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Biomedical subjects

M O'Grady

Publications and source records attributed to M O'Grady.

At least 19 recordsLinked to original sources
PubMed2001

A study design to investigate the effect of intense Tai Chi in reducing falls among older adults transitioning to frailty.

This paper describes the study design, methodological considerations, and baseline characteristics of a clinical trial to determine if intense (48 weeks, twice per week) Tai Chi practice can reduce the frequency of falls among older adults transitioning to frailty compared to a wellness education program. Twenty facilities will be stratified on socioeconomic status and facility type and randomly assigned to one of the two interventions. Secondary outcome measurements include variables related to function, behavior, and the biomechanics of movement. This study is unique because it represents an effort to offer a novel physical intervention to a large sample of transitional frail adults, a population that has received few formal exercise interventions. In addition to bringing the interventions into facilities, a 1-year follow-up is also included to assess rates of change in outcome measurements.

Accidental Falls↗
PubMed2001

Associations of demographic, functional, and behavioral characteristics with activity-related fear of falling among older adults transitioning to frailty.

OBJECTIVES: To determine, in a cohort of older individuals transitioning to frailty (defined by Speechley and Tinetti, 1991) who have previously fallen, whether there are significant associations between demographic, functional, and behavioral characteristics and activity-related fear of falling, using both the Falls Efficacy Scale (FES) and the Activities-Specific Balance Confidence Scale (ABC). DESIGN: Baseline cross-sectional analysis in a prospective cohort intervention study. SETTING: Twenty independent senior living facilities in Atlanta. PARTICIPANTS: Seventeen male and 270 female subjects (n = 287), age 70 and older (mean +/- standard deviation, 80.9 +/- 6.2), with Mini-Mental State Examination score > or = 24, transitioning to frailty, ambulatory (with or without assistive device), medically stable, and having fallen in the past year. MEASUREMENTS: Activity-related fear of falling was evaluated with the FES and ABC Scale. Because of the comparable data derived from each scale, associations with functional measures-related analyses were expressed using the latter. Depression was measured by Center for Epidemiological Studies Depression Scale. Functional measurements included timed 360 degrees turn, functional reach test, timed 10-meter walk test, single limb stands, picking up an object, and three chair stands. RESULTS: No statistically significant association was found between activity-related fear of falling and age. For the proposed activities, about half (ABC, 48.1%; FES, 50.1%) of the subjects were concerned about falling or showed lack of confidence in controlling their balance. A statistically significant inverse correlation was found between FES and ABC (r = -0.65; P < .001). African-American subjects showed more activity-related fear of falling than did Caucasians (odds ratio (OR): 2.7 for ABC; 2.1 for FES). Fearful individuals were more likely to be depressed and more likely to report the use of a walking aid than were nonfearful individuals. Fear of falling was significantly correlated to all of the functional measurements (P < .05). In a multivariable logistic regression model, depression, using a walking-aid, slow gait speed, and being an African-American were directly related to being more fearful of falling. CONCLUSIONS: Activity-related fear of falling was present in almost half of this sample of older adults transitioning to frailty. The significant association of activity-related fear of falling with demographic, functional, and behavioral characteristics emphasizes the need for multidimensional intervention strategies to lessen activity-related fear of falling in this population.

Accidental Falls↗
PubMed2001

Assessment of lithium dilution cardiac output as a technique for measurement of cardiac output in dogs.

OBJECTIVES: To determine agreement of cardiac output measured by use of lithium dilution cardiac output (LiDCO) and thermodilution cardiac output (TDCO) techniques in dogs and to determine agreement of low- and high-dose LiDCO with TDCO. ANIMALS: 10 dogs (7 males, 3 females). PROCEDURE: Cardiac output was measured in anesthetized dogs by use of LiDCO and TDCO techniques. Four rates of cardiac output were induced by occlusion of the caudal vena cava, changes in depth of anesthesia, or administration of dobutamine. Lithium dilution cardiac output was performed, using 2 doses of lithium chloride (low and high dose). Each rate of cardiac output allowed 4 comparisons between LiDCO and TDCO. RESULTS: 160 comparisons were determined of which 68 were excluded. The remaining 92 comparisons had values ranging from 1.10 to 12.80 L/min. Intraclass correlation coefficient (ICC) between low-dose LiDCO and TDCO was 0.9898 and between high-dose LiDCO and TDCO was 0.9896. When all LiDCO determinations were pooled, ICC was 0.9894. For determinations of cardiac output < 5.0 L/min, ICC was 0.9730. Mean +/- SD of the differences of TDCO minus LiDCO for all measurements was -0.084+/-0.465 L/min, and mean of TDCO minus LiDCO for cardiac outputs < 5.0 L/min was -0.002+/-0.245 L/min. CONCLUSIONS AND CLINICAL RELEVANCE: The LiDCO technique is a suitable substitute for TDCO to measure cardiac output in dogs. Use of LiDCO eliminates the need for catheterization of a pulmonary artery and could increase use of cardiac output monitoring, which may improve management of cardiovascularly unstable animals.

