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Detecting high-risk patients for early rehospitalization is crucial in heart failure patient care. An association of albuminuria with cardiovascular events is well known. However, its predictive impact on rehospitalization for acute decompensated heart failure (ADHF) remains unknown. In this study, 190 consecutive patients admitted due to ADHF between 2017 and April 2019 who underwent urinalysis were enrolled. Among them, 140 patients from whom urine albumin-to-creatinine ratio (UACR) was measured with spot urine samples on admission were further analyzed. The association between UACR and rehospitalization due to HF during 1 year after discharge was evaluated. The mean age of 140 participants was 77.6 years and 55% were men. Only 18% (n = 25) of patients presented with normoalbuminuria (UACR 30 mg/g∙creatinine), whereas 59% (n = 83) and 23% (n = 32) showed microalbuminuria (UACR 30-300 mg/g·creatinine) and macroalbuminuria (UACR 300 mg/g·creatinine), respectively. The level of UACR on admission was correlated with the risk of subsequent rehospitalization due to HF (p = 0.017). The receiver operating characteristic analysis indicated that the best cut-off values for the UACR and B-type natriuretic peptide (BNP) levels to predict ADHF rehospitalization were 50 mg/g·creatinine and 824 pg/ml, respectively. When the patients were divided into four groups using both cut-off values, the individual predictive impacts of UACR and BNP on rehospitalization were comparable. Patients with both elevated UACR and BNP levels had a higher rate of HF rehospitalization than those with elevated BNP levels alone (p 0.05). The combination of both values enabled more accurate prediction of HF rehospitalization than BNP levels alone. In conclusion, UACR could be a new useful biomarker to predict HF rehospitalization in patients with ADHF, especially in combination with the levels of BNP, and should be further evaluated in a prospective study.

Introduction: As Chimeric Antigen Receptor T cell (CAR-T) therapy gains its clinical advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it often accompanies cardiac dysfunction. Previous retrospective studies indicated the involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but their association is not fully investigated. Therefore, we designed a prospective study to clarify the association between the grade of CRS and cardiac dysfunction in the DLBCL patients after CAR-T therapy. Methods: In this prospective study, 14 DLBCL patients who underwent CAR-T therapy from July 2020 to May 2021 were enrolled. Before and after CAR-T therapy, we collected the levels of troponin T (TnT) as a marker for myocardial damage, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) as markers for systolic function, and E/e’ and left atrial volume index (LAVI) as markers for diastolic function. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely the low-CRS Group (CRS Results: Average age was 56.4 years and 7 patients (50%) were female. The number of patients in the low-CRS and high-CRS Group were 11 and 3, respectively. Before CAR-T therapy, there were no differences in cardiac function between the two groups. From the hyper-early phase of CAR-T therapy, the increase of TnT, E/e’ and LAVI from the baseline were significantly larger in the high-CRS Group compared to the low-CRS Group (P=0.023, 0.039, and 0.024, respectively). Subsequently, the decrease of GLS from the baseline became significantly larger in the high-CRS Group compared to the low-CRS Group (P=0.049). These results indicated that cardiac dysfunction after CAR-T therapy occurred in the order of myocardial damage, diastolic dysfunction, and systolic dysfunction. Conclusion: We for the first time demonstrated the association between high-grade CRS and cardiac dysfunction after CAR-T therapy through a prospective study.

Mid-diastolic forward flow velocity of transmitral flow (L wave) is known as a marker of diastolic dysfunction and is occasionally observed in patients with fluid retention, low heart rate, and atrial fibrillation (AF). However, how hemodynamic condition affects L wave is still unknown. An 81-year-old woman who underwent implantation of a DDD pacemaker due to complete atrioventricular block 38 years previously suffered from congestive heart failure and was admitted to our hospital. At the time of admission, electrocardiogram showed new-onset AF resulting in mode switch to VVI, and echocardiography showed a giant L wave. At the mid-term of the treatment, AF was converted to sinus rhythm resulting in mode switch to DDD, and pacemaker check-up was performed at pre- and post-cardioversion. During the pacemaker check-ups, L wave was assessed in various pacing rates. As pacing rate was increased, L wave altered according to heart rates and disappeared at 85 bpm in VVI with AF, whereas at 75 bpm in DDD. Through the treatment, L wave got smaller as fluid retention was improved and finally disappeared at the time of discharge. This case suggests that L wave is highly variable and affected by fluid volume, heart rate, and heart rhythm.

