Biomedical subjects
Publications and source records attributed to N F Gordon.
ImmunoDetection is a novel technique combining perfusion chromatography technology with antibodies to perform the steps of an immunoassay in a flow-through column format. Sensitive and precise measurements are performed in seconds to minutes using automated liquid chromatography instrumentation.
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Research studies over the past several decades confirm the health benefits of regular physical activity, a concept with foundations in antiquity. The effects of activity on certain individual health conditions, the precise dose of activity that is required for specific benefits, the role (if any) of intensity of effort, and the elucidation of biological pathways whereby activity contributes to health are topics for further research. Although details remain to be clarified, it is now clear that regular physical activity reduces the risk of morbidity and mortality from several chronic diseases and increases physical fitness, which leads to improved function. Table 3 outlines the relationship of activity to several diseases, a judgment on the strength of the evidence, and a rough determination of the amount of research extant. Results from clinical exercise studies and epidemiological investigations can be integrated into a consistent and coherent theory of healthful physical activity. However, some differences between these two research streams need to be reconciled. Exercise physiologists have generally recommended relatively intensive activity and a formal approach to exercise prescription. The epidemiological studies suggest a linear dose-response relationship, at least up to a point, between physical activity and health and functional effects. These data support public health recommendations directed toward the most sedentary and unfit stratum of the population and emphasize doing at least moderate physical activity. If this group of adults would accumulate 30 minutes of walking per day (or the equivalent energy expenditure in other activities), they would receive clinically significant health benefits. An important point is that it does not matter what type of physical activity is performed: Sports, planned exercise, household or yard work, or occupational tasks are all beneficial. The key factor is total energy expenditure; if that is constant, improvements in fitness and health will be comparable. There are probably 40 million adults in the US whose sedentary habits place them at considerably increased risk of morbidity and mortality from several diseases. These same individuals also are more likely to have functional limitations, especially as they move into the later years of life. The sizable independent relative risk for impaired health in sedentary persons, and the large number at risk, leads to a substantial public health burden. This problem deserves continued and increased attention by physicians and other health professionals, scientists, and the public health establishment.
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OBJECTIVE: To determine the association of baseline cardiorespiratory fitness to all-cause mortality across the range of blood glucose levels. RESEARCH DESIGN AND METHODS: Data from a prospective study of 8715 men (average age 42 yr), followed for an average of 8.2 yr (range 1-15 yr), were analyzed. Cardiorespiratory fitness was assessed by maximal-exercise treadmill testing. Men with evidence of clinical vascular disease or who did not achieve 85% of their age-predicted maximum heart rate during exercise testing were excluded from analyses. RESULTS: Age-adjusted death rates increased with higher levels, of fasting blood glucose. Regardless of glycemic status, fit men had lower age-adjusted all-cause death rates than their less fit counterparts. For men with fasting blood glucose greater than or equal to 7.8 mM or physician-diagnosed non-insulin-dependent diabetes mellitus (NIDDM), the age-adjusted death rates per 10,000 person-yr of follow-up in unfit and fit subjects were 82.5 and 45.9, respectively. The age-adjusted relative risk of death due to all causes was significantly elevated in the lower-fitness group within each of three glycemic status levels: fasting blood glucose less than 6.4 mM; relative risk (RR) = 1.93 (95% confidence interval [95% CI] 1.15-3.26); fasting blood glucose 6.4-7.8 mM; RR = 3.42 (95% CI 2.27-5.15); and fasting blood glucose greater than or equal to 7.8 mM or with NIDDM, RR = 1.80 (95% CI = 1.25-2.58). Multivariate analyses, controlling for risk factors of mortality (age, resting systolic blood pressure, serum cholesterol, body mass index, family history of heart disease, follow-up interval, and smoking habit) showed a higher risk of death due to all causes for unfit compared with fit men. Multivariate risks of death associated with low fitness, compared with higher fitness (RR), in the three glycemic status groups were: fasting blood glucose less than 6.4 mM, RR = 1.38 (95% CI 1.09-1.74); fasting blood glucose 6.4-7.8 mM, RR = 1.61 (95% CI 0.91-2.86); and fasting blood glucose greater than or equal to 7.8 mM or with NIDDM, RR = 1.92 (95% CI 0.75-4.90).
