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Background Malnutrition is one of the most important comorbidities in patients with heart failure with preserved ejection fraction. We recently reported the prognostic significance of serum cholinesterase level and superior predictive power of cholinesterase level to other objective nutritional indices such as the controlling nutritional status score, prognostic nutritional index, and geriatric nutritional risk index in patients with acute decompensated heart failure. The aim of this study was to clarify the prognostic role of cholinesterase in patients with heart failure with preserved ejection fraction/acute decompensated heart failure and investigate incremental cholinesterase value. Methods and Results We prospectively studied 274 consecutive patients from the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure With Preserved Ejection Fraction) study. During a follow-up period of 1.2±0.6 years, 56 patients reached the composite end points (cardiovascular death and readmission for worsening heart failure). In the multivariable Cox analysis, cholinesterase level was significantly associated with the composite end points after adjustment for major confounders. A Kaplan-Meier analysis revealed that patients with low cholinesterase levels (stratified by tertile) had significantly greater risk of reaching the composite end points than those with middle or high cholinesterase levels ( P =0.0025). Cholinesterase level showed the best C-statistics (0.703) for prediction of the composite end points among the objective nutritional indices. C-statistics of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for prediction of the composite end points were improved when cholinesterase level was added (C-statistics, from 0.601 to 0.705; P =0.0408). Conclusions Cholinesterase was a useful prognostic marker for prediction of adverse outcome in patients with heart failure with preserved ejection fraction/acute decompensated heart failure.

Aims: We examined the effectiveness of the Japanese Diabetes Risk Score (JPDRISC) and fatty liver markers for predicting incident diabetes., Methods: We created the JPDRISC. The study periods I and II were January 2007 to May 2009 and June 2009 to December 2011, respectively. A total of 2084 people (1389 men, 695 women; mean age: 46 years) were included. People with diabetes in the Period I and those with ethanol intake >140 g/week were excluded. A total of 1515 people were included. Fatty liver using ultrasonography scores (FLUS) were assigned., Results: The mean observation period was 26.3 months, and 24 people had developed diabetes between the Periods I and II. In logistic regression analysis, the JPDRISC (OR=1.197, 95% C.I.: 1.062-1.350, p=0.003) and FLUS (OR=2.591, 95% C.I.: 1.411-4.758, p=0.002) in the Period I were independent determinants of incident diabetes. In receiver operating characteristic analysis, sensitivity and specificity for incident diabetes were 0.885 and 0.536, respectively, in people with both FLUS≥1 and the total JPDRISC≥6 in the Period I. The sensitivity was better than the JPDRISC alone (sensitivity 0.696) and FLUS alone (sensitivity 0.750)., Conclusions: JPDRISC and FLUS were independently associated with incident diabetes and their combination is useful., (Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate longitudinal associations between serum cholinesterase (ChE) and lipid status., Methods: Hazard ratios (HRs) of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for baseline ChE and correlation coefficients between baseline ChE and changes in LDL cholesterol, log triglycerides and HDL cholesterol during 5 years were calculated in a health screening population., Results: During the 5-year follow-up period, 337 men (22.9%) and 208 women (26.3%), 330 men (24.3%) and 114 women (12.4%) and 137 men (8.3%) and 117 women (12.7%) developed hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia, respectively. The HRs of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for each 1 SD increase in baseline ChE were 1.15 (p = 0.009) in men and 1.17 (p = 0.017) in women, 1.25 (p < 0.001) in men and 1.37 (p < 0.001) in women and 1.15 (p = 0.113) in men and 1.12 (p = 0.248) in women, respectively adjusted for BMI and other confounders, while the HRs were not significant after further adjusted for each baseline lipid level except for the HR of hypertriglyceridemia in women (HR, 1.22 (p = 0.047)). The baseline ChE was inversely correlated with the changes in LDL cholesterol (r = -0.117, p < 0.001) and log triglycerides (r = -0.114, p < 0.001) in men and the change in LDL cholesterol (r = -0.191, p < 0.001) in women., Conclusion: ChE was positively associated with incident hyper-LDL cholesterolemia and hypertriglyceridemia adjusted for BMI, while with only incident hypertriglyceridemia in women after further adjusted for the baseline lipid level., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We determine the importance of indicators of nutrition including lymphocyte, total protein, albumin, cholinesterase and body mass index, and compare the prognostic significance in chronic heart failure (CHF). We examined consecutive 465 CHF patients (376 males, age 62 ± 14 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination including indicators of nutrition at the same time in our hospital. The patients were followed up [median period 766 days (interquartile range 500-1060)] to register cardiac deaths and rehospitalization due to worsening heart failure. There were 180 cardiac events during the follow-up periods. Patients with cardiac events had lower cholinesterase level than those without events (P < 0.001). On the receiver operating characteristic analysis, the best cut-off value for cholinesterase was 240 U/l (area under the curve 0.720). In the Kaplan-Meier analysis, patients with cholinesterase <240 U/l had significantly higher cardiac event rates than those with cholinesterase >240 U/l. Multivariable Cox proportional hazards model demonstrated that NYHA class III [hazard ratio (HR): 1.688, 95 % confidence interval (CI) 1.062-2.684, P = 0.027], eGFR (HR: 0.983, 95 % CI 0.971-0.995, P = 0.006), sodium concentration (HR: 0.947, 95 % CI 0.897-0.999, P < 0.046), log BNP (HR: 1.880, 95 % CI 1.509-2.341, P < 0.001), cholinesterase (HR: 0.996, 95 % CI 0.993-0.998, P = 0.002) and exertional periodic breathing (HR: 1.619, 95 % CI 1.098-2.388, P = 0.015) were independent factors to predict adverse clinical outcomes. Serum cholinesterase level was an important prognostic factor in CHF.