Left ventricular ejection fraction (LVEF) is critical for determining the prognosis and treatment of patients with heart failure (HF). However, the influence of serial LVEF changes in patients with stable chronic HF (CHF) has not yet been completely investigated. We analyzed data of 263 outpatients with CHF from the J-MELODIC study cohort and evaluated the frequency of cardiac events. We stratified patients into tertiles based on the relative difference in LVEF in 1 year and that at baseline. We found a significant difference in the cardiac event rate among the three groups (log-rank test, p = 0.042). We identified a relative 11% LVEF reduction as the optimal cutoff value based on the receiver operating characteristics analysis. LVEF (OR, 1.04; 95% CI, 1.01–1.07; p = 0.015) and E/e′ (OR, 1.06; 95% CI, 1.01–1.12; p = 0.023) at baseline were predictors of >11% LVEF reduction. After adjusting the variables including age and sex, >11% LVEF reduction was an independent predictor of subsequent cardiac events (HR, 5.79; 95% CI, 2.49–13.2; p 11% LVEF reduction may have subsequent worsening outcomes. Such patients should be carefully followed-up as high risk population for development of cardiac events.

Background Weight loss is a strong prognostic factor in chronic heart failure (CHF); however, little is known about its effects in patients with mild CHF. Therefore, we investigated the effects of weight loss in patients with mild CHF. Methods and Results We analyzed a total of 242 outpatients with mild CHF from the J-MELODIC study cohort. Weight loss was defined as ≥5% weight loss in 1 year. Twenty-seven patients (11.2%) lost ≥5% weight in 1 year. Weight loss was associated with higher rates of underweight and worsening renal function in 1 year compared with the absence of ≥5% weight loss. The predictors of weight loss included edema, B-type natriuretic peptide, and diabetes mellitus at baseline. Although weight loss was significantly associated with subsequent cardiovascular death or hospitalization for HF (log-rank P = .002) and subsequent death from any cause (log-rank P = .002), underweight was not associated with these outcomes (log-rank P = .356 and P = .168, respectively). Even after adjusting for covariates, weight loss was a significant and independent risk factor for subsequent cardiovascular death or hospitalization for HF (hazard ratio 3.22, 95% confidence interval 1.10–8.41; P = .034). Conclusions In patients with mild CHF, ≥5% weight loss was a significant predictor for subsequent cardiovascular death or hospitalization for HF.

Background Qing-Dai (QD) treatment of patients with ulcerative colitis (UC) sometimes causes pulmonary arterial hypertension (PAH). However, the relationship of QD treatment to pulmonary arterial systolic pressure (PASP) in patients with UC has not been clarified.Methods and Results:The 27 patients with UC who were screened for PAH by transthoracic echocardiography (TTE) and underwent repeat TTE at 1 year were analyzed in this prospective observational study. Mean age was 44.0 years old, and median follow-up duration was 392. During the follow-up, 21 patients continued QD treatment (continuous group) and 6 patients discontinued the treatment (discontinuous group). In all patients, no significant difference in PASP levels between baseline and at follow-up was observed (21.4 vs. 21.3 mmHg, P=0.802). Furthermore, the mean PASP of patients in the continuous group did not differ from baseline to follow-up (21.4 mmHg to 22.6 mmHg, P=0.212); however, in the discontinuous group mean PASP was significantly decreased (21.5 mmHg to 16.8 mmHg, P=0.005). Moreover, changes in PASP from baseline to follow-up differed between the continuous and discontinuous groups (+1.1 mmHg vs. -4.7 mmHg, P=0.004). In addition, multivariable analyses revealed that only the duration of oral QD at baseline affected the increase of PASP. Conclusions In patients with UC, QD treatment may have an undesirable association with an increase in PASP.

