Yuh Asano

Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki Disease A Retrospective Study

Background— Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. Methods and Results— We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17–0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38–0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20–0.44; P<0.001). Conclusions— UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.

Analysis of T wave changes by activation recovery interval in patients with atrial septal defect

We examined the distributions of the activation recovery interval (ARI), which is correlated with the local action potential duration (APD), to clarify the origin of the repolarization changes in ASD. The ECGs, QRST isointegral maps and ARI isochronal maps of 21 children with ASD from 3 to 5 years old in age were studied in comparison with 21 age-matched normal children. A conventional and 87 unipolar body surface ECG were simultaneously recorded. The ARIs were determined from the first derivatives of the ECG waveforms. Abnormal ST-T patterns were observed in 11 of 21 ASD, but only in two normal children. The QRST maps of a split positive area pattern were seen in 15 of ASD but none of the normal. In the ARI maps, all the normal children exhibited a short-ARI area on the left and a long-ARI area on the right side of the chest. In 19 of ASD, the ARI distribution revealed a leftward extension of the long-ARI area on the anterior chest, a relative shortening on the right anterior chest, and a localized prolonged ARI on the left anterior chest. The results suggest that right ventricular (RV) volume overload in ASD produces a localized prolongation of the APD on the RV epicardium.

Diagnosis of right ventricular overload by body surface QRST isointegral maps in children with postoperative right bundle branch block

The utility of body surface QRST isointegral maps (QRST-Imaps) for the detection of right ventricular (RV) overload was examined in children with postoperative development of right bundle branch block. In healthy children with no evidence of bundle branch block (n = 31), the QRST-Imap demonstrated a maximum at the left anterior chest and a minimum near the right shoulder with a single dipole distribution. The positive areas extended from the left anterior chest to the left back, and negative areas extended from the right anterior chest to the right back. Children with complete right bundle branch block but without heart disease demonstrated a QRST-Imap that was similar to that seen in normal children. In patients with RV overload (n = 15; 8 with ventricular septal defect and complicated anomaly and 7 with tetralogy of Fallot), the QRST-Imaps were abnormal and demonstrated double maxima, a rightward shift of the maximum, and extension of positive areas to the right chest. In the 10 patients who developed postoperative complete right bundle branch block, 4 had no evidence of RV overload by hemodynamic or echocardiographic assessment and demonstrated a normal QRST-Imap. In the six children who had residual RV overload during hemodynamic assessment, the QRST-Imap was abnormal. These results suggest that the QRST-Imap is a useful method for the detection of RV overload in pediatric patients complicated with conduction disturbances.

Precordial leads QRST time integrals for evaluation of right ventricular overload in children with congenital heart diseases

It was previously shown that body surface QRST isointegral maps of the anterior chest were abnormal in patients with right ventricular overload and that the abnormalities varied with hemodynamic status. The QRST isointegral maps were first characterized by using a departure index map for normal controls. The study group consisted of 14 patients with pulmonary stenosis (PS), 20 with tetralogy of Fallot, (TOF) and 43 with atrial septal defect (ASD). The QRST isointegral maps of these three groups were compared with the data on 23 to 65 age-matched normal children. In mean departure index maps, the patients with right ventricular pressure overload (PS or TOF) showed an increase in departure index on the anterior midchest, while those of right ventricular volume overload (ASD) showed two maxima on the anterior and left lateral chest, with a trough-like negative area between them. Since the abnormal findings were seen on the anterior chest, we evaluated the diagnostic usefulness of QRST time integral values for precordial leads of the routine electrocardiogram (ECG) in a second part of this study. The precordial QRST time integral values from 9 patients with PS and 11 with TOF (0-2 years of age, mean 1.1 years) and 22 ASD patients (6-15 years, mean 10.1 years) were compared with those of the age-matched control children. The QRST time integral values of the precordial leads in right ventricular pressure overload were significantly increased in the right precordial leads (V1, V2). In right ventricular volume overload, the QRST time integral values of the V1, V2, V4, and V6 leads demonstrated a significant deviation from those of the control group. Therefore, a discrimination formula was constructed by using the values of these leads, and the criteria derived from this formula revealed good (98%) diagnostic accuracy. In detection of right ventricular overload, the QRST time integral values of the precordial lead ECG, if confirmed in a larger data set, may be useful as a simple screening method.

Contribution of Sarcoplasmic Reticulum Ca 2+ Release and Ca 2+ Transporters on Sarcolemmal Channels to Ca 2+ Transient in Fetal Mouse Heart

Sarcoplasmic reticulum (SR) Ca2+ release has been shown not to be the predominant mechanism responsible for excitation-contraction (E-C) coupling in fetal myocytes. However, most of the studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density have been reported. We aimed to elucidate the contribution of SR Ca2+ release and Ca2+ transporters on sarcolemmal channels to Ca2+ transients in fetal mouse whole hearts. On embryonic day 13.5, ryanodine significantly reduced the amplitude of the Ca2+ transient to 27.2 ± 4.4% of the control, and both nickel and SEA0400 significantly prolonged the time to peak from 84 ± 2 ms to 140 ± 5 ms and 129 ± 6 ms, respectively, whereas nifedipine did not alter it. Therefore, at early fetal stages, SR Ca2+ release should be an important component of E-C coupling, and T-type Ca2+ channel and reverse mode sodium-calcium exchanger (NCX)-mediated SR Ca2+ release could be the predominant contributors. Using embryonic mouse cultured cardiomyocytes, we showed that both nifedipine and nickel inhibited the ability of NCX to extrude Ca2+ from the cytosol. From these results, we propose a novel idea concerning E-C coupling in immature heart.

Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki Disease

Background— Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. Methods and Results— We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17–0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38–0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20–0.44; P<0.001). Conclusions— UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.

Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki DiseaseClinical Perspective

Background— Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. Methods and Results— We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17–0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38–0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20–0.44; P<0.001). Conclusions— UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.

Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki DiseaseClinical Perspective: A Retrospective Study

Background— Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. Methods and Results— We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17–0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38–0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20–0.44; P<0.001). Conclusions— UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.