Differences in laboratory reporting standards leading to a difficult prenatal diagnosis for a patient with suspected 4p duplication.

Not all obstetric care facilities offer sufficient genetic counseling in Japan. When necessary, patients are referred to tertiary perinatal care centers for genetic counseling and further testing. Because each facility typically has an exclusive contract with a laboratory, the additional testing required may be performed at a different laboratory. With no reporting standards for normal chromosomal variants, differences between laboratories impede result interpretation, and clinical errors may occur. We present a case of a patient diagnosed with 46,XX,?dup (4)(p12p12) variant over two pregnancies. During the first pregnancy, the variant was determined to be a de novo, leading the parents to terminate the pregnancy. During the second pregnancy, further analysis revealed no 4p duplication, and we diagnosed as a normal variant, 4cenh+, inherited from the mother. Differences in reporting standards for a normal variant made evaluation of this patient difficult. Medical staff should be aware of this issue, and reporting standards should be standardized.

Prognosis of Coronary Artery Bypass Grafting in Preschool-Aged Patients with Myocardial Ischemia Due to Giant Aneurysm of Kawasaki Disease.

Coronary artery bypass grafting (CABG) for severe cardiac sequelae of Kawasaki disease (KD) complicated by myocardial ischemia is feasible even in childhood. However, no report has summarized the prognosis of CABG in preschool-aged children. Therefore, we evaluated the outcomes of seven preschool-aged children who underwent CABG for the cardiac sequelae of KD in our hospital. The median age at KD onset and CABG was 36 and 59 months, respectively. The median period from KD onset to CABG was 12 months. The median post-operative observation period was 108 months. CABG between the left internal thoracic artery and left anterior descending artery was performed in all patients. In all patients, postoperative cardiac catheter examination revealed good graft patency and no anastomotic stenosis. Further, pre-operative abnormality of coronary flow reserve returned to normal after CABG. Currently, only one patient is taking warfarin. Regarding school-life management, no patient has exercise limitations, except for one patient who had acute myocardial infarction before CABG. Further, the risk of graft stenosis or occlusion was evaluated in the included patients. However, no accidents have been reported to date, and myocardial ischemia and school-life management have improved. Thus, CABG is an effective treatment in preschool-aged children.

Early detection of subclinical anthracycline cardiotoxicity on the basis of QT dispersion.

BACKGROUND: We examined whether dobutamine-stress QT dispersion (QTd) and heart-rate corrected QT dispersion (QTcd) are useful for detecting subclinical anthracycline cardiotoxicity. METHODS: The subjects were 10 control subjects and 37 patients divided into 4 groups according to cumulative anthracycline dose: non-anthracycline group (group N), 7 patients; low anthracycline cumulative dose group (group L), 8 patients (< 200 mg/m²); medium anthracycline cumulative dose group (group M), 16 patients (200 to < 400 mg/m²); and high cumulative group (group H), 6 patients (≥ 400 mg/m²). Standard 12-lead electrocardiograms were recorded. QTd and QTcd were measured and calculated at rest and after administration of dobutamine at 5 or 30 µg/kg/min. We also estimated cardiac function and cardiac reserve function at rest and after administration of dobutamine at a dose of 5 or 30 µg/kg/min. RESULTS: At rest, QTd and QTcd were significantly greater in groups M and H. After administration of dobutamine at 30 µg/kg/min, QTd and QTcd were significantly greater in groups L, M, and H. There was good correlation between QTd and the cumulative anthracycline dose; the correlation formula was y=0.051 x + 42.2 (r = 0.81, p < 0.001). The cumulative anthracycline dose of 152.9 mg/m², calculated from the correlation formula, was the cut-off for detection of electrophysiological cardiac abnormalities. Cardiac performance data at rest and dobutamine stress by echocardiography and pulsed Doppler echocardiography are less sensitive for detecting cardiac abnormalities than are QTd and QTcd. CONCLUSIONS: Dobutamine-stress QTd and QTcd are useful for detecting anthracycline cardiotoxicity and subclinical cardiac abnormality at low cumulative anthracycline doses. We must be aware of the possibility of subclinical myocardial abnormalities in patients with a cumulative anthracycline dose of ≥ 150 mg/m².

