Association between N-methyl-D-aspartate Receptor Subunit 2B Gene Polymorphisms and Personality Traits in a Young Japanese Population.

OBJECTIVE: The N-methyl-D-aspartate receptor subunit 2B (GluN2B) is involved in regulation of anxiety and depression and nervous activity in the brain. Single nucleotide polymorphisms of the GluN2B gene (GRIN2B) are associated with human mental function and behaviour. We investigated whether four GRIN2B polymorphisms (rs7301328, rs1806201, rs1805247, and rs1805502) affect characterisation of personality traits. METHODS: In 248 young people, GRIN2B polymorphisms were analysed, and personality traits were assessed using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and State-Trait Anxiety Inventory (STAI). RESULTS: There was no main effect of the GRIN2B polymorphisms on the NEO-FFI and STAI dimension scores. Interaction between polymorphism and sex was found in rs1805247 (p = 0.034) and rs1805502 (p = 0.040) in terms of the conscientiousness score of the NEO-FFI. However, post hoc simple main effect analysis showed no significant effect. The preliminary haplotype analysis indicated that haplotype CTT (rs1806201-rs1805247-rs1805502) in the haplotype block was associated with the extraversion score of the NEO-FFI in female participants (p = 0.044), but the significance was lost on correction for multiple testing. CONCLUSION: There was no significant association between selected GRIN2B polymorphisms and personality traits, but this may be due to low statistical power. Further studies involving a larger study population are needed to clarify this.

Effects of orthotic therapeutic electrical stimulation in the treatment of patients with paresis associated with acute cervical spinal cord injury: a randomized control trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To determine the effects of orthotic therapeutic electrical stimulation (TES) on the hand in patients with paresis associated with acute cervical spinal cord injury. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: The study included patients treated for spinal cord injuries (Frankel classification, grades B and C) at our institution within 1 week post injury between May 2011 and December 2014. The patients were allocated randomly to TES and control groups at the time of admission and underwent TES+conventional training or conventional training alone, respectively. Both hands of each patient were treated in the same way. The primary outcome was total passive motion (TPM) of the fingers (degrees). The secondary outcomes were edema (cm) and the upper-extremity motor scores of the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). After randomization, outcomes were assessed at 1 week, 1 month and 3 months post injury in both groups. RESULTS: Twenty-nine individuals were assessed at 3 months (15, TES; 14, control). There were no significant between-group differences for TPM of the fingers, edema and upper-extremity motor scores at 1 week, 1 month and 3 months after injury, although TPM of the fingers tended to be lower in the control group. CONCLUSIONS: It is unclear from the results of this study whether TES has a therapeutic effect on TPM, edema or the upper-extremity motor score of the ISNCSCI. The results of this study provide useful data for future meta-analyses.

Splenectomy and antiviral treatment for thrombocytopenic patients with chronic hepatitis C virus infection.

Thrombocytopenic patients with chronic hepatitis C virus (HCV) infection are poor candidates for antiviral treatment with interferon (IFN), but no standard treatment for thrombocytopenia has yet been established. We evaluated the safety of splenectomy and its efficacy for the initiation and continuation of antiviral therapy. From March 2003 to April 2006, 10 patients (mean age 62.5 years) with HCV-related cirrhosis, low platelet count (<==106 000/mm(3)) and splenomegaly (spleen size >==10 cm) underwent splenectomy. Platelet counts significantly increased at 4-8 weeks after splenectomy [pre: 64 200 +/- 6900/mm(3)vs post 209 000 +/- 40 600/mm(3) (P = 0.004)]. No severe operative complications were observed. All patients subsequently received antiviral therapy. Of the eight patients who were infected with HCV genotype 1 and had a high viral load (>==100 KIU/mL), four received combination therapy with pegylated IFNalpha-2b plus ribavirin, and the other four received standard IFNalpha-2b plus ribavirin. One patient infected with HCV genotype 2 and another with HCV genotype 1 and a low viral load (<100 KIU/mL) were treated with pegylated IFNalpha-2a. Six patients achieved sustained virologic response (SVR). Among four patients who failed to achieve SVR, one was given retreatment with pegylated IFN plus ribavirin, and the other three received low-dose long-term IFN therapy. Although this study was small, the treatment results were similar to those for patients without thrombocytopenia and suggested that splenectomy would not reduce the antiviral efficacy of IFNalpha-based treatment.

