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PubMed1996

The cardinal features of cognitive and noncognitive dysfunction and the differential efficacy of tacrine in Alzheimer's disease patients.

The Alzheimer's Disease Assessment Scale (ADAS), frequently used in clinical trials to assess overall pathology of Alzheimer's disease (AD), comprises two subscales. The cognitive subscale (ADAS-COG) consists of 11 items, and the noncognitive subscale consists of 9 items. Factor analyses were carried out on ADAS-COG and ADAS-NONCOG item scores from the most recent and largest (n = 663) placebo-controlled, multicenter, 30-week study (970-61) of tacrine in patients with AD conducted by the clinical research group at Parke-Davis Pharmaceutical Research. Through factor analyses the primary dimensions of variation in the ADAS-COG and ADAS-NONCOG were defined. Obliquely rotated three principal factors of ADAS-COG and three principal factors of ADAS-NONCOG have been interpreted as three cardinal features of cognitive function corresponding to memory, language, and praxis, and three cardinal features of noncognitive function corresponding to agitation, depression, and lack of concentration. Reliably defined factors of ADAS-COG enabled comparisons of longitudinal changes in cognitive dysfunction. Factor scores at week 30, adjusted to baseline factor scores, were used to compare the effects of tacrine with those of placebo on cognitive cardinal features. Additionally, the effect of concurrent depression on cardinal features of cognitive dysfunction was evaluated by gender.

Aged↗

PubMed2005

Interstudy reproducibility of quantitative perfusion cardiovascular magnetic resonance.

PURPOSE: To determine the interstudy reproducibility of quantitative first-pass perfusion cardiovascular magnetic resonance with comparison of 2 previously described analysis techniques. There is no published data on the interstudy reproducibility of perfusion cardiovascular magnetic resonance which can be used to determine the significance of longitudinal changes in myocardial perfusion after pharmacologic or therapeutic interventions with defined sample sizes. METHODS: Sixteen subjects (7 normal volunteers, 9 patients with coronary artery disease) had rest and adenosine stress perfusion cardiovascular magnetic resonance studies on two separate visits. A short axis slice was studied on each visit using a fast low-angle shot sequence. The global and regional myocardial perfusion reserve indices were calculated using 2 methods: model based constrained deconvolution with the Fermi function, and normalized upslopes. Reproducibility was defined as the standard deviation of the measurement differences, divided by the mean (coefficient of variation). RESULTS: The reproducibility of global myocardial perfusion reserve indices was 21% in normal volunteers, which was similar to that in patients with coronary artery disease (CAD) (23%, p = .88). The reproducibility of regional myocardial perfusion reserve indices was 28% (p = .45 vs. global analysis). The reproducibility of global MPRi was superior with Fermi deconvolution compared with normalized upslopes (21% vs. 41%, p = .02). CONCLUSION: At this stage of clinical development, the reproducibility of quantitative perfusion cardiovascular magnetic resonance is good, and superior using Fermi deconvolution in preference to upslope analysis.

Adenosine↗

PubMed2003

Trunk muscles in persons with hemiparetic stroke evaluated with computed tomography.

OBJECTIVES: To analyse side difference in bilateral trunk muscles in patients with hemiparetic stroke, to relate it with impairment and disability variables and to evaluate longitudinal changes. METHODS: In a sample of 83 inpatients with hemiparetic stroke undergoing rehabilitation, we measured the cross-sectional area of the paravertebral muscle and thigh muscles using computed tomography at admission and discharge. Classifying them by paravertebral muscle side difference (group I: contralateral > ipsilateral; II: contralateral = ipsilateral; III: contralateral < ipsilateral) we analysed group difference in the Stroke Impairment Assessment Set, the Functional Independence Measure and walk velocity. RESULTS: In contrast to thigh muscles, the paravertebral muscle cross-sectional area was significantly greater on the side contralateral to the brain lesion. Discharge paravertebral muscle cross-sectional area increased significantly from admission values. The Stroke Impairment Assessment Set, Functional Independence Measure and walk velocity were significantly lower in group I. CONCLUSION: The contralateral paravertebral muscle cross-sectional area was larger than the ipsilateral ones, and this was related to the degree of impairment and functional limitations.

