Kansei Uno

Pancreas divisum as a predisposing factor for chronic and recurrent idiopathic pancreatitis: initial in vivo survey

Background It is a controversial issue whether pancreas divisum (PD) induces pancreatitis. All previous studies have investigated this issue based on endoscopic procedures, which inevitably involve a selection bias. Objectives To determine the unbiased prevalence rate of PD in a community population and to investigate the effect of PD on idiopathic pancreatitis using a non-invasive magnetic resonance (MR) technique. Design Cross-sectional study. Patients The study enrolled 504 subjects from the community who participated in the medical check-up programme and 46 patients with idiopathic pancreatitis (8 acute, 23 chronic, 15 recurrent) extracted from 70 122 consecutive MR studies performed at an academic tertiary care hospital. Interventions All subjects underwent magnetic resonance (MR) scanning and medical examination. Main outcome measures Statistical comparison between subjects from the community and patients with idiopathic pancreatitis was made for the rate of PD (and its subtypes: classical PD, PD with absent ventral duct, and incomplete PD), MR findings, and clinical features. Results Multiple logistic regression analysis revealed PD as a significant factor that induces pancreatitis (OR 23.4; p<0.0001). The PD rate was significantly higher for all/chronic/recurrent idiopathic pancreatitis patients (35%/43%/33%; p<0.001 for all) than for subjects in the community group (2.6%), but was not higher for acute pancreatitis (13%; p=0.357). All PD subtypes were indicated to induce idiopathic pancreatitis but showed different associations with each onset type of pancreatitis. Conclusions This is the first study to describe the prevalence of PD and PD subtypes in a community population and their association with idiopathic pancreatitis in vivo based on the findings of non-invasive MR and with minimal selection bias. It is concluded that PD should be considered a predisposing factor for chronic and recurrent pancreatitis.

ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity.

Body weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) function, and EE. In mice, Enpp2 was highly expressed in visceral white adipose tissue and BAT and is downregulated in hypertrophied adipocytes/adipose tissue. Enpp2+/− mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller body weight gains and less insulin resistance than control mice fed the same diet. BAT was functionally more active and EE was increased in Enpp2-deficient mice. In humans, ENPP2 expression in subcutaneous fat and ENPP2 levels in serum were reduced in obese subjects. Taken together, our results establish ENPP2 as an adipose-derived, secreted enzyme that regulates adipose obesity and systemic metabolism. They also suggest ENPP2 could be a useful therapeutic target for the treatment of metabolic disease.

Speckle tracking global strain rate E/E' predicts LV filling pressure more accurately than traditional tissue Doppler E/E'.

Background: The ratio of early diastolic transmitral flow velocity (E) to tissue Doppler (TD) mitral annular early diastolic velocity (E/E′VEL‐TD) has been widely used for the noninvasive assessment of LV diastolic filling pressures. However, it has been reported that E/E′VEL‐TD is not accurate particularly when being applied to patients with advanced heart failure. Methods: Fifty‐six ICU patients with decompensated heart failure underwent simultaneous echocardiography and PCWP measurements. Patients with elevated PCWP (n = 41) were compared with patients normal PCWP (n = 15) as well as age‐matched healthy controls (n = 32). In the apical 4‐chamber view, the ratio of E to speckle tracking (ST) mitral annular velocity (E/E′VEL‐ST) and early diastolic global LV longitudinal strain rate (E/E′SR‐ST) were evaluated as new surrogate markers of elevated PCWP. Results: Correlations with PCWP were observed for speckle tracking derived E/E′VEL‐ST (r = 0.40,P = 0.002) and E/E′SR‐ST (r = 0.56, P < 0.001), although the traditional E/E′VEL‐TD did not show a significant correlation (r = 0.23, P = 0.082). Compared with controls, patients with elevated PCWP had significant increases in all variables. The best cutoff values and diagnostic accuracies for identifying elevated PCWP were E/E′VEL‐TD>12 (Sensitivity/Specificity/area under the ROC curve: 0.58/0.90/0.78), E/E′VEL‐ST > 14 (0.60/0.85/0.80), and E/E′SR‐ST > 93 (0.80/0.88/0.89). Conclusion: Speckle tracking derived E/E′SR‐ST may be a robust surrogate marker of elevated LV filling pressure. In ICU patients, E/E′SR‐ST showed better correlation with PCWP and higher diagnostic accuracy than the tissue Doppler approach. (Echocardiography 2012;29:404‐410)

Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy — Prospective multicenter cohort study☆ , ☆☆

BACKGROUND The reported prevalence of left ventricular noncompaction (LVNC) varies widely and its prognostic impact remains controversial. We sought to clarify the prevalence and prognostic impact of LVNC in patients with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS We evaluated the presence of LNVC in patients with DMD/BMD aged 4-64 years old at the study entry (from July 2007 to December 2008) and prospectively followed-up their subsequent courses (n=186). The study endpoint was all-cause death and the presence of LVNC was blinded until the end of the study (median follow-up: 46 months; interquartile range: 41-48 months). RESULTS There were no significant differences in baseline characteristics between patients with LVNC (n=35) and control patients without LVNC (n=151), with the exception of LV function. Patients with LVNC showed, in comparison with patients without LVNC, a significant negative correlation between age and LVEF (R=-0.7 vs. R=-0.4) at baseline; and showed a significantly greater decrease in absolute LVEF (-8.6 ± 4.6 vs. -4.3 ± 4.5, p<0.001) during the follow-up. A worse prognosis was observed in patients with LVNC (13/35 died) than in patients without LVNC (22/151 died, Log-rank p<0.001). Multivariate Cox analysis revealed that LVNC is an independent prognostic factor (relative hazard 2.67 [95% CI: 1.19-5.96]). CONCLUSION LVNC was prevalent in patients with DMD/BMD. The presence of LVNC is significantly associated with a rapid deterioration in LV function and higher mortality. Neurologists and cardiologists should pay more careful attention to the presence of LVNC.

Usefulness of 18FDG/13N-ammonia PET imaging for evaluation of the cardiac damage in Churg-Strauss syndrome.

FDG/NH3 PET imaging has recently been shown to be useful for evaluating the status of the cardiac damage as well as predicting the reversibility of the cardiac wall motion abnormality in inflammatory diseases such as cardiac sarcoidosis [1]. We were able to evaluate cardiac FDG/NH3 PET imaging before and after treatment in a patient with another inflammatory disease, ChurgStrauss syndrome, in which there is systemic vasculitis with eosinophilic infiltration. A 52-year-old woman who had been treated medically for bronchial asthma was admitted with sensory disturbances and weakness of the left lower extremity. On admission, blood analysis revealed a marked increase in eosinophil count (10,800/mm3). Although there were no cardiac symptoms, the ECG showed the appearance of an abnormal Q wave in lead III and of a QS pattern in leads V1–V3. Left ventriculography demonstrated severe hypokinesis of the anteroseptal and inferior wall, with an estimated ejection fraction of 41%. Coronary angiography detected no stenotic lesions. The patient was diagnosed as having Churg-Strauss syndrome with myocardial involvement. She received an intravenous pulse of methylprednisolone, followed by daily oral prednisolone. Before treatment (a), a pattern of enhanced 18FDG uptake with reduced perfusion (the pattern of flowmetabolism mismatch) was observed in the anteroseptal (arrows) and posterolateral (arrowheads) regions. Three months after treatment (b), improved perfusion was apparent in the anteroseptal (arrows) and posterolateral (arrowheads) regions, and the pattern of flow-metabolism mismatch had largely disappeared. In the echocardiogram recorded at this time, no improvement in cardiac wall motion was observed. It was not until 40 days after this follow-up PET scan that the echocardiographic findings revealed improved cardiac wall motion.

