared with 2 (6%) of 31 healthy controls. Changes in serum ACE activity correlated with changes in total plaque volume on MRI. CONCLUSIONS: Serum ACE activity may be an indicator of disease activity in longitudinal analysis. Also, elevated ACE activity in a patient with otherwise typical MS need not raise suspicions of alternative diagnoses.

Adult↗
PubMed2000

Dynamic changes in cerebral glucose metabolism in conscious infant monkeys during the first year of life as measured by positron emission tomography.

Recently, advances in spatial resolution have provided the opportunity to utilize positron emission tomography (PET) to examine local cerebral metabolic rates for glucose (lCMR(glc)) in large animals noninvasively, thereby allowing repeated lCMR(glc) measurements in the same animal. Previous studies have attempted to describe the ontogeny of cerebral glucose metabolism in anesthetized nonhuman primates using [18F]fluorodeoxyglucose (FDG) and PET. However, the use of sedation during the tracer uptake period may influence lCMR(glc). This study was conducted to describe lCMR(glc) in conscious infant vervet monkeys (Cercopithecus aethiops sabaeus) during the first year of life utilizing FDG-PET. Cross-sectional studies (n=23) displayed lowest and highest lCMR(glc) in all structures at the 2-3 and 8-9 month age groups, respectively. The metabolic pattern suggested an increase in lCMR(glc) values between 2 and 8 months of age with decreased metabolism observed at 10-12 months of age in all regions. Peak lCMR(glc) values at 8 months were an average of 84+/-24% higher than values seen at the youngest age examined quantitatively (2-3 months). The regions of greatest and smallest increases in lCMR(glc) at 8 months were the cerebellar hemispheres (90%) and the thalamus (39%), respectively. Longitudinal analysis in 4 animals supported this developmental pattern, demonstrating the ability to detect changes in cerebral glucose metabolism within animals and the potential for FDG-PET in nonhuman primate models of brain maturation. By determining the normative profile of lCMR(glc) during development in monkeys, future application of FDG-PET will provide the opportunity to longitudinally assess the effects of environmental or pharmacological intervention on the immature brain.

Aging↗
PubMed1992

[Between- and within-subject variability of pulmonary function. Four year follow-up of adult males].

Maximal forced expiration of 326 adult males 30 to 55 yr of age was measured four times during a follow-up of 4 yr. Acceptable results were obtained in 270 subjects three times or more. Forced vital capacity (FVC), forced expiratory volume in one second, maximal expiratory flows at 50% and 25% FVC divided by squared height (CFVC, CFEV1, CVmax50, and CVmax25, respectively) were analyzed. Between- and within-subject variance were estimated by a linear model, including the effects of individual and age as explanatory variables. The goodness of fit of the model was satisfactory, since the coefficients of determination of the model were more than 0.96 for CFVC and CFEV1 and around 0.91 for CVmax50 and CVmax25. Estimated between-subject variance was far larger than within-subject variance, being more than ten times for CFVC and CFEV1, about eight times for CVmax50, and five times for CVmax25. At the same time, annual decline of pulmonary function determined cross-sectionally was significantly larger than that determined longitudinally. These results indicated the superiority of longitudinal analysis to cross-sectional analysis in evaluating relatively small effects on pulmonary function especially in the case of chronic exposure of toxic substances in low doses.

Adult↗
PubMed1996

Operations, total hospital stay and costs of critical leg ischemia. A population-based longitudinal outcome study of 321 patients.

In a longitudinal analysis of all 321 patients in a defined population having surgery for critical leg ischemia during 1 year in Malmöhus county (0.53 million inhabitants), Sweden, we investigated all vascular procedures and amputations on both legs, total hospital stay and hospital costs from the first procedure in each patient until death or at follow-up at least 6 years postoperatively. The first (key) operation during the inclusion year was a reconstructive vascular procedure in 96 patients, a restorative vascular procedure in 111 and a major amputation in 114 patients. One third of those with a reconstructive and half of those with a restorative key procedure had an ipsilateral major amputation. The mean number of surgical procedures and length of hospital stay among all patients were 3 (1-19) procedures and 117 (1-1097) days, respectively. Of the total number of days in hospital, less than half were in surgical departments, 10% in other acute-care departments and almost half in rehabilitation clinics and nursing homes. The total hospital and surgical costs among all patients were USD 15.1 million (mean USD 47,000/patient), with no significant differences in relation to the key operation. We conclude that patients who have undergone surgery for critical leg ischemia accumulate very high total long-term hospital costs due to the need for repetitive surgery and long hospital stays. Our findings also show that a longitudinal study, including hospital stay in departments other than surgical, is necessary for a correct cost-and-outcome analysis.

