Magnetic resonance imaging of old myocardial infarction in young patients with a history of Kawasaki disease.

BACKGROUND: On magnetic resonance imaging (MRI) using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) as contrast medium, images of infarct regions are enhanced in acute myocardial infarction (AMI). In old myocardial infarction (OMI), thinning of the myocardial walls is present, but images are no longer enhanced by Gd-DTPA. On the other hand, MI in children with a history of Kawasaki disease (KD), several differences from adult MI are observed. HYPOTHESIS: The aim of this study was to evaluate the lesions that result from OMI in children with a history of KD using MRI with Gd-DTPA as a contrast medium. METHODS: The subjects were 16 young patients with a history of KD who were diagnosed as having OMI. Of these, both thinning of the myocardial wall and MRI enhancement by Gd-DTPA were observed in 4 cases, thinning alone was observed in 6 cases, Gd-DTPA image enhancement alone was observed in 3 cases, and neither thinning nor Gd-DTPA image enhancement was observed in 3 cases. RESULTS: The Gd-DTPA-image-enhanced, OMI-induced lesions observed in patients with KD were different from those observed in adults; this might be attributable to histologic differences. CONCLUSION: Magnetic resonance imaging using Gd-DTPA can evaluate myocardial thinning and presence of circulation noninvasively at the same time and is considered to be useful for long-term follow up of the patients with KD and OMI.

Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy.

Previous studies have indicated that cardiac events in young patients with hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the values with those in adult HCM. We studied 12 patients with HCM including six paediatric (<20 years old; mean 13 years) and six adult patients (>20 years old: mean 62 years), and six healthy young adults (mean 29 years) as controls. Every patient underwent magnetic resonance imaging (MRI) for anatomical assessment. Myocardial blood flow at rest and after dipyridamole infusion was measured with dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume effect was corrected for using the anatomical data obtained with MRI. In adult patients with HCM, coronary flow reserve in the hypertrophied septal region was not significantly different from that in the non-hypertrophied lateral wall (1.38+/-0.29 vs 1.77+/-0.39, respectively). In the paediatric patients, coronary flow reserve in the hypertrophied septal region was significantly lower than in the non-hypertrophied lateral wall (0.84+/-0.33 vs 2.74+/-0.90, respectively, P<0.01). In addition, coronary flow reserve in adult patients was lower than in control subjects both in the septal wall (1.38+/-0.29 vs 2.94+/-0.35, respectively, P<0.0001) and in the lateral wall (1.77+/-0.39 vs 2.85+/-0.69, respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients was not significantly different from that in control subjects in the lateral wall (2.74+/-0.90 vs 2.85+/-0.69, respectively), while absolute reduction of myocardial blood flow was noted after pharmacological vasodilatation in the hypertrophied septal region. In conclusion, significant regional differences of coronary flow reserve were present in the paediatric patients with HCM. These results suggest that paediatric patients with HCM intrinsically have the potential to experience significant regional ischaemia even in the absence of coronary stenosis.

Tacrolimus and myocardial hypertrophy.

Tacrolimus has been used as an immunosuppressive agent in the transplantation of all solid organs. Tacrolimus-induced hypertrophic cardiomyopathy has been reported to be an unusual but serious complication. To elucidate the effects of tacrolimus on myocardial hypertrophy, we studied the relationship between the blood levels of tacrolimus and cardiac wall thickening. Our findings demonstrated that tacrolimus-induced myocardial hypertrophy correlated with tacrolimus blood levels, and that myocardial hypertrophy induced by tacrolimus was reversible. However, no patients developed clinically significant symptoms related to myocardial hypertrophy.

Intrapulmonary shunting in biliary atresia before and after living-related liver transplantation.

BACKGROUND: Intrapulmonary shunting (IPS) is frequently observed and causes hypoxaemia in liver cirrhosis. This study investigated the prevalence, predictors of reversibility and the effect of living-related liver transplantation (LRLT) on IPS using contrast echocardiography in patients with end-stage biliary atresia. METHODS: Fifty consecutive patients with biliary atresia were examined for IPS using contrast echocardiography before and after LRLT until IPS disappeared. The severity of IPS was classified into five grades according to the extent of contrast in the left ventricle (0, none; 1, trivial; 2, apparent; 3, complete but less than in right ventricle; 4, as dense as in right ventricle). RESULTS: Thirty-two patients (grade 1, n = 15; grade 2, n = 7; grade 3, n = 4; grade 4, n = 6) had IPS before LRLT. Forty-four patients have survived for 9-26 months after LRLT. Among patients with grade 3 or 4 IPS (n = 8), there was a significant correlation between age at LRLT and the duration of IPS persistence after LRLT (P = 0.044). CONCLUSION: IPS takes longer to disappear in older children than in younger ones, but always disappears eventually. LRLT is an effective treatment for biliary atresia with IPS. Presented to the 31st annual meeting of the Pacific Association of Pediatric Surgeons, Maui, Hawaii, June 1998

