Biomedical subjects

R G Thomas

Publications and source records attributed to R G Thomas.

At least 19 recordsLinked to original sources

PubMed2003

Idebenone treatment fails to slow cognitive decline in Alzheimer's disease.

OBJECTIVE: To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD). METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were over age 50 with a diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores between 12 and 25. Subjects were treated with idebenone 120, 240, or 360 mg tid, each of which was compared with placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog) and a Clinical Global Impression of Change (CGIC). Secondary outcome measures included measurements of activities of daily living, the Behavioral Pathology in Alzheimer's Disease Rating Scale, and the MMSE. RESULTS: Five hundred thirty-six subjects were enrolled and randomized to the four groups. Except for a slight difference in age, there were no differences in patient characteristics at baseline. For the primary outcome measures, there were no significant overall differences between the treatment groups in the prespecified four-group design. In an exploratory two-group analysis comparing all three treated groups combined with placebo, drug-treated patients performed better on the ADAS-Cog in both the intent-to-treat (ITT) and completers analyses. There were no differences in the CGIC scores for the ITT or completers analyses in either the four-group or the two-group analyses. There were no overall differences on any of the secondary outcome measures in any of the analyses. CONCLUSION: Idebenone failed to slow cognitive decline in AD that was of sufficient magnitude to be clinically significant.

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PubMed2003

Relationships among shoot sinks for resources exported from nodal roots regulate branch development of distal non-rooted portions of Trifolium repens L.

Two manipulative experiments tested hypotheses pertaining to the correlative control exerted by nodal roots on branch development of the distal non-rooted portion of Trifolium repens growing clonally under near-optimal conditions. The two experiments, differing in their pattern of excision to manipulate the number of branches formed at the first 9-10 phytomers distal to the youngest nodal root, each found that after 20 phytomers of growth the total number of lateral branches formed on the primary stolon remained between five and seven regardless of where the branches formed along the stolon. Additional treatments established that nodal roots influenced branch development via relationships among shoot sinks for the root-supplied resources rather than through variation in the supply of such resources induced by fluctuations in photosynthate supply to roots from branches. Regression analysis of data pooled from treatments of both experiments confirmed that shoot-sink relationships for root- supplied resources controlled the branching processes on the non-rooted portion of plants. A disbudding treatment, which removed all the apical and axillary buds present on basal branches, but left other branch tissues intact, increased branch development of the apical region in the same way as did complete excision of the basal lateral branches. The apical buds and the elongation processes occurring immediately proximal to the buds were thus identified as strong sinks for the root-supplied resources. Such results suggest that branch development on the non-rooted shoot portion distal to the youngest nodal root is regulated by competition among sinks for root-derived resources, of limited availability, necessary for the processes of elongation of axillary buds and the primary stolon apical bud.

Homeostasis↗

PubMed2003

Steroid-induced elevation of glucose in Alzheimer's disease: relationship to gender, apolipoprotein E genotype and cognition.

Glucose and insulin may play an important role in the pathophysiology and symptomatology of Alzheimers disease (AD), and prior studies suggest interactions among glucose, insulin, gender and apolipoprotein E genotype. We analyzed the relationship between steroid-induced glucose elevation and gender, presence of the apolipoprotein E epsilon 4 (APOE-4) allele and cognition using data from a multicenter trial of prednisone therapy in AD. The low-dose prednisone regimen (initial dose: 20 mg/day, maintenance dose: 10 mg/day) caused a moderate increase in random blood glucose (mean post-baseline glucose 115 mg/dl). There was a significant interaction between rise in glucose, gender and presence of the APOE-4 allele. There was no important relationship between glucose and cognitive function at baseline or with prednisone treatment. Meta-analysis including data from three other AD trials showed a small influence of random blood glucose on cognitive scores. These results support a relationship between gender, apolipoprotein E genotype and glucose metabolism, but do not indicate that mild changes in glucose have an important impact on cognitive function.

Alleles↗

PubMed2002

Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals.