Anesthesia↗
PubMed2000

Therapeutic and physical fitness exercise prescription for older adults with joint disease: an evidence-based approach.

Aging with joint disease does necessarily result in chronic pain, adoption of a sedentary lifestyle, and functional dependency. Several randomized controlled trials clearly show that regular exercise does not exacerbate pain or accelerate disease progression. On the contrary, these studies suggest that exercise training may increase the physiologic reserve and reduce the risk for functional dependency in older adults with joint disease. The goals for an exercise program should be directed toward increasing flexibility, muscle strength, endurance, and cardiovascular fitness. An exercise training program that is tailored specifically to an older adult's physical limitations may achieve these goals, and by optimizing patient safety lead to improve long-term exercise compliance.

Aged↗
PubMed2000

Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle.

PURPOSE: To examine the effects of prolonged systemic administration of diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective indices of exercise-induced muscle damage in humans. METHODS: Fifty-four volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized double-blind, placebo-controlled trial. To achieve steady-state tissue levels, either placebo or diclofenac was orally administered two times a day for 27 consecutive days. A strenuous 20-min stepping exercise program, about which the subjects were unfamiliar, was conducted on day 15. Creatine kinase (CK) activities were measured immediately before the exercise session and on days 16, 18, and 27. Vastus lateralis muscle samples were obtained immediately before exercise and on day 27 for subsequent histological characterization of muscle inflammation. RESULTS: The preexercise muscle samples revealed no difference in muscle damage between the two groups. However, the postexercise muscle samples showed that the diclofenac-treated group demonstrated less muscle tissue damage than placebo-treated subjects (P = 0.002). The administration of diclofenac also resulted in a significant lowering of post-/pre-exercise CK ratios on days 18 (P = 0.03) and 27 (P = 0.02) compared with the placebo group, an indirect finding that supports the possibility of diclofenac reducing exercise-induced muscle damage. CONCLUSION: These findings demonstrate preadministration of diclofenac (in accordance with tissue half-life pharmacokinetics) significantly reduces quantitative indices of exercise-induced skeletal muscle damage in human muscle.

Administration, Oral↗
PubMed1999

Neonatal cytomegalovirus exposure decreases prepulse inhibition in adult rats: implications for schizophrenia.

The goal of these studies was to determine whether neonatal viral exposure leads to a deficit in information processing in adulthood. To accomplish this, rats were infected neonatally with rat cytomegalovirus, and acoustic startle responses were measured when rats were 120 days old. Acoustic startle was elicited by using a 118-decibel (dB) white noise alone or after a prepulse 10 dB above background (65 dB); responses were measured after an injection of saline or the dopamine agonist apomorphine. Response amplitudes after the pulse alone were not significantly altered by either viral exposure or apomorphine. Responses of animals exposed to the prepulse before the pulse were approximately 10% of that after the pulse alone and did not differ between control or virus-exposed animals injected with saline. Animals injected with apomorphine exhibited a greater startle response than animals injected with saline, and control and virus-exposed rats injected with apomorphine differed in the magnitude of their responses. Apomorphine attenuated responses after the prepulse, and virus-exposed animals exhibited more than twice the attenuation than non-virus-exposed animals. Analysis of prepulse inhibition, calculated from the acoustic startle data, indicated that although viral exposure alone did not significantly affect information processing, when virus-injected rats were exposed to apomorphine, a significant 38% decrease in prepulse inhibition was apparent. Findings demonstrate that rats infected neonatally with rat cytomegalovirus exhibit a deficit in sensorimotor gating upon dopamine stimulation, supporting a possible link between viral infection and schizophrenia.

Acoustic Stimulation↗
PubMed1998

A family study of anterior mitral leaflet thickness and mitral valve prolapse.