[Aortic arch aneurysm with aortopulmonary fistula; report of a case].

A 77-year-old female was admitted to our hospital due to congestive heart failure. Computed tomography and angiography showed a saccular aneurysm with aortopulmonary fistula in the aortic arch. The patient underwent total arch replacement and patch closure of the pulmonary artery in an urgent operation. She was discharged after uneventful postoperative course, although staged sternal closure and 5 days of respiratory management were needed. A few cases of aortic arch aneurysm with perforation to the pulmonary artery are operated with success, which depends on severity of congestive heart failure and urgency. Therefore, it should be diagnosed exactly and rapidly. In the operation, special care should be taken to avoid right heart failure and postoperative respiratory distress.

Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.

Several studies indicate that the mu-opioid receptor plays a role in addiction not only to opiate drugs but also to alcohol and non-opiate addictive drugs. Our studies aim to reveal the associations between gene polymorphisms and methamphetamine (MAP) dependence/psychosis. We newly identified several polymorphisms and four substantial linkage disequilibrium (LD) blocks in the mu-opioid receptor (OPRM1) gene. We found significant differences in both genotype and allele frequencies of the single-nucleotide polymorphism (SNP) IVS2+G691C between control (n=232) and MAP-dependent/psychotic patients (n=128). There was also a significant association between IVS2+G691C and patients with transient psychosis. These results suggest that the OPRM1 gene variations may be a factor in development and prognosis of MAP psychosis.

[Pulmonary dirofilariasis resected by video-assisted thoracoscopy; report of a case].

A 35-year-old female was admitted for biopsy of abnormal shadow on chest X-ray. She was operated on for partial wedge resection of the right lower lobe by video-assisted thoracoscopy without complication. Pathological findings in operation showed inflammatory benign tissues and suggested pulmonary dirofilariasis. Serologic examination was negative after operation, however histological diagnosis supported pulmonary dirofilariasis because a pulmonary artery embolism of calcified tissues consisted of non-human cells. There may be many cases due to old infections like this one, so it is important to consider it for diagnosis and perform more positive surgical procedures. We review a case of pulmonary dirofilariasis safely resected by video-assisted thoracoscopy for diagnosis by exclusion.

Expression of the exocytotic protein syntaxin in mouse oocytes.

Syntaxin is an integral membrane protein that is involved in membrane fusion. The exocytosis of the contents of cortical granules, secretory vesicles located in the cortex of an egg, modify the extracellular environment to block additional spermatozoa from penetrating the newly fertilized egg. The aim of this study was to characterize syntaxin expression in mouse oocytes, and to determine the specific isoform that is expressed. Syntaxin was demonstrated in the mouse ovary and in mouse oocytes by both western blot and reverse transcription-polymerase chain reaction analyses. Syntaxin 4 was specifically expressed in metaphase II oocytes. Syntaxin was also immunolocalized within metaphase II oocytes and one-cell embryos with pronuclei using laser scanning confocal microscopy. In metaphase II oocytes, syntaxin was located on the plasma membrane and in the cortex, where cortical granules are present, but was not seen at sites free of cortical granules. In one-cell embryos, no cytoplasmic region was free of syntaxin immunoreactivity. Immunoelectron microscopy detected syntaxin on both the plasma membrane and the vesicle membranes in mouse metaphase II oocytes. In conclusion the results indicate that syntaxin 4 co-localizes with cortical granules and participates in membrane fusion and exocytosis during the cortical reaction.

Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.

We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.

Lack of association between smoking and CYP2A6 gene polymorphisms in A Japanese population.

