Gene polymorphism and frequencies of the NPC1L1 gene (rs2072183, rs217434 and rs217428) in Japanese patients with dyslipidemia.

WHAT IS KNOWN AND OBJECTIVE: Niemann-Pick C1-Like 1 (NPC1L1) plays a pivotal role in intestinal cholesterol absorption. Ezetimibe is known as an inhibitor for NPC1L1 and decreases concentration of low-density lipoprotein cholesterol (LDL-C) in blood. Responses of the decrease of serum LDL-C levels to ezetimibe have been reported to be different among NPC1L1 variants. However, there are still limited data concerning the genetic variation in the NPC1L1 gene, specifically, in Japanese patients with dyslipidemia. The purpose of this study is to elucidate genotype and allele frequencies of the NPC1L1 gene in Japanese patients with dyslipidemia. METHODS: Written informed consent was obtained from all participants. All patients were administered ezetimibe at the dose of 10 mg for once a day either alone or coadministered with statins. Patient's data were retrospectively obtained from their medical records. Genomic DNA was extracted from whole blood samples and analysed three NPC1L1 SNPs (rs2072183, rs217428 and rs217434) by the direct sequencing method. RESULTS AND DISCUSSION: We found that there is a significant difference of genotype frequencies between healthy Japanese and dyslipidemic subjects in rs2072183. No significant differences were observed in rs217428 and rs217434; however, comparison of our data with literature reports suggests that there are significant differences in the frequencies of rs217428 and rs217434 between Canadian and Japanese dyslipidemic patients. WHAT IS NEW AND CONCLUSION: Our study is the first report concerning the genotype and allele frequencies of the gene coding for NPC1L1 in Japanese patients with dyslipidemia. The most notable result was to demonstrate that there exists a significant difference in rs2072183 variant between healthy Japanese and dyslipidemic subjects and also found that there exists genetic variation of rs2072183 between Japanese and Canadian patients with dyslipidemia. Our results are expected to facilitate research in the proper use of ezetimibe-based mono- or combination therapies. Further studies will be required to evaluate the effects of rs2072183 on the efficacy of LDL cholesterol reduction by ezetimibe.

Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging.

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons.

A very rare anatomic variation of the right ventricular branch: right ventricular descending branch from the anterior interventricular branch.

The anterior interventricular branch of the left coronary artery has the most constant distribution in the human heart and rarely gives off right ventricular branches. Here we report a case with a right ventricular branch which diverged from the anterior interventricular branch and descended on the anterior right ventricular wall parallel to the anterior interventricular sulcus; we termed it the "right ventricular descending branch." This artery gave a collateral artery to the occluded anterior interventricular branch at the apex, and had prevented anterior myocardial infarction. The right ventricular descending branch should be precisely identified in order to perform successful myocardial revascularization procedures such as coronary artery bypass grafting and percutaneous coronary intervention, especially in a patient with anterior interventricular branch occlusion.

[Emergency coronary artery bypass grafting for acute coronary syndrome with preoperative intraaortic balloon pumping; comparative surgical outcome and long-term results].

With recent technical improvements in catheter interventional therapy, percutaneous coronary intervention (PCI) has now become the treatment of first choice for acute coronary syndrome (ACS). The objective of the present study was to evaluate critically the timing of coronary artery bypass grafting (CABG) for severe ACS with preoperative intraaortic balloon pumping (IABP). Since 1994, a total of 70 patients have gone emergency or urgent CABG for ACS. Of 70 patients, 50 patients required preoperative IABP. There were 22 patients (17 men, 5 women) with acute myocardial infarction (AMI), with a mean age of 67.7 years, and 28 patients (19 men, 9 women) with unstable angina pectoris (UAP), with a mean age of 69.2 years. There was a significant difference, between AMI and UAP, in the prevalence of emergency operation (95.5% vs 25.0%), in preoperative cardiogenic shock (81.8% vs 17.9%), in the level of preoperative CPK-MB (196.7 IU/l vs 2.0 IU/l) and in preoperative ejection fraction (41.8% vs 47.3%). Two patients in AMI required percutaneous cardiopulmonary support (PCPS). Thirteen patients in AMI and 22 patients in UAP presented left main trunk (LMT) disease. Of the 13 LMT patients in AMI, 4 patients were AMI due to acute occlusion in the LMT. The AMI patients received 2.45 distal anastomoses on average, while the UAP patients 3.14 distal anastomoses (p = 0.019). Excluding the mean number of distal anastomoses, there was no difference in the intraoperative technical factors, such as aortic cross clamping duration, cardiopulmonary bypass duration, rate of complete revascularization, between AMI and UAP. There were postoperative significant differences in low cardiac output syndrome (LOS) [45.6% in AMI vs 3.6% in UAP] and in prolongation of mechanical ventilation (59.1% in AMI vs 14.3% in UAP). The hospital mortality was 9.1% (2/22) in AMI, and 3.6% (1/28) in UAP, with no significant difference. Of these 3 patients, 1 patient died from perioperative cerebrovascular accident (CVA), another from LOS, and the other from postoperative mesenteric ischemia, with an overall mortality of 6.0% (3/50). The overall patency rate of the grafts was 100% in AMI and 96.6% in UAP. The 5-year-survival rate excluding in-hospital death was 72.5% in AMI, and 89.6% in UAP. The 5-year-cardiac event-free rate was 77% in AMI and 89.4% in UAP. The overall survival rate, and cardiac event-free rate, at 5 years was 80.8%, and 83.8%, respectively. In conclusion, for ACS cases, especially UAP cases of LMT, in which symptoms, findings of ischemia and hemodynamics are stabilized by medical intervention including IABP; emergency surgery could be avoided immediately after coronary angiography. Recovery in the ischemic myocardium is intended by IABP, and urgent surgery should be performed after sufficient and precise preoperative examinations. An improvement not only in the perioperative but also long-term results can be expected by performing complete revascularizations.

