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With a tandem DMAP-catalyzed reaction between o -AQM, in which it is generated in situ from propargylic amine, and acyl carbene surrogate (from pyridinium ylide), a variety of polyarylated chromenes are assembled in good yields. This process does not require transition-metal catalyst and exhibits easy manipulation of the arene group and good functional group compatibility, particularly the -Br group which can be further transformed to other functionalities by cross-coupling reactions. The modular feature of o -AQM substrates and the simple operation procedures add further advantages to this synthetic method.

A DMAP-catalyzed cascade approach allowing facile assembly of alkynyl coumarins is reported. By virtue of reactive o -AQM (in situ generated from modular propargylamine) and a new synthetic equivalent of acyl carbene (from pyridinium ylide), the reaction proceeds smoothly to afford a variety of alkynyl coumarins in good-to-excellent yields. This transition-metal-free and oxidant-free process features moderate functional group tolerance, particularly the -Br group; thus, this protocol circumvents the inherent shortcomings of the existing Sonogashira coupling of coumarin triflates. This versatile method is also found to be applicable to the preparation of β-alkenyl coumarins, resembling the outcomes of the current Heck-type coupling reaction.

Facile access to π-extended heterobiaryl compounds via a non-cross-coupling strategy has been achieved. In the presence of an inexpensive ZnI2 catalyst and versatile propargylamine and β-naphthol (or β-naphthylamine and β-naphthyl mercaptan) starting materials, a variety of sterically hindered heterobiaryl frameworks can be easily obtained. The present catalytic system offers excellent selectivity, good-to-excellent product yields, and good functional group tolerance including, for instance, -CN, -COOH, -C(O)R, -Br and -Cl groups. This cyclization process is proposed to proceed via in situ generated alkynyl o-quinone methides (o-AQMs), following a cascade intermolecular 1,4-conjugate addition/5-exo-dig annulation/1,3-H shift pathway.

Palladium-catalyzed C-N bond coupling reaction between NH-sulfoximines and aryl halides (e.g., -Br, -I, and -Cl and pseudohalides -OTf and -ONf) was successfully achieved. Nevertheless, aryl tosylates/mesylates left much to be achieved. In this report, a general N-arylation of sulfoximines with aryl sulfonates is described. Using Pd(OAc) 2 /MeO-CM-phos complex, the N-aryl sulfoximine products can be obtained in good-to-excellent yields (up to 99%) with good common functional group compatibility. In addition to arene moieties, alkenyl tosylates are shown to be successful coupling partners.

Aims: This pilot study investigated perceptual and electrophysiological characteristics of dyslexic children, and evaluated the immediate and prolonged effect of visual perceptual training on these characteristics in these children., Methods and Procedures: Seven dyslexic children and seven controls aged 7-8 years were recruited and completed this study. All dyslexic children completed 10-weeks of visual perceptual training. The visual perceptual skills were assessed and binocular visual evoked potentials (VEP) were recorded with two different pattern stimulations initially (Baseline), 3 months after the first assessment (Evaluation I) and 6 months after first assessment (Evaluation II)., Outcomes and Results: A significant reduction (p = 0.021) in VEP amplitudes in the dyslexic subjects in response to 15 Hz reversal frequency at 15% contrast stimulation was found, compared with controls, prior to perceptual training. A significant correlation (p = 0.005) was found between the VEP amplitude with 15 Hz reversal frequency and the total score of Test of Visual Perceptual Skills (non-motor) - revised (TVPS-R). After training, dyslexic subjects scored higher in some of the visual perceptual tasks and these improvements persisted for 3 months. However, the VEP amplitude in the dyslexics showed no significant change after perceptual training., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The first general examples of direct C-H arylation of electron-deficient polyfluoroarenes with challenging di- ortho-substituted aryl(heteroaryl) chlorides for tetra- ortho-substituted biaryl synthesis are reported. Key to success is the use of Buchwald-type biaryl phosphine ligand, notably with inexpensive -PPh 2 moiety (instead of -PCy 2 group). Pd(OAc) 2 associated with ligand L9 exhibits even higher efficiency than the corresponding SPhos toward this reaction. A wide range of sterically hindered di- ortho-substituted chloroarenes bearing electron-donating or -withdrawing groups are found applicable. Excellent product yields are obtained under mild reaction conditions, and the catalyst loading down to 0.25 mol % of Pd can also be achieved.

Children born very preterm are at a greater risk of abnormal visual and neurological development when compared to children born at full term. Preterm birth is associated with retinopathy of prematurity (a proliferative retinal vascular disease) and can also affect the development of brain structures associated with post-retinal processing of visual information. Visual deficits common in children born preterm, such as reduced visual acuity, strabismus, abnormal stereopsis and refractive error, are likely to be detected through childhood vision screening programs, ophthalmological follow-up or optometric care. However, routine screening may not detect other vision problems, such as reduced visual fields, impaired contrast sensitivity and deficits in cortical visual processing, that may occur in children born preterm. For example, visual functions associated with the dorsal visual processing stream, such as global motion perception and visuomotor integration, may be impaired by preterm birth. These impairments can continue into adolescence and adulthood and may contribute to the difficulties in learning (particularly reading and mathematics), attention, behaviour and cognition that some children born preterm experience. Improvements in understanding the mechanisms by which preterm birth affects vision will inform future screening and interventions for children born preterm., (© 2017 Optometry Australia.)

Objective: To develop an age-based weight estimation rule in a Chinese population and to compare its performance with existing formulae., Design: Population-based observational study., Setting: Schools and kindergartens in Hong Kong., Subjects: Healthy Chinese children aged 1-10&emsp14;years old on their last birthday., Interventions: Weight was measured to the nearest 0.2 kg., Main Outcome Measures: Linear regression was used to derive a simple formula relating weight to the child's age on his or her last birthday. The accuracy and precision of different age-based weight formulae was compared using coefficient of variation, Bland Altman plots, and by determining the proportion of children with estimates >30% outside the actual weight., Results: The Chinese Age Weight Rule is a simple linear formula that is more accurate than and at least as precise as any other age-based weight estimation rule: weight in kg=(3 × age last birthday)+5. It is accurate and precise in children <7 years old, but all age-based weight estimates are imprecise in older children., Conclusions: The Chinese Age Weight Rule should be used in a Chinese population in preference to any other age-based weight estimation rule. Caution should be taken when using it in older children in whom other weight-estimation tools may be more appropriate.

