Changes in cerebrovascular disease-related deaths and their location during the COVID-19 pandemic in Japan.

OBJECTIVE: The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated cerebrovascular excess deaths in Japan. STUDY DESIGN: Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare. METHODS: Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval. RESULTS: Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period. CONCLUSIONS: Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.

Excess deaths from COVID-19 in Japan and 47 prefectures from January through June 2021.

OBJECTIVES: In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. STUDY DESIGN: Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. METHODS: A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. RESULTS: Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12-18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31-June 6 (excess deaths: 1431-2587; excess percentage: 5.95-10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. CONCLUSIONS: For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

The relationship between fever rate and telework implementation as a social distancing measure against the COVID-19 pandemic in Japan.

OBJECTIVES: On March 28, the Japanese government decided on the "Basic Policies for Novel Coronavirus Disease Control" and called on the public to thoroughly implement social distancing measures (i.e., behavioral restrictions to limit the frequency and intensity of human contact), especially telework. METHODS: We used population-level questionnaire data from a social networking service (SNS), with 275,560 respondents from March 5 to April 6, to evaluate the relationship between telework implementation and the presence of a fever (body temperature higher than 37.5 °C) within 1 month as a surrogate indicator of COVID-19 infection, by occupation type and age-group. RESULTS: Among company employees, statistical significance was identified in the 15- to 29-year and 30- to 59-year age-groups, showing higher fever rates in the non-teleworker group (for the 15- to 29-year age-group, non-teleworkers: 7.64%; teleworkers: 6.45%; P = 0.02; for the 30- to 59-year age-group, non-teleworkers: 3.46%; teleworkers: 3.14%; P = 0.02). CONCLUSIONS: Telework remains a controversial topic in Japan as the government called for emergency measures. Although caution is warranted in interpreting our findings because our data are limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.

Trend change of the transmission route of COVID-19-related symptoms in Japan.

OBJECTIVES: The Japanese prime minister declared a state of emergency on April 7 2020 to combat the outbreak of coronavirus disease 2019 (COVID-19). This declaration was unique in the sense that it was essentially driven by the voluntary restraint of the residents. We examined the change of the infection route by investigating contact experiences with COVID-19-positive cases. STUDY DESIGN: This study is a population-level questionnaire-based study using a social networking service (SNS). METHODS: To assess the impact of the declaration, this study used population-level questionnaire data collected from an SNS with 121,375 respondents (between March 27 and May 5) to assess the change in transmission routes over the study period, which was measured by investigating the association between COVID-19-related symptoms and (self-reported) contact with COVID-19-infected individuals. RESULTS: The results of this study show that the declaration prevented infections in the workplace, but increased domestic infections as people stayed at home. However, after April 24, workplace infections started to increase again, driven by the increase in community-acquired infections. CONCLUSIONS: While careful interpretation is necessary because our data are self-reported from voluntary SNS users, these findings indicate the impact of the declaration on the change in transmission routes of COVID-19 over time in Japan.

Chemical properties of commercially available honey species and the functional properties of caramelization and Maillard reaction products derived from these honey species.

The chemical parameters and the functionalities of six monofloral honeys of different botanical and geographical origins were investigated. Vitamins B1, B2, and C and the protein content of majority of honeys were distinguishable from general honey. Honeys not only were rich in a variety of functional components like flavonoids but also had strong anti-oxidant activities, scavenging activities against ROS, and anti-hypertensive and anti-allergic activities. Honeys were heated at 100 °C for 24 h and their browning intensity during heating process was observed to vary with botanical origin. The functional properties of caramelization and maillard reaction (MR) products derived from honeys during heating were evaluated. The browning of honeys progressed regardless of honey species. Anti-oxidant activities and scavenging activities against superoxide and DPPH radicals of products drastically increased, but ACE and hyaluronidase activities gradually decreased with passage of heating time. It concluded that the products, mainly melanoidins, produced simultaneously to browning process in caramelization and MR contributed to the expression of its useful function.

Bidirectional Glenn procedure improves the mechanical efficiency of a total cavopulmonary connection in high-risk fontan candidates.

