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Biomedical subjects

J Keul

Publications and source records attributed to J Keul.

At least 55 records · Page 3Linked to original sources

Assessment of carotid wall motion and stiffness with tissue Doppler imaging.

In this study, the wall motion of the common carotid artery was characterized by measuring wall-motion velocity (Wv) with tissue Doppler imaging (TDI) in 78 male and female subjects (16-75 y) with no history of cardiovascular disease. The near and far arterial wall showed essentially different Wv patterns. To assess the vascular systolic distension, the Wv of the near and far arterial walls were measured and a Wv index was calculated by subtracting the far Wv from the near Wv. Aging was associated with a 2.0-2.5-fold decrease of peak Wv index. Corrected for carotid diameter and blood pressure, the peak Wv index and mean systolic acceleration to the peak Wv correlated highly with arterial distensibility (r = 0.81 resp. r = 0.75) and compliance (r = 0.73 resp. r = 0.68). This study demonstrates the feasibility of TDI in the characterization of wall motion patterns and in the assessment of common carotid artery stiffness.

Adolescent↗

[Injury risk of competitive, handicapped cross-country skiers in training nd competition].

Injuries caused by cross country skiing have been poorly investigated in handicapped athletes. The dynamic sliding shape of motion makes this sport to a suitable discipline for people with a deficit of locomotion. Visual handicapped people with a guide are able to improve their motoric skills, co-ordination, orientation and body self-consciousness in the track. Since handicapped athletes are performing in international competitions the training intensity to fulfill the requirements, but also the risk of overstrain induced injuries got increased, like in other high-performance sports. Our study examined injuries and overuse syndromes of the German National Team Ski Nordic during the Paralympics in Tignes/ Albertville (1992). Lillehammer (1994) and the training period in preparation for the Paralympics in Nagano (March 1998). The incidence and kind of injuries in the competitive handicapped cross country skier was comparable with non-handicapped athletes, but the injury pattern was different.

Adult↗

Aerobic exercise as therapy for cancer fatigue.

PURPOSE: Fatigue and impairment of physical performance are common and severe problems of cancer patients. We describe the effect of an aerobic exercise program designed for cancer patients suffering from these symptoms. METHODS: Five cancer patients (4 female, 1 male, age 18 to 55), participated in the training program. Fatigue had been present for a time ranging between 5 wk and 18 months and hindered the patients from carrying out normal daily activities. The training program consisted of walking daily on a treadmill with an intensity corresponding to a lactate concentration of 3 +/- 0.5 mmol.L-1 and was carried out for 6 wk. RESULTS: By the end of the exercise program we observed an improvement in maximal physical performance (from 6.4 +/- 0.4 km.h-1 to 7.5 +/- 0.9 km.h-1, P < 0.05) and maximal walked distance (from 1640 +/- 724 m to 3300 +/- 953 m, P < 0.05). Heart rate and lactate concentration by an equivalent submaximal workload (5 km.h-1) were significant reduced (from 138 +/- 21 beats.min-1 to 113 +/- 20 beats.min-1, P < 0.05, and from 2.6 +/- 1.4 mmol.L-1 to 1.3 +/- 0.6 mmol.L-1, P < 0.05); all patients experienced a clear reduction of fatigue and could carry out normal daily activities again without substantial limitations. CONCLUSION: We conclude that an aerobic exercise program of precisely defined intensity, duration, and frequency can be prescribed as therapy for primary fatigue in cancer patients.

Adolescent↗

Cardiovascular differences between sedentary and wheelchair-trained subjects with paraplegia.

