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Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Patients or Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results (odds ratio [OR], 5.475; 95% confidence interval [CI], 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively). No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Early intervention to manage high blood pressure (BP) in young adulthood is a promising approach for the prevention of future cardiovascular diseases. We aimed to examine the ability of childhood health information to predict the incidence of young adults with high BP. This cohort study included baseline clinical data of Japanese individuals aged 12-13 years. A total of 1129 participants were followed up for an average of 8.6 years. We examined the association of childhood variables consisting of body weight, body mass index, systolic BP, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, uric acid, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the development of high BP defined as ≥120/80 mmHg at 18-22 years old. At follow-up, the prevalence of high BP was 42.2% in men and 7.7% in women. Young men with high BP had childhood baseline characteristics that included higher body weight, body mass index, systolic BP, red blood cell count, hemoglobin, hematocrit, and uric acid than normotensive men. Young women with high BP had higher body weight, systolic BP, and uric acid at baseline. Multivariable logistic regression analysis revealed that a model including body weight, systolic BP, hematocrit, and uric acid had the highest predictive power (AUC 0.65 [95% CI, 0.62-0.69]) for men, and a model including body weight, systolic BP, and uric acid had the highest predictive power (AUC 0.70 [95% CI, 0.58-0.81]) for women. Comprehensive childhood health information contributes to the prediction of high BP in young adults.

Background Coronary artery fistulas are rare and most commonly asymptomatic; however, they can become enlarged and rupture in some cases. Case summary We report a case of a 51-year-old woman who was brought to our hospital unconscious in an ambulance. Cardiac tamponade caused by the rupture of an aneurismal coronary-pulmonary artery fistula (CPAF) was detected by contrast-enhanced computed tomography and confirmed by invasive coronary angiography. Due to prompt diagnosis and subsequent surgical intervention, the patient’s condition was rapidly improved, and she was discharged from the hospital. Discussion Coronary-pulmonary artery fistula aneurysm rupture requires rapid diagnosis and treatment, and thus, in cases with cardiac tamponade and coronary aneurysm, CPAF aneurysm rupture should be considered.

Hypertension is the most common non-communicable disease among adults and is the most important modifiable risk factor for premature cardiovascular disease. The increasing worldwide burden of hypertension is a major global health issue. Early prevention with lifestyle modification or pharmaceutical treatment reduces the incidence of hypertension and the risk of subsequent cardiovascular disease. Therefore, identification of young persons at risk for hypertension has the obvious benefit of providing a chance for early intervention. Previous studies have demonstrated the positive association of elevated childhood blood pressure with hypertension in adulthood. Accumulated evidence also indicates the possibility that elevated pediatric blood pressure is associated with increased risk of future cardiovascular disease. In this article, we review the tracking of blood pressure from childhood to adulthood and emphasize the importance of pediatric blood pressure monitoring and control for predicting and preventing adult hypertension and cardiovascular disease.

Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated. In this study, we investigated the sex-specific effect of LBW on renal function. Annual cross-sectional data of 2417 Japanese adolescents (males 1736; females 681), aged 15–16 years, were evaluated over 8 years (2007–2014). Over the study period, mean birth weights decreased significantly in males (p

Hypertension is a global public health issue and the most important preventable cause of cardiovascular diseases. Despite the clinical availability of many antihypertensive drugs, many hypertensive patients have poor medication adherence and blood pressure control due, at least partially, to the asymptomatic and chronic characteristics of hypertension. Immunotherapeutic approaches have the potential to improve medication adherence in hypertension because they induce prolonged therapeutic effects and need a low frequency of administration. The first attempts to reduce blood pressure by using vaccines targeting the renin-angiotensin system were made more than half a century ago; however, at the time, a poor understanding of immunology and the mechanisms of hypertension and a lack of optimal vaccine technologies such as suitable antigen design, proper adjuvants, and effective antigen delivery systems meant that attempts to develop antihypertensive vaccines failed. Recent advances in immunology and vaccinology have provided potential therapeutic immunologic approaches to treat not only infectious diseases but also cancers and other noncommunicable diseases. One important biotechnology that has had a major impact on modern vaccinology is virus-like particle technology, which can efficiently deliver vaccine antigens without the need for artificial adjuvants. A human clinical trial that indicated the effectiveness and safety of a virus-like particle-based antiangiotensin II vaccine marked a turning point in the field of therapeutic antihypertensive vaccines. Here, we review the history of the development of immunotherapies for the treatment of hypertension and discuss the current perspectives in the field.