BACKGROUND: A total cavopulmonary connection (TCPC) is a widely performed surgical procedure for Fontan candidates. High-risk candidates who have undergone the bidirectional Glenn procedure (BDG) before TCPC have shown good results. The exact mechanism of this procedure, however, is still poorly understood. We hypothesized that a volume reduction with BDG improved ventricular contractility, thereby optimizing mechanical efficiency after TCPC. METHODS AND RESULTS: We measured percent normal systemic ventricular end-diastolic volume (%N-EDV), contractility (end-systolic elastance; E(es)), afterload (effective arterial elastance; E(a)), and mechanical efficiency (ventriculoarterial coupling; E(a)/E(es)) on the basis of the cardiac catheterization data before and after TCPC. Eighteen patients who underwent staged TCPC after BDG (staged group) were compared with 29 patients who underwent primary TCPC (primary group). E(es) and E(a) were approximated as follows: E(es)=mean arterial pressure/minimal ventricular volume, and E(a)=maximal ventricular pressure/(maximal ventricular volume-minimal ventricular volume), and E(a)/E(es) was then calculated. The ventricular volume was normalized with the body surface area. A canine experimental model with conductance catheter was used to validate the accuracy of this approximation of E(es) and E(a). %N-EDV decreased after TCPC in both groups. In the staged group, a smaller ventricular volume resulted in better contractility (E(es)). Although afterload (E(a)) increased in both groups, the increment of E(a) was smaller in the staged group. These changes resulted in an improvement of E(a)/E(es) in the staged group, whereas E(a)/E(es) increased in the primary group. CONCLUSIONS: The volume reduction of BDG preceding TCPC allows for any afterload mismatch to be corrected, thereby improving ventricular energetics after TCPC.

Inhibition of lipid peroxidation with the lazaroid U74500A attenuates ischemia-reperfusion injury in a canine orthotopic heart transplantation model.

BACKGROUND: The lazaroid U74500A is a 21-aminosteroid that inhibits lipid peroxidation and attenuates ischemia-reperfusion injury. We examined the effect of U74500A on heart preservation with the use of a clinically relevant canine orthotopic heart transplantation model. METHODS AND RESULTS: Six donor dogs (group L) were pretreated intravenously with U74500A (10 mg/kg), and the dogs without pretreatment served as a control (group C, n = 6). The donor heart was preserved in cold University of Wisconsin solution for 24 hours. The heart was then transplanted orthotopically. Myocardial biopsy was performed to measure the adenosine triphosphate level at the end of ischemia. Before reperfusion, recipients in group L received another dose of U74500A (10 mg/kg) intravenously. After 3 hours of reperfusion, left ventricular function was evaluated by left ventricular pressure-volume relations with the use of a Millar catheter and conductance catheter, thereby deriving the slope of the end-systolic pressure-volume relation, the slope of the stroke work-- end-diastolic volume relation, and the slope of the maximum dP/dt--end-diastolic volume relation. At the same time, serum creatine kinase MB isoenzyme and lipid peroxide levels were measured. The slopes of the end-systolic pressure-volume relation, the stroke work--end-diastolic volume relation, and the maximum dP/dt--end-diastolic volume relation for group L were significantly higher than those for group C. The adenosine triphosphate levels for group L were significantly higher than those for group C. Serum creatine kinase MB isoenzyme and lipid peroxide levels for group L were significantly lower than those for group C. CONCLUSIONS: Inhibition of lipid peroxidation by the administration of U74500A was effective for 24-hour canine cardiac preservation. These results indicate that U74500A is a promising agent for heart allograft preservation.

Effects of amrinone, a phosphodiesterase inhibitor, on right ventricular/arterial coupling immediately after cardiac operations.

