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Background: Chronic high Epstein–Barr virus loads (CHEBV) are commonly observed in pediatric liver transplant patients. However, it is unclear how CHEBV impacts the liver graft. The aim of this study was to clarify the clinical and pathological impacts of CHEBV on the liver graft. Methods: From 2012 to 2020, we retrospectively investigated 46 pediatric liver transplant patients (under 16 years) who survived ≥6 months. The patients were divided into two groups: CHEBV group (EBV DNA >10 000 IU/ml of whole blood for ≥6 months) and nonchronic high EBV (NCHEBV) group (patients who did not meet CHEBV criteria). Tacrolimus was reduced to <3.0 ng/ml in patients with EBV DNA >5000 IU/ml. Blood biochemistry data and pathological findings, obtained at the time of protocol and episodic biopsies, were compared between the two groups. Results: Out of 46 patients, 28 CHEBV and 18 NCHEBV patients were enrolled. The blood biochemical examination did not show a significant difference between the two groups. In addition, no significant differences between the two groups were found in the pathological findings, including frequency of late acute rejection and the progression of fibrosis at the time of both protocol and episodic biopsies. Appropriate adjustment of immunosuppression for CHEBV management may have contributed to the prevention of the progression of fibrosis. Conclusion: CHEBV had little adverse effect on the liver graft. Graft fibrosis might have been avoided through optimal dose modification of tacrolimus. Further long-term monitoring is necessary because CHEBV may affect the pediatric liver graft in the long term.

NASDA Special Publication, 宇宙開発事業団特別報告

NASDA Special Publication, 宇宙開発事業団特別報告

Objectives: The aim of this study was to investigate the conformational change of arterial structure in the vasospastic lesion with optical coherence tomography. Background: Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases. The conformational change of each arterial layer during vasospasm has not been studied in detail. Methods: We assessed 19 coronary arteries (10 spasm and 9 nonspasm lesions) with optical coherence tomography during the provocation test for coronary spasm. An intimal bump was defined as 1 or more intimal projections into the lumen that disappeared after the administration of nitroglycerine (NTG). Intimal gathering was defined as a folding/gathering of the intima, resulting in multiple kinks in the luminal contour that resolved after the administration of NTG. Results: The spasm lesion more frequently showed an intimal bump at baseline and intimal gathering during spasm compared with the nonspasm lesion (spasm 80% vs. nonspasm 0%, p < 0.01, spasm 100% vs. nonspasm 0%, p < 0.01, respectively). The spasm lesion demonstrated a thicker maximum media thickness (spasm 0.24 ± 0.04 mm vs. nonspasm 0.12 ± 0.03 mm, p < 0.01) at baseline, whereas no differences were observed after the administration of NTG (spasm 0.13 ± 0.03 mm vs. nonspasm 0.13 ± 0.02 mm, p = 0.65). Conclusions: Our results suggest that medial contraction occurs even in an asymptomatic state and facilitates the formation of an intimal bump in patients with vasospastic angina. Luminal narrowing during spasm is associated with intimal gathering without alteration of intimal area.

Yasushi Kono,1 Shota Fukuda,1 Kenei Shimada,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Tomoichiro Kubo,1 Satoshi Jissho,1 Haruyuki Taguchi,1 Junichi Yoshikawa,3 Minoru Yoshiyama21Department of Medicine, Osaka Ekisaikai Hospital, Nishi-ku, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Abeno-ku, Osaka, Japan; 3Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanBackground: It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function.Purpose: This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin.Methods: This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration.Results: The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group.Conclusion: The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.Keywords: coronary artery disease, statin, microvascular function

We described a 19 year old female case with renovascular hypertension, whose blood pressure was high taking antihypertensive medications. The right renal artery was completely occluded at its ostium, and percutaneous transluminal renal angioplasty was unsuccessful. After aorto-renal bypass surgery, blood pressure was normalized without administration of antihypertensive medication.

We described a 19 year old female case with renovascular hypertension, whose blood pressure was high taking antihypertensive medications. The right renal artery was completely occluded at its ostium, and percutaneous transluminal renal angioplasty was unsuccessful. After aorto-renal bypass surgery, blood pressure was normalized without administration of antihypertensive medication.

Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in

Background : Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, and induces radiographic regression and symptomatic improvement in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response, never smoking history and adenocarcinoma were associated with survival. We attempted to identify additional clinical features associated with response and survival. / Methods : We reviewed medical records and imaging studies of all 68 NSCLC patients treated by gefitinib monotherapy in our institution. We identified patients experiencing disease control and compared their clinical features with those of other patients....