Meandering Main Pancreatic Duct as a Relevant Factor to the Onset of Idiopathic Recurrent Acute Pancreatitis

Background Meandering main pancreatic duct (MMPD), which comprises loop type and reverse-Z type main pancreatic duct (MPD), has long been discussed its relation to pancreatitis. However, no previous study has investigated its clinical significance. We aimed to determine the non-biased prevalence and the effect of MMPD on idiopathic pancreatitis using non-invasive magnetic resonance (MR) technique. Methods and Findings A cross-sectional study performed in a tertiary referral center. The study enrolled 504 subjects from the community and 30 patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent acute). All subjects underwent MR scanning and medical examination. MMPD was diagnosed when the MPD in the head of pancreas formed two or more extrema in the horizontal direction on coronal images of MR cholangiopancreatography, making a loop or a reverse-Z shaped hairpin curves and not accompanied by other pancreatic ductal anomaly. Statistical comparison was made among groups on the rate of MMPD including loop and reverse-Z subtypes, MR findings, and clinical features. The rate of MMPD was significantly higher for all idiopathic pancreatitis/idiopathic recurrent acute pancreatitis (RAP) (20%/40%; P<0.001/0.0001; odds ratio (OR), 11.1/29.0) than in the community (2.2%) but was not higher for acute/chronic pancreatitis (14%/8%; P = 0.154/0.266). Multiple logistic regression analysis revealed MMPD to be a significant factor that induces pancreatitis/RAP (P<0.0001/0.0001; OR, 4.01/26.2). Loop/reverse-Z subtypes were found more frequently in idiopathic RAP subgroup (20%/20%; P = 0.009/0.007; OR, 20.2/24.2) than in the community (1.2%/1.0%). The other clinical and radiographic features were shown not associated with the onset of pancreatitis. Conclusions MMPD is a common anatomical variant and might be a relevant factor to the onset of idiopathic RAP.

Effects of Rapid Saline Infusion on Orthostatic Intolerance and Autonomic Tone After 20 Days Bed Rest

To test whether acute volume expansion can normalize orthostatic intolerance and autonomic tone after prolonged bed rest (BR), 23 men were subjected to 20 days BR. Left ventricular (LV) echocardiography was performed during the lower body negative pressure (LBNP) test before and after BR with and without preceding rapid infusion of saline (1,500 ml/30 min). Saline infusion restored heart rate, LV dimension, and stroke volume during LBNP, increased cardiac output (from 4.1 +/- 1 to 5.3 +/- 1 L/min), and normalized LBNP tolerance time (from 11 +/- 4 to 23 +/- 6 minutes). In 9 men, a Holter electrocardiogram was recorded on the day before BR, the fourth and twentieth days of BR, and the day after BR. The high-frequency component of heart rate variability during sleep gradually decreased and reached the lowest level on the day after BR (100%, 66 +/- 16%, 39 +/- 18%, 10 +/- 8%). Thus, restoring decreased blood volume is an effective countermeasure for orthostatic intolerance after BR. However, decreased vagal tone persisted, suggesting reset autonomic tone.

Cardiac rehabilitation decreases plasma pentraxin 3 in patients with cardiovascular diseases

Background: Inflammatory markers such as serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma pentraxin 3 (PTX3), which belong to the pentraxin superfamily, increase due to various inflammatory diseases. Some studies demonstrated that serum CRP and SAA are predictors of cardiovascular diseases, and cardiac rehabilitation (CR) induces anti-inflammatory effects. In the present study, we investigated the effects of CR on pentraxins (serum CRP, SAA, and plasma PTX3) in patients with cardiovascular diseases. Methods: Fifty patients with cardiovascular diseases [61 ± 13 (mean ± SD) years old, male/female 44/6] participated. Each subject performed CR using aerobic bicycle exercise two or three times per week for 3–6 months. We measured resting serum high-sensitivity CRP (hsCRP), SAA, and plasma PTX3 before and 3 and 6 months after CR, and compared them with VO2peak determined using a standard increment cycle ergometer protocol, B-type natriuretic peptide (BNP), and other biochemical data such as HbA1c. Results: There was a significant positive correlation between hsCRP and SAA (r = 0.92, p < 0.001), but no relations between these parameters and PTX3. Plasma PTX3 significantly decreased time dependently during CR (at baseline 3.2 ± 2.0 ng/ml, at 3 months 2.3 ± 0.8 ng/ml, at 6 months 2.1 ± 0.7 ng/ml; all p < 0.05). Serum hsCRP tended to decrease, but not statistically significantly. At baseline, plasma PTX3 was negatively correlated with the percentage of the predicted values of VO2peak and positively correlated with BNP. CR significantly increased the percentage of the predicted values of VO2peak and decreased BNP. Conclusions: Plasma PTX3, an inflammatory marker, which was quite different from CRP and SAA, decreased during cardiac rehabilitation with an improvement of exercise capacity in patients with cardiovascular diseases.

