Healthy Middle-aged Volunteers Research Articles

Randomized controlled trial of home-based exercise training to evaluate cardiac functional gains

There is evidence that multiple benefits can be obtained through exercise training that leads to increases in peak oxygen consumption (V(O(2))). It is unclear whether significant improvements can also be achieved through unsupervised low-budget home-based training regimes, especially in terms of cardiac functional gains. A randomized cross-over trial was conducted to investigate the effects of a home-based unsupervised exercise training programme of moderate intensity on aerobic capacity, cardiac reserve and peak cardiac power output in healthy middle-aged volunteers. Nine subjects with no known cardiovascular diseases performed symptom-limited treadmill cardiopulmonary exercise tests after an 8-week period of exercise training, and results were compared with those obtained after a similar 'non-exercising' control period. Cardiac output was measured non-invasively during exercise tests using the CO(2)-rebreathing method. With exercise training, resting heart rate decreased significantly from 88.3+/-3.4 to 78.7+/-3.2 beats.min(-1) (P<0.05), heart rate at a submaximal workload (V(O(2))=1.5 litres.min(-1)) decreased from 125.5+/-2.4 to 115.5+/-1.6 beats.min(-1), and peak V(O(2)) increased by 9% from 2.62+/-0.19 to 2.85+/-0.18 litres.min(-1) (P<0.01). Baseline cardiac power output was 1.11+/-0.05 W, and this remained unchanged with training. Peak cardiac power output increased by 16% from 4.1+/-0.3 to 4.7+/-0.3 W (P<0.001), and cardiac reserve increased by 21% (P<0.01). A major contribution to these increases was from the 11% increase in stroke volume, from 100.1+/-5.3 to 111.2+/-6.2 ml (P<0.001). All subjects reported more positive perceptions of their health (P<0.05), fitness (P<0.01) and levels of activity (P<0.01) after the training period. These results show that motivated subjects undergoing low-budget unsupervised home-based exercise training of moderate intensity can derive benefit in terms of symptoms, aerobic capacity and cardiac functional reserve.

GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden.

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.

A Ginkgo biloba/Panax ginseng combination enhances memory in healthy middle aged volunteers

Major scholars in the field, on the basis of a 3-day consensus, created an in-depth review of current knowledge on the role of diet in cardiovascular disease (CVD), the changing global food system and global dietary patterns, and potential policy solutions. Evidence from different countries and age/race/ethnicity/socioeconomic groups suggesting the health effects studies of foods, macronutrients, and dietary patterns on CVD appear to be far more consistent though regional knowledge gaps are highlighted. Large gaps in knowledge about the association of macronutrients to CVD in low- and middle-income countries particularly linked with dietary patterns are reviewed. Our understanding of foods and macronutrients in relationship to CVD is broadly clear; however, major gaps exist both in dietary pattern research and ways to change diets and food systems. On the basis of the current evidence, the traditional Mediterranean-type diet, including plant foods and emphasis on plant protein sources provides a well-tested healthy dietary pattern to reduce CVD.

The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers

A multicenter European study (FoodCue) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo. The present work describes the effect of Cu supplementation on (2,2′-azo-bis(2-amidinopropane) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people. Double-blinded copper supplementation was achieved in 26 healthy volunteers (50–70 years) with pills containing 3 mg CuSO 4, 3 mg Cu glycine chelate (CuG) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout (WO) on placebo. The results show significant increases in time necessary to achieve 50% hemolysis (LT 50) after 3CuSO 4 and 6CuG compared with values after WO periods. Cu supplementation did not increase the levels of (Cu,Zn)SOD activity in red blood cells. Resistance to hemolysis was significantly and positively correlated (r = .30, p < .01) with α- and β-carotene content in the plasma. Together, these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation. The decreased oxidizability of red blood cells did not result from increased (Cu,Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content.

