A Single-Year Cosmic Ray Event at 5410 BCE Registered in 14C of Tree Rings.

The annual 14C data in tree rings is an outstanding proxy for uncovering extreme solar energetic particle (SEP) events in the past. Signatures of extreme SEP events have been reported in 774/775 CE, 992/993 CE, and ∼660 BCE. Here, we report another rapid increase of 14C concentration in tree rings from California, Switzerland, and Finland around 5410 BCE. These 14C data series show a significant increase of ∼6‰ in 5411-5410 BCE. The signature of 14C variation is very similar to the confirmed three SEP events and points to an extreme short-term flux of cosmic ray radiation into the atmosphere. The rapid 14C increase in 5411/5410 BCE rings occurred during a period of high solar activity and 60 years after a grand 14C excursion during 5481-5471 BCE. The similarity of our 14C data to previous events suggests that the origin of the 5410 BCE event is an extreme SEP event.

A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B) may underlie abnormal cardiac excitation manifested by coved-type ST-elevation compatible with Brugada syndrome in Japanese.

OBJECTIVE: Brugada syndrome (BrS) is a rare sodium channelopathy typically seen in middle-aged, Southeast Asian males conferring high risks of cardiac sudden death. Loss-of-function mutations in SCN5A encoding the alpha-subunit of cardiac sodium channels may account partially for its etiology. We aimed to study whether mutations in the beta-subunits of sodium channel (SCN1B and SCN2B) would also be associated with abnormal cardiac excitation in BrS. METHODS: 85 Japanese patients suspected to have BrS undertook a diagnostic challenge test with a sodium channel blocker, pilsicainide. Genetic screenings were performed for SCN5A, SCN1B and SCN2B by PCR-SSCP and direct sequence of amplicons in the patients and 50 healthy controls. RESULTS: 30 patients exhibited BrS-like ECG pattern (i.e., a coved-type ST-segment elevation) either at baseline or after the drug challenge. Genetic screenings revealed a sequence variation (p.R190Q) and 3 polymorphisms (p.H558R, p.R1193Q, IVS24+53T > C) in SCN5A, a sequence variation (g.-26G > T) and 2 polymorphisms (IVS1+53G > T and IVS3 +2996(TTA)8-15) in SCN1B and 2 polymorphisms (IVS2+27A > G, IVS2+76G > A) in SCN2B. A logistic analysis revealed that male, middle age (40 - 59 years of age) and IVS3+2996(TTA)8 of SCN1B were significantly (p < 0.05) associated with the development of BrS-like ECG pattern with odds ratios (95% confidence intervals) of 5.9 (1.8 - 19.6), 2.9 (1.4 - 6.1) and 2.3 (1.1 - 4.9), respectively. While the IVS3+2996(TTA)8 allele has not been reported in Caucasians previously, its allelic frequency in the patients exhibiting the BrS-like ECG pattern (0.250) was comparable to that in the healthy controls (0.260). CONCLUSION: The IVS3+ 2996(TTA)8 allele commonly seen in Japanese would not be pathogenic itself but may render male, middle-aged Japanese more susceptible to BrS.

Scintigraphic imaging in Tako-Tsubo cardiomyopathy.

Tako-Tsubo cardiomyopathy (TTC, stress cardiomyopathy) is more common in elderly women and its symptoms can be deceptively similar to those of acute myocardial infarction. Although coronary arteries appear normal on coronary angiograms, a shape like a Tako-Tsubo (a Japanese fishing pot for trapping octopuses) can be observed on left ventriculogram. TTC is generally considered to be a trigger for sudden cardiac death. The onset mechanism of TTC is still controversial. Catecholamine cardiotoxicity and/or coronary circulation disturbance due to coronary microvascular spasm and/or neurogenic stunned myocardium as a result of autonomic imbalance are considered to be the most likely causes. In this review, we assess the usefulness of myocardial scintigraphic imaging in TTC patients on the basis of the results obtained from earlier studies and case reports in order to establish a deeper understanding of the pathophysiological mechanism of this syndrome.

Radiocarbon Production Events and their Potential Relationship with the Schwabe Cycle.

