Serial left ventricular adaptations in world-class professional cyclists: implications for disease screening and follow-up

OBJECTIVES: The purpose of this research was to study long-term left ventricular (LV) adaptations in very-high-level endurance athletes. BACKGROUND: Knowledge of cardiac changes in athletes, who are at particularly high risk of sudden cardiac death, is mandatory to detect hypertrophic cardiomyopathy (HCM) or dilated (DCM) cardiomyopathy. METHODS: We carried out echocardiographic examinations on 286 cyclists (group A) and 52 matched sedentary volunteers (group C); 148 cyclists participated in the 1995 "Tour de France" race (group A1), 138 in the 1998 race (group A2), and 37 in both (group B). RESULTS: In groups A, A1, A2, and C, respectively, diastolic left ventricular diameter (LVID) was 60.1 +/- 3.9 mm, 59.2 +/- 3.8 mm, 61.0 +/- 3.9 mm, and 49.0 +/- 4.3 mm (A vs. C and A1 vs. A2, p < 0.0001), and maximal wall thickness (WT) was 11.1 +/- 1.3 mm, 11.6 +/- 1.3 mm, 10.6 +/- 1.1 mm, and 8.6 +/- 1.0 mm (A vs. C and A1 vs. A2, p < 0.0001). Among group A, 147 (51.4%) had LVID >60 mm; 17 of them had also a below normal (<52%) left ventricular ejection fraction (LVEF). Wall thickness exceeded 13 mm in 25 athletes (8.7%) (always <15 mm), 23 with LVID >55 mm. In group B, LVID increased (58.3 +/- 4.8 mm to 60.3 +/- 4.2 mm, p < 0.001) and WT decreased (11.8 +/- 1.2 mm to 10.8 +/- 1.2 mm, p < 0.001) with time. CONCLUSIONS: Over one-half of these athletes exhibited unusual LV dilation, along with a reduced LVEF in 11.6% (17 of 147), compatible with the diagnosis of DCM. Increased WT was less common (always <15 mm) and scarce without LV dilation (<1%), eliminating the diagnosis of HCM. Serial examinations showed evidence of further LV dilation along with wall thinning. These results might have important implications for screening in athletes.     

Studies on the regulation of myocardial blood flow in man II. Effects of acute arterial hypoxia

To determine whether adjustment of myocardial blood flow (MBF), myocardial oxygen consumption (MVO₂) and myocardial substrate uptake (MSU) to acute arterial hypoxia is influenced by training effects on the heart, 7 trained and 7 untrained healthy individuals were investigated. MBF (argon method), MVO₂ and MSU of glucose, lactate and free fatty acids were measured at rest during normoxia and two different stages of acute arterial hypoxia: a) 12.82 vol% O₂; b) 8.74 vol% O₂. Measurements were carried out during hemodynamic and respiratory steady state conditions. Myocardial flow and metabolism of athletes were significantly (p<0.01) lower compared to untrained subjects. In the trained cohort, MBF increased from 65 ± 19 to 73 ± 16 (a) and 98 ± 23 (b) ml/min·100 g. MVO₂ remained at normoxic control level of 8.00 ± 2.27 ml/min·100g. In the untrained group, MBF increased from 77 ± 15 to 84 ± 20 (a) and 108 ± 18 (b) ml/min · 100g. Again, there was no significant deviation in MVO₂ from the normoxic level of 10.11 ± 1.90 ml/min·100g. Decrease in arterial oxygen content was overcompensated by an increase in coronary conductance resulting in a significantly improved efficiency of myocardial perfusion during severe hypoxia. MSU of glucose, lactate and free fatty acids as well as calculated ATP production did not change significantly during hypoxia. It is concluded that training effects on the heart do not influence regulation of MBF, MVO₂ and MSU during moderate or severe acute arterial hypoxia. Reaction of coronary smooth muscle tone to a decrease in oxygen partial pressure is independent from training effects. However, both acute arterial hypoxia and physical training exert synergetic effects on the heart by reducing myocardial oxygen consumption per heart beat. Thus, it is assumed that adaptive properties of myocardial blood flow and metaboüsm to severe hypoxia are more pronounced in trained than in untrained individuals.     

Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin

The extracellular fluid is a metastable system with regard to calcium and phosphate ions. Active inhibitors of calcification must be present in serum to prevent the spontaneous formation of Ca2+.Pi solid phases which could otherwise precipitate to cause renal calcinosis and block small blood vessels. alpha 2-HS glycoproteins/fetuins, AHSGs, are ideal candidates for this function. AHSGs are ubiquitous and highly abundant in serum; they bind calcium and efficiently prevent de novo formation of apatitic mineral. Normocalcemic AHSG-deficient mice develop sporadic perivascular calcification. Hypercalcemia induced by dietary means or by hormone treatment results in lethal calcinosis in Ahsg-/-mice. A mineral binding structure is proposed for domain D1 of AHSG suggesting that the proposed EF-hand motif for calcium binding does not exist in AHSG. Unlike serum albumin, AHSG does not preferentially bind ionic Ca2+, but rather in the form of apatitic microcrystals.     