The Japanese hypertension guidelines report that essential hypertension is detected in 1–3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background and aims: Low birth weight is associated not only with poor birth outcome but also chronic health conditions such as hypertension in later life. B-type natriuretic peptide (BNP) is a prognostic factor of cardiovascular events in the general population. However, the association between birth weight and BNP remains unclear. Here, we examined the relationships among birth weight and risk factors for atherosclerosis, including BNP, in Japanese workers. Methods: A total of 1109 (517 male, 592 female; age 40–70 years) participants in an annual medical checkup were enrolled. Subjects were divided into three groups according to birth weight, and the associations between their birth weight and risk factors for atherosclerosis were examined by statistical analysis. Results: Jonckheere–Terpstra trend test according to birth weight category revealed that although birth weight was not correlated with BNP level, it was inversely associated with HbA1c in men and with diastolic blood pressure in women. Correlation coefficient tests for both categorical and continuous birth weight data confirmed the trend test findings. Multiple regression analysis indicated that birth weight was an explanatory factor for HbA1c in men and for diastolic blood pressure in women. Conclusions: Although no significant association was observed between birth weight and BNP, inverse associations between birth weight and HbA1c in men and diastolic blood pressure in women were found. These findings suggest that birth weight may partially predict future risk of cardiovascular events.

Clinical availability of anti-obesity drugs is limited, and their inadequate effectiveness and safety concerns sometimes discourage widespread use. A therapeutic vaccine has the potential to be an attractive tool for preventing and treating obesity, because of the possibility of prolonged therapeutic effect and low frequency of administration. Experimental investigations have shown that vaccines targeting endogenous molecules that promote obesity could be a viable alternative. Recent novelties in drug-delivery systems and biotechnology will support further progress in vaccine development. This chapter provides an overview of recent advances in the area.

Obesity prevalence continues to increase in both adults and children worldwide and greatly contributes to increased morbidity and mortality. Although there are some anti-obesity drugs globally available for clinical use, their inadequate effectiveness coupled with safety concerns sometimes discourage the widespread use of anti-obesity medication. Because of its prolonged therapeutic effect and low frequency of administration, a therapeutic vaccine may be an attractive strategy for the prevention and treatment of obesity. Over the last two decades, several attempts have been made to develop vaccines for the control of obesity. Animal studies have shown that vaccines targeting ghrelin, glucose-dependent insulinotropic polypeptide, adipocytes, somatostatin, and adenovirus 36 successfully led to a reduction in weight gain without serious adverse effects. This chapter provides an overview of recent progress toward a therapeutic vaccine against obesity.

Proteinuria is a central component of chronic kidney disease and an independent risk factor for cardiovascular disease. Kidney podocytes have an essential role as a filtration barrier against proteinuria. Kruppel-like Factor 4 (KLF4) is expressed in podocytes and decreased in glomerular diseases leading to methylation of the nephrin promoter, decreased nephrin expression and proteinuria. Treatment with an angiotensin receptor blocker (ARB) reduced methylation of the nephrin promoter in murine glomeruli of an adriamycin nephropathy model with recovery of KLF4 expression and a decrease in albuminuria. In podocyte-specific KLF4 knockout mice, the effect of ARB on albuminuria and the nephrin promoter methylation was attenuated. In cultured human podocytes, angiotensin II reduced KLF4 expression and caused methylation of the nephrin promoter with decreased nephrin expression. In patients, nephrin promoter methylation was increased in proteinuric kidney diseases with decreased KLF4 and nephrin expression. KLF4 expression in ARB-treated patients was higher in patients with than without ARB treatment. Thus, angiotensin II can modulate epigenetic regulation in podocytes and ARB inhibits these actions in part via KLF4 in proteinuric kidney diseases. This study provides a new concept that renin-angiotensin system blockade can exert therapeutic effects through epigenetic modulation of the kidney gene expression.

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Macro-reentrant ventricular tachycardias (VT) utilizing the bundle branches and Purkinje fibers have been reported as verapamil sensitive VT (idiopathic left VT), bundle branch reentrant VT (BBRT) and inter-fascicular reentrant tachycardia (inter-fascicular VT). However, diagnostic confusion exists with these VTs due to the difficulty in differentiating between them with conventional electrophysiological (EP) studies. The aim of this study was to clarify the EP and anatomical entity of inter-fascicular VT, and provide successful methods for the radio frequency catheter ablation (RFCA) of inter-fascicular VT. A total of nine patients were included in this study. All patients were diagnosed with idiopathic left VT in the first session, and underwent a second session after a failed RFCA. Detailed EP studies guided by a three-dimensional (3D) mapping system were performed to further analyze the VTs. All VTs were finally diagnosed as inter-fascicular VT. They were successfully cured with RFCA targeting the left anterior or posterior fascicle, which was regarded as a requisite part of the reentrant circuit of the inter-fascicular VT, using 3D and fluoroscopic images combined with a detailed EP investigation instead of the conventional RFCA method targeting Purkinje potentials for the RFCA of idiopathic left VT. Inter-fascicular VT could be misdiagnosed as idiopathic left VT due to the limitations of the conventional EP study. Failed RFCA in presumptive idiopathic left VT cases has to be carefully investigated by further analysis, and a tailored RFCA strategy targeting the requisite portions of the left fascicles in the inter-fascicular VT reentrant circuit will be required for the successful elimination of the inter-fascicular VT.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Previous studies have shown that renin-angiotensin (Ang) system vaccines may be effective for the treatment of hypertension, but their efficacy for the prevention of renal disease is unclear. The aim of this study was to compare the effects of an Ang II type 1 (AT1) receptor vaccine with an Ang II receptor blocker (ARB) and a vasodilator on blood pressure (BP) and renal injury in the L-NAME nephropathy model. Male spontaneously hypertensive rats (SHRs) were divided into six groups and treated transiently with three injections of vehicle or AT1 receptor vaccine (0.1 mg) at age 4, 6 and 8 weeks, or continuously with candesartan cilexetil (0.1 mg kg(-1) per day) or hydralazine hydrochloride (5 mg kg(-1) per day), then administered NG-nitro-L-arginine methyl ester (L-NAME) from age 18 to 21 weeks to induce renal injury. Vaccination against the AT1 receptor caused a significant increase in AT1 receptor titers, and a sustained decrease in BP. L-NAME treatment resulted in a marked increase in proteinuria in the control groups, which was completely suppressed in the AT1 vaccine-treated group, and glomerular injury scores were also significantly decreased. Real-time RT-PCR and immunofluorescence studies revealed increased renin mRNA, and increased glomerular expression of nephrin. Comparable results were seen in rats treated continuously with the ARB candesartan, but not with hydralazine. These results suggest that transient AT1 vaccination is as effective as continuous treatment with ARB, not only for the attenuation of hypertension, but also for the prevention of L-NAME-induced nephropathy in SHR.

