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This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features.We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed.A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa-associated lymphoid tissue (MALT) lymphoma (9%), peripheral T-cell lymphoma-NOS (2%), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine.Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

Eradication therapy of Helicobacter pylori may be safe if hemin has been intravenously administered in advance, even in patients with a history of recurrent acute porphyria attack.

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Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis. Case presentation An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband’s bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients’ clinical outcomes were different from each other; i.e., the husband survived, and the wife died. Conclusions SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient’s clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife’s clinical course. Our findings demonstrate that a patient’s immune response contributes to their prognosis following SFTSV infection.

Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070–2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs.

High-density lipoprotein (HDL) mediates reverse cholesterol transport. In this process, the human homolog of the B class, type I scavenger receptor (SR-BI), CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. In endothelial cells, HDL activates endothelial nitric oxide synthase (eNOS) via hSR-BI/CLA-1, and 17β-estradiol (E2) modulates nitric oxide (NO) synthesis. In this study, we elucidated the effect of E2 on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). HSR-BI/CLA-1 expression was examined by real-time PCR, western blot analysis and reporter gene assay in HUVECs incubated with E2. eNOS activity was assessed by detection of phosphorylation (Ser 1179) of eNOS. We investigated the effect of the constitutively active form or dominant negative form of protein kinase C on hSR-BI/CLA-1 promoter activity. Our results showed that E2 increased the endogenous expression of hSR-BI/CLA-1. E2 also enhanced the activity of the hSR-BI/CLA-1 promoter and the expression of its mRNA. However, bisindolylmaleimide I, an inhibitor of protein kinase C, blocked the stimulatory effect of E2 on hSR-BI/CLA-1 promoter activity. Moreover, constitutively active PKC increased the activity of the hSR-BI/CLA-1 promoter, and a dominant-negative mutant of PKC prevented E2 from stimulating promoter activity. In cells treated with E2, HDL stimulated the phosphorylation of serine 1179 of eNOS in HUVECs. These results suggested that E2 upregulates the expression of the endothelial hSR-BI/CLA-1 via the PKC pathway, which may be a novel mechanism of the anti-atherosclerotic potential of E2 in vascular endothelial cells.

Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R (2) = 0.048, p < 0.001 and R (2) = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.

Cardio-ankle vascular index (CAVI) has been demonstrated as a parameter of arterial stiffness, which antihypertensive therapy may improve. However, little information is available about the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. We performed a study to examine the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. Eighty treated hypertensive patients (71 ± 10 years) were divided into two groups: 50 patients showing a decrease in CAVI (Group 1) and 30 patients showing an increase (Group 2) during observation (24 ± 11 months) of antihypertensive therapy. The groups did not differ in the rates of use of angiotensin II receptor blockers or calcium channel blockers. Age (Group 1: 67 ± 11 versus Group 2: 74 ± 8 years), left ventricular mass index (LVMI) (Group 1: 103 ± 19 versus Group 2: 120 ± 24 g/m(2)) and systolic blood pressure (Group 1: 133 ± 17 versus Group 2: 144 ± 23 mm Hg) at the start of observation were significantly higher in Group 2 than in Group 1 (p = 0.003, p = 0.001 and p = 0.027, respectively). The changes in CAVI during observation were correlated only with LVMI (r = 0.289, p = 0.009) at the start of observation for all 80 patients. It may be difficult to improve arterial stiffness assessed by CAVI during antihypertensive therapy in hypertensive patients with left ventricular hypertrophy.

Objective To examine factors affecting systolic blood pressure (SBP) variability during a single clinic visit, in treated hypertensive patients. Methods Hypertensive patients were recruited to this observational study. Blood pressure was measured using an automated blood pressure monitor when each patient arrived at the outpatient clinic and again when they saw the physician. Mean SBP and SBP variability during a single clinic visit were calculated. The cardio–ankle vascular index (CAVI), as a marker of arterial stiffness, was also measured. Results A total of 57 treated hypertensive patients (mean age 71 years) were included in the study. The mean SBP was positively correlated with age ( r = 0.457), while SBP variability was positively correlated with age ( r = 0.383), CAVI ( r = 0.330), and glycosylated haemoglobin ( r = 0.345) and triglyceride levels (r = 0.299). Conclusion Variability in SBP during a single clinic visit showed better correlations with arterial stiffness and risk factors for atherosclerosis than did mean SBP. Large SBP variability during a single clinic visit may reflect progression of atherosclerosis, in treated hypertensive patients.

Recent studies have elucidated a lower level of serum insulin-like growth factor-I (IGF-I) or a decrease in the IGF-I/IGF-binding protein-3 (IGFBP-3) ratio in patients with type 2 diabetes mellitus or hepatic steatosis. Persistent hepatitis C virus (HCV) infection often evokes metabolic abnormalities including hepatic steatosis and insulin resistance. We hypothesized that the relationship between the ratio of IGF-I/IGFBP-3 and the severity of hepatic steatosis or insulin resistance would be observed in patients with HCV-related chronic liver disease (CLD). On the basis of the classifications proposed by Brunt and colleagues ( Am J Gastroenterol 1999; 94: 2467-2474), among the 42 enrolled patients with HCV-related CLD, 23 of them had no hepatic steatosis (grade 0), 14 had grade 1 steatosis, and 5 had grade 2 steatosis. The levels of serum IGF-I in the enrolled patients declined in proportion to the severity of hepatic steatosis, whereas serum IGFBP-3 levels did not affect its severity. Therefore, the ratio of IGF-I/IGFBP-3, which corresponds to the circulating free IGF-I status, was significantly lower in those patients with hepatic steatosis (grades 1 and 2) than in those without hepatic steatosis. Serum IGF-I levels significantly correlated with serum zinc levels ( r = 0.370, P = .0266), but IGFBP-3 levels did not. However, the linear regression analysis revealed an inverse correlation between the IGF/IGFBP-3 ratio and the value of homeostasis model for assessment of insulin resistance ( r =−0.411, P = .0094). These findings suggest that the decline of the circulating free IGF-I level, which derives from zinc deficiency, may contribute to hepatic steatosis and insulin resistance in patients with HCV-related CLD.