Transverse aortic constriction (TAC) has been widely used to create pressure overload induced heart failure in mice. However, this conventional model has some limitations such as low reproducibility and long creation period of cardiac failure. In order to establish a highly reproducible cardiac failure model that mimics adverse cardiac remodeling (ACR) we combined pressure overload and beta-adrenergic receptor stimuli using isoproterenol (ISO) and explored the optimal TAC model by changing the durations of TAC and the doses of ISO. Thus we constructed a suitable model for ACR with an effective combination of 3-week TAC and subsequent one-week ISO (3 mg/kg/day) infusion. Using RNA-Seq analyses, we identified that the up-regulated genes were mainly related to fibrosis including Fbn1, C1qtnf6 and Loxl2; and that the down-regulated genes were associated with mitochondrial function including Uqcrc1, Ndufs3, and Idh2 in failing hearts of our ACR model. Next, we followed the changes in cardiac function after ceasing ISO infusion. Left ventricular function gradually recovered after cessation of ISO, suggesting cardiac reverse remodeling (CRR). Gene expression signatures of hearts, which exhibited CRR, were almost identical to that of TAC hearts without ISO. In conclusion, our new model exhibits a transition to ACR and subsequent CRR with high reproducibility. This murine model might add new insights into the experiments of heart failure technically as well as scientifically.

Background Systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) had poor survival rate. Usual index of estimating PH is tricuspid regurgitate jet pressure gradient (TRPG). Accurate assessment of PAH is important for the management of SSc patients. However, estimated mean pulmonary arterial pressure (mPAP) using TRPG by echocardiography does not always reflect actual mPAP by right heart catheterization (RHC) in SSc patients. On the other hand, recent reports have shown that rPA, a ratio of diameter of pulmonary artery to ascending aorta (PA/Ao) calculated by computed tomography (CT), was associated with mPAP. However, both index are not sufficient for evaluation of PH. We hypothesized that the product of TRPG and rPA (pPAT) could estimate mPAP of SSc patients more accurately than TRPG or rPA. Purpose We investigated the usefulness of the product of TRPG and rPA for detecting actual mPAP in SSc patients. Methods Thirty-six SSc patients who suspected PH were enrolled retrospectively. We defined PH as resting mPAP from RHC of >25 mmHg. We measured both a widest pulmonary artery diameter and an adjacent ascending aorta diameter at the same level of the bifurcation of the main pulmonary artery using CT images. Results The average age was 67 years old and average mPAP by RHC was 24.7 mmHg. Mean TRPG and mean rPA were 35.1 mmHg and 1.06, respectively. Furthermore, mean pPAT was 37.9. We found pPAT had a stronger correlation with actual mPAP (r=0.848, p Figure 1 Conclusion The product of TRPG and PA/Ao (pPAT) could be a novel and useful noninvasive index for identifying PH in SSc patients.

Background The purpose of this study is to analyze the impact of average contact force (CF) and its regional variability during pulmonary vein isolation (PVI) for atrial fibrillation (AF) on periprocedural parameters and midterm outcome. Methods This retrospective cohort study enrolled 57 drug-refractory AF patients who underwent initial PVI for AF using an open-irrigated CF catheter (SmartTouch Thermocool, Biosense Webster, Diamond Bar, CA, USA). Thirty patients were assigned to a lower CF (LCF) group (average CF ≤ 10 g) and 27 patients to a higher CF (HCF) group (average CF > 10 g). The relationship between CF and clinical outcome was analyzed. Results Patients were followed-up for 317 ± 57 days after PVI. The CF was 8.1 ± 1.3 g in the LCF group and 12.4 ± 1.5 g in the HCF group. Higher average CF was associated with shorter ablation time (28 ± 6 min vs. 36 ± 9 min, p = 0.0002) and lower radiofrequency energy delivery (79 ± 18 vs. 99 ± 26, p = 0.0016) for PVI. The rate of acute PV reconnection (APVR) was similar in both groups (LCF group 60% vs. HCF group 44%, p = 0.36). Four patients (13%) in the LCF group and nine patients (33%) in the HCF group experienced AF-recurrence. Average CF did not impact on AF-recurrence during midterm clinical outcome ( p = 0.09 by log-rank test). In the non-recurrence group ( n = 44), average CF was higher at left posterosuperior PV and right anteroinferior PV than that in the recurrence group ( n = 13) ( p = 0.012 and p = 0.004, respectively). Conclusions Higher average CF decreased ablation time and radiofrequency energy delivery for PVI, but did not decrease APVR rate or improve midterm clinical outcome.