Background Acute aortic dissection (AAD) is often missed on initial assessment. Purpose The aim of our study was to identify features associated with misdiagnosis of AAD. Methods and results We examined a total of 109 emergency room (ER) patients who were ultimately diagnosed with AAD. Misdiagnosis of AAD was defined as failure to diagnose AAD at the end of the initial assessment in the ER, and occurred in 17 patients (16%). The alternate diagnosis consisted of acute coronary syndrome (n = 10), other cardiovascular disease (n = 3), abdominal disease (n = 3), and cerebral infarction (n = 1). In the misdiagnosed patients, walk-in mode of admission to the ER (29% vs. 10%, p = 0.042) and anterior chest pain (71% vs. 41%, p = 0.025) were more frequent, and widened mediastinum (25% vs. 55%, p = 0.023) was less frequent than in diagnosed patients. The number of imaging studies performed per patient was also fewer in misdiagnosed patients than in diagnosed patients (0.82 ± 0.81 vs. 1.53 ± 0.52, p

We performed a systematic review of randomised controlled trials in order to identify the best available evidence to compare the outcome between cemented and uncemented hemiarthroplasty for treatment of intracapsular hip fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, MEDLINE and the National Research Register (UK) to retrieve all of the published randomised controlled trials designed to address these issues, in order to perform a meta-analysis. Eight studies involving 1169 patients were determined to be appropriate for meta-analysis. The following statistically significant differences were found between the cemented and uncemented prostheses: (1) longer operative time for cemented prosthesis; (2) lower reduction in mobility score for those treated with cemented prosthesis; (3) fewer patients with residual pain in the hip and lower pain score (signifying less pain) for those treated with a cemented prosthesis. Our meta-analysis has shown that there is good evidence that the use of cement during hemiarthroplasty will reduce the amount of residual hip pain and also allow better restoration of function. There is no evidence of significant adverse effects of cement on mortality or other complications encountered. These observations apply to older designs, and there is a need for randomised trials comparing hydroxyapatite-coated modern stems with cemented prostheses.

Background: Acute aortic dissection (AAD) often accompanies acute respiratory failure. The aim of this study was to clarify the relationship between the incidence of oxygenation impairment and the extent of distal type AAD. Methods and Results: A total of 49 patients with medically treated distal type AAD were retrospectively examined. AAD% was defined as the percentage of the volume of false lumen to that of aorta in the descending aorta. AAD% was measured by computed tomography. C-reactive protein (CRP) levels, white blood cell (WBC) counts, body temperature and arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio were measured serially. Oxygenation impairment was defined as a PaO2/FiO2 ratio ≤200. This occurred in 19 patients (39%). In patients with oxygenation impairment, AAD% (50.8±10.9% vs 28.0±11.9%, P

Back ground: Three-dimensional mapping systems such as the non-contact mapping system (EnSite) have been utilized for radiofrequency catheter ablation (RFCA) in cases with various kinds of arrhythmias. Methods: An EnSite system was utilized for RFCA in 12 patients with right-sided atrial tachycardia (AT). The patients were classified into two groups according to the focus of the AT in the right atrium (RA). The patients in whom the EnSite array was positioned near the focus of the AT were defined as group A, whereas those patients in whom the EnSite array was located less near the focus were defined as group B. RF energy was applied under the guidance of the mapping with the EnSite array. We investigated the relationship between the position of the EnSite array and the focus of the AT in terms of the mapping accuracy in both groups. Results: Even though the accuracy of the mapping of the breakout site and arrhythmia origin was comparable between groups A and B, the distance between the successful CA sites and the presumed AT focus according to the EnSite mapping was significantly shorter in group A than group B. Conclusions: As the location of the focus of the AT becomes closer to the proximal and distal ends of the ESB, the mapping accuracy deteriorates.

