Astrocyte-mediated metaplasticity in the hippocampus: Help or hindrance?

For over two decades it has been increasingly appreciated that synaptic plasticity mechanisms are subject to activity-dependent metaplastic regulation. In recent years it has also become apparent that astrocytes are active partners with neurons at synapses, and have the capability to powerfully regulate synaptic plasticity. However, the field of astrocyte-mediated metaplasticity is still very much in its infancy. Further, what contribution astrocyte-mediated metaplasticity makes to hippocampal dysfunction is almost entirely unknown. This contribution may be particularly important given that altered plasticity in the hippocampus is a hallmark of several disease states. The known ways by which astrocytes exert metaplasticity are reviewed here, and hypothetical mechanisms of astrocyte-mediated metaplasticity are considered for the benefit of future investigation. The latter half of this review focuses on what part these mechanisms, and others, may play in the diseased or injured hippocampus, and how this might contribute to the altered cognition seen in several pathologies common to the hippocampus.

Cardiac assessment in childhood carriers of Duchenne and Becker muscular dystrophies.

Cardiac disease in adult female carriers of the X-linked dystrophinopathies, Duchenne and Becker muscular dystrophies, is a well-recognised entity. A single study has reported a 15% incidence of cardiac abnormalities in female carriers under 16 years. Our study aims, clinically and with electrocardiograph and echocardiograph, to determine the incidence of cardiac abnormality in young girls who are proven carriers of X-linked dystrophinopathies. Twenty-three girls aged 6.2-15.9 years were assessed. All had normal cardiac examination. None had electrocardiograph abnormalities consistent with dystrophic cardiomyopathy. Left ventricular fractional shortening ranged from 33 to 55% (normal>28%). Septal thickness, posterior wall thickness and wall thickness ratio were within normal limits. No cardiac abnormalities have been demonstrated in young girls who are proven carriers of X-linked dystrophinopathies in our study. This has important implications for planning timing of carrier determination and cardiac assessment.

The value of counter-current aortography in infants.

Counter-current aortograms were performed on five infants weighing from 1.6 to 2.8 kg. All had symptoms suggestive of congenital heart disease. The images obtained were all of diagnostic quality. In only one, who had anomalous origin of the subclavian artery on the side chosen for the injection, was the diagnosis not made by this technique. No complications directly attributable to the procedure occurred. Counter-current aortography is a safe and effective minimally invasive method of elucidating the anatomy of the aortic arch in young infants.

Balloon aortoplasty for recoarctation following the subclavian flap operation.

Transluminal balloon aortoplasty was successfully performed 7 times in 5 children between 3 and 14 months of age who had had the subclavian flap operation for coarctation of the aorta in the neonatal period. In two the balloon aortoplasty was performed twice. All recoarctations presented with upper limp hypertension and marked upper to lower limb pressure gradients. The pressure gradient decreased immediately after the procedure from 57.1 +/- 13.8 mm Hg to 17.9 +/- 15.5 mm Hg, P less than 0.001. The diameter of the recoarcted region increased from 2.67 +/- 1.0 mm to 3.85 +/- 1.23 mm, P less than 0.05. There were no complications attributable to the dilatation technique. Intermediate term success was unpredictable from the initial results or the angiographic appearance of the recoarctation. Follow-up has been for an average of 12.7 months (range 2-30 months). Four patients have pressure gradients from upper to lower limbs of 20 mm Hg or less. In one this has been achieved by repeat balloon aortoplasty. Severe restenosis has occurred in one other patient despite repeating the angioplasty. The procedure is safe and although intermediate term success cannot be predicted in all cases, we propose that balloon aortoplasty be the initial treatment of choice for recoarctation of the aorta. The place of repeating the procedure when early restenosis occurs has yet to be defined.

Acute renal failure following cardiopulmonary bypass in children: results of treatment.

Following open heart surgery using cardiopulmonary bypass, 18 (4%) of 441 operated children required treatment with peritoneal dialysis for acute renal failure or refractory oliguria. Nine recovered renal function (50%) and 5 (28%) survived. Only 2 died from renal causes. Despite both adequate symptomatic treatment of renal failure and few complications of dialysis itself, the prognosis remains poor, even with early treatment, but an aggressive approach is justified because some survivors can be expected.

