Detecting small-scale genotype-environment interactions in apomictic dandelion (Taraxacum officinale) populations.

Studies of genotype × environment interactions (G × E) and local adaptation provide critical tests of natural selection's ability to counter opposing forces such as gene flow. Such studies may be greatly facilitated in asexual species, given the possibility for experimental replication at the level of true genotypes (rather than populations) and the possibility of using molecular markers to assess genotype-environment associations in the field (neither of which is possible for most sexual species). Here, we tested for G × E in asexual dandelions (Taraxacum officinale) by subjecting six genotypes to experimental drought, mown and benign (control) conditions and subsequently using microsatellites to assess genotype-environment associations in the field. We found strong G × E, with genotypes that performed poorly under benign conditions showing the highest performance under stressful conditions (drought or mown). Our six focal genotypes comprise > 80% of plants in local populations. The most common genotype in the field showed its highest relative performance under mown conditions (the most common habitat in our study area), and almost all plants of this genotype in the field were found growing in mowed lawns. Genotypes performing best under benign experimental conditions were found most frequently in unmown conditions in the field. These results are strongly indicative of local adaptation at a very small scale, with unmown microsites of only a few square metres typically embedded within larger mown lawns. By studying an asexual species, we were able to map genotypes with known ecological characteristics to environments with high spatial precision.

Hypoglycaemic syncope in children secondary to beta-blockers.

It has been reported that young children taking beta-blockers may be at risk of hypoglycaemia when fasting. However, hypoglycaemia is not listed as a side effect of beta-blockers in the British National Formulary for Children. We present five patients (out of approximately 570 patients at our institution who were prescribed regular beta-blockers over the same time period) who had severe hypoglycaemic episodes whilst taking beta-blockers for prevention of arrhythmia. We demonstrate how such an episode may be misinterpreted as an arrhythmic event and how this could lead to inappropriate escalation of medical therapy or even implantation of an automatic implantable cardiac defibrillator.

Syncope in childhood.

Syncope in childhood is very common. The vast majority of episodes are benign, and are due to neurocardiogenic syncope. Only a minority are due to something potentially more serious or life threatening. The diagnosis and differentiation of benign from more serious causes of syncope is made primarily by the history. Investigations are often unfruitful. The mainstay of management in neurocardiogenic syncope is reassurance. An increase in dietary fluid and salt can be helpful. Drug treatment is reserved for those with more frequent and severe attacks. Cardiac pacemakers should be reserved for those with very severe symptoms who are refractory to drug therapy.

Dysautonomia and neurocardiogenic syncope.

Syncope in childhood is a common problem. In most children, syncope is benign, secondary to a disturbance in autonomic control of heart rate and blood pressure. It is increasingly evident that neurally mediated syncope is a heterogeneous group of conditions, necessitating a reclassification of autonomic disorders. New entities, such as postural orthostatic tachycardia and cerebral vasoconstrictive syncope, are recognized. The key to the diagnosis of syncope is a careful history. Tilt testing can be useful when the history is unclear. Unfortunately tilt test protocols vary, affecting specificity and sensitivity. The mainstay of therapy is reassurance. If symptoms are troublesome, Fludrocortisone and B-blockers remain the favored drugs. The efficacy of Midodrine and Serotonin Uptake Inhibitors is currently under review. Cardiac pacing is effective for those patients with severe episodes and demonstrated asystole. It is not known whether pacing would be effective for the majority who have neurally mediated syncope without significant bradycardia.

Myocardial perfusion scanning in patients considered for late arterial switch.