There currently is inconsistent information regarding the role that musculoskeletal strength (one component of musculoskeletal fitness) may have in lipid and lipoprotein metabolism, and consequently the risk of cardiovascular disease. Results of existing studies have been conflicting and have been influenced by several weaknesses. We provide cross-sectional analyses of the relation between muscular strength and serum lipid and lipoprotein status in a group of 1,193 women and 5,460 men. The large proportion of patients were not involved in formal weight training. As part of a preventive medical examination, patients were tested for maximal upper and lower body strength (one repetition maximum (1RM) bench and leg press). Fasting serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), triglyceride (TG), and high density lipoprotein (HDLC) were evaluated for their relation to muscle strength, after adjusting for simultaneous associations with age, body composition, and cardiovascular fitness. Results showed no association between muscular strength and serum TC or LDLC for either men or women and a direct association between upper and lower body strength and TG in men. The direct association between strength and TG in women was not significant. A statistically significant inverse association was seen between muscular strength and HDLC in men only. These data suggest no beneficial effect, and perhaps an adverse association of muscular strength on lipid and lipoprotein status.
Thirty-six sedentary, mildly obese (30-40% fat), premenopausal women (29-49 yr) were randomly assigned to one of two dietary regimens for an 8-wk double-blind, parallel study of the effect of moderate caloric restriction and macronutrient variation on maximal physical performance. Group 1 (N = 19) consumed 4186 kJ.d-1 (1000 kcal.d-1) with a diet composition of 40% fat, 40% carbohydrate (CHO), and 20% protein. Group 2 (N = 17) also consumed 4186 kJ.d-1 but varied the percent kilojoules to 20% fat, 60% CHO, and 20% protein. Maximal aerobic power was measured using a modified Balke protocol, strength was assessed using isotonic bench and leg press machines and a Cybex 340 isokinetic device during knee flexion and extension, and muscular endurance was taken as the number of sit-ups performed in 1 min. Pre- to post-testing revealed significant (P less than or equal to 0.05) reductions in body weight (group 1, -7.4 kg; group 2, -6.5 kg) within both groups. No significant changes were seen in maximal aerobic power within both groups. Strength measures for both groups showed a trend toward reduction but statistical significance was only evident in right knee extension for group 1 and left knee extension for group 2 (P less than or equal to 0.05). Sit-up number increased nonsignificantly for both groups. Between group differences were not found in any body weight, body composition, or physical performance index. We therefore conclude that in mildly obese women, maximal exercise performance is relatively unimpaired after 8 wk of caloric restriction with either of two diets differing moderately in their macronutrient content.
OBJECTIVE: We studied whether the quantity and quality of walking necessary to decrease the risk of cardiovascular disease among women differed substantially from that required to improve cardiorespiratory fitness. DESIGN: A randomized, controlled, dose-response clinical trial with a follow-up of 24 weeks. SETTING: A private, nonprofit biomedical research facility. PARTICIPANTS: One hundred two sedentary premenopausal women, 20 to 40 years of age, were randomized to one of four treatment groups; 59 completed the study (16 aerobic walkers [8.0-km/h group], 12 brisk walkers [6.4-km/h group], 18 strollers [4.8-km/h group], and 13 sedentary controls). Eighty-one percent were white, 17% black, and 2% Hispanic. INTERVENTION: Intervention groups walked 4.8 km per day, 5 days per week at 8.0 km/h, 6.4 km/h, or 4.8 km/h on a tartan-surfaced, 1.6-km track for 24 weeks. MAIN OUTCOME MEASURES: Fitness (determined by maximal oxygen uptake) and cardiovascular risk factors (determined by resting blood pressure and serum lipid and lipoprotein levels). RESULTS: As compared with controls, maximal oxygen uptake increased significantly (P less than .0001) and in a dose-response manner (aerobic walkers greater than brisk walkers greater than strollers). In contrast, high-density lipoprotein cholesterol concentrations were not dose related and increased significantly (P less than .05) and to the same extent among women who experienced considerable improvements in their physical fitness (8.0-km/h group, +0.08 mmol/L) and those who had only minimal improvements in fitness (4.8-km/h group, +0.08 mmol/L). High-density lipoprotein cholesterol also increased among the 6.4-km/h group, but did not attain statistical significance (+0.06 mmol/L; P = .06). Dietary patterns revealed no significant differences among groups. CONCLUSION: Thus, we conclude that vigorous exercise is not necessary for women to obtain meaningful improvements in their lipoprotein profile. Walking at intensities that do not have a major impact on cardiorespiratory fitness may nonetheless produce equally favorable changes in the cardiovascular risk profile.