The purpose of this study was to assess whether the magnitude of change in aerobic power was different in boys (mean age 10.25 +/- 0.50 y) who followed a high-intensity interval training protocol, compared to those who followed a moderate-intensity continuous training protocol. Boys were assigned to either a control group (n = 15), a continuous training group (n = 10), or an interval training group (n = 10). They completed peak oxygen uptake tests at baseline and following an 8-week training period. The control group continued with normal activity habits, whilst the continuous training group followed a 20-minute steady-state cycle protocol at 80-85 % of the maximal heart rate, and the interval training group completed 30-s sprints on a cycle ergometer, interspersed with active rest periods. The two training protocols were designed to incur similar cardiovascular work over the 20 minutes of each training session. Significant increases (p < 0.05) in peak oxygen uptake were noted for both the interval and continuous training groups. The interval training group showed marked pre- to post-increases in both peak oxygen pulse, oxygen pulse at the ventilatory threshold, and ventilatory threshold that were not apparent in the continuous group boys. It would appear that a high-intensity interval protocol confers a different training effect in comparison to continuous steady-state training in boys. Possible mechanisms that underpin these adaptations may include increased blood volume and a concomitant adjustment in stroke volume.

Objectives: To use dobutamine stress echocardiography to determine left ventricular (LV) function and wall motion of children long term after arterial switch operation (ASO) for transposition of the great arteries., Design and Patients: 31 patients (24 boys) with ASO performed at a mean (SD) of 15.5 (4.3) days of life were studied at an age of 9.4 (2.0) years. All had normal coronary angiographic findings. LV echocardiographic indexes, including fractional shortening, ejection fraction, rate corrected velocity of circumferential fibre shortening (VCFc), and wall stress, as well as LV wall motion abnormalities were determined at rest and under dobutamine stress. The results were compared with those of 20 healthy age matched control participants., Setting: Tertiary paediatric cardiac centre., Results: Fractional shortening, ejection fraction, and VCFc were significantly lower in patients than in controls at rest (all with p < 0.001). Stress-velocity index detected impaired LV contractility in 19 (61%) patients at rest. An older age at operation (p = 0.01), longer bypass (p = 0.01) and circulatory arrest times (p = 0.045), and an unusual coronary artery pattern (p = 0.059) were associated with impaired resting LV contractility. Dobutamine stress echocardiography unmasked wall motion abnormalities in 23 (74%) patients. Exercise myocardial perfusion scan, performed in 22 patients, showed reversible myocardial perfusion defects in 17. These defects corresponded to segments of hypokinesia as detected by dobutamine stress echocardiography., Conclusion: A significant proportion of children, albeit asymptomatic, had impaired baseline LV contractility and reversible myocardial perfusion defects and mild wall motion abnormalities on stress after ASO.

This cross-sectional study was designed to provide baseline information on peak oxygen uptake for Southern Chinese children in relation to age and sexual maturation. Sixty-three boys and 84 girls, classified for stage of sexual maturation using Tanner's stages, successfully completed a peak oxygen uptake test. ANOVA was used to examine differences in absolute and mass-related peak VO(2). The least-squares log-linear relationship between mass and peak VO(2) was examined using analysis of covariance. We found no difference between boys' and girls' peak VO(2) prior to puberty. Absolute peak VO(2) values for under-10-year-old Chinese girls and boys were 17% and 19%, respectively, lower than Caucasian predicted values. Log-linear adjusted means for prepubertal boys and girls were 34% and 33% lower than Caucasian boys and girls, respectively. By adolescence, values were comparable to Caucasian values. South Chinese children show a distinct pattern of development relative to Caucasian children, particularly in the younger age groups., (Copyright 2004 Wiley-Liss, Inc.)

Objective: To identify genes expressed in the fetal heart that are potentially important for myocardial development and cardiomyocyte proliferation., Methods: mRNAs from fetal (29 weeks) and adult cardiomyocytes were use for suppression subtractive hybridization (SSH). Both forward (fetal as tester) and reverse (adult as driver) subtractions were performed. Clones confirmed by dot-blot analysis to be differentially expressed were sequenced and analyzed., Results: Differential expressions were detected for 39 out of 96 (41%) clones on forward subtraction and 24 out of 80 (30%) clones on reverse. For fetal dominating genes, 28 clones matched to 10 known genes (COL1A2, COL3A1, endomucin, HBG1, HBG2, PCBP2, LOC51144, TGFBI, vinculin and PND), 9 clones to 5 cDNAs of unknown functions (accession AK021715, AF085867, AB040948, AB051460 and AB051512) and 2 clones had homology to hEST sequences. For the reverse subtraction, all clones showed homology to mitochondrial transcripts., Conclusions: We successfully applied SSH to detect those genes differentially expressed in fetal cardiac myocytes, some of which have not been shown relative to myocardial development.

We assessed the spectrum of airway disorders in children with congenital cardiac anomalies, and reviewed our experience in using flexible bronchoscopy for assessment of airway problems in this patient group. The clinical records, flexible bronchoscopic findings, and cardiac imaging results of pediatric cardiac patients who presented with either clinical or radiological signs of airway obstruction between 1992-1999 were reviewed. Flexible bronchoscopic assessment was performed with the patients under sedation and topical anesthesia, using one of two bronchoscopes, i.e., an Olympus BFN20 or Olympus BF3C20. Of a total of 52 patients, 33 had acyanotic cardiovascular lesions, the commonest being left-to-right shunts (61%), while 19 had cyanotic heart lesions, with right ventricular outflow obstruction being the commonest (63%). Twenty-seven patients had undergone either surgical or transcatheter interventions. The median age at bronchoscopic assessment was 6 months (range, 4 days to 6 years). None of the patients developed significant procedural complications. A definitive diagnosis was made in 48 (92%) patients, 8 of whom had abnormalities involving only the upper airways, 35 only the lower airways, and 5 both. Abnormalities of the upper airway included laryngomalacia (n = 6), subglottic stenosis (n = 3), pharyngeal collapse (n = 2), and 1 each of choanal stenosis and supraglottitis. Extrinsic compression was the commonest lower airway abnormality that was found in 27/40 patients (67%), with a predilection for the left main bronchus (18/27, 67%). The structures that caused extrinsic compression included dilated pulmonary arteries with or without left atrial dilation (n = 20), an anomalous aortic or pulmonary arterial course (n = 3), a dilated aorta (n = 1), and a shunt (n = 1), but were not obvious in 2 patients. Intrinsic lower airway abnormalities included bronchomalacia (n = 4), tracheal stenosis (n = 4), and one each of variant bronchial bifurcation and a pouch arising from the tracheal wall. Intraluminal mucus plugging of the lower airways occurred in the remaining 3 patients. Children with congenital heart disease are at risk of airway obstruction both before and after surgery. Flexible bronchoscopy, being safe and effective in diagnosing airway disorders in this patient group, should be considered as the first line of investigation., (Copyright 2002 Wiley-Liss, Inc.)