BACKGROUND: Our aims were to evaluate left ventricular uptake of radionuclide in patients with Mustard's or Senning's procedure, comparing them with patients who had undergone banding of the pulmonary trunk and conversion to the arterial switch. METHODS: Technetium perfusion scans were performed on 27 patients (25 male), aged from 10 to 28 years with a mean of 17.8 years and a standard deviation of 5.8 years, who had undergone Mustard's or Senning's procedure for correction of complete transposition. Of the 27 patients, six had been accepted for staged conversion to an arterial switch. At the time of the study, two of the six patients had undergone completion to the switch and four had undergone banding of the pulmonary trunk with two then proceeding to the arterial switch. Cardiac catheterisation to measure left ventricular pressure was performed in all six patients and scores for left ventricular uptake of isotope were compared with echocardiographic index of the thickness of the left ventricular posterior wall and measurements of left ventricular pressure. RESULTS: Uptake of isotope by the left ventricle was generally poor, but was higher in patients following banding and conversion to the arterial switch, as well as in two patients with native obstruction of the left ventricular outflow tract, and one other who subsequently was found to have pulmonary venous obstruction. There was a positive correlation between the thickness of the left posterior wall in diastole and left ventricular uptake of isotope (r = 0.74, p < 0.05). There also a positive correlation between left ventricular pressure and uptake of the isotope (r = 0.68, p < 0.05). CONCLUSIONS: Uptake of radionuclide by the left ventricle after Mustard's or Senning's procedure for complete transposition appears to reflect ventricular pressure and myocardial mass. A prospective study would be required to determine the predictive ability of such scans regarding the ultimate outcome of conversion to arterial switch, but our initial findings suggest that the technique provides an additional non-invasive method of monitoring left ventricular response to pulmonary arterial banding.

Transhepatic approach for cardiac catheterisation in children: initial experience.

AIM: To assess initial experience of cardiac catheterisation in children by the transhepatic approach where conventional venous access is impossible. PATIENTS AND METHODS: Percutaneous transhepatic cardiac catheterisation was performed on six occasions in five children (three male) aged 4 to 36 months (mean 17 months). All children had documented femoral venous occlusion and all but one had occlusion of the superior vena cava. Ultrasound was used in five of the six procedures to help identify a large hepatic vein. A 4 F or 5 F sheath was introduced into the vein using the Seldinger technique. In the fourth patient, hepatic venous access was obtained immediately without the assistance of ultrasound. RESULTS: Percutaneous transhepatic catheterisation was successfully performed at all six attempts. Total procedure time ranged from 120 to 200 minutes (mean 138 minutes) and screening time from 14 to 22 minutes (mean 16.8 minutes). A serious complication was encountered in only one patient who had a retroperitoneal bleed after administration of thrombolysis for loss of femoral arterial pulse. CONCLUSIONS: The percutaneous transhepatic technique can provide a safe alternative approach for cardiac catheterisation in children with multiple venous occlusion. The procedure can be performed very simply using the Seldinger technique and equipment normally used for conventional venous cannulation for cardiac catheterisation.

Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures.

OBJECTIVE: To determine whether permanent cardiac pacing could prevent syncope and seizures in children with frequent severe neurally mediated syncope, and if so whether dual chamber pacing was superior to single chamber ventricular pacing. METHODS: Dual chamber pacemakers were implanted into 12 children (eight male, four female) aged 2-14 years (median 2.8 years) with frequent episodes of reflex anoxic seizures and a recorded prolonged asystole during an attack. The pacemaker was programmed to sensing only (ODO), single chamber ventricular pacing with hysteresis (VVI), and dual chamber pacing with rate drop response (DDD) for four month periods, with each patient allocated to one of the six possible sequences of these modes, according to chronological order of pacemaker implantation. The parent and patient were blinded to the pacemaker mode and asked to record all episodes of syncope or presyncope ("near miss" events). The doctor analysing the results was blinded to the patient and pacemaker mode. RESULTS: One patient was withdrawn from the study after the pacemaker was removed because of infection. In the remaining children, both dual chamber and single chamber pacing significantly reduced the number of syncopal episodes compared with sensing only (p = 0.0078 for both). VVI was as effective as DDD for preventing syncope, but DDD was superior to VVI in reducing near miss events (p = 0.016). CONCLUSIONS: Permanent pacing is an effective treatment for children with severe neurally mediated syncope and reflex anoxic seizures. VVI is as effective as DDD in preventing syncope and seizures, but DDD is superior in preventing overall symptoms.

Morphology of the elastic pulmonary arteries in pulmonary hypertension: a quantitative study.