OBJECTIVE: Amrinone, a selective phosphodiesterase III inhibitor, is reported to have a potent inotropic effect on the left ventricle, but the effects of this drug on right ventricular contractility in the clinical setting are unknown. The concept of ventricular/arterial coupling was applied to investigate the effects of amrinone on right ventricular contractility and afterload with transesophageal echocardiography. METHODS AND RESULTS: The study was performed in the intensive care unit with 11 patients who had undergone cardiac operations. Right ventricular cross-sectional area was measured with transesophageal echocardiography equipped with a capability of automated border detection as a surrogate for right ventricular volume. Multiple pressure-area loops were obtained by reducing preload to measure end-systolic elastance and effective arterial elastance. External work and pressure-volume area were also measured to calculate the efficiency of energy transfer from pressure-volume area to external work. Nitroprusside (0.3 to 0.5 microg x kg(-1) x min(-1)) and amrinone (1 mg x kg(-1) intravenously followed by 10 microg x kg(-1) x min(-1)) were administered. With nitroprusside infusion, end-systolic elastance and effective arterial elastance remained unchanged (end-systolic elastance, 4.73 +/- 2.18 mm Hg/cm2 to 4.65 +/- 2.09 mm Hg/cm2; effective arterial elastance, 8.05 +/- 3.84 mm Hg/cm2 to 7.70 +/- 3.64 mm Hg/cm2). In contrast, amrinone reduced afterload (effective arterial elastance, 8.82 +/- 3.99 mm Hg/cm2 to 7.05 +/- 4.01 mm Hg/cm2, p = 0.004) and enhanced contractility (end-systolic elastance, 4.47 +/- 1.79 mm Hg/cm2 to 6.56 +/- 2.22 mm Hg/cm2, p = 0.007). Consequently, amrinone decreased the ventricular/arterial coupling ratio (effective arterial elastance/end-systolic elastance, 2.40 +/- 1.45 to 1.16 +/- 0.63, p = 0.009) and improved the efficiency of energy transfer (external work/pressure-volume area, 0.44 +/- 0.15 to 0.54 +/- 0.15, p = 0.013). CONCLUSIONS: Right ventricular pressure-area relations obtained with transesophageal echocardiography could successfully separate the simultaneous change in right ventricular systolic mechanics and afterload caused by amrinone. Amrinone caused enhancement of right ventricular contractility and afterload reduction.

Nitroglycerin as a nitric oxide donor accelerates lipid peroxidation but preserves ventricular function in a canine model of orthotopic heart transplantation.

BACKGROUND: Nitric oxide has cardioprotective effects through several mechanisms. However, nitric oxide may have deleterious effects in the presence of superoxide because it is converted to peroxynitrite, which then initiates lipid peroxidation. Using a canine model of orthotopic heart transplantation, we examined whether adding an organic nitric oxide donor, nitroglycerin, to preservation solution elicits lipid peroxidation after reperfusion and causes deleterious effects on coronary endothelial function and left ventricular function. METHODS AND RESULTS: The donor heart was preserved for 24 hours in cold University of Wisconsin solution with nitroglycerin (0.1 mg/mL) supplementation (group NTG, n = 8) or in standard University of Wisconsin solution (group C, n = 8). After reperfusion, changes of coronary resistance were measured during the infusion of acetylcholine (0.1 mg/min) and of sodium nitroprusside (1 mg/min), and percent coronary relaxation was calculated. Left ventricular function was evaluated by pressure-volume relations with the use of a conductance catheter, thereby deriving the slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation. Serum lipid peroxide level was measured. Percent coronary relaxation was similar for the 2 groups. The slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation in group NTG were significantly higher than those in group C. On the other side, serum lipid peroxide level in group NTG was significantly higher than that in group C. CONCLUSIONS: Nitroglycerin may have detrimental effects evidenced by the increase in lipid peroxidation, which implied peroxynitrite formation. However, the overall effect of nitroglycerin was cardioprotective. Although the exact mechanism is yet to be clarified, the superb cardioprotective effect of nitroglycerin overwhelms the exaggeration of lipid peroxidation.

Successful twenty-four-hour canine lung preservation with lazaroid U74500A.

BACKGROUND: Lipid peroxidation is known to contribute to ischemia-reperfusion injury. U74500A is a 21-aminosteroid (lazaroid) that prevents lipid peroxidation without corticoid side effects. We examined the effect of U74500A on lung preservation using a canine orthotopic single left lung transplantation model. METHODS: Twelve adult mongrel dogs underwent left lung allotransplantation. The lungs of the donor dogs were flushed with University of Wisconsin solution (50 ml/kg). Six donor dogs were pretreated with U74500A (5 mg/kg intravenously) before preservation (group L, n = 6), whereas those dogs without pretreatment served as controls (group C, n = 6). Allografts were stored in University of Wisconsin solution for 24 hours at 1 degrees C. Left single lung transplantations were performed by means of standard technique. Before reperfusion, recipients in group L received another dose of U74500A. Arterial blood gas analysis and hemodynamic measurements were made by occluding the right pulmonary artery to evaluate the transplanted left lung function at a inspired oxygen fraction of 1.0. Serum lipid peroxide level was measured after 2 hours of reperfusion. RESULTS: Arterial oxygen tension, arterial carbon dioxide tension, and left pulmonary vascular resistance at 6 hours after reperfusion were significantly better in group L than in group C (arterial oxygen tension: 510 +/- 66 and 219 +/- 149 mm Hg; arterial carbon dioxide tension: 47 +/- 16 and 68 +/- 14 mm Hg; left pulmonary vascular resistance: 2412 +/- 826 and 3904 +/- 1251 dyn center dot sec/cm5, group L and group C, respectively). Serum lipid peroxide level was significantly lower in group L (0.25 +/- 0.24 nmol/ml) than in group C (0.92 +/- 0.53). CONCLUSIONS: The administration of U74500A prevented lipid peroxidation and preserved pulmonary allograft function after 24 hours of ischemia.