Objective: We report our experience in combining tracheobronchography and angiocardiography in the assessment of a selected cohort of paediatric cardiac patients with problematic airway disorders., Methodology: The clinical records of 11 patients who underwent 17 studies at a median age of 5.5 months (range 3 months to 10.8 years) were reviewed. Tracheobronchography and angiocardiography were performed under general anaesthesia using a non-ionic contrast agent. The findings were compared with those of flexible bronchoscopy and magnetic resonance imaging (MRI)., Results: Seven patients had cardiac lesions associated with vascular anomalies potentially compressing the airway, while four had no identifiable aberrant or enlarged vessels. All examinations but one were performed without complications. Tracheobronchography demonstrated extrinsic vascular compression with secondary airway malacia in three (27%), intrinsic tracheobronchial stenosis in five (45%), and airway malacia in three patients (27%). Precise measurement of the airway calibre and real-time fluoroscopic monitoring facilitated transcatheter tracheobronchial interventions (six balloon dilations, three stent implantations) in four patients. In conjunction with angiocardiography, cine-tracheobronchography provided detailed information on the spatial relationship between vascular and airway structures in all patients; allowed dynamic assessment of airway malacia; and facilitated preoperative planning in six patients. In contrast, bronchoscopy failed to differentiate malacia from extrinsic compression in four patients (36%), while MRI, performed in six patients, was unsatisfactory in one due to a motion artefact and failed to diagnose airway malacia and extrinsic compression in three patients., Conclusions: Tracheobronchography is relatively safe in paediatric cardiac patients. Combined tracheobronchography and angiocardiography, a less operator-dependent imaging modality compared to bronchoscopy and MRI, delineated the airway and vascular anatomy in detail; facilitated preoperative planning; and permitted transcatheter tracheo-bronchial interventions. The dynamic capability of tracheobronchography supplements that of flexible bronchoscopy and MRI in the diagnosis of airway malacia.

Objective: Ten percent povidone-iodine (PVI) is commonly used as a bactericidal solution before amniocentesis is performed. Warming PVI may increase patient comfort; however, the effect of warming on its bactericidal properties is not known. The objective of this study was to determine the effect of warming 10% PVI on its bactericidal properties., Study Design: Room temperature of PVI was 25 degrees C, and temperature in an ultrasonic gel warmer was 32 degrees C. In vitro experiments were conducted in 25 degrees C and 32 degrees C water baths. Nine milliliters of PVI at each temperature was added to 1 mL of bacteria (10(7) organisms/mL Staphylococcus aureus, Enterococcus species, Escherichia coli, group B Streptococcus). After 0.25, 0.5, 1, 2, 4, and 8 minutes, 1-mL samples were removed and added to 4 mL of 0.5% sodium thiosulfate (to neutralize the iodine and interrupt bactericidal action). The number of viable organisms was determined by plating 0.1-mL samples on trypticase soy agar plates. Plates were incubated at 37 degrees C for 24 hours and colony-forming units (CFUs) were counted. For in vivo experiments in 40 volunteers, a 9-cm2 area of the dorsum of each hand was wiped with a sterile cotton swab to obtain a sample of bacteria for culture. The area was then wiped for 15 seconds with PVI at 25 degrees C or 32 degrees C and recultured. The bactericidal properties of PVI at each temperature were compared. The Mann-Whitney U test was used as appropriate, and P <.05 was considered significant., Results: In vitro, PVI was bactericidal against E coli, S aureus, Enterococcus species, and group B Streptococcus within 0.25 minutes at both 25 degrees C and 32 degrees C, with median bacterial growth of 0 CFU/plate for each species of bacteria studied (3 replicates at each temperature). Median bacterial growth from skin was 4 CFU/plate (range, 0 to >100). After hands were wiped with PVI at 25 degrees C and 32 degrees C, median bacterial growth was 0 CFU/plate (range, 0-8) and 0 CFU/plate (range, 0-15), respectively (not significant)., Conclusion: PVI is as effective at 32 degrees C as it is at 25 degrees C. Use of PVI at 32 degrees C should be considered to increase patient comfort in procedures performed without the use of anesthetics.

Objective: To compare the outcome of infants and children who have right atrial isomerism and normal pulmonary venous drainage with those who have anomalous drainage, and to determine factors associated with poor outcome., Design and Patients: Retrospective review of management and outcome of 116 infants and children determined to have right atrial isomerism between January 1980 and December 2000., Setting: Tertiary paediatric cardiac centre., Results: The 116 patients presented at a median of one day (range 1 day to 3.7 years) with cyanosis in the majority (96%). No interventions were planned in 31 (27%) patients, all of whom died. The early surgical mortality for pulmonary venous repair was 25% (2 of 8), Fontan procedure 26% (5 of 19), cavopulmonary shunting 7.7% (1 of 13), and systemic pulmonary arterial shunt insertion 1.9% (1 of 53). Late mortality was related to infection (n = 10), sudden death of unknown aetiology (n = 7, 5 with history of arrhythmia), and documented arrhythmia (n = 1). Patients with obstructed anomalous pulmonary venous drainage had the worst survival (p < 0.001). The mean (SEM) survival estimates for those with normal pulmonary venous drainage at 1, 5, 10, and 15 years was 81 (5.3)%, 67 (6.6)%, 60 (7.8)%, and 43 (12)%, respectively, similar to those for patients with non-obstructed anomalous drainage (p = 0.06). Independent risk factors for mortality included pulmonary venous obstruction (relative risk 3.8, p = 0.001) and a single ventricle (relative risk 2.9, p = 0.016). An analysis of only patients with normal pulmonary venous drainage identified no risk factors for mortality., Conclusions: The long term outcome of infants and children with right atrial isomerism in association with a normal pulmonary venous drainage remains unfavourable. Sepsis and sudden death that may potentially be related to cardiac arrhythmia are major causes of late mortality.

