The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction.

Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive mitral flow pattern is well recognized as a finding of severely elevated LVEDP. On the other hand, an abnormal relaxation pattern can be interpreted many ways. For example, some patients who display an abnormal relaxation pattern have a mild impairment of left ventricular (LV) relaxation as a result of aging, and others have severely impaired LV diastolic function. To evaluate LVEDP in patients with abnormal relaxation mitral filling patterns, we studied 55 patients who had coronary artery disease with abnormal relaxation pattern who underwent elective cardiac catheterization. We recorded the transmitral and pulmonary venous flow velocity curves and measured the duration of the mitral A wave (MAd) and pulmonary venous reversal wave during atrial contraction (PAd). Positive correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd-MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV end-diastolic pressure in patients with an abnormal relaxation pattern in the transmitral flow velocity curve.     

Usefulness of free-angle M-mode echocardiography in assessing left ventricular dimension and left ventricular systolic function

Objectives To assess the usefulness of free-angle M-mode echocardiography in measuring left ventricular (LV) dimension and global systolic function. Background The validity of conventional M-mode echocardiography in assessing LV dimension and global systolic function is well known; the incidental angle between the M-mode cursor and true LV minor axis diameter, however is a potential cause of measurement error. Free-angle M-mode echocardiography may overcome the limitation of M-mode cursor arrangement in conventional M-mode echocardiography. Methods Thirteen normal volunteers and 10 patients in whom abnormal left ventricular wall motion was not detected by echocardiography (mean age, 53±17 years) were enrolled in this study. Conventional and free-angle M-mode echocardiographic images of the LV were obtained by echocardiography (ALOKA SSD-5500) using a 2.5-MHz transducer, and the LV end-diastolic (LVDd) and end-systolic (LVDs) dimensions were measured by the leading edge method. LV end-diastolic and end-systolic volumes were calculated using a formula by Teichholz, and the LV ejection fraction (LVEF) was obtained. Data from conventional M-mode echocardiography and free-angle M-mode echocardiography were then compared. Results Measurements obtained with conventional M-mode and free-angle M-mode echocaardiography were strongly correlated. Correlation coefficients for LVDd, LVDs, and LVEF were 0.98, 0.98, and 0.96, respectively (p<0.001 in each case). Conclusions Assessment of left ventricular dimension, and global systolic function with free-angle M-mode can be as accurate as conventional M-mode in subjects in whom left ventricular wall motion abnormality is not detectable by echocardiogram. Moreover, when there is improper M-mode cursor direction in conventional echocardiography, free-angle M-mode echocardiography can assess global left ventricular systolic function more accurately and conveniently than conventional M-mode echocardiography.     

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones

In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12 α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education, Science and Culture of Japan, and a grant from University of Tsukuba Project Research.     

Alterations of bile acid composition in gallstones,bile, and liver of patients with hepatolithiasis,and their etiological significance

A detailed comparison was made of the bile acid composition in gallstones (brown pigment stones) and paired bile and liver from both affected and unaffected lobes by gallstones, which were taken at operation from 16 patients with hepatolithiasis, with the aim of elucidating whether stone formation is derived from possible local disturbances limited to intrahepatic bile ducts. Brown pigment stones in the intrahepatic bile ducts, most of which were accompanied by bile with high cholesterol saturation, had significantly more cholesterol, and less calcium bilirubinate and bile acid than those found in the extrahepatic bile ducts. Intrahepatic gallstones had significantly lower amounts of secondary and unconjugated bile acids, the bile acids modified by bacterial intervention, than extrahepatic stones. Bile specimens from both affected and unaffected lobes showed significantly increased molar percentages of cholesterol and decreased percentages of bile acids than bile from controls. In contrast, liver specimens from both lobes showed significantly higher concentrations of total bile acids. Secondary bile acids were present in a much lower proportion in bile and liver from both lobes than in bile and liver from controls. On the other hand, unconjugated bile acids were present in a much higher proportion in bile and liver from patients and only in negligible amounts in bile from controls. Furthermore, the plasma levels of mevalonate and those of 7α-hydroxy-4-cholestene-3-one were found to be significantly higher and lower in patients than in controls, respectively, indicating that in hepatolithiasis cholesterol synthesis might increase and bile acid synthesis might decrease in the liver. These findings suggested that alterations of bile acid composition in gallstones, bile, and liver of patients with hepatolithiasis may be attributed to not only secondary changes resulting from local disturbances limited to intrahepatic bile ducts but also possible primary alterations of hepatocyte metabolism, such as bile acid conjugation and primary defects in cholesterol and bile acid synthesis.     

Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin

Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific for hepatic binding protein (HBP), a receptor that resides exclusively on hepatocytes.In vivo measurement of receptor concentration was obtained via kinetic analysis of liver and blood time-activity data obtained during the hepatic clearance of intravenously administered TcNGA. The purpose of this study was to assess receptor concentration as a measure of the functioning hepatocyte mass. Therefore, TcNGA and dualinjection indocyanine green maximal removal rate (ICG R_max) studies were performed on nine patients with hepatic cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration was compared with ICG R_max, which is a validated method for the estimation of the functioning hepatocyte mass. The correlation coefficient was 0.76 (P=0.017). It is concluded that HBP concentration ([HPB]_o) as measured by functional imaging is a measure of functioning hepatocyte mass. This implies that measurement of an individual's receptor concentration by using nuclear medicine techniques provides an objective index of hepatic functional mass and supports attempts to rigorously evaluate [HBP]_o for its clinical efficacy.     

Asymptomatic acute hepatitis E in a female patient with ulcerative colitis

We present a 60-year-old female patient with asymptomatic acute hepatitis E that was fortuitously detected during the course of ulcerative colitis (UC). She was admitted to hospital on October 30, 2015. Endoscopy and histological examination of the colon showed typical findings of UC. All parameters of liver function tests were normal on this date. Combination therapy with oral prednisolone and mesalazine was started and intravenous administration of infliximab once every 8 weeks was added later. Her symptoms gradually improved after these treatments, and she was discharged on February 7, 2016. In a periodic check-up on July 7, 2016, high levels of serum transaminases were detected in liver function tests. Although drug-induced liver injury was first suspected, anti-hepatitis E virus (HEV) immunoglobulin A was positive. The genotype and subgenotype of this HEV are 3 and 3a, respectively, although the infectious route of the HEV was unclear. Within 2 weeks after the onset of acute liver injury, the HEV viremia disappeared and her liver function tests improved. Examination of serum anti-HEV immunoglobulin A should be added at the time of abnormal liver function tests in patients with UC receiving immunosuppressive and biological drugs.     

Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart failure and control

We studied the effect of intravenous pirenzepine (3 mg) in normal subjects (n=15, 43+/-16 years old) and in patients with chronic heart failure (n=15, 61+/-12 years old) to assess the effect of low-dose pirenzepine on vagal activity. R-R intervals and the standard deviations, low-frequency power (LF: ln ms2, 0.04-0.15 Hz), high-frequency power (HF: ln ms2, 0.15-0.40 Hz) and the ratio of low- to high-frequency power (LF/HF ratio) were measured 10 min before and after pirenzepine using a Holter analysis system. Pirenzepine was found to cause a significant increase in the R-R interval from 903+/-112 to 956+/-129 ms in the control group (P<0.0001) and from 927+/-141 to 958+/-168 ms in patients with chronic heart failure (P<0.01). Pirenzepine also increased HF significantly from 4.29+/-0.32 to 5.16+/-0.38 ln ms2 in the control group (P<0.0001) and from 4.04+/-0.16 to 4.48+/-0.24 ln ms2 in the chronic heart failure group (P<0.05). Pirenzepine did not significantly alter the LF/HF ratio in either group. We emphasize that pirenzepine appears to have a vagoinimetic effect in patients with chronic heart failure and that it may be useful for augmenting vagal control of the heart in some patients with chronic heart failure.     

The impact of portal vein thrombosis on the prognosis and liver function of nonmalignant cirrhotic patients

Abstract

Objectives: The clinical impact of portal vein thrombosis (PVT) in cirrhotic patients remains unclear. The aim of the study is whether recanalization of acute PVT in nonmalignant cirrhotic patients is associated with their prognosis.

Materials and methods: We identified subject with PVT in cirrhotic patients from institutional database. Patients with ≥50% reduction in thrombus size were classified into the improved group and those with ≤49% reduction in thrombus size, or thrombus development in other branches were classified into the deteriorated group. We compared the cumulative survival rate, event-free survival rate (EFS), and liver function (albumin-to-bilirubin (ALBI) and model for end-stage liver disease XI (MELD-XI) between the two groups.

Results: Twenty-seven patients were enrolled in this retrospective study. Sixteen patients were classified into the improved group, and 11 were classified into the deteriorated group. In the improved group, the ALBI grade and MELD-XI measured before the onset of PVT and at one year after the onset of PVT were not significantly different. In contrast, MELD-XI was significantly aggravated in deteriorated group (MELD-XI [p?=?.02]). The cumulative survival of the two groups did not differ significantly; however, the EFS of the deteriorated group was significantly lower (p?=?.049).

Conclusions: Residual thrombosis of PVT in cirrhotic patients increased the incidence of liver-related events and was associated with the deterioration of the liver function.