Extreme cosmic radiation events occurred in the years 774/5 and 993/4 CE, as revealed by anomalies in the concentration of radiocarbon in known-age tree-rings. Most hypotheses point towards intense solar storms as the cause for these events, although little direct experimental support for this claim has thus far come to light. In this study, we perform very high-precision accelerator mass spectrometry (AMS) measurements on dendrochronological tree-rings spanning the years of the events of interest, as well as the Carrington Event of 1859 CE, which is recognized as an extreme solar storm even though it did not generate an anomalous radiocarbon signature. Our data, comprising 169 new and previously published measurements, appear to delineate the modulation of radiocarbon production due to the Schwabe (11-year) solar cycle. Moreover, they suggest that all three events occurred around the maximum of the solar cycle, adding experimental support for a common solar origin.

Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy.

BACKGROUND: Although in reversible takotsubo cardiomyopathy (TC), wall motion generally recovers dramatically within a few weeks, there are few data on changes in autonomic function in this condition. AIM: To investigate cardiac autonomic function in the acute and chronic phases of TC. METHODS: Ten patients with TC (mean age 70.1 +/- 13.7 years) underwent cardiac catheterization on the first hospital day, when left ventricular (LV) ejection fraction (EF) was calculated. A Holter electrocardiographic study was performed within 3 days after the onset of symptoms (0 months) and 3 months after discharge (3 months). The standard deviation of the mean cycle length of normal-normal R-R (NN) intervals over 24 h (SDNN), and the 24-h standard deviation of the mean value of the difference between the NN intervals for each 5-min segment (SDANN), were calculated according to time-area analysis of heart rate variability over 24 h. Frequency domain analysis was also done. RESULTS: Coronary angiography in the acute and chronic phases revealed no significant stenosis in any TC patient. LV wall motion returned to normal in 17.6 +/- 6.4 days. LVEF was 45.7 +/- 8.8% in the acute phase and 69.8 +/- 6.8% after the improvement of wall motion (p < 0.001). Between 0 months and 3 months, SDNN and SDANN improved significantly, from 88.8 +/- 35.5 to 109.5 +/- 33.4 ms (p = 0.01) and from 79.9 +/- 34.7 to 99.3 +/- 40.3 ms (p = 0.03), respectively. No significant changes were observed in frequency domain parameters. DISCUSSION: These results support our previous hypothesis that TC might be caused by neurogenic stunning of the myocardium, due to acute autonomic dysfunction.

Canine epidermal langerhans cells express alpha and gamma but not beta chains of high-affinity IgE receptor.

Epidermal Langerhans cells (LC) express a high-affinity receptor for IgE (FcepsilonRI), consisting of two chains (alpha and gamma chains) in humans that allows LC to perform Fc receptor-mediated uptake of allergens. We found that canine LC express alpha and gamma chains but not beta chain of FcepsilonRI, identical to human but not to mouse LC, which do not express functional FcepsilonRI (only gamma chain is expressed). This finding indicates that canine LC have FcepsilonRI-mediated function similar to or identical to human LC, raising the possibility that canine species provides a better model than mouse to understand the pathogenesis of human atopic dermatitis and investigate the therapeutic effect of drugs.

A facile synthesis of dragmacidin B and 2,5-bis(6'-bromo-3'-indolyl)piperazine.

A short synthesis of dragmacidin B (1), 2,5-bis(6'-bromo-3'-indolyl)piperazine (2), and corresponding didebromo analogues 8 and 9 is described. The key steps involve the dimerization of oxotryptamines 4 and 11 to give bis(indolyl)pyrazines 5 and 12, which upon selective reduction and reductive methylation with sodium cyanoborohydride afforded the requisite piperazine natural products.

A concise synthesis of topsentin A and nortopsentins B and D.

[reaction: see text] A concise synthesis of topsentin A (R(1) = R(2) = H) and nortopsentins B (R(1) = Br, R(2) = H) and D (R(1) = R(2) = H) is described from oxotryptamine 5 via reduction of acyl cyanide 4. Regiospecific bromination of 3-cyanoindole afforded 6-bromo-3-cyanoindole (10) as the major product.