Reproducibility and Diagnostic Accuracy of Three-Layer Speckle Tracking Echocardiography in a Swine Chronic Ischemia Model

Background: The subendocardial myocardium normally has higher systolic strain than the subepicardial myocardium and can be damaged first in face of ischemia. We investigated the reproducibility and feasibility of novel three‐layer speckle tracking system and compared the diagnostic accuracy with experienced visual interpretation. Methods: An ameroid constrictor was placed around the proximal left circumflex (LCX) coronary artery in 19 pigs. Four weeks later, subtotal stenosis was confirmed in all pigs by coronary angiogram. Two dead pigs and three pigs with pathological infarction were excluded. Transthoracic left ventricle (LV) short‐axis echocardiograms were recorded at rest before and 4 weeks after the operation. LV posterior wall motion was scored by two experienced doctors and analyzed by the speckle tracking system (n = 14). Results: Strain variables gave reasonable intra/interobserver reproducibility (mean absolute percentage errors = 13/19, intraclass correlation coefficients = 0.97/0.92). All strain variables and visual wall‐motion scores changed significantly during stenosis (P < 0.05). Of all variables, endocardial strains, particularly the circumferential strain demonstrated the highest area under curve (AUC), showing better diagnostic accuracy than experienced visual interpretation (sensitivity 0.93 vs. 0.79, specificity 0.93 vs. 0.73, AUC 0.95 vs. 0.77, P < 0.05). Conclusion: Three‐layer speckle tracking is a feasible and reproducible modality. In particular, endocardial speckle tracking provides incremental value in accurately identifying regional ischemia even in the rest echocardiography. (Echocardiography 2011;28:1148‐1155)

Development of an enzymatic assay for sphingomyelin with rapid and automatable performances: Analysis in healthy subjects and coronary heart disease patients

BACKGROUND Sphingomyelin (SM) is an important choline group-containing phospholipid and is considered to be an independent risk factor for coronary heart disease. METHODS We have developed a specific enzymatic assay for SM measurement with rapid and automatable performances by using two-reagent system involving sphingomyelinase. We performed within-run and between-run precision, linearity test, detection limit, recovery test and interference to validate this assay. Then, we measured the serum SM concentration in 194 healthy subjects and 141 consecutive patients undergoing coronary angiography. RESULTS The within-run and between-run coefficients of variation for SM concentrations were 1.1-1.3% and 1.0-1.2%, respectively. Quantitative measurements to a lower limit of 30 μmol/L were shown to be possible. The recoveries of the exogenously added SM to the control samples were 98.7%-101.5%. No effect was observed after the addition of some interference materials. The mean ± SD of the serum SM concentration in the 194 healthy subjects was 553.3 ± 100.1 μmol/L. We found that the SM concentration was significantly higher among an acute coronary syndrome subjects than among the healthy subjects (P<0.01) and that the serum SM concentrations were significantly correlated with the serum magnesium concentration. CONCLUSIONS We have developed a rapid and automatable enzymatic assay for SM that enables the automatic measurement of choline-containing phospholipids. This assay may be useful for various types of biochemical and clinical research.