Tatsuo Shimizu

Horizontal transmission of hepatitis B from a father to two brothers.

We report on two brothers with horizontal transmission of hepatitis B virus infection from their father, proved by identical genotype of the virus. On January 8 2001, an 18-month-old boy (case 1) was admitted to our department with fever and vomiting since the day before. His father was an asymptomatic hepatitis B virus (HBV) carrier (AST 40 IU/l and ALT 41 IU/l), positive for both hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg) with an increased serum level of HBV DNA polymerase (3320 cpm). His mother was negative for HBsAg and positive for anti-HBs. The boy’s father was considered to have been infected vertically from his own mother during delivery. Laboratory tests revealed increased serum levels of transaminases (AST 133 IU/l and ALT 127 IU/l), as well as positive HBsAg and HBeAg. The serum level of HBV DNA was 2.0·10 mega-equivalents/l and HBV DNA polymerase was 7658 cpm. In September 2001, hepatitis B nephropathy was diagnosed by renal biopsy and demonstrated HBV-associated membranous glomerulopathy. Treatment with interferon-alpha plus dipyridamole was effective. The serum level of HBeAg decreased and anti-HBe increased, and seroconversion to anti-HBe was observed. At follow-up in July 2003, he was well, but still had slight proteinuria and positive HBsAg.

Myocardial excitation-contraction coupling in the fetus of alloxan-diabetic rabbit.

ABSTRACT: This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o (control), the force of myocardial contraction in FDM was not significantly dfferent from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]o caused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+ and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+ from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+ uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+ is greater and the toxic effect of Ca2+ is less than in the control fetus. This difference may be due, at least in part, to a sarcolemmal alteration induced by the maternal diabetes.

Caffeine effect on myocardial mechanical function in the neonatal rabbit heart.

The effects of 20 mM caffeine on myocardial mechanical function were studied in isolated, arterially perfused cardiac preparations of newborn and adult rabbits. Caffeine caused a significant increase in the maximal rate of tension development in the adult (141% of control) but not in the newborn (111%). The resting tension increased significantly in both age groups. However, the increase in the adult (245% of control) was also significantly greater than in the newborn (132%). At the points of maximum effect, caffeine perfusion in the newborn resulted in a decrease in the maximal rate of relaxation (29% of control) and an increase in the half relaxation time (144% of control) that were significantly greater than they were in the adult (41% and 103%, respectively). These data show distinct age-related differences in the effects of caffeine on myocardial mechanical function. These differences may be due to maturational changes that occur in the sarcoplasmic reticulum and T tubule system of the rabbit heart. However, maturational changes in the activity of phosphodiesterase and/or the sympathetic nervous system may play a role.

Persistent high fever for more than 10 days during acute phase is a risk factor for endothelial dysfunction in children with a history of Kawasaki disease

BACKGROUND Endothelial dysfunction has previously been reported in children with a history of Kawasaki disease, but the determinants of endothelial function in Kawasaki disease patients are still unknown. In this study, we investigated endothelial function in Kawasaki disease patients and attempted to identify risk factors for persistent endothelial dysfunction. METHODS Using high-resolution ultrasound, we measured the percent flow-mediated dilatation, an arterial response to reactive hyperemia, to evaluate endothelial function in 67 patients with a history of Kawasaki disease and 28 age- and sex-matched control subjects. We divided the Kawasaki disease patients into a group with impaired endothelial function (the percent flow-mediated dilatation below -2 standard deviations of the control group) and a group with normal endothelial function (the percent flow-mediated dilatation more than -2 standard deviations of control). Logistic multiple regression analysis was performed to identify independent predictors of impaired endothelial function. RESULTS In Kawasaki disease patients, the percent flow-mediated dilatation was significantly lower than in the control subjects (9.8±3.6%, compared with 13.1±3.4%, p<0.01). In 13 Kawasaki disease patients (3 patients with coronary artery lesions and 10 patients without coronary artery lesions), the percent flow-mediated dilatation was below -2 standard deviations of control. Logistic multiple regression analysis showed that a febrile period of longer than 10 days during the acute phase was the significant risk factor for endothelial dysfunction (odds ratio: 8.562; 95% confidence interval: 1.366-53.68). Presence of coronary artery lesions was not a determinant of endothelial dysfunction. CONCLUSIONS Systemic endothelial dysfunction exists in children with a history of Kawasaki disease, and a febrile period of longer than 10 days during the acute phase is an independent predictor of endothelial dysfunction irrespective of coronary artery involvement.