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

Background: Brain natriuretic peptide (BNP) is routinely measured for evaluating the severity of acute decompensated heart failure (ADHF). However, there are no other biomarkers for stratification of ADHF patients in clinical settings. Cardiac myosin I (CM-I) is one of a superfamily of motor proteins, which is mainly distributed in myocardium. Several papers reported that serum CM-I levels increased in patients with acute coronary syndrome (ACS). However, the role of CM-I in ADHF patients is not yet elucidated. Purpose: The aim of this study was to clarify the utility of CM-I in ADHF patients. Methods: We assessed 114 ADHF patients who visited our institution between December 2017 and May 2018 in a retrospective study. All patients were diagnosed ADHF using Framingham criteria. Eight ACS patients and 22 patients lacking in data of serum CM-I levels were excluded. Finally, we analyzed 84 patients. We calculated the difference in serum BNP levels between on admission and at discharge (delta BNP) as a prognostic surrogate marker. Results: Average age was 77.5 years old and 44 patients were male. Numbers of patients with NYHA III and IV were 30 and 36, respectively. Mean serum levels of BNP and Troponin T (TrT) on admission were 934.0 pg/ml and 0.092 ng/ml, respectively. Average left ventricular ejection fraction (LVEF) by echocardiography was 46.1%. Serum CM-I levels on admission and at discharge were 12.8 mg/ml and 7.30 mg/ml, respectively. Serum CM-I levels had a significant correlation with TrT levels (R=0.46, p Conclusion: We found CM-I was associated with the difference in BNP between on admission and at discharge in ADHF patients. CM-I may be a new potential prognostic biomarker in ADHF patients.

Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure > 90 mmHg, and estimated glomerular filtration rate > 15 ml/min/1.73 m2). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and

Optimal Contact Force for AF Ablation Background Regional differences in optimal contact force (CF) to prevent acute pulmonary vein reconnection (APVR) during catheter ablation for atrial fibrillation (AF) remain unclear. Objective The purpose of this study was to evaluate regional difference in optimal CF during AF ablation. Methods This single-center observational study evaluated data from 57 consecutive drug-refractory AF patients (mean age, 62 ± 11 years; 43 males) who underwent initial pulmonary vein isolation (PVI) using the THERMOCOOL® SMARTTOUCH™ (Biosense Webster, Diamond Bar, CA, USA) catheter from June to August 2013. APVR was defined as the time-dependent reconnection >20 minutes after initial PVI and/or reconnection evoked by intravenous adenosine administration (20 mg). Point-by-point relationships between the reconnected points and their CF values were evaluated. Results Total 72 gaps causing APVR were observed. Of a total of 4,421 ablation points, 285 (6.4%) were associated with APVR. The average CF value of the points with APVR was significantly lower than that of those without (APVR vs. no APVR; 7.5 ± 6.7 g vs. 9.9 ± 8.4 g; P < 0.0001). The areas under the curve and optimal CF values differed between segments (range 0.593–0.761 and 10–22 g, respectively). The optimal CF value was highest in bottom of the right PV and posterosuperior right PV segments (22 g) and lowest in posteroinferior right PV segment (10 g). Conclusions There was a regional difference in optimal CF values to prevent APVR, and the optimal CF value to prevent APVR with >95% probability was 10–22 g, depending on the individual peri-PV segments.

Introduction: Although chest compression is an effective emergency maneuver for cardiopulmonary arrest (CPA), it carries the risk of complications such as rib fracture, sternal fracture, and organ injury. Methods: We summarized thirteen case reports of CPA patients presenting with liver injury associated with CPR including chest compression reported between 1993 and 2015 in Japan. Five were male and eight were female; their ages ranged from 31 to 83 years old. Unfractionated heparin was administered to ten patients as a treatment for embolism or indication of veno-arterial extra corporeal membrane oxygenation (VA-ECMO). Twelve cases survived surgery or non-surgical management, but one could not survive with non-surgical management. Case: Two cases of CPA due to pulmonary thromboembolism were admitted to our department. Spontaneous circulation was restored due to cardiopulmonary resuscitation (CPR), including chest compression. After use of an anticoagulant drug and indication of VA-ECMO, contrast-enhanced computed tomography (CE-CT) revealed infra-diaphragmatic liver injury in both cases. One patient could survive with damage control surgery (DCS), while the other patient could not survive with non-surgical management. Conclusion: Patients with hemorrhagic diathesis are at critical risk for complications from chest compression. Aggressive treatments, including DCS, might be effective, even for patients treated with anticoagulant drugs.