PURPOSE: Heart dimensions, left ventricular function, and internal dimensions of limb arteries, as well as physical fitness, were examined in sedentary male subjects with paraplegia (SP, N = 20), national elite male athletes with paraplegia (PA, N = 29), and untrained able-bodied males (AB, N = 30). METHODS: All subjects underwent two-dimensional echocardiography, duplex sonography of common femoral artery and subclavian artery at rest, and an incremental wheelchair ergometer exercise test. RESULTS: Heart volume in relation to body weight was not different in PA as compared with that in AB (11.5 +/- 1.6 vs 11.6 +/- 2.2 mL.kg-1; mean +/- SD), whereas SP showed significantly lower values (9.7 +/- 1.5 mL.kg-1). Left ventricular ejection fraction was similar in all subjects (59.9-60.8%). In relation to body surface area, subclavian artery cross-sectional area was significantly higher in PA compared with that in AB and SP, respectively (PA: 0.32 +/- 0.05, AB: 0.21 +/- 0.06, SP: 0.22 +/- 0.05 cm2/m2). The corresponding values for the common femoral artery were significantly lower in all subjects with paraplegia as compared with those in AB, whereas no difference was found between PA and SP (AB: 0.31 +/- 0.05, PA: 0.14 +/- 0.05, SP: 0.15 +/- 0.04 cm2/m2). Peak oxygen uptake (VO2peak) determined in the wheelchair ergometer exercise test was within the same range in PA and AB, but significantly (P < 0.05) lower in SP (PA: 34.5 +/- 4.3, AB: 31.5 +/- 4.1, SP: 23.9 +/- 3.8 mL.kg-1.min-1). CONCLUSIONS: In conclusion, cardiac dimensions and VO2peak of PA were larger than in SP but do not exceed those of AB. Intensive wheelchair training was associated with larger dimensions of the subclavian arteries in PA, whereas a hypotrophy of the common femoral artery was found in SP and PA compared with that in AB.

Adult↗

Three mitochondrial DNA restriction polymorphisms in elite endurance athletes and sedentary controls.

This study examined the associations between elite endurance athlete (EEA) status and three mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) in the subunit 5 of the NADH dehydrogenase (MTND5) locus and one in the D-loop region. A group of 125 Caucasian male EEA well endowed with the phenotypic expression of VO2max (78.9 +/- 3.8 mL x kg(-1) x min(-1), mean +/- SD) and 65 sedentary controls (SCON: VO2max = 39.8 +/- 8.2 mL x kg(-1) x min(-1)) participated in the study. VO2max was determined during an incremental exercise test on a cycle ergometer or a motor-driven treadmill. mtDNA was extracted from white blood cells or lymphoblastoid cell lines and specific regions were amplified by the polymerase chain reaction. The Pearson Chi-square statistic test and Fisher exact test revealed no significant association (P > 0.05) between any of the three mtDNA RFLPs and EEA status. The MTND5-BamHI RFLP at bp 13,470 (morph 3) was found in 12.8% of the EEA and 12.3% of the SCON (chi2 = 0.009, P = 0.92). The prevalence of the MTND5-Ncil RFLP at bp 13,364 (morph 2) was 12.9% and 14% for the EEA and SCON, respectively (chi2 = 0.043, P = 0.83). The D-loop-KpnI RFLP at bp 16,133 (morph 1) was found in 5.8% of the EEA and in 1.6% of the SCON (Fisher exact test = 1.80, P = 0.18). The MTND5-HincII RFLP at bp 12,406 (morph 1) was not present in this study sample. These results indicate no evidence for a difference in the frequency of two polymorphic restriction sites in the subunit 5 of the NADH dehydrogenase gene of mtDNA and one in the D-loop region between elite endurance athletes and sedentary controls.

Adolescent↗

Catecholamines, heart rate, and oxygen uptake during exercise in persons with spinal cord injury.

