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Biomedical subjects

Timothy M Morgan

Publications and source records attributed to Timothy M Morgan.

16 recordsLinked to original sources
PubMed2006

Leg flow-mediated arterial dilation in elderly patients with heart failure and normal left ventricular ejection fraction.

BACKGROUND: flow-mediated arterial dilation (FMAD), an indicator of endothelial function, is reduced in patients with heart failure and reduced left ventricular ejection fraction (HFREF). Many elderly patients with heart failure exhibit a normal left ventricular ejection fraction (HFNEF). It is unknown whether FMAD is severely reduced in the elderly with HFNEF. METHODS AND RESULTS: 30 participants >60 yr of age, 11 healthy, 9 with HFNEF, and 10 with HFREF, underwent a cardiovascular magnetic resonance (CMR) assessment of FMAD in the superficial femoral artery followed within 48 h by symptom-limited exercise with expired gas analysis. Elderly patients with HFREF and HFNEF had severely reduced peak oxygen consumption (Vo(2 peak); 12 +/- 2 and 13 +/- 1 ml.kg(-1).min(-1), respectively) vs. their healthy age-matched contemporaries (20 +/- 3 ml.kg(-1).min(-1)). FMAD was 3.8 +/- 1.3% (0.85 +/- 0.22 mm(2)) in patients with HFREF; it was 12.1 +/- 3.6% (3.1 +/- 1.2 mm(2)) and 13.7 +/- 5.9% (3.9 +/- 1.7 mm(2)), respectively, in patients with HFNEF and age-matched healthy older individuals. After adjustment for age and gender, the association of FMAD with Vo(2) was high in healthy and HFREF subjects (P = 0.05 and 0.02, respectively) but less so in HFNEF participants (P = 0.58). CONCLUSIONS: elderly patients with HFNEF do not exhibit marked reduction in leg FMAD. These data suggest that mechanisms other than impaired femoral arterial endothelial function contribute to the severe exercise intolerance experienced by these individuals.

Aged↗
PubMed2005

Synergistic enhancement of testosterone transdermal delivery.

In this study, the effects of occlusion, octisalate (OS), and propylene glycol (PG) on the in vitro skin permeability of testosterone (TES) have been investigated. TES (either alone or with OS 5% w/v) was applied as a finite dose to full-thickness neonatal porcine skin mounted in flow-through diffusion cells and the amount of TES appearing in the receptor solution (20% v/v ethanol) was determined over 24 h. The skin was occluded with a microscope glass cover slip and to determine the effect of PG, 400 microl of PG/water mixtures (of varying PG concentration) was applied. In addition, the effect of Solugel (a proprietary hydrogel containing PG 25% w/w) and Tegaderm (a semipermeable film dressing) on the permeation of TES was assessed. Occlusion had no effect on the permeation of TES, however, OS increased the flux of TES 2.9-fold. The concentration of PG which produced optimal TES flux was 20% v/v, and this concentration resulted in a 1.9-fold increase in TES permeation. By combining OS, PG, and occlusion, TES permeation was increased 8.7-fold, which was a synergistic enhancement. In addition, Solugel and Tegaderm, when applied to the skin, produced a similar enhancement in TES permeation to that produced by PG 25% w/w and occlusion.

Administration, Cutaneous↗
PubMed2005

Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis).

This paper describes a behavior pattern in adult female cynomolgus monkeys that has several behavioral and physiological characteristics in common with human depression including reduced body fat, low levels of activity, high heart rate, hypothalamic-pituitary-adrenal (HPA) axis disturbances, and increased mortality. Under certain circumstances, this depressive behavior appears more common in socially stressed subordinate, than dominant, females. This is the first animal model of social stress-related depression in females and the first primate model of adult depression. It is important to have a female animal model of depression because women are more likely to experience a clinically significant depression than men, and depression in women is often associated with changes in reproductive system function. This model is particularly useful because these monkeys have menstrual cycles that are similar to those of women, and those that exhibit depressive behavior have relatively low levels of ovarian steroids. These monkeys may be a useful model of reproductive system-associated mood disorders in females.

Adrenocorticotropic Hormone↗
PubMed2005

Intestinal perforation in very low birth weight infants: growth and neurodevelopment at 1 year of age.