Background This study aimed to evaluate the association between left atrial (LA) structural remodeling and very late recurrence [VLR; initial recurrence >12 months after catheter ablation (CA)] after successful CA for non-paroxysmal atrial fibrillation (AF). Methods We retrospectively evaluated 63 patients who underwent initial, single ablation for drug-refractory persistent or long-standing persistent AF and those who had no recurrence in the first year after CA. We followed patients for a mean of 3.2 ± 1.5 years and divided them into VLR and no-recurrence (NR) groups. Before and 3 months after ablation, all patients were subjected to 64-slice multidetector computed tomography scanning to estimate LA volume, including maximum and minimum volume during the cardiac cycle (LAMaxV and LAMinV, respectively), and the LA emptying fraction. Results VLR occurred in 21 patients. The reduction rate of LAMaxV after CA was significantly larger in the NR group than in the VLR group (25 ± 19% vs. 5 ± 18%, p = 0.0002). Receiver operating characteristic analysis was performed to determine the best cut-off values in the prediction of VLR. The highest area-under curve was obtained with post-CA LAMinV [0.828 (95% confidence interval, 0.712–0.912), p

We investigated the dynamics of the induction of apolipoprotein E (apoE) in the human brain after death caused by traumatic brain injury (TBI). A striking difference in apoE immunoreactivity in the traumatised cortical hemisphere compared with the contralateral non-traumatised hemisphere was observed. ApoE was detected within the neurons of the traumatised cortical hemisphere in cases surviving only about 2 h, as well as in those surviving for extended periods. In contrast, no apoE staining within the neurons was seen in the contralateral cortical hemisphere. ApoE staining within astrocytes was faint in both traumatised and contralateral hemispheres of cases surviving only 2 h. However, staining was intense in the traumatised hemispheres in short as well as long surviving cases, even those surviving more than 1 month. ApoE immunoreactivity was also observed in areas adjacent to capillaries and surrounding the neuropil of the injured hemisphere. These observations corroborated the idea of a prolonged induction of apoE within the neurons and also in the extracellular matrix after TBI. Furthermore, the possibility is suggested that the alteration of apoE distribution may contribute to a cerebroprotective mechanism immediately after TBI.

Introduction: Assessment of left ventricular (LV) dyssynchrony by echocardiography has only a limited ability to predict response to cardiac resynchronizing therapy (CRT) because of high variability of the measurement.Tissue mitral annular displacement (TMAD) is a rapid and robust method for the assessment of left ventricular (LV) longitudinal deformity. We previously reported that TMAD predicts good responders to CRT among patients with severe heart failure (AHA scientific meeting 2012). In the present study, we investigated whether TMAD could predict the long-term prognosis after CRT implantation. Methods: We performed echocardiography study in 41 patients with dilated cardiomyopathy (DCM) before and at 6 month of CRT, using iE33 (Philips Medical Systems). TMAD was measured on an apical 4-chamber image using QLAB software (Philips Medical Systems) to assess the movement of septal- and lateral part of mitral annulus toward apex. We measured the interval between QRS complex to peak of displacement on both regions, and calculated the differences in time-to-peak (dTTP). We defined good response to CRT as decrease in LV end-systolic volume (LVESV) > 15% at 6 month of CRT. We followed the patients to observe cardiovascular events including death, myocardial infarction, stroke and hospital admission for heart failure. Results: The 27 good responders (65.8%) had significantly longer dTTP than the non-responders (156±64 vs. 63±61 msec, p Conclusion: TMAD is a promising method for predicting long-term prognosis in patients with DCM receiving CRT.

