Regional and global left ventricular function following a simulated 5 km race in sports-trained adolescents.

The effects of a short, high-intensity bout of exercise on cardiac systolic and diastolic function are not well understood in adolescent athletes. Consequently, the aims of the study were to evaluate global left ventricular (LV) systolic and diastolic function, as well as segmental wall motion responses (cardiac strain), prior to as well as 45 and 225 min following a simulated 5 km cross-country race. Twenty trained, adolescent males (age: 15.2 ± 0.7 years) volunteered for exercise testing. LV fractional shortening and the ratio of early (E) and late (A) peak flow velocities reflected global systolic and diastolic function, respectively. Peak longitudinal mitral annular septal tissue velocities were also determined during systole and diastole. Longitudinal strain (ε) and strain rates were determined across the LV. LV fractional shortening was significantly (P < 0.05) higher at 225 min post-race (37.6 ± 5.8%) compared to pre-race (34.5 ± 4.7%) and 45 min post-race (34.9 ± 5.4 %). This difference was abolished after adjusting for post-race heart rates. There was a significant (P < 0.05) decrease in the E:A ratio at both 45 min (2.04 ± 0.57) and 225 min post-race (2.20 ± 0.66) compared to the pre-race value (2.80 ± 0.68). When these data were adjusted for post-race heart rates, these pre-post-race differences in E:A ratio were abolished. There were no significant alterations in either tissue Doppler velocities or longitudinal ε. The evidence suggests that a 5 km race does not lead to any significant post-exercise attenuation in global or regional LV systolic and diastolic function in trained adolescents.

Effect of exercise, heat stress and dehydration on myocardial performance.

BACKGROUND: Myocardial dysfunction is a well-documented outcome of extended periods of high cardiac output. Whether similar effects occur during firefighting, an occupation characterized by repeated periods of work compounded by dehydration and heat stress, is uncertain. AIMS: To investigate the independent and combined effects of moderate heat stress and dehydration on indicators of myocardial performance following intermittent, submaximal treadmill exercise while wearing personal protective equipment (PPE). METHODS: Twelve aerobically fit young men (age 21.5±2.6 years; maximal oxygen uptake [VO2max] 60.3±4.4ml kg(-1) min(-1)) performed intermittent treadmill walking exercise consisting of three 20min bouts at an intensity of ~40% VO2max separated by two periods of rest in four different conditions in random order: (i) no heat stress-euhydrated, (ii) heat stress-euhydrated (heat stress created by wearing PPE, (iii) no heat stress-dehydrated and (iv) heat stress-dehydrated. We measured core temperature by a telemetric gastrointestinal pill. We determined cardiac variables by standard echocardiographic techniques immediately before and ~30min after exercise. RESULTS: We recorded no significant changes in markers of systolic (ejection fraction, shortening fraction, tissue Doppler-S) or diastolic (mitral peak E velocity, tissue Doppler-E' and E/E') function following exercise in any of the four conditions. CONCLUSIONS: In this model of exercise designed to mimic the work, heat stress and dehydration associated with firefighting activities, we observed no negative effects on myocardial inotropic or lusitropic function.

Right ventricular myocardial responses to progressive exercise in young adult males.

Recent attention has been focused on possible unique features of the right ventricular response to exercise. This study investigated a) the responses of right ventricular cardiac dynamics and myocardial function to a standard bout of progressive cycle exercise in healthy young males, and b) the effect of level of aerobic fitness on these responses. 14 athletically-trained males (20.4±1.5 years) and 11 normally-active males (21.1±1.3 years) underwent a progressive upright cycle test to exhaustion with measurement of gas exchange variables and assessment of right ventricular stroke volume, systolic and diastolic myocardial velocities, and tricuspid inflow velocities by standard Doppler echocardiographic techniques at rest, submaximal and peak exercise. Stroke volume rose initially by approximately 27% in each group, followed by stable values to exhaustion. Values of maximal stroke index and maximal oxygen uptake were significantly greater in the trained group than the normally-active males (62±10 ml m(-2), 54.3±4.0 ml kg(-1) min(-1); 49±7 ml m(-2), 40.3±5.6 ml kg(-1) min(-1), respectively). No significant differences were observed in increases in systolic or diastolic myocardial velocities, peak pulmonary outflow velocity, systolic ejection rate, or tricuspid inflow velocity between the 2 groups. The magnitude of change of these variables was similar to those previously described for left ventricular responses to similar exercise. This study revealed no unique features of right ventricular functional responses to an acute exercise challenge in young males.