[Demand for cleanliness of anesthesia machines and apparatus].

(1) Outer surface of anesthesia machines and patient monitors, and breathing bags are exposed to the contaminated anesthetists' hands and fingers. Disinfection by wiping surface of anesthesia machines with alcohol, and disinfecting hands and fingers with rubbing-type, alcohol-based antiseptics are encouraged. (2) Anesthesia equipments' breathing circuit part is contaminated by patients' breath and respiratory secretions. It is necessary to set rules for exchange of breathing circuit tubes and breathing bags, periodical cleansing and disinfection of canisters as well as inhalation and exhalation valves, and usage of bacteria filters. (3) Anesthesia apparatus (laryngoscope, tracheal tube and suction tube) contact with patients' oral cavity and airway, and thus they are categorized as semi-critical items that require high-level disinfection.

Virtual histology intravascular ultrasound evaluation of coronary artery lesions within 1 year and more than 10 years after the onset of Kawasaki disease.

BACKGROUND: Coronary artery evaluation by virtual histological intravascular ultrasonography (VH-IVUS) late in Kawasaki disease (KD) shows intimal thickening, calcification, fatty components, and necrosis of regressed coronary artery lesions (CALs). However, it is not clear when these VH-IVUS findings start to occur. Therefore, we evaluated coronary arteries using VH-IVUS in patients with early-stage KD and tried to determine whether these atherosclerotic findings on VH-IVUS were different from that in patients with late-stage KD. METHODS: Eighteen patients with KD aged between 1 and 32 years who had CALs and underwent cardiac catheterization between January 1, 2008 and December 31, 2014 were included. They were divided into 2 groups-those with the disease for <1 year (group A) and those with it for >10 years (group B). VH-IVUS findings were compared between the groups. The coronary arteries were divided based on coronary angiography findings into normal, regressed (dilated CALs regressed to a normal size), and aneurysmal lesions. The Wilcoxon signed-rank test was used in the statistical analysis. RESULTS: In both regressed and aneurysmal lesions, marked intimal proliferation and atherosclerotic findings (fibro-fatty and necrotic core lesions) were observed. In addition, there was no difference in the area percentage of atherosclerosis between the groups. CONCLUSIONS: VH-IVUS revealed that atherosclerotic-like findings exist in CALs in patients with KD, even within a year of onset. The findings were almost the same in those with the disease for >10 years. Because there is no histological evidence of atherosclerosis in KD, these VH-IVUS findings may indicate complex histological findings of KD. Nevertheless, early interventions to help reduce the risk factors of atherosclerosis may be required in these patients.

Two cases of restrictive cardiomyopathy in children.

A 3-year-old girl was diagnosed with restrictive cardiomyopathy (RCM) after showing symptoms of heart failure, and a 6-year-old boy was found to have RCM after abnormal electrocardiographic findings were seen during school-based heart disease screening. Both had typical clinical features of the disease. Plasma levels of brain natriuretic peptide increased significantly in both patients, allowing us to distinguish this disease from constrictive pericarditis which has similar clinical and hemodynamic features. The early diastolic mitral annular velocity recorded by tissue Doppler echocardiography was also useful to discriminate RCM from constrictive pericarditis. The former case successfully received heart transplantation, but the latter case died suddenly prior to receiving a heart transplant. The plasma level of brain natriuretic peptide and tissue Doppler echocardiography helped us to diagnose this disease earlier and follow it more carefully, which has important implications in optimal treatment and improved prognosis of RCM in children.

A New Z Score Curve of the Coronary Arterial Internal Diameter Using the Lambda-Mu-Sigma Method in a Pediatric Population.

BACKGROUND: Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established. METHODS: Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot. RESULTS: Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel-based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/). CONCLUSIONS: Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.

Estimation of myocardial hemodynamics before and after intervention in children with Kawasaki disease.