Objective: Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia., Methods: Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining., Results: 157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029)., Conclusion: The prevalence of the C5 variant was relatively high, and the C5 variant is associated with decreased risk of CAD in outpatients with severe hypercholinesterasemia.

Organic phosphate pesticides were used worldwide after World War II and experiences on poisoning and treatment have been accumulated. An organic phosphate "nerve agent" Sarin was used in two terrorist attacks in Japan in the 1990s. Sarin effects on humans were well documented in these two incidents. Sarin gas inhalation caused instantaneous death by respiratory arrest in several victims in Matsumoto. Severely injured victims presenting with coma and generalized convulsion were resuscitated and recovered rapidly without sequelae. Miosis and blurred-dark vision, ocular pain, copious secretions from respiratory and gastrointestinal tract (muscarinic effects), and headache were common in severely to slightly affected victims. Plasma cholinesterase (ChE) activity decreased in parallel with the severity of signs and symptoms in victims. Oximes, atropine sulphate, diazepam, and ample intravenous infusion were effective treatments. Follow-up examinations on victims were conducted up to 10 years in Matsumoto, and 5 years in Tokyo. No neurological sequelae or abnormalities were observed after 1 year, except for a few EEG abnormalities or delay in sensory nerve conduction velocity. Posttraumatic stress disorder (PTSD) was observed in several of the victims in the 5-year follow up, irrespective of the severity of poisoning at Matsumoto. Psychological symptoms continue in victims of both incidents.

Open heart surgery in patients with liver cirrhosis is considered to be very risky, but the predictors of poor outcomes in such cases have not been established. We report the perioperative results of open heart surgery in patients with liver cirrhosis in our hospital. We reviewed the results of 13 cases in 12 patients with liver cirrhosis who underwent open heart surgery between January 2001 and December 2010. The Child-Turcotte-Pugh classification, the model for end-stage liver disease score, EuroSCORE, and perioperative data were used to identify risk factors for morbidity and mortality retrospectively. Ten patients had postoperative complications. Significant differences in morbidity were evident for Child-Turcotte-Pugh class, cardiopulmonary bypass time, and crossclamp time. Two patients died of liver failure, one at 40 days and the other at 2 years after surgery. Statistically significant differences in liver-related mortality were evident in the model for end-stage liver disease scores and serum cholinesterase levels. We concluded that a high Child-Turcotte-Pugh class was associated with increased morbidity. Cardiopulmonary bypass and crossclamp times were also related to high morbidity, while high model for end-stage liver disease scores and low serum cholinesterase levels predicted liver-related mortality.