Background: Electrical isolation of pulmonary veins (PV) by radiofrequency (RF) ablation is often performed in patients with atrial fibrillation (AF). Current catheter technology usually requires the use of a multielectrode catheter for mapping in addition to the ablation catheter. Purpose: We evaluated the feasibility and safety of using a single, expandable electrode catheter (MESH) to map and to electrically isolate the PV. Methods and Results: Nineteen closed-chest mongrel dogs, weighing 23–35 kg, were studied under general anesthesia. Intracardiac echocardiography (ICE) was used to guide transseptal puncture and to assess PV dimensions and contact of the MESH with PV ostia. ICE and angiography of RSPV were obtained before and after ablation, and prior to sacrifice at 7–99 days. An 11.5 Fr steerable MESH was advanced and deployed at the ostium of the RSPV. Recordings were obtained via the 36 electrodes comprising the MESH. For circumferential ablation, RF current was delivered at a target temperature of 62–65°C (4 thermocouples) and maximum power of 70–100 W for 180 to 300 seconds. Each animal received 1–4 RF applications. Entrance conduction block was obtained in 13/19 treated RSPVs. Pathological examination confirmed circumferential and transmural lesions in 13 of 19 RSPV. LA mural thrombus was present in 3 animals. There was no significant PV stenosis. Conclusion: Based on this canine model, a new expandable MESH catheter may safely be used for mapping and for PV antrum isolation. This approach may decrease procedure time without compromising success rate in patients undergoing AF ablation.

The objectives of this study were to identify the position where optimal leg muscle force occurs and to analyze the lower extremity muscle activity by comparing different hip and knee joint angle positions using a newly developed closed kinetic chain (CKC) leg press exercise device. Muscle force and electromyogram (EMG) measurements during maximum voluntary isometric leg presses (MVC-CKC) were performed on 6 healthy women in 6 different knee flexion angles (15°, 30°, 45°, 60°, 75°, 90°) and 2 different postures (supine and trunk upright posture). Results showed that the muscle force of MVC-CKC reached its peak at 60° knee flexion angle in both postures. Significant knee angle-dependent differences in EMG activity for both rectus femoris and gastrocnemius muscles were observed, while posture-dependent differences in EMG were found in biceps femoris. These particular joint-dependent EMG activities may be explained by the architectural characteristics of bi-articular muscles and muscle length-tension relationship theory. Co-activation of an antagonist muscle may appear with activation of the gastrocnemius muscle when the knee approaches full extension. Consequently, measurement of isometric CKC leg extension muscle force at 60° knee flexion angle in the trunk upright posture seems to be the optimal position.

Coronary heart disease (CHD) is recognized as a lifestyle-related disease and is the second leading cause of death in Japan. However, the cardiac risk factor profile of young patients with CHD has not been clarified in suburban areas of Japan. Our study aimed to determine metabolic and lifestyle risk factors in young patients and compare them with older patients living in suburban areas of Nagano Prefecture. A multicenter study was conducted in 86 young (aged less than 40 years) and 91 older (aged 50 years and over) patients diagnosed with CHD from 1992 to 2002. There was a strong association between obesity and the occurrence of CHD events in young patients (odds ratio = 3.61, P = 0.006). Lifestyle in the young patients was characterized by a lack of physical activity and regular physical activity was found to decrease the risk of the CHD events in these patients (odds ratio = 0.31, P = 0.030). In older patients, hypertension was identified as an independent risk factor for CHD events. The results of the present study have demonstrated that obesity and a lack of regular physical exercise are independent risk factors for CHD events in younger patients. Thus, the data may be useful for the effective screening of high-risk individuals and the development of educational programs for the prevention of CHD, especially in younger Japanese.

Spatial Resolution of Mapping. Background: The purpose of this study was to compare the spatial resolution of activation mapping and pacemapping in patients undergoing ablation of idiopathic ventricular tachycardia (VT) arising from the right ventricular outflow tract (RVOT). A direct comparison of the two techniques has not been undertaken. Methods and Results: Electroanatomical activation maps of the RVOT were obtained during VT in 15 patients. Pacemaps were obtained from multiple sites, tagged on the activation map, and scored according the degree of concordance between the paced QRS configuration and that of VT. The site of successful ablation was considered the VT site of origin. Initial endocardial activation away from the site of origin was rapid; the mean area of myocardium activated within the first 10 msec (early activation area, EAA) was 3.0 ′ 1.6 cm 2 (range: 1.3-6.4 cm 2 ). Best pacemap scores were always obtained adjacent to the site of origin. Pacemap concordance, and the probability of an exact pacemap match significantly decreased with increasing distance of the pacing site from the site of origin (P < 0.01). All patients had more than one pacing site yielding a best pacemap score. The greatest distance between such sites in an individual patient ranged from 11 to 26 mm (mean: 18 ′ 5 mm), and was strongly correlated with the size of the EAA (r = 0.77, P < 0.001). Conclusions: Pacemapping and activation mapping provide similar localizing information. The spatial resolution of each technique is modest, varies between patients, and may be optimized by three-dimensional data display.