To determine whether mitral valve prolapse (MVP) with or without mitral leaflet thickening (> or =5 mm) represents distinct heritable conditions, 13 patients with MVP with leaflet thickening and their relatives were compared with 67 patients with MVP with normal leaflets and their relatives. The 2 groups of relatives had similar mitral leaflet thicknesses and similar long-term outcome, arguing against the existence of a distinctive subtype of MVP characterized by increased mitral leaflet thickness.

Adult↗
PubMed1997

Unique gene organization: alternative splicing in Drosophila produces two structurally unrelated proteins.

The Ub80 gene in eukaryotes produces a ubiquitin fusion protein in which ubiquitin is fused in frame to a tail protein (Redman and Rechsteiner, 1988; Finley et al., 1989; Barrio et al., 1994). The tail protein is incorporated into the ribosome, and ubiquitin is thought to act as a chaperone. The DUb80 gene of Drosophila melanogaster was cloned by Barrio et al. (1994) and contains a 5'-untranslated exon, followed by a large intron and then the first coding exon. We report that the large intron of DUb80 contains an open reading frame, which produces a 259-aa protein (IP259) that is conserved in eukaryotes from yeast to mammals. Transcription of the DUb80 and IP259 mRNAs begins at the same start sites. However, alternate splicing of the primary transcript produces two structurally unrelated proteins. This is the second reported instance of two structurally unrelated proteins being produced via alternate splicing, suggesting that this form of genomic organization may be more common than previously thought.

Amino Acid Sequence↗
PubMed1997

Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses.

Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV and systolic, diastolic and mean blood pressures (SBP, DBP, and MBP, respectively), central venous pressure (CVP), mean pulmonary artery pressure, heart rate (HR), CO, and arterial and mixed venous blood gases were measured at the following times: baseline, 2, 5, and 10 min post-SAL or GLY; and 2, 5, 10, 15, 30, 45 and 60 min post-XYL. Determination of cardiac index (CI), stroke index (SI), left ventricular work, systemic vascular resistance (SVR), DO2, oxygen uptake, and oxygen extraction ratio were made at the same time. Gastrointestinal (GI) motility was evaluated by four-quadrant auscultation for 24 h post-XYL. Statistical analysis of continuous variables was carried out using ANOVA for repeated measures and Wilcoxon's rank-sum test for non-parametric data. In GLY treated horses, HR, SBP, MBP, DBP, CI, DO2 and mixed venous oxygen tension were significantly higher up to 30 min after XYL (P < or = 0.02) while CVP and SI were significantly lower 2 and 5 min post-XYL, respectively. In both groups, GI motility as assessed by auscultation was virtually abolished for an hour, with a non-significant tendency for the decrease in motility to last longer in the GLY/XYL group. None of the treated horses developed abdominal discomfort. No significant difference was observed in the other variables. The study shows that 2.5 micrograms/kg GLY premedication reduces the cardiovascular depression caused by 1 mg/kg XYL, without adversely affecting GI motility.

Adjuvants, Anesthesia↗
PubMed1996

Lack of association between mitral valve prolapse and history of rheumatic fever.

To determine whether rheumatic fever is associated with mitral valve prolapse (MVP) diagnosed by echocardiography, records from 561 subjects participating in a prospective family study were reviewed. The prevalence of a history of rheumatic fever by modified Jones criteria was determined in 92 probands and 112 affected relatives or spouses with M-mode and two-dimensional echocardiographic findings of MVP, accompanied in most instances by classic auscultatory findings, and in 357 family members without MVP. The prevalence of rheumatic fever was 5.4% in both MVP sub-groups and 2.2% in the family members without MVP (p<0.05 vs the combined MVP group). However, people with a history of rheumatic fever were older than the remaining subjects (48 +/- 17 vs 36 +/- 20 years, p<0.01) as expected because of the decline in rheumatic fever in the twentieth century, and subjects with MVP were older than subjects without MVP (39 +/- 16 vs 34 +/- 22 years, p<0.01). Multiple logistic regression showed that after the independent relation of older age with a positive history of rheumatic fever (p<0.01) was taken into account, there was a trend toward a lower likelihood of previous rheumatic fever associated with MVP (odds ration 0.42, p=0.07). These results do not support either a true association or a causal role of rheumatic fever in the pattern of mitral leaflet motion and auscultatory abnormalities in adults, for which the term MVP is generally used.

Adult↗
PubMed1993

Compensatory downregulation of myocardial Ca channel in SR from dogs with heart failure.

