Muscle-specific creatine kinase gene polymorphisms in elite endurance athletes and sedentary controls

The purpose of this study was to investigate the association between elite endurance athlete (EEA) status and two restriction fragment length polymorphisms (RFLPs) at the muscle-specific creatine kinase (CKMM) gene locus. Genomic DNA was extracted from white blood cells or lymphoblastoid cell lines of 124 unrelated Caucasian male EEA (VO2max > 73 mL.kg-1.min-1) and 115 unrelated Caucasian sedentary male controls (SCON). The genetic polymorphism at the CKMM locus was detected by the polymerase chain reaction and DNA digestion with the NcoI and TaqI restriction endonucleases. The allelic frequencies for the NcoI and TaqI RFLPs were not different (P > 0.05) between EEA and SCON subjects. The three expected genotypes for CKMM-NcoI (1170/1170 bp, 1170/985 + 185 bp, and 985 + 185/985 + 185 bp) and CKMM-TaqI (1170/1170 bp, 1170/1020 + 150 bp, and 1020 + 50/1020 + 150 bp) were observed in the EEA and SCON groups. These genotype frequencies were in Hardy-Weinberg equilibrium, but they were not significantly (P > 0.05) different between the EEA and SCON. A strong (P < 0.001) linkage disequilibrium was detected among the NcoI and TaqI RFLPs in both EEA and SCON. These findings indicate that the skeletal muscle CK-NcoI and CK-TaqI gene polymorphisms are not associated with the elite endurance athlete status.     

Hypertension in master endurance athletes

OBJECTIVE: To determine whether long-term very vigorous endurance training prevents hypertension. DESIGN: Cohort study of master orienteering runners and controls. SETTING: Finland. SUBJECTS AND METHODS: In 1995, a health questionnaire was completed by 264 male orienteering runners (response rate 90.4%) who had been top-ranked in competitions among men aged 35-59 years in 1984, and by 388 similarly aged male controls (response rate 87.1%) who were healthy at the age of 20 years and free of overt ischemic heart disease in 1985. MAIN OUTCOME MEASURE: Self-report of medication for hypertension. RESULTS: In the endurance athlete group, the crude prevalence (8.7%) of subjects who had used medication for hypertension was less than a third of that in the control group (27.8%). Even after adjusting for age and body mass index, the difference between the groups was still significant (odds ratio for athletes 0.43, 95% confidence interval 0.25-0.76). CONCLUSIONS: Long-term vigorous endurance training is associated with a low prevalence of hypertension. Some of the effect can be explained by a lower body mass, but exercise seems to induce a lower rate of hypertension by other mechanisms than by decreasing body weight     

Overtraining in endurance athletes: a brief review

Overtraining is an imbalance between training and recovery, exercise and exercise capacity, stress and stress tolerance. Stress is the sum of training and nontraining stress factors. Peripheral (short-term overtraining, STO) or peripheral and central fatigue may result (long-term overtraining, LTO). STO lasting a few days up to 2 wk is termed overreaching. STO is associated with fatigue, reduction, or stagnation of the 4 LT performance capacity (performance at 4 mmol lactate or comparable criterion), reduction of maximum performance capacity, and brief competitive incompetence. Recovery is achieved within days, so the prognosis is favorable. LTO lasting weeks or months causes overtraining syndrome or staleness. The symptomatology associated with overtraining syndrome has changed over the last 50 yr from excitation and restlessness (so-called sympathetic form) to phlegmatic behavior and inhibition (so-called parasympathetic form). Increased volume of training at a high-intensity level is likely the culprit. The parasympathetic form of overtraining syndrome dominates in endurance sports. Accumulation of exercise and nonexercise fatigue, stagnation, or reduction of the 4 LT performance capacity, reduction in maximum performance capacity, mood state disturbances, muscle soreness/stiffness, and long-term competitive incompetence can be expected. Complete recovery requires weeks and months, so the prognosis is unfavorable. Other optional or further confirmation requiring findings include changes in blood chemistry variables, hormone levels, and nocturnal urinary catecholamine excretion. Based on the findings reported, recommendations for training monitoring can be made, but their relevance in the practice must still be clarified.     

Lipoprotein(a) in health and disease

Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a).     

Lipoprotein (a) and plasminogen in atherosclerosis

The aim of this study was to evaluate plasma levels of lipoprotein (a) [LP(a)] and plasminogen in patients affected with atherosclerotic disease and to understand the mutual relationships. Eighty-four patients affected with atherosclerosis were examined and divided as follows: group I, 24 patients with peripheral arteriopathy; group II, 40 patients with ischemic heart disease (myocardial infarction and/or angina pectoris); group III, 20 patients with multi-infarct dementia; group IV (control group) with 20 healthy young subjects. The results show that Lp(a) plasma levels, in atherosclerotic patients, are higher than 30 mg/dl, while the plasminogen levels are lower than 80 mg/dl. There is an inverse correlation between these two data. Moreover, a different behaviour of Lp(a) and plasminogen rate related to age of patients, to number of atherosclerotic lesions or to acuteness of ischemic heart disease, was observed.     