BACKGROUND: The growing propensity to diagnose AD in individuals with very mild cognitive impairment increases the danger of false-positive diagnostic errors. Unfortunately, there is little systematically acquired information about the accuracy of the AD diagnosis in very mildly impaired patients. OBJECTIVE: To determine the accuracy of the diagnosis of AD in very mildly impaired patients and to identify objective measures that effectively distinguish these patients from elderly normal controls (NC). METHODS: Consecutive patients with Mini-Mental State Examination scores of > or = 24 who received a clinical diagnosis of AD were evaluated annually for at least 3 years. The initial diagnosis was verified or refuted by autopsy or by information obtained in subsequent evaluations. Initial neuropsychological test scores of verified AD patients were compared with those of NC subjects to identify effective diagnostic measures. RESULTS: The diagnosis of AD was confirmed in 98 of 110 (89%) very mildly impaired patients (33/36 by autopsy, 65/74 by disease progression). The diagnosis was inaccurate in 12 patients (11%): Seven were subsequently diagnosed with other neurologic disorders, and five were ultimately found to be normal. Neuropsychological measures of delayed recall, verbal fluency, and global cognitive status (i.e., Mattis Dementia Rating Scale) provided excellent sensitivity (> or = 96%) and specificity (> or = 93%) for differentiating between very mildly impaired AD patients and NC subjects. CONCLUSIONS: When comprehensive assessment procedures are employed, AD can be diagnosed with reasonably high accuracy in very mildly impaired individuals. However, the dementia evaluation should be repeated after approximately 1 year to ensure the accuracy of the initial diagnosis.

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PubMed2002

A developmentally based categorization of branching in Trifolium repens L.: influence of nodal roots.

This study describes the successive stages of development of branches from axillary buds in fully rooted plants of Trifolium repens grown in near optimal conditions, and the way in which this developmental pathway differs when nodal root formation is prevented as plants grow out from a rooted base. Cuttings of a single genotype were established in a glasshouse with nodal root systems on the two basal phytomers and grown on so that nodal rooting was either permitted (+R) or prevented (-R). In +R plants, axillary tissues could be assigned to one of four developmental categories: unemerged buds, emerged buds, unbranched lateral branches or secondarily branched lateral branches. In -R plants, branch development was retarded, with the retardation becoming increasingly pronounced as the number of -R phytomers on the primary stolon increased. Retarded elongation of the internodes of lateral shoots on -R plants resulted in the formation of a distinct fifth developmental category: short shoots (defined as branches with two or more leaves but with mean internode length equal to, or less than, 10% of that of the immediately proximal internode on the parent stolon) which had reduced phytomer appearance rates but retained the potential to develop into lateral branches. Transfer of +R plants to -R conditions, and vice versa, after 66 d demonstrated that subsequent branch development was wholly under the control of the youngest nodal root present, regardless of the age and number of root systems proximal to it.

Plant Roots↗

PubMed2001

Metabolic syndrome and ischemic heart disease in elderly men and women.

Associations between metabolic syndrome components and prevalent ischemic heart disease (IHD) were investigated in a cross-sectional, community-based study of elderly men (n = 1,015) and women (n = 1,259) in Rancho Bernardo, California, in 1984-1987. In both sexes, there were significant positive associations between IHD defined by resting electrocardiogram criteria and age, systolic blood pressure, fasting and postchallenge hyperglycemia, total cholesterol/high density lipoprotein cholesterol (HDL cholesterol) ratio, and triglycerides and an inverse significant association with HDL cholesterol. High collinearity and interactions between serum insulin and metabolic syndrome variables were accounted for by uncorrelated principal components identified by factor analysis. In both men and women, three uncorrelated principal components were identified, representing a central metabolic factor (body mass index, fasting and 2-hour serum insulin, high serum triglycerides, and low HDL cholesterol), a glucose factor, and a blood pressure factor. In a multivariate model with age and sex, all three factors were significantly associated with IHD by electrocardiogram criteria; central metabolic factor (odds ratio (OR) = 1.6, p = 0.001), glucose factor (OR = 1.4, p < 0.001), blood pressure factor (OR = 1.2, p = 0.005), age (10 years) (OR = 1.8, p < 0.001), and female sex (OR = 0.5, p < 0.02). Similar results were obtained in analyses using clinically manifest IHD as the outcome. These results support the thesis that the metabolic syndrome exerts effects through different risk factors by different mechanisms.

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PubMed2001

Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease.

This study describes two well-characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference-whether AD patients with higher levels of behavioral disturbance (n = 148) differ from less disturbed AD patients (n = 235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized 'diversity of behaviors' and 'frequency' with respect to the item-level responses on the Cohen-Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD.