The significance of antibodies to cardiolipin (anti-CL) remains uncertain in patients with chronic hepatitis C (CH-C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH-C seropositive for anti-CL. The prevalence of anti-CL and clinical parameters associated with anti-CL in those patients were examined. Six of the 45 (13%) patients with CH-C had anti-CL. However, none of these six CH-C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH-C patients with anti-CL were significantly higher than those in CH-C patients without anti-CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH-C patients with anti-CL had significantly more progressive hepatic fibrosis than those without anti-CL. The degree of 8-hydroxy 2′-deoxyguanosine (8-OHdG) expression in the liver tissue was more severe in CH-C patients with anti-CL than in those without it. However, the emergence of anti-CL in CH-C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti-CL is associated with oxidative stress and that CH-C patients seropositive for anti-CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis. J. Clin. Lab. Anal. 26:342-348, 2012. © 2012 Wiley Periodicals, Inc.

Morning hypertension is an independent risk factor for cardiovascular diseases, particularly stroke. However, the optimal time at which to take antihypertensive medication to treat morning hypertension remains unclear. We prospectively enrolled elderly patients (over 65 years old) with morning hypertension who had suffered an ischemic stroke (or strokes). Additional treatments (one of six arms) were randomly administered for 10 weeks in the morning, in the evening or at bedtime (n=15 for each time point/medication). The patients measured their blood pressure and heart rate at home for 14 days prior to the intervention and for the final 14 days, and recorded the data in a blood pressure diary. The patients' urinary albumin/creatinine ratios were evaluated before and after the 10-week intervention. A total of 270 patients were enrolled in this study (mean age: 75.6±5.8 years; female/male ratio: 125/145). Their morning and evening systolic blood pressures were significantly decreased after following any of the study medication dosing schedules (P

Mutations in thep53gene leading to conformational changes in the p53 protein have been well established in many human cancers. Conformational changes and/or cellular accumulation of the protein may induce an immune response, resulting in circulating autoantibodies to p53, which have been documented in several types of cancers. Although rarely associated with autoimmune disease, a few reports have documented titres of anti-p53 autoantibodies in patients with autoimmune hepatitis and primary biliary cirrhosis. The clinical relevance of circulating autoantibodies to p53, therefore, remains unclear. Accordingly, this study aimed to examine the prevalence and clinical relevance of anti-p53 autoantibodies in patients with selected autoimmune liver diseases.BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies.OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases.METHODS: Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53.RESULTS: Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213).CONCLUSION: The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity ( E)/peak late transmitral flow velocity ( A) (the E/A ratio), peak early diastolic mitral annular velocity ( e′) and the E/e′ ratio. Although LVMI, E/A and e′ did not differ between the two groups, E/e′ was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Although visit-to-visit variability in systolic blood pressure (SBP) has recently been demonstrated to be a strong predictor of stroke, there are no data about relationships between SBP variability and cardiac damage in hypertensive patients. We compared relationships between visit-to-visit variability in SBP and left ventricular (LV) diastolic dysfunction with the relationships between the mean SBP value and cardiac parameters in treated patients. Forty treated hypertensive patients (69 ± 9 years of age) had their blood pressure measured at outpatient clinics every 1 or 2 months over a 1-year period. The standard deviation (s.d.) of SBP and the difference between the maximum and minimum SBPs during this year were calculated to assess visit-to-visit variability. The mean SBP during the year was also calculated. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (e') and the ratio (E/e') of E to e' using Doppler echocardiography. E/A only correlated with the s.d. of SBP (r=-0.327, P=0.040), whereas e' correlated with s.d. of SBP (r=-0.496, P=0.001) and maximum-minimum SBP difference (r=-0.490, P=0.001). E/e' correlated with s.d. of SBP (r=0.384, P=0.014), maximum-minimum SBP difference (r=0.410, P=0.009), and the mean value of SBP (r=0.349, P=0.028). Multiple regression analysis demonstrated only the maximum-minimum SBP difference independently associated with E/e' (β=0.410, P=0.009). Thus, the visit-to-visit variability of SBP showed better correlation with LV diastolic dysfunction than mean values of SBP. High visit-to-visit variability of SBP was associated with LV diastolic dysfunction and may constitute a high risk for diastolic heart failure in hypertensive patients.

