Long-term antihypertensive effects of aliskiren, a direct renin inhibitor, in chronic hemodialysis patients.

The renin-angiotensin-aldosterone system is not necessarily suppressed in end-stage renal disease patients undergoing dialysis. Of all the inhibitors of this system, the clinical efficacy of the renin inhibitor, aliskiren, has not been well demonstrated in dialysis patients. We evaluated the antihypertensive effect of aliskiren, administered as a single daily dose of 150 mg for 24 weeks, in 23 chronic hemodialysis patients (age 65 ± 12 years, 15 men and eight women) with blood pressure ≥140/90 mm Hg, and assessed the factors relating to blood pressure reduction. At 4 weeks, the average systolic blood pressure before the dialysis session was insignificantly reduced from 163 ± 10 mm Hg to 160 ± 15 mm Hg, while it was significantly lowered at 12 (154 ± 13 mm Hg) and 24 weeks (155 ± 10 mm Hg), although the pulse rate was not significantly altered. Serum K increased at 24 weeks from 4.9 ± 0.6 mEq/L to 5.2 ± 0.8 mEq/L. Only 10 out of 23 patients showed systolic blood pressure reduction by ≥10 mm Hg. Naturally, plasma renin immunoreactivity increased, while plasma renin activity, along with angiotensin II and aldosterone levels decreased. Basal levels of the components of the renin-angiotensin-aldosterone system were not significantly different in patients showing systolic blood pressure reduction by ≥10 mm Hg (n = 10) vs. those with <10 mm Hg changes (n = 13). The reduction in systolic blood pressure in all 23 patients taken as a whole correlated with changes in plasma renin activity (r = -0.432, P < 0.05) and angiotensin II (r = 0.467, P < 0.05). In chronic hemodialysis patients, aliskiren modestly lowers blood pressure over the long term, although the antihypertensive effect seems dependent on the changes, but not on the basal levels of plasma renin activity and angiotensin II.

Redo surgery for biliary atresia.

The Kasai redo surgery is important for treating biliary atresia. In the era of liver transplantation (LTx), pediatric surgeons must accurately select patients for redo surgery and ensure that potential LTx can be performed later. Although optimal timing for redo varies among cases, appropriate timing is essential. We reviewed the significance, optimal timing, operative procedures, and indications of Kasai redo surgery. Between 1989 and 2011, 2,630 patients were registered in the Japanese Biliary Atresia Registry (JBAR), and the data collected from JBAR regarding Kasai redo surgery were analyzed. Patients were divided into two groups, Group 1 (1989-1999, n = 1,423) and Group 2 (2000-2011, n = 1,207). The redo incidence significantly reduced in Group 2. Although no significant difference was found in the native liver jaundice-free survival rates between the two groups, the overall survival rate at initial registry was significantly higher in Group 2. This may be because of the limited number of patients selected for redo and increased availability of early LTx. Patients who achieved sufficient bile drainage following the initial Kasai surgery but developed sudden bile flow cessation were the best candidates for Kasai redo surgery; it should be performed only once for this subset.

Participation of natural killer cells in the pathogenesis of bile duct lesions in biliary atresia.

AIMS: Immunological disturbances including innate immunity after a suspected viral infection are considered important to the pathogenesis of bile duct lesions in cases of biliary atresia (BA). In this study, we tried to evaluate whether natural killer (NK) cells and CX3CL1 (Fractalkine) and its receptor (CX3CR1) are involved in the bile duct injury. METHODS: Using the section of BA (22 cases) and controls, immunohistochemistry for CD56, CD16, CD68, CX3CL1 and CX3CR1 was performed. Moreover, using cultured biliary epithelial cells (BECs) and NK cells, the production of CX3CL1 in BECs and the migration of NK cells were evaluated. RESULTS: It was found that CD56(-)CD16(+)CD68(-) NK cells were increased around the damaged small and large bile ducts in BA and hepatitis C virus-related chronic hepatitis in comparison with other controls. CX3CL1 was strongly expressed on the damaged bile ducts in BA, while this expression was relatively weak or absent in the bile ducts of normal liver. The results suggest the CD56(-)CD16(+) NK cells to be involved in the development of bile duct injuries in BA. These CD16(+) NK cells were positive for CX3CR1, and attracted by CX3CL1 expressed on bile ducts. Further study revealed that stimulation with poly(I:C) (a synthetic analogue of viral dsRNA) increased the expression of CX3CL1 on cultured BECs followed by increased migrational activity of cultured NK cells. CONCLUSIONS: CD56(-)CD16(+) NK cells with reduced NK activity may be involved in the bile duct damage in BA, and CD16(+) NK cells expressing CX3CR1 may be attracted by and interact with bile ducts expressing CX3CL1.