The purpose of this study was to investigate the influence of different injury levels in persons with spinal cord injury (SCI) on epinephrine (Epi) and norepinephrine (NE) at rest and during graded wheelchair exercise and the related changes in heart rate and O2 uptake (VO2). Twenty tetraplegics (Tetra), 10 high-lesion paraplegics (HLPara), 20 paraplegics with SCI below T5 (MLPara), and 18 able-bodied, nonhandicapped persons (AB) were examined. Because of the higher level of interruption of the sympathetic pathways, Tetra persons showed lower Epi and NE at rest and only slight increases during exercise compared with all other groups; the Tetra subjects' impaired cardiac sympathetic innervation caused restricted cardioacceleration and strongly reduced maximal VO2. When compared with AB persons, HLPara had comparable NE but lower Epi levels as a result of partial innervation of the noradrenergic system and denervation of the adrenal medulla. MLPara subjects showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity compared with AB subjects. The increase in heart rate in relation to VO2 was higher in HLPara because of a smaller stroke volume as a result of venous blood pooling. The different exercise response in persons with SCI is a result of the interruption of pathways in the spinal cord to the peripheral sympathetic nervous system in addition to the motor paralysis.

Adult↗

[Sports in the heart rehabilitation group--experiences with ambulatory rehabilitation at home].

Regular physical exercise has shown to be beneficial for patients with cardiovascular disease. Therefore cardiac rehabilitation in Germany is continued for years after hospital discharge in outpatient cardiac exercise groups which meet twice a week under the guidance of a physician and a sports instructor. Before participation cardiac patients have to be examined including exercise tests and echocardiography for assessment of contraindications for exercise therapy as well as individual exercise capacity. Patients are assigned to two groups with different levels of exercise intensity according to their symptom-free work-capacity (cutoff level 1 W/kg). During exercise sessions sports-specific forms of exercise such as stretching, aerobic exercise or ball games are accompanied by psychosocial elements such as stress management. This global approach is intended to improve cardiovascular risk factors, cardiac function, and work capacity as well as to stabilize the patient psychologically in order to accelerate social integration. Recently these groups have opened towards patients after cardiac transplantation or with severe heart failure. Therefore, cardiac exercise groups play a central role in cardiac rehabilitation long after the acute cardiac event.

Ambulatory Care↗

Ultra-triathlon-related blood-chemical and endocrinological responses in nine athletes.

BACKGROUND: Objective of this study was to get more insight in hematology, biochemistry, and endocrinology of ultra-endurance exercise, to improve knowledge in this field, supplementation, and medical care of affected athletes. METHODS: A large body of individual hematological, biochemical, and endocrinological parameters was analyzed in the blood taken from ultra-athletes before and after completing the 1993 Colmar ultra triathlon covering 7.5 km swimming, 360 km cycling, and approximately 85 km running. PARTICIPANTS: Nine experienced ultra-athletes participated in the study. A follow-up was not possible since the athletes left Colmar within 24 hrs after the contest. RESULTS: The athletes finished the ultra-contest at rankings 4, 5, 7, 8, 9, 11, 18, 22, 23 in a total time between 23:38:53 and 27:54:30 hr:min:sec. Their final body mass (68.6 +/- 1 kg) was significantly lower than at baseline (71.9 +/- 4.2 kg). Non of the athletes made use of medical care. Data after this contest reflect mild hyponatremia, intravascular hemolysis, increased triglyceride turnover, acute-phase reaction, hyperaldosteronemia 2061 +/- 1013 pmol.L-1), hypercortisolemia 971 +/- 486 nmol.L-1), hyper-growth-hormonemia (median 6.8 ng.ml-1), hypoinsulinemia, hypo-free-testosteronemia (42 +/- 17 pmol.L-1), protein catabolism, depressed testicular function, oliguria, and muscle cell leakage. CONCLUSIONS: In our opinion, data presented do not reflect any acute health risks in healthy athletes who are well prepared and carefully supplied during such a contest.

Adult↗

Zinc, iron, and magnesium status in athletes--influence on the regulation of exercise-induced stress and immune function.