The GLUT2 glucose transporter plays an important role in glucose-induced insulin secretion in pancreatic β-cells by catalyzing the uptake of glucose into the cell. In this study, we investigated whether exendin-4, a long-acting agonist of glucagon-like peptide-1, mediates stimulatory effects on GLUT2 gene expression through the Ca²+/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) cascade. GLUT2 expression was examined by real-time polymerase chain reaction, Western blot analysis, and a reporter gene assay in rat insulin-secreting INS-1 cells incubated with exendin-4. An increased expression level of GLUT2 protein was noted in response to increasing concentrations of exendin-4, with maximal induction at 10 nmol/L. Real-time polymerase chain reaction analysis similarly revealed a significant increase in the amount of GLUT2 messenger RNA by 10 nmol/L exendin-4. Exendin-4 also stimulated GLUT2 promoter activity in response to increasing exendin-4 concentrations, but failed to do so in the presence of STO-609, a CaMKK inhibitor. We also investigated the effect of the constitutively active form of CaMKK (CaMKKc) on GLUT2 promoter activity. The result is consistent with the observations that CaMKKc/CaMKIV enhanced or up-regulated GLUT2 promoter activity in INS-1 cells. Furthermore, exendin-4 induction of GLUT2 protein expression was significantly suppressed in the cells knocking down the CaMKIV. In summary, activation of the CaMKK/CaMKIV cascade might be required for exendin-4-induced GLUT2 gene transcription, indicating that exendin-4 plays an important role in insulin secretion in pancreatic β-cells.

We examined which echocardiographic parameter correlated best with plasma brain natriuteric peptide (BNP) levels in treated hypertensive patients. Enrolled in the study were 122 treated hypertensive patients (70 ± 9 y). The left ventricular mass index and left atrial dimension (LAD) were measured using echocardiography as indexes of left ventricular hypertrophy and left atrial enlargement, respectively. Among all the echocardiographic parameters, LAD correlated best with BNP (r = 0.343, p < 0.001). Stepwise regression analysis showed that LAD (β coefficient = 0.513, p < 0.001) was independently associated with BNP. Left atrial enlargement, rather than left ventricular hypertrophy, may be clinically useful for predicting elevated BNP levels in treated hypertensive patients.

Scheie's classification regarding hypertensive and atherosclerotic lesions in retinal arteries is generally used to assess the severity of hypertensive retinopathy and the risks of cardiovascular events in hypertensive patients. However, the differences between these two types of retinal artery lesions have not been fully examined. Both arterial stiffness and aortic root diameter are increased in hypertensive patients. The aim of this study was to elucidate differences in the two types of lesions by comparing their relationships to arterial stiffness and aortic root diameter in hypertensive patients following stroke. Fifty-two hypertensive patients following stroke were divided into five stages according to Scheie's classification of hypertensive (H stage 0-4) and atherosclerotic (S stage 0-4) lesions by ophthalmologists. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV) using an automatic waveform analyzer. Aortic root diameter was measured using M-mode echocardiography. The H and S stages in retinal arteries correlated with each other (ρ = 0.443, p < 0.001). However, the S stage correlated with baPWV (ρ = 0.385, p = 0.005) and the aortic root diameter (ρ = 0.285, p = 0.043), while the H stage did not correlate with these parameters. Multiple stepwise regression analysis demonstrated that the aortic root diameter was independently associated with S stage (β = 0.373, p = 0.006), even though baPWV was independently associated with neither S stage nor H stage. In conclusion, hypertensive lesions (H stage) in retinal arteries are associated with atherosclerotic lesions (S stage) in retinal arteries. However, S stage may reflect arterial stiffening and aortic root dilatation better than H stage in hypertensive patients following stroke. This difference between H and S stages of Scheie's classification should be kept in mind when considering the association between retinal microcirculation and large vessel arteriosclerosis.

Although left ventricular (LV) hypertrophy and diastolic function assessed by echocardiography and chronic kidney disease (CKD) have been established as predictors of cardiovascular events in hypertensive patients, the relationships between the echocardiographic parameters and renal function have not been fully examined. We examined which echocardiographic parameter correlates best with estimated glomerular filtration rate (eGFR) in patients with cardiovascular risk factors. Enrolled in the study were 309 patients (mean age 67 +/- 13 y) with cardiovascular risk factors. Echocardiography was performed to measure left ventricular mass index (LVMI) as an index of LV hypertrophy. Transmitral early to atrial velocity (E/A) ratio and peak early diastolic mitral annular velocity (E') were measured as indexes of LV diastolic function. E/E' was calculated as a parameter of LV preload. eGFR was measured using the equation proposed by the Japanese Society of Nephrology. The correlations of LVMI (r = -0.333, p0.001) and hypertension (r = -0.326, p0.001) to eGFR were closer than those of E' (r = 0.276, p0.001) and E/A (r = 0.224, p0.001) to eGFR. Stepwise regression analysis showed that hypertension (beta coefficient = -0.211, p0.001) and LVMI (beta coefficient = -0.206, p0.001) were independently associated with eGFR. The E/E' increased with a decrease in eGFR, and E/E' in CKD stage 5 (16.0 +/- 6.8) was significantly higher than that in patients in whom eGFRor = 90 mL/min/1.73 m(2) (10.5 +/- 4.5) (p0.001). Left ventricular diastolic function may be influenced by the increase in LV preload due to progression of CKD stage. Therefore, LV hypertrophy may be superior to LV diastolic dysfunction in predicting low eGFR in patients with CKD using echocardiography.