Age dependence of perimacular white blood cell flux during isometric exercise

Purpose. To investigate the age dependence of perimacular white blood cell flux (WBCF) during isometric exercise. Methods. Fourteen healthy young (age range: 21–29 years; 24 ± 3 years, mean ± SD, 12 male and 2 female) and 15 healthy middle-aged (age range: 45–57 years; 53 ± 4 years, mean ± SD; 5 male and 10 female) volunteers were studied. Subjects performed isometric handgrip for 10 minutes and squatting for 6 minutes. WBCF was assessed with the blue field entoptic technique, mean arterial pressure (MAP) was measured with an automated oscillometric device, intraocular pressure (IOP) was measured by Goldmann applanation tonometry and ocular perfusion pressure (OPP) was calculated as 2/3 MAP – IOP. Results. Baseline WBCF was significantly higher in young subjects than in middle-aged subjects (191 ± 28 vs 142 ± 23; p = 0.001). Isometric handgrip induced a significant increase in WBCF in the middle-aged subjects (23 ± 24%; p = 0.005), but not in the young subjects. Squatting significantly increased WBCF in both groups (young: 42 ± 23%; p = 0.004 and middle aged: 51 ± 27%; p < 0.001). A significant deviation from baseline WBCF was observed when OPP increased by 42 ± 4% (p = 0.003) and 35 ± 4% (p < 0.001) for the young and middle-aged subjects, respectively. The OPP-WBCF relationship was not different between the two study groups. Conclusion. Altered retinal autoregulation as observed in vascular ocular disease appears to be unrelated to the normal physiological aging process.

Lack of effects of moderate-high altitude upon lung function in healthy middle-aged volunteers

This study investigates the effects of moderate-high altitude on lung function and exercise performance in 46 volunteers (19 females, 27 males), with a mean age of 42·4±1·4 years (± sem) and varying smoking and exercise habits, who were not previously acclimatized. Measures obtained in the base camp (1140 m) and at altitude (2630 m), in random order, included forced spirometry, maximal voluntary ventilation, maximal inspiratory and expiratory pressures, arterial oxygen saturation and capillary lactate concentration after a standardized exercise test. The smoking history, Fagerström test and degree of habitual physical activity were also recorded for each participant. The percentage of smokers was similar in males (19%) and females (21%) ( P=n.s.). Mean habitual physical activity index was 8·2±0·2 (range, 5·88-11·63). At the base camp, all lung function variables were within the normal range. Lactate concentration after exercise averaged 3·7±0·3 mm 1 −1. No significant change was observed at altitude, except for a higher heart rate and a lower arterial oxygen saturation (SaO 2) (both at rest and after inspiratory manoeuvres). The smoking history and the degree of physical activity did not influence lung function or exercise performance at altitude. The results of this study show that in middle-aged, healthy, not particularly well-trained individuals, lung function is not significantly altered by moderate-high altitude, despite the absence of any acclimatization period and independent of their smoking history and previous exercise habits.

Diabetic alteration of cardiac vago-sympathetic modulation assessed with tone-entropy analysis.

No clear evidence of diabetic alteration of cardiac sympatho-vagal balance has been reported to date. We assessed heart rate variability of diabetic patients with the tone-entropy analysis that has been published elsewhere (Oida et al. 1997). Tone reflects the cardiac vago-sympathetic balance and entropy the total autonomic efferent activity. Diabetic influence on tone and entropy was examined in two groups of patients (38-52 years and 60-69 year, total 106) stratified according to the occurrence of impaired glucose tolerance or diabetes mellitus. Ten healthy middle-aged volunteers were also examined as a reference. Electrocardiographic data were collected at rest for 10 min. Tone increased and entropy decreased significantly with severity of diabetic disorders. The alterations were depicted as a curvi-linear relation in tone-entropy space, which superimposed adequately on the standard tone-entropy values obtained in a pharmacological experiment. The results demonstrate that the vago-sympathetic balance is altered with diabetic disorders: vagal predominance is impaired significantly in proportion to a withdrawal of total autonomic efferent activity.