Smooth muscle cells (SMCs) are the major cellular component of neointimal tissues after percutaneous coronary intervension (PCI). Endothelin-1 (ET-1) is a powerful vasoconstrictor and has a mitogenic effect on SMCs. Endothelin-converting enzyme (ECE) is a key enzyme in the process of ET-1 generation. However, the expression of ECE in association with post-PCI repair processes has not been reported. Thirteen coronary sites after PCI obtained at autopsy and 6 atherectomy specimens obtained from restenotic sites were investigated....

Smooth muscle cells (SMCs) are the major cellular component of neointimal tissues after percutaneous coronary intervension (PCI). Endothelin-1 (ET-1) is a powerful vasoconstrictor and has a mitogenic effect on SMCs. Endothelin-converting enzyme (ECE) is a key enzyme in the process of ET-1 generation. However, the expression of ECE in association with post-PCI repair processes has not been reported. Thirteen coronary sites after PCI obtained at autopsy and 6 atherectomy specimens obtained from restenotic sites were investigated....

Background : Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, and induces radiographic regression and symptomatic improvement in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response, never smoking history and adenocarcinoma were associated with survival. We attempted to identify additional clinical features associated with response and survival. / Methods : We reviewed medical records and imaging studies of all 68 NSCLC patients treated by gefitinib monotherapy in our institution. We identified patients experiencing disease control and compared their clinical features with those of other patients....

Background : Recent studies suggest that granulocyte colony-stimulating factor (G-CSF) may be beneficial in the treatment of myocardial infarction (MI). However, the effects of G-CSF on MI are still controversial and the molecular mechanism of G-CSF treatment for repair of the infarcted heart is not fully understood. / Methods : Mice were divided into three groups: Control, MI and MI treated with G-CSF. Four weeks after MI, we examined cardiac function by Doppler echocardiography and measured noninfarcted myocardial mRNA expression by northern blot analysis....

Background : Spatially resolved (SR) spectroscopy has enabled non-invasive and continuous measurement of muscle oxygen saturation during exercise. In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction has been widely studied histochemically and biochemically. However, impairment of muscle oxygenation during exercise has not been elucidated yet. / Methods : We measured oxygen saturation in the vastus lateralis muscle (SmO_2) using SR spectrometry during incremental cycle exercise in 16 COPD patients and 10 age-matched healthy subjects....

Background : We have recently emphasized that airway microcirculation has the potential to contribute to the pathophysiology of asthma. We therefore hypothesized that increased production of airway nitric oxide (NO) plays an important role in the pathogenesis of asthma through microvascular hyperpermeability. To test our hypothesis, we compared exhaled NO levels in normal subjects and asthmatic patients, and examined the contribution of airway microvascular permeability to the pathophysiology of asthma. / Methods : Inflammatory indexes in induced sputum, exhaled NO levels, and airway vascular permeability index were examined in 11 normal controls, 19 beclomethasone dipropionate (BDP)-treated asthmatics, and 20 BDP-untreated asthmatics....

Background : We have recently emphasized that airway microcirculation has the potential to contribute to the pathophysiology of asthma. We therefore hypothesized that increased production of airway nitric oxide (NO) plays an important role in the pathogenesis of asthma through microvascular hyperpermeability. To test our hypothesis, we compared exhaled NO levels in normal subjects and asthmatic patients, and examined the contribution of airway microvascular permeability to the pathophysiology of asthma. / Methods : Inflammatory indexes in induced sputum, exhaled NO levels, and airway vascular permeability index were examined in 11 normal controls, 19 beclomethasone dipropionate (BDP)-treated asthmatics, and 20 BDP-untreated asthmatics....

Background : Recent studies suggest that granulocyte colony-stimulating factor (G-CSF) may be beneficial in the treatment of myocardial infarction (MI). However, the effects of G-CSF on MI are still controversial and the molecular mechanism of G-CSF treatment for repair of the infarcted heart is not fully understood. / Methods : Mice were divided into three groups: Control, MI and MI treated with G-CSF. Four weeks after MI, we examined cardiac function by Doppler echocardiography and measured noninfarcted myocardial mRNA expression by northern blot analysis....