Plasma brain natriuretic peptide in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy is a reversible left ventricular dysfunction with symptoms resembling acute myocardial infarction, but without coronary lesions. Patients have wall motion abnormalities (apical akinesis and basal hyperkinesis), and characteristic left ventricular morphology. AIM: To investigate plasma brain natriuretic peptide (BNP) concentrations in takotsubo cardiomyopathy. METHODS: Ten consecutive patients with takotsubo cardiomyopathy underwent cardiac catheterization on their first hospital day, and blood was collected to measure BNP. To evaluate acute basal hyperkinesis, the difference in diameter between systole and diastole was measured at 10 mm below the aortic valve (the deltaBase value). RESULTS: Coronary angiography revealed no significant stenosis in any patient. Initial ejection fraction was 42.2 +/- 7.3%, cardiac index was 1.90 +/- 0.39 l/min/m(2), and plasma BNP was 522.5 +/- 632.9 pg/ml. Ventricular contraction and the ejection fraction were normalized on echocardiography after 17.9 +/- 6.3 days. BNP was significantly correlated with deltaBase, but not with other cardiac parameters. DISCUSSION: Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition.

The clinical features of takotsubo cardiomyopathy.

BACKGROUND: Cardiologists have recently recognized a reversible form of heart failure of unknown origin characterized by a takotsubo-shaped hypokinesis of the left ventricle on left ventriculography. AIM: To clarify the clinical features of this cardiomyopathy. DESIGN: Observational study. METHODS: Seven patients with reversible ventricular dysfunction were followed for 4.5 years. Clinical course, routine examinations, and cardiac catheterizations in each patient were documented. RESULTS: The cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments, together with hyperkinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology. The cardiac events did not recur over a 1-4 year follow-up. DISCUSSION: Coronary vasospasm, myocarditis and other substantial diseases previously described were ruled out as the cause of takotsubo cardiomyopathy in our subjects. Prognosis was good without any form of treatment, provided that the patients survived the severe heart failure state. Catecholaminergic or adrenoceptor-hyperactive cardiomyopathy may be the cause of this cardiomyopathy.

Variant angina due to deficiency of intracellular magnesium.

A 51-year-old man was diagnosed as having variant angina by documentation of typical ST elevation during anginal attack and also by showing coronary arterial spasm (#2 and #12) during hyperventilation on coronary arteriography. Large quantities of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). After hourly infusion of magnesium sulfate (80 mEq), coronary spasm could not be induced by ergonovine.

Assessment of posterior aortic wall motion using echocardiogram in patients with atrial fibrillation.

BACKGROUND AND HYPOTHESIS: Noninvasive evaluation of left ventricular (LV) diastolic function was performed on 12 patients with atrial fibrillation (AF) using posterior aortic wall echocardiogram and a parameter for determining the optimal heart rate in patients with chronic atrial fibrillation was considered. METHODS: Subjects were divided into two groups; one with no underlying cardiac disease (AF only group; n = 7) and the other with dilated cardiomyopathy (DCM group; n = 5). Left atrial emptying index (LAEI) obtained from the posterior aortic wall echocardiogram was used as the parameter of LV diastolic function, and R-R interval-LAEI relation and minimum R-R interval showing LAEI = 1.0 were investigated and compared between the two groups. RESULTS: There was a good correlation between R-R interval and LAEI until LAEI of 1.0 was obtained in all patients. Slope of the regression line was significantly steeper in the AF only group than in the DCM group, and minimum R-R interval showing LAEI = 1.0 was significantly shorter in the AF only group. CONCLUSION: Assessment of R-R interval-LAEI relation was useful for the noninvasive evaluation of LV diastolic function, and this parameter could be used for clinical application to determine the optimal heart rate in atrial fibrillation.

Heart failure in 3 patients with acromegaly: echocardiographic assessment.

We evaluated 3 patients with acromegaly who developed heart failure. Heart failure appeared to be due to acromegalic cardiomyopathy in 2 patients who did not have hypertension or evidence of coronary artery disease, and it was possibly due to acromegalic cardiomyopathy combined with familiar hypertrophic cardiomyopathy in 1 patient. The common echocardiographic findings in the present three cases were: 1) enlargement of the left atrium, 2) markedly dilated left ventricular cavity with diffuse hypokinesis, 3) decrease of indices of the left ventricular systolic function, and 4) no evidence of left ventricular hypertrophy. Echocardiographic findings in acromegaly with congestive heart failure resemble those of idiopathic dilated cardiomyopathy.

