[Middle and long-term follow-up of 101 children with giant coronary artery aneurysm of Kawasaki disease].

Objective: To summarize the clinical features, middle-and long-term prognosis of Kawasaki disease (KD) with giant coronary artery aneurysm (GCAA). Methods: In this retrospective cohort study, a cross-sectional analysis was conducted on 101 KD children with GCAA in the KD with GCAA database established by Beijing Children's Hospital, Capital Medical University in 2004. GCAA was diagnosed as coronary artery absolute lumen diameter ≥8.0 mm. All patients were followed up regularly. The endpoint was the time of last follow-up or the death time. T test or χ2 test was used for comparison between groups. Results: A total of 101 KD children with GCAA were enrolled, including 82 males (81.2%) and 19 females (18.8%). The age of disease onset was 2.5 (1.0, 4.5) years. The follow-up duration was 4.5 (2.7, 7.5) years, with a longest of 19 years. All children received routine treatment with aspirin and warfarin, and clopidogrel was added in severe cases. At the end of follow-up, 13 cases (12.9%) had cardiac enlargement, 11 cases (10.9%) developed heart failure, 13 cases (12.9%) experienced myocardial infarction, 2 cases (2.0%) underwent coronary artery bypass graft and 6 cases (5.9%) died. A total of 170 coronary arteries were involved, including 24 (14.1%) GCAAs on the main trunk of left coronary artery, 10 (5.9%) GCAAs on left circumflex, 57 (33.5%) GCAAs on left anterior descending, 78 (45.9%) GCAAs on the middle segments of right coronary artery, and 1 (0.6%) GCAA in the distal segments of right coronary artery. Eleven cases (10.9%) recovered with the coronary artery absolute lumen diameter of all GCAAs below 4.0 mm. Among 170 branches with GCAAs, 28 (16.5%) regressed below 4.0 mm. No significant difference was found in the regression rates between right and left GCAA (18.7% (17/91) vs. 13.9% (11/79), χ²=2.473, P=0.116). There was no statistically significant difference in retraction between unilateral GCAA and bilateral GCAA (16.1% (9/56) vs. 4.4% (2/45), χ2=2.381, P=0.123). Conclusions: GCAA of KD occurred more common in the middle segments of right and left anterior descending coronary arteries. The incidence of adverse cardiac events and the mortality rate in children with GCAA complicated with KD was high. Their long-term prognosis was poor.

Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis.

BACKGROUND: Oxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity. METHODS: Two independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects. RESULTS: This meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR=0.26; 95% confidence interval (CI), 0.11 to 0.62; P=0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR=0.42; 95% CI 0.26-0.65; P=0.0001; OR=0.60; 95% CI 0.39-0.92; P=0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD=246.73 mg/m2; 95% CI 3.01-490.45; P=0.05; MD=1.55; 95% CI 0.46-2.63; P=0.005, respectively). No significant differences were found in median PFS (MD=0.71 month; 95% CI -0.59-2.01; P=0.29), median OS (MD=0.10 month; 95% CI -0.41-0.61; P=0.70) or RRs (OR=0.82; 95% CI 0.61-1.10; P=0.18). CONCLUSION: Ca/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.

Microarray analysis of differential gene expression in sensitive and resistant pig to Escherichia coli F18.

In this study, Agilent two-colour microarray-based gene expression profiling was used to detect differential gene expression in duodenal tissues collected from eight full-sib pairs of Sutai pigs differing in adhesion phenotype (sensitivity and resistance to Escherichia coli F18). Using a two-fold change minimum threshold, we found 18 genes that were differentially expressed (10 up-regulated and eight down-regulated) between the sensitive and resistant animal groups. Our gene ontology analysis revealed that these differentially expressed genes are involved in a variety of biological processes, including immune responses, extracellular modification (e.g. glycosylation), cell adhesion and signal transduction, all of which are related to the anabolic metabolism of glycolipids, as well as to inflammation- and immune-related pathways. Based on the genes identified in the screen and the pathway analysis results, real-time PCR was used to test the involvement of ST3GAL1 and A genes (of glycolipid-related pathways), SLA-1 and SLA-3 genes (of inflammation- and immune-related pathways), as well as the differential genes FUT1, TAP1 and SLA-DQA. Subsequently, real-time PCR was performed to validate seven differentially expressed genes screened out by the microarray approach, and sufficient consistency was observed between the two methods. The results support the conclusion that these genes are related to the E. coli F18 receptor and susceptibility to E. coli F18.

Investigation of the relationship between SLA-1 and SLA-3 gene expression and susceptibility to Escherichia coli F18 in post-weaning pigs.