Delivering effective Defence Engagement (Health): lessons from Operation TRENTON (South Sudan).

This paper describes the Defence Engagement (Health) (DE(H)) component of the medical mission within the UK deployment to South Sudan under Op TRENTON, the UK troop contribution to the United Nations Mission in South Sudan (UNMISS). The DE(H) activities provided advice and mentoring to the Vietnamese military medical services to support the predeployment preparation and training of their medical contingent that would undertake a relief in place of the UK personnel providing a Level 2 hospital in Bentiu, South Sudan. The paper describes these UK DE(H) activities at the strategic, operational and tactical levels to show the integration across these levels from January 2017 until the handover of command in South Sudan on 26 October 2018. The UK worked alongside personnel from the US and Australian military medical services to deliver a Field Training Exercise and other capability-building events for personnel from the Vietnamese 175 Military Hospital. The paper shows how a DE(H) programme can have strategic effects by bringing another nation into a United Nations mission, increasing UK diplomatic activity with a partner country, and by ensuring continuity of medical cover to a key UNMISS location after the withdrawal of the UK medical contingent. This paper forms part of a special issue of BMJ Military Health dedicated to DE(H).

Using network analysis to detect associations between suspected painful health conditions and behaviour in dogs.

Pain associated with chronic health conditions in non-human animals is an important animal welfare issue. To identify animals in pain and develop an understanding of the mechanisms by which pain affects behaviour, it is therefore important to establish the direct behavioural effects of painful health conditions. We reanalyse data from a cross-sectional survey that considered the presence or absence of a painful condition in dogs and quantified their affective predispositions using the Positive and Negative Activation Scale (PANAS). By applying ideas from network theory, we conceptualise pain as a stressor that exerts direct effects on a network of interacting behavioural variables, and subsequently estimated a network model of conditional dependence relations. Painful health conditions were positively conditionally associated with age (posterior mean partial correlation, ρ = 0.34; standard deviation [SD]=0.05), and negatively conditionally associated with the item 'your dog is full of energy' (ρ = -0.14; SD=0.06). In turn, the energy item was conditionally associated with other PANAS items which were marginally associated with pain, such as items representing ease of excitability and persistence in play. This suggests these marginal effects might be indirectly mediated via the energy item. Further, utilising the posterior predictive distribution we estimated that the median conditional probability (95% credible interval) of a painful health condition given an answer of 'strongly agree' on the energy item was 0.08 (0.05, 0.11), which increased to 0.32 (0.09, 0.58), given a response of 'strongly disagree'. This provides a potentially clinically useful interpretation of the conditional dependencies detected in the network.

Influence of sex on ventricular remodeling in collegiate athletes.

AIM: Previous reports indicate that the "athlete's heart" is more prominent in males than females, but the mechanisms responsible for this sex difference have not been elucidated. This study examined male-female differences in cardiac mass and volume in highly trained athletes and normally active individuals to assess the relative contributions of pre-existing sex differences and sports training to cardiac findings. METHODS: Echocardiographic and electrocardiographic findings were compared between 20 male and 21 female collegiate athletes and 22 male and 29 female normally-active subjects. RESULTS: Cardiac mass (per kg lean body mass) was significantly greater in the male compared to female athletes (3.62±0.55 and 3.31±0.56 g.kg-1, respectively). A similar magnitude of difference in average relative cardiac mass was observed between the normally active males and females, and cardiac mass was greater in athletic versus nonathletic groups by +14.9% in the males and +13.3% in the females. Relative left ventricular volume was greater in the male athletes (47.5±6.3 ml•BSA-1.5) compared to male nonathletes (42.9±6.1 ml•BSA-1.5); no such difference was observed in the females. CONCLUSION: These findings suggest that sex differences in both the untrained state and magnitude of training response contribute to male-female differences in the "athlete's heart"

Skin microvascular reactivity in trained adolescents.