Two infants who developed chylothorax after surgery for congenital heart disease were treated successfully with subcutaneous octreotide. Apart from reducing chyle output, octreotide decreased the triglyceride content of the pleural fluid.

Subarterial ventricular septal defect (VSD) is relatively common in Orientals. We reviewed the outcome of 214 patients (137 males) who were followed for 8.6 +/- 5.2 years (range 0.1 to 24.3) and addressed the issue regarding the necessity and optimum timing of closing subarterial defects before development of aortic valve deformities. Demographic data, transthoracic and transesophageal echocardiographic findings, cardiac catheterization results, and operative findings were reviewed. Kaplan-Meier actuarial analysis was performed to assess the development of aortic valve complications over time. Seventy-five patients with heart failure and pulmonary hypertension underwent surgical closure of VSD at the age of 2.4 +/- 2.9 years. No patient had aortic cusp prolapse before operation and none developed aortic cusp prolapse or aortic regurgitation (AR) on follow-up. In contrast, of the 139 asymptomatic patients managed conservatively, 102 (73%) developed aortic cusp prolapse, 78% of whom (80 of 102) developed AR. The prevalence of aortic cusp prolapse and AR at 1, 5, 10, and 15 years old was 8%, 30%, 64%, and 83%, and 3%, 24%, 45%, and 64%, respectively. Significant prolapse or AR prompted surgical closure of VSD with (n = 22) or without (n = 26) valvoplasty in 48 of 102 patients (47%). The size of the VSD was significantly larger in patients with heart failure (9.6 +/- 3.3 mm) or aortic cusp prolapse (11.7 +/- 4.1 mm) compared with those without heart failure (4.5 +/- 1.4 mm, p <0.001). All patients with aortic cusp prolapse and all but 1 with heart failure had a defect size of > or =5 mm. In conclusion, subarterial VSD of > or =5 mm should be closed as early as possible to prevent development of aortic cusp prolapse and AR. Asymptomatic patients with small defects <5 mm could be managed conservatively.

A 20-year-old young man suffered from severe protein-losing enteropathy 4 years after Fontan operation. His postoperative haemodynamics were unfavourable in terms of poor myocardial contractility and moderate atrioventricular prosthetic paravalvar leakage. A 2-week trial of steroid therapy for protein-losing enteropathy was given without success. The clinical course was complicated by Legionella pneumophila pneumonia and bacteraemia, which respond to the combination therapy with intravenous erythromycin and ciprofloxacin. The vulnerability of the patient to infection was related to an immuno-deficiency state secondary to protein-losing enteropathy and steroid therapy. Steroids should be used with caution in the management of protein-losing enteropathy after Fontan operation., (Copyright 2001 The British Infection Society.)

Background: Different types of coils have been designed for transcatheter closure of persistent arterial ducts. We compared the efficacy and safety of three types of coils: Gianturco coils (Cook), Cook detachable coils (Cook), and Duct Occlud devices (pfm)., Methods: Sixty-three patients underwent coil occlusion of arterial ducts between April 1995 and July 2000. The mean age and weight were 4.8+/-3.4 years and 16.5+/-7.6 kg, respectively. The results and complications of ductal occlusion among the three types of coils were compared. Kaplan-Meier analysis was used to assess reduction in the prevalence of residual shunt with time, and multiple regression analysis was performed to identify predictors of complete occlusion., Results: Coil occlusion of persistent arterial ducts that measured 2. 2 +/- 0.8 mm was feasible in 90% (57/63) of patients. Gianturco coils were used in 29, Duct Occlud devices in 16, and Cook detachable coils in 12 patients. The prevalence of residual shunt at 24 hours, 6 months, 12 months, and 24 months was 42%, 20%, 18%, and 14%, respectively. The reduction in prevalence of residual shunt with time tended to be greater when Gianturco coils were used (P =. 067). Logistic regression identified the use of Gianturco coils to be a significant predictor of complete ductal occlusion on follow-up (P =.04). Pull-through of coils occurred in 4.8% (3/63) and coil embolization in 6.3% (4/63). There was no association between the type of coil and the risk of embolization (P = 1.00)., Conclusions: Transcatheter occlusion of small persistent arterial ducts with coils is safe and effective. There is no advantage of detachable coils (Cook detachable coils and Duct Occlud devices) over nondetachable Gianturco coils in reducing the risk of embolization. Our findings are in favor of the inexpensive, but more effective, Gianturco coils for occluding small arterial ducts of 3 mm or less.

A 15-year-old girl with Noonan syndrome, intestinal lymphangiectasia and severe valvar pulmonary stenosis had an abnormal lymphangioscintigram that showed intense activity in the inguinal regions bilaterally. Cutaneous oozing of lymphatic fluid from the groin wound complicated percutaneous balloon pulmonary valvoplasty. This previously unreported complication highlights the risk of damage to abnormal lymphatic channels in patients with Noonan syndrome who undergo interventional catheterization.

The effects of beta-adrenoceptor stimulation with isoproterenol on electrically induced contraction and intracellular calcium ([Ca(2+)](i)) transient, and cAMP in myocytes from both hypertrophied right and nonhypertrophied left ventricles of rats exposed to 10% oxygen for 4 wk, were significantly attenuated. The increased [Ca(2+)](i) transient in response to cholera toxin was abolished, whereas increased cAMP after NaF significantly attenuated. The biologically active isoform, G(s)alpha-small (45 kDa), was reduced while the biologically inactive isoform, G(s)alpha-large (52 kDa), increased. The increased electrically induced [Ca(2+)](i) transient and cAMP with 10-100 microM forskolin were significantly attenuated in chronically hypoxic rats. The content of G(i)alpha(2), the predominant isoform of G(i) protein in the heart, was unchanged. Results indicate that impaired functions of G(s) protein and adenylyl cyclase cause beta-adrenoceptor desensitization. The impaired function of the G(s) protein may be due to reduced G(s)alpha-small and/or increased G(s)alpha-large, which does not result from changes in G(i) protein. Responses to all treatments were the same for right and left ventricles, indicating that the impaired cardiac functions are not secondary to cardiac hypertrophy.