174 EFFECTS OF HYPOXIA AND REOXYGENATION (re-O2) ON CREATINE KINASE (CK) RELEASE AND TISSUE Ca2+ UPTAKE IN THE NEWBORN MYOCARDIUM

Sarcolemmal damage and tissue Ca2+ uptake were determined during hypoxia and re-O2 in isolated, arterially perfused newborn (NB) and adult (A) rabbit hearts. Tissue 47Ca2+ uptake was measured by δ -probe. CK release from the tissue was determined in the venous effluent and was used as an indicator of the sarcolemmal damage. During 40 min of hypoxia, tissue Ca2+ was unchanged. CK release (IU/g dry wt) was observed only in the A. During re-O2, tissue Ca2+ increased [Δ Ca2+ (mmol/kg dry wt)] and CK release was observed, and these two values in the A were significantly greater than in the NB. Recovery of mechanical function [+dT/dt (max), % of control] during re-O2 in the NB was significantly greater than in the A.These data suggest that tissue Ca2+ gain and/or sarcolemmal damage may be responsible for the impaired recovery of myocardial mechanical function after hypoxia.

A Case of Kawasaki Disease with Re-dilatation of the Coronary Artery Five Years after the Onset

We experienced a case of Kawasaki disease with re-dilatation of coronary artery aneurysm five years after the onset. [Patient profile] The patient is a 12-year-old boy. He suffered from Kawasaki disease at the age of four years. Intravenous gamma-globulin (IVGG) therapy with 300 mg/kg/day was administered for 5 days, and additional IVGG with 1g/kg/day was administered furthermore. However, in spite of IVGG therapy, the aneurysms were developed on the both coronary arteries, which were confirmed by the cardiac catheterization one year later. (AHA Committee Report: Segment 2: two aneurysms; 4.8mm, 5.0mm in diameter, Segment 6: 4,3mm, Segment 11: 4.1mm). Thereafter, the coronary aneurysm on LAD regressed gradually. We depicted this regression of LAD aneurysm by the echocardiography at 4 years after the onset. (Segment 6: 2.4mm in diameter). However, further follow-up echocardiography revealed re-dilatation of the aneurysm on the same region of LAD one year later. (Segment 6: 7.4mm in diameter). We also confirmed this re-dilatation of the aneurysm without stenotic lesions by cardiac catheterization. [Discussion] There have been reported that the regressed aneurysms sometimes develop to the stenotic lesions late after the onset. However, there are a few reports in which a newly developed aneurysm emerged late after the onset of Kawasaki disease. [Conclusions] Re-dilatation of the regressed aneurysm is a very unique clinical course as a long-term Kawasaki disease. While the mechanism of the re-dilatation of this patient is still un-known, we must be careful to follow him up.

EFFECT OF OUABAIN ON MYOCARDIAL MECHANICAL FUNCTION AND SODIUM PUMP IN THE PREMATURE NEWBORN RABBIT

Effects of ouabain (0.75, 1, 1.5, 2.5, or 5 × 10−6M) on mechanical function and sodium pump were studied in the isolated arterially perfused fetal and newborn rabbit heart. Measurements of myocardial 86Rb+ active uptake was used as a marker of the sodium pump activity. The inotropic effect of ouabain in the fetus was not significantly different from that in the newborn at all ouabain concentrations. 2.5 × 10−6M ouabain caused mechanical toxicity in the fetus but not in the newborn. In the fetal muscle, perfusion with low calcium (0.5 mM) solution reduced mechanical toxicity of ouabain. High extracellular calcium (30 mM) per se caused mechanical toxicity in the fetus, but not in the newborn. Ouabain infusion decreased tissue potassium content, and this decrease in the fetus was not significantly different from the newborn. The ouabain inhibition of Rb+ uptake was similar in the two age groups. These data indicate that mechanical toxicity in the fetus is observed at lower ouabain concentrations than in the newborn. This difference in mechanical toxicity may not be explained by the age-related difference in sodium pump activity. The greater calcium toxicity in the fetus may be the reason for the increased ouabain toxicity in this age group.