Background The aim of the present multicenter study was to investigate whether there is a seasonal difference in the onset of coronary heart disease (CHD) in young patients compared with older patients living in Nagano Prefecture, Japan. Methods and Results The study group comprised 101 young (aged ≤40 years) and 94 older (aged ≥50 years) patients diagnosed with CHD from 1992 to 2002. In young patients, the prevalence of the onset of CHD events was significantly higher from June to September than from December to March (odds ratio =2.23, p=0.035). Obesity was found in 56%, hypertension in 29%, dyslipidemia in 54%, diabetes in 24%, smoking history in 82%, and habitual physical activity in 13% in young patients. There was a trend for an association between the presence of acute myocardial infarction (p=0.082) and history of smoking and the onset of CHD events during the summer months in young patients (p=0.077). Conclusions There is a seasonal difference in the onset of CHD events, with an increase in the prevalence during the summer months in young patients. The data may provide insights into preventive approaches to CHD in the young population. (Circ J 2005; 69: 1176 - 1179)

Electrical Remodeling and Paroxysmal AF. Introduction: Rapid atrial pacing alters atrial electrophysiology, promoting initiation and maintenance of atrial fibrillation (AF). The aim of this study was to assess differencesin the electrophysiologic properties of atrial tissue between patients with and without AF episodes and to determine whether electrophysiologic properties can predict the clinical efficacy of antiarrhythmic agents. Methods and Results: Sixty patients were studied, 33 with documented episodes of paroxysmal atrial fibrillation (PAF) and 27 control patients. Atrial effective refractory period (AERP), atrial vulnerability, and intra-atrial conduction time were measured at baseline and after rapid constant atrial pacing for 5 minutes at rates of 130, 150,170, and 190 beats/min. The clinical efficacy of antiarrhythmic agents for PAF prophylaxis was assessed over 14 months with an antiarrhythmic agent identical to that administered intravenously, and the antiarrhythmic agent effects on AERP, atrial vulnerability, and intra-atrial conduction time were assessed. AERP shortening and atrial vulnerability increase were significantly larger in the PAF group. Antiarrhythmic agents that were clinically effective in suppressing PAF significantly attenuated AERP shortening, but antiarrhythmic agents that were clinically ineffective did not. Conclusion: Changes in AERP and atrial vulnerability observed after rapid atrial pacing are considered indicative of the electrophysiologic substrate of PAF. Attenuation of AERP and atrial vulnerability by antiarrhythmic agents might be useful in predicting their clinical efficacy.

The effects of the type V phosphodiesterase (PDE V) inhibitors, MBCQ, zaprinast and dipyridamole, on the relationship between relaxation and cyclic nucleotide content were investigated in rat ileal smooth muscle. Each of MBCQ (0.01-10 microM), zaprinast (0.1-100 microM) and dipyridamole (0.1-100 microM) inhibited carbachol (CCh; 10 microM)-induced contractions in a concentration-dependent manner. When compared with the concentrations of these agents producing 50% relaxation (IC50) of CCh-induced contraction, MBCQ was 14-20 fold more potent than the other agents. The inhibitory potency of these agents against high K+ (65 mM KCl)-induced contractions were similar to that for CCh. MBCQ (1, 10 microM) did not significantly increase the cGMP content above control levels in the presence of CCh (10 microM). Both Zaprinast (1-100 microM) and dipyridamole (1-100 microM) increased the cGMP content of smooth muscle preparations in a concentration-dependent manner. There was a positive correlation between the inhibition of the CCh-induced contraction and the increase in cGMP content elicited by zaprinast and dipyridamole (zaprinast; r=0.72, P0.05, dipyridamole; r=0.92, P0.05). However, MBCQ at a concentration which induced a medium-sized relaxation did not significantly increase the cGMP content. Neither MBCQ, zaprinast nor dipyridamole significantly increased the cAMP content of the preparations above control. In summary, it is suggested that the inhibition of CCh-induced contractions by zaprinast and dipyridamole involves increases in cGMP content via inhibition of PDE V. However the inhibition of CCh-induced contraction by MBCQ may not involve cyclic nucleotides in rat ileal smooth muscle.