We investigated the significance of analyzing substances causing intoxication in emergency centers. The poison analysis room was established 6 years before this study. We analyzed a total of 504 patients with intoxication (203 males and 301 females). Concerning the prognosis, 23 patients died; 16 patients (10 males, 6 females) died of paraquat/diquat intoxication, 3 patients (3 males) died of intoxication with organic phosphate agents, 1 patient (male) died of intoxication with a phenoxy agent, and 3 patients (1 male, 2 females) died of intoxication with antipsychotic agents. The other 481 patients were discharged after improvement or referred to another department. Furthermore, we examined the presence or absence of information on intoxication at consultation in the patients with intoxication. In 69 (71.9%) of 96 episodes of intoxication with pesticides, the results of analysis were consistent with the information. In 27episodes (28.1%), there was no information at consultation, or the results of analysis were not consistent with the information. In 299 (79.9%) of 374 episodes of drug poisoning, the results of analysis were consistent with the information. In 75 episodes (20.1%), there was no information at consultation, or the results of analysis were not consistent with the information. These results suggest that the analysis of substances causing intoxication is essential in 20% of patients. We investigated the serum cholinesterase (ChE) level on the initial consultation in the patients with intoxication with pesticides. Ingestion of organic phosphate agents markedly reduced the serum ChE level. However, our results suggest that the serum ChE level depends on the type/amount of pesticides and the interval after ingestion. In addition, many patients took several types of pesticides or drugs, suggesting the importance of analyzing substances causing intoxication.

Chronic neurobehavioral effects of acute sarin poisoning were evaluated in 9 male and 9 female patients who were exposed to sarin poisoning in the Tokyo subway incident in Japan. The investigators used nine neurobehavioral tests, as well as a posttraumatic stress disorder checklist, 6-8 mo after the poisoning occurred. Serum cholinesterase activity in patients on the day of poisoning (i.e., March 20, 1995) ranged from 13 to 131 IU/l (mean=72.1 IU/l). The results of analysis covariance, in which age, education level, alcohol consumption, and smoking status (covariates) were controlled in 18 sarin cases and in 18 controls, showed that the score on the digit symbol (psychomotor performance) test was significantly lower in the sarin cases than in controls. Nonetheless, the scores for the General Health Questionnaires, fatigue of Profile of Mood States, and posttraumatic stress disorder checklist were significantly higher in the sarin cases than controls. The investigators added posttraumatic stress disorder to the covariates, and only the score on the digit symbol test was significantly lower in sarin cases. In addition, the results of stepwise multiple regression analysis in 18 sarin cases revealed that scores for the General Health Questionnaires, fatigue of Profile of Mood States (i.e., fatigue, tension-anxiety, depression, and anger-hostility)-together with the paired-associate learning test-were associated significantly with posttraumatic stress disorder. The association did not remain significant for the digit symbol test score. Perhaps a chronic effect on psychomotor performance was caused directly by acute sarin poisoning; on the other hand, the effects on psychiatric symptoms (General Health Questionnaire) and fatigue (Profile of Mood States) appeared to result from posttraumatic stress disorder induced by exposure to sarin.

A patient severely poisoned with sarin in the Sarin Attack in Matsumoto is described. A 19-year-old man was exposed to sarin at 23:00 on 27 June, 1994. At 1:00 of the following day, a rescue team found and brought him to the hospital. His blood pressure was 150-80mmHg and the heart rate was 120/min with frequent premature ventricular contractions (PVC). His respiration was shallow and copious salivation and excretion from the respiratory tract were observed. Consciousness disturbance, generalized convulsion, severe miosis and fasciculation of tongue, facial muscle and extremities were also marked. Serum cholinesterase was 21 U/l (normal 109-249) and acetylcholinesterase in erythrocyte (E-AchE) was 0.1U/l (normal 1.2-2.0). Electroencephalogram (EEG) 30 hours after exposure showed polispike and wave complexes. Ventilatory assistance, forced urination and injection of diazepam and atropin improved his general condition and he was discharged 18 days after exposure. Three months after exposure, E-AchE was normalized and there was no complaint. But one year after exposure, EEG showed epilecpic discharges during sleep, and Holter electrocardiogram showed frequent PVC. As no clinical cases of severe sarin poisoning like this patient was reported, a longterm follow-up of this patient is very important.