In this study we tested the hypothesis that the ryanodine-binding Ca-release channel activity and density of the sarcoplasmic reticulum (SR) terminal cisternae were decreased in congestive heart failure (CHF) that occurs spontaneously in doberman pinschers or experimentally with rapid ventricular pacing of mongrels. We used a novel, sensitive, and easy-to-perform microassay and demonstrated a 50% decrease in activity of the myocardial SR Ca pump and a 75% reduction in SR Ca-release channel activity in CHF. Decreases in Ca channel content were associated with increases in net Ca sequestration. 45Ca-release experiments from passively loaded SR terminal cisternae and ryanodine-binding studies confirmed a 53-68% downregulation of the Ca-release channel activity. As a consequence of release channel downregulation, there was partial restoration of net Ca sequestration activity in dogs with CHF and complete compensation in dogs with mild cardiac dysfunction. Deterioration of Ca cycling correlated with deterioration of myocardial performance, apparently due to decreased Ca-adenosinetriphosphatase (ATPase) pump and not Ca channel content. One-half the reduction in Ca-release activity could be attributed to decreased Ca sequestration and one-half to decreased Ca channel density. Downregulation of Ca channel content decreases the amplitude of the Ca cycle and maximizes the downregulation of Ca pumps that may occur. Although these adaptations may reduce cellular energy expenditure, they are likely to render the myocardium more susceptible to fatigue and failure.

Animals↗
PubMed1993

Clinical pathologic profiles of dogs and turkeys with congestive heart failure, either noninduced or induced by rapid ventricular pacing, and turkeys with furazolidone toxicosis.

Characteristic alterations in the serum and urine biochemical profiles of Doberman Pinschers with congestive heart failure (CHF) resulting from idiopathic dilated cardiomyopathy were determined. We compared these alterations with those observed in 2 other models of CHF: rate overload induced by rapid ventricular pacing in dogs, and biventricular hypertrophy and dilatation induced in turkey poults by furazolidone toxicosis. Serum and urine biochemical changes in both models of CHF in dogs were mild to moderate in degree, and were moderately consistent. They could be attributed to secondary neurohumoral, hepatic, and renal effects of heart failure. The most marked and consistent changes observed were mildly decreased anion gap that developed, in part, because of decreased serum sodium concentration, moderately increased catecholamine concentrations, moderate lactaciduria, hyposthenuria, and mildly increased urea concentrations and liver enzyme activities. In birds with furazolidone cardiomyopathy, we observed mild increases in serum urate concentration, liver and muscle enzyme activities, but moderately increased sodium concentration with decreased chloride concentration. In the pacing and furazolidone models, in which CHF was rapidly induced, moderate to marked hypoproteinemia was attributable to decreases in albumin and globulin concentrations. Using the avian model we found that the hypoproteinemia could be largely attributed to blood volume expansion, and to a lesser extent, inanition. Development of hypoalbuminemia during rapid ventricular pacing and furazolidone treatment may contribute to the effects of rate overload or drug toxicity in the pathogenesis of CHF, because hypoalbuminemia may contribute to altered hemodynamics and neuroendocrine system activation. Our data indicate that clinical biochemical analysis of serum and urine may be useful for assessing progression of CHF.

Animals↗
PubMed1992

Rapid, simple and sensitive microassay for skeletal and cardiac muscle myoglobin and hemoglobin: use in various animals indicates functional role of myohemoproteins.

A novel, simple, rapid, sensitive and reproducible microassay is described for determination of myoglobin and hemoglobin content of myocardial and skeletal muscle biopsy specimens from various mammals, birds and fish. As little as 50 mg of tissue is needed and myoglobin concentrations lower than 1 mg% can be detected. Myoglobin and hemoglobin are separated at alkaline pH by ammonium sulfate extraction followed by ultrafiltration. Heme content is determined by absorption of the Soret band when the hemoprotein extract is visibly colored or more sensitively by its peroxidase activity when the extract has low color. The heme reacts with tertiary-butyl hydroperoxide and orthotolidine to generate a blue color. Hemoglobin content is correlated with myoglobin content and is related to aerobic capacity and blood flow to the tissue. Myoglobin content varied over 5 orders of magnitude up to 7 per cent of the weight of tissue, whereas hemoglobin content varied over 2 orders of magnitude up to 6 per cent of tissue weight. Myoglobin content is increased in species with high basal metabolic rate, high physical activity, prolonged diving capacity, fatigue resistance, and red muscle, whereas it is decreased in white muscle, iron-deficient animals, animals with sedentary lifestyles, and in animals and tissues with small fiber diameters such as avian or fish hearts.

Animals↗
PubMed1992

Myocardial myoglobin deficiency in various animal models of congestive heart failure.