Whilst endothelial dysfunction is associated with a sedentary lifestyle, enhanced endothelial function has been documented in the skin of trained individuals. The purpose of this study was to investigate whether highly trained adolescent males possess enhanced skin microvascular endothelial function compared to their untrained peers. Seventeen highly and predominantly soccer trained boys (V(O)(2)(peak): 55 +/- 6 mL kg(-1) min(-1)) and nine age- and maturation-matched untrained controls (V(O)(2)(peak): 43 +/- 5 mL kg(-1) min(-1)) aged 13-15 years had skin microvascular endothelial function assessed using laser Doppler flowmetry. Baseline and maximal thermally stimulated skin blood flow (SkBF) responses were higher in forearms of trained subjects compared to untrained participants [baseline SkBF: 11 +/- 4 vs. 9 +/- 3 perfusion units (PU), p < 0.05; SkBF(max): 282 +/- 120 vs. 204 +/- 68 PU, p < 0.05]. Similarly, cutaneous vascular conductance (CVC) during local heating was superior in the forearm skin of trained versus untrained individuals (CVC(max): 3 +/- 1 vs. 2 +/- 1 PU mmHg(-1), p < 0.05). Peak hyperaemia following arterial occlusion and area under the reactive hyperaemia curve were also greater in forearm skin of the trained group (peak hyperaemia: 51 +/- 21 vs. 35 +/- 15 PU, p < 0.05; area under curve: 1596 +/- 739 vs. 962 +/- 796 PUs, p < 0.05). These results suggest that chronic exercise training in adolescents is associated with enhanced microvascular endothelial vasodilation in non-glabrous skin.

Aerobic cost in elite female adolescent swimmers.

Maximal performance in swimming depends on metabolic power and the economy of swimming. Thus, the energy cost of swimming (economy= VO(2)/V, C(s)) and maximal aerobic power (VO(2max)) in elite young female swimmers (n=10, age: 15.3+/-1.5 years) and their relationships to race times (50-1,000 m) and national ranking were examined. VO(2) increased exponentially with velocity (V), (VO(2)=5.95+(-10.58 V)+5.84 V(2)) to a maximal VO(2) of 2.71+/-0.50 L x min(-1) (46.7+/-8.2 mL x kg(-1) x min(-1)) at a free swimming velocity of 1.37+/-0.07 m x s(-1). C(s) was constant up to 1.2 m x s(-1) (21.5 mL x m(-1)), however was significantly higher at 1.36 m x s(-1) (27.3 mL x m(-1)). Peak [La] was 5.34+/-2.26 mM. C(s) expressed as a percentage of Cs at maximal swimming velocity was significantly correlated with race times and ranking across a number of distances. The data for these elite females demonstrate that the energy cost of swimming is a good predictor of performance across a range of distances. However, as swimming performance is determined by a combination of factors, these findings warrant further examination.

Biologically active heteroarotinoids exhibiting anticancer activity and decreased toxicity.