Specialty-related disparities of readmission in patients with chronic heart failure: the importance of hospital-clinic cooperation.

OBJECT: The purpose of this study was to elucidate differences in readmission rates and late outcome in outpatients with chronic heart failure treated in different clinical settings. PATIENTS AND METHODS: This study included 65 consecutive patients who were admitted to our CCU due to acute heart failure for the first time and discharged from our institution. After their discharge, 31 were cared for by a cardiologist in the outpatient clinic of our institution (group A) and the other 34 were cared for by a general practitioner in a clinic (group B). The various findings during the acute phase and the follow-up period were retrospectively compared between the two groups. In addition, the incidence of unexpected readmission and prolonged outcomes were compared between the two groups. RESULTS: The patients in group B were older than those in group A, but no other differences were noted in patient characteristics. More patients in group A required more than one hospitalization within 6 months from discharge (group A, 35.5%; group B, 8.9%, p<0.01; follow-up period, 17.1+/-5.9 months). There was no difference in the survival rate between the groups. CONCLUSION: We concluded that stabilized outpatients should receive comprehensive care from a general practitioner to avoid the need for readmission after discharge.

Assessment of reflection pulse wave in patients with cardiomyopathy: evaluation of noninvasive measurement of wave intensity.

OBJECTIVE: We assessed the reflection pressure wave using noninvasive measurement of wave intensity (WI) in patients with cardiomyopathy. METHODS AND RESULTS: Subjects included 8 patients with hypertrophic cardiomyopathy (HCM group) and 10 patients with dilated cardiomyopathy (DCM group). Twelve healthy subjects were used as a control group. By using a combined Doppler and echo-tracking system, changes in vascular diameter (dD) and blood flow velocity (dV) were recorded simultaneously at the common carotid artery and dD x dV was measured as WI. In the components of WI, the positive component of early systolic phase (FE) and the negative component following FE (B) were significantly reduced in the DCM group. There was a significant positive correlation between FE and B in all 3 groups. The appearance time of B was significantly shorter in the HCM group and significantly longer in the DCM group compared with the control group. CONCLUSIONS: It was suggested that the value of the reflection pressure wave was influenced by the left ventricular contractility, and that the effect of the reflection pressure wave appeared earlier in patients with HCM and later in patients with DCM compared with the control subjects.

[A case of Vietnamese immigrant with tuberculous mediastinopericarditis].

A case of vietnamese immigrant with tuberculous mediastinopericarditis was reported and the literature was reviewed. A 39 year-old man was admitted to our hospital with chief complaints of dyspnea and weakness. Blood chemistry suggested the existence of congestive liver dysfunction. Chest X-ray film revealed marked cardiomegaly and a abnormal mass in the anteriorly superior area which was confirmed as anterior mediastinum on CT scan. Echocardiogram disclosed a large volume of pericardial effusion and thickened pericardium. Tuberculin test was positive. Firstly, this mediastinal mass was believed to be malignant tumor and the pericardial effusion had originated from it. Finally, tuberculous mediastinopericarditis was diagnosed by detecting tuberculous mycobacterium from the cultured pericardial effusion and also the biopsied lymph nodes. Although occurrence of tuberculous mediastinopericarditis is rare at the present time in Japan, this disease has not been exterminated and should be kept in mind.

[Influence of aging and circadian fluctuation of fibrinolytic factors to the responses of these factors during venous occlusion test in healthy subjects].

This study was aimed to clarify the influence of aging and circadian fluctuation of fibrinolytic factors to changes of tissue plasminogen (t-PA) and its inhibitor (PAI-I) during venous occlusion test. Venous occlusion was achieved by application of a sphygmomanometer cuff to the upper arm of elderly healthy subjects (n = 12) and young healthy subjects (n = 12) at 10:00 am and 4:00 pm. Plasma concentration of t-PA, free PAI-1 and total PAI-1 were measured by ELISA. The activity of t-PA was measured by bioimmunoassay using monoclonal antibody for t-PA. Circadian variation was observed in the change of t-PA activity and total PAI-1. These were highly increased in the evening. However, this phenomenon was different between age groups and increase of t-PA activity occurred in elderly subjects, whereas PAI-1 was observed in young subjects. In conclusion, circadian variation and the influence of age should be considered to evaluate results of venous occlusion test.

