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Biomedical subjects

T Harris

Publications and source records attributed to T Harris.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effect of Pneumovax II vaccination in high-risk individuals on specific antibody and opsonic capacity against specific and non-specific antigen.

Pneumovax II vaccine has been used in many countries including the UK for adults in high-risk groups to prevent pneumococcal infections. However, its effectiveness has been a controversial issue. In this study, the specific antibody concentration and opsonic capacity of serum against specific and non-specific antigens were measured in 16 high-risk adults vaccinated with Pneumovax II. The results indicated that 38% of these individuals could make an antibody response to specific antigens post-vaccination; vaccination had a clear effect in increasing the opsonic capacity of serum against specific pneumococcal antigen (S14 serotype) in 31% of patients, but did not have any effect against non-specific antigen. The specific antibody concentration did not significantly positively correlate with the opsonic capacity of serum. Therefore, it is concluded that the protective effect of Pneumovax II vaccination against a specific serotype in high-risk individuals will only be around 30%.

Adult↗
PubMed2002

Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging.

OBJECTIVE: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. METHODS: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). RESULTS: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. CONCLUSIONS: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.

Aged↗
PubMed2002

Limitations of Pneumovax as a detection antigen in the measurement of serotype-specific antibodies by enzyme-linked immunosorbent assay.

BACKGROUND: Measurement of antibody responses to polysaccharide antigens is regarded as an important assessment of an individual's ability to respond to carbohydrate antigens. The currently used assays for the measurement of pneumococcal-specific antibody use the multi-serotype vaccine Pneumovax as the detection antigen. METHODS: An equal potency enzyme-linked immunosorbent assay (ELISA) system was used to compare the measurement of serotype-specific antibody with the multi-serotype assay. RESULTS: Our results show that the concentration of specific antibody to Pneumovax is not related to the concentration of antibody to the individual serotypes. Neither is any correlation found between the antibody concentrations to any of the three single serotypes investigated, to the mixture of the three serotypes or to Pneumovax. CONCLUSION: We conclude that the measurement of the concentration of the specific antibody to the mixed serotypes present in Pneumovax has serious limitations when used to evaluate the protection acquired from Pneumovax immunization against any specific serotype.

Antibodies, Bacterial↗
PubMed2002

The promise of structural genomics in the discovery of new antimicrobial agents.

Structural Genomics stands out among the emerging fields of proteomics since it influences the drug discovery process at so many points. Recent developments in protein expression technologies, x-ray crystallography and NMR spectroscopy provide the essential elements for high-throughput structure determination platforms. Bioinformatics methods to interrogate the resulting data will provide comprehensive, genome-wide databases of protein structure. Genomic sequencing and methods for high-throughput expression and protein purification are furthest advanced for microbial genes and so these have been the early targets for structural genomics initiatives. The information will be invaluable in understanding gene function, designing broad-spectrum small molecule inhibitors and in better understanding drug-host interactions.

Anti-Bacterial Agents↗
PubMed2001

Absolute kinetic characterization of 17-beta-estradiol as a radical-scavenging, antioxidant synergist.

We directly measured the absolute reactivity of 17-beta-estradiol (E2) and several phenolic model compounds for E2 toward t-butoxy radical (t-BuO*) by nanosecond time-resolved optical spectroscopy. Compared to other phenols, E2 is a moderate, but not strong deactivator of oxyradicals. The absolute bimolecular rate constant for H-atom transfer from E2 to t-BuO* is 1.3 +/- 0.3 x 10(9) M(-1) x s(-1) (23 degrees C, benzene). We estimate the O-H bond strength of 17-beta-estradiol to be approximately 85 +/- 2 kcal/mol and calculate the reaction rate constant of E2 toward peroxy radical to be 10(5) M(-1) x s(-1) at 37 degrees C. The conjugate phenoxy radical of 17-beta-estradiol, E2O*, is unusually reactive toward alpha-tocopherol and ascorbate by H-atom transfer in homogeneous solution (10(8)-10(9) M(-1) x s(-1)). Our findings suggest that E2 functions in vivo as a highly localized, synergistic biological antioxidant. This may partly explain the clinical effectiveness of ovarian steroids in delaying the manifestations of Alzheimer's Disease as well as in protecting against cardiovascular pathologies. In the absence of complementary antioxidant synergists, E2O* is expected to be a pro-oxidant.