Over the years, management of critical pulmonary stenosis in young infants has evolved from surgical reconstruction of the right ventricular outflow tract and closed pulmonary valvotomy to transcatheter balloon valvoplasty. Our study aimed at evaluating how the changing policy for management had affected the immediate and long term outcomes of babies with this cardiac lesion. Interventions were made in 34 infants at a median age of 8.5 days (2-90 days). Reconstruction of the right ventricular outflow tract reconstruction was performed in 10 patients, closed pulmonary valvotomy in 13, and balloon valvoplasty in 11. Initial procedure-related mortality was 50%, 15% and 0% respectively. Multivariate analysis revealed transannular patching of the right ventricular outflow tract, and male sex, to be significant factors for death. For the 27 survivors, the ratio of right ventricular to systemic systolic pressure decreased from 1.6 +/- 0.3 to 0.3 +/- 0.2 after reconstruction of the outflow tract, 1.8 +/- 0.5 to 0.8 +/- 0.4 after closed valvotomy, and 1.8 +/- 0.6 to 0.9 +/- 0.3 after balloon valvoplasty. The decrease was significantly greater after patch reconstruction (p=0.025) that required no further reinterventions. The overall rate of reintervention for the survivors was 37% (10/27). The freedom from reintervention after closed valvotomy was 82%, 64% and 51% at 1, 5 and 10 years respectively. The figure remained at 78% at both 1 and 5 years (p=0.66) after balloon valvoplasty. The higher reintervention rate for closed valvotomy corresponded to the significantly greater residual gradient across the pulmonary valve noted on follow-up (p=0.01). Reinterventions included balloon dilation (n=6), reconstruction of the outflow tract (n=4), and 1 each of ligation of an arterial duct and systemic-pulmonary arterial shunting. The risk factor for reintervention was a hypoplastic right ventricle. In conclusion, transcatheter balloon valvoplasty appears to be the optimum initial approach in view of its low mortality, efficacy at relieving the obstruction, and low rate of reintervention.

Accurate evaluation of secundum atrial septal defect (ASD) is important for the success of transcatheter closure. The purpose of this study was (1) to describe a quantitative evaluation by transthoracic (TTE) and transesophageal (TEE) echocardiography of the various morphologic features of ASD that might be important for patient selection for transcatheter closure, and (2) to assess the reliability of these 2 methods by surgical findings. Preoperative TTE and TEE were used to evaluate the ASD of 27 children undergoing surgical closure. Measurements included the diameters of ASD and the atrial septal lengths in the transverse and longitudinal axis, and the width of the superior, inferior, anteroinferior, and posterior septal margins. The shape and location of the ASD and the adequacy of the septal margins for anchoring occluding devices were determined. Echocardiographic data were compared with corresponding surgical measurements. No significant difference occurred in the means of all the parameters measured with the 3 methods, except for the transverse ASD diameter (p <0.05). Good agreement occurred between TTE and TEE and surgical data, except for the transverse ASD diameter, transverse atrial septal length, and the posterior septal margin on TTE. Intraclass correlations between TTE and TEE and surgical measurements of all parameters were good, except for the transverse ASD diameter. The accuracy in determining shape and location of the ASD by TTE and TEE were 100%, whereas that for determining the adequacy of septal margins was 98% and 97%, respectively. In conclusion, TTE and TEE are reliable methods for quantitative evaluation of ASD.

Many Western children with congenital heart disease (CHD) show significant growth retardation. In this study postnatal growth was examined in Chinese children with symptomatic CHD in Hong Kong, in relation to their diagnosis and the time of surgery. 363 children of four years old or younger, who were admitted at Grantham Hospital, Hong Kong, in 1994 and 1995, were subdivided into six diagnostic categories and categorised into cyanotic and acyanotic groups. While a reduced birth weight SDS was present in 18% of patients, at the time of operation approximately 40% of them had subnormal weight and height values. Girls were more impaired in weight and weight-for-height than boys (-1.90 SDS vs -1.52 SDS, and -0.90 SDS vs -0.46 SDS, respectively). Children with acyanotic lesions were more affected in growth than those with cyanotic lesions, but they were also operated on at an older age than children in the latter group. Left to right shunt and common intracardiac mixing were particularly associated with wasting; transposition of the great arteries and pulmonary outflow tract obstruction with stunting; while children with left ventricular outflow obstruction revealed a proportional growth retardation in weight and height. Age at operation did not seem to have an independent effect on postnatal growth in children with CHD. As with Western children, growth retardation is a common feature in Chinese children with symptomatic cardiac defects. Haemodynamics, age at operation and nutritional influences are discussed as potential aetiologic factors.