Adult↗

PubMed2026

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p = 0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference +28.0%, 95% CI 4.2-47.7; Fisher p = 0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks; +0.205 at 12 months; both p < 0.01). A modest between-group beta-diversity difference at 6 months (R2 = 0.035; p = 0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans↗

PubMed2004

Internalizing, social competence, and substance initiation: influence of gender moderation and a preventive intervention.

Using latent growth curve modeling, the current study investigated gender moderation of the longitudinal pathways from internalizing to both social competency (i.e., social assertiveness) and the initiation of substance use (i.e., tobacco, alcohol, marijuana), as well as the effect of a preventive intervention on that process. Rural Midwestern adolescents who were participating in a school-based preventive intervention study were an average of 12.3 years old at the pretest assessment conducted in 1998. A latent growth curve comparison analysis found that internalizing was related inversely to initial levels of social assertiveness skill among girls; further, internalizing was related positively to substance use initiation growth trajectories among girls. Girls who participated in the preventive intervention demonstrated a slower increase over time in substance use initiation and a faster increase in social assertiveness. Gender moderation of the impact of internalizing and social assertiveness on substance use initiation and response to the intervention, as well as the utility of latent growth curve modeling in the study of longitudinal change, are discussed.

Adolescent↗

PubMed1999

Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis.

Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients. Microbiology results from two multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with decreased tobramycin susceptibility. Clinical response was examined to determine whether current susceptibility standards are applicable to aerosolized administration. Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans; however, isolation of Candida albicans and Aspergillus species did increase. Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group, there was no evidence of selection for the most resistant isolates to become most prevalent. The definition of resistance for parenteral administration does not apply to inhaled tobramycin: too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to define a new break point on the basis of clinical response.

Administration, Inhalation↗

PubMed2001

Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeficiency virus during highly active antiretroviral therapy.

Longitudinal changes in neutralizing antibody responses against autologous human immunodeficiency virus (HIV) type 1 were investigated in 19 chronically infected patients who were undergoing highly active antiretroviral therapy (HAART). Reconstitution of or increase in neutralization activity was observed in 4 of 19 patients during HAART, but neutralization activity was more or less unchanged in most patients. Three of 4 patients with increased neutralization activity had low-level viral rebound ("blips") during HAART. No correlation was found between neutralization activity and HIV-specific CD4+ T cell frequencies. There was a correlation between neutralization activity and CD4+ T cell counts. The reconstituted antibody represented limited cross-reactivity, compared with that of preexisting antibody. Binding activity to monomeric gp120, V2, and V3 peptides was reduced. Both prolonged virus suppression, for CD4+ T cell recovery, and blips, for stimulation of the immune system in vivo, may be required for development of neutralizing antibody in vivo.

Adult↗

PubMed2002

Types of alternative medicine used by patients with breast, colon, or prostate cancer: predictors, motives, and costs.

OBJECTIVE: Assess predictors and costs of various types of alternative medicine used by adult patients with cancer. DESIGN, LOCATION, SUBJECTS: Telephone survey of 356 patients with colon, breast, or prostate cancer identified from the population-based Cancer Surveillance System of western Washington. RESULTS: Overall, 70.2% of patients used at least one type of alternative medicine, with 16.6% seeing alternative providers, 19.1% using mental/other therapy, and 64.6% taking dietary supplements. Compared to males, females were five times more likely to see an alternative provider and about twice as likely to use mental therapies or supplements (p < 0.05 for all). Older patients were less likely to use mental/other therapy. Higher education (but not income) was associated with use of all types of alternative medicine. Patients with multiple medical treatments were two times more likely to take dietary supplements compared to patients having only surgery (p < 0.01). Varying by the type of alternative therapy, 83%-97% of patients reported that they used alternative medicine for general health and well-being while 8% to 56% reported use for treatment of cancer. Almost all patients reported that the alternative therapy improved their well-being. Expenditures for alternative medicine averaged $68 per user per year, but ranged from $4 to $14,659. CONCLUSIONS: Given the high prevalence of use and that patients believed that alternative medicine improved their well-being, clinicians should show an open mind toward these treatment choices and encourage frank discussion. Familiarity and some knowledge regarding use of alternative medicine is important in cases where interactions between conventional and alternative medicine may occur. It is also important to identify potential patient needs for mental health support beyond conventional care and support patients who want to make healthful lifestyle changes. Longitudinal investigations are urgently needed to investigate associations of alternative medicine use with survival and quality of life in patients with cancer.