OBJECTIVES: We used myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR) to estimate cut-off values for assessment of the functional severity of coronary stenosis and myocardial ischemia, and we tested the usefulness of coronary blood hemodynamic measurements before and after plain old balloon angioplasty (POBA) and coronary artery bypass graft surgery (CABG). BACKGROUND: Fractional flow reserve and CFR are useful for assessing the functional severity of coronary artery stenosis, coronary microvascular dysfunction, and myocardial ischemia during cardiac catheterization in adults. However, there have been no reports on the use of these measurements in children with Kawasaki disease (KD). METHODS: The study group included 128 patients with 314 coronary branches. The subjects were classified into three groups: normal coronary group, with 206 branches; abnormal coronary artery without ischemia group, with 58 branches; and ischemia group, with 50 branches. RESULTS: In each branch, CFR and FFR(myo) were significantly lower in the ischemia group than in the other groups. Cut-off values for assessing the functional severity of coronary stenosis and CFR were approximately equal to those obtained for adults (CFR: <2.0; FFR(myo): <0.75). We obtained very high sensitivity and specificity for estimating myocardial ischemia using CFR and FFR(myo) (CFR: 94.0% and 98.5%, respectively; FFR(myo): 95.7% and 99.1%, respectively). Both CFR and FFR(myo) were reliable indicators of coronary hemodynamics before and after POBA and CABG. CONCLUSIONS: Together, CFR and FFR(myo) provide a useful index for assessing the functional severity of coronary artery stenosis and myocardial ischemia and estimating the effectiveness of POBA and CABG in children with KD, the same as they do for adults.

Effects of plant genotype and nitrogen level on bacterial communities in rice shoots and roots.

To examine whether microbial community structure differs across rice genotypes, automated ribosomal intergenic spacer analysis (ARISA) was conducted. Nine cultivars of Oryza sativa ssp. indica or japonica and seven lines of other Oryza species were grown in paddy fields with low, standard, and high levels of N fertilization. Multidimensional scaling plots of bacterial ARISA for aerial parts of rice (shoots) revealed that the structure of shoot bacterial communities was significantly affected by plant genotype (indica or japonica) based on similarity tests, whereas root microbiomes were largely affected by the N fertilization level.

Reduced shear stress and disturbed flow may lead to coronary aneurysm and thrombus formations.

BACKGROUND: With Kawasaki disease it is important to clarify the mechanisms of coronary artery aneurysm and thrombus to avoid acute myocardial infarction. The authors tested the hypothesis that shear stress is reduced at coronary branching sites and in coronary artery aneurysms, and that this reduction of shear stress can promote formation of coronary artery aneurysms and thrombus. METHODS: The subjects were 111 children with Kawasaki disease with left coronary artery aneurysms, classified into three groups: giant coronary artery aneurysm (n= 28, diameter of coronary artery >8 mm), aneurysm (n= 44, diameter of coronary artery =8 mm), and normal-appearing coronary (n= 39). Averaged peak flow velocity (APV), flow patterns and shear stress were measured and calculated at normal-appearing coronary vessels, left coronary artery branching sites and intra-coronary aneurysm using flow wire, and coronary angiography. Also, presence and appearance of thrombus were detected by intravascular ultrasonography. RESULTS: The authors found that 90.3% of the coronary artery aneurysms occurred at major left coronary branching sites. APV and shear stress were significantly decreased in giant coronary artery aneurysms (APV, 7.1 +/- 2.1 cm/s; shear stress, 3.8 +/- 2.1 dyne/cm(2)) and at the left coronary artery branching site (APV, 9.1 +/- 1.2; shear stress, 1+/-+/-.2 3.0). In total, 20 of 24 thrombi were detected only in giant aneurysm, and all patients exhibited disturbed flow pattern in their giant coronary artery aneurysms. CONCLUSIONS: Reduced shear stress and disturbed flow pattern may lead to coronary artery aneurysm and thrombus formation.

Evaluation of cardiac reserved function by high-dose dobutamine-stress echocardiography in asymptomatic anthracycline-treated survivors of childhood cancer.