This study determined the genotypes of the CYP2A6 gene in 96 smokers and 141 non-smokers in a Japanese population. The frequencies of wild-type of the CYP2A6* 1 and those with a whole deletion of the CYP2A6 gene were 93 (96.9%) and 3 (3.1%) in 96 smokers, and 134 (95.0%) and 7 (5.0%) in non-smokers, respectively. In addition, neither the CYP2A6* 2 nor CYP2A6* 3 alleles were observed in the population studied. There were no significant differences in the CYP2A6 genotype frequencies between smokers and non-smokers, as well as in the number of cigarettes smoked and the nicotine amounts inhaled per day between the CYP2A6* 1 and the deletion of CYP2A6. These results suggest that either the deletion or non-deletion of the CYP2A6 gene shows no significant effect on smoking behavior for the Japanese population examined.

Analysis of the metabolism of haloperidol and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism.

The blood levels of the neurotrophic drug haloperidol (HP) and its pyridinium metabolite, HPP(+), have been analyzed by liquid chromatography/electrospray ionization-mass spectrometry in 10 schizophrenic patients treated with HP, without carbamazepine (HP, oral daily dose of 0.3-0.5 mg/kg body weight for more than 1 year, females, aged 41 +/- 8.5 years). There was a significant difference (t-test, d.f. = 8, p (t(0) = 7.2) <0.005) in the blood HPP(+) level between the 5 patients with (18.5 +/- 6.4 ng/ml) and the 5 without (6.3 +/- 2.4 ng/ml) severe side effects such as drug-induced parkinsonism (Extrapyramidal Symptom Rating Scale (ESRS) parkinsonism severity scores 2.8 +/- 1.5 and 1.8 +/- 1.1, respectively). Moreover, it is suggested that vitamin E may be effective for drug-induced parkinsonism through a change in the blood HPP(+) level. It is necessary to investigate the HPP(+) metabolism in psychiatric patients to avoid severe side effects such as drug-induced parkinsonism and cardiac functional disorders.

[A case of pseudomyxoma peritonei treated successfully with intraperitoneal administration of CBDCA and etoposide, followed by local delivery of dextran with CDDP during surgery].

A 77-year-old woman was diagnosed as having pseudomyxoma peritonei originating in the ovary or appendix. Low-molecular dextran and CDDP 70 mg was administered directly into the peritoneal cavity, followed by initial exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and omentectomy. During surgery, an implantable port system was positioned to facilitate repeated intraperitoneal administration. Dextran was used with mucolytic therapy and augmentable efficacy of drug administered simultaneously. Within three weeks after surgery, four courses of intraperitoneal CBDCA 300 mg and etoposide 100 mg were administered at four-week intervals. The patient has remained in good general condition with no sign of recurrence for one year. This chemotherapy regimen has minimum side effects and seems effective in maintaining quality of life.

Mitral valve replacement through right thoracotomy after coronary arterial bypass grafting with functioning conduits.

A 67-year-old man who had undergone coronary artery bypass grafting 3 years previously suffered from severe mitral regurgitation associated with Streptococcal infective endocarditis. He was placed in New York Heart Association functional class III. Preoperative angiography demonstrated good opacification of all 3 conduits implanted in the previous operation. We replaced the mitral valve through an anterolateral right thoracotomy, approaching the mitral valve as an alternative to redoing sternotomy to minimize potential injury to patent grafts. His postoperative course was uneventful. After a 1-month course of antibiotics, the patient was discharged as New York Heart Association class II and at present, 3 months after discharge, is doing well. This approach is an effective alternative to redoing sternotomy for mitral valve operation, especially in patients undergoing a previous coronary arterial bypass grafting via median sternotomy.

Early results of coronary grafting using ultrasonically skeletonized internal thoracic arteries.

BACKGROUND: We have developed an ultrasonic complete skeletonization technique for obtaining internal thoracic artery (ITA) grafts and have used this method clinically since January 1998. In this report, we discuss the early results of bilateral ITA grafts obtained with our method. METHODS: We studied 200 consecutive patients who underwent coronary artery bypass grafting using ITAs obtained by this technique. Angiography of the grafts was performed in 188 patients (94%) within 1 month after coronary artery bypass grafting. RESULTS: The ITA grafts were about 4 cm longer than pedicled ITA grafts. The free flow through the grafts was at least 30% higher than through pedicled ITAs. The early patency rate determined by postoperative angiography of the grafts was 99.7% for left ITAs and 100% for right ITAs. No patient required postoperative intervention or repeated surgery. CONCLUSIONS: Ultrasonic complete skeletonization increases the effective length of ITA bypasses, improves free flow through the bypasses, and it is less invasive than conventional pedicled harvesting. These excellent early results indicate that this technique is a straightforward, safe, less invasive, and optimal method for obtaining ITA bypass grafts.