216 EFFECTS OF HYPOXIA AND REOXYGENATION ON MITOCHONDRIAL FUNCTION IN THE NEWBORN MYOCARDIUM

This study was designed to evaluate the effect of hypoxia (N2) and reoxygenation (re-O2) on mitochondrial function (MF) in the newborn (NB) and adult (A) rabbit heart. The heart was isolated, arterially perfused with Krebs-Henseleit solution, and maintained at 27°C. After hypoxia or hypoxia and reoxygenation, the mitochondria was isolated and MF was determined by polarographic technique. In the oxygenated perfused muscle (control), state 3 respiration (QO2) and respiratory control index (RCI) in NB (QO2=128 ±6 nAO/min/mg protein; RCI=16.0 ± 0.8; n=8) were significantly (P<0.001) greater than the values in the A (QO2=86 ± 4; RCI= 9.2 ± 0.7; n=9). After 40 or 60 min N2, QO2 decreased significantly (P<0.01) to 78 ± 5% of control in the NB (n=10) and 67 ± 13% of control in the A (n=8). During reoxygenation following 40 min N2, QO2 was not significantly different from control in both the NB and A. Reoxygenation following 60 min N2, however, did not improve MF and QO2 in the NB (51 ± 6% of control) and A (59 ±6%) remained significantly (P<0.001) less than control. The changes in RCI were similar to QO2 in all groups. The ADP/O ratio was not significantly different from control in all groups. These data indicate that the depression in mitochondrial function is reversible after 40 min N2 but is irreversible after 60 min N2, and there was no difference between the NB and A hearts.

193 THE INOTROPIC EFFECT OF OUABAIN ON THE NEWBORN MYOCARDIUM DURING REOXYGENATION FOLLOWING HYPOXIA

The effect of ouabain on myocardial mechanical function was studied during reoxygenation (re-O2) following 40 min of hypoxia in 8 newborn (NB) rabbits and the results were compared with those obtained in 9 NB control rabbits (without hypoxia). All studies were performed in the isolated, arterially perfused hearts. The hearts were perfused with Krebs-Henseleit (K-H) solution, maintained at 27°C, and paced at 36 beats/min. The muscles were initially perfused with oxygenated solution, and then perfused with hypoxic solution. After 40 min of hypoxia, oxygenated solution was reinstituted. Ouabain was infused during re-O2 after mechanical function reached a steady state (approximately 20 min after re-O2). Paired electrical stimulation was also performed before hypoxia and after re-O2 (N=5). Parameters of mechanical function were recorded continuously. +dT/dt (max) decreased significantly during hypoxia and returned to control value during re-O2. The positive inotropic effect of paired electrical stimulation after re-O2 (156 ± 7% of control) was not significantly different from that in the control group (168 ± 8%). Inotropic effect of ouabain during re-O2 (52 ± 7% of control) was significantly (p=0.02) less than that in the control group (95 ± 16%). These data suggest that the inotropic effect of ouabain is reduced in the reoxygenated NB heart after hypoxia and this is not due to a change in excitation-contraction coupling.

142 EFFECT OF VERAPAMIL ON MECHANICAL FUNCTION OF THE NEONATAL RABBIT HEART

Previous data from our laboratory suggest that the newborn (NB) rabbit heart is greatly dependent on extracellular calcium (Ca) for excitation-contraction coupling. Verapamil (V), a calcium antagonist, is currently being used to treat arrhythmias in infaits. Little is known about the negative inotropic effects of this agent on NB hearts. This study was designed to evaluate the effects of V on mechanical function of the neonatal heart. NB (n=6) and adult (A,n=6) rabbit hearts were studied utilizing an isolated, arterially perfused cardiac preparation that was maintained at 27°C and paced at 36 beats/min. The muscles were perfused initially with a control Krebs-Henseleit solution (K-HS) and then with a K-HS containing 0.1 uM of V. Peak (PT), developed (DT), resting (RT) tensions; rate of tension development (+dT/dt); time to peak tension (TPT); and time to half relaxation (1/2 RLT) were recorded continuously. The negative inotropic effect of V in the NB was significantly (P<0.01) less than that in the A. In the NB, 50% of the maximal decrease in function occurred significantly (P=0.03) later than it did in the A. V significantly (P<0.04) increased the RT in the NB but not in the A. V had no significant effect on either the TPT or the 1/2 RLT in the two age groups. These data suggest that the negative inotropic effect of V in the NB is less than that in the A and that the NB is less dependent on the slow inward calcium current for excitation-contraction coupling than is the A.