Differential matrix degradation and turnover in early cartilage lesions of human knee and ankle joints

OBJECTIVE: To determine whether there are differences in matrix turnover within early cartilage lesions of the ankle (talocrural) joint compared with the knee (tibiofemoral) joint that may help explain differences in the prevalence of osteoarthritis in these 2 joints. METHODS: Cartilage removed from lesions of the tali and femoral condyles was analyzed for type IIB collagen messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). The content of collagen, glycosaminoglycan, and epitope 846 of aggrecan was quantitated. RESULTS: In ankle lesions, there was an up-regulation of markers of synthesis (CPII [P = 0.07]; epitope 846 [P < or = 0.0001]), but these were down-regulated in the knee (CPII [P = 0.1]; epitope 846 [P = 0.004]). In lesions of the knee, but not the ankle, there was an up-regulation of collagen degradation markers (P = 0.008). On a molar basis, there was 24 times more cleavage epitope than denaturation epitope in knee lesions compared with ankle lesions. CONCLUSION: The up-regulation of matrix turnover that is seen in early cartilage lesions of the ankle would appear to represent an attempt to repair the damaged matrix. The increase in collagen synthesis and aggrecan turnover seen in ankle lesions is absent from knee lesions. Instead, there is an increase in type II collagen cleavage. Together with the differences in collagen denaturation, these changes point to an emphasis on matrix assembly during early lesion development in the ankle and to degradation in the knee, resulting in fundamental differences in matrix turnover in these lesions.     

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.     

Menarche,pregnancy, birth spacing and menopause among the Agta women foragers of Cagayan Province,Luzon, the Philippines

The reproductive histories of 74 post-menarcheal Agta Negrito women, tropical foragers of Cagayan province, north-eastern Luzon, the Philippines are described and analysed in comparison with data collected by Howell on Dobe! Kung hunter-gatherers. Among the Agta, mean age at menarche is 17, mean age at first live birth is 20·14 years, mean completed parity is 6·53 and mean age at menopause is 44. Average height is 141·24cm and average weight 36·72 kg. No time trends were detected in age at menarche and age at first live birth among the Agta. Average spacing between live births where an infant survives until the birth of the next sibling was 2·85 years. Compared to the Dobe !Kung, Agta women have later menarche, but shorter birth spacing and a longer active childbearing span.     

Phone-Based Intervention under Nurse Guidance after Stroke (PINGS II) Study: Protocol for a Phase III Randomized Clinical Trial

ObjectivesThe Sub-Saharan African (SSA) region now has the highest estimated effect size of hypertension for stroke causation worldwide. An urgent priority for countries in SSA is to develop and test self-management interventions to control hypertension among those at highest risk of adverse outcomes. Thus the overall objective of the Phone-based Intervention under Nurse Guidance after Stroke II study (PINGS-2) is to deploy a hybrid study design to assess the efficacy of a theoretical-model-based, mHealth technology-centered, nurse-led, multi-level integrated approach to improve longer term blood pressure (BP) control among stroke survivors.Materials and methodsA phase III randomized controlled trial involving 500 recent stroke survivors to be enrolled across 10 Ghanaian hospitals. Using a computer-generated sequence, patients will be randomly assigned 1:1 into the intervention or usual care arms. The intervention comprises of (i) home BP monitoring at least once weekly with nurse navigation for high domiciliary BP readings; (2) medication reminders using mobile phone alerts and (3) education on hypertension and stroke delivered once weekly via audio messages in preferred local dialects. The intervention will last for 12 months. The control group will receive usual care as determined by local guidelines. The primary outcome is the proportion of patients with systolic BP <140 mm Hg at 12 months. Secondary outcomes will include medication adherence, self-management of hypertension, major adverse cardiovascular events, health related quality of life and implementation outcomes.ConclusionAn effective PINGS intervention can potentially be scaled up and disseminated across healthcare systems in low-and-middle income countries challenged with resource constraints to reduce poor outcomes among stroke survivors.     

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral,microarchitectural, biomechanical and matrix properties of rat bone

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid–postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized–steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below −2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.     

Visually detected NREM Stage 2 sleep spindles in kindergarten children are associated with current and future emotional and behavioural characteristics

Sleep electroencephalogram spindles are associated with efficient cortical–subcortical connectivity, and intellectual and learning abilities. In the present study, we assessed healthy preschoolers with a twofold aim: (i) to explore associations of non‐rapid eye movement S2 spindles with emotional/behavioural characteristics cross‐sectionally; and (ii) longitudinally. A total of 43 children who were 5 years old underwent objective sleep electroencephalogram monitoring in their homes. Emotional and behavioural dimensions were assessed by parents and teachers with the Strengths & Difficulties Questionnaire at baseline and at follow‐up 1 year later. Non‐rapid eye movement S2 spindles were visually scored and compared with Strengths & Difficulties Questionnaire dimensions. High non‐rapid eye movement S2 spindle density was associated with less internalizing behaviour, more prosocial behaviour and a low total problem score. In girls, high non‐rapid eye movement S2 spindle density was related to low hyperactivity, while in boys it was associated with less internalizing behaviour, more externalizing behaviour and more hyperactivity. Longitudinally, a higher number of non‐rapid eye movement S2 spindles at 5 years old predicted fewer peer problems 12 months later. In kindergarten children, high non‐rapid eye movement S2 spindle density is associated with observable current and future favourable emotional/behavioural patterns. However, gender differences were also found, as should be taken into account in future studies.