[Management of coronary artery disease combined with aortic stenosis: how to do with mild aortic stenosis].

A total of fourteen patients with combined operation of coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) for coronary artery disease (CAD) and aortic stenosis (AS) were reviewed to evaluate the indication of the combined operation. Preoperative pressure gradient across the valve and effective orifice area were 21-89 mmHg (mean 64 mmHg), 0.5-1.9 cm2 (mean 0.92 cm2), respectively. The extent of CAD was 1-3 (mean 2.0). Fractional shortening (%FS) ranged from 13% to 43% with mean value of 28%. All patients underwent CABG and AVR. The number of grafts was 1-4 (mean 2.3) with internal thoracic artery used in 7 cases. Mechanical valves were employed for all patients except 1 case with cerebral aneurysm. There was no operative death, although low output syndrome developed in 2 cases. One had poor left ventricular function preoperatively, and the other was emergency case. Fractional shortening improved postoperatively even in two cases with preoperative %FS less than 20%, and all grafts were patent on postoperative coronary angiography. The event-free survival was 100% during 32 months of mean follow-up. Combined AVR with CABG is recommended to avoid risky secondary operation in patients of CAD and AS, even if one of which is relatively mild, because of the fact that operative and late results of the combined surgery are satisfactory.

Coronary artery bypass grafting using the "Super Pulse" dynamic pulsatile cardiopulmonary bypass device in patients with cerebrovascular occlusive disease.

Patients with coronary disease complicated by severe carotid or intracranial arterial stenosis underwent coronary artery bypass graft surgery (CABG) using a novel method of dynamic pulsatile cardiopulmonary bypass (Super Pulse CPB). The Super Pulse technique can maintain the systolic pressure and systolic-diastolic amplitude in such a way that they mimic the physiologic circulation. Forty-five patients (33 males and 12 females, mean age 65.1 years) with coronary disease who had a greater than 75% stenosis of the carotid or intracranial arteries were evaluated. Evaluation was performed for the following 3 groups: 8 patients with conventional pulsatile CPB (Group I), 8 patients with conventional pulsatile CPB plus intraaortic balloon pumping (Group II), and 29 patients with Super Pulse CPB. Maximum, minimum, and mean perfusion pressures during CPB were 112.7, 53.6, and 76.9 mmHg (integrated mean), respectively, in Group III. The systolic-diastolic amplitude was significantly better than for Group I and similar to baseline pressures. No patients in Group II or Group III developed perioperative cerebral disorders or myocardial infarction, while in Group I perioperative cerebral disorders developed in 3 patients, myocardial infarction occurred in 2 patients, and 2 patients died during hospitalization. The initial performance of the Super Pulse CPB indicates excellent safety, and is useful for patients with co-morbid cerebral arterial disease.

Nontransplant cardiac surgery for end-stage cardiomyopathy.