Dichotic listening in patients with situs inversus: brain asymmetry and situs asymmetry.

In order to investigate the relation between situs asymmetry and functional asymmetry of the human brain, a consonant-vowel syllable dichotic listening test known as the Standard Dichotic Listening Test (SDLT) was administered to nine subjects with situs inversus (SI) that ranged in age from 6 to 46 years old (mean of 21.8 years old, S.D. = 15.6); the four males and five females all exhibited strong right-handedness. The SDLT was also used to study twenty four age-matched normal subjects that were from 6 to 48 years old (mean 21.7 years old, S.D. = 15.3); the twelve males and twelve females were all strongly right-handed and served as a control group. Eight out of the nine subjects (88.9%) with SI more often reproduced the sounds from the right ear than sounds from the left ear; this is called right ear advantage (REA). The ratio of REA in the control group was almost the same, i.e., nineteen out of the twenty-four subjects (79.1%) showed REA. Results of the present study suggest that the left-right reversal in situs inversus does not involve functional asymmetry of the brain. As such, the system that produces functional asymmetry in the human brain must independently recognize laterality from situs asymmetry.

Acute pure red cell aplasia associated with allopurinol therapy.

Several investigators have reported patients with acute pure red cell aplasia (PRCA) caused by anticonvulsants, antibiotics, or antithyroid agents. Allopurinol is known to be a causative agent of aplastic anemia, but there have been few reports of acute PRCA induced by allopurinol. We describe here a 15-year-old boy who suffered from anemia 6 weeks after initiation of allopurinol therapy; his anemia immediately improved after cessation of the drug. His bone marrow showed severe erythroid hypoplasia with a myeloid/erythroid ratio of 18.6 and low expression of glycophorin A detected on cell-surface antigen analysis. No morphological abnormalities were observed in myeloid series and megakaryocytes. The prolonged plasma iron disappearance rate and the decreased plasma iron turnover rate also indicated erythroid hypoplasia. He had been free from any infections, including parvovirus B19, before manifestation of PRCA. Taken together, these results suggest a diagnosis of acute PRCA. This side effect of allopurinol should be taken into consideration.

Elevated plasma levels of adrenomedullin in congenital cyanotic heart disease.

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma. Accumulating evidence suggests the possible involvement of adrenomedullin in the physiology of the pulmonary circulation and the pathophysiology of hypoxaemia. The aim of the present study was to investigate the pathophysiological significance of adrenomedullin in hypoxaemia caused by congenital cyanotic heart disease. Subjects were 16 patients with congenital cyanotic heart disease aged 0.8-10 years (Group C) and 12 age-matched control subjects (patients with coronary artery dilatation after Kawasaki disease; Group N). Plasma adrenomedullin concentrations were measured, using radioimmunoassay, in femoral venous, pulmonary arterial and pulmonary venous blood obtained during cardiac catheterization. Plasma adrenomedullin concentrations in Group C were significantly (3-fold) higher than those in Group N at all sampling sites. In Group C, plasma adrenomedullin concentrations in pulmonary venous blood were significantly lower than those in pulmonary arterial blood. Pulmonary uptake of adrenomedullin in Group C was significantly greater than that in Group N. Patients with congenital cyanotic heart disease showed elevated plasma adrenomedullin concentrations and an increased uptake of adrenomedullin in the pulmonary circulation, which may act to dilate pulmonary vessels and increase pulmonary blood flow to alleviate hypoxaemia. Intrinsically increased adrenomedullin levels may function as a compensatory mechanism for hypoxaemia in congenital cyanotic heart disease.

Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications.