[Left atrial thrombus without mitral disease; report of a case].

A 76-year-old man was admitted to our hospital because of surgical treatment for mass in the left atrium(LA). Echocardiography and computed tomography(CT) revealed mobile mass in LA which had stalk at the left atrial appendage. It was difficult to distinguish myxoma from thrombus. LA mass has risk of sudden circulatory collapse and systemic emboli, so it is indicated for emergent operation. Mass resection with appendage was performed through the transseptal superior incision using cardiopulmonary bypass. Pathological diagnosis was thrombus. Most of LA thrombus were complicated with mitral stenosis, LA thrombus without mitral disease is rare. A few authors reported the useful of CT and echocardiography, but we could not lead to precise diagnosis from preoperative image.

[Combined carotid endarterectomy and off-pump coronary artery bypass grafting].

Patients with angina undergoing carotid endarterectomy have a high mortality. A 74-yaer-old man who has severe carotid stenosis was performed combined carotid endarterectomy and off-pump coronary artery bypass grafting successfully. At first, carotid endarterectomy was performed with Jamieson's specially designed dissector, which allow simultaneous dissection and removal blood from the surgical field. Secondly, then off-pump CABG was performed. Skeletonized internal mammary artery was harvested with ultrasound dissector. The advantage of that the dissected artery is not only long and greater blood flow, but also less damage to sternal blood flow which prevent infection and complications. Then internal mammary artery was anastomosed to left anterior discending artery with Octopus II stabilizer. After the operation, he recovered uneventfully without neurological complication. Combined single staged carotid endarterectomy and off-pump CABG appears to be a safe method.

[A successful case report of emergency coronary artery bypass grafting for left main trunk obstruction with profound cardiogenic shock: bridge use of balloon pumping and percutaneous cardiopulmonary support system to surgical intervention].

A 73-year-old man was admitted for sudden onset of dyspnea with cardiogenic shock. Chest X-P showed bilateral severe pulmonary edema. Echocardiogram demonstrated diffuse severe hypokinesis of left ventricle. Emergency coronary angiography showed 99% stenosis of left main trunk with delay. After insertion of intraaortic balloon pump (IABP) and percutaneous cardiopulmonary support system (PCPS), vital signs and consciousness were improved. Emergency coronary artery bypass grafting (CABG) was performed, LIMA to left anterior descending artery, saphenous vein grafts to circumflex and right coronary artery. Left ventricular wall motion was improved after bypass grafting and cardiopulmonary bypass was weaned with catecholamine and IABP support. The patient was discharged from hospital 60 days after the operation with good cardiac function. We emphasized a usefulness of combined use of IABP and PCPS to provide systemic organ perfusion and reduce myocardial infarct size and ischemic damages after re-vascularization for coronary insufficiency with profound shock.

Coronary endothelial damage during off-pump CABG related to coronary-clamping and gas insufflation.