Intense physical exercise has been shown to be associated with immunosuppression and increased rate of infection. The immunosuppressive effect of exhaustive exercise has been attributed to a reduced helper/suppressor T-cell ratio, low salivary levels of immunoglobulin-A, decreased lymphocyte proliferative response and natural killer cell activity, and elevation of stress hormones. Yet some athletes can withstand intense training periods without health problems while others are prone to infections. Thus it has been postulated that other factors may interfere with immunoregulation. The notion that macro- and micronutrients are involved in the regulation of immunological processes and the ability to cope with muscular and systemic exercise stress has been gaining attention. Particularly trace elements have been shown to be related to cell mediated and humoral immunity such as NK-cell activity, T- and B-cell functions, and cytokine release. Many investigations have reported decreased concentrations of trace elements in blood and tissues after training and competition. However, the magnitude of losses is highly dependent on the type and intensity of exercise, the individual regulatory state, and most important, nutrition. This paper reviews the data on zinc, iron, and magnesium status in athletes and summarizes the consequences of deficiencies in these trace elements regarding exercise tolerance and immune function. These elements were chosen since there is evidence they are related to exercise-induced stress and immune function.

Animals↗

Importance of TNF-alpha and leptin in obesity and insulin resistance: a hypothesis on the impact of physical exercise.

Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.

Animals↗

Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy.

Loss of physical performance is a universal problem of cancer patients undergoing chemotherapy. We postulated that this impairment can be partially prevented by aerobic exercise. In a randomized study, 33 cancer patients receiving high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group, T) performed an exercise program consisting of biking on an ergometer in the supine position after an interval-training pattern for 30 minutes daily during hospitalization. Patients in the control group (C, n = 37) did not train. Maximal physical performance was assessed with a treadmill test by admission and discharge. Physical performance of the two groups was not different on admission. The decrement in performance during hospitalization was 27% greater in the control group than in the training group (P = .05); this resulted in a significantly higher maximal physical performance at discharge in the trained patients (P = .04). Duration of neutropenia (P = .01) and thrombopenia (P = .06), severity of diarrhea (P = .04), severity of pain (P = .01), and duration of hospitalization (P = . 03) were reduced in the training group. We conclude that aerobic exercise can be safely carried out immediately after high-dose chemotherapy and can partially prevent loss of physical performance. Based on the potential significance of the observed outcomes, further studies are warranted to confirm our results.

Adult↗

Physical activity and lipoprotein metabolism: epidemiological evidence and clinical trials.

Prospective epidemiological studies have proven a close link between the lipoprotein profile and cardiovascular morbidity and mortality. As physical activity is accepted as a significant factor improving physical fitness and lipoprotein metabolism, there is evidence that physically active men have a lower cardiovascular risk due to their higher metabolic fitness. Physical activity and physical fitness are generally linked to higher HDL cholesterol and lower LDL cholesterol as well as lower triglyceride and insulin levels. However, in cross-sectional studies the differences in lipoprotein cholesterol evaluated by routine measures in healthy physically active individuals and sedentary controls are only minor compared to therapeutical aims. The impact of exercise and training is often more significant when the effect of exercise on lipoprotein subfractions and apolipoprotein levels are taken into account. Dramatic differences can be documented in concentrations of cardioprotective HDL subset2 and atherogenic small, dense LDL subset6 levels in relation to the individual status of aerobic fitness and body composition in adults. These observations indicate that the preventive and therapeutical use of physical activity is of particular significance in a population of cardiovascular risk or patients with reduced daily activity. Our own experience in clinical trials shows that even in short-term programs (4 weeks to 6 months) changes in activity and eating behavior may lead to important improvements of the metabolic risk and lipid profile. Understanding the complex interaction between exercise and metabolic control of the lipid profile as well as the correlation with other risk parameters will improve the knowledge of prescribing exercise programs in patients at risk.

Adult↗

Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation.