BACKGROUND: In 320 living related liver transplantation performed between June 1990 and September 1997, there were 21 living related liver transplantation for patients with intrapulmonary shunting, manifested by digital clubbing, cyanosis, and dyspnea. We report the long-term outcome for more 6 months and our strategy to overcome complications in these recipients. PATIENTS: A total of 21 patients (age range 2-33 years, 19 children and 2 adults, 6 males and 15 females) were classified into three grades according to shunt ratio calculated by TcMAA pulmonary scintigraphy; 5 in mild group (shunt ratio: less than 20%), 6 in moderated group (20%-40%), and 10 in severe group (more than 40%). The original underlying liver disease was biliary atresia in all patients. RESULTS: Spearmen's correlation coefficient rank test revealed that shunt ratio correlated significantly with PaO2 in room air (P=0.0001), PaO2 in 100% oxygen (P=0.0004), hematocrit (P=0.0276), and period of dyspnea before transplantation (P=0.023). COMPLICATIONS: Wound infection occurred in 80, 66, and 80%, and bile leakage in 20, 0, 40% in mild, moderate, and severe group, respectively. Patients who had portal vein thrombosis, and intracranial complication were classified as severe group and the incidence was 20 and 20%, respectively. The patient actuarial one year survival was 80, 66.7, and 48%, in mild, moderate, and severe group, respectively, although there was no significant difference. All patients who survived improved hepatopulmonary syndrome and the length of period required for the resolution was significantly correlated to the preoperative shunt ratio (P=0.023). COMMENTS: Patients with severe shunting are susceptible to wound infection and bile leak. The trend of higher incidence of portal thrombosis and intracranial complications in the severe group was closely related high hematocrit. Secure surgical technique to reduce bile leak and delayed primary wound closure to reduce wound infection were found to be effective. Anticoagulant therapy by infusing heparin through the portal vein followed by coumadin could prevent fatal portal vein thrombosis without counter risk of fatal cerebral hemorrhage.

Ectopic bronchus: an insufficiently recognized malformation causing respiratory morbidity in VATER association.

An 11-month-old boy presented with recurrent wheezing and atelectasis in the right upper lobe of the lung. Bronchoscopy and bronchography confirmed an ectopic bronchus arising from the right main bronchus. The diagnosis of VATER association was made on the basis of multiple vertebral and rib anomalies, imperforate anus with a perineal fistula, unilateral hydronephrosis, atrial septal defect, and a preauricular tag, he did not have tracheo-esophageal fistula. We emphasize the importance of recognizing tracheobronchial anomalies in VATER association.

Impairment of BMIPP uptake precedes abnormalities in oxygen and glucose metabolism in hypertrophic cardiomyopathy.

UNLABELLED: Impairment of fatty acid uptake is shown to precede myocardial perfusion abnormality using 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in an experimental model of hypertrophic cardiomyopathy (HCM) and in human studies. We have recently demonstrated that abnormalities of both glucose and oxidative metabolism precede the reduction of blood flow in HCM. The main purposes of this study were to assess the frequency of abnormal findings in FDG uptake, BMIPP uptake and oxygen metabolism and to clarify the relationship among these metabolic parameters by using PET and SPECT. METHODS: Twenty-eight subjects with HCM underwent FDG- and acetate-PET and thallium- and BMIPP-SPECT studies at rest, respectively. After correcting for partial volume effect, real percentages of FDG and BMIPP uptake were calculated. In addition, the clearance rate constant (K mono) of acetate was measured and normalized (%) to estimate the oxygen metabolism. RESULTS: There were various metabolic abnormalities observed in patients with HCM. BMIPP uptake was often impaired without significant reduction of K mono values or FDG uptake. Thus, abnormality of BMIPP uptake was more frequently observed than that for FDG uptake or K mono values (p < 0.0001, respectively). FDG uptake was relatively maintained even in the segments with reduced K mono values and reduced BMIPP uptake. CONCLUSION: HCM shows a variety of metabolic patterns; however, the results of our study suggest that reduction of BMIPP uptake appears to be the most sensitive indicator of metabolic abnormalities followed by reduction of oxidative metabolism in patients with HCM.

Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age.

To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM-LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.

Myocardial metabolic changes in hypertrophic cardiomyopathy.