Effects of high- and low-fat meals on the diurnal response of plasma lipid metabolite concentrations in healthy middle-aged volunteers

Three experiments were conducted in healthy middle-aged volunteers (six males and six females in Expt 1, six males and two females in Expt 2 and twelve males in Expt 3) with a mean BMI of 27 kg/m2to determine whether there is a difference between morning and afternoon dietary fat clearance and utilization, and to determine in what way the fat and starch contents of the meal influence postprandial blood lipid metabolites over 4·5 h. Over 4 days in Expt 1 each subject received isoenergetic, high-carbohydrate (L, 5·5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a high fat lunch (NM) in a randomized and balanced arrangement. Each evening a standard meal was given. The following effects were significant (P&lt;0·05): plasma triacylglycerol (TAG) responses were greater following M meals; plasma TAG concentrations were greater in the afternoon than in the morning, following two meals of the same composition, although the postprandial incremental response was less following lunch than following breakfast and peak responses were reached much earlier than after breakfast; a low-fat breakfast, or fasting at breakfast time, delayed the peak TAG response to a M lunch. The plasma concentrations of non-esterified fatty acids (NEFA) and of free glycerol were higher in the afternoon following M meals at breakfast and lunch, especially in males. This response was reduced, by the L breakfast preceding the M lunch. Two M meals in succession lowered plasma HDL-cholesterol concentration. In Expt 2 each subject received a very low-fat (VL) breakfast, followed by a lunch of the same composition. Each of these meals was followed, 110 min from the start of eating, by an infusion of Intralipid 10% emulsion at the rate of 1 ml/kg body weight over 60 s. Clearance rates of Intralipid were faster in the afternoon than in the morning (P= 0·024). In Expt 3 twelve subjects were randomly allocated to either treatment MM or LM meal patterns, as given in Expt 1. These were given daily for a period of 17 d, during which the change in fasting plasma TAG concentration was similar in both treatments. On days 1, 16 and 17 responses were measured to the M lunch and to a glucose tolerance test (GTT), conducted 2 h 17 min after lunch. The post-lunch responses confirmed those found in Expt 1; but immediately following the glucose dose there was an abrupt increase in plasma TAG that was greater in treatment LM than in treatment MM (P= 0·025), whereas plasma NEFA concentration decreased rapidly in both treatments at that time (P = 0·00066)

Magnetic Resonance Imaging of the Discs and Trunk Muscles in patients with Chronic Low Back Pain and Healthy Control Subjects

This study aimed to evaluate the lumbar intervertebral discs and the maximum isometric strength and size of the trunk muscles of middle-aged healthy volunteers (60 persons) and low back pain patients (48 persons). Disc degeneration was more frequently seen in the patients than in the healthy volunteers. The psoas and back muscles (erector spinae and multifidus) of the patients were smaller than those of the volunteers. Patients had also more fat deposits in the back muscles than controls. The maximum isometric strength of trunk muscles of the patients was on average weaker than that of the volunteers. However, the size of the back muscles was not related to the maximum isometric extension strength of the trunk.

Metabolic and hemodynamic effects of insulin on human hearts.

Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta-hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of Aggregated Leukocytes in the Circulating Pool during Stress – Demargination Is Not Necessarily a Result of Decreased Leukocyte Adhesiveness

Leukocyte endothelial interactions are essential for a normal immune response. It is known that this response is influenced by stress and that the latter induces demargination. We examined the question of whether stress demargination results from a decreased state of leukocyte adhesiveness. Included were various volunteers and patients under different degrees of stress. 66 young athletes before beginning their daily exercises, 67 middle-aged healthy volunteers, 25 patients before ergometry for evaluation of chest pain, 75 patients who were referred to the emergency room with chest pain without ischemia/infarction, 78 patients with ischemia/infarction, 65 patients with minor trauma, 25 with a fracture and 12 with polytrauma. The leukocyte adhesiveness/aggregation (LAA) values were measured with a direct slide test. The respective LAA values were 7.4 +/- 4.7, 6.3 +/- 4.4, 5.8 +/- 3.6, 5.2 +/- 3.5, 10.8 +/- 8.5, 9.1 +/- 5.8, 12.2 +/- 6.6 and 19 +/- 12.6% of aggregated leukocytes. We conclude that an increase in aggregated white blood cells can be detected in the circulating pool during major stress. It is therefore suggested that stress demargination is not necessarily a result of diminished leukocyte adhesiveness.