We conducted a series of studies aimed at investigating the effect of beta-blockers on exercise physiology. On the basis of these and other existing studies, it is possible to draw the following conclusions and to make the following tentative recommendations for patients engaged in exercise training who receive beta-blocker therapy: i) CAD patients treated with beta-blockers are capable of deriving the expected enhancement of cardiorespiratory fitness during training, irrespective of the type of drug used; ii) beta1-selective blockers are preferable to nonselective agents for hypertensive patients engaged in exercise training; iii) because beta1-selective blockers impair exercise tolerance in some hypertensive patients, physicians should look out for this adverse reaction and, if present, consider alternative antihypertensive therapy; iv) intrinsic sympathomimetic activity confers no advantage during exercise training; v) exercise intensity prescription for patients receiving beta-blockers should be in accordance with traditional guidelines and based on results of individualized exercise testing performed on medication; vi) exercise training is desirable during beta-blocker therapy in that it appears to offset adverse alterations in lipoprotein metabolism; and vii) nonselective beta-blockers may increase predisposition to exertional hyperthermia, and patients must therefore be encouraged to adhere strictly to accepted guidelines for heat injury prevention.
The achievement of chronic blood pressure (BP) control in persons with mild hypertension is of central strategic concern in the prevention of hypertension-related morbidity and mortality. Epidemiologic and longitudinal studies suggest that regular participation in physical activity may be beneficial both in preventing hypertension and in lowering an already elevated BP. Moreover, preliminary analyses from our center suggest that cardiorespiratory fitness and, by inference, aerobic exercise may be of benefit in reducing mortality rates in hypertensive patients. When prescribing exercise with the intention of reducing an elevated BP and attenuating the risk for coronary artery disease, several factors must be considered to optimize the likelihood of a safe and effective response. These factors include specific safety aspects, and the type, frequency, intensity, and duration of exercise. In this respect, we recommend that aerobic exercise be performed at an intensity corresponding to 55 and 85% of the maximal heart rate and that the duration and frequency of training be modulated to achieve a weekly energy expenditure of between 14 and 20 kcal/kg of body weight. For those patients who require drug therapy, the interaction between the specific antihypertensive agent and exercise must also be considered.
Over the past 30 years, mortality rates from coronary artery disease (CAD) have decreased by more than 30% in the United States. However, CAD remains the major public health problem in this country. There is now substantial evidence linking exercise training to a reduced risk for CAD and for mortality after myocardial infarction. The actual mechanism by which physical activity aids in reducing the risk for developing or dying from CAD has still to be elucidated. Several highly plausible mechanisms have been postulated, including decreased myocardial oxygen demand, increased myocardial oxygen supply, reduced propensity toward ventricular arrhythmias, reduced platelet aggregation, increased plasma fibrinolytic activity, and modification of multiple CAD risk factors. Irrespective of the precise mechanism, it now appears that lower levels of physical activity are needed to reduce the risk for CAD than are needed to optimize cardiorespiratory fitness. In this regard, we recommend that the type, frequency, intensity, and duration of exercise training be modulated to achieve a weekly energy expenditure of between 14 and 20 kilocalories per kilogram of body weight. Although aerobic activities should be emphasized, muscle strengthening and flexibility exercises should also be incorporated into the training program in order to promote musculoskeletal health.
This paper reports a new technique for reducing resistance to stagnant mobile phase mass transfer without sacrificing high adsorbent capacity or necessitating extremely high pressure operation. The technique involves the flow of liquid through a porous chromatographic particle, and has thus been termed "perfusion chromatography". This is accomplished with 6000-8000 A pores which transect the particle. Data from electron microscopy, column efficiency, frontal analysis and theoretical modelling all suggest that mobile phase will flow through these large pores. In this manner, solutes enter the interior of the particles through a combination of convective and diffusional transport, with convection dominating for Peclet numbers greater than one. The implications of flow through particles on bandspreading, resolution and dynamic loading capacity are examined. It is shown that the rate of solute transport is strongly coupled to mobile phase velocity such that bandspreading, resolution of proteins and dynamic loading capacity are unaffected by increases in mobile phase velocity up to several thousand centimeters per hour. The surface area of this very large-pore diameter material is enhanced by using a network of smaller, 500-1500 A interconnecting pores between the throughpores. Scanning electron micrographs show that the pore network is continuous and that no point in the matrix is more than 5000-10,000 A from a through-pore. As a consequence, diffusional path lengths are minimized and the large porous particles take on the transport characteristics of much smaller particles but with a fraction of the pressure drop. Capacity and resolution studies show that these materials bind and separate an amount of protein equivalent to that of conventional high-performance liquid chromatography as well as low performance agarose-based media at greater than 10-100 times higher mobile phase velocity with no loss in resolution.