BACKGROUND: Fatigue and loss of physical performance are frequent problems of cancer patients. In a pilot study, the authors evaluated the feasibility and effects of aerobic training in the rehabilitation of cancer patients after completing high dose chemotherapy. METHODS: Sixteen patients participated in a specially designed rehabilitation program for 6 weeks. The patients entered the program, which consisted of walking on a treadmill, shortly after completing treatment. Sixteen patients who did not train served as controls. Physical performance (maximum speed on the treadmill test), cardiac function, and hemoglobin concentration were compared at the time of discharge from the hospital and 7 weeks later. At the second examination, fatigue and limitations in daily activities due to impaired endurance were assessed during personal interviews. RESULTS: At the time of discharge from the hospital, maximum physical performance (training group: 6.2 +/- 1.1 km/hour; controls: 6.2 +/- 1.3 km/hour) and hemoglobin concentration (training group: 10.1 +/- 1.4 g/dL; controls: 10.1 +/- 1.2 g/dL) were similar for both groups. After 7 weeks, improvement in maximum physical performance (training group: 8.3 +/- 1.6 km/hour; controls 7.5 +/- 1.3 km/hour) and hemoglobin concentration (training group: 13 +/- 1 g/dL controls: 12 +/- 1.4 g/dL) were significantly higher for the training group (P < 0.05). By the second examination, no patient in the training group but 4 controls (25%) reported fatigue and limitations in daily activities due to low physical performance. CONCLUSIONS: Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.

Adult↗

Relationship of serum ferritin concentrations with metabolic cardiovascular risk factors in men without evidence for coronary artery disease.

Elevated serum ferritin concentrations between 200 and 500 microg/l have been found to be a strong risk factor for acute myocardial infarction in Finnish men, but the reason for this association is still uncertain. In the Finnish population ferritin concentrations correlated with factors of insulin resistance syndrome. As these factors have been found to be associated with an LDL subfraction phenotype of increased concentrations of small, dense LDL particles, we hypothesized an association between ferritin and an atherogenic LDL subfraction profile, a finding which could be an explanation for the observed relationship between ferritin and atherosclerosis. Therefore we determined serum ferritin levels, metabolic cardiovascular risk factors, and the LDL subfraction phenotype in 93 healthy men without signs for infection or coronary heart disease. We found that men with moderately elevated ferritin levels (200-500 microg/l; n = 31) had a significantly worse coronary risk profile than men with lower levels ( < 200 microg/l; n = 62). Elevated ferritin concentrations were associated with significantly higher values for serum triglycerides, VLDL cholesterol, VLDL apolipoprotein B (P < 0.01), IDL cholesterol, fasting glucose (P < 0.05) and uric acid (P < 0.01), and lower levels for HDL2b and HDL2a cholesterol and apolipoprotein A-I (P < 0.05), and lipoprotein(a) (P < 0.01). Elevated ferritin levels were, however, not associated with an unfavourable LDL subfraction profile of increased concentrations of small, dense LDL particles.

Adult↗

[Rationale for a specific diet from the viewpoint of sports medicine and sports orthopedics. Relation to stress reaction and regeneration].

The relation between nutrition and sport has been studied extensively during recent decades. Nevertheless, research interest was focused mainly on the role of dietary macro- and micronutrients as ergogenic aids. Today, there is increasing support for the hypothesis that the nutrient status also has relevance for the prevention and rehabilitation of systemic and muscular stress induced by intense physical exercise. The increase in muscular stress is indicated by the rise in creatine kinase and myoglobin; the systemic stress is associated with characteristic immunological and hormonal changes and an acute-phase response. During and following exercise, the course of cytokines (especially interleukin 6) and acute-phase proteins (C-reactive protein, fibrinogen) as well as cortisol levels are an indirect measure of the exercise intensity and the individual ability to cope with physical stress. It has been shown that the dietary intake and, consequently, the systemic or intracellular concentrations of minerals such as magnesium and zinc, vitamins with antioxidant capacity (vitamin E, C, E, and beta carotine), and the composition of fatty acids can be related to the exercise-induced stress response. Therefore, this review deals specifically with the impact of these nutritional components on the reduction of sports specific muscular damage and systemic stress, especially under the aspect of increased losses during and following intense physical exercise.

Antioxidants↗

Stage duration and increase of work load in incremental testing on a cycle ergometer.