A series of retinoids, containing heteroatoms in a cyclic ring and called heteroarotinoids, were synthesized, and their biological activity was evaluated using tissue culture lines that have measurable responses to trans-retinoic acid (t-RA). Transglutaminase (TGase) was assessed in the human erythroleukemia cell line (GMO6141A) as an indicator of differentiation and apoptosis. Proliferation was evaluated in a human cervical cell line, CC-1, which exhibits dose-dependent alterations in growth rate in response to treatment with trans-retinoic acid. Activation of nuclear retinoic acid receptors was determined in a reporter cell line established from CC-1. The reporter line, called CC-B, contains a reporter gene controlled by a retinoic acid responsive element (RARE) and a thymidine kinase (tk) promoter. Treatment of the CC-B line with the heteroarotinoids resulted in a dose-responsive and retinoid-dependent regulation of reporter gene expression. The heteroarotinoids exhibited activity in all assays and correlated in a statistically significant manner between assays. RARE transactivation activity in CC-B cells correlated with induction of TGase in GMO6141A (R = 0.96) and with a decrease in the growth rate of CC-1 cells (R = -0.90). The ability of the selected heteroarotinoids to induce differentiation, inhibit proliferation, and activate nuclear receptors demonstrates the chemotherapeutic potential of these agents. In view of the biological activity cited, an in vivo toxicity study was conducted on male B6D2F1 mice with three heteroarotinoids, namely 8 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylthiochroman-6-yl)-2,4,6-heptatrienoic acid], 10 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylchroman-6-yl)-2, 4,6-heptatrienoic acid], and 13 [(E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid]. The mice were used with gavage of heteroarotinoids in corn oil [0.1, 0.2, 0.4, or 0.8 mg/kg] and with 0.01 or 0.05 mg/kg of TTNPB (5) [(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1- propenyl]benzoic acid] as reference controls. The target organs affected in the mice by the three heteroarotinoids were those typically associated with t-RA (1) toxicity. The maximum tolerated dose (MTD) of 13 was 9.4 mg/kg/day, which was equal in toxicity to that of t-RA (1) and 1000-fold less toxic than TTNPB (5). The MTDs of 8 and 10 were 34 and 32 mg/kg/day, respectively, which is 3-fold less toxic than t-RA (1) and 3000-fold less toxic than TTNPB (5). The 3000-fold reduced toxicity, compared with only a 27% reduction biological activity of 8 and 10 with respect to that of TTNPB, observed in our assays indicates a good therapeutic ratio of these heteroarotinoids over the parent compound. The biological activity and reduced toxicity of these heteroartinoids demonstrate the potential efficacy as anticancer agents.

The pediatrician and congenital heart disease--1979.

Technologic advances in the diagnosis and treatment of children with congenital heart disease have created new, expanded roles for the practicing pediatrician. Early identification of infants with serious lesions continues to be vital, and support of children and their families following surgery is central to the solution of emotional, employment, and childbearing problems these patients may eventually face.

Traumatic aortic insufficiency in children: case report and review of the literature.

Aortic valve regurgitation and saccular aneurysm of the ascending aorta developed in a 5-year-old boy following severe compressive injury to the chest. While rare, traumatic aortic valve disruption may lead to serious cardiac dysfunction. Recognition of acute arotic insufficiency and other forms of cardiac damage requires special attention in patients with nonpenetrating chest injury.

Aerobic response to endurance exercise training in children.

OBJECTIVE: To investigate the ability of children to improve aerobic fitness, as indicated by changes in maximaal oxygen uptake (VO2max), after a 12-week period of endurance training. DESIGN: Longitudinal prospective training with control period. SETTING: Middle school physical education class. SUBJECTS: Twenty-four girls and 13 boys, ages 10.9 to 12.8 years. INTERVENTION: Three 30-minute sessions of aerobic activity weekly for 12 weeks at an intensity-producing a mean heart rate of 166 beats per minute. Maximal treadmill testing was performed 12 weeks before the training program and again at the start and end because each child served as his/her own control. RESULTS: Mean VO2max did not change significantly during the control period but rose from 44.7 (5.8) to 47.6 (6.4) mL kg-1min-1 (6.5%) with training (P < .05). No differences in training response were observed relative to sex, pretraining VO2max, or sports participation. CONCLUSION: These findings support the concept that VO2max can be improved with endurance training during the childhood years, but the degree of aerobic train-ability is limited in healthy, active children.

Idiopathic atrial flutter in infancy: a review of eight cases.

The experience of three institutions in the management of atrial flutter in infants under 2 years of age without associated heart disease is reviewed. Five babies with neonatal onset were treated with digoxin and had uncomplicated resolution of their arrhythmia, although one continued to have episodes of paroxysmal supraventricular tachycardia for six years. Two of the three older infants required DC cardioversion for complications after quinidine was substituted for digoxin therapy. Digoxin continues to be the preferred initial therapy for non-acutely ill patients; those showing signs of cardiac decompensation should be converted with DC countershock.