Although mitral annular velocity assessed by tissue Doppler echocardiography has been established as a parameter of left ventricular (LV) diastolic function, aortic annular velocity has never been investigated as a parameter of cardiovascular function. We investigated whether aortic annular velocity can be measured using the same tissue Doppler echocardiographic method that is used for measuring mitral annular velocity, as well as the correlation between the aortic annular velocity thus measured and arterial stiffness that was assessed by the cardio-ankle vascular index (CAVI). Sixty-three patients (69 +/- 13 years) with hypertension, diabetes, or dyslipidemia, who had no overt heart disease, were enrolled. The mitral and aortic annular velocities were measured at the mitral and aortic annuluses, respectively, using tissue Doppler echocardiography. Aortic annular velocity was successfully obtained in all patients. The correlation between the peak early diastolic aortic annular velocity (r = -0.803, p0.001) and CAVI as an index of arterial stiffness was greater than that of the peak early diastolic mitral velocity and CAVI (r = -0.649, p0.001). Stepwise regression analysis showed that the age (beta coefficient = 0.488, p = 0.002) and the peak early diastolic aortic annular velocity (beta coefficient = -0.405, p = 0.008) were independent determinants of the CAVI. The strong inter-relationship was found between left ventricular diastolic function assessed by the aortic annular velocity and arterial stiffness assessed by CAVI. In conclusion, the aortic annular velocity may be helpful for assessing arterial stiffness in patients with cardiovascular risk factors.

The diameter of the inferior vena cava (IVC) measured with echocardiography is clinically used as a parameter to estimate right atrial pressure, which reflects dehydration or overhydration. Because elderly patients fall easily into dehydration, normal values for IVC diameters in elderly patients may be helpful for geriatric medicine. However, normal values of IVC diameter in relation to age have not been investigated. The purpose of this study was to elucidate age-related changes in IVC diameter using echocardiography. Enrolled in the study were 200 patients (67 ± 15 yrs: range 17-94 yrs) with cardiovascular risk factors but no overt cardiac diseases. IVC diameters throughout the respiratory cycle were measured as maximum and minimum IVC diameters (IVC(max), IVC(min)) using M-mode echocardiography. To assess IVC collapsibility, the respirophasic variation of IVC diameter was calculated as (IVC(max) - IVC(min))/(IVC(max)) ×100. Maximum IVC diameter was decreased with advancing age (r = -0.221, p = 0.002). The respirophasic variation of the IVC diameter was increased with advancing age (r = 0.244, p = 0.001). Stepwise multiple regression analysis showed that age was an independent determinant for both maximum IVC diameter (s coefficient = -0.249, p < 0.001) and respirophasic variation of the IVC diameter (s coefficient = 0.268, p < 0.001). Age-related decrease in maximum IVC diameter and increase in the respirophasic IVC collapsibility may indicate the decrease in right atrial pressure in some elderly patients. Therefore, elderly patients with decreased maximum IVC and increased respirophasic IVC collapsibility may need prevention for dehydration.

Chronic hepatitis C virus (HCV) infection frequently evokes metabolic abnormalities including insulin resistance. A decrease in serum zinc (Zn) levels is often observed in association with hepatic fibrosis. Zn also plays important roles in insulin secretion. However, little is known about the relationship between Zn deficiency and insulin resistance in patients with HCV-related chronic liver disease. The main purpose of this study was to examine the contribution of Zn deficiency to insulin resistance in patients with chronic hepatitis C (CH-C). Forty-eight non-diabetic patients with CH-C were enrolled. Serum alanine aminotransferase (ALT), ferritin and Zn levels were examined in the enrolled patients with CH-C. Insulin resistance was determined by the Homeostasis model for assessment of insulin resistance (HOMA-IR). Zn deficiency was defined as serum Zn levels

Aortitis syndrome is a chronic vasculitis that leads to arterial wall thickening and stiffening in large elastic arteries. However, there are no established markers for assessing arterial stiffening in aortitis syndrome. The cardio-ankle vascular index (CAVI) has recently been utilized to assess arterial stiffening that is associated with atherosclerosis-related diseases. We hypothesized that CAVI can be applicable for assessing alterations in arterial stiffness during immunosuppressive therapy for aortitis syndrome. A 69-year-old woman with a 2-month history of recurrent fever, fatigue, and malaise, showed intense 18F-fluorodeoxyglucose (18F-FDG) uptake in the thoracic aorta and common carotid arteries in 18F-FDG-positron emission tomography. These clinical and imaging findings resulted in the diagnosis of aortitis syndrome. The patient also showed the elevated CAVIs on both sides (right, 10.3; left, 10.4) (normal value for her age, 9.1 +/- 0.8), indicating the arterial stiffness due to aortitis syndrome. The patient was treated for 34 weeks with immunosuppressive therapy, which included oral prednisolone and methotrexate. C-reactive protein (from 4.24 to 0.49 mg/dL) and immunoglobulin G (from 2,627 to 1,524 mg/dL) were decreased by 7 weeks after initiation of the treatment. The decrease in these inflammatory parameters suggests the effectiveness of the immunosuppressive therapy. In addition, after the 34-week treatment, the CAVIs on both sides (right, 9.3; left, 9.2) were within the normal range. These data indicate that the immunosuppressive therapy ameliorates the degree of arterial stiffness. In conclusion, CAVI may be a promising marker for evaluating the effectiveness of immunosuppressive therapy in patients with aortitis syndrome.