Objectives: We report on the early and intermediate-term follow-up results of self-expanding Wallstent (Schneider, Switzerland) implanted in children with congenital heart disease., Background: The inherent shortcomings of balloon-expandable stents prompted the trial of an alternative stent., Methods: Twenty patients underwent 22 implantations of 25 self-expanding Wallstents between December 1993 and June 1997 in two institutions. The mean age and weight were 10.8+/-4.5 years and 30.5+/-14.2 kg, respectively. The patients were divided into two groups: 1) Group I comprised 17 patients with pulmonary arterial stenoses, 2) Group II comprised four patients with venous stenoses (one belonged to both groups). Sixteen patients underwent recatheterization at a median of 5.8 months (range 0.5 to 31, mean 8.1 months) after stenting. Hemodynamic and angiographic changes after the interventional procedures and complications were documented., Results: All the stents were successfully deployed in the intended position. In Group I, the narrowest diameter of the stented vessel increased from 4.1+/-1.5 to 8+/-2 mm (95% increase, p < 0.0001) while the systolic pressure gradient across decreased from 24.6+/-15.8 to 12.1+/-11.4 mm Hg (51% decrease, p = 0.001). In Group II, the dimensional changes of the narrowest segment increased from 4.3+/-0.5 to 7.5+/-0.4 mm (75% increase, p = 0.003), and the pressure gradient reduced from 5.0+/-2.9 to 0.9+/-1.0 mm Hg (82% decrease, p = 0.04) across the stented venous channel. Distal migration of two optimally positioned stents occurred within 24 h of implantation. At recatheterization, significant neointimal ingrowth (>30% of the expanded diameter) was noted in 7 (28%) of the 25 implanted stents. This responded poorly to balloon dilation. Predisposing factors for the neointimal ingrowth included stents of smaller diameter (<9 mm) and longer period after implantation., Conclusions: Self-expanding Wallstent could be deployed easily and safely to relieve vascular stenoses in children. The complications of distal migration, significant neointimal ingrowth and its unyielding design to overdilation limit its application to this patient group.

Racial group studies have identified differences in the occurrence of congenital heart disease (CHD) among ethnic populations. The aim of this study was to characterize the proportionate frequency and clinical profile of children with symptomatic cardiac abnormalities in Hong Kong. The hospital records of 666, mainly Southern Chinese children with symptomatic CHD, who were 4 years of age or younger and who were admitted to Grantham Hospital, Hong Kong, in 1994 and 1995 were analyzed retrospectively. Left-to-right shunting (45.0%) and pulmonary outflow obstruction (34.4%) were the most frequently diagnosed categories, followed by left ventricular outflow obstruction (8.3%), transposition of the great arteries (4.2%), conditions with intracardiac mixing (3.9%), and other cardiac lesions (4.2%). Compared with Western studies, pulmonary outflow obstruction (p<0.0001), particularly tetralogy of Fallot and critical pulmonary stenosis, were more frequent in Chinese children. In contrast with previous reports, coarctation of the aorta (5%) does not seem to be uncommon in Chinese patients. Conversely, aortic stenosis and hypoplastic left ventricle may be rare in these children (1% vs 3% and 3-7%). Other cardiac lesions showed no consistent racial difference in the frequency of occurrence. Chinese patients with Down's syndrome had ventricular septal defect (38%) as the predominant lesion followed by atrioventricular septal defect (25%). Western studies usually report a reverse pattern for these two lesions. The mortality rate for the total cohort was 7.5%. However, of those with conditions with intracardiac mixing and left ventricular outflow tract obstruction many did not survive childhood (20% and 21%, respectively).

Background and Hypothesis: Transesophageal echocardiography (TEE) is increasingly utilized for the monitoring of interventional cardiac catheterization in children. The initial nondiscriminant use is giving way to a more selective approach. The current role and usefulness of this imaging modality are described., Methods: Between 1991 and 1995, 44 patients (mean age 7.4 +/- 5 years, weight 22.8 +/- 14.2 kg) underwent interventional cardiac catheterizations performed under TEE monitoring. The interventional procedures included (1) those involving creation, enlargement, or closure of an interatrial communication; (2) balloon dilatation of stenotic lesions; and (3) occlusion of arterial ducts. Transesophageal echocardiographic monitoring was judged to be either of great value, contributory, or of little use if the interventional procedure and choice of instrument relied heavily upon, was guided, or not affected by the information obtained from the ultrasonic investigation, respectively., Results: Transesophageal echocardiography was judged to be of great value in the monitoring of 18 (40%) procedures involving either the creation, enlargement, or closure of interatrial communications. This included 4 transseptal punctures, 4 blade septectomies for relieving restrictive atrial septal defects (n = 3) and an enlargement of the communication between the superior and inferior chambers of the divided left atrium in cortriatriatum, and 11 closures of a secundum atrial septal defect. Only the ultrasonic monitoring could clearly visualize the interatrial partition to provide real-time guidance on the positioning of the instrument to carry out the invasive procedures. Transesophageal echocardiography provided clear images of the hinge points of the aortic and mitral valves, the dimension of the narrowed pulmonary venous pathway in patients after venous switch operation. This facilitated the choice of the correct size of the balloon for dilatation in 11 patients (24%) and provided immediate postdilatation hemodynamic assessment. As for balloon dilation of subvalvar ventricular outflow tract obstruction (n = 3), aortic coarctation (n = 6), and occlusion of persistent arterial duct (n = 7), TEE offered no obvious advantage over fluoroscopy with angiography. The monitoring was judged to be of little value for the 16 (36%) procedures., Conclusion: Transesophageal echocardiographic monitoring is of great value in interventional procedures involving the atrial septum and enhances interventional procedures involving obstructive lesions of the left heart in children.

The aim of the study was to provide logical steps, alternative to the sequential chamber analysis, for diagnosing major congenital heart malformation prenatally. Between 1988 and 1995, of the 14,885 high-risk pregnancies screened at the Departments of Obstetrics and Paediatric Cardiology, University of Hong Kong, 92 fetuses with major congenital heart malformations were detected at 17-36 weeks' gestation (mean=24.6 weeks) by extended fetal echocardiographic screening. These were classified according to obvious abnormalities related to the partition of the heart or ventricular dimensions depicted by the four-chamber view. Subgrouping according to the presence of normal or abnormal ventriculo-arterial connection, with or without outflow tract anomalies, was further attempted. Five groups were identified: (1) septal defects with all four chambers identified (n=62, 67 per cent); (2) intact septation with dilatation of either the right or all four chambers of the heart (n=12, 13 per cent); (3) intact septation with hypoplasia of either one of the ventricles (n=11, 12 per cent); (4) a rudimentary interventricular septum giving an apparent three-chamber heart (n=6, 7 per cent); (5) miscellaneous causes (n=1, 1 per cent). Combined with the information related to the ventricular outflow tracts, the accuracy of arriving at a definitive diagnosis was 97 per cent, when compared with postnatal investigations, surgery and/or autopsies. This simple classification could provide logical steps to arrive at a definitive diagnosis for most major fetal heart malformations.