Porcine post-weaning diarrhea and edema disease are principally caused by Escherichia coli strains that produce F18 adhesin. FUT1 genotyping and receptor binding studies divided piglets into E. coli F18-resistant and -sensitive groups, and the roles of SLA-1 and SLA-3 were investigated. SLA-1 and SLA-3 expression was detected in 11 pig tissues, with higher levels of SLA-1 in lung, immune tissues and gastrointestinal tract, and higher levels of SLA-3 also in lung and lymphoid tissues. Both genes were expressed higher in F18-resistant piglets, and their expression was positively correlated in different tissues; a negative correlation was observed in some tissues of F18-sensitive group, particularly in lung and lymphatic samples. Gene ontology and pathway analyses showed that SLA-1 and SLA-3 were involved in 37 biological processes, including nine pathways related to immune functions. These observations help to elucidate the relationship between SLA class I genes and E. coli F18-related porcine gastrointestinal tract diseases.

Increased pulmonary arterial pressure in children with nephrotic syndrome.

AIMS: To evaluate the pulmonary arterial pressure in children with nephrotic syndrome (NS). METHODS: Doppler echocardiography was performed in 40 children with NS (aged 1.5-13 years) at NS onset (n = 28) or relapse (n = 12), and 40 normal controls. Pulmonary pressure was estimated by: (1) measuring the systolic transtricuspid gradient from tricuspid regurgitation; and (2) measuring the time to peak velocity of pulmonary flow. RESULTS: Thirty five of the 40 patients with NS had measurable tricuspid regurgitation with a pulmonary systolic pressure ranging from 21 to 48 mm Hg. Pulmonary systolic pressure was >40 mm Hg in seven patients. The pulmonary time to peak velocity was shortened and the ratio of time to peak velocity and right ventricular ejection time decreased compared with controls. The patients with increased pulmonary pressure had a longer time since onset of NS. One patient developed thrombus in the inferior vena cava during hospitalisation. CONCLUSION: Pulmonary arterial pressure was increased in children with NS. Further work is needed to evaluate the aetiology and clinical implications of this abnormality.

Immediate and six-month results of the profile of the Amplatzer septal occluder as assessed by transesophageal echocardiography.

Catheter closure of secundum atrial septal defect (ASD) using the Amplatzer septal occluder (ASO) is a potential alternative for open surgical repair. However, the large profile of the device obtained immediately after closure continues to raise some concerns regarding its long-term safety. To evaluate the changes in the profile of the device after being deployed, transesophageal echocardiography was performed in 70 patients (17 men and 53 women) who underwent catheter closure of ASDs immediately after and at 6-month follow-up. The median age at closure was 16 years (range 1.9 to 75) and the median size of the ASD as assessed by transesophageal echocardiography was 14 mm (range 3 to 25). The thickness (profile) of the device was assessed in the 4-chamber, short- and long-axis views of the interatrial septum, and measured at its middle and at the junction of the waist with the disc at its 2 ends. Seventy-three devices were deployed in the 70 patients. The median size of the device was 19 mm (range 8 to 34). Complete closure was achieved in 81.4% and 91.4% immediately after and at 6-months follow-up, respectively. The thickness of the device at its middle decreased from 12.2 +/- 4.3, 12.2 +/- 3.7, and 12.5 +/- 4.3 mm in the 4-chamber, short- and long-axis views to 6.5 +/- 2.0, 6.3 +/- 1.9, and 6.5 +/- 2.2 mm, respectively. The thickness of the device at its superior, inferior, anterior, and posterior edges also decreased by 41.8% +/- 14.0% to 43.7% +/- 9.8%. The changes in the thickness were related to device size. Larger devices were thicker after being deployed. We conclude that the thickness of the ASO decreases by 42% to 48% within 6 months after deployment, resulting in a lower profile.

Head-up tilt test without intravascular cannulation in children and adolescents.

Previous studies of head-up tilt test have shown that testing at high degrees lacks specificity in children. We suspected that the high false positive rate might be related to the intravascular catheter and other maneuvers incorporated in the test and therefore studied the sensitivity and specificity of standing and HUT at 80 degrees without any invasive procedure and other maneuvers in children and adolescents. Twenty three patients (11.8+/-2.7 years) with recurrent typical neurally mediated syncope and 35 normal control children (11.6+/-3.0 years) underwent motionless standing for 15 min and tilting to 80 degrees for 30 min. Continuous finger arterial pressure monitoring and ECG were performed during the test. Eight (35%) of the 23 patients developed symptoms of near syncope during motionless standing. Thirteen (57%) of them had positive results at 80 degrees tilting for 30 min. The symptoms of syncope were not always corresponding to excessive haemodynamic changes. None of the controls developed any symptoms or excessive hemodynamic changes. Without intravascular instrumentation and other autonomic maneuvers, active motionless standing or HUT at 80 degrees for 30 min is highly specific but of limited sensitivity for the investigation of vasovagal syncope.