The role of salt intake in the development of hypertension is prominent, but its mechanism has not been fully elucidated. Our aim was to examine the effect of transient salt intake during the prehypertensive period in hypertensive model animals. Dahl salt-sensitive rats and spontaneously hypertensive rats were fed from 6 to 14 weeks with low-salt (0.12% NaCl), normal-salt (0.8% NaCl), high-salt (7% NaCl), or high-sodium/normal-chloride diet and returned to normal-salt diet for 3 months. Rats in the high-salt group saw elevations in blood pressure (BP) not only during the treatment period but also for the 3 months after returning to normal-salt diet. We named this phenomenon salt memory. Renal arteriolar injury was found in the high-salt group at the end of experiment. Dahl salt-sensitive rats were fed from 6 to 14 weeks with high-salt diet with angiotensin receptor blocker, vasodilator, calcium channel blocker, and calcium channel blocker+angiotensin receptor blocker and returned to normal-salt diet. Although BP was suppressed to control levels by vasodilator or calcium channel blocker, elevated renal angiotensin II and renal arteriolar injury were observed, and salt memory did not disappear because of sustained renal arteriolar injury. Calcium channel blocker+angiotensin receptor blocker suppressed renal arteriolar injury, resulting in the disappearance of salt memory. Cross-transplantation of kidneys from Dahl salt-sensitive rats on high salt to control rats caused increase of BP, whereas control kidneys caused reduction in BP of hypertensive rats, inducing the central role of the kidney. These results suggest that renal arteriolar injury through BP and renal angiotensin II elevation plays important roles in the development of salt memory for hypertension.

心尖部肥大型心筋症 (AHCM) は通常予後良好とされているが, 当施設で最近10年間に経験したAHCM31例中2例に重症心室性不整脈が合併し“aborted sudden death”をきたした例や失神例が見られ, 植え込み型除細動器およびアミオダロン治療を必要とした.重症心室性不整脈合併例と非合併例にて, 加算平均心電図検査, 運動負荷検査, ホルター心電図検査, 123-I-MIBG心筋シンチグラムを施行した結果, 合併例においてMIBG心筋シンチグラム検査で左室広範囲に有意なtraoer uptakeの低下が見られたが, それ以外の検査では両者間に有意な相違点は見られなかった.また, 他の2例において頻脈性心房細動による重症心不全をきたしたため長期入院加療を要した.AHCM例は概ね予後良好であるが, まれに予後不良例もみられるため, 通常の肥大型心筋症と同様の注意深い対応が必要であると考えられる.

A review of the literature on the mechanical aspects of the etiology for idiopathic scoliosis reveals that the buckling hypothesis has been presented as a purely mechanical phenomenon. In an attempt to confirm the buckling hypothesis, a numerical simulation of growth and the resulting buckling phenomena was done by means of finite element analysis. It previously was observed that growth was induced in the T4 to T10 vertebrae. Only the sacrum was assumed to be stationary. From the growth analysis, a deformation process that mitigated thoracic kyphosis was obtained as observed in healthy children during early adolescence. From the buckling analysis, the first to the fourth buckling modes that correspond to the first side bending, first forward bending, first rotation, and second side bending modes were obtained. The shape of the fourth buckling mode (second side bending mode) was in good agreement with the clinical shape. Considering the potential for controlling these modes by posture change, it is concluded that the second bending mode in the coronal plane is one of the most likely etiologic candidates in the mechanics of thoracic idiopathic scoliosis.

通常型房室結節回帰頻拍 (AVNRT) 55例と稀有型18例, 計73例において, 遅伝導路の心房挿入部位に高周波通電を施行した.その時, ヒス束領域, 冠状静脈洞領域及び, アブレーション部位の電位を高周波ノイズフィルターを用いて記録し分析した.房室接合部の異所性調律 (ER) は, ヒス東電位が他の心房電位に先行するType1 ERと, アブレーション部位の心房電位がヒス束やその他の心房電位に先行するType 2 ERとに分類された.Type 1 ERはType2ERに比してその接続時間が長かった.Type 1 ERは通常型AVNRT全例でみられ, 遅伝導路アブレーションの成功指標である.また, このことは房室結節領域の後方部とCompaot AV nodeとの間に, 周囲より電気的に絶縁された伝導路が存在し, 高周波通電による傷害電流が, この部位を選択的に流れ, 房室結節ないしヒス束の自動能を亢進させることを示唆した.

A 41-year-old female had pheochromocytoma which secreted adrenocorticotropic hormone (ACTH). She was admitted to our hospital because of weight loss and excessive sweating. Not only urinary metanephrine but also plasma ACTH was extremely high. An abdominal echogram showed a cystic tumor in the left adrenal gland. An abdominal magnetic resonance imaging scan showed a hyperintense T2-weighted abnormality inside the tumor. Left adrenalectomy was done. The tumor consisted of benign pheochromocytoma cells diffusely stained with anti-ACTH antibody. The present case did not show any typical Cushingoid symptoms which are common in ACTH-secreting pheochromocytomas.