UNLABELLED: We evaluated myocardial blood flow, glucose and oxygen metabolism using PET in hypertrophic cardiomyopathy (HCM). METHODS: PET studies using 18F-fluorodeoxyglucose (FDG) and 11C-acetate were performed at rest in patients with HCM and normal subjects as a control group. The metabolic rate of glucose (MRGlu), K mono value as a marker of oxidative metabolism, and myocardial blood flow were estimated from serial dynamic FDG and 11C-acetate PET studies. RESULTS: Myocardial blood flow (%) did not differ significantly in hypertrophic and nonhypertrophic myocardium (90.3 +/- 3.1 versus 91.7 +/- 3.4). The MRGlu in hypertrophic myocardium, however, was lower than that of hypertrophic and normal myocardium (0.44 +/- 0.10 versus 0.52 +/- 0.15 and 0.53 +/- 0.15 mumole/min/g, respectively, p < 0.05). The K mono values were also lower in hypertrophic myocardium than in nonhypertrophic and normal myocardium (0.05 +/- 0.010 versus 0.066 +/- 0.0011 and 0.065 +/- 0.017 per min, respectively, p < 0.05). The %FDG/%perfusion values in hypertrophic myocardium did not differ significantly from those in nonhypertrophic myocardium (0.96 +/- 0.10 versus 1.02 +/- 0.07). CONCLUSION: Myocardial ischemia at rest is observed less frequently in patients with HCM. Impairment of oxidative and glucose metabolism may precede decreased blood flow. Primary metabolic impairment is considered to be dominant in hypertrophic myocardium.

Plasma brain natriuretic peptide concentrations in healthy children from birth to adolescence: marked and rapid increase after birth.

The aim of the present study is to establish the normal range and to determine the developmental changes of plasma brain natriuretic peptide (BNP) concentrations in children. We measured plasma BNP concentrations as well as atrial natriuretic peptide (ANP) concentrations in 58 healthy children from birth to adolescence and in the umbilical vein of 20 healthy neonates using highly sensitive immunoradiometric assays. The plasma BNP concentration was the highest at 0 days of age and descended through maturation to be almost constant and to be at the adult level at 3 months of age. The plasma BNP concentration at 0 days of age (56.7 +/- 49.6 fmol/ml; mean +/- SD) was 25 to 30 times higher than the adult level and 21 times higher than that in the umbilical vein (2.7 +/- 1.4 fmol/ml). The plasma ANP concentration at 0 days of age was not significantly different from that in the umbilical vein. The ratio of BNP to ANP was also the highest at 0 days of age (1.39 +/- 0.72) and decreased through maturation to be at the adult level at 3 months of age. Thus, the plasma BNP concentration in healthy subjects showed a marked, rapid and preferential increase immediately after birth, suggesting that BNP has a physiological role distinct from that of ANP in the perinatal circulatory changes from fetus to neonate.

Significance of dipyridamole loading in ultrafast x-ray computed tomography for detection of myocardial ischemia. A study in patients with Kawasaki disease.

BACKGROUND AND RATIONALE: To examine the significance of dipyridamole loading as a stress in ultrafast computed tomography (CT) to improve the detection of left ventricular myocardial ischemia. METHODS: Thirty-eight patients with coronary arterial involvement of Kawasaki disease and 18 control subjects received cardiac ultrafast CT with intravenous long-bolus iodinated contrast injection; dipyridamole was loaded in 40 examinations. Early (first-pass) and late (4 minutes) M/Ls (ratio of postcontrast incremental increases in the left ventricular myocardial [M] and luminal [L] CT number) were analyzed. RESULTS: Dipyridamole induced a prominent increase in early M/L of the normal myocardium in control subjects (no loading: 26.8%, dipyridamole: 39.2%; P < 0.001) with small influence on late M/Ls. In ischemic or infarcted myocardium in Kawasaki disease, dipyridamole early M/Ls (20.4%, 16.0%) and late M/Ls showed no difference from corresponding values without loading. Using early M/L with dipyridamole, sensitivity and specificity for detection of ischemic abnormalities were 89% and 100%, respectively. CONCLUSIONS: Dipyridamole-loaded first-pass contrast ultrafast CT was proven to have excellent detectability for myocardial ischemia comparable with stress thallium scintigraphy.

Diagnosing infection of extracardiac conduit in children.