The pathology of balloon pulmonary valvoplasty.

The pulmonary valve was examined following balloon dilation of pulmonary valve stenosis in six children. Stenosis was due to commissural fusion in two. In these patients, cineangiography showed that the valve was slightly thickened and "domed" during systole. Balloon valvoplasty produced complete separation of fused commissures in one and partial separation in the other. Commissural splitting is likely to be the most common mechanism of relief of pulmonary stenosis by balloon dilation. Incomplete separation could account for the partial reduction of the gradient in most children treated with this technique. Four children had pulmonary valve dysplasia. Balloon valvoplasty did not produce haemodynamic improvement or morphological changes that were identifiable at the time of surgical correction. Tearing of pulmonary valve tissue and avulsion of pulmonary cusps were not seen in this series.

Reproductive autonomy and evolutionary biology: a regulatory framework for trait-selection technologies.

The Constitution protects, in some measure, each person's autonomy in making basic decisions about family, parenthood, and procreation. This Article examines the extent to which courts should protect from government intrusions a parent's access to technologies that influence specific characteristics of offspring. Beginning with Supreme Court opinions that articulate constitutional and social values regarding reproductive autonomy, the Article explores how important new insights from evolutionary biology may supplement an understanding of human procreation. Specifically, the Article explains how trait selection can constitute an important part of larger "reproductive strategies" that powerfully affect an individual's "inclusive fitness" (itself a measure of reproductive success). It concludes that access to trait-selection technologies should receive the same federal protection from government intrusions as that afforded access to abortion. It proposes the first limit to that protection, however, when a parent seeks to select for a trait, or to use a technique, that would be clearly and significantly damaging to the future child. The Article subsequently divides the use of trait-selection technologies (TSTs) into eight contexts and proposes a preliminary framework by which a regulatory system could legitimately distinguish among them.

Pulmonary regurgitation in transposition of the great arteries.

A female infant who presented with cyanosis and tachypnoea was found to have transposition of the great arteries, a ductus arteriosus, and a ventricular septal defect. An aortogram showed evidence of mild pulmonary regurgitation, which persisted after a Senning's operation; this is a hitherto unrecognised clinical finding.

Internal jugular catheterisation in small children. The use of a posterior approach.

Internal jugular catheterisation, using a posterior approach, was attempted in 50 infants and children aged from 1 day to 12 years, weighing 1.25 to 30 kg. Thirty-five of the patients weighed less than 10 kg. Catheterisation was successful in 49 cases. Initial catheter position was satisfactory in 48 of the 49 cases and satisfactory pressure waveform and flow characteristics were achieved in all 49 cases. There were no complications attributable to the technique. The technique proved reliable and easily learnt and is recommended as a particularly suitable approach to central venous catheterisation in small children.

Use of radionuclide labelled microspheres to show the distribution of the pulmonary perfusion with multifocal pulmonary blood supply.

In pulmonary atresia with a ventricular septal defect and similar congenital heart disorders the pulmonary blood supply is often multifocal. The relative distribution of pulmonary perfusion from individual sources is usually demonstrated by selective angiography. A new technique using a selective injection of radionuclide labelled human albumin microspheres was performed in four patients with a complex pulmonary blood supply. In these cases the physiological distribution of each of the multiple sources of pulmonary perfusion was demonstrated. This is a useful additional technique in the assessment of such patients.

Comparative analysis of pattern, management and outcome of pre- versus postnatally diagnosed major congenital heart disease: a population-based study.

OBJECTIVES: Most pregnant women in New South Wales undergo obstetric ultrasound examination, including some assessment of fetal cardiac anatomy. We aimed to review the spectrum of cardiac defects, management and outcome data of all fetuses with diagnosis of major congenital heart disease between 1994 and 1996 and compare them to major congenital heart disease in infants born during the same 3-year study period. METHODS: Descriptive comprehensive study of the New South Wales population. Study centers included the single fetal echocardiographic referral service and the two pediatric cardiac centers of New South Wales. RESULTS: Ninety-seven fetuses and 562 infants with major congenital heart disease were identified (240,000 livebirths), resulting in a prenatal detection rate of 15%. Anomalies detectable by cardiac four-chamber views were diagnosed at an average rate of 30% (68/229) in utero. By contrast, lesions associated with abnormal ventricular outflow and great artery views were detected in only 6.7% (29/430; P < 0.0001) of cases prior to birth. Of the 97 fetuses, 29 were aborted, 16 died in utero, and 9 died early postnatally without treatment. Within 2 weeks of age, 23% with fetal and 40% (P < 0.05) with infant major congenital heart disease diagnosis required an intervention, mainly for patent ductus arteriosus dependent lesions. Postnatal survival was similar for the fetal and infant series up to 2 years of age: 77% (95% confidence interval 64-90%) vs. 85% (95% confidence interval 82-88%). CONCLUSIONS: Prenatal diagnosis has important implications for pregnancy outcome, in particular for univentricular lesions. However, the present mode of obstetric routine ultrasound scanning fails to identify most ductus arteriosus dependent cardiac lesions with a predictable need for early postnatal intervention.