The purpose of this study was to examine the usefulness of 11C-acetate positron emission tomography (PET) for assessing the efficacy of cardiac resynchronization therapy (CRT). Enrolled in this study were 20 patients with severe heart failure. All patients underwent 11C-acetate PET within 1 week after CRT. The oxygen consumption was measured by the monoexponential clearance rate of 11C-acetate (Kmono) for both CRT-off and -on. Cardiac efficiency (CE) was determined using the concept of the work metabolic index (WMI). WMI was calculated as WMI = (stroke volume index) × (systolic blood pressure) × (heart rate)/Kmono. The patients were divided into two groups: 14 patients with improved CE (from 5.27 ± 0.91 to 6.77 ± 1.12) and 6 patients with deteriorated CE (from 5.35 ± 0.92 to 4.86 ± 0.84) by CRT-on. Kmono decreased from 0.053 ± 0.006 to 0.046 ± 0.003 by CRT-on in the improved CE group (p = 0.028), but increased from 0.049 ± 0.006 to 0.050 ± 0.006 in the deteriorated-CE group (p = 0.036). Stroke volume index, systolic blood pressure, and heart rate did not change by CRT-on for either group. At the one-year follow-up, there were significantly higher rates of major cardiac adverse events in the deteriorated-CE group than in the improved-CE group (p = 0.032). Therefore, the improvement of CE, as assessed by 11C-acetate PET in the early period after CRT, is produced by the decrease in oxygen consumption in patients showing good responses to CRT. The decrease in oxygen consumption in the early period after CRT is thus a useful marker for predicting a good clinical outcome after CRT.

Involvement of the gastrointestinal tract in cytomegalovirus (CMV) infection is commonly observed in immunocompromised hosts. We encountered an immunocompetent patient with CMV associated-acute gastric mucosal lesion (AGML). The emergence of inclusion bodies characteristic of CMV infection in the specimens obtained from the patient's gastric ulcers was helpful in identifying the cause of AGML. The patient recovered without the administration of antiviral drugs. This case illustrates that CMV infection can be one of the causative agents that trigger AGML even in immunocompetent hosts, and that gastric biopsies are extremely useful for ascertaining the etiology of AGML.

There are no data regarding changes in plasma brain natriuretic peptide (BNP) levels in patients with Fabry's diseases during enzyme replacement therapy (ERT). We describe a patient with Fabry's disease who demonstrated the improvement in plasma brain BNP levels in response to ERT. Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, which results in progressive intracellular accumulation of globotriaosylceramide (Gb3) in various organs including the heart. Cardiac involvement is frequent in Fabry's disease, resulting in cardiac dysfunction due to hypertrophic changes of the myocardium and thickening of the valves. Although ERT has been reported to improve cardiac function, no consensus has been reached regarding the effectiveness of ERT in female patients with heterozygous Fabry's disease. We report a 44-year-old woman having heterozygous Fabry's disease, who showed mitral valve thickening and regurgitation on echocardiogram. ERT was performed by intravenous infusion of recombinant alpha-galactosidase A every 2 weeks. We assessed the influences of ERT on cardiac function by measuring echocardiograhic parameters and monitoring BNP levels, which show treatment-induced drop in patients with heart failure. Although her cardiac function and mitral regurgitation assessed by echocardiography had not improved 18 months after the beginning of ERT, the plasma BNP level, which was 91.5 pg/ml before ERT, fell to 18.9 pg/ml. In conclusion, plasma BNP levels may be useful for evaluating the effectiveness of ERT for heterozygous Fabry's disease, even in patients who demonstrate no improvement in echocardiographic parameters of cardiac structure and function.

Cardio-ankle vascular index (CAVI) has been established as a marker of arterial stiffness, which is increased in hypertensive patients. CAVI reflects the stiffness of the aorta, femoral artery, and tibial artery. Sunitinib, multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activities, has been proved effective in patients with gastrointestinal stromal tumors. However, the treatment with sunitinib is often complicated by side effects such as hypertension. We describe an 84-year-old woman with gastrointestinal stromal tumor, who showed changes in arterial stiffness preceding the appearance of hypertension in the early phase after sunitinib initiation. The patient received sunitinib (50 mg given daily) for gastrointestinal stromal tumor. We assessed the influence of sunitinib on arterial stiffness every 7 days by measuring CAVI. The CAVI, which reflects arterial stiffness, was increased from 9.95 at baseline to 11.65 at 7 days after the initiation of sunitinib, whereas the blood pressure remained unchanged (117/72 and 119/76 mmHg). At 14 days after sunitinib initiation, the blood pressure was increased to 159/89 mmHg, indicating the occurrence of hypertension, while the CAVI was 11.90, the similar level detected at 7 days. Subsequently, sunitinib treatment was discontinued, because of the marked decrease in blood platelets. Both blood pressure and CAVI, together with blood platelets, were restored to the baseline values at 12 days after cessation of sunitinib. In conclusion, the increase in the CAVI preceded the appearance of sunitinib-induced hypertension. Arterial stiffness assessed by CAVI may be useful for early detection of sunitinib-induced hypertension.