Regional differences in optimal contact force (CF) to prevent acute pulmonary vein reconnection (APVR) during catheter ablation for atrial fibrillation (AF) remain unclear.The purpose of this study was to evaluate regional difference in optimal CF during AF ablation.This single-center observational study evaluated data from 57 consecutive drug-refractory AF patients (mean age, 62 ± 11 years; 43 males) who underwent initial pulmonary vein isolation (PVI) using the THERMOCOOL® SMARTTOUCH™ (Biosense Webster, Diamond Bar, CA, USA) catheter from June to August 2013. APVR was defined as the time-dependent reconnection20 minutes after initial PVI and/or reconnection evoked by intravenous adenosine administration (20 mg). Point-by-point relationships between the reconnected points and their CF values were evaluated.Total 72 gaps causing APVR were observed. Of a total of 4,421 ablation points, 285 (6.4%) were associated with APVR. The average CF value of the points with APVR was significantly lower than that of those without (APVR vs. no APVR; 7.5 ± 6.7 g vs. 9.9 ± 8.4 g; P0.0001). The areas under the curve and optimal CF values differed between segments (range 0.593-0.761 and 10-22 g, respectively). The optimal CF value was highest in bottom of the right PV and posterosuperior right PV segments (22 g) and lowest in posteroinferior right PV segment (10 g).There was a regional difference in optimal CF values to prevent APVR, and the optimal CF value to prevent APVR with95% probability was 10-22 g, depending on the individual peri-PV segments.

Glutamate is the major excitatory neurotransmitter and the greater part of this amino acid is removed from the synaptic cleft by excitatory amino acid transporter 2 (EAAT2) located on perisynaptic astrocytes. Recently, it was reported that the EAAT2 protein content changed in rats following forebrain ischemia and administration of methamphetamine. We planned to demonstrate the immunohistochemical distribution of EAAT2 in the human brain and discuss the significance of its pathophysiological roles. Thirty-two cases were used from forensic autopsies. The tissues were sampled from the cerebral cortex, striatum and hippocampus. The distribution of EAAT2 was difficult to identify in cases of electrical fatalities. However, continuous and extensive staining of EAAT2 was observed in cases of death from hypothermia. In almost all asphyxia death, we were able to observe a weak stain of EAAT2. In case of solvent abuse, EAAT2 staining was continuous and extensive as in the cases of hypothermia, and patchy negative zones were mixed. This study clearly showed the differences in EAAT2 localization according to the cause of death. These findings suggested that the differences in EAAT2 staining depended on the cause and course (pathophysiological conditions) of death.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder. In forensic cases, post-mortem diagnosis of NMS is sometimes difficult if ante-mortem information, such as neuroleptic ingestion or signs and symptoms, cannot be obtained. A 39-year-old Japanese male on a neuroleptic treatment regimen suddenly became agitated and died. Autopsy revealed muscle rigidity and hyperthermia. Post-mortem examination of blood revealed elevation of creatine phosphokinase-MM (CK-MM) and lactate dehydrogenase-4 and dehydrogenase-5 (LDH-4 and LDH-5). In renal glomeruli and tubules, myoglobin was stained immunohistochemically. From these findings, the cause of death was considered to be NMS. To support the diagnosis of NMS, both skeletal and cardiac muscles were stained with actin, myoglobin, desmin and mitochondria antibodies immunohistochemically. Actin, myoglobin, desmin, and mitochondria had been lost from skeletal, but not from the cardiac muscle, which suggested that only the skeletal muscle was damaged. Moreover, because mitochondria had disappeared only from the skeletal muscle, it was considered that skeletal muscle degeneration was caused by mitochondrial damage. Therefore, it is suggested that immunostaining of skeletal muscle by antibodies for muscle-associated proteins and mitochondria is useful to corroborate a diagnosis of NMS.

We assessed the value of an alternative light source for detecting white composite dental materials in burned and unburned teeth. Teeth filled with 18 different restorative materials (composite, glass ionomer or hybrid composite), were viewed with a Polilight®. Between 415 nm and 555 nm, the glass ionomers showed distinctly different optical properties from the other materials: they either fluoresced or appeared darker. Wavelengths 415 nm to 530 nm gave a general enhancement in composite detection (17 of 18 materials). Light above 590 nm was of little value, enhancing detection in only 2 of 18 materials. After simulated burning of the teeth, there was enhanced visibility of 8 of 18 materials at wavelengths under 350 nm. Burning destroyed the previously distinct optical properties of the glass ionomers. Overall, this alternative light source aids the identification of white composite dental materials and could be used in routine forensic odontology practice.