We designed a clinical study to determine the effect of prostaglandin E1 (PGE1) on functional recovery of the liver after hepatectomy. Thirty-five patients with primary hepatic neoplasms accompanied by chronic liver disease were randomly divided into two groups: 13 patients received intravenous PGE1 at 0.06 micro g/kg per minute for 3 postoperative days (PGE1[+] group) and 22 patients did not (PGE1[-] group). All postoperative values of hepatic function tests were calculated as a ratio to each preoperative value. Significantly higher cholinesterase ratios were observed in the PGE1[+] group than in the PGE1[-] group 2 weeks postsurgery (P < 0.05). The alanine aminotransferase (ALT) ratios at 1 and 2 weeks postsurgery were 118% and 123% in the PGE1[+] group and 207% and 175% in the PGE1[-] group, respectively. The ratio of the maximum postoperative ALT level was 503% in the PGE1[+] group and 792% in the PGE1[-] group (P < 0.05). We concluded that PGE1 would have the effect of conditioning the postoperative ALT elevation and cholinesterase deterioration and that the patient's postoperative course might be more favorable with the use of PGE1.

We detected 121 individuals with silent type of serum cholinesterase from 36 families in Japan. DNA analysis totaling 37 members of eleven blood unrelated families were carried out by four useful methods, namely, 1) PCR-SSCP analysis, 2) dot blot hybridization (DBH) with the use of synthetic oligonucleotide probe, 3) restriction endonuclease analysis (REA) and 4) direct sequencing analysis. Their mutations were classified into four groups, namely, 1) a G-->C transversion at codon 365, 2) a frameshift mutation with insertion of an extra A at codon 315, 3) an A-->G transition at codon 128 and 4) a C-->A transition at codon 400. The three procedures including (PCR-SSCP, DBH, REA) without the use of radio labeled materials (non-RI) are recommendable for the analyses. However, the direct sequencing analysis of bases with RI might be, at present, necessary for the final identification.

Two different gene mutations associated with the silent phenotype for human serum cholinesterase were demonstrated. DNA from five individuals with silent gene phenotype of three unrelated Japanese families was amplified by the polymerase chain reaction (PCR) and analyzed by direct sequencing. The first instance demonstrated a G----C transversion at codon 365 from GGA (Gly) to CGA (Arg), which was seen in three individuals of the two families. This mutation was resulted to create a new Taq 1 restriction site (TCGA). The second mutation was shown by a double heterozygous condition with two different silent gene mutations in two members of remaining one family. These mutations were as follows: 1) one type was a frameshift mutation, in which an extra A was inserted in codon 315 (ACC----AACC) to create a new stop codon at position 322 and 2) the other was the same point mutation at codon 365 as seen in the first instance. These results indicated that many silent variants can be distinguished by direct sequence analyses of genomic DNA.

Chlorpyrifos, an organophosphate insecticide, has often been used as a termite-control agent since the advent of regulatory measures against the use of chlordanes in September 1986. A current concern is hazards such as organophosphorus poisoning among termite-control workers. In this study, the blood cholinesterase activity, the number of hours engaged in termite-control work, general conditions, and various test values were examined regularly in eight workers at a termite-control office. The results are summarized as follows. 1. The plasma cholinesterase level was within the normal range from October 1986 until April 1987 in all workers, but started decreasing after May following the initiation of the full-scale termite-control season. It remained lower than the normal range (0.6 pH) from June until August in five of the six termite-control workers. The lowest level observed during this period was less than 50% of the mean value for each worker prior to the busy season in the six termite-control workers and was less than 10% of the pre-season values in three of them. In two workers, engaged mainly in sales, the plasma cholinesterase activity remained higher than in termite-control workers throughout the season. The lowest level in this minimally-exposed group during this period was not less than 50% of the mean value for each worker before the busy season. With the arrival of the off season, the level began to recover and returned to normal in all workers in January 1988. 2. The red cell cholinesterase activity remained within the normal range throughout the observation period, but it was generally low during the busy season from June to September and relatively high during the off season from December 1987 to January 1988. On the average, the red cell cholinesterase activity during the season was about 30% lower than that in the off season. 3. No marked subjective or objective abnormalities were seen in the workers. The results of other tests were generally normal, although a slight decrease in the red cell and white cell counts as well as abnormalities in serum lipid and lipase were noted in some workers. Further observations are necessary. 4. A significant negative correlation was noted between the number of hours engaged in termite-control work and variations in the plasma cholinesterase activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum lipids were studied in 97 overseas and 282 Japanese university students. As compared with Japanese, serum total cholesterol levels were low and high density lipoprotein/total cholesterol ratio was high in the overseas students, especially in Chinese and Korean students. 30-39-year-old Chinese students, moreover, showed elevated high density lipoprotein levels. Choline esterase levels were significantly lower in 30-39-year-old Chinese and Korean students than in Japanese and Taiwanese.