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Biomedical subjects

J R Stratton

Publications and source records attributed to J R Stratton.

At least 55 records · Page 3Linked to original sources

The effect of intensive endurance exercise training on body fat distribution in young and older men.

Little is known about the effects of exercise interventions on the distribution of central and/or intra-abdominal (IA) fat, and until now there were no studies in the elderly. Therefore, in this study we investigated the effects of an intensive 6-month endurance training program on overall body composition (hydrostatic weighing), fat distribution (body circumferences), and specific fat depots (computed tomography [CT]), in healthy young (n = 13; age, 28.2 +/- 2.4 years) and older (n = 15; age, 67.5 +/- 5.8 years) men. At baseline, overall body composition was similar in the two groups, except for a 9% smaller fat free mass in the older men (P less than .05). The thigh and arm circumferences were smaller (P = .001 and P less than .05, respectively), while the waist to hip ratio (WHR) was slightly greater in the older men (0.92 +/- 0.04 v 0.97 +/- 0.04, P less than .01). Compared with the relatively small baseline differences in body composition and circumferences, CT showed the older men to have a twofold greater IA fat depot (P less than .001), 48% less thigh subcutaneous (SC) fat (P less than .01), and 21% less thigh muscle mass (P less than .001). Following endurance (jog/bike) training, both the young (+18%, P less than .001) and the older men (+22%, P less than .001) significantly increased their maximal aerobic power (VO2max). This was associated with small but significant decrements in weight, percent body fat, and fat mass (all P less than .001) only in the older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

The relation between radionuclide angiography and Doppler echocardiography during contractile changes with infusions of epinephrine.

To define the quantitative relations between radionuclide and Doppler measures of systole during sympathetic activation with epinephrine, 10 young normal men were studied with simultaneous radionuclide angiography and M-mode and Doppler echocardiography during graded infusions of epinephrine (10, 25 and 50 ng/kg/min for 12 minutes each). During a nine-fold increase in circulating levels of epinephrine in arterialized plasma (94 +/- 59 to 879 +/- 310 pg/ml, P less than 0.001), the heart rate increased from 58 +/- 8 to 73 +/- 7 beats/min (P less than 0.01), whereas the mean arterial pressure fell from 82 +/- 3 to 75 +/- 6 mmHg (NS) and end-systolic wall stress decreased from 97 +/- 6 to 67 +/- 10 dynes/sec (P less than 0.01). The ejection fraction as estimated using radionuclide techniques increased from 68 +/- 6 to 83 +/- 6%, the peak ejection rate measured in this way increased from -3.36 +/- 0.3 to -5.10 +/- 0.5 end-diastolic volumes/sec, the ejection fraction as estimated with M-mode echocardiography increased from 66 +/- 5 to 83 +/- 5%, the echocardiographic ventricular dimension shortening increased from -1.78 +/- 0.2 to -2.7 +/- 0.4 sec-1, the peak aortic outflow velocity as measured with Doppler techniques increased from 98 +/- 13 to 147 +/- 25 cm/sec, and the aortic outflow acceleration velocity increased from 11 +/- 3 to 27 +/- 7 m/sec2 (all P less than 0.001). There was a significant correlation between the changes in radionuclide and M-mode estimations of ejection fractions (r = 0.82), between the radionuclide peak ejection rate and M-mode peak dimension shortening (r = 0.80) and between the radionuclide peak ejection rate and the Doppler peak aortic outflow velocity (r = 0.90) (all P less than 0.01). We conclude that corresponding radionuclide and Doppler echocardiographic measurements of systolic function are altered similarly during increased sympathetic activation with epinephrine.

Adult↗

Radionuclide ventriculographic quantitation of left ventricular dimensions. Comparison to echocardiography.

Left ventricular internal cavity dimensions (LVID) were determined from radionuclide ventriculographic (RNVG) studies using a spatial calibration algorithm and visually defined edges and were compared to the results from two-dimensional echocardiography. Routine clinical cases were used with no additional views and no attenuation or scatter correction. In an initial set of 21 patients, mean RNVG LVID was 5.7 +/- 1.1 (mean +/- 1 S.D.) cm compared to 5.3 +/- 1.0 cm for echocardiography. In a prospective validation of the regression equations derived in the initial set of patients, regression-corrected RNVG results were within 5 mm of those determined echocardiographically in 18/22 patients and the mean LVID values were the same. Quantitative estimation of LVID by RNVG is simple, rapid, and reproducible. Systematic overestimation of dimensions compared to echocardiography can be corrected using a regression equation.