Comparative study of retrograde and selective cerebral perfusion with transcranial Doppler.

BACKGROUND: Retrograde cerebral perfusion (RCP) is a simple technique and is expected to provide cerebral protection. However, its optimum management and limitations remain unclear. Transcranial Doppler has been used to monitor cerebral perfusion. Using this Doppler technique, we compared cerebral blood flow for RCP with that for selective cerebral perfusion. METHODS: Thirty-two consecutive patients underwent elective surgical repair of an aortic aneurysm involving the aortic arch at Kyushu University Hospital. Retrograde cerebral perfusion was used in 15 patients and selective cerebral perfusion, in 17 patients. Continuous measurement of middle cerebral artery blood flow velocities was performed by transcranial Doppler technique. RESULTS: Retrograde middle cerebral artery blood flow velocities during RCP could be measured in only 3 patients, whereas middle cerebral artery blood flow velocities during selective cerebral perfusion could be measured in all but 1 woman. The increase in middle cerebral artery blood flow velocities after RCP was significantly greater than that after selective cerebral perfusion. CONCLUSIONS: The measurement of middle cerebral artery blood flow velocities with transcranial Doppler technique is practicable during selective cerebral perfusion but difficult during RCP. The increase in middle cerebral artery blood flow velocities after RCP indicates reactive hyperemia and reflects the critical decrease in cerebral blood flow during this type of perfusion.

Use of transesophageal echocardiography for postoperative evaluation of right ventricular function.

BACKGROUND: No method has been available to assess the right ventricular (RV) pressure-volume relation in the operating room or intensive care unit. Left ventricular cross-sectional area measured by echocardiography using the technology of automated border detection has been used to construct left ventricular pressure-area (P-A) loops. In the human right ventricle, however, this approach has not been validated. METHODS: We recorded RV P-A loops in 14 patients in the intensive care unit using transesophageal echocardiography. Multiple RV P-A loops were obtained by reducing preload with intravenous nitroglycerin, thereby elucidating the end-systolic P-A relation. RESULTS: With an incremental dose of dobutamine, the slope of the RV end-systolic P-A relation increased (from 4.56+/-2.42 to 7.34+/-3.62 mm Hg/cm2, p<0.01), with no change in the x-axis intercept, which implied increased contractility. Furthermore, in the operating room we validated the use of RV cross-sectional area as a surrogate for RV volume by demonstrating the close correlation between the stroke area (maximal RV area minus minimal RV area) and stroke volume (r = 0.962; p<0.0001). CONCLUSIONS: Transesophageal echocardiography with automated border detection is a promising tool for elucidating RV function through the analysis of RV P-A loops.

Weaning time of children with infantile autism.

Since early weaning in infancy has been known to result in vulnerability to infection, weaning times of 145 children diagnosed as autistic by DSM-III were statistically compared with those of 224 normal children in the same catchment area: 24.8% of the patients and 7.5% of the controls were weaned by the end of 1 week, a significant difference. Early weaning because of the mother's rather than the child's condition occurred with 17.9% of the patients and 5.8% of the controls, also a significant difference. Historical studies on infantile autism revealed that the disease developed more prevalently in the socioeconomic status where the incidence of breast-feeding was less frequent. These results suggest that early weaning may contribute to the etiology of infantile autism.

Epidemiology of infantile autism in southern Ibaraki, Japan: differences in prevalence in birth cohorts.

Infantile autism was diagnosed by DSM-III criteria in 132 children (26 girls) who were outpatients of the Tsuchiura Child Guidance Center during the years 1977-1985. The children, all Japanese except for one Laotian boy born in Laos, were classified according to year and month of birth. The prevalence rate of infantile autism in southern Ibaraki, Japan, within the birth cohort born between 1972 and 1978 was 13.9/10,000 children. The month of birth for infantile autism increased in the second quarter of the year. The prevalence rate of infantile autism in each 1-year birth cohort fluctuated in a 4-year cycle, which was closely correlated (r = .92) with the number of children admitted with pneumonia and bronchiolitis in that area. These findings led us to postulate that infectious factors of children's pneumonia and bronchiolitis may have some role in the cause of infantile autism.