The effect of intrinsic sympathomimetic activity (ISA) on the ability of patients with high blood pressure (BP) to derive a cardiorespiratory training effect during long-term beta-blocker therapy was studied. Fifty sedentary hypertensive subjects were randomly assigned to propranolol (n = 23) or pindolol (n = 27) therapy for a 22 week double-blind parallel study. Over the first 2 weeks, during which subjects remained sedentary, drug doses were titrated to produce equipotent, clinically significant BP reductions. Subjects subsequently continued drug therapy and completed 20 weeks of exercise training. Although pindolol tended to preserve submaximal exercise heart rates to a greater degree than propranolol, the initial 2 weeks of drug therapy resulted in equivalent reductions in maximal oxygen uptake with propranolol (6% reduction) and pindolol (8% reduction). Likewise, 20 weeks of training induced similar, statistically significant (P = .0001) increases in maximal oxygen uptake during propranolol (10% increase) and pindolol (11% increase) treatment. We therefore conclude that ISA does not confer any advantage to patients with high BP who receive chronic beta-blocker therapy and wish to improve their cardiorespiratory fitness by participating in exercise training.
This study compared the effects of a high-carbohydrate and a mixed diet on core temperature responses to prolonged exercise in six male competitive cyclists (age = 22.2 +/- 1.9 years). This study, the first to investigate the effect of a high-carbohydrate diet on exercise core temperature in humans, therefore suggests that three days of increased dietary carbohydrate intakes do not evoke any deleterious thermoregulatory responses during prolonged submaximal exercise.
Chronic essential hypertension is a major public health problem afflicting an estimated 15 to 30% of persons from most Western industrialised countries. Persons with mild hypertension (diastolic blood pressure between 90 and 104mm Hg and/or systolic blood pressure between 140 and 159mm Hg) represent the overwhelming majority of hypertensive individuals in the general population. The achievement of long term blood pressure control in these individuals is of central strategic concern in the prevention of hypertension-related morbidity and mortality. Epidemiological studies suggest that regular participation in physical activity may be beneficial in preventing hypertension. The findings of epidemiological studies are supported by a recent meta-analysis of 25 longitudinal aerobic training studies, in which the average sample-size-weighted reductions in resting systolic and diastolic blood pressures were 10.8mm Hg and 8.2mm Hg, respectively. Moreover, preliminary analyses from our centre suggest that cardiorespiratory fitness and, by inference, aerobic exercise training may be of benefit in reducing mortality rates in hypertensive patients. When compiling an exercise prescription with the intention of reducing an elevated blood pressure and attenuating the risk for coronary artery disease, several factors must be considered in order to optimise the likelihood of a safe and effective response. Specifically, the 5 basic components of the exercise prescription for patients with mild hypertension are safety aspects, the type of exercise to be performed, and the frequency, intensity and duration of exercise training. For those patients who require pharmacotherapy, the interaction between the specific antihypertensive agent and exercise responses must also be considered. We recommend that aerobic exercise training be performed at an intensity corresponding to 60 to 85% of the maximal heart rate and that the duration and frequency be modulated to achieve a weekly energy expenditure of between 14 and 20 kcal/kg of bodyweight.
Simulation and optimization of continuous affinity recycle extraction (CARE), a protein purification unit operation based on protein adsorption to solid phase adsorbents, is described in this paper. Rather than packing conventional adsorbent particles in a fixed bed (column), solid/liquid contact is carried out in well-mixed reactors. Continuous operation is achieved by recirculation of the adsorbent particles between two or more contactors. The feasibility of this purification scheme was established with the recovery and isolation of the enzyme beta-galactosidase from E.coli, using the affinity support PABTG/Agarose. A mathematical model describing system performance was developed. The mathematical model was used to optimize several facets of the system design and operation. The base two-stage contractor design was modified by the addition of an intermediate wash stage as well as the incorporation of multiple adsorption stages. These design modifications serve to increase purification, concentration and recovery while utilizing the same amount of adsorbent. The methodology for defining and optimizing objective functions was developed and experimentally validated. Finally, optimum system start-up protocols, minimizing the time required to reach steady-state operation, were developed and experimentally validated. The impact of early introduction of adsorptive purification in a downstream processing sequence, with CARE, was evaluated and is described. Through the early introduction of a highly specific adsorptive step, significant purification is achieved simultaneously with clarification and concentration. In addition, purification performance in CARE was contrasted with that achievable in conventional column chromatography.