Myoglobin is known to protect the mechanical function of the heart from hypoxia by acting as a sarcoplasmic oxygen reservoir and shuttle. We postulated a role for myoglobin in the pathogenesis of congestive heart failure. Several models of congestive heart failure were employed to test the hypothesis, including spontaneous inherited dilated cardiomyopathy in Doberman Pinschers, and heart failure produced by rapid ventricular pacing in dogs, volume overload in chickens and furazolidone toxicity in turkeys. Myocardial myoglobin was decreased by approximately 50% for all models (P less than 0.05). In Doberman Pinschers dogs which are predisposed to the development of dilated cardiomyopathy and have mild subclinical depression of cardiac performance, myocardial myoglobin (1.05 +/- 0.22 mg/g) is approximately 50% decreased compared to healthy mongrel dogs (2.15 +/- 0.52 mg/g), approximately twice as much as dobermans with heart failure (0.47 +/- 0.25 mg/g) but similar to the concentration found in dogs paced to heart failure (1.09 +/- 0.34 mg/g). Myocardium from poultry had remarkably decreased myoglobin compared to mammals (34 +/- 4 micrograms/g) with heart failure produced either by furazolidone or salt toxicity causing a further 50% reduction. In the canine models of heart failure, myocardial myoglobin concentration was demonstrated to be correlated with biochemical and physiological indicators of myocardial performance, namely, mitochondrial and sarcoplasmic reticular ATPase activities, and cardiac output, systemic vascular resistance, pulmonary capillary wedge pressure and mean arterial pressure, respectively. Our data implicates a role for myoglobin deficiency in the pathogenesis of congestive heart failure and in the predisposition of doberman pinschers to dilated cardiomyopathy.

Animals↗
PubMed1992

Respiratory chain defect of myocardial mitochondria in idiopathic dilated cardiomyopathy of Doberman pinscher dogs.

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause. We tested the hypothesis that IDCM was associated with a myocardial metabolic defect by determining a comprehensive biochemical profile of metabolite concentrations and enzyme activities for the major metabolic pathways of the myocardium. We used the Doberman pinscher breed as a naturally occurring canine model of IDCM and compared its myocardial profile with that of healthy adult mongrels. Compared with controls, myocardium in IDCM had markedly reduced mitochondrial electron transport activity and myoglobin concentration, in association with acidosis and energy depletion following anoxic challenge: 60% decreased NADH dehydrogenase and 50% decreased ATP synthetase activities; 90% decreased myoglobin concentration; and 30% reduced ATP and 50% increased lactate and proton concentrations. Sarcoplasmic reticulum Ca(2+)-transport ATPase was decreased by 42%. There was a 15% compensatory increase in fatty acid oxidation and Krebs cycle activity. Other biochemical changes were mild by comparison with the mitochondrial defects. We conclude that IDCM is associated with a marked impairment of mitochondrial production of ATP, arising from decreased activity of the mitochondrial electron transport system, including myoglobin. These changes may be secondary to an underlying genetic defect or may indicate a deficiency of the mitochondrial respiratory chain that predisposes this breed to heart failure.

ATP Synthetase Complexes↗
PubMed1992

Normal pressure hydrocephalus. A potentially reversible form of dementia.

1. Normal pressure hydrocephalus (NPH) is a rare but potentially treatable form of dementia. Shunting will improve functioning in 40% to 50% of patients. 2. The classic symptoms of NPH are dementia characterized by mild memory impairment and apathy, ataxic gait, and urinary hesitancy or incontinence. 3. The patient with NPH may present with psychiatric symptoms of depression, paranoia, visual hallucinations, irrational hostility, and aggression or mania. 4. Patients with NPH are indifferent about activities of daily living and personal safety and require close supervision.

Aged↗
PubMed1990

[The role of drugs, irradiation, autoimmune diseases and age in the development of xerostomia in the Irish Republic].

The effects are described of xerostomia on the oral mucosa and dental structures. The various conditions which give rise to extreme dryness are listed; a rough estimate is made on the prevalence of these conditions. The contribution of drug induced xerostomia, of post irradiation mouth dryness and of autoimmune associated salivary disorders are dealt with. Reference is made to studies of xerostomia in various subpopulations. The prevalence of diseases known to be associated with mucosal dryness, and the yearly patterns of drug prescription in Ireland are used to justify an estimate of 2.1% to 3.3% of the population to be the incidence of xerostomia in the Republic of Ireland.

Age Factors↗