Cerebral blood flow during vasovagal syncope induced by active standing or head up tilt.

BACKGROUND: Vasovagal syncope is usually associated with a sudden drop of blood pressure and/or heart rate. However, occasionally the symptoms of syncope induced by orthostatic stress testing are not associated with obvious haemodynamic changes. The mechanisms of syncope in these patients are not clear. AIM: To evaluate changes in cerebral blood flow velocities during orthostatic stress testing in children and adolescents with vasovagal syncope. METHODS: Electrocardiogram, instantaneous arterial blood pressure, and right middle cerebral artery blood flow velocity were recorded at rest, during active standing, and 80 degrees head up tilt. 32 children and adolescents aged between 7 and 18 years with a history of repeated vasovagal syncope and 23 healthy control subjects were studied. RESULTS: Presyncope occurred in 10 patients during standing, and 13 patients during head up tilt. None of the controls had symptoms during the test. The transcranial Doppler study showed that the symptoms were associated with significant decreases of diastolic cerebral blood flow velocity and an increase of pulsatility. There was no significant change of the systolic cerebral blood flow velocity. The changes of cerebral blood flow velocities occurred in all episodes of presyncope, including those not associated with severe drop of blood pressure or heart rate. CONCLUSIONS: Diastolic cerebral blood flow velocity decreased significantly during episodes of presyncope induced by orthostatic stress. Impairment of autoregulation of cerebral blood flow might play an important role in the pathophysiology of syncope.

Spontaneous closure of muscular ventricular septal defect identified by echocardiography in neonates.

Muscular ventricular septal defects were diagnosed by echocardiography in 97 neonates within 7 days of birth. In 82 of the neonates (84.5%), the defect was solitary, while 15 had multiple defects. The solitary defects was located at mid-septal, apical, anterior and inlet locations in 42 (51.2%), 21 (25.6%), 14 (17.1%) and 5 (6.1%) neonates, respectively. Multiple defects occurred in the apical, anterior and mid-septal areas. The diameter of the solitary defects ranged from 1 to 6 mm (2.3 +/- 0.8 mm), while the multiple lesions were 1 to 4 mm in diameter (2.1 +/- 0.8 mm) in 28 instances in which they could measured. It proved possible to follow 79 of the patients for period of 10 to 13 months. The defects closed spontaneously in 56 (84.8%) of 66 patients with a single defect, and in 7 (53.8%) of 13 of those with multiple defects (P<0.05). For the solitary defects, the position and size were factors determining the likelihood and speed of closure. Defects located at the apical septum, or defects larger than 4 mm in diameter, closed slowly and at a later stage. Echocardiography is an useful technique in establishing of natural history of muscular ventricular septal defects encountered in neonates.

Pulmonary hypertension in patients with thalassemia major.

To evaluate the pulmonary artery pressure in patients with thalassemia major, Doppler echocardiography was performed in 33 patients with thalassemia major (aged 2 to 24 years) and 33 normal controls. Pulmonary artery pressure was estimated by (1) measuring the systolic transtricuspid gradient from tricuspid regurgitation and adding it to the right atrial pressure, estimated by the response of the inferior vena cava to deep inspiration, and (2) measuring the time to peak velocity of pulmonary flow. The results showed that of 33 patients, 28 had tricuspid regurgitation with a pulmonary systolic pressure ranging from 18 to 94 mm Hg (47 +/- 15 mm Hg). Pulmonary systolic pressure was > 30 mm Hg in all 22 patients > 10 years old and in four of six patients < 10 years old. Pressure correlated with left ventricular ejection fraction (r = -0.74), the ratio of mitral peak early diastolic flow velocity and peak velocity during the atrial contraction (r = 0.52), age (r = 0.56), and total blood transfusion units (r = 0.59). The pulmonary time to peak velocity was shortened compared with controls (p < 0.05). We concluded that pulmonary hypertension, as another cardiovascular complication of multiple factors of cause, seems to occur more frequently and at an early stage of the cardiac involvement in patients with thalassemia major.

Clinical and echocardiographic evaluation of neonates with heart murmurs.