Characterization of yellowfin tuna (Thunnus albacares, Scombroidei) tryptophan hydroxylase.

Tryptophan hydroxylase (EC 1.14, 16.4) was purified from yellowfin tuna liver and properties of this enzyme were compared with those of tryptophan hydroxylase from some other species (mouse mastocytoma and rat brain-stem). The molecular weight of the yellowfin tuna enzyme was estimated to be about 280,000 Da. This value is similar to that for the enzymes from mouse mastocytoma and rat brain-stem. On SDS-polyacrylamide gel electrophoresis analysis, yellowfin tuna enzyme was estimated to be about 96,000 Da. This value is different from that for the enzymes from mouse mastocytoma (53,000 Da) and rat brain-stem (59,000 Da) and suggests that yellowfin tuna enzyme may be a dimer of identical subunits of Mr 96,000 Da.

Surgical management of aortopulmonary window.

OBJECTIVE: Aortopulmonary window is a rare congenital malformation involving a window-like communication between the ascending aorta and the pulmonary artery. Here, we present our experience regarding the surgical repair of an aortopulmonary window, and also assess the long-term outcome. METHODS: Thirteen children with an aortopulmonary window associated with various congenital lesions underwent a repair of the defect. The age at operation ranged from 3 days to 1 year (median age, 19 days). The patient's weight ranged from 2.1 to 7.0 kg (mean weight, 3.6 kg). The associated lesions included an interrupted aortic arch (5 patients), a ventricular septal defect (2), an atrial septal defect (1), mitral valve regurgitation (1), and tricuspid atresia [Ic] with mitral valve regurgitation (1). The aortopulmonary window was repaired with a cardiopulmonary bypass in 11 patients, and 2 patients were ligated without a cardiopulmonary bypass. RESULTS: One patient associated with tricuspid atresia died (mortality rate of 7.7%). There has been no late death during a mean follow-up of 7 years and 3 months. CONCLUSIONS: The surgical results for an aortopulmonary window are encouraging, even if such patients are associated with major cardiac anomalies and an interrupted aortic arch. Most have shown a good long-term outcome.

Effect of phosphodiesterase III inhibitor on contractility, afterload, and vascular capacitance during right heart bypass preparation.

OBJECTIVES: Phosphodiesterase III inhibitors, which have both positive inotropic and vasodilatory effects, occasionally cause hypotension due to afterload reduction and possibly due to preload reduction caused by the increase in vascular capacitance. METHODS: Six open-chest adult mongrel dogs were used to compare the effects on left ventricular contractility, afterload, and vascular capacitance of the phosphodiesterase III inhibitor, olprinone, with those of dobutamine using a right-heart-bypass model. Contractility and afterload were evaluated by the left ventricular pressure-volume relations with the use of a conductance catheter to derive the end-systolic elastance (Ees) and the effective arterial elastance (Ea). Vascular capacitance change was evaluated by reservoir volume change under a constant bypass flow (80 ml/kg per minute). RESULTS: Ees increased significantly both with dobutamine (7.6 +/- 2.8 to 14.3 +/- 4.8 mmHg/ml, p < 0.05) and with olprinone (7.6 +/- 2.9 to 11.5 +/- 4.2 mmHg/ml, p < 0.05). Ea did not change with dobutamine (14.4 +/- 3.5 to 14.5 +/- 3.6 mmHg/ml, p = 0.9), whereas it decreased with olprinone (14.0 +/- 4.1 to 11.4 +/- 3.8 mmHg/ml, p = 0.093). Reservoir volume increased after the infusion of dobutamine (-94.0 +/- 39.8 ml), and decreased after the infusion of olprinone (-114.0 +/- 62.3 ml). The difference was statistically significant (p = 0.007). The reservoir volume change indicated that vascular capacitance decreased with dobutamine, and increased with olprinone. CONCLUSIONS: Pre- and afterload reduction of olprinone combined with the positive inotropic effect are useful in treating congestive heart failure and managing low cardiac output syndrome after cardiac surgery.

Heart donation in Japan before and after the revision of the Japanese Transplantation Act.