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PubMed2000

Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.

BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.

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PubMed2000

A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's Disease Cooperative Study.

BACKGROUND: Laboratory and epidemiologic studies suggest that anti-inflammatory/immunosuppressive therapy may be useful in the treatment of AD. In preliminary studies, a regimen of low to moderate dose prednisone was found to suppress peripheral inflammatory markers without adverse effects in subjects with AD. METHODS: We conducted a randomized, placebo-controlled multicenter trial to determine whether prednisone treatment slowed the rate of cognitive decline in AD. The active treatment regimen consisted of an initial dose of 20 mg of prednisone daily for 4 weeks tapered to a maintenance dose of 10 mg daily for 1 year, followed by gradual withdrawal during an additional 16 weeks. The primary outcome measure was the 1-year change in the cognitive subscale of the AD Assessment Scale. RESULTS: A total of 138 subjects were randomized to the drug and placebo groups. There was no difference in cognitive decline between the prednisone and placebo treatment groups in the primary intent-to-treat analysis, or in a secondary analysis considering completers only. Subjects treated with prednisone showed behavioral decline compared with those in the placebo group. CONCLUSION: A low-dose regimen of prednisone is not useful in the treatment of AD.

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PubMed2000

Unaltered cytochrome oxidase, glutamate dehydrogenase and glutaminase activities in platelets from patients with sporadic amyotrophic lateral sclerosis--a study of potential pathogenetic mechanisms in neurodegenerative diseases.

Sporadic Amyotrophic Lateral Sclerosis (SALS) is a fatal neurologic disease characterized by degeneration of motor neurons in the spinal cord, brainstem and cortex. While familial cases of ALS exist, the sporadic form accounts for the majority of adult-onset cases. It has been hypothesized that the neurodegenerative mechanisms underlying SALS might arise from glutamate-mediated excitotoxicity and mitochondrial dysfunction. Studies on autopsied SALS spinal cord and brain have reported decreased cytochrome oxidase activity, decreased astrocytic glutamate-transporter protein, and alterations of glutamate levels and glutamate metabolizing enzyme activities. We conjectured that if alterations in glutamate metabolism and cytochrome oxidase activity occur in the SALS central nervous system these alterations may also be manifested in peripheral tissues such as platelets in living SALS patients. In this study we compared the activities of cytochrome oxidase, citrate synthase, glutamate dehydrogenase and glutaminase in platelets from SALS and control subjects. We found that there were no differences in any of the enzyme activities measured between the two groups. Our data argue against generalized ubiquitous biochemical alterations of these enzymes in SALS patients.

Blood Platelets↗

PubMed2000

Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy.

Individuals given a series of words to memorize normally show better immediate recall for items from the beginning and end of the list than for mid-list items. This phenomenon, known as the serial position effect, is thought to reflect the concurrent contributions of secondary and primary memory, respectively, to recall performance. The present study compared the serial position effects produced on Trial 1 of the California Verbal Learning Test (CVLT) in mildly demented (N = 25; M MMSE = 20.0) and very mildly demented (N = 25; M MMSE = 25.5) patients with Alzheimer's disease (AD), and age- and education-matched normal control (NC) participants (N = 50). In addition, the serial position effects of the very mildly demented AD patients were compared to those of patients with a transient, circumscribed amnesia arising from a prescribed series of electroconvulsive therapy (ECT) treatments for the relief of depressive illness (N = 11). While the NC group exhibited the typical serial position effect, AD patients recalled significantly fewer words than NC participants overall, and exhibited a significantly reduced primacy effect (i.e., recall of the first 2 list items) with a normal recency effect (i.e., recall of the last 2 list items). Patients with circumscribed amnesia due to ECT were as impaired as the very mildly demented AD patients on most standard CVLT measures of learning and memory, but exhibited primacy and recency effects, which were within normal limits. These results suggest that a reduction in the primacy effect, but not the recency effect, is an early and ubiquitous feature of the memory impairment of AD. It is not, however, a necessary feature of all causes of memory impairment.

Adult↗

PubMed2000

Risk factors for pulmonary disease due to culture-positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners.