Algorithms↗

Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults.

BACKGROUND: The effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24-30 years) and in 13 old male subjects (60-82 years). METHODS AND RESULTS: After training, maximum oxygen consumption was increased in the young group by 18% (44.9 +/- 5.0 to 52.9 +/- 6.6 ml/kg/min, p less than 0.001), whereas it was increased in the old group by 22% (29.0 +/- 4.2 to 35.5 +/- 3.6 ml/kg/min, p less than 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 +/- 0.47 to 1.14 +/- 0.42 IU/ml, p less than 0.03), a 141% increase in the percentage of t-PA in the active form (11.1 +/- 7.7 to 26.8 +/- 15.1%, p less than 0.01), a 58% decrease in PAI-1 activity (8.4 +/- 4.9 to 3.5 +/- 1.7 AU/ml, p less than 0.01), and a 13% decrease in fibrinogen (3.57 +/- 0.79 to 3.11 +/- 0.52 g/l, p less than 0.01). CONCLUSIONS: We conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease.

Adult↗

Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy.

To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/- 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity.

Aged↗

Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity.

To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis.

Adult↗

Influence of myocardial infarction size on radionuclide and Doppler echocardiographic measurements of diastolic function.

To assess the relation between myocardial infarction size and diastolic function as measured by radionuclide ventriculography and Doppler echocardiography, 83 patients (aged 58 +/- 9 years) without significant valvular disease were studied 8 to 12 weeks after an acute myocardial infarction. Myocardial infarction size was measured by resting thallium-201 tomography. Peak early filling rate (in end-diastolic volumes/s) was measured by gated blood pool scintigraphy. Doppler measures of mitral inflow were peak early (E) and atrial (A) filling velocities, slopes of E and A, percent E and A filling, E/A ratio and diastolic filling period. In univariate analyses, there was a significant inverse correlation between infarction size and the peak early filling rate (r = -0.59, p less than 0.001), and this remained significant (r = -0.63, p less than 0.0001) in an analysis that included 2 other determinants of the filling rate, age and diastolic filling period. Infarction size was directly correlated to the peak E velocity (r = 0.37, p less than 0.01), deceleration of E (r = 0.41, p less than 0.01) and percent E filling (r = 0.31, p less than 0.01), and was inversely correlated to peak A (r = -0.27, p less than 0.05) and percent A filling (r = -0.26, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Echocardiographic evaluation of segmental wall motion early and late after thrombolytic therapy in acute myocardial infarction: the Western Washington Tissue Plasminogen Activator Emergency Room Trial.

In 92 acute myocardial infarction (AMI) patients treated with tissue plasminogen activator 2.3 +/- 1.2 hours after the onset of chest pain, echocardiography was performed at 11 +/- 14 hours (early) and, in 49 patients, again at 13 +/- 7 weeks (late). Infarct location and the left ventricular wall motion score index--the average score (normal = 1, hypokinetic = 2, akinetic = 3, dyskinetic = 4) for 20 segments--were determined by 2 observers unaware of clinical, angiographic or electrocardiographic data. Concordance between noninvasive infarct location by electrocardiography or echocardiography and infarct-related artery at angiography 4 +/- 2 days later (n = 85) was 76 and 81%, respectively. The early wall motion score index was worse for anterior (1.8 +/- 0.4) versus inferior (1.3 +/- 0.2, p less than 0.0001) or posterior-lateral (1.6 +/- 0.2, p = 0.0003) infarcts. Overall, the wall motion score index improved from early to late echocardiography (n = 49, 1.5 +/- 0.3 to 1.3 +/- 0.3, p = 0.0008). However, improvement was confined to those with time to treatment less than or equal to 2 hours (n = 22, 1.4 +/- 0.3 to 1.2 +/- 0.2, p less than 0.0001), and evidence of reperfusion at angiography (n = 38, 1.5 +/- 0.3 to 1.2 +/- 0.3, p less than 0.0001). The decrease in the wall motion score index was related to a decrease in the number of adjacent involved segments (5.5 +/- 3.0 to 3.7 +/- 3.9/patient, p = 0.0006). Thus, echocardiography early after AMI identifies infarct location. Improvement in regional wall motion is seen after early treatment with intravenous tissue plasminogen activator.

Aged↗

Body fat distribution in healthy young and older men.