OBJECTIVE: Although off-pump coronary artery bypass grafting (CABG) has been recognized less invasive than conventional CABG on cardiopulmonary bypass, off-pump CABG may be partly invasive especially to the coronary endothelium. The present study was designed to evaluate the adverse effects of coronary snaring with looped sutures and gas insufflation on the coronary endothelium. The protective efficacies on the coronary endothelium of coronary snaring with elastic sutures or humidified gas insufflation with/without heparin and dipyridamole-added were also tested. METHODS: Thirty-six mongrel dogs were used. After systemic heparinization (150 U/kg), a 5 mm longitudinal coronary incision was made with looped non-elastic monofilament sutures or elastic sutures applied proximally and distally. The incised coronary artery was exposed to non-humidified carbon dioxide, humidified carbon dioxide with lactated Ringer solution, or humidified carbon dioxide with heparin and dipyridamole-added lactated Ringer solution for 10 or 20 min in each group. After gas insufflation, the incised coronary artery was repaired, then, the coronary was reperfused. Perfusion-fixation was done for observation of the coronary endothelium by scanning electron microscopy. The adverse effect on the endothelium was graded as follows: grade 1, appeared normal; grade 2, few blood cells deposited; grade 3, many blood cells deposited; grade 4, few endothelial cells delaminated with blood cells deposited; grade 5, many endothelial cells delaminated with blood cells deposited. RESULTS: Non-elastic looping caused much more endothelial tears than elastic looping (P<0.00001). Non-humidified gas blowing for 20 min caused more endothelial cell damage than humidified gas blowing (P=0.00005). Non-humidified gas blowing for 10 min caused less damage than for 20 min (P=0.00326), but still caused more damage than humidified gas blowing (P=0.00253). Heparin and dipyridamole-added humidification reduced coronary endothelial area mottled by the deposited cells when compared with simple humidification (P=0.00120). CONCLUSIONS: Coronary snaring resulted in coronary endothelial injury, which was ameliorated by using elastic sutures instead of non-elastic sutures. Non-humidified gas insufflation made blood cells deposited and endothelial cells delaminated with time. Humidified gas insufflation attenuated these adverse effects. Heparin and dipyridamole-added humidification had potential advantage in terms of reducing deposited blood cells on the endothelium over simple humidification.

Role of carbohydrate moiety in granulocyte colony stimulating factor.

Biological activities of two granulocyte-colony stimulating factor (G-CSF) preparations with (Lenograstim) or without (Filgrastim) sugar moiety were compared. Both G-CSF preparations similarly enhanced the N-Formyl-Met-Leu-Phe-induced-migration of human peripheral blood polymorphonuclear cells, but did not significantly affect the proliferation of human oral tumor cell lines (HSC-2, HSG). However, Lenograstim induced cytotoxicity (accompanied by the production of cytoplasmic vacuoles and large DNA fragments) in human promyelocytic leukemic cells HL-60, more potently than Filgrastim. Lenograstim, but not Filgrastim, enhanced the cytotoxic activity of sodium ascorbate. In contrast to Lenograstim, Filgrastim was degraded gradually, but too slowly to explain its lower biological activity. These data suggest that the carbohydrate moiety in G-CSF might confer unique biological activities.

Analysis of the human sleep electroencephalogram by the correlation dimension.

Sleep electroencephalograms (EEG) of healthy male subjects were analyzed by the correlation dimension. The mean correlation dimensions significantly decreased from stage 'awake' to stages 1, 2 and 3 and increased during rapid eye movement sleep. The mean correlation dimensions of the sleep EEG in the second half of the night were significantly higher than those in the first half of the night. These significant changes were also seen during sleep stage 2.

Correlation dimension of the human sleep electroencephalogram.

Sleep electroencephalogram (EEG) was analyzed by nonlinear analysis. Polysomnography of a healthy male subject was analyzed and the correlation dimension was calculated. The mean correlation dimensions decreased from stage 'awake' to stages 1, 2 and 3, and increased during rapid eye movement (REM) sleep. These results were also seen at every sleep cycle. During each sleep cycle the correlation dimensions decreased for slow wave sleep, then increased for REM sleep. The mean correlation dimension of the sleep EEG in the second half of the night was significantly higher than those in the first half of the night. A significant change was seen both during REM sleep as well as in sleep stage 2. Nonlinear analysis may be a useful method in the analysis of the entire sleep electroencephalogram.

Non-linear analysis of the sleep EEG.

A sleep electroencephalogram was analyzed by non-linear analysis. The polysomnography of a healthy male subject was analyzed and the correlation dimensions calculated. The correlation dimensions decreased from the 'awake' stage to sleep stages 1-3 and increased during rapid eye movement (REM) sleep. These results were seen during each sleep cycle. In each sleep cycle, the correlation dimensions decrease for slow wave sleep, and increase for REM sleep.

Surgery of the dissecting aneurysm involving a right aortic arch.

A dissecting aneurysm in association with a right aortic arch is extremely rare. However, a 50-year-old male was diagnosed as having a dissecting aneurysm (DeBakey IIIa) with a right aortic arch, right descending aorta and an aberrant retro-esophageal left subclavian artery. A graft replacement of the right descending aorta was successfully performed under right thoracotomy and partial cardiopulmonary bypass. Precise anatomical definition and proper surgical procedure permitted a successful surgical result.