Recent studies of intravascular ultrasound of the pulmonary arteries suggest that the technique can detect intimal and medial thickening in patients with pulmonary hypertension, potentially providing a method of assessing severity of pulmonary vascular disease in life. A major drawback of the technique is that only the elastic pulmonary arteries are accessible to current ultrasound catheters. The aim of this study was to determine whether morphological changes in vessels accessible to intravascular imaging reflect severity of pulmonary vascular disease and are of a sufficient degree to be detectable by current ultrasound catheters. Morphometric studies of the elastic pulmonary arteries were performed in specimens of lungs from 24 patients who had died with pulmonary hypertension (aged 3 weeks-9 years) and compared with measurements from infants who had died from sudden infant death syndrome. Morphological changes evident in the elastic pulmonary arteries in pulmonary hypertension included luminal dilation and medial thickening but these changes were too variable to be predictive of the severity of peripheral pulmonary vascular disease. Intimal thickening and atherosclerosis were present only in those with advanced pulmonary hypertensive disease. The changes of medial thickening and luminal dilation, nonetheless, are too variable to be predictive of the severity of peripheral pulmonary vascular disease. Thus, imaging by intravascular ultrasound may help confirm advanced pulmonary vascular disease, but is unlikely to differentiate less severe pulmonary vascular disease when the patient may still potentially be operable.

Reduced heart rate variability following repair of tetralogy of Fallot.

OBJECTIVE: To examine autonomic function as assessed by heart rate variability in patients 10 or more years after repair of tetralogy of Fallot, and to relate this to cardiac structure, function, and electrocardiographic indices. METHODS: Heart rate variability was measured by standard time domain techniques on a 24 hour Holter ECG in 28 patients, aged 12 to 34 years (mean 19.5), who had undergone repair of tetralogy of Fallot at least 10 years previously. Echocardiography was performed to assess left ventricular size and function, right ventricular size and pressure, and any proximal pulmonary arterial stenosis. Right ventricular function was evaluated by radionuclide scan. QRS duration, QT interval, and QT dispersion were measured on a standard 12 lead ECG. Measurements of heart rate variability were compared with values from 28 age matched healthy controls (mean age 19.9 years). Interrelations between variables were assessed using Pearson correlation coefficients and stepwise regression analysis. RESULTS: Heart rate variability was reduced, compared with values for age matched normal controls, in 12 of the 28 patients. Reduced heart rate variability was associated with increased age, increased right ventricular size and pressure, and widening of the QRS complex. CONCLUSIONS: Reduced heart rate variability is a feature following repair of tetralogy of Fallot. It is associated with increasing age, impaired right ventricular haemodynamics, and widening of the QRS complex. Under these circumstances, reduced heart rate variability may be a marker for deteriorating right ventricular function. Increased QRS duration has been identified as a risk factor for sudden death following repair of tetralogy of Fallot, and impaired cardiac autonomic control may be one of the mechanisms involved.

1:1 atrioventricular conduction in congenital complete heart block.

A female neonate with congenital complete heart block developed atrioventricular conduction through an accessory pathway. Despite sinus rhythm and an adequate heart rate she developed severe dilated cardiomyopathy and died at age 14 months. This case illustrates that underlying heart block can be present in individuals with asymptomatic Wolff-Parkinson-White syndrome and that the dilated cardiomyopathy that occasionally accompanies autoimmune congenital heart block is not primarily caused by bradycardia.

Stenting of stenosed aortopulmonary collaterals: a new approach to palliation in pulmonary atresia with multifocal aortopulmonary blood supply.

A patient with complex pulmonary atresia and increasing cyanosis due to stenoses of aortopulmonary collateral vessels improved after implantation of balloon expandable stents into the stenosed vessels. Stent implantation may provide an alternative to surgical palliation in this group of patients.

Neutrophil activation and morbidity in young adults with cyanotic congenital heart disease.

Young adults with cyanotic congenital heart disease have a high incidence of respiratory and haemostatic problems. Activated neutrophils release vasoactive and chemotactic factors which result in endothelial injury, lung parenchymal damage and the activation of platelets and coagulation pathways. To investigate the contribution of neutrophil activation to morbidity in young adults with cyanotic congenital heart disease, plasma neutrophil elastase levels were measured in 25 cyanotic patients and the results compared to patients with acyanotic heart disease and normal controls. Neutrophil elastase levels were significantly elevated in the group with cyanotic congenital heart disease (P < 0.001). Platelet activation was significantly increased in the patients with cyanotic heart disease (P < 0.001). Platelet aggregation was impaired only in those with haematocrits greater than 0.50 (P < 0.02). Whole blood coagulation, as determined by thrombelastography, was within normal limits. The reason for neutrophil activation in patients with cyanotic congenital heart disease is unclear, but activated neutrophils may contribute to the respiratory and haemostatic problems common to these patients.