Non-invasive measurement of coronary flow reserve in children with Kawasaki disease.

OBJECTIVE: To investigate whether transthoracic Doppler echocardiography (TTE) can reliably measure the coronary flow reserve in the left anterior descending coronary artery in children with Kawasaki disease. DESIGN: Coronary flow velocity in the distal left anterior descending coronary artery was measured by TTE and was compared with that obtained by intracoronary Doppler guide wire. The ratio of maximum hyperaemia (intravenous administration of adenosine triphosphate, 160 microg/kg/min) to baseline peak (mean) diastolic coronary flow velocity in the distal artery was used as an estimate of coronary flow reserve. SETTING: University hospital. PATIENTS: 10 patients with significant left anterior descending coronary stenosis (> 70% diameter stenosis) (group A) in the proximal or middle portion of the artery and 14 patients (group B) without significant stenosis, all with Kawasaki disease documented by previous coronary angiography. RESULTS: The reduced hyperaemic coronary flow velocity in group A compared with group B resulted in a markedly lower coronary flow reserve, derived from both peak diastolic velocity and mean diastolic velocity by either technique of investigation. Multivariate analysis identified the best predictor of left anterior descending coronary artery stenosis to be a coronary flow reserve of < or = 2.2, derived from mean diastolic flow velocity measured using TTE (sensitivity 90%, specificity 100%, accuracy 96%). A good correlation was found between diastolic velocity derived values for coronary flow reserve measured using both TTE and Doppler guide wire (r = 0.92, p = 0.0001). CONCLUSIONS: Coronary flow reserve in the distal left anterior descending coronary artery can be accurately measured using TTE without any intravascular instrumentation in children with Kawasaki disease.

Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions.

OBJECTIVES: The severity of carotid arteriosclerosis, defined as increased intima-media thickness (IMT) visible with B-mode ultrasound, is correlated with risk factors for coronary heart disease. Little is known, however, about the relation of IMT, the stiffness of the common carotid artery, and the progression of atherosclerosis in children with Kawasaki disease (KD) and coronary artery lesions (CAL). DESIGN: We investigated the associations among total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, TC/HDL-C, ApoE genotype, glycohemoglobin, IMT, and arterial stiffness by high resolution ultrasound in 20 adolescents with KD and CAL (age: 16.6 +/- 4.1 years, males: 60%) and 20 sex- and age-matched healthy controls (Cont). RESULTS: No significant differences were observed in the values of body mass index and blood pressure between the 2 groups. Also no significant differences were observed in the levels of TC, LDL-C, HDL-C, triglyceride, TC/HDL-C within normal values, or the allele frequency of Apo E4 between the 2 groups. However, the values of IMT, stiffness, and glycohemoglobin in patients with KD were significantly higher than those in Cont (0.53 +/- 0.07 vs 0.46 +/- 0.05 mm, P <.05; 4.11 +/- 0.86 vs 2.94 +/- 0.91, P <.001; 5.0 +/- 0.4 vs 4.6 +/- 0.2%, P <.05). A significant relationship was observed between sex and the mean IMT (r = 0.46) in Cont; however, no significant correlation was found between mean IMT and other variables in either group. Although the arterial stiffness was strongly related to body mass index (r = 0.58) and systolic blood pressure (r = 0.55) in Cont, no significant relationship was observed between the stiffness and any variable tested in patients with KD. CONCLUSIONS: The less distensible carotid wall in patients with KD compared with that in Cont without major alteration of the lipid profile is likely to be secondary to the changes in arterial walls after a diffuse vasculitis involving noncoronary arteries. These results indicate that the coronary arteries may be predisposed to accelerated atherosclerosis in patients with KD and CAL.

[Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging].

OBJECTIVES: Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5 +/- 6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. METHODS: Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). RESULTS: The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33 +/- 0.22 in chronic heart failure class I, 2.50 +/- 0.34 in class II, 1.95 +/- 0.61 in class III, and 1.39 +/- 0.29 in class IV (p < 0.05). %WR was 24.8 +/- 12.8% in chronic heart failure class I, 23.3 +/- 10.2% in class II, 49.2 +/- 24.5% in class III, and 66.3 +/- 26.5% in class IV (p < 0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. CONCLUSIONS: Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure.

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers.

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12-13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P = 0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003), and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003) were significantly lower in obese boys than in non-obese boys. The serum levels of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non-obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti-atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central-type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central-type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Measurement of coronary flow reserve in children by transthoracic Doppler echocardiography.

Noninvasive measurement of coronary flow reserve was performed by transthoracic color Doppler echocardiography in 28 children with Kawasaki disease.

[Optimum protocol of technetium-99m tetrofosmin myocardial perfusion imaging for the detection of coronary stenosis lesions in Kawasaki disease].