The aim of this study was to determine risk factors for disease due to nontuberculous mycobacteria (NTM) compared to those due to Mycobacterium tuberculosis in South African gold miners with pulmonary mycobacterial disease. A case/control study comparing tuberculosis and NTM cases amongst all patients with a positive sputum mycobacterial culture in 1995 was carried out. The 51 cases of disease due to NTM and 425 tuberculosis cases were similar with regard to age, education, home region, smoking habits and percentage of CD4 cells. After adjustment for confounders, those with NTM were more likely to have had previous tuberculosis treatment (odds ratio (OR) 3.61; 95% confidence interval (CI) 1.9-6.9), have worked longer underground (p-value for trend=0.05) or have evidence of silicosis (OR 12.6; 95% CI 2.2-71) and were less likely to drink regularly (OR 0.12; 95% CI 0.02-0.93) than patients with tuberculosis. In patients with disease due to NTM, 35.3% were human immunodeficiency virus-positive compared with 48.8% of tuberculosis patients (p=0.2) and an estimated 21% overall in the mines at the time of the study. Previous tuberculosis treatment, silicosis and duration of underground work are even more strongly associated with disease due to nontuberculous mycobacteria than with tuberculosis. Attempts to reduce the incidence of all pulmonary mycobacterial disease in this community should address recognized risk factors and ensure that those with tuberculosis are diagnosed, treated and cured.

Adult↗

PubMed2000

Prevalence of symptoms on the CERAD behavior rating scale for dementia in normal elderly subjects and Alzheimer's disease patients.

The authors sought to define "abnormal" levels for total scores on the CERAD Behavioral Rating Scale for Dementia (BRSD) and for 37 BRSD items by comparing 242 patients with Alzheimer's disease (AD) and 64 normal elderly control subjects (NEC). BRSD total scores for NEC ranged as high as 52 (out of a maximum 167), and although item prevalence rates were higher for AD patients, not all of these differences were significant. Many symptoms were observed in < or = 10% of AD subjects. Lower Mini-Mental State Examination scores were not consistently associated with lower or higher levels of endorsement across all items. Over 6 and 12 months, endorsement rates were relatively stable for both groups. The authors conclude that assessment of behavior in long-term studies will be needed to quantify "abnormal" levels, and that item-level BRSD information could be important in clinical trials.

Aged↗

PubMed2000

Qualifying change: a method for defining clinically meaningful outcomes of change score computation.

OBJECTIVES: To identify clinically meaningful change in longitudinal assessment. DESIGN: A novel approach that qualifies item-level change over time by the degree to which it is clinically meaningful. SETTING: The classification method was tested by applying it to changes over 12 months in the frequency ratings of the items of a behavioral assessment instrument that is used commonly in clinical trials with Alzheimer's disease (AD) patients. PARTICIPANTS: Responses from a cohort of 235 well characterized, community-dwelling subjects with AD were analyzed by this method. MEASUREMENTS: The approach allowed us to describe the proportions of items that emerged, ceased, worsened, and improved between the baseline and 12-month visits. RESULTS AND CONCLUSIONS: One-year change in the behavioral symptoms of persons with AD was used to exemplify the methodology. This approach can be used in other populations and with other measurements and was designed for analyses of clinical trial data. This method uses item-level changes to generate global impressions of clinically meaningful change; it also facilitates the definition of change that can be used in the clinical setting.

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PubMed1999

Age-related macular degeneration: a randomized clinical trial of a self-management intervention.

The purpose of this study was to conduct a randomized clinical trial to assess whether a self-management group intervention can improve mood, self-efficacy, and activity in people with central vision loss due to age-related macular degeneration (AMD). Ninety-two elderly patients with AMD (average age = 79) from a university ophthalmology clinic were randomly assigned to the self-management intervention (n = 44) or to a wait-list (n = 48). All patients were legally blind in at least one eye. The intervention consisted of 6 weekly 2-hour group sessions providing education about the disease, group discussion, and behavioral and cognitive skills training to address barriers to independence. All participants eventually completed the intervention allowing pre-post comparisons for all patients. The battery of measures included the Profile of Mood States (POMS); Quality of Well-Being Scale; and assessments of self-efficacy, participation in activities, and use of vision aids. Participants' initial psychological distress was high (mean total POMS = 59.72) and similar to distress experienced by other serious chronic illness populations (e.g. cancer, bone marrow transplant). Analysis of covariance testing the primary hypothesis revealed that intervention participants experienced significantly (p = .04) reduced psychological distress (pre mean = 61.45; post mean = 51.14) in comparison with wait-list controls (pre mean = 57.72; post mean = 62.32). Intervention participants also experienced improved (p = .02) self-efficacy (pre mean = 70.16; post mean = 77.27) in comparison with controls (pre mean = 67.71; post mean = 69.07). Further, intervention participants increased their use of vision aids (p < .001; pre mean = 3.37, post mean = 6.69). This study demonstrates that a relatively brief behavioral intervention can substantially reduce psychological distress and increase self-efficacy in elderly adults experiencing vision loss due to macular degeneration. Self-management intervention appears to improve mood, self-efficacy, and use of vision aids, further enhancing the lives of poorly sighted individuals with AMD.