Alzheimer Disease↗
PubMed2001

Comparison of a virtual microscope laboratory to a regular microscope laboratory for teaching histology.

Emerging technology now exists to digitize a gigabyte of information from a glass slide, save it in a highly compressed file format, and deliver it over the web. By accessing these images with a standard web browser and viewer plug-in, a computer can emulate a real microscope and glass slide. Using this new technology, the immediate aims of our project were to digitize the glass slides from urinary tract, male genital, and endocrine units and implement them in the Spring 2000 Histology course at the University of Iowa, and to carry out a formative evaluation of the virtual slides of these three units in a side-by-side comparison with the regular microscope laboratory. The methods and results of this paper will describe the technology employed to create the virtual slides, and the formative evaluation carried out in the course. Anat Rec (New Anat) 265:10-14, 2001.

Computer-Assisted Instruction↗
PubMed2001

Weight loss from maximum body weight among middle-aged and older white women and the risk of hip fracture: the NHANES I epidemiologic follow-up study.

Although weight loss increases bone loss and hip fracture risk in older women, little is known about the relation between weight loss in middle-aged women and subsequent hip fracture risk. The objective of this study was to determine the association between weight loss from reported maximum body weight in middle-aged and older women and the risk of hip fracture. Data were from a nationally representative sample of 2180 community-dwelling white women aged 50-74 years from the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey (NHEFS). In this prospective cohort study, incident hip fracture was ascertained during 22 years of follow-up. The adjusted relative risks associated with weight loss of 10% or more from maximum body weight were elevated for both middle-aged (RR 2.54; 95% CI 1.10-5.86) and older women (RR 2.04; 95% CI 1.37-3.04). For both ages combined, women in the lowest tertile of body mass index at maximum who lost 10% or more of weight had the highest risk of hip fracture (RR 2.37; 95% CI 1.32-4.27). Weight loss from maximum reported body weight in women aged 50-64 years and 65-74 years increased their risk of hip fracture, especially among those who were relatively thin. Weight loss of 10% or more from maximum weight among both middle-aged and older women is an important indicator of hip fracture risk.

Aged↗
PubMed2001

The Cardiff Depression Study: a sib-pair study of dysfunctional attitudes in depressed probands and healthy control subjects.

BACKGROUND: Current cognitive theories propose that depression develops as a result of the interaction between dysfunctional cognitive schemata and environmental stressors. There is also consistent evidence of a substantial genetic contribution to depression. This study examines the familiality and stability of dysfunctional attitudes and attempts to distinguish whether they reflect trait vulnerability to depression or the state of being depressed. METHOD: The 24-item Dysfunctional Attitude Scale (DAS-24) was completed by 108 depressed probands and their nearest-aged siblings and 105 healthy control probands and their nearest-age siblings, at the time of a semi-structured clinical interview and 10-12 months later. Subjects also completed self-report measures of depressed mood on both occasions. RESULTS: Measures of clinical depression were significantly correlated with DAS scores. At retest, DAS scores remained elevated despite improvement in mood, giving support for earlier findings, that dysfunctional attitudes remain active following recovery. The dependency subscale (DAS-D) of the DAS showed modest familiality, although there were no significant differences for DAS-D scores between the two groups of siblings. In a multiple regression analysis, current mood-state was the overwhelming predictor of DAS scores. However for DAS-D, gender as well as current mood influenced scores on this subscale. CONCLUSION: Although there was modest evidence for temporal stability and familiality for some DAS-24 subscale scores, dysfunctional attitudes were predominantly influenced by current low mood, and therefore reflect the state of being depressed rather than a familial vulnerability trait underpinning depression.

Adolescent↗
PubMed2001

The Cardiff sib-pair study: suicidal ideation in depressed and healthy subjects and their siblings.