[Daily activity evaluated from total energy consumption in the chronic stage of myocardial infarction and limiting factors in elder patients].

In chronic case of myocardial infarction (OMI), alternation of a daily total energy consumption (DTEC) between in OMI and in the pre-infarction stage was investigated. The limiting factors of DTEC, including functional classification according to New York Heart Association (NYHA) subset, Forrester's hemodynamic subset (FS) in the stage of acute myocardial infarction (AMI), numbers of significant coronary arterial stenosis (NCAG), cardiac function at rest in OMI, for example; cardiac index (CI), pulmonary capillary wedge pressure (PCW), left ventricle end-diastolic pressure (EDP) and exercise tolerance in OMI, were considered. Subjects, consisting of 191 OMI cases, were classified into the younger group less than 59 years old (79 males and 10 females) and the older group greater than 60 years old (102 males and 23 females). Daily physical activity was examined by questionnaires from these patients and DTEC was calculated based on daily physical activity. Results in the younger group and older group were investigated separately. Reduction of DTEC after myocardial infarction was recognized in all ages and both sexes, however, reduction of DTEC in the older group was less than in the younger group, especially in males. Concerning the limiting factors of the older group, exercise tolerance in OMI was related to reduction of DTEC. NYHA category, FS in the AMI stage, NCAG, CI, PCW and EDP had no significant relation to DTEC. In addition, the effects of social limiting factors, for instance retirement, and mental limiting factors were considered to be important.

[Outcomes of primary angioplasty in patients aged 85 years old and older who have acute myocardial infarction].

Outcomes of primary angioplasty in 6 elderly patients with acute myocardial infarction who were admitted to the hospital between July of 1994 and June of 1997 were reviewed retrospectively. Emergency coronary angiography was done in 7 of 16 patients (44%) who were at least 85 years old and primary angioplasty was done in 6 patients (38%). Dilatation was successful in all 6 patients. Congestive heart failure occurred in 4 patients and cardiogenic shock occurred in 1 patient, but no patient died during hospitalization. Blood transfusion and surgical resection were done in 1 patient because of a giant hematoma and pseudoaneurysm at the puncture site. Although the creatinine level increased after angioplasty in all 6 patients, dialysis therapy was not needed. All patients were alive and none had angina at follow-up (mean follow-up period = 16.5 months). Primary angioplasty was successful in patients at least 85 years old; both short-term and long-term outcomes were good. Primary angioplasty should be considered to be an effective treatment for acute myocardial infarction in people 85 years old and older.

[Successful non-surgical treatment of acute coronary syndrome involving the left main coronary trunk in four elderly patients].

We encountered 4 patients aged over 80 with acute coronary syndrome involving the left main coronary trunk (LMT) who obtained a successful outcome by non-surgical management. CASE 1: An 80-year-old women suffered acute myocardial infarction. A coronary stent was placed at the orifice of the LMT for dilatation of severe 90% stenosis. Cardiac function was markedly improved after treatment during the chronic period. CASE 2: An 81-year-old man who developed non-sustained ventricular tachycardia. Coronary angiography demonstrated severe stenosis with haziness of the LMT. Intra-aortic balloon pumping was performed for one whole day after the attack and the follow-up study performed one month later revealed that the stenosis was markedly diminished to an insignificant grade without residual ischemia. CASE 3: An 81-year-old man developed acute inferior wall infarction with a background of severe triple vessel disease accompanied by an LMT lesion. Coronary stents were placed at three sites, i.e., the right coronary, LMT, and left anterior descending branch. Though initial treatment was successful, this patient died due to severe arrhythmia. Patients in who CABG is strongly indicated due to LMT lesion complicated with multiple organ disorders will increase as the population of the aged continues to increase in Japan. We obtained satisfactory results by intensive intense non-surgical management including PTCA. From our experience, adequate selection of therapeutic regimens for individual patients is important to improve the long-term prognosis as well as the immediate outcome in the acute stage.