OBJECTIVE: To treat end-stage cardiomyopathy, we evaluated endoventricular circular patch plasty, partial left ventriculectomy, and valvular reconstruction alone in our 2-year experience. METHODS: Among 86 patients with heart failure evaluated between December 1996 and February 1999, 33 patients with ischemic cardiomyopathy (25 men and 8 women; mean age 61 +/- 7.8 years; New York Heart Association class 3.5 +/- 0.5) were treated with endoventricular circular patch plasty combined with coronary bypass grafting (84%) and mitral reconstruction (36%). The other 53 patients with nonischemic cardiomyopathy (45 men and 8 women; mean age 48 +/- 14.3 years, New York Heart Association class 3.7 +/- 0.5), were treated by left ventricular reduction by partial left ventriculectomy (n = 37) or patch plasty (n = 3) and valve reconstruction alone (n = 13). The first 24 patients (group I) underwent ventriculectomy with or without valve reconstruction; the more recent 29 patients (group II) underwent left ventricular reduction (n = 16) or valve reconstruction alone (n = 13) on the basis of the intraoperative echocardiographic evaluation to observe changes of wall motion and thickness during cardiopulmonary bypass. RESULTS: Ischemic Group: Hospital mortality in elective (n = 26) and emergency (n = 7) operations was 4% and 43%, and 3 patients died in the late postoperative period. Mean New York Heart Association class and ejection fraction improved from 3.5 +/- 0.5 to 1.5 +/- 0.7 and from 23% +/- 7.7% to 36% +/- 8.6%, respectively. Left ventricular end-diastolic and end-systolic volume indexes decreased from 162 +/- 46 mL/m(2) to 110 +/- 39 mL/m(2) and from 130 +/- 47 mL/m(2) to 70 +/- 32 mL/m(2), respectively. Nonischemic Group: In 40 patients with left ventricular reduction, hospital mortality in elective (n = 33) and emergency (n = 7) operations was 6% and 86%, and 5 patients died in the late postoperative period. Mean New York Heart Association class and ejection fraction improved from 3.7 +/- 0.5 to 1.7 +/- 0.6 and from 18% +/- 6.4% to 31% +/- 5.9%. Left ventricular end-diastolic and end-systolic volume indexes decreased from 203 +/- 45 mL/m(2) to 110 +/- 37 mL/m(2) and from 164 +/- 40 mL/m(2) to 79 +/- 33 mL/m(2), respectively. In 13 patients undergoing valve reconstruction alone (12 mitral with or without tricuspid and 1 tricuspid plus left ventricular assist device), hospital mortality in elective (n = 9) and emergency (n = 4) operations was 0% and 50% with no late deaths. Mean New York Heart Association class and ejection fraction improved from 3.6 +/- 0.5 to 2.0 +/- 0.5 and from 22% +/- 6.0% to 30% +/- 14.5%, respectively. Mean left ventricular end-diastolic and end-systolic volume indexes decreased from 170 +/- 34 mL/m(2) to 150 +/- 50 mL/m(2) and from 140 +/- 38 mL/m(2) to 104 +/- 40 mL/m(2), respectively. Overall mortality decreased from 50% in group I to 10% in group II. The survival estimates at 2 years were 77% (confidence limits 57%-88%) in the ischemic group and 63% (confidence limits 47%-75%) in the nonischemic group (no significant difference). The analysis of our data showed that the factors influencing the surgical results for dilated cardiomyopathy were presence of severe mitral regurgitation, preoperative New York Heart Association functional class IV with emergency operation, and operative procedures with randomly performed partial left ventriculectomy without an intraoperative echo test. CONCLUSION: Endoventricular circular patch plasty, partial left ventriculectomy, and solo valve reconstruction can be performed with an acceptably low risk as elective operations. The selection of operative procedures in idiopathic dilated cardiomyopathy and avoidance of emergency surgery improved operative mortality and morbidity. Among patients who survived at least 1 year, there were no late deaths up to 30 months' follow-up.

The effects of the ALDH2*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination.

The effects of CYP2E1 genotypes on the blood ethanol and acetaldehyde levels were investigated in a pair of Japanese volunteers whose ADH2, ADH3 and ALDH2 genotypes were identical but whose CYP2E1 genotypes were different. In the same way, the effects of ALDH2 and ADH2 on the ethanol elimination kinetics were also studied. The predicting 95% confidence bounds determined on regression analysis of the data suggested that after venous injection of ethanol, the blood ethanol and acetaldehyde concentrations in a volunteer normal homozygous for ALDH2 (ALDH2*1/1) were lower than in a heterozygous one (ALDH2*1/2). Also, the blood ethanol and acetaldehyde concentrations in a volunteer with the c2 and C alleles of CYP2E1 (c1/c2 and C/D) were lower than in one without the c2 and C alleles (c1/c1 and D/D). However, there were no significant differences in the blood ethanol and acetaldehyde concentrations between volunteers with ADH2*1 (ADH2*1/1) and without ADH2*1 (ADH2*1/2).