Any variation of the test protocol for incremental testing (IT) in cycle ergometry may affect the accuracy of the determination of anaerobic threshold (AnT). For lactate threshold concepts, indicating the maximum lactate steady-state (max Lass), the formation of the quasi-steady-state (QSS=95% of steady-state level) is evident. Previous studies have not specified the time that it takes for blood lactate to stabilize following incremental changes in WL. The purpose of this study was to identify the minimum duration of exercise necessary to establish QSS following various increments in WL (10, 20, 30, 40 and 50 W). Eight male endurance-trained cyclists [relative maximal oxygen consumption = 64.8 (4.2) ml x kg(-1) x min(-1)] performed three different exercise tests on a cycle ergometer: (1) an exhaustive IT with a starting WL of 100 W, followed by 20-W increments every 3 min; (2) a threshold test with 20-W increments every 9 min to determine the MaxLaSS; and (3) five incremental exercise tests (from 100/110 W, with 20-W increments every 3 min) with a final 10-, 20-, 30-, 40- or 50- W increment lasting 10 min, at 10 W below MaxLaSS (T10-T50 experiments). The time constant of lactate kinetics (tau), the time constant of lactate elimination, and the time taken to elicite QSS, defined as 95% of the time taken to reach steady-state level (t95%), were calculated in the T10-T50 experiments. The tau and t95% increased significantly with WL increment size: the correlation was not linear. Smaller WL increments required proportionally longer durations. Mean (SD) t95% values (min:s) were 1:57 (0:27) (T10), 2:58 (0.16) (T20), 4:08 (0:23) (T30), 4:45 (0:45) (T40) and 5:06 (0:43) (T50). The application of these references in IT protocols may lead to an extension of total test duration, particularly with smaller increments. Therefore, lactate threshold modelling, the training status of the athletes and comparability with lactate measurements obtained during training events should be considered. IT protocols not accomplishing QSS criteria may effect an underestimation of WL-related lactate values and an overestimation of lactate thresholds, which indicate MaxLaSS, especially in highly trained athletes. This suggests that the establishment of an increment-size-dependent t95% may reduce protocol-related influences on AnT and standardize the use of the AnT in IT procedures in the training management of elite cyclists.

Adult↗

Differences in the concentration and composition of low-density lipoprotein subfraction particles between sedentary and trained hypercholesterolemic men.

There is evidence that a low-density lipoprotein (LDL) subfraction profile of increased concentrations of small, dense LDL particles is less common among trained than among sedentary normocholesterolemic men, but it is still uncertain whether there is a similar association in hypercholesterolemia also. Therefore, we determined the lipid and apolipoprotein concentration and composition of six LDL subfractions (density gradient ultracentrifugation) in 20 physically fit, regularly exercising (>three times per week) hypercholesterolemic men and 20 sedentary hypercholesterolemic controls. Trained (maximal oxygen consumption [VO2max], 57.3 +/- 7.4 mL/kg/min) and sedentary (VO2max, 37.5 +/- 8.8 mL/kg/min) individuals (aged 35 +/- 11 years; body mass index [BMI], 23.9 +/- 2.7 kg/m2) were matched for LDL apolipoprotein (apo) B levels (108 +/- 23 and 112 +/- 36 mg/dL, respectively). Trained subjects had significantly lower serum triglyceride (P < .05) and very-low-density lipoprotein (VLDL) cholesterol levels (P < .05) and higher high-density lipoprotein 2 (HDL2) cholesterol levels (P < .01) than sedentary controls. LDL particle distribution showed that trained individuals had significantly less small, dense LDL (d = 1.040 to 1.063 g/mL) and more large LDL (d = 1.019 to 1.037 g/mL) subfraction particles than sedentary controls, despite equal total LDL particle number. Analysis of LDL composition showed that LDL particles of hypercholesterolemic trained men had a higher free cholesterol content than LDL of untrained hypercholesterolemic men. Small, dense LDL in hypercholesterolemic trained men were richer in phospholipids than those in sedentary controls. These data demonstrate the significant influence of aerobic fitness on lipoprotein subfraction concentration and composition, thereby emphasizing the role of exercise in the treatment and risk reduction of hypercholesterolemia.

Centrifugation, Density Gradient↗