OBJECTIVE: To compare growth and neurodevelopment in surviving very low birth weight (VLBW) infants with an intestinal perforation (IP) caused by necrotizing enterocolitis (NEC) versus spontaneous intestinal perforation (SIP). STUDY DESIGN: Retrospective, observational cohort study. Infants born between January 1996 and December 1999 with birth weight <1500 g and a diagnosis of intestinal perforation were identified and data extracted from NICU, surgical and hospital databases. RESULTS: IP was identified in 62 of 1357 VLBW infants (5%); 39 infants (63%) had surgical NEC and 23 (37%) had SIP. Among survivors, 21/28 with surgical NEC (75%) and 13/18 with SIP (72%) returned for follow-up. At 1-year adjusted age, there were no differences in growth parameters but the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were lower in survivors with NEC versus SIP (mean difference in MDI=15; 95% confidence limits=3, 28; p=0.02; mean difference in PDI=14; 95% confidence limits=0.4, 28; p=0.04). CONCLUSIONS: Intestinal perforation caused by NEC, as compared to SIP, is associated with worse neurodevelopmental outcome at 1 year.

Child Development↗
PubMed2004

Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys.

The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to approximately 5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P = 1.00). Treatments did not affect serum IL-6 (P = 0.40), soluble E-selectin (P = 0.17), or C-reactive protein (P = 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01). We conclude that, in this well-established nonhuman primate model of atherosclerosis, this dose of soy IF provided an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE extended to both sVCAM-1 and MCP1. It is possible that the atheroprotective effects of IF and CEE are mediated, at least in part, by effects on VCAM-1. The sites of IF inhibitory effects on sVCAM-1 production are not known, but likely candidates include the liver and/or the cardiovascular system.

Animals↗
PubMed2004

Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial.

OBJECTIVE: The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was a randomized, single-blind clinical trial lasting 18 months that was designed to determine whether long-term exercise and dietary weight loss are more effective, either separately or in combination, than usual care in improving physical function, pain, and mobility in older overweight and obese adults with knee osteoarthritis (OA). METHODS: Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older, with a body mass index of > or =28 kg/m(2), knee pain, radiographic evidence of knee OA, and self-reported physical disability, were randomized into healthy lifestyle (control), diet only, exercise only, and diet plus exercise groups. The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included weight loss, 6-minute walk distance, stair-climb time, WOMAC pain and stiffness scores, and joint space width. RESULTS: Of the 316 randomized participants, 252 (80%) completed the study. Adherence was as follows: for healthy lifestyle, 73%; for diet only, 72%; for exercise only, 60%; and for diet plus exercise, 64%. In the diet plus exercise group, significant improvements in self-reported physical function (P < 0.05), 6-minute walk distance (P < 0.05), stair-climb time (P < 0.05), and knee pain (P < 0.05) relative to the healthy lifestyle group were observed. In the exercise group, a significant improvement in the 6-minute walk distance (P < 0.05) was observed. The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures. The weight-loss groups lost significantly (P < 0.05) more body weight (for diet, 4.9%; for diet plus exercise, 5.7%) than did the healthy lifestyle group (1.2%). Finally, changes in joint space width were not different between the groups. CONCLUSION: The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone.

Aged↗
PubMed2003

Relation of cardiac prognosis to segment location with apical left ventricular ischemia.

Previously, we have shown that myocardial ischemia induced during intravenous dobutamine in the distal segments composing the left ventricular apex is associated with a heightened risk of future myocardial infarction or cardiac death. In this study, we find this heightened risk is present independent of the location of the distal segment within the left ventricular apex.

Adult↗
PubMed2003

Design of Phase II cancer trials evaluating survival probabilities.

BACKGROUND: Phase II cancer studies are undertaken to assess the activity of a new drug or a new treatment regimen. Activity is sometimes defined in terms of a survival probability, a binary outcome such as one-year survival that is derived from a time-to-event variable. Phase II studies are usually designed with an interim analysis so they can be stopped if early results are disappointing. Most designs that allow for an interim look are not appropriate for monitoring survival probabilities since many patients will not have enough follow-up by the time of the interim analysis, thus necessitating an inconvenient suspension of accrual while patients are being followed. METHODS: Two-stage phase II clinical trial designs are developed for evaluating survival probabilities. These designs are compared to fixed sample designs and to existing designs developed to monitor binomial probabilities to illustrate the expected reduction in sample size or study length possible with the use of the proposed designs. RESULTS: Savings can be realized in both the duration of accrual and the total study length, with the expected savings increasing as the accrual rate decreases. Misspecifying the underlying survival distribution and the accrual rate during the planning phase can adversely influence the operating characteristics of the designs. CONCLUSION: Two-stage phase II trials for assessing survival probabilities can be designed that do not require prolonged suspension of patient accrual. These designs are more efficient than single stage designs and more practical than existing two-stage designs developed for binomial outcomes, particularly in trials with slow accrual.