Between August 1985 and July 1992, at our center, 142 Japanese children had an extracardiac conduit operation to reconstruct the right ventricular outflow tract. The study group consisted of 22 of these 142 children who had a persistent fever and whose serum was positive for acute-phase reactants after the operation. We present the diagnostic findings for 10 children with infection of an extracardiac conduit that had been placed to restore the continuity of the right ventricle-pulmonary artery. They were part of the group of 22 children who were followed over the past 7 years with blood cultures, echocardiography, and 67Ga imaging. All 10 developed a persistent fever and were seropositive for acute-phase reactants. Conduit infection was diagnosed in only 2 patients by the detection of vegetation on echocardiography and was diagnosed in 9 of the 10 patients by an abnormal 67Ga uptake in the area of the artificial vessels used to reconstruct the pulmonary artery. The present study compared the use of blood cultures, echocardiography, and 67Ga imaging in diagnosing an infection of the extracardiac conduit. The sensitivity of blood cultures in diagnosing an extracardiac conduit infection was 70% (7/10), and the specificity was 92% (1/12). 67Ga imaging showed a higher sensitivity than echocardiography in diagnosing infection of an extracardiac conduit.

Age-related acute adriamycin cardiotoxicity in mice.

Myocardial mitochondrial function after acute adriamycin exposure was compared in infant and adult mice. Heart mitochondrial were isolated 48 h after an intraperitoneal injection of adriamycin. Concentrations of adriamycin in serum and heart tissue were not significantly different between infant and adult mice. Oxygen consumption (state 3 respiration), and respiratory control ratio (RCR) were studied polarographically. Enzyme activities in the respiratory chain [succinate-cytochrome c reductase (SCCR), NADH-cytochrome c reductase (NCCR), cytochrome c oxidase (CCO)], and adenine nucleotide translocase (ANT) were assayed. After saline injection (control), no significant differences were detected in state 3 respiration, RCR, and enzyme activity of ANT between infant and adult mice. The respective enzyme activities of SCCR, NCCR, and CCO in adult mice were significantly lower than those in infant mice. After adriamycin injection in adult mice, there were significant decreases in state 3 respiration (using glutamate and malate as substrates from 239 +/- 25 to 160 +/- 50 nanoatom O2/min/mg protein), RCR (using glutamate and malate as substrates from 7.2 +/- 1.0 to 4.4 +/- 1.4), and enzyme activities of SCCR (from 279 +/- 30 to 178 +/- 28 nmol/min/mg protein) and NCCR (from 331 +/- 43 to 237 +/- 30 nmol/min/mg protein), but there were no significant changes in infant mice. No significant changes in enzyme activities of CCO and ANT were found in either infant or adult mice following the administration of adriamycin. In conclusion, adriamycin is less toxic on the myocardial mitochondrial function in infant mice than in adult mice.

[Ischemic myocardial injury evaluated using positron emission tomography in children with coronary artery disease: comparison with thallium-201 SPECT].

Regional myocardial perfusion and glucose metabolism were evaluated by positron emission tomography (PET) in children with coronary artery disease. Also, PET findings were compared with those of thallium-201 myocardial single photon computed tomography (SPECT). The study patients consisted of 11 children ranging in age from 3 to 14 years. Ten patients had significantly stenotic coronary arterial lesions due to Kawasaki disease, and one patient had a left coronary artery with an anomalous origin from the pulmonary artery. Evaluation was made before and after surgical revascularization in 3 patients. Regional myocardial perfusion was assessed at rest using 13N-ammonia, and regional myocardial glucose metabolism was assessed at rest under fasting conditions using 18F-fluorodeoxyglucose (18FDG). SPECT was performed after dipyridamole infusion. Initial and delayed images were obtained 7 min and 3 hrs after dipyridamole infusion, respectively. Left ventricular myocardial images were categorized as the septal, anterior, lateral, apical, and inferior segments, and evaluation was made for each segment. A total of 70 myocardial segments in 11 patients were classified into 4 groups according to the PET findings: 1) segments with normal perfusion and without enhanced 18FDG uptake (normal segments; n = 55), 2) normal perfusion with enhanced 18FDG uptake (metabolically abnormal segments; n = 3), 3) hypoperfusion with enhanced 18FDG uptake (ischemic but viable segments; n = 9), and 4) hypoperfusion without enhanced 18FDG uptake (non-viable segments; n = 3). On SPECT, the numbers of myocardial segments showing no perfusion defects, complete redistribution, incomplete redistribution, and persistent perfusion defects were 38, 12, 14, and 6, respectively. Comparisons were made between PET findings and SPECT findings.(ABSTRACT TRUNCATED AT 250 WORDS)