Risk factors affecting late-presenting liver failure in adult patients with biliary atresia.

PURPOSE: Following the Kasai operation, a number of patients have developed liver failure, even after long-term postoperative courses. We assessed the clinical parameters to clarify the early risk factors affecting late-presenting liver failure in biliary atresia. MATERIALS AND METHODS: From 1955 to 1991, 277 patients underwent a Kasai operation. Among those patients, 92 survived with their native liver for more than 20 years, and 72 continue to survive with their native liver in good condition (Group 1). In 20 patients, persistent jaundice recurred after the age of 20 years (Group 2). The postoperative courses of these patients were assessed retrospectively, and the clinical parameters, including age at the time of the Kasai operation (AGE, days), the period required for jaundice to disappear (PJD, days), and the association with early cholangitis (CG), were compared between the 2 groups. RESULTS: Of the 20 patients in Group 2, 8 survived after a liver transplantation (LTx). Eight patients had recurrent jaundice, including 4 on the waiting list for anLTx. Additionally, 2 patients died after anLTx at the ages of 22 and 39. Another patient died of liver failure at the age of 28. One patient died of massive esophageal variceal bleeding at the age of 29. Significant differences were confirmed with respect to AGE (Group 1

Synbiotic therapy reduces the pathological gram-negative rods caused by an increased acetic acid concentration in the gut.

BACKGROUND: The mechanisms for the improvement of the gut flora and the intestinal environment by synbiotic therapy are unclear. AIMS: This study evaluated the changes in the gut flora and the intestinal environment after synbiotic therapy, and tried to clarify the mechanisms by which synbiotic therapy reduces pathological bacteria in the gut. METHODS: A total of 47 enteral feeding patients with long-term mechanical ventilation support were enrolled in the study. Patients were randomly assigned to synbiotic and control groups, at a two to one ratio. Patients in the synbiotic group were administrated Lactobacillus, Bifidobacterium, and galactooligosaccharides as synbiotics for 8 weeks. RESULTS: The characteristics of the patients were not significantly different between the control (n = 16) and synbiotic (n = 31) groups. In the synbiotic group, the counts of Bifidobacterium and Lactobacillus in the gut increased significantly to 100 times the initial level following synbiotic treatment. The acetic acid concentration increased (71.1 ± 15.9 vs. 46.8 ± 24.1 µmol/g) and pH decreased in the gut in comparison with the control group. The concentration of acetic acid in the gut increased in proportion to the Bifidobacterium counts. The counts of pathological gram-negative rod decreased significantly to one-tenth of the initial level in inverse proportion to the Bifidobacterium counts. Furthermore, the amount of Pseudomonas aeruginosa in the lower respiratory tract decreased significantly after synbiotic therapy compared to the controls. CONCLUSION: Synbiotic therapy reduces the pathological Gram-negative rods by increasing the acetic acid concentration in association with an increased counts of Bifidobacterium.

Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary organs.

Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases of mixed adenoneuroendocrine carcinoma (MANEC) have been reported. In this study, we characterized the neuroendocrine component of biliary MANEC. A total of 274 cases of biliary cancer including 17 intrahepatic cholangiocarcinomas (CCs), 15 hepatic hilar CCs without preceding hepatobiliary disease, 55 hepatic hilar CCs with hepatolithiasis, 49 gallbladder cancers, 53 extrahepatic CCs, and 85 hepatocellular carcinomas were examined for a neuroendocrine component using immunohistochemistry with neuroendocrine markers (chromogranin A and synaptophysin). In the MANEC cases, in addition to a close histological examination, the proliferative activity and the expression of somatostatin receptor 2A were also evaluated. In addition to an ordinary adenocarcinoma, a neuroendocrine component occupying more than 30% of the entire tumor was also found in 4% (2/55 cases) of hepatic hilar cholangiocarcinomas with hepatolithiasis, 10% (5/49 cases) of gallbladder cancers, and 4% (2/53 cases) of extrahepatic cholangiocarcinomas, but not in the intrahepatic cholangiocarcinomas, hilar cholangiocarcinomas without preceding hepatobiliary disease, and hepatocellular carcinomas. Two cases were positive for somatostatin receptor 2A. The adenocarcinoma components were predominately located at the surface of the tumors, and the majority of stromal and vascular invasion and lymph node metastasis involved neuroendocrine components, showing the features of neuroendocrine tumor G2 or neuroendocrine carcinomas (NECs). NEC components showed higher proliferative activity on Ki67 immunostaining, compared to the adenocarcinoma components. Biliary MANECs are found in hepatic hilar cholangiocarcinomas with hepatolithiasis, gallbladder cancers, and extrahepatic cholangiocarcinomas and show a characteristic histology. Since the neuroendocrine component in biliary MANEC defines the prognosis, it is important to identify it and consider the indications for adjunctive therapy with somatostatin analogues.

Monocyte chemoattractant protein-1 derived from biliary innate immunity contributes to hepatic fibrogenesis.

AIMS: Monocyte chemoattractant protein-1 (MCP-1) is a major chemotactic factor for hepatic stellate cells (HSCs) associated with hepatic fibrosis. In this study, among several fibrogenetic factors derived from biliary epithelial cells (BECs), MCP-1 produced by the biliary innate immune system was found to be most critical in the histogenesis of hepatic fibrogenesis. METHODS: Using cultured human BECs, the expression of five fibrogenetic factors including MCP-1 on stimulation with Toll-like receptor ligands, inflammatory cytokines or bile acids was examined. Moreover, in situ detection of MCP-1 and α-smooth muscle actin proteins was performed using sections from normal and diseased livers by immunohistochemistry. RESULTS: All fibrogenetic factors were detected in BECs, but only MCP-1 expression was upregulated, by all the Toll-like receptor ligands, IL-1ß, and tumour necrosis factor-alpha. Proliferating bile ductules in interface areas expressed MCP-1 in diseased livers accompanying α-smooth muscle actin-positive activated HSCs. CONCLUSIONS: Bile ductules proliferate in various hepatobiliary diseases, and its significance is still unknown. This study demonstrated that BECs in bile ductules could produce MCP-1, particularly, via biliary innate immunity, suggesting that MCP-1 derived from BECs plays an important role in the recruitment of HSCs to interface areas and the activation of HSCs resulting in the progression of periportal fibrosis.

Effect of elevated left ventricular diastolic filling pressure on the frequency of left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

We investigated the relation between left ventricular diastolic dysfunction and left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF). We performed transesophageal echocardiography to examine LAA thrombus or spontaneous echo contrast (SEC) and to measure LAA emptying flow velocity in consecutive 376 patients with AF. We estimated diastolic filling pressure as the ratio of early transmitral flow velocity (E) to mitral annular velocity (e') on transthoracic echocardiogram. E/e' ratio in 28 patients (7.4%) with LAA thrombi was higher than that in patients without thrombus (18.3 ± 9.3 vs 11.4 ± 5.9, p <0.0001). The fourth quartile of E/e' (>13.6) consisted of 19 patients with thrombi and had a higher prevalence of thrombi than the others (p <0.0001). Multivariate regression analysis selected E/e' ≥13 as an independent predictor of LAA thrombus with an odds ratio of 3.50 (1.22 to 10.61) in addition to LA dimension and ejection fraction. Increased quartile of E/e' was negatively associated with LAA flow velocity and positively with rate of SEC. In conclusion, increased diastolic filling pressure is associated with a higher rate of LAA thrombus in AF, partly through blood stasis or impaired LAA function.