房室結節回帰頻拍 (AVNRT) におけるslow pathway (sp) の選択的焼灼時に高頻度に出現する房室接合部調律 (AVJR) に対し, 通電中にsignal separatorを用い, AVJRの起源とその出現頻度を通常型 (31名) と稀有型 (13名) について比較検討した.AVJRの出現頻度は通常型で100%稀有型で76%であった.また, AVJRには (1) : ヒス東電位が先行するtype (His rhythm) , (2) : ヒス束電位よりアブレーション電極でのA波が先行するtype (Ablation site rhythm) (3) : (1) と (2) とが混在するtypeとが観察され, (1) の出現頻度は通常型で (84%) 稀有型 (46%) , (2) は通常型で (0%) 稀有型 (30%) , (3) は通常型で (16%) 稀有型 (0%) であり, His rhythmは通常型において100%にみられ, 稀有型で46%であった.また, 焼灼部位からヒス束電極先端までの距離は通常型で15.8mm-39.6mm (25.6±5.8mm) 稀有型で13.2mm-38.5mm (26.7±7.5mm) であり, 両者に有意差はみられなかった.type (1) のAVJRの出現は, 房室結節後方部に周囲の心房筋から絶縁された特殊刺激伝導系が存在し, 高周波加熱によって生じた興奮波または傷害電流がoompaot AVnodeに伝導するために生ずると考えられた.またこの出現頻度に通常型と稀有型で差があるのは, アブレーション法の違いに加えて, SPの順向性不応期が稀有型で長いためと考えられた.

Recent studies have suggested that the attenuation of the local electrogram amplitude recorded from the ablation electrode during radiofrequency (RF) application predicts lesion growth. This study examined the time course of local electrogram amplitude during ongoing RF delivery in patients with common atrial flutter (AFl). In 71 patients with AFl. RF energy was applied to the anatomical isthmus. Termination of AFl was noted during 68 of 625 applications of RF energy. The changes in local atrial electrogram amplitude observed at all successful sites were analyzed. With increasing duration of the RF delivery, the electrogram amplitude decreased exponentially to reach a steady state within a mean duration of 17+/-3 sec, which was significantly longer than that of the steady-state temperature. The average decrease in the amplitude was 67+/-13%. In 16 patients in whom an increase in the power of RF energy had resulted in AFl termination, there was a dose-response relationship between the power and the amplitude decrease. The decrease in local electrogram amplitude appears to be a reliable marker for the efficacy of tissue heating and may be useful as an endpoint for individual applications. Local electrogram monitoring may offer an optimal energy strategy in AFl ablation.

Slow AV nodal pathway ablation using RF is highly effective for patients with refractory AV nodal reentrant tachycardia (AVNRT). We report three catheter ablation cases using RF current in patients associated with persistent left superior vena cava (PLSVC). Three patients with drug refractory AVNRT of common variety were involved in this study. An electrode catheter introduced through the left subclavian vein inserted directly into the coronary sinus, a typical anatomical finding of PLSVC. The ablation procedure was initially performed at the posteroinferior region of Koch's triangle. A slow pathway potential could not be found from that area; nonsustained junctional tachycardia (NSJT) did not occur during the delivery of RF current; there was failure to eliminate slow AV nodal pathway conduction. The catheter then was moved into the bed of the proximal portion of the markedly enlarged coronary sinus. A slow AV nodal pathway potential was recorded through the ablation catheter, and the delivery of RF current caused NSJT in two patients. Complete elimination of slow AV nodal pathway conduction was accomplished in these two patients by this method. No adverse effects were provoked by this procedure. Catheter ablation of the slow AV nodal pathway guided by a slow pathway potential and the appearance of NSJT was feasible and safe in the area of the coronary sinus ostium in patients associated with PLSVC.

We performed radiofrequency catheter ablation in five patients associated with Ebstein's anomaly to cure their refractory tachyarrhythmias. The presenting arrhythmias were four cases of orthodromic circus movement tachycardia using accessory pathways as a requisite limb, including one case of a Mahaim fiber and one of atrial flutter of common variety. All accessory pathways, including the Mahaim fiber, were ablated by RF energy delivered through the catheter placed at the AV annulus rather than the displaced anatomical AV groove. Interestingly, the antegrade or retrograde conduction interval over these accessory pathways was relatively longer than that of usual accessory pathways, and the accessory pathway potential was fractionated in some cases. The location of the atrioventricular node was displaced from the usual position to the postero-inferior area of Koch's triangle in one case. The configuration of the flutter wave was larger than usual in height as well as in width. All tachyarrhythmias were cured by RF catheter ablation. In the case of RF catheter ablation for patients with Ebstein's anomaly, close attention is indispensable in order to accomplish it safely and successfully, because of the anatomical and functional differences peculiar to Ebstein's anomaly.

Ischemic preconditioning (IP) は虚血による心筋障害に対する防御機構のひとつと考えられる現象であるが, IPの電気生理的作用について検討するため, 心室筋の再分極過程のばらつきを反映し, 電気的不安定性を表わすとされているQT間隔dispersion (QTd) の経皮的冠動脈形成術 (PTCA) 中の変化を解析した.結果はballoon inflation (BI) , deflation (BD) を繰り返す度にQTdは有意に縮小した (P

The term developmental dysplasia of the hip (DDH) describes a spectrum of disorders that results in abnormal development of the hip joint. If not treated successfully in childhood, these patients may go on to develop hip symptoms and/or secondary osteoarthritis in adulthood. In this review we describe the altered anatomy encountered in adults with DDH along with the management options, and the challenges associated with hip arthroscopy, osteotomies and arthroplasty for the treatment of DDH in young adults. Cite this article: Bone Joint J 2013;95-B:732–7.