Radionuclide measurement of left ventricular ejection fraction in tricuspid atresia.

In 15 patients with tricuspid atresia and one with tricuspid stenosis the left ventricular ejection fraction was measured by equilibrium gated radionuclide angiography and the results compared with those from a control group of 16 patients. The patients with tricuspid atresia had a significantly depressed ejection fraction. Those who had a surgical shunt or who had had pulmonary artery banding had significantly lower ejection fractions than the remainder. There was no significant correlation between the ejection fraction and age, the arterial oxygen saturation, or the haemoglobin concentration. Five patients were also studied during isometric exercise; three had an abnormal response. Volume overload of the ventricle is identified as one cause of the dysfunction, but other factors may be important. Radionuclide angiography offers a non-invasive method of studying ventricular function in this condition.

Balloon atrial septostomy in the neonatal intensive care unit.

In eight infants with complete transposition of the great arteries balloon atrial septostomy was performed in the neonatal intensive care unit solely under cross sectional echocardiographic control. One infant developed necrotising enterocolitis; otherwise there were no complications. This technique eliminates the need for radiographic screening during the procedure, is quick, and causes little disturbance to the infant who does not have to be removed from the incubator.

Two dimensional echocardiographic categorisation of the univentricular heart. Ventricular morphology, type, and mode of atrioventricular connection.

Most univentricular hearts have two chambers in their ventricular mass, only one of which possesses an atrioventricular connection. Categorisation into univentricular heart of right, left, or indeterminate type, using two dimensional echocardiography has been successfully achieved in 122 out of 132 patients to whom this technique has been applied. Thus, right ventricular rudimentary chambers in 84 univentricular hearts of left ventricular type were shown to be anterosuperior and either to the right or left. In contrast, left ventricular rudimentary chambers in 25 univentricular hearts of right ventricular type were posteroinferior and to the right, left, or directly posterior. Thirteen univentricular hearts of indeterminate morphology were characterised by absence of rudimentary chamber on angiography and echocardiography. The trabecular pattern of both main and rudimentary chambers were separately identified in some of the patients with univentricular hearts of right and left ventricular type and two dimensional echocardiography also illustrated the mode of atrioventricular connection, either via two atrioventricular valves, a common valve, or a valve straddling or overriding the trabecular septum. Finally it was also possible to distinguish absent atrioventricular connection from an imperforate valve in 10 patients.

Percutaneous balloon pulmonary valvuloplasty.

Percutaneous pulmonary valvuloplasty was performed in 27 patients with congenital pulmonary valve stenosis. A fall in the transvalve gradient of at least 15 mm Hg occurred in 22 patients. In five there was little change in the severity of the stenosis; in three of these the pulmonary valve was dysplastic. None of the successfully treated patients had a dysplastic valve. The two other failures, early in the series, were probably due to inadequate balloon size. In one patient the procedure was performed twice, with a successful result from the second dilatation with a larger balloon. Follow up studies in a further six patients showed no evidence of restenosis in those who had been successfully treated and no late improvement in the remainder. There were no important complications. Percutaneous pulmonary valvuloplasty should be the initial treatment for congenital pulmonary valve stenosis, although when the valve is dysplastic the result is less likely to be satisfactory.

Embolisation procedures in congenital heart disease.