Automated assessment of myocardial viability after acute myocardial infarction by global longitudinal peak strain on low-dose dobutamine stress echocardiography.

BACKGROUND: Low-dose dobutamine stress echocardiography (DSE) assesses myocardial viability at the early stage of acute myocardial infarction (AMI), but its assessment is subjective and variable. Automated function image (AFI) determines global longitudinal peak strain (GLPS) based on tissue tracking technique. The ability of GLPS obtained by AFI during dobutamine stress to assess myocardial viability after AMI was investigated. METHODS AND RESULTS: Low-dose DSE at day 3 in 23 consecutive patients with AMI was performed using Vivid 7 (GE Healthcare). Segmental longitudinal peak strain with AFI and obtained GLPS was analyzed. Wall motion score index (WMSI) by echocardiography 1 month later was determined. In 18 patients, left ventriculography was also performed at 3.2±1.5 months later to obtain left ventricular ejection fraction (LVEF) and regional wall motion (RWM, SD/chord). GLPS was improved during dobutamine infusion at 10 µg · kg(-1) · min(-1) (-12.9 ± 3.5% to -15.2 ± 3.6%, P=0.0004). GLPS during dobutamine stress showed good correlations with follow-up WMSI (R=0.47, P=0.02), with peak CK-MB (R = 0.52, P=0.01), with RWM (R = -0.48, P=0.04), and with LVEF (R = -0.54, P=0.02), whereas GLPS at baseline showed no correlations with them. Averaged segmental peak strain at baseline and during stress were correlated with follow-up WMSI (R = 0.50 and 0.43, respectively), but not with LVEF. CONCLUSIONS: GLPS during dobutamine stress determined by AFI is a promising, objective index to assess myocardial viability on the early stage of AMI.

Effects of efonidipine, an L- and T-type calcium channel blocker, on the renin-angiotensin-aldosterone system in chronic hemodialysis patients.

Components of the renin-angiotensin-aldosterone system such as angiotensin II and aldosterone are believed to contribute to the development and progression of cardiovascular tissue and organ injuries. We compared the effects of two calcium channel blockers, efonidipine and amlodipine, on the renin-angiotensin-aldosterone system in patients with end-stage renal diseases on maintenance hemodialysis. Twenty hypertensive patients on chronic hemodialysis were given efonidipine 20-60 mg twice daily and amlodipine 2.5-7.5 mg once daily for 12 weeks each in a random crossover manner. The average blood pressure was comparable between the efonidipine and amlodipine periods (151 + or - 15/77 + or - 8 versus 153 + or - 15/76 + or - 8 mmHg). The pulse rate did not change significantly during the administration periods. Although the plasma renin activity and plasma angiotensin II were not significantly different between the efonidipine and amlodipine periods, plasma aldosterone was significantly lower in the efonidipine period than in the amlodipine period (123 + or - 118 versus 146 + or - 150 pg/mL, P = 0.027). The findings suggest that efonidipine reduces plasma aldosterone levels in patients on maintenance hemodialysis, and this seems to be an additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease.

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension.