Adaptation, Psychological↗

PubMed1999

Mini-Mental State Examination and Mattis Dementia Rating Scale performance differs in Hispanic and non-Hispanic Alzheimer's disease patients.

Little information exists regarding the performance of Spanish-speaking versus English-speaking patients with Alzheimer's disease (AD) on the Mini-Mental State Examination and the Mattis Dementia Rating Scale. In an attempt to identify culturally biased MMSE items or DRS subscales, we matched Spanish-speaking Hispanic and English-speaking non-Hispanic White community-dwelling AD patients by their MMSE scores and examined specific items within each scale. Our findings indicate that Hispanic AD patients perform significantly worse than non-Hispanics in terms of total DRS score, scores on the DRS subscales for Conceptualization and Memory, and on serial subtraction (or backward spelling item) of the MMSE. While mildly to moderately demented Hispanic and non-Hispanic patients obtained comparable scores on the DRS, severely impaired Spanish-speaking participants obtained considerably lower DRS scores than their English-speaking counterparts. The discrepancy in the DRS scores of the severely impaired Hispanic and non-Hispanic examinees might reflect a cultural bias in the test or educational differences between the groups. Alternatively, the DRS may be more sensitive than the MMSE for detecting severe cognitive impairment in Hispanic patients.

Aged↗

PubMed1999

Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease.

Nondemented older adults genotyped for the Apolipoprotein E (ApoE) epsilon4 allele (n = 43) were neuropsychologically compared to participants without a copy of the epsilon4 allele (n = 90). At baseline, the groups did not differ on age, education, gender, or global cognitive status. ApoE-epsilon4 participants demonstrated significantly poorer mean performances on delayed recall, but no significant group differences emerged on attention, language, constructional skills, psychomotor speed, or executive function. Significantly more ApoE-epsilon4 participants developed probable or questionable Alzheimer's disease (AD) compared with non-epsilon4 participants, suggesting that the group differences resulted from a preponderance of preclinical AD cases within the epsilon4 group and not from a direct influence of ApoE genotype on cognition. Cox proportional hazards analysis, adjusting for age, years of education, and global cognitive status, revealed that ApoE-epsilon4 allele status and measures of recall performance were significant and independent predictors of conversion to AD. Results support the importance of specific episodic memory changes and possession of the ApoE-epsilon4 allele in the preclinical detection of AD.

Aged↗

PubMed1999

A normative study of Nelson's (1976) modified version of the Wisconsin Card Sorting Test in healthy older adults.

A modified version of the Wisconsin Card Sorting Test (mWCST) proposed by Nelson (1976) was administered to 229 healthy community-dwelling older adults, composed of 97 men and 132 women, ages 45 to 91. Investigating the impact of demographic factors such as age, education, and gender on mWCST performance, results indicated that mWCST performance was significantly affected by both age and education. Unlike the standard WCST, however, gender did not significantly influence mWCST performance. Because demographic factors appear to exert a significant influence on mWCST performance of normal older adults, demographically-corrected norms were calculated according to the procedure described by Heaton, Grant, and Matthews (1991). In addition, longitudinal analysis of mWCST performance revealed that significantly fewer nonperseverative errors were committed at retest approximately one year later. Number of categories completed and perseverative errors did not appear to demonstrate significant practice effects in this sample. Accounting for demographic influences and the inspection of practice effects on serial administration of the mWCST may improve upon its sensitivity and specificity for use in the clinical assessment of executive function in older adults.

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