Clinical Trials, Phase II as Topic↗
PubMed2003

Exercise responses of elderly patients with diastolic versus systolic heart failure.

PURPOSE: Little information is available regarding peak and submaximal exercise performance in elderly heart failure (HF) patients, particularly in those with diastolic dysfunction (DD). Therefore, the purpose of this investigation was to compare exercise responses of elderly patients with HF due to either systolic dysfunction (SD) or DD, to age-matched healthy volunteers (HV). METHODS: Patients with chronic HF > or = 60 yr (N = 119) due to SD (N = 60) or primary DD (N = 59) underwent a maximal cycle ergometry test with expired gas analysis and venous lactate measurement. Twenty-eight HV > or = 60 yr served as a control group. Anaerobic threshold was determined by gas analysis (ATVEN) and by plasma lactate rise (ATLAC). RESULTS: Peak oxygen consumption (VO(2peak)) was significantly (P < 0.001) reduced in both SD and DD patients (13 +/- 0.4 vs 14 +/- 0.4 ml x kg(-1) x min(-1), respectively) versus HV (20 +/- 0.6 ml x kg(-1) x min(-1)). Peak heart rate was reduced in patients versus HV (131 +/- 3 bpm vs 145 +/- 4, respectively; P < or = 0.01), but heart rate at a given submaximal work rate was significantly lower (P < or = 0.01) in HV than in SD and DD patients. ATVEN of 11.8 +/- 0.3 ml x kg(-1) x min(-1) for HV was significantly higher than SD (8.9 +/- 0.2) and DD (9.2 +/- 0.3). Peak lactate concentration was 6.6 +/- 0.6 mmol x kg(-1) x l(-1) in HV and was significantly reduced in both SD and DD HF patients. ATVEN correlated well with ATLAC in HV and in DD patients, but not in SD patients. CONCLUSIONS: Submaximal and peak exercise performance are markedly altered in elderly HF patients compared with age-matched HV but do not appear to be different between SD and DD patients.

Aged↗
PubMed2003

A randomized, controlled trial comparing two different continuous positive airway pressure systems for the successful extubation of extremely low birth weight infants.

OBJECTIVE: To determine whether the use of the Infant Flow continuous positive airway pressure (IF CPAP) system reduces the rate of extubation failure among extremely low birth weight (ELBW) infants (infants with birth weight <1000 g) when compared with conventional CPAP delivered with a conventional ventilator and nasal prongs. METHODS: A prospective, unmasked, randomized, controlled clinical trial was conducted in 162 eligible intubated ELBW infants who were hospitalized in 2 intensive care nurseries in Winston-Salem, North Carolina, between July 1997 and November 2000. Successful extubation was defined as no need for reintubation for any reason for at least 7 days after the first extubation attempt. RESULTS: The individual extubation success rates were 61.9% (52 of 84) in the conventional CPAP group and 61.5% (48 of 78) in the IF CPAP group. There were no significant differences in the extubation success rate in any birth weight subset between the 2 cohorts. The most common cause of extubation failure was apnea/bradycardia. Infants who were randomized to IF CPAP had fewer days on supplemental O(2) and shorter hospital stays. CONCLUSIONS: Extubation failure is a common problem, occurring in nearly 40% of ELBW infants who require mechanical ventilation. IF CPAP was as effective but no more effective than conventional CPAP in preventing extubation failure among ELBW infants. New strategies are needed to identify predictors of extubation success and to treat apnea/bradycardia, the most common cause of extubation failure, thereby reducing the likelihood of prolonged intubation in this high-risk cohort of premature infants.

Apnea↗
PubMed2002

Relation of aortic distensibility determined by magnetic resonance imaging in patients > or =60 years of age to systolic heart failure and exercise capacity.