The commonly accepted indication for surgical intervention in necrotizing enterocolitis (NEC) is perforation of the bowel. In this study, the indication and role of surgery was assessed in neonates born with symptomatic congenital heart disease (CHD). Records of neonates admitted to a single institution in Hong Kong between January 1981 and December 1997 with symptomatic CHD who subsequently developed NEC were reviewed. The patients were categorized into cyanotic and acyanotic groups. Of 850 neonates with CHD admitted during the period, 30 developed NEC (3.5%); 17 had cyanotic and 13 had acyanotic heart disease. The average Apgar scores at 1 and 5 min were 7.5 and 8.6, respectively. The mean gestational age was 37.7 weeks and the mean birth weight was 2.5 kg. The mean age at which NEC developed was 16 days. The overall mortality in the proven cases of NEC was 57%. After excluding the suspected NEC cases (stage I), it was found that surgery in the proven NEC cases without perforation, i.e., stages II and IIIA, resulted in higher survival than in those managed medically (75% vs 44%). The cyanotic patients had higher mortality than the acyanotic group (71% vs 39%). Neonates with CHD who develop NEC belong to a unique group of mature babies with reasonable birth weights and Apgar scores, unlike the common NEC patient population. The mortality of these patients is extremely high, and a modified management approach is required. Surgical intervention may be indicated at a much earlier stage of proven NEC before gut perforation occurs.

Objectives: This study aims to evaluate the efficacy of a low dose warfarin regimen for Chinese children requiring anticoagulation therapy and its safety when monitored on an outpatient basis. Current recommendations are based on extrapolations from the adult experience and a high target international normalised ratio (INR) is adopted amongst the Western countries., Methodology: This is a 10-year retrospective study from January 1986 to June 1996. Effectiveness of warfarin therapy was monitored by the prothrombin time, standardised and expressed as the INR. A target INR of 1.5-2.5 was adopted for children with cardiac diseases requiring anticoagulation therapy for primary and secondary prophylaxis against thromboembolism. From the clinical records, demographic data, induction warfarin dosage, changes of dosages and related events on follow-up, frequency of outpatient visits, complications and serial INR results were reviewed., Results: Thirty-five patients (23 boys, 12 girls) were included with a mean age at initiation of warfarin therapy of 8.4+/-5.8 years. Amongst these, 66% (n = 23) were after isolated valvar replacement, 28% (n = 10) after Fontan operation with or without valvar replacement and 6% (n = 2) after deep vein thrombosis. Regression estimate of the induction dose was 0.05-0.13 mg x kg(-1) in order to achieve the target INR range after 2 days of warfarin therapy. The daily maintenance warfarin dose was correlated with the bodyweight [dose (mg x day(-1))= 0.04 x bodyweight (kg) + 0.87, r = 0.63, P<0.0001]. Young children required significantly higher daily warfarin maintenance dose when adjusted for bodyweight [dose (mg x kg day(-1)) = antilog(10)¿-0.02 x age (years)- 0.80¿, r = -0.74, P<0.0001]. The mean maintenance warfarin dosage was significantly lower in patients after the Fontan operation, with or without valvar replacement, in the absence of apparent liver dysfunction. The total period of followup was 159 patient-years. No serious bleeding complications or embolic phenomena were documented. One patient died of thrombosis of the mitral valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient-years., Conclusions: A low dose warfarin regimen to maintain a target INR of 1.5-2.5 provides adequate protection in Chinese children against thromboembolism whilst allowing safe outpatient monitoring of the anticoagulation status.

Intraventricular together with atrial-axis and nodoventricular discontinuity, in which various parts of the conduction system are replaced by fibrous or fatty tissue, constitute the three major pathological categories of isolated congenitally complete heart block. Intraventricular discontinuity is distinctly rare, with only two previous cases reported in the literature, one of which was associated with a familial history of heart block. The cardiac conduction systems of two cases of isolated congenitally complete heart block were serially sectioned and analyzed histopathologically. The findings were correlated with the clinical features, in particular, the family histories and maternal serum anti-Ro antibodies. Both cases, a 9-day-old neonate and an 8-year-old schoolgirl, showed a combination of nodoventricular and intraventricular discontinuity, with absence of the atrioventricular penetrating bundle, the entire right, and the proximal portion of the left bundle branch. The branching bundle was absent in the first case and replaced by fatty tissue in the second. In contrast to the commoner atrial-axis discontinuity in which the atrioventricular node itself is usually replaced by fibrous or fatty tissue with variable involvement distally, the sinus node, and in particular, the atrioventricular node were normal in both of our cases. There was no family history in either case, whereas tests for the maternal serum anti-Ro antibody were positive in the first but negative in the second case. Intraventricular discontinuity as a cause of isolated congenitally complete heart block is very rare. In our cases, it co-existed with nodoventricular discontinuity. It can be sporadic, familial, or associated with positive maternal serum anti-Ro antibodies.

1. The surgical outcome of congenital heart diseases may be adversely affected by residual branch pulmonary artery stenosis, which is difficult to treat surgically. 2. The objective of the present study was to evaluate the effectiveness, safety and follow-up results of two transcatheter procedures, balloon angioplasty and endovascular stenting, for treatment of branch pulmonary artery stenosis. 3. From December 1988 to March 1997, 22 children (group 1) underwent 30 balloon angioplasties and 12 children (group 2) underwent 14 endovascular stent implantations. The overall success rates for groups 1 and 2 were 67 (20/30) and 93% (13/14), respectively, with significant increases in vessel diameter (P < 0.001, t-test, 29 d.f.; P = 0.0001, t-test, 12 d.f., respectively) and decreases in pressure gradient (P < 0.0001, t-test, 29 d.f.; P = 0.001; t-test, 12 d.f., respectively). One death (3.3%) in group 1 was due to post-dilation reactive pulmonary hypertension. No mortality occurred in group 2 children, but two migrated stents required re-implantation of another stent. Mean follow-up periods were 28.2 and 26.3 months for groups 1 and 2, respectively. For group 1, no significant change in vessel diameter or pressure gradient was noted on recatheterization in 12 patients. Restenosis occurred in four of 16 (25%) initial successes. Balloon redilation in four vessels were all successful. For group 2 children, although vessel diameter remained unchanged, a significant increase in pressure gradient (P = 0.02; t-test, 11 d.f.) was noted on recatheterization. Balloon dilations on two narrowed stents caused by intimal proliferation showed only partial improvements. 4. In conclusion, both balloon angioplasty and endovascular stent implantation are effective and safe, with satisfactory intermediate-term results, for the treatment of branch pulmonary artery stenosis. Balloon angioplasty is the choice for initial treatment, whereas stent implantation, the long-term outcome of which remains to be determined, should be reserved for older children after repeated failures with balloon dilation.