Objectives. The aim of this study was to examine the effect of ischemic preconditioning on the manner of ventricular repolarization by assessing the change in QT dispersion during coronary angioplasty. Background. QT interval dispersion regional variations in ventricular repolarization and cardiac electrical instability. Previous studies have suggested that increased QT dispersion is associated with an increased incidence of malignant ventricular arrhythmias, whereas brief episodes of myocardial ischemia can render the heart more resistant to subsequent ischemic episodes, a phenomenon called ischemic preconditioning. Methods. To assess the effects of ischemic preconditioning on myocardial repolarization by examining the change in QT dispersion during coronary angioplasty, we studied 47 consecutive patients (39 men and 8 women; mean age 57 ± 16 years). QT dispersion was measured after each balloon inflation during coronary angioplasty. Statistical analysis was performed by using repeated measurement of analysis of variance. Results. There were significant differences in QT dispersion as the number of balloon inflations increased (mean ± SD 52 ± 14, 42 ± 11, 36 ± 9, 31 ± 10 and 29 ± 11 ms, respectively [p < 0.01], for the first, second, third, fourth and fifth balloon inflations). The magnitude of decrease in QT dispersion was significant in the first and second balloon inflations, then became insignificant with later inflations. Conclusions. These data indicate that the gradual decrease in OT dispersion provoked by coronary artery occlusion and reperfusion during coronary angioplasty may be associated with electrophysiologic effects of ischemic preconditioning on myocardium in the human heart.

A 62-year-old male patient presented to the hospital with sustained fever and refractory skin ulcers. He had been under haemodialysis for 11 years and had received anti-coagulation therapy via warfarin following the artificial valve replacement surgery for 4 years. From his painful skin ulcers and necrotizing skin nodules with surrounding purpura over a wide range of the inferior limb, perineum, penis and breech and penile gangrene (Figure 1), calciphylaxis was diagnosed by a criteria proposed by the Japanese Calciphylaxis Study Group [1]. On admission, the white blood cell counts were 19.0 × 109 /L and the C-reactive protein level was 160 mg/L. Skin culture revealed isolation of methicillin-resistant Staphylococcus aureus, while standard culturing of blood had never resulted in the isolation of any microorganisms. Administration of antibiotics was started and warfarin was replaced with continuous infusion of heparin, because warfarin is considered a risk factor for the aggravation of calciphylaxis [2]. Since prosthetic valves can be a focus for infectious endocarditis, transthoracic echocardiography was performed and verrucous vegetation on the mitral valve was detected (Figure 2a). Culture-negative infectious endocarditis was clinically diagnosed. Administration of 0.5 g of vancomycin and 80 mg of gentamicin was started. However, the infection was still uncontrolled and he died of septic shock 13 days after admission. Autopsy revealed a thrombus in the mitral valve with leukocyte infiltration consistent with the diagnosis of infectious endocarditis (Figure 2b). In the skin lesions, calcified arterial media with concentric intimal hypertrophy, the typical pathology of calciphylaxis, were detected throughout the body (Figure 3). Although infection is the main cause of morbidity and mortality for patients with calciphylaxis [3], superinfection in calciphylaxis with endocarditis is very rare. Only one case is reported in English-language literature [4]. This report stresses the need for exploring superinfection in the patient with calciphylaxis, including infectious endocarditis. Fig. 1. Skin lesions of right inferior limb (a), breech (b) and penis (c). Fig. 2. Vegetation and thrombus in the patient's heart. Dotted circles represented the lesions in echocardiogram (a) and autopsy (b). Fig. 3. Microscopic findings of vascular lesions of calciphylaxis. H–E staining showed media with concentric intimal hypertrophy. (a) EVG staining also showed the same findings. (b) Von Kossa staining showed the accumulation of calcium in the vessel wall ...

Four kinds of polymer materials (polyurethane sheet, polyurethane beads, polysulfone powder, and polysulfone beads) were implanted into the subcutaneous tissue of F-344 male rats for 104 weeks. Subcutaneous tumors developed in 6 out of 20 rats with implanted polyurethane sheets. In the group with implanted polyurethane beads, 2 out of 20 rats also developed a subcutaneous tumor. All of these tumors were histologically diagnosed as malignant fibrous histiocytoma (MFH). No tumors were noted in the groups with implanted polysulfone powder or polysulfone beads. For investigation of early cellular reactions to implanted materials during foreign body carcinogenesis, polyurethane sheets were implanted into the subcutaneous tissue of F-344 male rats, and the implanted sites were examined by light and electron microscope at 2, 4, 8, and 12 weeks after implantation. Uptake of bromodeoxyuridine (BrdU) or 3H-thymidine was also studied with enzyme histochemistry or electron microscopic autoradiography. By 8 weeks after implantation, focal proliferation of atypical cells was observed in the subcutis adjacent to the polymer sheet. These atypical cells showed a high labeling index for BrdU as well as 3H-thymidine. These results indicate that atypical cell foci play the most important role as lesions in foreign body tumorigenesis.