Adult↗

PubMed1986

Zinc requirements and zinc intakes of breast-fed infants.

Longitudinal changes in dietary zinc requirements for infants at different levels of net absorption were estimated using a factorial approach. Apart from variations in net absorption, the zinc needed for new lean body mass is the major determinant of requirements. As growth velocity declines progressively, estimated zinc requirements for growth and for replacement of urine and sweat losses decrease from a high for male infants of 780 micrograms/day at 1 mo to 480 micrograms/day in the 5th mo and then remain quite constant through the 1st yr. Calculated percentage absorption of zinc from human milk necessary to meet estimated requirements increases with duration of lactation. For infants of mothers whose zinc intake approximated 25 mg/day the calculated percentage absorption remained within plausible limits. It is suggested that the progressive decrease in milk zinc concentrations provides a mechanism for conserving maternal zinc while meeting infant needs.

Absorption↗

PubMed2004

Bone mass is recovered from lactation to postweaning in adolescent mothers with low calcium intakes.

BACKGROUND: Adolescent mothers may be at increased risk of irreversible bone loss during pregnancy and lactation, particularly when calcium intake is low. OBJECTIVE: Longitudinal changes in bone mass from lactation to postweaning were evaluated in 10 adolescent mothers aged 15-18 y who habitually consumed <500 mg Ca/d. DESIGN: Total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), and lumbar spine bone mineral density (LSBMD) were measured at lactation (6-24 wk postpartum) and after weaning (12-30 mo postpartum). Serum hormones (intact parathyroid hormone, estradiol, and prolactin), serum calcium, and markers of bone turnover [urinary N-telopeptide cross-linking region of type I collagen (NTx) and plasma activity of bone alkaline phosphatase] were measured at lactation. RESULTS: TBBMC, total calcium content, TBBMD, and LSBMD increased from lactation to postweaning (P < 0.01). TBBMD and LSBMD were, respectively, 3.6% and 9.7% lower than predicted at lactation and 0.3% and 4.8% lower than predicted in the postweaning period. The increase in age-matched TBBMD adequacy was correlated with the time after resumption of menses (r = 0.86, P < 0.01). Calcium accretion from lactation to postweaning correlated negatively with estradiol (r = -0.86) and prolactin (r = -0.69) and positively with intact parathyroid hormone (r = 0.72) and NTx (r = 0.84) measured at lactation (P < 0.05). CONCLUSIONS: It appears that adolescent mothers with habitually low calcium intakes recover from lactation-associated bone loss after weaning. The rate of bone accretion, however, may not be sufficient to attain peak bone mass at maturity. Hormones regulating bone turnover during lactation may influence bone recovery in adolescent mothers.

Adolescent↗

PubMed2006

Bone calcium turnover during pregnancy and lactation in women with low calcium diets is associated with calcium intake and circulating insulin-like growth factor 1 concentrations.