BACKGROUND: The aim of this study was to evaluate cardiac function and cardiac reserved function in asymptomatic anthracycline-treated long-time survivors of childhood cancer using dobutamine (DOB) stress echocardiography. METHODS: A total of 26 patients (19 males and 7 females) were divided into four groups according to cumulative dose of anthracycline (ATC): non-anthracycline group (N group), seven cases; low anthracycline cumulative dose group (L group), five cases (or=400 mg/m(2)). DOB infusion was begun at 5 microg/kg per min (gamma) and increased up to 30 gamma. Cardiac function and cardiac reserved function at rest, after low-dose and high-dose DOB stress, were estimated. RESULTS: In the H group, % left ventricular posterior wall thickening (%PWT) at rest and ratio of maximum early filling peak velocity (E) and atrial contraction peak velocity (A) from the left ventricular transmitral flow wave (E/A) and %PWT at DOB 5 gamma stress were significantly lower than in other groups (P<0.05). After DOB 30 gamma stress in groups given>00 mg/m(2) end-systolic wall stress was significantly higher and E/A and %PWT were significantly lower than those of other groups (P<0.05). ATC cumulative dose strongly correlated with %PWT after DOB 30 gamma stress (P<0.001). CONCLUSIONS: Subclinical ATC cardiotoxicity was detected by high-dose DOB stress echocardiography at lower cumulative doses than with other methods. %PWT appears to be a useful index for detection of ATC cardiotoxicity.

Longitudinal estimation of signal-averaged electrocardiograms in patients with Kawasaki disease.

BACKGROUND: Myocarditis associated with Kawasaki (KD) disease is prominent, but rarely detected by conventional methods. The hypothesis of this study is to see if signal-averaged electrocardiogram can detect myocarditis with KD. METHODS: We obtained signal-averaged electrocardiograms from 71 patients with KD (mean age 2.8 +/- 2.9 years) in the acute (1st-4th week), subacute (5-7th week), and chronic (8th week or later) phases (mean study period 3.5 +/- 1.7 years). Sixteen patients who had pericardial effusion, bundle branch block or myocardial ischemia were excluded from this study. The results were compared with those of Holter and 12-lead electrocardiograms, echocardiography and serum myocardial enzymes. They were also contrasted with the course of each patient. RESULTS: The incidence of abnormal findings on signal-averaged electrocardiogram was 18.2% in the acute phase versus 10.9% in the subacute and chronic phases. It differed significantly higher than the other conventional tests (P < 0.05). Four patients had abnormalities of signal-averaged electrocardiograms through all three phases. Among these four, two had reduced left ventricular contractility. However, these changes were transient and resolved in the subacute phase. All patients had good courses and no residue. CONCLUSION: This study shows the possibility that signal-averaged electrocardiogram is more useful to detect myocarditis associated with KD than the other conventional tests. However, we could not define the prognostic value of abnormal signal-averaged electrocardiograms during this study period.

Possible synergic effect of angiotensin-I converting enzyme gene insertion/deletion polymorphism and angiotensin-II type-1 receptor 1166A/C gene polymorphism on ischemic heart disease in patients with Kawasaki disease.

ACE I/D and AT1R 1166A/C polymorphisms are considered to comprise individual risk factors for the development of coronary disease. We sought to demonstrate that the ACE I/D and AT1R 1166A/C polymorphisms affect coronary artery stenosis in patients with Kawasaki disease (KD). We examined 147 healthy controls and 281 Japanese children with KD. The patients were further divided into group N (n = 246, no ischemia) and group I (n = 35, severe coronary artery stenosis with myocardial ischemia), and we studied the genotype of ACE I/D and AT1R 1166A/C polymorphisms. We also examined ACE activity in patients with acute KD. We did not detect any prevalent genotypes of the ACE and AT1R polymorphisms between controls and KD patients. However, the prevalence of the D allele in the ACE polymorphism and of the C allele in the AT1R polymorphism tended to be higher in group I than in group N (odds ratios, 2.00 and 2.32, respectively). In addition, the presence of the D and/or C alleles significantly increased the relative risk of developing myocardial ischemia (odds ratio, 2.71; p = 0.038). During the convalescent phase of KD, ACE activity was increased despite significant attenuation during the acute phase. These results suggested that the renin-angiotensin system is associated with the formation of severe coronary artery stenosis and myocardial ischemia.