Eight therapeutic embolisation procedures were performed by the transcutaneous catheter technique in seven patients with congenital heart disease. After surgical correction of tetralogy of Fallot (four patients), catheter embolisation was used to occlude two large aortopulmonary collaterals (one patient), three small aortopulmonary collaterals (one patient), and two Blalock-Taussig shunts (two patients). In two patients congenital coronary anomalies were occluded--a coronary arteriovenous malformation and a coronary artery/bronchial artery anastomosis. In one patient a pulmonary arteriovenous malformation was embolised. Detachable balloons were used to occlude six large arteries, the three small arteries were occluded with small gelfoam fragments, and the pulmonary arteriovenous malformation was occluded with multiple steel coils and large gelfoam pieces. Successful occlusion was achieved in all cases. No complications were encountered and the procedure was well tolerated even in the two patients receiving postoperative intensive care. Therapeutic embolisation in suitable cases is a safe and effective alternative to surgery and the detachable balloon technique is effective in occluding high flow vessels.

Superiority of radionuclide over oximetric measurement of left to right shunts.

In 100 children with suspected left to right shunts the ratio of pulmonary to systemic flow was measured both by oximetry and first pass radionuclide angiography. The pulmonary time activity curve from the radionuclide study was analysed by the method of gamma variate fits. There was strong correlation between the two techniques; weaker correlation was found when the shunt was at atrial rather than ventricular level. This difference can be explained only by problems with the oximetric rather than the radionuclide technique. Although there are important limitations to the radionuclide method, it is the more precise and less invasive of the two and is to be preferred when the accurate measurement of left to right shunts is required.

Experience with flecainide for the treatment of cardiac arrhythmias in children.

We treated 22 children, aged 3 days to 16 years 6 months (median 11 years 1 month), with flecainide for a variety of arrhythmias where a Class I agent was indicated. In 16, conventional antiarrhythmic treatment had failed. Structural heart disease was present in nine. The arrhythmia was paroxysmal re-entry atrioventricular tachycardia in nine; paroxysmal atrial tachycardia, flutter or fibrillation in five; paroxysmal ventricular tachycardia in five and frequent ventricular extrasystoles (with couplets) in three. Sinus rhythm was achieved in all four children who received flecainide during tachycardia (three received intravenous flecainide, one oral). During follow-up of 3-24 months (median 12 months), arrhythmia control was obtained in 13 children (59%). Combination therapy was used in seven of these; with digoxin in four and a beta blocker in three. Flecainide doses used in this study ranged from 1-11 mg kg-1 day-1 (median 4 mg kg-1 day-1), 25-297 mg m-2 day-1 (median 113 mg m-2 day-1). The median, pre-dose flecainide concentration in those responding to therapy was 225 micrograms l-1 and in those failing to respond was 417 micrograms l-1. An arrhythmogenic effect occurred in one child.

The use of tolazoline hydrochloride as a pulmonary vasodilator in potentially fatal episodes of pulmonary vasoconstriction after cardiac surgery in children.

Infants and children with highly reactive pulmonary vasculature may die of an acutely increased pulmonary vascular resistance (PVR) during or after correction of congenital heart defects. Fifteen patients, 11 infants ages 2--12 months (mean 5.3 months) and 4 children ages 2--10 years (mean 5.8 years), were treated with tolazoline to reduce an acutely elevated PVR during or after operation. Five patients had total anomalous pulmonary venous drainage, six had ventricular septal defect and four had truncus arteriosus. Preoperatively, the ratio of systolic pulmonary artery pressure to systemic artery pressure (PAP/SAP) was 0.57--1.54 (mean 0.93), and PVR was 1.8--20 units/m2 (mean 6.2 units/m2). The pulmonary artery pressure was monitored postoperatively by pulmonary artery lines placed at surgery (12 patients) or by balloon flotation catheters (two patients). Acute elevations in PAP/SAP accompanied by clinical deterioration occurred during attempted withdrawal from cardiopulmonary bypass in three patients, during apparently optimal ventilation postoperatively in eight patients, and after withdrawal of ventilatory support in four patients. Administration of tolazoline as a bolus (1--2 mg/kg) followed by infusion of 1--2 mg/kg/hour resulted in a rapid and sustained decrease in PAP/SAP, from 1.00 +/- 0.18 (mean +/- SD) to 0.40 +/- 0.09 (p less than 0.001), and was effective management for all these clinical crises. The use of tolazoline may prevent a fatal outcome from acute elevation of PVR in the perioperative period.