Central and/or intraabdominal (IA) fat is an independent predictor of obesity-related metabolic abnormalities in young and middle-aged subjects. The elderly are "fatter" at any given relative weight and often have similar metabolic abnormalities. In this study we compare body composition, circumferences, and specific fat depots areas in a population of healthy young and older men. Although the two groups were similar in body mass index and percent body fat, their distribution of adiposity was different. The young subjects had 16% and 10% larger thigh (p = .0001) and arm (p less than .01) circumferences respectively, while the ratio of waist-to-hip circumference was greater in the older subjects (0.93 +/- 0.04 vs 0.97 +/- 0.04, p = less than .01). The most striking differences between the groups were noted on computed tomography, with a twofold greater IA fat area (72.6 +/- 38.2 vs 143.6 +/- 56.2 cm2, p less than .0001), and a twofold lesser thigh subcutaneous fat area (156.3 +/- 69.3 vs 82.4 +/- 29.7 cm2, p less than .001) in the older subjects. We conclude there is an age-related central and intraabdominal redistribution of adipose mass, even in healthy older subjects. Since these changes occur in the absence of clinical disease, the associations between metabolic abnormalities and a central and or IA distribution of adiposity in the elderly must be investigated further.

Adipose Tissue↗

Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging.

To assess the effect of exercise training on the insulin resistance and impaired pancreatic B-cell function of aging, we studied 13 healthy older men (ages 61-82 yr) before and after 6 mo intensive endurance exercise. An index of insulin sensitivity (SI) was measured using Bergman's minimal model. Intravenous glucose tolerance was quantified using the glucose disappearance constant (KGlc) while oral glucose tolerance was assessed after a 100-g glucose load. B-cell function was evaluated by measuring the acute insulin response (AIR) to glucose injection at fasting glucose (AIRGlc) and the AIR to arginine at multiple clamped glucose levels. Exercise produced an endurance training effect as demonstrated by an 18% increase in maximum O2 consumption (VO2max) [38.2 +/- 1.4 to 45.0 +/- 1.1 (SE) ml.kg fat-free mass-1.min-1, P less than 0.001]. An unchanged fasting glucose (5.3 +/- 0.2 to 5.4 +/- 0.2 mM) despite a reduced fasting insulin (61 +/- 6 to 48 +/- 6 pM, P less than 0.01) suggested exercise training improved insulin sensitivity. This was confirmed by a 36% increase in SI from 3.47 +/- 0.41 to 4.71 +/- 0.42 x 10(-5) min-1/pM (P = 0.01). Intravenous glucose tolerance did not change as measured by KGlc, which was 1.46 +/- 0.09 before and 1.48 +/- 0.16%/min after exercise training. Likewise, the incremental glucose response to oral glucose (633 +/- 49-618 +/- 45 mM.min) was unchanged. B-cell function was decreased as reflected by AIRGlc (351 +/- 73-245 +/- 53 pM, P less than 0.01) and the AIRArg at maximal glycemic potentiation (AIRmax, 1,718 +/- 260-1,228 +/- 191 pM, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

111In platelet imaging of left ventricular thrombi. Predictive value for systemic emboli.

To determine whether a positive indium 111 platelet image for a left ventricular thrombus, which indicates ongoing thrombogenic activity, predicts an increased risk of systemic embolization, we compared the embolic rate in 34 patients with positive 111In platelet images with that in 69 patients with negative images during a mean follow-up of 38 +/- 31 (+/- SD) months after platelet imaging. The positive and negative image groups were similar with respect to age (59 +/- 11 vs. 62 +/- 10 years), prevalence of previous infarction (94% vs. 78%, p less than 0.05), time from last infarction (28 +/- 51 vs. 33 +/- 47 months), ejection fraction (29 +/- 14 vs. 33 +/- 14), long-term or paroxysmal atrial fibrillation (15% vs. 26%), warfarin therapy during follow-up (26% vs. 20%), platelet-inhibitory therapy during follow-up (50% vs. 33%), injected 111In dose (330 +/- 92 vs. 344 +/- 118 microCi), and latest imaging time (greater than or equal to 48 hours in all patients). During follow-up, embolic events occurred in 21% (seven of 34) of patients with positive platelet images for left ventricular thrombi as compared with 3% (two of 69) of patients with negative images (p = 0.002). By actuarial methods, at 42 months after platelet imaging, only 86% of patients with positive images were embolus free as compared with 98% of patients with negative images (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

Optimum conditions for the stabilization and measurement of tissue plasminogen activator activity in human plasma.