Lipoprotein(a) in health and disease

Lipoprotein(a) [Lp(a)] represents an LDL-like particle to which the Lp(a)-specific apolipoprotein(a) is linked via a disulfide bridge. It has gained considerable interest as a genetically determined risk factor for atherosclerotic vascular disease. Several studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke, and peripheral atherosclerosis. In healthy individuals, Lp(a) plasma concentrations are almost exclusively controlled by the apo(a) gene locus on chromosome 6q2.6-q2.7. More than 30 alleles at this highly polymorphic gene locus determine a size polymorphism of apo(a). There exists an inverse correlation between the size (molecular weight) of apo(a) isoforms and Lp(a) plasma concentrations. The standardization of Lp(a) quantification is still an unresolved task due to the large particle size of Lp(a), the presence of two different apoproteins [apoB and apo(a)], and the large size polymorphism of apo(a) and its homology with plasminogen. A working group sponsored by the IFCC is currently establishing a stable reference standard for Lp(a) as well as a reference method for quantitative analysis. Aside from genetic reasons, abnormal Lp(a) plasma concentrations are observed as secondary to various diseases. Lp(a) plasma levels are elevated over controls in patients with nephrotic syndrome and patients with end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus result mainly from insufficient sample sizes of numerous studies. Large studies and those including apo(a) phenotype analysis came to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In noninsulin-dependent diabetics, Lp(a) is not elevated. Conflicting data also exist from studies in patients with familial hypercholesterolemia. Several case-control studies reported elevated Lp(a) levels in those patients, suggesting a role of the LDL-receptor pathway for degradation of Lp(a). However, recent turnover studies rejected that concept. Moreover, family studies also revealed data arguing against an influence of the LDL receptor for Lp(a) concentrations. Several rare diseases or disorders, such as LCAT- and LPL-deficiency as well as liver diseases, are associated with low plasma levels or lack of Lp(a).     

Low LDL oxidation in veteran endurance athletes

In this observational study, multiplanar three-dimensional ultrasound images were reconstructed from tomographic views obtained by scanning seven cadavaric fetal hearts with various congenital heart defects. Comparisons were made with multiplanar three-dimensional magnetic resonance imaging (MRI) of the hearts. Good-quality echocardiographic images were obtained in all but one of the fetal hearts. Multiplanar as well as three-dimensional reconstructions were possible and allowed accurate assessment of complex cardiac defects. Overall, the MRI projections had better image quality and revealed more structural details than the sonographic views, although both imaging modes showed the same cardiac anatomical abnormalities. Our initial results demonstrate that simultaneous multiplanar display of cross-sectional echocardiographic views can be performed to provide three-dimensional images of the fetal heart, demonstrating structural cardiac malformation. However, the clinical application of three-dimensional fetal echocardiography is at present limited by the time required for image data acquisition and the need for accurate temporal and positional gating in the living fetus.     

Overtraining and immune system: a prospective longitudinal study in endurance athletes

A prospective longitudinal study investigated for 19 +/- 3) months whether immunophenotypes of peripheral leukocytes were altered in periods of severe training. Leukocyte membrane antigens (CD3, CD4, CD8, CD14, CD16, CD19, CD45, CD45RO, and CD56) of endurance athletes were immunophenotyped (dual-color flow cytometry) and list mode data analyzed by a self-learning classification system in a state of an overtraining syndrome (OT; N = 15) and several occasions without symptoms of staleness (NS; N = 70). Neither at physical rest nor after a short-term highly intensive cycle ergometer exercise session at 110% of the individual anaerobic threshold did cell counts of neutrophils, T, B, and natural killer cells differ between OT and NS. Eosinophils were lower during OT, activated T cells (CD3+HLA/DR+) showed slight increases (NS: 5.5 +/- 2.7; OT 7.3 +/- 2.4% CD3+ of cells; means +/- SD; P < 0.01) during OT without reaching pathological ranges. The cell-surface expression of CD45RO (P < 0.001) on T cells, but not cell concentrations of CD45RO+ T cells, were higher during OT. OT could be classified with high specificities (92%) and sensitivities (93%). It is concluded that OT does not lead to clinically relevant alterations of immunophenotypes in peripheral blood and especially that an immunosuppressive effect cannot be detected. Immunophenotyping may provide help with the diagnosis of OT in future, but the diagnostic approach presented here requires improvements before use in sports medicine practice is enabled.     

Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

Left ventricular function during exercise in athletes and in sedentary men

Galactose-1-phosphate uridyltransferase (GALT) is a key enzyme in the metabolism of galactose. GALT activates the galactose-glucose interconversion and enables the synthesis of glucose-1-phosphate and UDP-galactose (UDP-Gal). UDP-Gal is the galactosyl donor for the incorporation of galactose into complex oligosaccharides, glycoproteins and glycolipids. The expression of GALT was characterized both in vivo and in vitro during late embryonic and postnatal development of the brain and peripheral nerve of the rat. Assays of GALT mRNA and protein showed that it is weakly expressed during late embryonic development with a second peak of expression concomitant with myelinogenesis. GALT was prominently expressed in myelinating Schwann cells in a rat dorsal root ganglia culture system. GALT deficiency in humans results in galactosemia, a disease characterized by long-term intellectual impairment, and probably dysmyelination. The developmentally regulated pattern of GALT expression during maturation of the nervous system may provide a molecular basis for these neurological complications which seriously compromise the outcome of many galactosemic patients.     

Lipoprotein profile, diet and body composition in athletes practicing mixed an anaerobic activities

To investigate the prevalence and possible role of anti-endothelial cell antibodies (AECA) in the pathogenesis of systemic lupus erythematosus (SLE), cell membrane antigen was prepared from cultured human umbilical vein endothelial cells and immunoblotting performed to detect AECA in SLE sera. IgG-AECA could be detected in 41 (86%) of 47 SLE patients. They were highly specific and failed to react with membrane antigens of human peripheral blood mononuclear cells or granulocytes. IgG-AECA reacted with endothelial membrane antigens which ranged from 15 to 200 kDa in molecular size. Further analysis of the antigens reacting with IgG-AECA revealed some interesting correlations between specific species of antibodies with certain clinical manifestations. Thus, patients having lupus nephritis, vasculitis, and hypocomplementemia had IgG-AECA against a 66-kDa membrane antigen; those with thrombocytopenia had IgG-AECA against a 55-kDa antigen; those with pleuritis had IgG-AECA against an 18-kDa antigen. These results indicate that IgG-AECA in the sera of SLE patients consist of heterogenous species.     

Lipoprotein(a) and diabetes. An update

On the basis of the available data (much of which is contradictory), I suggest that the following might summarize the role of Lp(a) in diabetes currently. 1. Lp(a) in IDDM: Concentrations are probably elevated. Concentrations are probably related to metabolic control. Concentrations are increased with microalbuminuria. 2. Lp(a) in NIDDM: Concentrations are not elevated. Concentrations do not change with metabolic control. Too few data exist to make an assessment of relation of Lp(a) to microalbuminuria in NIDDM. 3. Lp(a) and CHD in diabetes: Little current evidence shows that Lp(a) is a risk factor for CHD in diabetes. More studies--especially prospective studies with larger numbers of subjects--need to be done.     

Lipoprotein (a): effect of detraining

Plasma levels of lipoprotein (a), total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apo-protein Al and apoprotein B were evaluated for 8 long-distance runners during the XXIII New York Marathon, with blood samples being taken before and after the race, and after one month of detraining. After detraining lipoprotein (a) increased significantly both with respect to basal values and especially with respect to immediately post-race values. Negligible and predictable modifications of the other metabolic parameters evaluated, were observed. No correlation was found between lipoprotein (a) and the anthropometrical data and metabolic parameters considered.     

Cardiovascular adaptations to endurance training and detraining in young and older athletes

A cross-sectional survey was carried out in a sugar estate in central Ethiopia to identify a subgroup for a cohort study on the natural history of HIV infection. HIV prevalence was 2.8% (95% confidence interval [CI], 1.7%-3.9%) in 957 adults aged 15 to 54 years randomly selected for the initial survey. A follow-up survey including only factory workers of the estate aged 18 to 45 years (n = 280) showed a higher HIV prevalence in male factory workers (n = 262) compared with the male estate workers of the same age of the initial survey (n = 484; 8.8% versus 3.1 %; p < .05). Factors independently associated with HIV infection in male factory workers were number of lifetime sexual partners, positive syphilis serology, higher income, and absence of travel outside the residential area. Among male estate workers, only older age was associated with HIV infection. Both factory workers and male estate workers were stable residents and were willing to participate in a long-term study on HIV/ AIDS. However, because of the higher HIV prevalence in factory workers and the higher prevalence of behaviors associated with an increased risk for HIV infection, factory workers were selected for the long-term cohort study on the natural history of HIV infection.     