We present a case of fatal adrenal crisis due to isolated adrenocorticotropic hormone (ACTH) deficiency. Autopsy revealed each adrenal gland weighed 0.9 g and the adrenal cortexes were very thin and atrophic. Additionally, cortisol could not be observed in the adrenal cortex by immunohistochemical staining. Furthermore, urine cortisol and 17-OHCS concentration had decreased to a very low level, 20 mg/L and 0.8 mg/L respectively. The anterior pituitary gland was atrophic, and showed fibrosis and lymphocytosis was suspected. Immunohistochemically growth hormone (GH)-stained pituitary gland cells were observed, but there were no cells stained with anti-ACTH antibody. From the history and pathological findings, no other deficiencies of pituitary hormones were evident. Therefore, isolated ACTH deficiency was suspected. Furthermore, as the thyroid gland showed lymphocytic thyroiditis, is was considered that isolated ACTH deficiency was associated with an autoimmune cause. Generally, as patients of chronic adrenocortical insufficiency are exposed to stress and, therefore, have an increased requirement for glucocorticoids, the blood pressure falls, leading to hypovolemic shock called " an adrenal crisis." Without treatment, patients die in crisis within several hours. In our case, the deceased had drunk alcohol without sleep for 2 days. We believe that the stress of drinking and sleeplessness induced adrenal crisis and caused his death.

We examined the species specificity of six commercially available human short tandem repeat systems (for CSF1PO, TPOX, TH01, F13A01, FESFPS and vWA) using six samples obtained from the Japanese monkey Macaca fuscata. Macaque genes were amplified with human TPOX and F13A01 primers. During electrophoresis, macaque polymerase chain reaction (PCR) products amplified with the TPOX primer migrated more slowly than human ones, and migrated close to human CSF1PO bands. Macaque PCR products amplified with the F13A01 primer also migrated more slowly than the human equivalent. The six macaque samples were classified into three types by the TPOX primer and into six types by the F13A01 primer. These results suggest that the primers for human TPOX and F13A01 loci can be used to distinguish between human and Japanese macaque samples.

Using immunohistochemical staining, the histological changes and the presence of neuropeptides (enkephalin and VIP) in the carotid body have been investigated in medico-legal autopsy cases, especially asphyxia cases. Only in cases of manual and/or ligature strangulation cases that sustained a force near the carotid body, were the chief cells mainly lightly stained, indicating that they had been "active" cells. Furthermore, these cells and their nuclei were enlarged in comparison to the chief carotid body cells in other autopsy groups. It was thus felt that these changes had resulted from the force that had directly affected the carotid body. Based on these findings, it was concluded that immunohistochemical investigation of the carotid body offers a useful possibility for diagnosing manual asphyxia, especially in autopsy cases involving strangulation.

We report an autopsy case of a death associated with ingestion of liquid windshield-washer detergent. The deceased was a 49-year-old man who was found dead on a road near his truck. A bottle of liquid windshield-washer detergent containing an anionic surfactant and methanol was found under the passenger seat of the truck. At autopsy, slight abrasions and bruises were observed on his body. The small intestine contained dark greenish-brown mucoid matter with abundant froth. The mucous membranes of the esophagus, stomach and superior small intestine showed extensive necrosis, erosion, hemorrhage, edema and congestion. Using the methylene blue method to examine the contents of the small intestine, the presence of an anionic surfactant was indicated. We conclude that the cause of death was ingestion of liquid windshield-washer detergent.

We investigated the dynamics of the induction of heme oxygenase-1 (HO-1) in the human brain after death caused by traumatic brain injury (TBI). HO-1 was found to stain neurons and microglia/macrophages in cases with TBI, whereas no positive staining except for a few round cells in the arachnoidal space was observed in control cases. In a case with 7h survival, a considerable number of HO-1 positive neurons and microglia were observed. The number of HO-1 positive cells and level of HO-1 staining gradually increased up to 24h survival. Although HO-1 positive neurons were seldom observed in cases with more than 7-day survival, HO-1 positive microglia were still observed even in cases with 5-month survival. The results indicate that HO-1 may be induced by TBI in human cases, and suggest that prolonged HO-1 induction in microglia might reflect its role in protecting those cells from secondary damage including oxidative stress.