Amputation, Surgical↗
PubMed2002

Extension of variance components approach to incorporate temporal trends and longitudinal pedigree data analysis.

Here we present a method that permits one to evaluate genetic effects and to detect genetic linkages by using serial observations of quantitative traits in pedigrees. We developed a statistical method that incorporates longitudinal family data and genetic marker information into an estimating equations framework. With this approach, we can study changes in components over time that measure polygenic and major genetic variances as well as shared and individual-specific environmental effects. Our method provides a measure of heritability from analysis of longitudinal data. Results using longitudinal family data from the Center for Preventive Medicine (Nancy, France) are presented. The results of our analysis show that the apolipoprotein E locus has no effect on interindividual variability in systolic blood pressure. We found that the longitudinal measure of heritability of systolic blood pressure is 0.32.

Apolipoproteins E↗
PubMed2001

Benzodiazepine use in an elderly community-dwelling population. Characteristics of users and factors associated with subsequent use.

OBJECTIVES: The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort. METHODS: The study was conducted on a cohort of 2,792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. Benzodiazepine use and its correlates were studied with data collected at inclusion in the cohort. Longitudinal analysis over a 5-year period of follow-up was done to identify baseline predictors of subsequent use. RESULTS: At baseline, prevalence rate of benzodiazepine use was 31.9%. It was associated with female gender [odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.66, 2.46], previous psychiatric disease (OR = 2.87; 95% CI: 2.31, 3.56), concomitant antidepressant use (OR = 2.45; 95% CI: 1.59, 3.78), depressive symptomatology (OR = 1.70; 95% CI: 1.28, 2.26), multiple drug use (OR = 1.82; 95% CI: 1.50, 2.21), multiple chronic diseases (OR = 1.37; 95% CI: 1.12, 1.67) and poor self-perceived health (OR = 1.63; 95% CI: 1.33, 2.0). For the 1926 benzodiazepine non-users at inclusion and followed during 5 years, incidence rate of subsequent use was 5.37 per 100 person-years (95% CI: 4.76, 5.98). In multivariate Cox proportional hazards regression analysis, previous psychiatric diseases, poor self-perceived life satisfaction and polymorbidity were significantly associated with subsequent benzodiazepine use. CONCLUSIONS: Elderly people are heavy users of benzodiazepines. Independently from mental health status, those in poor health were most at risk of benzodiazepine use.

Aged↗
PubMed2006

The effects of cumulative risks and promotive factors on urban adolescent alcohol and other drug use: a longitudinal study of resiliency.

Resiliency theory provides a conceptual framework for studying why some youth exposed to risk factors do not develop the negative behaviors they predict. The purpose of this study was to test compensatory and protective models of resiliency in a longitudinal sample of urban adolescents (80% African American). The data were from Years 1 (9th grade) and 4 (12th grade). The study examined effects of cumulative risk and promotive factors on adolescent polydrug use including alcohol, tobacco and marijuana. Cumulative measures of risk/promotive factors represented individual characteristics, peer influence, and parental/familial influences. After controlling for demographics, results of multiple regression of polydrug use support the compensatory model of resiliency both cross-sectionally and longitudinally. Promotive factors were also found to have compensatory effects on change in adolescent polydrug use. The protective model of resiliency evidenced cross-sectionally was not supported in longitudinal analysis. The findings support resiliency theory and the use of cumulative risk/promotive measures in resiliency research. Implications focused on utilizing multiple assets and resources in prevention programming are discussed.

Adolescent↗
PubMed1999

The great escape - AIDS viruses and immune control.

Many studies have been designed to address the role of CTL immune escape in HIV-1 infection, but have not given conclusive answers. Now, an elegant longitudinal analysis clearly demonstrates that progression to disease in SIV-infected macaques is associated with evasion of the CTL response (pages 1270-1276).

Animals↗
PubMed2004

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.

Animals↗
PubMed1999

Choosing a national survey to investigate smoking behaviour: making comparisons between the General Household Survey, the British Household Panel Survey and the Health Survey for England.