Depression is associated with high rates of suicidal ideation, which varies in intensity from transient thoughts of wishing to be dead to the making of plans and, Finally, to attempts to kill oneself. There is limited evidence from family, twin, and adoption studies that completed suicide is familial and has a genetic etiological component. However, it is unclear whether suicidal ideation is also familial. The familiality of suicidal ideation has been examined in the subjects who participated in the Cardiff Depression Study, namely, 108 depressed probands. their nearest-aged siblings, and 105 healthy control subjects and their siblings. The study showed that 66% of depressed subjects had experienced suicidal ideation in the week prior to the interview, and that this was significantly associated with recurrent illness. Suicidal ideation was not shown to be familial. However, somewhat surprisingly, 6% of healthy, never-depressed subjects admitted to having had transient suicidal thoughts. Suicidal ideation was significantly associated with high neuroticism and psychoticism scores and severe threatening life events.

Adult↗
PubMed2001

Measuring fitness in healthy older adults: the Health ABC Long Distance Corridor Walk.

OBJECTIVES: The Health ABC Long Distance Corridor Walk (LDCW) was designed to extend the testing range of self-paced walking tests of fitness for older adults by including a warm-up and timing performance over 400 meters. This study compares performance on the LDCW and 6-minute walk to determine whether the LDCW encourages greater participant effort. DESIGN: Subjects were administered the LDCW and 6-minute walk during a single visit. Test order alternated between subjects, and a 15-minute rest was given between tests. SETTING: The Baltimore Veterans Affairs Medical Center. PARTICIPANTS: Twenty volunteers age 70 to 78. MEASUREMENTS: The LDCW, consisting of a 2-minute warm-up walk followed by a 400-meter walk and a 6-minute walk test were administered using a 20-meter long course in an unobstructed hallway. Heart rate (HR) and blood pressure (BP) were recorded at rest and before and after all walks. RESULTS: All 20 subjects walked a faster pace over 400 meters than for 6 minutes, in which the mean distance covered was 402 meters. From paired t-tests, walking speed was faster (mean difference = 0.23 m/sec; P < .001), and ending HR (mean difference = 7.6 bpm; P < .001) and systolic BP (mean difference = 8.3 mmHg; P = .024) were greater for the 400-meter walk than for the 6-minute walk. Results were independent of test order and subject fitness level. CONCLUSIONS: Providing a warm-up walk and using a target distance instead of time encouraged subjects to work closer to their maximum capacity. This low-cost alternative to treadmill testing can be used in research and clinical settings to assess fitness and help identify early functional decline in older adults.

Aged↗
PubMed2001

The association of bone mineral density and depression in an older population.

OBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population. DESIGN: Population-based, cross-sectional study. SETTING: Study subjects were participants in the Cardiovascular Health Study (CHS), a longitudinal, long-term, follow-up study, at the University of California Davis (Sacramento, California) and the University of Pittsburgh (Pittsburgh, Pennsylvania) clinical centers. PARTICIPANTS: A random sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS. MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry (DEXA), after adjustment for multiple covariates, was compared with depression evaluated with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for osteoporosis were compared in depressed and nondepressed participants. Potential correlates were entered into a regression model. Depression scores were compared in normal, osteopenic, and osteoporotic individuals. RESULTS: Sixteen percent of participants were clinically depressed; 9% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm2 lower in those with clinical depression. High CES-Dm scores were associated with lower BMD (P < .001) when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen use, gender, race, smoking and drinking. When stratified by race, this remained true for all Caucasians (P < .01), all African Americans (P < .05), and when stratified by race and gender the association remained only for all Caucasian women (P < .001). In women and Caucasian men there was an increase in depression scores among individuals with osteoporotic-range BMDs. CONCLUSIONS: A significant association was found between BMD and depressive symptoms after adjustment for osteoporosis risk factors. In Caucasians, depressive symptoms were associated with both osteoporotic and osteopenic levels of BMD. Causality cannot be ascribed, with only one measurement of BMD. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression.

Absorptiometry, Photon↗
PubMed2001

Weight change in old age and its association with mortality.