To achieve the target blood pressure recommended by the latest guidelines, multiple antihypertensive drugs are needed in most patients. In this study, the efficacy of treatment using an angiotensin II receptor antagonist (ARB) combined with a calcium channel blocker (CCB) or a diuretic was compared from multiple perspectives in patients with hypertension. Twenty-nine patients with essential hypertension, who had failed to achieve their target blood pressure (<130/85 mm Hg for patients <65 years old and <140/90 mm Hg for those >/=65 years) when treated with the ARB olmesartan at 20 mg day(-1), were additionally given 8-16 mg day(-1) of the CCB azelnidipine or 1-2 mg day(-1) of trichlormethiazide (a thiazide diuretic) in a randomized crossover manner for 4 months each. At the end of each combination therapy period, blood and urine samples were collected and arterial stiffness was evaluated by measuring the cardio-ankle pulse wave velocity. Compared with monotherapy, the blood pressure was reduced similarly by adding azelnidipine (-12/-10 mm Hg) or trichlormethiazide (-14/-9 mm Hg). The heart rate was decreased with the CCB by 4 b.p.m. (P<0.05), whereas it was unchanged with the thiazide. Serum K, lipids and blood glucose were not significantly changed with either combination, whereas serum uric acid was increased with the thiazide (P<0.01) but was unchanged with azelnidipine. Plasma levels of renin, angiotensin II and aldosterone were also increased with the thiazide period, whereas high-sensitivity C-reactive protein and oxidized low-density lipoprotein were decreased with azelnidipine. In addition, the cardio-ankle vascular index, a parameter of arterial stiffness, was decreased with the azelnidipine period but was unchanged with the thiazide period (P<0.01). It is suggested that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding hyperuricemia, sympathetic activation, renin-angiotensin-aldosterone system stimulation, inflammation, oxidative stress, and increased arterial stiffness in patients with moderate hypertension. These properties may provide cardiovascular protection in addition to the hypotensive effect.

Stereochemical determination of the unique acrylate moiety at the 17-position in chlorophylls-c from a diatom Chaetoseros calcitrans and its effect upon electronic absorption properties.

Chlorophyll (Chl)-c1 and Chl-c2 were extracted from a commercially available diatom Chaetoseros calcitrans, and the former (8-ethyl) and the latter (8-vinyl) were efficiently separated by reverse-phase HPLC using a polymeric octadecylsilyl column to afford analytically pure compounds in an amount adequate for further chemical modification. The conformation of the unique acrylate moiety at the 17-position of isolated Chls-c in THF was unambiguously determined to be "cisoid" around the C17-C17(1) bond using 1H-1H NOE correlations: C17(1)=C17(2) was on the same side as C17=C18. Interestingly, correlations originating from the "transoid" conformer could not be observed under the present NMR conditions, indicating that the rotation of the acrylate was considerably restricted. To elucidate the function of the rigid acrylate in Chls-c, we examined their electronic absorption properties using two synthetic types of esters possessing a porphyrin pi-system: acrylate-type (17-CH=CH-COOR) prepared by esterification of natural Chl-c1 and Chl-c2, and propionate-type (17-CH2-CH2-COOR) by 17,18-oxidation of natural Chl-a and its 8-vinyl analog. The Soret absorption bands at around 450 nm of the acrylate-type were red-shifted and broadened more than those of the propionate-type. Consequently, the unique acrylate in Chls-c serves as an aid for expanding the absorption region around 400-500 nm in order to capture intense irradiation from the sun for photosynthesis.

Nicorandil treatment in patients with acute myocardial infarction: a meta-analysis.

BACKGROUND: It is controversial as to whether nicorandil would have cardioprotective effects in patients with acute myocardial infarction (AMI) who are undergoing reperfusion therapy. A meta-analysis was performed to study the impacts of nicorandil on functional outcomes after AMI. METHODS AND RESULTS: Randomized prospective cohort or retrospective cohort publications were identified up to October 2007 by means of a computer search of MEDLINE and Google Scholar databases. Two reviewers checked the quality of the studies and extracted data regarding patient and disease characteristics, study design, functional parameters such as Thrombolysis In Myocardial Infarction (TIMI) flow grade after reperfusion, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI). Seventeen studies were included for the meta-analysis in this study. Nicorandil treatment reduced the incidence of TIMI flow grade < or =2 in 1,337 patients of 10 studies (risk ratio 0.63; 95% confidence interval (CI) 0.44 to 0.91). While no beneficial effect was observed on the peak creatine kinase value, nicorandil treatment was associated with greater LVEF (by 3.7%, 95%CI 1.8 to 5.7%), and lower LVEDVI (by 8.8 ml/kg, -14.4 to -3.3 ml/kg) in 905 patients of 11 studies. CONCLUSIONS: The meta-analysis demonstrated that nicorandil treatment adjunctive to reperfusion therapy has beneficial effects on microvascular function and on functional recovery after AMI.