BACKGROUND: Smoking behaviour is of central concern to enhanced population health and there is a recognized need for detailed information concerning many different aspects of this behaviour. This paper assesses the utility of three large-scale national surveys according to their ability to provide such information. These are the General Household Survey (GHS), the British Household Panel Survey (BHPS) and the Health Survey for England (HSE). METHODS: A number of important data items are identified and a comparative content analysis of the surveys is undertaken to indicate whether these items are present or absent in each source. RESULTS: Although current smoking status and consumption are covered in all three data sets, the GHS and the HSE provide information on many other aspects of the behaviour. Information on the major contextual variables can be found in each of the surveys. All sources can be used within a repeated cross-sectional analytical framework, and limited population-based longitudinal analyses can be undertaken with the GHS and the HSE. The BHPS theoretically opens up potential for a true longitudinal analysis of the cohort dynamics of individual smoking behaviour. Issues of place are best explored using the HSE, where the geographical information is most detailed. CONCLUSIONS: The paper highlights the importance of all three data sets as statistical modelling resources for investigating patterns of smoking prevalence. Although the advantages of the panel approach are noted for cohort-based longitudinal studies, there still remain some problems in undertaking these analyses because of the small number of BHPS waves carried out to date.

Adolescent↗
PubMed2001

Stature as a prognostic factor in cystic fibrosis survival.

OBJECTIVE/DESIGN: This study provides a longitudinal analysis of the National Cystic Fibrosis Patient Registry to determine if height-for-age percentile would be a useful predictor of survival. SUBJECTS: All patients were selected from the national registry (n = 19,000) maintained by the Cystic Fibrosis Foundation's 115 accredited Cystic Fibrosis Care Centers in the United States. Inclusion in our analysis required that subjects were born between 1980 and 1989; had a minimum of 4 records each; the subject was alive at age 7; and the subject had a recorded height measurement at age 7 to 8 (n = 2,773). STATISTICAL ANALYSIS: The Cox proportional hazards model was used to compare height-for-age with survival. We recorded whether a subject was less than the 5th National Center for Health Statistics (NCHS) percentile at age 5 and then in a separate analysis at age 7. Cohort effect was coded as "1" if they were born before 1982 and "0" otherwise. RESULTS: Stature is a significant prognostic indicator of survival. The relative hazard associated with height below the 5th NCHS percentile for age was significant for both males and females. In males at age 5 the relative hazard was 2.9, [95% confidence interval (CI) 1.23, 6.91; P < .02] and at age 7 it was 6.3 (95% CI 2.1, 18.8; P < .001). The relative hazard in females at age 5 was 4.3 (95% CI 2.4, 7.3; P < .0001) and at age 7 was 5.8 (95% CI 2.5, 13.1; P < .0001). APPLICATION: These highly significant relative hazard values strongly suggest that shorter patients are much more likely to die before taller patients. The dietetic professional should consider using height-for-age as an effective screening tool to identify patients at risk. Based on these data, short stature should not be considered benign to patients with cystic fibrosis. The CF team, clinicians, family, and patients need work together to maximize linear growth through medical and nutritional intervention.

Age Factors↗
PubMed2005

Central corneal thickness and progression of the visual field and optic disc in glaucoma.

AIMS: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. METHODS: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. RESULTS: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. CONCLUSIONS: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

Adult↗
PubMed2005

Analysis of the effect of highly active antiretroviral therapy during acute HIV-1 infection on HIV-specific CD4 T cell functions.

BACKGROUND: It has been reported that antiretroviral therapy (HAART) during acute HIV-1 infection may rescue HIV-1-specific CD4 T cell responses. OBJECTIVE: To determine the duration of this preserved response by investigating the long-term effects of HAART during acute infection on HIV-specific CD4 T cell function related to possible immune control during subsequent therapy interruption. METHODS: A longitudinal analysis followed HIV-specific CD4 T cell reactivity in 17 individuals with well-documented acute HIV-1 infection where five out of 11 HAART-treated patients stopped therapy and six were untreated. Peripheral blood mononuclear cells were stimulated with overlapping peptide pools derived from Gag and Nef. Production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by CD4 T cells was analysed together with proliferative responses. RESULTS: Absolute numbers, but not percentages, of Gag-specific IFN-gamma-, IL-2- or IFN-gamma/IL-2-producing CD4 T cells were increased in treated compared with untreated individuals up to 2 years after seroconversion. HAART during acute HIV-1 infection was associated with lower viral load but did not result in increased proliferation of HIV-specific CD4 T cells. One out of five individuals who discontinued therapy showed evidence for immune control. However, patients who failed to control viraemia also had measurable proliferative HIV-specific CD4 T cell responses and preserved numbers of cytokine-producing CD4 T cells. CONCLUSIONS: Early HAART during acute HIV-1 infection resulted in higher numbers of HIV-specific IFN-gamma- and IL-2-producing CD4 T cells, but this preservation in four out of five patients was not associated with control of viraemia upon treatment interruption.

Acute Disease↗