Current studies show a more than 50-fold variation in the estimated level of tissue-type plasminogen activator (t-PA) activity in normal resting blood samples that result from major differences in the methods used to sample, preserve, and assay t-PA activity in blood. In this study we developed optimized methods for stabilizing and measuring t-PA activity in plasma by using a coupled plasminogen-chromogenic substrate (amidolytic) assay. To maximize the recovery of t-PA activity, blood should be acidified within 60 seconds after being drawn by adding 2 parts whole blood to 1 part 0.5 mol/L sodium acetate, pH 4.2. This method prevents hemolysis and eliminates 70% of the alpha 2-plasmin inhibitor. Optimum conditions for measuring t-PA activity are pH 8.0 to 8.3 (37 degrees C), ionic strength 0.02 to 0.04, 0.5 mumol/L plasminogen, 80 micrograms/ml CNBr-cleaved fibrinogen, and a chromogenic substrate concentration of 0.65 mmol/L D-valyl-leucyl-lysyl-p-nitroanilide, 0.25 mmol/L D-valyl-phenylalanyl-lysyl-p-nitroanilide, or 0.2 mmol/L D-norleucyl-hexahydrotyrosyl-lysyl-p-nitroanilide. The final assay is linear with respect to added one-chain t-PA, two-chain t-PA, and acidified plasma. There was no difference in t-PA activity measured with ethylenediaminetetraacetic acid anticoagulant versus that measured with citrate anticoagulant after correction for dilution effects (average resting t-PA activity in plasma from 20 healthy individuals = 1.59 IU/ml). We conclude that assay conditions can have major effects on the measurement of t-PA activity in plasma and that suboptimal conditions may result in a significant underestimation of t-PA activity.

Citrates↗

Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets.

Using autologous 111In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction. The magnitude of spleen and liver destruction appears to be of considerable importance in the severity of the disease, as reflected in the platelet survival and platelet count.

Autoimmune Diseases↗

Standardization of methods for measuring plasminogen activator inhibitor activity in human plasma.

We have standardized the measurement of plasminogen activator inhibitor type 1 (PAI-1) activity in plasma. One-chain tissue-type plasminogen activator (t-PA; EC 3.4.21.31; final activity, 5 int. units/mL) was incubated with plasma (final dilutions 1:4 to 1:40) in phosphate buffer (pH 7.4, ionic strength = 0.15) for 15 min at 37 degrees C, followed by acidification and measurement of residual t-PA activity by an amidolytic method. The PAI-1 activity assay was 98% specific for PAI-1 activity in samples from both pregnancy and nonpregnancy, and varied linearly with added plasma volume when the percent inhibition of t-PA was between 8% and 50%. For the standardized method, analytical recovery was 93 +/- 5%, the detection limit was 1.6 arbitrary units per milliliter (1 arb. unit of PAI-1 activity = inhibition of 1 int. unit of t-PA activity), and total imprecision was 10.2 (SD 0.7) arb. units/mL (CV = 7%, n = 20). The average PAI-1 activity in 10 healthy individuals drawn between 0800 and 1000 hours was 23.9 +/- 15.4 arb. units/mL. Compared with the standardized assay, two of three previously described assays underestimated PAI-1 activity in plasma by 77% and 85%, respectively.

Blood Chemical Analysis↗

Swallow syncope associated with complete atrioventricular block: a case report and review of the literature.

Swallow or deglutition syncope is a very unusual but treatable disorder. A 44-year-old male presented with multiple, recurrent episodes of complete atrioventricular block associated with swallowing. Over a 24-hour period, 92 episodes of complete atrioventricular block occurring with meals were recorded by Holter monitoring. Evaluation did not demonstrate any underlying esophageal or cardiac disease. A trial of anticholinergic medications was unsuccessful. The patient's symptoms resolved following placement of a demand cardiac pacemaker. This is a rare but potentially lethal disorder that can be successfully treated if recognized. Physicians should be alerted to symptoms of lightheadedness or syncope during meals.

Adult↗

Common causes of cardiac emboli--left ventricular thrombi and atrial fibrillation.

This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Drs Paul G. Ramsey, Associate Professor of Medicine, and Philip J. Fialkow, Professor and Chair of the Department of Medicine.

Anticoagulants↗