Sonographic evaluation of visceral fat by measuring para- and perirenal fat.

PURPOSE: To evaluate a new method of determining visceral fat amount by measuring para- and perirenal fat on abdominal sonography. METHODS: Fifty-seven patients hospitalized for treatment of their diabetes were examined via waist circumference, abdominal sonography, and CT. On sonography, the thickness of combined para- and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the ultrasound fat thickness (UFT). The visceral fat area was measured on abdominal CT scans at the umbilicus level. Visceral fat deposition was considered elevated above 100 cm2. RESULTS: UFT correlated significantly with VFA and waist circumference (p < 0.0001). A VFA of 100 cm2 was equivalent to a UFT of 10 mm. Waist circumference values of 85 cm in males and 90 cm in females were equivalent to UFT measurements of 11 and 10 mm, respectively. CONCLUSION: A UFT of > or =10 mm reflects increased visceral fat deposition.

Comparison of two- versus three-dimensional myocardial contrast echocardiography for assessing subendocardial perfusion abnormality after percutaneous coronary intervention in patients with acute myocardial infarction.

Myocardial contrast echocardiography (MCE) visualizes myocardial perfusion abnormalities after acute myocardial infarction. However, the limited view of 2-dimensional echocardiography reduces its ability to estimate perfusion abnormalities, especially in the subendocardial region. Three-dimensional echocardiography provides images of the left ventricular endocardium directly. This study was conducted to evaluate the ability of 3-dimensional MCE to assess abnormalities of subendocardial perfusion. Intracoronary 2- and 3-dimensional MCE was performed after primary percutaneous coronary intervention in 47 patients with acute myocardial infarction. Myocardial perfusion within the risk area was evaluated as good, poor, or no reflow on 2-dimensional MCE or as good, poor, or no myocardial opacification in endocardium on 3-dimensional MCE. The 2 methods showed different distributions of perfusion patterns: good, poor, and no reflow on 2-dimensional MCE in 31 (66%), 9 (19%), and 7 (15%) patients and good, poor, and no myocardial opacification in endocardium on 3-dimensional MCE in 17 (36%), 16 (34%), and 14 (20%) patients, respectively. Although only 19 patients (61%) with good reflow on 2-dimensional MCE showed myocardial perfusion grade 3 on angiography, 16 of 17 patients (94%) with good myocardial opacification in endocardium on 3-dimensional MCE showed myocardial perfusion grade 3. Although there were no significant differences in peak creatine kinase among the 3 subsets classified by 2-dimensional MCE, peak creatine kinase showed significant differences not only among the 3 groups but also among the subsets classified by 3-dimensional MCE. Classification by 3-dimensional MCE also predicted regional wall motion after 4.6 +/- 2.7 months, with significant differences between each pair of groups, whereas there was significant overlap of these values between the group with poor reflow and other 2 groups by 2-dimensional MCE. In conclusion, 3-dimensional MCE is a feasible way to assess subendocardial perfusion and predicts infarct size and functional recovery more precisely than 2-dimensional MCE.

Laparoscopy-assisted resection of an appendiceal mucinous cystadenoma.

We present a 48-year-old man with a complaint of dull right-lower abdominal pain who was diagnosed with mucocele of the appendix. He underwent laparoscopy-assisted resection of the tumor. In the procedure, the entire right colon was freed from the retroperitoneal structures without rupturing the tumor; and ileocecal resection and anastomosis were performed extracorporeally. The pathological diagnosis of the tumor was mucinous cystadenoma of the appendix, measuring 9.0 cm × 8.0 cm × 4.0 cm. The postoperative course was uneventful, and he had no recurrent disease at a 2-year follow up. When resecting an appendiceal mucinous tumor laparoscopically, it is essential (1) to keep the tumor intact during manipulation, and to use a wound-protecting device when delivering the lesion; (2) to consider the extent of tumor resection with a negative surgical margin as well as prophylactic lymph node dissection in cases of suspected adenocarcinoma, even though the oncological adequacy of the laparoscopic procedure for carcinoma remains to be elucidated; and (3) to check whether any mucinous fluid has accumulated in the abdominal cavity, which represents an indication for open surgery.