The clinical usefulness of a new myocardial perfusion imaging agent, technetium-99m tetrofosmin, was assessed in 58 patients for a total of 76 times (mean age 9.7 years, 1-15 years) including 20 with and 26 without significant coronary stenotic lesions in Kawasaki disease. Pharmacological (dobutamine or adenosine triphosphate disodium) or exercise stress technetium-99m tetrofosmin single photon emission computed tomography was performed under stress and at rest on the same day. The sensitivity for detection of stress-induced perfusion defects by this method was 90% (18/ 20) and the specificity was 85% (22/26). The dose was 9.3 +/- 2.5 MBq/kg under stress and 18.7 +/- 5.6 MBq/kg at rest. No significant correlation was recognized between the dose and the image quality. Adequate image quality was provided by projection time 20-40 sec per frame. Increased liver accumulation was seen in 24% (18/76), especially in younger and pharmacological stress cases. The acquisition starting time after tetrofosmin injection was 58.4 +/- 18.7 min in the negative increased liver accumulation group and 43.7 +/- 18.3 min in the positive group (p < 0.01). We recommend that the following protocol is used for pediatric imaging. 1) The standard tetrofosmin dose is rougly 10 MBq/kg (upper limit 370 MBq) at stress and the double dose for the rest imaging. 2) SPECT projection time of 20-40 sec per frame. 3) In practice, the patient should be fasting prior to stress injection, and the imaging should be done 1 hour after eating. The rest injection should be done immediately thereafter, and the rest image should be obtained 1 hour later.

A case of Guillain-Barré syndrome accompanied by sympathetic overactivity and hypertensive encephalopathy.

Hypertension has often been observed in patients with Guillain-Barré syndrome, and various underlying mechanisms have been implicated. We report the case of a child with the Guillain-Barré syndrome whose hypertension was associated with increases in both renin activity and circulating catecholamines. This case also appeared to be complicated by hypertensive encephalopathy. Following administration of intravenous regitine, a blood pressure change was observed and cardiac performance was assessed by two-dimensional echocardiography. Results indicated that increased total peripheral resistance may have been responsible for the symptoms and the hypertension. The hypertension was effectively managed by nifedipine, captopril and prazosin without the need for beta-blockade.

Dobutamine stress echocardiography for detection of coronary artery stenosis in children with Kawasaki disease.

OBJECTIVES: This study was designed to assess the feasibility and diagnostic accuracy of dobutamine stress echocardiography for detection of coronary artery stenosis in children with Kawasaki disease. BACKGROUND: Dobutamine stress echocardiography is valuable as an alternative test for detection of coronary artery disease in adult patients; however, its usefulness for children has been demonstrated only in limited cases. METHODS: Dobutamine stress echocardiography (up to 30 microgram/kg body weight per min) was performed in 50 patients at the convalescent stage of Kawasaki disease, including 26 patients with coronary sequelae documented by previous coronary angiography (sequelae group, 3 to 15 years old) and 24 patients with normal coronary arteries documented by echocardiography (normal group, 7 to 16 years old), who underwent quantitative coronary angiography on a separate day. Left ventricular regional wall motion divided into 16 segments was assessed in relation to the extent of coronary artery disease. A positive test response was defined as a new or worsened wall motion abnormalities. RESULTS: Significant coronary artery disease (> or = 50% diameter stenosis of major vessels) was present in 21 patients in the sequelae group. There was no significant difference in the maximal dose of dobutamine between the sequelae and normal groups ([mean +/- SD] 22.4 +/- 5.1 vs. 24.2 +/- 2.5 microgram/kg per min). Heart rate and systolic blood pressure were significantly increased (p < 0.01) at maximal dose of dobutamine compared with values at rest in both groups; consequently, the rate-pressure product exceeded 20,000 in 20 (40%) of the 50 patients during dobutamine infusion. Ten patients had self-limiting side effects; however, there were no serious complications from stress-induced ischemia. New wall motion abnormalities corresponding to the extent of coronary artery disease were detected in 19 of 21 patients in the sequelae group, whereas no wall motion abnormalities were detected in the normal group. Thus, the sensitivity and specificity of dobutamine stress echocardiography for the detection of coronary artery disease were 90% and 100%, respectively. CONCLUSIONS: We conclude that dobutamine stress echocardiography is a safe and accurate diagnostic method for detection of coronary artery stenosis in Kawasaki disease. Moreover, this is a possible alternative method for patients unable to exercise adequately, even if they are small children.

[An operative case of solitary interruption of the aortic arch in adult].