BACKGROUND: Few data exist on longitudinal changes in bone calcium turnover rates across pregnancy and lactation. OBJECTIVE: Our aim was to characterize calcium kinetic variables and predictors of these changes across pregnancy and early lactation in women with low calcium intakes. DESIGN: Stable calcium isotopes were administered to 10 Brazilian women during early pregnancy (EP; weeks 10-12 of gestation), late pregnancy (LP; weeks 34-36 of gestation), and early lactation (EL; 7-8 wk postpartum). Multicompartmental modeling was used to assess the rates of bone calcium turnover in relation to calcium intakes and circulating concentrations of parathyroid hormone (PTH), insulin-like growth factor 1, and 1,25-dihydroxyvitamin D. RESULTS: Rates of bone calcium deposition increased significantly from EP to LP (P = 0.001) and were significantly associated with serum PTH during LP (P < or = 0.01). Rates of bone calcium resorption were also higher during LP and EL than during EP (P < or = 0.01) and were associated with both PTH (P < or = 0.01) and IGF-1 (P < or = 0.05) during LP but not during EL. Net balance in bone calcium turnover was positively associated with dietary calcium during EP (P < or = 0.01), LP (P < or = 0.01), and EL (P < or = 0.01). The mean (+/-SD) calcium intake was 463 +/- 182 mg/d and, in combination with insulin-like growth factor 1, explained 68-94% of the variability in net bone calcium balance during pregnancy and lactation. CONCLUSIONS: Net deficits in bone calcium balance occurred during pregnancy and lactation. Increased dietary calcium intake was associated with improved calcium balance; therefore, greater calcium intakes may minimize bone loss across pregnancy and lactation in women with habitual intakes of <500 mg calcium/d.

Adult↗

PubMed2001

Well-being as a moving target: measurement equivalence of the Bradburn Affect Balance Scale.

Although the Bradburn Affect Balance scale (ABS) is a frequently used two-factor indicator of well-being in later life, its measurement and invariance properties are not well documented. We examined these issues using confirmatory factor analyses of cross-sectional (adults ages 54-87 years) and longitudinal data from the Victoria Longitudinal Study. Stability of the positive and negative affect factors was moderate across a 3-year period. Overall, factor loadings for positive affect items were invariant over time with the exception of the pleased item. Negative affect items were time invariant. However, age-group comparisons between young-old and old-old groups revealed age differences in loadings for the upset item at Time 1. Finally, gender groups differed in loadings for the top of the world and going your way items. Thus a pattern of partial measurement equivalence characterized item response to the ABS. Our results suggest that group comparisons and longitudinal change in ABS scale scores of positive and negative affect should be interpreted with caution.

Affect↗

PubMed2003

Exposure and reactivity to negative social exchanges: a preliminary investigation using daily diary data.

Negative social exchanges have the potential to detract from well-being in later life, but the factors that influence older adults' vulnerability to such exchanges remain poorly understood. Two dimensions of vulnerability, exposure and reactivity, were investigated using daily diary data collected at two time points from a sample of community-residing older adults (N = 129). Three categories of predictors were examined: individual characteristics, life stress, and social network characteristics. Greater exposure to negative social exchanges was related to greater life stress and to less supportive networks. Greater reactivity was related to lower self-esteem, less supportive networks, less satisfying friendships and family relationships, and surprisingly, to less life stress. Longitudinal changes in exposure and reactivity were related to changes in friendship satisfaction, the positive functions performed by the network, and health status. The findings suggest that personal characteristics and life circumstances play a role in influencing older adults' vulnerability to negative social exchanges.

Adult↗

PubMed2004

Retirement transitions and spouse disability: effects on depressive symptoms.

OBJECTIVES: The purpose of this study was to investigate the effects of type of retirement (forced, early, abrupt) and spouse's disability on longitudinal change in depressive symptoms. METHODS: The analyses rely on Waves 1-4 of the Health and Retirement Survey (N = 2,649). Generalized estimating equations models with bootstrapped standard errors and adjustment for survey design and non-independence of dyad members estimate effects of retirement, type of retirement, and spouse's disability on depressive symptoms, controlling for relevant covariates. RESULTS: The results suggest that depressive symptoms increase when retirement is abrupt and perceived as too early or forced. Women retirees who stopped employment and were either forced into retirement or perceived their retirement as too early report significantly more depressive symptoms with increasing spouse activities of daily living (ADLs) limitations. There is no similar effect for men. In contrast, for working retirees who retired on time, depressive symptoms decrease with increasing spouse ADLs. DISCUSSION: These results highlight the importance of retirement context on postretirement well-being. They suggest that both type of retirement transition and marital contexts such as spouse's disability influence postretirement well-being, and these effects differ by gender.

Activities of Daily Living↗

PubMed1988

A longitudinal study of energy expenditure in males during steady-state exercise.