'Athlete's heart' in prepubertal children.

Bradycardia, cardiomegaly, heart murmurs, and ECG changes are typically observed in adult endurance athletes, but frequency of such changes among children involved in sports training is unclear. Pediatricians need to be aware of whether these features of the "athlete's heart" occur in their patients, because such features may mimic those of cardiac disease. Fourteen prepubertal competitive male swimmers were evaluated by physical examination, ECG and echocardiogram, and findings were compared to those of a group of active but nontrained control boys. Lower resting heart rates and echocardiographic manifestations of chronic left ventricular volume overload were observed among the swimmers. These changes were not manifest on physical examination, however, and no significant ECG alterations were identified among the athletes. These findings indicate that, although features of the athlete's heart are present in children involved in endurance training, seldom will these findings simulate heart disease or be apparent on routine clinical examination.

Apnea documentation for determination of brain death in children.

Discontinuing ventilatory support for determination of respiratory drive is a recognized means of assessing clinical brain death. Methodology must include a means for assuring adequate oxygenation during the test as well as providing sufficient duration for appropriate hypercarbia. Nine patients with other findings of clinical brain death were prospectively assessed with a standardized apnea test protocol. None demonstrated spontaneous respirations. Whereas adequate oxygenation was maintained in each case, wide variability was evident in degree of hypercarbia and acidosis.

Selective down-regulation of T cell- and non-T cell-derived tumour necrosis factor alpha by thalidomide: comparisons with dexamethasone.

Both thalidomide and dexamethasone have been shown to inhibit the production of tumour necrosis factor alpha (TNF-alpha), but little is known of their cellular selectivity. Inhibition of monocyte TNF-alpha expression has been implicated in the clinical efficacy of thalidomide, and it has been suggested that the drug modulates only monocyte-derived cytokines. Given the importance of T lymphocyte responses in immunological disorders in which treatment with thalidomide has been successful, it is pertinent to study the effects of this drug on T cell-derived TNF-alpha. In the present investigations we have examined the influence of both thalidomide and dexamethasone on mitogen-induced elaboration of TNF-alpha by CD3+ peripheral blood mononuclear cells (PBMC) and the T cell line MOLT-4. PBMC from healthy human volunteers were stimulated optimally with phytohaemagglutinin (PHA) in the presence of varying concentrations of thalidomide or dexamethasone, and supernatants assayed for TNF-alpha and interleukin 2 (IL-2). Concurrently, PHA-stimulated PBMC were treated with 1 x 10(-1) mM thalidomide or dexamethasone and the cells fixed, permeabilised, stained with anti-CD3 and anti-TNF-alpha fluorescently labelled antibodies and analysed by flow cytometry. MOLT-4 cells were cultured in the presence or absence of the drugs following activation with phorbol myristate acetate (PMA)/ionophore, and supernatants analysed by enzyme-linked immunosorbent assay (ELISA) for cytokine expression. Thalidomide was found to inhibit PBMC-derived TNF-alpha, but not IL-2. In contrast, dexamethasone down-regulated both TNF-alpha and IL-2 in a dose-dependent manner. Thalidomide and dexamethasone both suppressed intracellular levels of TNF-alpha in CD3+ PBMC, reducing percentages of double positive staining cells by 28 and 52%, respectively, compared with controls. In addition, TNF-alpha production by CD3- PBMC was inhibited by 31% by thalidomide and by 47% by dexamethasone. In order to determine whether thalidomide was acting directly on T cells, or indirectly through effects on accessory cells, TNF-alpha production in the T cell line MOLT-4 was investigated. TNF-alpha secretion by PMA/ionophore activated MOLT-4 cells was reduced by 80% following thalidomide treatment and close to background levels following dexamethasone treatment. To verify that thalidomide was acting selectively to down-regulate TNF-alpha, IL-2 production by MOLT-4 cells was also measured and found to be unaffected by the drug. In contrast, dexamethasone reduced MOLT-4-derived IL-2 levels by 20%. These observations suggest that thalidomide, in addition to its known inhibitory effect on monocyte-derived TNF-alpha, is capable also of down-regulating T cell-derived TNF-alpha in a direct and selective manner. In addition, the inhibition of intracellular levels of TNF-alpha strengthens the evidence that the inhibitory effect of thalidomide is at the level of transcription and/or translation and does not reduce cellular TNF-alpha secretion. Such effects could explain the efficacy of thalidomide treatment in various immunological disorders where T cell activation plays an important role in the pathogenesis of the disease.