A 43-year-old lady was hospitalized due to easy fatiguability in the legs during exercise, and for evaluation of an abnormal shadow in the chest X-ray, and hypertension. Her blood pressure was 200/80 mmHg in the right arm, 140/70 mmHg in the left, and 110/70 mmHg in both lower extremities. Systolic vascular bruit radiating to her neck and back was audible in the Erb's area. DSA and aortogram disclosed extremely dilated vessels around the origin of the left common carotid artery. The left subclavian artery was opacified retrogradely as a subclavian blood steal via the left vertebral artery, and mild stenosis was seen at its origin. There was no evidence of associated congenital anomaly such as VSD, PDA, or ASD. The final diagnosis, solitary interruption of the aortic arch (S-IAA, type B), was made by MRI. The patient had an extra-anatomical bypass operation by using Cooley woven dacron graft from the ascending to the abdominal aorta. The result was good. S-IAA is a very rare congenital anomaly. As far as we know, only 21 patients with S-IAA including this case have been reported. A physician should be aware that a patient with S-IAA tends to have a difference of blood pressure not only between the upper and lower extremities but also between both arms, and pressure in the right arm is usually higher than that in the left. These are good signs to suspect S-IAA. And they also can be helpful to differentiate S-IAA from coarctation of the aorta.

[A case of acute myocardial infarction due to coronary embolism from left atrial thrombus with atrial fibrillation].

A 55-year-old man, who has been on follow-up observation with chronic atrial fibrillation, came in with a sudden onset of chest pain on July 31, 1986. He was diagnosed as having acute myocardial infarction indicated by abnormal ECG, elevated serum enzyme and characteristic signs of echocardiography. Emergency coronary angiography was performed 2 hours after the onset of chest pain, and it was reported as showing total obstruction of the distal left anterior descending artery. Percutaneous transluminal coronary recanalization using 1,200,000 units of urokinase was unsuccessful. The repeated angiography performed 40 days later, showed normal coronary arteriogram, but left ventriculogram revealed akinesis of the apical segment. Furthermore, left atrium opacified in the levophase of pulmonary arteriogram indicated left atrial thrombus. The cause of the myocardial infarction was considered to be coronary embolism from the left atrial thrombus with atrial fibrillation. It must be the first report documented by coronary angiography, of coronary thrombo-embolism due to chronic atrial fibrillation without any underlying disease.

Follow-up results of surgical treatment for chronic pancreatitis. Present status in Japan.

The results of surgical treatment for chronic pancreatitis at our clinic and in the eight leading institutions of Japan were reviewed in a total of 328 cases. Abdominal pain disappeared or was alleviated in about 90 percent of the patients who survived more than 6 months after operation. There was no significant differences in the effect of pain among the three main types of operations: pancreaticoduodenectomy, distal resection and pancreatic ductal drainage. In the collected cases, however, complete disappearance of pain was reported more often in patients subjected to Puestow's operation than in those who underwent Nardi's operation. The patients who underwent pancreatic ductal drainage had a greater postoperative weight gain than those without drainage, in both our patients and the collected cases. In the collected cases, Puestow's operation was predominantly linked to postoperative weight gain. Evidence of pancreatic functional improvement, either in endocrine or in exocrine, was very meager.

Studies on porcine pancreatic elastase activity. I. Radioimmunoassay of porcine pancreatic elastase.

An improved method of radioimmunoassay was devised to offer a successful formula for determining blood concentration of elastase. With porcine pancreatic elastase as the antigen, rabbits were immunized to obtain antiserum. Iodinated elastase labeled by the chloramine-T procedure using 131I (or 125I) had a specific activity of 200-300 mCi/mg. The double antibody method was used for BF separation. While the usual method of radioimmunoassay was not always successful in obtaining accurate serum concentration of elastase, the use of diisopropyl fluorophosphate (DFP) was able to eliminate the disturbing influence of intra-serious inhibitors, alpha 1-AT and alpha 2-M, eventually producing satisfactory results. With the use of DFP, the elastase standard curve and the porcine serum dilution curve had a statistically significant correlation; precision and recovery were both satisfactory; cross-reactivity of the antiserum with trypsin and chymotrypsin was less than 0.001%. The minimal detectable concentration of elastase was 5 ng/ml, and the range of normal fasting porcine serum level was 70-100 ng/ml.

Studies on porcine pancreatic elastase activity. II. Immunoreactive elastase level during acute hemorrhagic pancreatitis in pigs.

Acute hemorrhagic pancreatitis was produced in pig to study serum concentration of elastase and its physiological role. Pancreatitis was induced in two groups of young pigs by the injection of autologous bile. One group was injected with autologous bile (0.5 ml/kg) at high pressure, and the second group was injected as low pressure (100 cm H2O). Then femoral blood, portal blood and thoracic lymph were sampled at scheduled time intervals. The control level of immunoreactive elastase was around 90 ng/ml in each site, which significantly increased beginning 15 min after bile injection; the level of immunoreactive elastase was higher in the thoracic lymph duct than in the femoral and portal vein. The total and free elastase of both groups in pancreatic tissue were significantly decreased in pancreatitis, and an abundance of immunoreactive elastase was found in the ascites. The increasing pattern of immunoreactive elastase and amylase after bile injection was very similar. Therefore, the level of immunoreactive elastase was considered to be inadequate to determine the grade of severity of pancreatitis as well as the level of amylase which is already known.