Effects of imidapril on left ventricular mass in chronic hemodialysis patients.

Left ventricular hypertrophy is considered to be a major cardiovascular risk factor in hemodialysis patients. Not only high blood pressure but also humoral factors such as angiotensin II and aldosterone are thought to contribute to the increase in left ventricular mass. We examined the effects of an angiotensin converting enzyme (ACE) inhibitor, imidapril, on left ventricular mass in patients with end-stage renal diseases on maintenance hemodialysis. Thirty patients on chronic hemodialysis were randomly divided into 2 groups of 15 patients each and given placebo or 2.5 mg imidapril once daily for 6 months. Before and after the 6-month period, left ventricular mass was evaluated by echocardiography, and circulating factors of the renin-angiotensin-aldosterone system were measured. Background characteristics such as age, gender ratio, causes of renal failure, duration of hemodialysis, body mass index and pre-dialysis blood pressure were comparable between the placebo and the imidapril groups. Systolic and diastolic blood pressures were not significantly changed in either group during the study period. In the imidapril group, serum ACE was reduced (12 +/- 1 to 5 +/- 2 U/l, p < 0.01) and plasma renin activity was increased (3.3 +/- 0.8 to 8.1 +/- 3.2 ng/ml/h, p < 0.01), but plasma angiotensin II and aldosterone were not significantly changed after 6 months (13 +/- 3 to 17 +/- 3 pg/ml and 365 +/- 125 to 312 +/- 132 pg/ml, respectively). On the other hand, left ventricular mass index was significantly decreased in the imidapril group (132 +/- 10 to 109 +/- 6 g/m2, p < 0.05) but was unchanged in the placebo group (129 +/- 6 to 126 +/- 5 g/m2). These results suggest that an ACE inhibitor reduces left ventricular mass in hemodialysis patients by a mechanism that is independent of changes in blood pressure.

Comparison of orifice area by transthoracic three-dimensional Doppler echocardiography versus proximal isovelocity surface area (PISA) method for assessment of mitral regurgitation.

Effective regurgitant orifice area is a useful index of the severity of mitral regurgitation (MR). The calculation of regurgitant orifice area using the proximal isovelocity surface area (PISA) method has some technical limitations. Three-dimensional reconstruction of the MR jet was performed using the Live 3D system on a Sonos 7500 to measure regurgitant orifice area directly in 109 cases of MR. Regurgitant orifice area was also measured by quantitative 2-dimensional echocardiography and by the PISA method. To analyze the shape of the regurgitant orifice, the ratio of the long axis to the short axis of the orifice (the L/S ratio) was calculated. Regurgitant orifice area on 3-dimensional echocardiography showed an almost identical correlation with that obtained by quantitative echocardiography (r = 0.91, p <0.0001, slope = 0.97) regardless of the L/S ratio. It was also significantly correlated with orifice area obtained using the PISA method (r = 0.93, p <0.0001). However, orifice area on 3-dimensional echocardiography was significantly larger than that obtained using the PISA method in the whole study group and in the 62 cases of MR with L/S ratios >1.5, whereas the correlation was almost identical in cases of MR with L/S ratios < or =1.5. Orifice area obtained using the PISA method also underestimated that obtained by quantitative echocardiography in cases of MR with L/S ratios >1.5. Three-dimensional echocardiography provided robust values independent of the eccentricity of the MR jet or of cardiac rhythm. In conclusion, the direct measurement of the regurgitant orifice area of MR with 3-dimensional Doppler echocardiography could be a promising method to overcome the limitations of the PISA method, especially in cases of MR with elliptic orifice shapes.