Pharmacokinetics of Diltiazem and Its Metabolites After Single and Multiple Dosing in Healthy Volunteers

The pharmacokinetics of diltiazem in healthy middle-aged volunteers have been investigated after single and multiple doses. Twenty men or women were recruited and were given one single dose and one steady-state treatment in a crossover fashion. Ten were given 60-mg single dose and 60-mg t.i.d. during 14 days and 10 received 120 mg as a single dose and as 120-mg t.i.d. The single dose and the last dose in steady state were pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be described using a two-compartment model with terminal half-lives of 6.27 +/- 3.23 h (mean +/- SD) after a single dose of 60 mg diltiazem, 6.05 +/- 1.59 h after 60-mg diltiazem t.i.d., 5.85 +/- 1.04 h after 120-mg diltiazem and 5.90 +/- 0.69 h after 120-mg diltiazem t.i.d. The half-life of the metabolite N-demethyldiltiazem was similar to that of diltiazem whereas the half-lives of the metabolites deacetyldiltiazem and N-demethyldeacetyldiltiazem were longer. The area under the curve of diltiazem in a dosing interval at steady state increased significantly compared with the single dose, indicating an increased bioavailability after repeated dosing, probably because of decreased presystemic elimination. The cumulative excretions of radioactivity in urine within 120 h were 72 +/- 5%, 71 +/- 8%, 71 +/- 6%, and 73 +/- 4%, respectively. The remaining amounts were excreted in feces.

Pharmacokinetics of Diltiazem and Its Metabolites After Repeated Multiple-Dose Treatments in Healthy Volunteers

In a complete crossover study, balanced for sex and treatment order, we have investigated the pharmacokinetics of diltiazem in 10 healthy middle-aged volunteers. The treatments were 60 mg t.i.d. and 120 mg t.i.d. during 14 days' treatment, with the last dose pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be appropriately described using a two-compartment model with terminal half-lives of 6.57 +/- 1.41 h (mean +/- SD) after 60 mg t.i.d. and 5.44 +/- 0.66 h after 120 mg t.i.d. The half-life of the metabolite N-demethyldiltiazem (MA) was similar to that of diltiazem, whereas the half-lives of deacetyldiltiazem (M1) and N-demethyldeacetyldiltiazem (M2) were longer. The plasma concentrations and areas under the curve found after doubling of the dose were not significantly different from dose-adjusted directly proportional estimations. However, the mean concentration of MA in percent of diltiazem concentration was significantly higher at the lower-dose regimen 41 +/- 11% versus 36 +/- 8%, whereas the corresponding values for M1 were 11 +/- 3% versus 11 +/- 4% and for M2 12 +/- 4% versus 12 +/- 6%, respectively. The median cumulative excretions of radioactivity during 120 h were 90 and 93%, respectively. The drug was mainly excreted in urine (73 versus 73%, median), the remaining amounts were eliminated in feces.

Influence of demographic parameters on rectal epithelial proliferation.

Measurement of rectal epithelial proliferation is now being used as a biomarker for assessing risk for colorectal cancer and response within dietary intervention studies. We examined the possible confounding effects of demographic parameters on the proliferation of 52 healthy middle-aged volunteers without known risk factors for colorectal cancer. No significant effects on proliferation of age, sex or ethnic grouping were found other than marked urban-rural differences amongst men. We hypothesise that these could be explained by differences in dietary habits and their deleterious effects in the older male population. Careful matching of controls are probably needed in order to demonstrate the minor changes in mucosal proliferation that could reflect risk for neoplasia. Further human studies are needed to examine the effects of diet and extremes of age on proliferation.