Left ventricular mass, geometry, and filling in endurance athletes: association with exercise blood pressure

We studied whether left ventricular (LV) mass and concentricity [relative myocardial volume (RMV)] are associated with exercise blood pressure (BP) in athletes. LV structure and filling were evaluated by Doppler echocardiography and BP in maximal bicycle ergometry and isometric handgrip tests on 32 male endurance athletes and 15 age-matched controls. Indexed LV mass was 145 +/- 14 (SD) g/m in athletes and 93 +/- 20 g/m in controls. Mass was not associated with BP at rest or in low-grade exercise, but with heavier exercise loads this association strengthened in athletes, being maximal at peak exercise (r = 0.65 for mass and 0.58 for indexed mass; P < 0.001). Multivariate analysis indicated that BP at peak exercise accounted for 34% and the amount of training for an additional 11% of the variance in indexed LV mass. RMV was 21% larger in athletes. Only the increase in systolic BP during handgrip explained significantly (19%) the variance in RMV. LV filling velocities were not associated with mass, RMV, or BP. We conclude that in endurance athletes LV mass is associated with BP in heavy dynamic exercise and LV concentricity with BP response in static exercise.     

Lipoprotein (a) concentrations in patients with various dyslipidaemias

The results of operative treatment of 45 flexible flat feet (29 patients) using the sinus tarsi spacer are reported. Although radiological improvement in both the talar declination and the ground-navicular distance was found, our patients suffered from pain and functional impairment for an average period of 5 months. An unacceptably high rate of spacer dislocation was noted. Furthermore, the literature indicates spontaneous improvement as the natural history of flexible flat feet. We therefore no longer advise the sinus tarsi spacer as a routine treatment for flexible flat feet.     

Lipoprotein(a)--possible role in the fibrinolysis process

The clinical and epidemiological features of 120 episodes of Streptococcus pyogenes bacteraemia in St. Thomas' Hospital between 1970 and 1997 were analysed. One-third of episodes were nosocomial. M1 was the most common serotype, and 29% of strains were non-typable. There was a variety of presenting features, but nearly half of the patients had cellulitis, 15% were shocked, and 6% had necrotic infections. There was no focus of infection in 13%. 54% of patients had an underlying disease, and 23% of infections were associated with a medical procedure or device. The mortality rate was 19%, and was associated with shock, coma, no focus of infection, and underlying disease. Since 1989, the annual incidence has more than doubled, and M1 strains and necrotic infections have increased, but the mortality rate and the proportion of patients presenting with shock have decreased, and the increase in cases involved many different M-types.     

Lipoprotein Lp(a) excess and coronary heart disease

A pharmacokinetic study of all-trans retinoic acid (ATRA) was performed in 8 patients with various types of leukemia and MDS. After oral administration at a dose of 30 mg/m2, the mean peak plasma concentration was 430 ng/ml and was reached at 150 min. In one patient who failed to respond a very low plasma ATRA level was seen. Though the plasma ATRA exposure decreased significantly with daily drug administration, an intermittent schedule of ATRA administration would yield higher plasma drug concentrations. We treated 2 patients with refractory acute promyelocytic leukemia (APL) in a pilot study of ATRA followed by intensive chemotherapy (APL-ATRA protocol). Two patients successfully achieved complete remission with ATRA after failing under conventional chemotherapy. Based on the pharmacokinetic study of ATRA, an intermittent schedule of ATRA in addition to chemotherapy suggests an effective regimen for children with APL. Phase II trials to evaluate the role of intermittent schedules of ATRA are planned in Children's Cancer and Leukemia Study Group.     

Lipoprotein(a): a link between thrombosis and atherosclerosis?

Lipoprotein(a) (Lp(a)) represents a class of plasma lipoproteins similar to low-density lipoprotein (LDL), but containing an unique apolipoprotein(a) with striking homology to plasminogen. Plasma Lp(a) is inherited as a quantitative genetic trait, with a continuous distribution in Caucasian populations (< 10-2000 mg/l), where high levels are associated with an increased risk of atherosclerotic disease. The physiological role of Lp(a) is unknown, and the metabolism is obscure. Plasma Lp(a) is apparently resistent to diets and drug therapy, and LDL-apheresis is currently the most effective way of reducing plasma Lp(a). However, clinical benefits of lowering plasma Lp(a) have not been demonstrated, and specific therapeutic goals cannot be recommended at present. The structural similarity between apo(a) and plasminogen has generated several experimental observations indicating a prothombogenic and proatherogenic role of Lp(a), but the exact pathophysiological mechanisms have not been determined.