OBJECTIVES: Previous studies of weight change and mortality in older adults have relied on self-reported weight loss, have not evaluated weight gain, or have had limited information on health status. Our objective was to determine whether 5% weight gain or loss in 3 years was predictive of mortality in a large sample of older adults. DESIGN: Longitudinal observational cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand seven hundred fourteen community-dwelling older adults, age 65 and older. MEASUREMENTS: Weight gain or loss of 5% in a 3-year period was examined in relationship to baseline health status and interim health events. Risk for subsequent mortality was estimated in those with weight loss or weight gain compared with the group whose weight was stable. RESULTS: Weight changes occurred in 34.6% of women and 27.3% of men, with weight loss being more frequent than gain. Weight loss was associated with older age, black race, higher weight, lower waist circumference, current smoking, stroke, any hospitalization, death of a spouse, activities of daily living disability, lower grip strength, and slower gait speed. Weight loss but not weight gain of 5% or more was associated with an increased risk of mortality that persisted after multivariate adjustment (Hazard ratio (HR) = 1.67, 95% CI = 1.29-2.15) and was similar in those with no serious illness in the period of weight change. Those with weight loss and low baseline weight had the highest crude mortality rate, although the HR for weight loss was similar for all tertiles of baseline weight and for those with or without a special diet, compared with those whose weight was stable. CONCLUSIONS: This study confirms that even modest decline in body weight is an important and independent marker of risk of mortality in older adults.

Aged↗
PubMed2001

Recent developments in understanding the psychosocial aspects of depression.

Recent advances in the psychosocial understanding of depression have elaborated an already complex aetiological model. Yet each new strand seems to echo, and forge links with, themes uncovered earlier, making it easier to see what is common about the 'final common pathway' to onset. For example, although recent stressors have for some time been recognised predictors of onset, new insights about the origins of these stressors have overlapped with other new work on depression and childhood adversity to identify a group who 'produce' their own severe life events in response to early negative experience. And recent studies have traced the well-known gender difference in depressive prevalence to differences both in gender role involvement with the provoking life events and in styles of support-seeking/ support-giving. What emerges is the powerlessness, loss and humiliation characterising the final pathway. Both naturalistic studies and controlled trials suggest that psychosocial situations reflecting the opposite emotional meaning, that is new hope, characterise a similar pathway to remission. Conclusions speculate whether awareness of this pathway might enhance purely pharmacological treatment.

Adult↗
PubMed2001

Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals.

The catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) are believed to be active constituents of green tea accounting for the reported chemoprevention of certain cancers. The molecular mechanisms by which the measured low concentrations (ca. micromolar) of catechins in humans can reduce the incidence of carcinogenesis is not clear. Using an in vitro plasmid DNA system and radiolytically generating reactive oxygen species (ROS) under constant scavenging conditions, we have shown that all four catechins, when present at low concentrations, ameliorate free radical damage sustained by DNA. A reduction in both prompt DNA single-strand breaks and residual damage to the DNA bases, detected by subsequent incubation with the DNA glycosylases formamidopyrimidine (FPG), endonuclease III (EndoIII) and 5' AP endonuclease exonuclease III (ExoIII), was observed. EGCG was found to be the most active of the catechins, with effects seen at micromolar concentrations. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from catechins to ROS-induced radical sites on the DNA. These results support an antioxidant role for catechins in their direct interaction with DNA radicals.

Catechin↗
PubMed2001

General practice survey of the management of chickenpox: appropriate targeting of antiviral therapy.

BACKGROUND: A working party of specialists and GPs recently published their consensus on recommended treatments for chickenpox. These are the closest to recommended guidelines available in the UK. They offer a rational basis for targeting those groups most at risk of complications with antiviral treatment. OBJECTIVES: The aim of the present study was to compare current practice by GPs in the management of chickenpox, particularly in targeting of antiviral therapy, with the working party recommendations. METHOD: A questionnaire survey was conducted of all GP principals within a single London Health Authority Responses to nine chickenpox clinical scenarios were compared with the working party recommendations. RESULTS: The response rate was (69.2%) 227/328. In five of the nine scenarios, fewer than 70% of GPs selected the correct response according to the recommendations. There was both underuse and overuse of antivirals according to the recommendations, with only 42% (96/227) advising oral antivirals or referral for an asthmatic treated with oral steroids 1 month previously, and 24% (53/221) advising oral antivirals 3 days after the chickenpox rash appeared. CONCLUSIONS: The results suggest some high risk groups may be being undertreated with oral antivirals and there may be considerable use of oral antivirals in situations where they are of no proven benefit.

Adult↗