We examined six human short tandem repeat (STR) loci (c-fms proto-oncogene for CSF-1 receptor, CSF1PO; thyroid peroxidase, TPOX; tyrosine hydroxylase, TH01; coagulation factor XIII a subunit, F13A01; c-fes/fps proto-oncogene, FESFPS and von Willebrand factor, vWA) in the Japanese macaque, Macaca fuscata, using commercially available human STR kits. No products were amplified by polymerase chain reaction (PCR) using the human CSF1PO, TH01, FESFPS and vWA primers. Macaque DNAs were amplified with human TPOX and F13A01 primers. Macaque PCR products amplified with the TPOX and F13A01 primers migrated more slowly than human ones during electrophoresis. Sequencing results showed that the nucleotide sequences of the counterpart of the TPOX and F13A01 STR loci in the Japanese macaque were closely similar to those of the human genes except for tandem repeat regions. The macaque products amplified with human TPOX and F13A01 primers were highly polymorphic, with four variants of the former and 15 variants of the latter in the nine samples. These results indicate that the commercially available kits can be used to discriminate the Japanese macaque samples from human samples.

We investigated the dynamic induction/expression of inducible nitric oxide synthase (iNOS) using human brains made available through death by traumatic brain injury (TBI). Astrocytes, microglia, and neutrophils were identified in tissue using immunohistochemical staining with antibodies against glial fibrillary acidic protein (GFAP), MHC class II antigen, and neutrophil elastase, respectively. The localization of iNOS protein in each of these cell types was evaluated using immunohistochemistry. Within 2 days of injury, iNOS immunoreactivity was not detected. However, after 2 days, immunoreactivity was detected in the traumatized brain. The iNOS immunoreactivity was localized on neutrophils and microglia/macrophages in the areas around the tissue necrosis in the traumatized cortical hemisphere, in the deep part of the cortex and the dentate gyri of the hippocampi adjacent to the hemorrhage, and within the cytoplasm of vascular smooth muscle cell of a small artery or arteriole surrounding the injured region. This reactivity was absent after 8 days post-injury. These observations confirmed the prolonged induction of iNOS within various cells in the injured brain. These responses suggest that iNOS plays a crucial role in cerebrovascular damage and/or secondary brain damage subsequent to traumatic brain injury. Furthermore, the dense nitric oxide (NO) generated by iNOS may play a role in neuronal cell death after injury.

A polymorphic CA repeats (YCA II) was previously reported on the human Y chromosome. We have used a simple technique based on polymerase chain reaction amplification followed by native polyacrylamide gel electrophoresis to study the inheritance, the genetic stability, and the allele frequency distribution of this polymorphism in the Japanese. We found seven haplotypes which were tentatively designated as: A[(CA)19/(CA)21], B[(CA)19/(CA)22], C[(CA)19/(CA)23], D[(CA)19/(CA)19], E[(CA)21/(CA)21], F[(CA)22/(CA)22], and G[(CA)23/(CA)23]. The frequencies of these haplotypes were: A, 0.21; B, 0.29; C, 0.37; D, 0.02; E, 0.02; F, 0.07; G, 0.01. There was complete concordance with each father-son pairs. The results indicate the dinucleotide system YCA II is very useful for investigation of forensic samples, especially mixed stains in sexual offence cases.

The intra-abdominal accumulation of fat is more common in men; it is an independent risk factor for diabetes mellitus and cardiovascular disease.1 The assessment of obesity usually focuses on abdominal fatness, but the most appropriate clinical measurement of obesity has been disputed. 2 3 We evaluated several measures of obesity by comparing them with observed intra-abdominal and subcutaneous fat during postmortem examination. A series of 100 men was studied. Cases of prolonged hospitalisation, severe trauma, chronic wasting disease, and postmortem decomposition were excluded from analysis. Measurements were made using techniques suitable for supine cadavers. Body weight was measured to within 1 kg, body length to within 1 cm, hip circumference at the iliac crests to within 1 cm, and waist circumference at the umbilicus to within 1 cm. Uniform cores of subcutaneous fat were obtained from over the biceps, anterior thigh, anterior chest, and anterior abdomen. These samples were weighed to within 0.1 g. The greater omentum was excised as was the pararenal fat; these were weighed to within 1 g. The mean age at the time of death was …