Test-retest reproducibility of maximum cardiac output by Doppler echocardiography.

Test-retest reproducibility of stroke volume and cardiac output using Doppler echocardiography was examined during maximum cycle exercise in 13 young men. A coefficient of variation of 8.5% and 8.1% and intraclass correlation coefficient of 0.90 and 0.91 for maximum stroke volume and cardiac output, respectively, indicate a high degree of reproducibility using this technique.

Dynamics of left ventricular diastolic filling during exercise: a Doppler echocardiographic study of boys 10 to 14 years old.

STUDY OBJECTIVE: Factors influencing diastolic filling of the left ventricle may serve as critical determinants of both maximal cardiac output and oxygen uptake. This study was conducted to assess diastolic filling dynamics of the left ventricle during progressive upright cycle exercise in children. METHODS: Twelve boys aged 10 to 14 years underwent cycle testing with determination of transmitral flow velocities and pressure gradients as well as cardiac stroke volume using Doppler echocardiography. RESULTS: Estimated diastolic filling period shortened from 0.479 +/- 0.043 s at rest to 0.138 +/- 0.015 s at peak exercise. The peak and mean transmitral pressure gradient rose fourfold from rest to peak exercise. Mitral flow volume per beat rose by only 40% and remained stable beyond mild-to-moderate intensity work. CONCLUSIONS: Increases in transmitral pressure gradient with exercise may serve principally to augment velocity of ventricular filling with the progressively shortening diastolic time period.

Development of ventilatory responses to exercise in normal white children. A longitudinal study.

Cross-sectional studies have indicated that the pattern of ventilatory responses to exercise evolves during the course of childhood. This 5-year study was designed to provide a longitudinal assessment of minute ventilation (VE), tidal volume (VT), and breathing frequency (fR) in 20 children (11 girls, nine boys) between the ages of 9 and 13 years. Subjects performed maximal and identical submaximal steady-state treadmill walking tests annually. No significant gender differences were observed in any of the three variables. At submaximal exercise, VT per kilogram remained stable, with a progressive fall in fR. As a result, submaximal VE per kilogram declined with age. A similar pattern was observed at maximal exercise, but the decrease in VE per kilogram was not statistically significant. Ventilatory equivalent for oxygen (VE/VO2) fell with age at submaximal exercise but declined only in the boys with maximal testing. VE/VO2 at maximal and submaximal exercise was greater in the girls at all ages. These findings support previous data derived from cross-sectional studies.

Oxygen uptake plateau during maximal treadmill exercise in children.

The leveling of oxygen uptake at high work loads has been utilized to define maximal VO2 during progressive exercise testing. Exercise studies in children have indicated, however, that a VO2 plateau can commonly be demonstrated in less than one half of subjects. To examine the potential contributions of subject effort, aerobic fitness, and nonaerobic performance to this variability, 15 children ages 7 to 10 years performed progressive treadmill walking to exhaustion with a ramp protocol. The VO2 plateau was defined as a change in VO2 during the final minute of exercise less than 2 SD below the mean of increases between the previous 4 to 5 submaximal minutes. Five subjects (33.3 percent) demonstrated a plateau. No significant differences in mean peak VO2, heart rate, or respiratory exchange ratio were observed between plateau and nonplateau groups. Testing results of speed (50-yard sprint) and leg power (vertical jump) were also similar. These findings suggest that following: (1) subject effort, aerobic fitness, and nonaerobic factors do not explain the presence or absence of a VO2 plateau during exercise testing of children; and (2) a VO2 plateau should not be used as a requirement for defining VO2max during treadmill testing in this age group.