INTRODUCTION: After the revision of the Organ Transplant Act in July 2010, brain dead organ donation increased from 13 to 45 per year, and heart donation increased. The purpose of this study was to review 166 consecutive brain dead heart donors to evaluate our strategies to identify and manage organ donors. METHODS: This study reviewed 166 consecutive brain dead heart donors since the Act was issued. Whereas 69 heart donations were performed between October 1997 and July 2010 before the revision of the Act, 97 heart donations were performed for the 3 years after the revision. Since November 2002, special transplant management doctors were sent to donor hospitals to assess donor organ function and to identify which organs could be transplanted. They also intensively cared for the donors to stabilize hemodynamics and to improve cardiac function by giving intravenous antidiuretic hormones and by pulmonary toileting via bronchofiberscope. RESULTS: The mean heart donor age increased from 41.0 to 43.9 years after the revision. Notably, 11 hearts from donors more than 60 years old were transplanted successfully after the revision. Before the revision, the cause of death was 37 cerebrovascular disease (SAH 34, stroke 1, bleeding 2), 18 head trauma, 13 asphyxia, and 2 postresuscitation brain damage. After the revision, there were 49 cerebrovascular disease (SAH 37, stroke 2, bleeding 16, and other 4), 17 head trauma, 10 asphyxia, and 11 postresuscitation brain damage. A total of 58 donors had a history of cardiac arrest, 58 required a high dose of catecholamine drip infusion, and only 1 recipient died of primary graft dysfunction. Patient survival rate at 3 years after heart transplantation was not different before and after the revision of the Act (98.6% vs 92.2%). CONCLUSIONS: Although donor age was increased and donors who died of cerebral bleeding or postresuscitation after the revision of the Act increased, the outcome after heart transplantation was not changed.

Japanese strategies to maximize heart and lung availabilities: experience from 100 consecutive brain-dead donors.

OBJECTIVE: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies have been established to maximize heart and lung transplantations (HTs and LTs, respectively). We reviewed 100 consecutive brain-dead donors to evaluate our strategies to identify and manage heart and lung donors. METHODS: We retrospectively reviewed all 100 consecutive brain-dead donors procured since the law was issued in 1997. There were 56 mens and the overall mean donor age was 43.5 years. The causes of death were cerebrovascular disease (n = 62), head trauma (n = 20), and asphyxia (n = 16): Since November 2002, special transplant management doctors were sent to donor hospitals to assess cardiac and lung functions, seeking to identify transplant opportunities. They stabilized donor hemodynamics and lung function by administering antidiuretic hormone intravenously and performing bronchofibroscopy for pulmonary toilet. RESULTS: Seventy-nine HTs, 1 heart-lung transplantations, and 78 LTs (46 single and 32 bilateral) were performed. By applying these strategies organs per donor were increased from 4.5 to 6.8. Among heart donors, 61/80 were marginal: high inotrope requirement (n = 29), cardiopulmonary resuscitation (n = 28), and/or >55 years old (n = 20). None of the 80 HT recipients died of primary graft failure (PGF). Patient survival rate at 10 years after HT was 95.4%. Among lung donors, 48/65 were marginal: pneumonia (n = 41), chest trauma (n = 4), and >55 years old (n = 9). Only 2/78 LT recipients died of PGF. Patient survival rate at 3 years after LT was 72.2%. After inducing frequent pulmonary toilet, lung procurement and patient survival rates increased significantly after LT. CONCLUSIONS: Although the number of cases was still small, the availability of organs has been greater and the outcomes of HT/LT acceptable.

Identification and characterization of cell-specific enhancer elements for the mouse ETF/Tead2 gene.

We have identified and characterized by transient transfection assays the cell-specific 117-bp enhancer sequence in the first intron of the mouse ETF (Embryonic TEA domain-containing factor)/Tead2 gene required for transcriptional activation in ETF/Tead2 gene-expressing cells, such as P19 cells. The 117-bp enhancer contains one GC-rich sequence (5'-GGGGCGGGG-3'), termed the GC box, and two tandemly repeated GA-rich sequences (5'-GGGGGAGGGG-3'), termed the proximal and distal GA elements. Further analyses, including transfection studies and electrophoretic mobility shift assays using a series of deletion and mutation constructs, indicated that Sp1, a putative activator, may be required to predominate over its competition with another unknown putative repressor, termed the GA element-binding factor, for binding to both the GC box, which overlapped with the proximal GA element, and the distal GA element in the 117-bp sequence in order to achieve a full enhancer activity. We also discuss a possible mechanism underlying the cell-specific enhancer activity of the 117-bp sequence.