In this study, 116 neonates (58M, 58F), aged 12h to 14d, with heart murmurs were examined by echocardiography: 26 were preterm and 90 full-term neonates. The clinical diagnosis was classified into definite heart disease, possible heart disease and innocent murmur. The final diagnosis was based on echocardiography and, in some cases, cardiac catheterization or surgery. The results showed that 97 (84%) neonates had heart diseases; 19 (16%) had a normal heart, including 7 with tricuspid regurgitation and 9 with physiological peripheral pulmonic stenosis. Out of 88 neonates with clinically definite heart disease, the final diagnosis was changed to normal heart in 9 (10%) cases and the lesion-specific diagnosis was changed in 9 (10%) neonates. In four cases, the clinical diagnosis of ventricular septal defect or pulmonary stenosis was changed to double-outlet right ventricle, single ventricle, hypoplastic left heart syndrome or tetralogy of Fallot. The clinical diagnosis was correct in 77-85% for varying simple lesions. In 5 of 21 neonates with clinically possible heart disease, the diagnosis was changed to normal heart. In one of six neonates with clinically innocent murmurs, the diagnosis was changed to small muscular ventricular septal defect. We concluded that 84% of heart murmurs in neonates were due to heart diseases and only 16% were innocent murmurs. Although clinical evaluation could determine the presence or absence of heart disease in most neonates, the lesion-specific diagnosis was not quite satisfactory. Echocardiography is necessary for neonates with a clinically diagnosed heart disease or possible heart diseases, and may be unnecessary for those with innocent murmurs diagnosed by paediatricians.

Doppler echocardiographic study of the pulmonary artery and its branches in 114 normal neonates.

It has been shown that there are pressure gradients between the main pulmonary artery (MPA) and its two branches in infants undergoing catheterization. This study investigated the blood flow velocities and pressure gradients in the right and left pulmonary arteries (RPA and LPA, respectively) in normal neonates. The MPA and its two branches were examined echocardigraphically in 114 term consecutive healthy neonates aged 1-6 days. The pressure gradients between the MPA and RPA or LPA were calculated. Thirty neonates with pressure gradients above 2.5 mmHg were followed by 3-6 months. The peak velocities in the RPA and LPA (1.16 +/- 0.19 and 1.01 +/- 0.18 m/s) were significantly higher than that in the MPA (0.84 +/- 13 m/s) (both p < 0.001), with that in the RPA slightly higher than in the LPA (p < 0.001). There was an estimated pressure gradient of 2.5-8.3 mmHg between the MPA and RPA in 43% and of 2.5-6.6 mmHg between the MPA and LPA in 16.7% of all neonates. The gradients disappeared within 3-6 months in 12 (40%) of the 30 neonates with an initial gradient above 2.5 mmHg. The differences in blood flow velocities or pressure gradients in the RPA or LPA were probably attributable to the variations in pulmonary arterial pressure, cardiac output, age, and birth weight and can be considered physiologically characteristic in neonates.

High prevalence of muscular ventricular septal defect in preterm neonates.

Isolated muscular ventricular septal defect was identified in 9 of 159 consecutive preterm neonates by color Doppler echocardiography, a prevalence of 56.6/1,000 live births. The neonates with ventricular septal defects appear clinically healthy, and in 87.5% of them the defect spontaneously closed within 6 to 11 months. The prevalence and rate of spontaneous closure are similar to those in full-term neonates.

High prevalence of muscular ventricular septal defect in neonates.

OBJECTIVES: This study sought to use echocardiography to evaluate the prevalence of muscular ventricular septal defect in neonates. BACKGROUND: Ventricular septal defect is usually asymptomatic and closes spontaneously. An increase in its prevalence has been noted recently. One reason is the improved detection of small defects, especially with the increased used of echocardiography. Therefore, one would expect a higher prevalence in neonates on the basis of echocardiographic screening. METHODS: Color Doppler echocardiography was performed in 1,053 consecutive neonates 6 to 170 h old at Western Galilee Hospital, Israel. Data on the neonates, parents and family were obtained to analyze the influencing factors. The identified patients were followed up for 1 to 10 months or until ventricular septal defect closure. RESULTS: Muscular ventricular septal defect was found in 56 (25 male, 31 female) of the 1,053 neonates, a prevalence of 53.2/1,000 live births. All neonates were asymptomatic. Six had a systolic murmur. Electrocardiographic findings were normal in 44 (97.8%) of 45 neonates followed up, and left ventricular hypertrophy occurred in 1 (2.2%). By echocardiography, 50 ventricular septal defects (89.3%) were single and 6 (10.7%) were multiple. The defects (range 1 to 5 mm in diameter, mean [+/- SD] 2.3 +/- 0.8) occurred anywhere along the muscular septum; 43 (76.8%) were detectable only on color Doppler imaging. The left atrium and left ventricle were mildly dilated. Of 45 neonates who were followed up for 6 to 10 months or until closure of the defects, 40 (88.9%) had defects that closed spontaneously. The risk of ventricular septal defect was not significantly associated with gestational age, birth weight, birth order, maternal age, diabetes, smoking, exposure to drugs or infection, paternal age, familial congenital heart disease, religion or consanguinity. CONCLUSIONS: There is a prevalence of muscular ventricular septal defect in neonates of 53.2/1,000 live births. The patients were asymptomatic, and 88.9% had defects that closed spontaneously within 1 to 10 months. These defects may be caused by environmental factors. In many cases, muscular ventricular septal defect may also result from delayed physiologic development.