Our purpose was to investigate longitudinal changes in gross energy expenditure (GEE) of 20 middle-aged and older men during submaximal exercise in 1969 and in 1985. GEE (kcal/min) was estimated using the caloric equivalent for each liter of oxygen consumed at the measured respiratory exchange ratio during submaximal exercise. The men performed a 10-min submaximal cycle ergometer exercise test at a power output (PO) of 100 W. Pedalling frequency was 50 rpm. Results showed a significant 5.9% decrease in GEE (p less than .01) from 8.5 +/- 0.8 (M +/- SD) kcal/min in 1969 to 8.0 +/- 0.4 (M +/- SD) Kcal/min in 1985. In addition, the effects of chronological age and leisure time physical activity on GEE were assessed and found to be nonsignificant, although a significant decrease in GEE over time (p less than .02) was observed in both groups. The present results support a decrease in GEE in middle-aged and older men over the 16-year time period. Furthermore, this decrease in GEE persisted regardless of chronological age or leisure time physical activity status.

Adult↗

PubMed2004

Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.

Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target.

Administration, Inhalation↗

PubMed1987

Specific effects of weight loss, protein deficiency and energy deprivation on the water and electrolyte composition of young rats.

Specific effects of weight loss, protein deficiency and energy deprivation on the water and electrolyte content of the body were studied. Longitudinal changes in total body Na and Cl were measured by neutron activation analysis in young rats fed either a low protein diet (LP) ad libitum or a control diet in restricted amounts (ER). Total body Ca was determined to monitor growth of skeletal mass. Four balance periods were defined to represent various stages of protein or energy deprivation. The chemical composition of the rats was determined at the end of the study and compared with that of rats killed at the start of the study. Changes in body composition of LP rats were attributable chiefly to wasting of body cell mass. There was no retention of Na and Cl until severe hypoalbuminemia and edema developed after chronic protein deprivation; at this time, Na and Cl were retained in the same proportion as their molar ratio in extracellular fluid (ECF). The resulting increase in ECF volume accounted for the high total body water values in LP rats. Energy restriction to approximately 80% of maintenance requirements for 20 d resulted in Na retention in a compartment distinct from either the Cl or Ca space. With prolonged ER, there was preferential wasting of cell mass and adipose tissue but relative preservation of the ECF compartment; there was no net retention of Na and Cl, and hydration of fat-free mass was normal. The differences in the body compositions of ER and LP rats suggested that protein and energy deprivation can have separate effects on Na and Cl homeostasis that are distinct from changes induced by a loss of cell mass.

Animals↗

PubMed1998

Evaluation of dual-energy X-Ray absorptiometry for body-composition assessment in rats.

Recent developments in dual-energy X-ray absorptiometry (DXA) have rendered feasible the determination of whole-body composition in small laboratory animals by directly measuring fat, fat-free and mineral bone masses. Our aim was to evaluate this technique by cross-calibrating the DXA method with the carcass chemical analysis in a heterogeneous population of nondiabetic Wistar and diabetic GK rats (21 animals were used for precision error and reproducibility determinations and 26 were used for accuracy studies). We report that this technique is optimized for weights >200 g. The respective CV for lean mass, fat mass and percentage of fat mass determined in short-term or transversal studies was 1.1 +/- 0.1, 3.0 +/- 1.3 and 3. 1 +/- 0.4% (mean +/- SD) respectively. Further, this technique is valid for rats weighing from 130 to 200 g by using three successive scans. In longitudinal studies, daily calibrations significantly increased the percentage of fat mass CV to 6.6 +/- 3.3%, but it was significantly decreased to 3.0 +/- 2.7% by the use of triplicate scans. The accuracy for DXA was excellent in reference to the chemical extraction technique (r2 = 0.95 for percentage of fat mass, P < 0.0001), using an adjustment factor of 0.75 (limits of agreement between the two methods for percentage of fat mass = -1.7-2.3%). Mimicry of longitudinal changes in body composition with intraperitoneal injections of saline solution demonstrated a satisfactory detection of body component changes (</=2% of error for each final component analyzed, when increasing total lean mass by 11. 8%). We conclude that DXA is appropriate for rat whole-body composition determination, allowing reliable long-term follow-up of individual animals for the first time.

Absorptiometry, Photon↗