Background : Spatially resolved (SR) spectroscopy has enabled non-invasive and continuous measurement of muscle oxygen saturation during exercise. In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction has been widely studied histochemically and biochemically. However, impairment of muscle oxygenation during exercise has not been elucidated yet. / Methods : We measured oxygen saturation in the vastus lateralis muscle (SmO_2) using SR spectrometry during incremental cycle exercise in 16 COPD patients and 10 age-matched healthy subjects....

Background : Although dipyridamole and adenosine have been used as vasodilator agents, we believe they are inadequate for vasodilator perfusion magnetic resonance imaging, due to adverse effects (flushing, warmth, headaches, and arrhythmia). Nicorandil, a potassium channel opener, has been reported to increase coronary blood flow and it was associated with fewer adverse effects than adenosine or dipiridamole. We set out to investigate whether the coronary artery stenosis could be assessed by nicorandil stress perfusion magnetic resonance imaging. / Methods : First-pass contrast-enhanced magnetic resonance images of the left ventricle acquired from 50 patients at rest and during intravenous administration of nicorandil using multi-slice turbo field echo with multi shot echo-planar-imaging. Coronary angiography was performed within 1 week....

Previous studies have shown larger target vessel or greater stent area contribute to reduced restenosis rate. Thus, intravascular ultrasound (IVUS)-guided bare metal stent (BMS) implantation for selected lesions might achieve drug-eluting stent-like outcomes. The aim was to examine the long-term outcomes of BMS using IVUS-guided optimization. / Methods : Consecutive 103 coronary artery lesions suitable for IVUS were enrolled. Using IVUS, final stent balloon size selected was 90 percent of media-to-media diameter at the lesion or distal reference. The balloon size was listed as follows: group A (3.0-3.5 mm, n=15), group B (3.5-3.75 mm, n=64), and group C (3.75-4.5 mm, n=24)....

Background : Abnormal left ventricular (LV) diastolic relaxation is an early sign of hypertensive heart disease. Whether diastolic dysfunction differs between LV geometric patterns remains controversial. / Methods and Results : We examined 220 hypertensive patients by echocardiography to assess the relationship between diastolic function and LV geometric pattern. We identified four LV geometric patterns: normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Diastolic function was evaluated by the E/A ratio, E wave deceleration time (Dct), and isovolumic relaxation time (IRT)....

Background : Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI. / Methods : Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group....

Background : HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis. / Methods and Results : In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n=22) or the non-prescribed group (control group, n=26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up....

Background : Although dipyridamole and adenosine have been used as vasodilator agents, we believe they are inadequate for vasodilator perfusion magnetic resonance imaging, due to adverse effects (flushing, warmth, headaches, and arrhythmia). Nicorandil, a potassium channel opener, has been reported to increase coronary blood flow and it was associated with fewer adverse effects than adenosine or dipiridamole. We set out to investigate whether the coronary artery stenosis could be assessed by nicorandil stress perfusion magnetic resonance imaging. / Methods : First-pass contrast-enhanced magnetic resonance images of the left ventricle acquired from 50 patients at rest and during intravenous administration of nicorandil using multi-slice turbo field echo with multi shot echo-planar-imaging. Coronary angiography was performed within 1 week....

Background : Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI. / Methods : Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group....

Previous studies have shown larger target vessel or greater stent area contribute to reduced restenosis rate. Thus, intravascular ultrasound (IVUS)-guided bare metal stent (BMS) implantation for selected lesions might achieve drug-eluting stent-like outcomes. The aim was to examine the long-term outcomes of BMS using IVUS-guided optimization. / Methods : Consecutive 103 coronary artery lesions suitable for IVUS were enrolled. Using IVUS, final stent balloon size selected was 90 percent of media-to-media diameter at the lesion or distal reference. The balloon size was listed as follows: group A (3.0-3.5 mm, n=15), group B (3.5-3.75 mm, n=64), and group C (3.75-4.5 mm, n=24)....

Background : HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis. / Methods and Results : In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n=22) or the non-prescribed group (control group, n=26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up....

Background : Abnormal left ventricular (LV) diastolic relaxation is an early sign of hypertensive heart disease. Whether diastolic dysfunction differs between LV geometric patterns remains controversial. / Methods and Results : We examined 220 hypertensive patients by echocardiography to assess the relationship between diastolic function and LV geometric pattern. We identified four LV geometric patterns: normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Diastolic function was evaluated by the E/A ratio, E wave deceleration time (Dct), and isovolumic relaxation time (IRT)....