No abstract

No abstract

Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.

Objective-To determine the sensitivity and specificity of our transthoracic echocardiographic technique using high frequency (7.5 MHz) transducers for identification of the presence and type of coronary artery disease in patients with Kawasaki disease. Design-The results of the prospective echocardiographic study in each of seven segments of the four major coronary arteries were compared with the selective coronary angiograms. Setting-Kitasato University Hospital. Subjects-60 patients with Kawasaki disease, ranging in age from 8.0 months to 22 years (median, 6.0 years). Results-Adequate echocardiographic images were obtained in 397 (95%) of 420 coronary segments. Coronary angiography showed the presence of coronary aneurysms in 87 segments and stenosis or occlusion in 28. The overall sensitivity and specificity of cross sectional echocardiography for correctly identifying coronary aneurysms were 95% and 99%, respectively; for correctly identifying coronary stenosis or occlusion the values were 85% and 98% for the right coronary artery, and 80% and 97% for the left anterior descending coronary artery. Agreement on the presence or absence of coronary aneurysms and obstructive lesions on echocardiograms between the two observers was 1.0 and 0.98, respectively. Conclusions-Echocardiography may provide a non-invasive means of identifying the presence and type of coronary artery disease in patients with Kawasaki disease. (Heart 2000;83:400-405)

The pulsed Doppler technique was used to record the flow velocity patterns in the ductus arteriosus and the pulmonary artery in 26 patients with either isolated or complicated patent ductus arteriosus (PDA). In all patients, abnormal Doppler signals indicating left-to-right (L-R) or right-to-left shunt flow or both could be obtained at the site of the ductus arteriosus. These Doppler flow patterns determined within the ductus coincided with the direction of ductal flow seen on the contrast two-dimensional echocardiogram. No Doppler signals of shunt flow were demonstrated in any of 42 control subjects. The peak, mean, and diastolic velocities of the L-R shunt flow within the ductus were measured from the ductal flow velocity profiles. With the Doppler-derived measurements of the mean and diastolic velocities, patients with normal pulmonary arterial pressure and those with evidence of pulmonary hypertension could be correctly identified. In addition, the mean velocity of the diastolic antegrade flow portion obtained from the proximal left pulmonary artery, which was related to ductal L-R shunting, was measured in 16 patients with isolated PDA. This Doppler flow determinant showed a good linear correlation with the L-R shunt ratio determined by Fick's method (r = .88, p < .01). Our technique permits the noninvasive evaluation of shunt flow dynamics in patients with PDA. Circulation 75, No. 6, 1146-1153, 1987 ALTERATION of Doppler flow patterns in the pulmonary artery and descending aorta has been useful in the diagnosis of patent ductus arteriosus (PDA).1 Twodimensional echocardiography has allowed visualization of the ductus from the parasternal, suprasternal, and subxyphoid windows.6'7 Recent reports8'9 have demonstrated that two-dimensional/Doppler echocardiography is a highly sensitive technique for detection of ductal patency. However, few studies have been reported concerning the assessment of shunt flow within the ductus.°l We therefore designed the present study to (1) evaluate the ability of two-dimensional/ Doppler echocardiography to determine the direction of shunt flow in the ductus and (2) assess the pulmonary-to-systemic peak pressure ratio and the degree of left-to-right (L-R) shunting with Doppler-derived indexes of the flow velocity.