Objective: The aim of this investigation was to determine the factors influencing acute intracerebral hemorrhage severity on admission and clinical outcomes at discharge. Methods: Sixty acute stroke hospitals throughout Japan participated in the Japan Standard Stroke Registry Study (JSSRS), documenting the in-hospital course of 16,630 consecutive patients with acute stroke from January 2001 to March 2004. We identified 2,840 adult patients from the JSSRS who had intracerebral hemorrhage. Results: Intracerebral hemorrhage severity on admission was strongly related to age, previous stroke history, and hemorrhage size in a monotone fashion [χ2(9) = 374.5, p < 0.0001]. Drinking history was also predictive of intracerebral hemorrhage severity on admission, but the association was not monotone. Interestingly, intracerebral hemorrhage severity on admission was increased in nondrinking and heavy drinking compared to mild drinking (p < 0.05). Unsuccessful outcome (modified Rankin scale score = 3–6) was related to age, previous stroke history, hemorrhage size, and intracerebral hemorrhage severity on admission [χ2(9) = 830.4, p < 0.0001]. Mortality was related to hemorrhage size, intraventricular hemorrhage, intracerebral hemorrhage severity on admission, and surgical operation [χ2(7) = 540.4, p < 0.0001]. Conclusion: We could find four varied factors associated with intracerebral hemorrhage severity and its outcomes. Interestingly, intracerebral hemorrhage severity tended to be greater in nondrinking and heavy drinking than mild drinking. Additionally, surgical operation decreased intracerebral hemorrhage mortality.

Although patients with type 2 diabetes demonstrate cardiac diastolic dysfunction, it is well known that cardiac diastolic dysfunction is produced by hypertension and aging. The purpose of the present study was to elucidate the cardiac structure and function in normotensive patients with type 2 diabetes in various age strata in order to assess the effect of diabetes mellitus itself on cardiac function. Echocardiographic examination was performed in 77 normotensive patients with type 2 diabetes (age: 63+/-11 years) and 76 healthy control subjects (age: 60+/-11 years) who were in their forties, fifties, sixties, and seventies. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) using the transmitral flow velocity, which were obtained by Doppler echocardiography. No difference was observed in the relative wall thickness, LV mass index, or LVEF between the diabetic patients and control subjects in any of the age strata. The E/A ratio in the patients with type 2 diabetes was not different from that in the control subjects in their 40s (1.17+/-0.35 versus 1.20+/-0.36). However, E/A was significantly lower in the diabetic patients than in the control subjects in their 50s (0.87+/-0.28 versus 1.14+/-0.24), 60s (0.78+/-0.22 versus 0.97+/-0.27), and 70s (0.66+/-0.19 versus 0.84+/-0.21) (p0.05). The duration of type 2 diabetes was significantly longer in patients in their 50s (7.0+/-2.5 years), 60s (8.0+/-3.2 years), and 70s (10.4+/-3.2 years) than in patients in their 40s (3.3+/-1.9 years) (p0.001). The value of E/A in the diabetic patients correlated with the duration of type 2 diabetes (r=-0.62, p0.001). These results indicate that cardiac diastolic dysfunction without LV systolic dysfunction in patients with well-controlled type 2 diabetes is related neither to hypertension nor LV hypertrophy, but rather to aging and the duration of type 2 diabetes.

The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 +/- 6 years), rank B (chair-bound) (n = 16, age, 84 +/- 8 years), and rank C (bed-bound) (n = 19, age, 85 +/- 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 +/- 0.17) than in rank A (0.39 +/- 0.06) and rank B (0.48 +/- 0.17), and a statistically significant difference was observed between rank A and rank C (P < 0.05). Serum albumin and blood hemoglobin were significantly lower in rank C (3.1 +/- 0.4 and 10.6 +/- 1.8 g/dL) than in rank A (4.1 +/- 0.3 and 12.4 +/- 1.2 g/dL) (P < 0.001 and P < 0.05, respectively). These results indicate that latent cardiac dysfunction and poor nutritional status may exist in bed-bound patients (rank C) following cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.

Objective: Although echocardiography is used for diagnosing right ventricular (RV) infarction produced by right coronary artery (RCA) occlusion, there has been no data on the spatial distribution of RV perfusion abnormalities following acute RCA occlusion. We examined this distribution by myocardial contrast echocardiography (MCE) and blue dye staining in canine models. Methods: The RCA was occluded in 10 open-chest dogs. MCE was performed with 0.27 g/min Levovist infusion by harmonic power Doppler with electrocardiogram gated intermittent triggered imaging at baseline and at 90 min after RCA occlusion. The opacification defects were assessed at the basal, middle, and apical levels of the RV free wall by short-axis view. The extent of the risk area of the occluded RCA, expressed as a percentage of the RV free wall, was measured at each level by injecting blue dye at the end of the experiments. In 10 other dogs, the left anterior descending coronary artery (LAD) was occluded by ligating the proximal portion of the LAD to examine the territory of the LAD on the same levels of the RV free wall by injecting blue dye. Results: Although patchy opacification defects accompanying RV dilation were observed at the basal and middle levels during RCA occlusion, no apical defects were observed in any dogs by MCE. The risk area of the occluded RCA, as delineated by blue dye, was larger in the basal than apical level of the RV free wall in all 10 dogs (basal: 79 ± 9%; middle: 48 ± 14%; apical: 3 ± 6%, p