After major open heart surgery, a significant number of infants and children are dependent on peritoneal dialysis as a result of renal impairment. They often require broad-spectrum antibiotics for the treatment of ongoing infections or as prophylactic therapy and have an increased risk of fungal infection. Fluconazole is a new thiazole antifungal agent that has been widely used in adults, but its use in children with acute renal impairment requiring peritoneal dialysis has not been documented. The purpose of this investigation was to study the pharmacokinetics of fluconazole in infants and children who developed various degrees of renal impairment, with or without the need for peritoneal dialysis, after major open heart surgery. Between January 1992 and June 1995, 17 children ranging in age from 2 weeks to 3 years (mean, 6 months) who received fluconazole therapy intravenously (3 mg/kg per day for 2 to 3 weeks) after major open heart surgery were enrolled in a prospective study. They were divided into two groups--those who required peritoneal dialysis (PD group; n = 8) and those who did not (non-PD group; n = 9). Blood, urine, and peritoneal dialysate samples were collected for 4 days to determine the pharmacokinetics of the drug, and data were compared between the two groups. The two groups of children had similar demographic characteristics, and their plasma concentrations of fluconazole showed no statistically significant differences. For children dependent on peritoneal dialysis, fluconazole was excreted almost solely through dialysis. Despite a significantly longer terminal elimination half-life for this group of infants, they tended to have a marginally larger volume of distribution of the drug. This, coupled with the continuous hourly exchange of dialysate, provided a large sink volume to effectively remove flu- conazole from the circulation. Thus the plasma clearance and the accumulation ratio were comparable for the two groups of children. Continuous cycling peritoneal dialysis effectively removed fluconazole from the circulation and was the main mode of excretion of the drug in children dependent on dialysis.

An 18 month old girl with an angiographically measured ductus of 4.5 mm underwent transcatheter occlusion of the persistent arterial duct with a 17 mm Rashkind umbrella and an occluding spring coil. Severe intravascular haemolysis developed 20 hours later. Significant residual ductal leakage was noted and the residual duct measured 6 mm. Previous underestimation might have been related to ductal spasm as a catheter was placed across the duct before angiography. The haemolysis was abolished within 48 hours by a previously unreported approach of antegrade transcatheter closure of the residual duct by multiple spring coils.

Background: It is desirable to repair but not replace the aortic valve in patients with ventricular septal defect and acquired aortic regurgitation. Precise definition of the valvar pathology with monitoring of its repair perioperatively would enhance the surgical management of this condition., Methods: Fourteen consecutive patients (age, 10.6 +/- 6 years; weight 29.7 +/- 5.7 kg) who underwent repair of ventricular septal defect with aortic regurgitation were studied by intraoperative transesophageal echocardiography. The severity of prolapse of each of the individual aortic cusps and its adjacent sinus was assessed and the valvar regurgitation quantified by Doppler-derived regurgitant indices. The echocardiographic and surgical findings were correlated and the preoperative and postoperative echocardiographic data were compared to assess the effectiveness of operation., Results: Eight subarterial and six perimembranous defects were located accurately and their sizes (11.8 +/- 3.0 mm) correlated well (r = 0.80) with the surgical measurements. Transesophageal echocardiography detected prolapse of the aortic valve and its sinus in all 14 patients. The severity of the prolapse was severe in 10, moderate in 4, and mild in 5 leaflets. One the basis of these findings, together with the Doppler-derived mean regurgitant indices, exploration of the valve and valvuloplasty were executed appropriately in 12 of 14 patients. In all 14 patients, transesophageal echocardiography after bypass revealed no further cuspal prolapse and significant reduction of the mean regurgitant index (0.55 +/- 0.23 to 0.17 +/- 0.15, p < 0.0001). Residual ventricular septal defect was detected in 5 patients and the only patient with significant shunting who required reexploration was identified correctly., Conclusions: Intraoperative transesophageal echocardiography can assess effectively the surgical repair of ventricular septal defect with aortic regurgitation and provide information that directs and alters surgical plans to the benefit of patients.

Between October 1979 and January 1993, 85 Chinese neonates in Hong Kong underwent surgical repair for coarctation of the aorta. Their mean (s.e.) age and body weight at operation was 15.6(8.5) days and 3.06(0.56) kg, respectively. Simple coarctation was present in 17 babies, while 36 had additional ventricular septal defect and 31 had associated major complex intracardiac lesions. Subclavian flap aortoplasty was performed in 56 babies, resection with end-to-end anastomosis in 18 and aortoplasty with the use of a GORETEX patch in 11. The overall early mortality rate was 16.5%. To identify risk factors for early operative mortality, various clinical variables, surgical options, associated heart lesions and dimensions of the aortic arch at different sites for each patient were reviewed. Univariate analysis identified statistically significant differences between the survivors and non-survivors for the following factors: preoperative body-weight, arterial pH and base excess, serum urea and creatinine levels. Stepwise logistic regression further distinguished serum creatinine levels and the period of operation as two significant risk factors. Contrary to previous reports, the dimensions of the aortic arch and type of surgery did not affect early operative mortality. Among the 71 hospital survivors followed for 38.2(38) months, residual or recurrent coarctation of the aorta was detected in 12(17%). The different surgical operations were not related to the incidence of late complication. The size of the distal transverse arch, however, was different (P=0.05) in those who did and did not develop aortic sequela. Successful balloon angioplasty was subsequently performed in 11 patients. In an era of echocardiography with prenatal diagnosis and therapeutic catheterization, early recognition of the disease with prompt prostaglandin infusion should prevent collapse of the baby, thus avoiding renal impairment and sever metabolic acidosis. Balloon angioplasty would offer a simple effective treatment of patients who developed aortic re-coarctation.