Aortic stiffness increases with advancing age and is associated with the age-related decline in exercise capacity in healthy persons. Previous studies have suggested that aortic compliance is reduced in heart failure (HF). Older persons with systolic HF can have particularly severe exercise intolerance. However, the relation between increased aortic stiffness and exercise intolerance in elderly patients with systolic HF has not been examined. Therefore, aortic distensibility of the proximal ascending aorta (assessed by magnetic resonance imaging) and exercise tolerance (assessed by maximal exercise ergometry with expired gas analysis) was measured in 28 subjects (10 healthy subjects aged 20 to 30 years, 10 healthy subjects aged > or =60 years, and 8 subjects aged > or =60 years with systolic HF). Compared with healthy older subjects, patients with systolic HF had markedly decreased distensibility of the proximal aorta (0.5 +/- 0.4 vs 2.2 +/- 1.2 10(-3) mm Hg(-1), p <0.002), decreased peak exercise volume of oxygen consumption (VO2) (858 +/- 248 vs 1,436 +/- 344 ml/min, p <0.001), and increased aortic wall thickness (3.6 +/- 0.7 vs 2.9 +/- 0.4 mm, p <0.04). Aortic distensibility was significantly correlated with peak VO2 (r = 0.80, p <0.0001) and remained so even after being adjusted for age and left ventricular (LV) ejection fraction. These data suggest that decreased aortic distensibility may contribute to exercise intolerance in older patients with HF due to LV systolic dysfunction.

Adult↗
PubMed2002

Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure.

CONTEXT: Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure. OBJECTIVE: To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF). DESIGN AND SETTING: Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC. PARTICIPANTS: A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF < or =35%). Twenty-eight were age-matched healthy volunteer controls. MAIN OUTCOME MEASURES: Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life. RESULTS: By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P =.002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P =.40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P =.001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P =.56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P =.007 and.03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P =.02 and.001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]). CONCLUSION: Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Aged↗
PubMed2002

Magnetic resonance imaging determination of cardiac prognosis.

BACKGROUND: Regional assessments of left ventricular (LV) wall motion obtained during MRI cardiac stress tests can be used to identify myocardial injury and ischemia, but the utility of MRI stress test results for the assessment of cardiac prognosis is not known. METHODS AND RESULTS: Two hundred seventy-nine patients referred (because of poor LV endocardial visualization with echocardiography) for dobutamine/atropine MRI for the detection of inducible ischemia were followed for an average of 20 months. After MRI stress testing, the occurrence of myocardial infarction, cardiac death, death attributable to any cause, coronary arterial revascularization, and unstable angina or congestive heart failure requiring hospitalization was determined. In a multivariate analysis, the presence of inducible ischemia (hazard ratio 3.3, CI 1.1 to 9.7) or an LV ejection fraction <40% (hazard ratio 4.2, CI 1.3 to 13.9) was associated with future MI or cardiac death independent of the presence of risk factors for coronary arteriosclerosis. CONCLUSIONS: In patients with poor echocardiograms, the results of cardiac MRI stress tests can be used to forecast myocardial infarction or cardiac death.

Adult↗
PubMedDate not supplied

Cardiovascular magnetic resonance measurement of coronary arterial blood flow at rest and after submaximal exercise.

OBJECTIVE: Because most daily activities are conducted at submaximal exercise level, treatments are implemented to improve submaximal coronary artery blood flow (CABF). We sought to validate the reproducibility of cardiovascular magnetic resonance imaging measurements of submaximal CABF. METHODS: We measured CABF in the left anterior descending artery in 11 healthy postmenopausal women at rest and after submaximal bike exercise on 2 occasions 8 to 16 weeks apart. RESULTS: After exercise, CABF increased by 42% and 47% on the first and second examination, respectively. These changes in CABF in the 2 examinations were highly correlated (r=0.86). CONCLUSIONS: These data indicate that cardiovascular magnetic resonance assessments of CABF before and after submaximal exercise are feasible, reproducible, and consistent with those obtained invasively. In future studies, 24 patients would be needed per group to detect a 20% change of submaximal exercise blood flow at 80% power.

Coronary Circulation↗
PubMedDate not supplied

Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study.

OBJECTIVE: To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms (hot flashes and night sweats) in peri- and postmenopausal women. DESIGN: A double-masked, randomized, controlled, clinical trial was conducted. A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were randomized into one of three groups. In all groups, participants consumed a daily supplement containing 25 g of soy protein and were randomly assigned to one of three groups: (a) isoflavone extracted soy protein (control), (b) soy protein with a medium dose of isoflavones (42 mg/day), or (c) soy protein with a higher dose of isoflavones (58 mg/day). The primary outcome measure in this trial was change in reported vasomotor symptoms. RESULTS: A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups. No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone, middle isoflavone, or control groups. The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy. CONCLUSIONS: These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women.

Climacteric↗