The purpose of the present study was to analyze the relationships between echocardiographic findings, brachial-ankle pulse wave velocity, and carotid atherosclerosis in type 2 diabetic patients. In 70 type 2 diabetic patients without cardiovascular disease, pulse wave velocity was measured using an automatic waveform analyzer, and the carotid plaque score was obtained by carotid ultrasonography. The left ventricular wall thickness and the indexes of left ventricular diastolic function (the peak velocity of early rapid filling [E velocity], the peak velocity of atrial filling [A velocity], and the E/A ratio) were obtained by echocardiography. Brachial-ankle pulse wave velocity correlated significantly with the carotid plaque score, but the correlation was weak (r=0.37, p=0.001). The brachial-ankle pulse wave velocity demonstrated a strong correlation with the A velocity (r=0.73, p0.001), the ratio of E to A (E/A) (r=-0.63, p0.001), and the deceleration time of the E velocity (r=0.48, p0.001). Stepwise regression analysis showed that the A velocity (beta coefficient=0.42, p0.001) and ventricular septal thickness at the left ventricular outflow tract (beta coefficient=0.27, p=0.001) were independently associated with brachial-ankle pulse wave velocity. Stepwise regression analysis indicated that ventricular septal thickness at the left ventricular outflow tract (beta coefficient=0.38, p=0.001) was independently associated with the plaque score. These results indicate that left ventricular diastolic dysfunction as revealed by increased peak velocity of atrial filling reflects arterial stiffening in type 2 diabetic patients. In addition, myocardial wall thickening at the left ventricular outflow tract reflects not only arterial stiffening but also carotid atherosclerosis. Therefore, these abnormal echocardiographic findings of left ventricular diastolic dysfunction and myocardial wall thickening may be useful markers of the presence of progressive arteriosclerosis in type 2 diabetic patients.

The authors examined the ability of real-time myocardial contrast echocardiography (MCE) to assess adenosine-induced coronary steal in the setting of coronary artery occlusion. The left anterior descending (LAD) coronary artery was occluded in 8 open-chest dogs. Real-time MCE was performed during LAD occlusion, and the extent of opacification defects from MCE was measured without and with adenosine infusion. Microsphere-derived myocardial blood flow (MBF) was measured in the LAD and left circumflex (LCx) coronary artery beds, and the LAD/LCx ratio of MBF was calculated. The LAD/LCx ratio of MBF decreased in response to adenosine administration (without adenosine: 0.66, with adenosine: 0.43, p < 0.01). The extent of opacification defects from MCE increased in response to adenosine administration (without adenosine: 18%, with adenosine: 22%, p < 0.01). Thus, real-time MCE allows for the detection of adenosine-induced coronary steal as changes in the extent of opacification defects in the setting of occlusion of 1 coronary artery accompanying another normally patent coronary artery.

RATIONALE AND OBJECTIVES The objective of the present study was to compare the data regarding the ability of real-time myocardial contrast echocardiography (MCE) to assess altered myocardial blood flow produced by graded coronary stenoses between open- and closed-chest canine models. MATERIALS AND METHODS Three grades of left anterior descending coronary artery stenosis and occlusion were created in 6 open- and 6 closed-chest canine models. MCE used FS-069 infusion and real-time imaging. Myocardial signal intensity versus time plots were fitted to a 1-exponential function to obtain the peak signal intensity (A) and rate of signal intensity rise (b) for quantification of myocardial blood flow. RESULTS The value of b obtained from closed-chest canine models (without stenosis = 0.995 +/- 0.087, mild stenosis = 0.968 +/- 0.076, moderate stenosis = 0.569 +/- 0.077, severe stenosis = 0.288 +/- 0.032, occlusion = 0.085 +/- 0.031) was not significantly different from that obtained from open-chest canine models (without stenosis = 1.028 +/- 0.107, mild stenosis = 0.998 +/- 0.098, moderate stenosis = 0.601 +/- 0.055, severe stenosis = 0.321 +/- 0.029, occlusion = 0.079 +/- 0.028) at any grade of stenosis (P = 0.09, 0.08, 0.44, 0.11, 0.74, respectively). CONCLUSIONS In myocardial regions where attenuation of the ultrasound beam and artifacts produced by the chest wall are minimal, the data from transthoracic MCE in the closed-chest model may show values similar to those from MCE in the open-chest model.

Objectives We sought to validate the ability of real-time myocardial contrast echocardiography (MCE) measures of opacification defect and contrast refilling parameters to estimate risk area (RA) and infarct area (IA) during coronary occlusion and reperfusion. Background No data exist establishing the accuracy of MCE in determining RA and IA size. We hypothesized that in the setting of coronary occlusion, MCE should identify RA as a perfusion defect early after bubble destruction, collateral flow to viable myocardium as opacification late during refilling and IA as absent opacification. Methods Three hours of coronary occlusion and reperfusion were each produced in 11 dogs in which real-time MCE was performed during intravenous infusion of Sonovue (Bracco). Real-time contrast echocardiography was performed at baseline, during occlusion and reperfusion. Early (BEGIN) and end (END) images from a FLASH refilling sequence were acquired, as well as late refilling images (LATE) 1 min after FLASH. Real-time contrast echocardiography defect size and quantitative refilling parameters were compared with RA and IA determined by tissue staining. Results During occlusion, defect size varied with refilling time; defects from BEGIN images correlated best to RA and those from LATE images to IA. Refilling parameters, but not LATE peak intensity, did not predict the IA size during occlusion. During reperfusion, defects from BEGIN images were well correlated to RA and END images to IA, whereas peak plateau intensity and refilling slope parameters predicted IA size. Conclusions Real-time contrast echocardiography defect size varies throughout microbubble refilling. Appropriately selected defect sizes and refilling parameters provide estimates of RA and IA during coronary occlusion and reperfusion.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that is pathologically characterized by α‑synuclein positive glial cytoplasmic inclusions in oligodendrocytes. The clinical diagnosis of MSA is often challenging as there are no established biomarkers and diagnoses are now based on clinical findings alone. At present, the etiology and pathogenesis of MSA are unclear. It has been reported that dysregulation of microRNA (miRNA/miR) serves an important role in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. The miRNA profile of patients with MSA remains to be established. The present study investigated the serum miRNA expression level of 10 patients with MSA, using microarray chips including 668 miRNAs. It was identified that 50 miRNAs were significantly upregulated and 17 miRNAs were significantly downregulated in the serum of the patients with MSA. The most upregulated miRNA was miR‑16, which may induce the accumulation of α‑synuclein. The target genes of some miRNAs upregulated in MSA (including miR‑17, 20a, 24, 25, 30d and 451) were associated with autophagy‑associated molecules. The present study concluded that the expression pattern of miRNAs may be a clinical biomarker for MSA and targeting these miRNAs may provide a novel treatment for MSA.

Real-time myocardial contrast echo (MCE) provides the potential to assess myocardial blood flow from time intensity refilling curves after high-energy bubble destruction. This study validated the accuracy of this approach and the effect of specific examination variables and instrument settings on results. The effects of examination depth and angle as well as dynamic range, pulse repetition frequency, and line density were assessed with the use of in vitro incremental flow rates produced in an in vitro tissue phantom. In vivo recordings of real-time imaging with an infusion of a contrast agent (Optison) were obtained in 7 open-chest dogs with graded left anterior descending artery stenosis at baseline and during adenosine hyperemia, and were compared with flow probe measurements. After bubble destruction, time-intensity data were fitted to an exponential function, and the rate of intensity increase ( b ) and peak plateau intensity ( A ) were derived from refilling curves. In vivo real-time values for b, but not A, correlated closely with flow probe measures ( r = 0.93). A similar correlation for b was observed in vitro ( r = 0.98). The correlation between flow rate and b was influenced by several examination variables, including depth, angle, and instrument settings-Real-time MCE provides accurate quantification of coronary flow by assessing the rate of microbubble refilling. However, this parameter may be affected by several examination and instrument variables. Therefore, real-time MCE refilling measures are best applied by comparing baseline values with those of stress studies.

Background Both intermittent triggered and real-time myocardial contrast echocardiography (MCE) have been proposed to detect impaired myocardial perfusion. We compared the ability of these 2 methods to quantify altered myocardial blood flow (MBF) and transmural distribution of MBF produced by graded coronary stenoses. Methods and Results In 8 open-chest dogs, we created 4 graded left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced adenosine hyperemia (non–flow-limiting at rest) and 1 grade of flow-limiting at rest. Real-time MCE was performed with SonoVue infusion using low-energy power pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI) was plotted versus time by real-time MCE and versus pulsing intervals by triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A) and the rate of SI rise (b). Visual detection of decreased opacification was equivalent by triggered and real-time MCE. Fluorescent microsphere–derived MBF ratio in LAD/left circumflex artery beds demonstrated close correlation with both real-time imaging (b, r =0.79; A×b, r =0.81) and triggered imaging (b, r =0.78; A×b, r =0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated closer correlation with the endocardial/epicardial ratios of b ( r =0.71) and A×b ( r =0.67) obtained by real-time than triggered imaging (b, r =0.42; A×b, r =0.52). Conclusions Real-time and triggered MCE are equivalent in their ability to identify coronary stenosis and quantify altered MBF.

We aimed to investigate whether the improvement of left ventricular (LV) diastolic function by cibenzoline, a class Ia antiarrhythmic drug, in hypertrophic obstructive cardiomyopathy (HOCM) is due to LV afterload reduction or a primary lusitropic effect on LV. Twenty-three patients with hypertrophic cardiomyopathy (11; HOCM, 12; non-obstructive HCM; HNCM) were examined. Pulsed-wave Doppler, color M-mode and tissue Doppler echocardiography were performed before and 90 minutes after oral administration of cibenzoline (300 mg), and were compared with a treatment of bisoprolol (5 mg/day, 10 days). Early (E) and late diastolic LV inflow velocity, E flow propagation velocity (FPV) and early diastolic mitral annulus velocity (Ea) were measured. E/FPV and E/Ea were calculated as indices of LV filling pressure. LV outflow pressure gradients estimated using continuous-wave Doppler in HOCM markedly decreased after cibenzoline (83 ± 42 to 40 ± 33 mmHg, p < 0.005) and bisoprolol (44 ± 40 mmHg, p < 0.005). Following cibenzoline, E/FPV and E/Ea were significantly decreased in both HOCM (1.75 ± 0.53 to 1.32 ± 0.28, p < 0.05, 18.9 ± 6.2 to 14.8 ± 5.0, p < 0.05, respectively) and HNCM (1.75 ± 0.58 to 1.41 ± 0.73, p < 0.05, 13.0 ± 4.3 to 9.7 ± 3.6, p < 0.01, respectively). Those in HNCM did not change by bisoprolol. Cibenzoline improved LV diastolic function in HCM, whereas bisoprolol did not affect it. Thus, the primary lusitropic effect of cibenzoline rather than LV after load reduction might have contributed to the improvement of diastolic function in HOCM.