[A case of the ascending aorta and aortic arch replacement with thrombo-occlusion of distal arch and descending aorta surround the modified elephant trunk graft].

We report a 65-year-old female who had a extensive thoracic aneurysm from ascending aorta to descending thoracic aorta. The patient underwent a graft replacement of ascending aorta and aortic arch using modified elephant trunk method. The surgery was carried out through median sternotomy with profound hypothermia and selective cerebral perfusion. Postoperatively, the patient was recovered without any complications except bronchial asthma. Postoperative chest computed tomography showed that the surrounding space of the elephant trunk vascular graft inserted into distal arch and descending aneurysm was mostly occupied with thrombus. Therefore, we considered that the second operation on the descending aorta is not necessary at this point and careful attention to the size and shape of the descending aneurysm should be paid.

Delayed signal propagation via CA2 in rat hippocampal slices revealed by optical recording.

Signal propagation from mossy fibers to CA1 neurons was investigated in rat hippocampal slices by a combination of electrical and optical recordings. The slices were prepared by oblique sectioning of the middle part of the hippocampus to preserve fiber connections. The mossy fibers were stimulated to induce population spikes (PSs) and excitatory postsynaptic potentials in the middle part of the CA1 region. Latencies of maximal PSs in CA1 varied widely among slices; they ranged from 7 to 13.5 ms, with two maxima at 9 and 11.5 ms. The fastest PSs probably are evoked by the Schaffer collaterals that connect the CA3 and CA1 regions in the well-known trisynaptic circuit. However, the slower PSs suggest the existence of additional delayed inputs. To determine the source of the delayed input, slices were stained with a voltage-sensitive dye, RH482, and the optical signals relevant to membrane potential changes were detected by a high-resolution optical imaging system. Optical recording of responses to mossy fiber stimulation indicated two distinct types of signal propagation from CA3 to CA1. In preparations evincing the fast type of propagation, signals spread to CA1 within 7.2 ms after the mossy fiber stimulation. During such propagation, activity flowed directly from CA3 to the stratum radiatum of CA1. Other preparations illustrated slow signal propagation, in which optical signals were generated in CA2 before spreading to CA1. During such slow signal transmission, activity persisted in CA2 and its surrounding area for 3 ms before propagating to the strata radiatum and oriens in CA1. In such cases, CA1 activity was detected within 10.8 ms of mossy fiber stimulation. In some slices, a mixture of the fast and slow propagation patterns was observed, indicating that these two transmission modes can coexist. Our data reveal that CA2 neurons can transmit delayed excitatory signals to CA1 neurons. We therefore conclude that consideration of electrical signal propagation through the hippocampus should include flow through the CA2 region in addition to the traditional dentate gyrus-CA3-CA1 trisynaptic circuit.

Clinical evaluation of the centrifugal pump in open heart surgery: a comparative study of different pumps.

The centrifugal pump is now widely used in open heart surgery for its clinical benefits related to the blood elements and the coagulation system. The purpose of this study was to compare the clinical performances of and the outcomes offered by 4 types of centrifugal pumps. For each pump, we investigated the effects on the blood elements, coagulation system, complements, and immunoglobulins during open heart surgery. Four types of centrifugal pumps were used: the HPM-15 (Nikkiso Co.), the Capiox (Terumo Co.), the Lifestream (St. Jude Medical Co.), and the BP-80 (Medtronic, BioMedicus Co.). The platelet count, lactate dehydrogenase (LDH), antithrombin III (AT III), thrombin-antithrombin complex (TAT), complements (C3, C4, and CH50), and immunoglobulins (IgG, IgA, and IgM) were measured before and after cardiopulmonary bypass (CPB). The platelet count was decreased more significantly by the HPM-15 than by any of the other pumps. The other parameters showed no difference among the 4 pumps. In clinical use, each of the 4 types of centrifugal pumps was safe.

Glycophorin-induced differentiation of human myelogenous leukemic cell lines.

Human myelogenous leukemic cell lines, U-937, ML-1, and THP-1, were induced to differentiate into maturing macrophage-like cells upon treatment with any glycophorins from either human, monkey or cow erythrocyte membrane. The differentiated cells expressed lower growth potential, and higher nitroblue tetrazolium-reducing activity, Fc-receptor, phagocytic activity and non-specific esterase activity. The differentiation-inducing activities of the glycophorins were significantly reduced after neuraminidase treatment. On the other hand, sialic acid and colominic acid (a polymer of sialic acid) were inactive. These results suggest that some conformational requirement involving the linkage of sialic acid residues in the glycoproteins is necessary for the observed differentiation-inducing activity.

[A successful surgical case report of impending rupture of the true thoraco-abdominal aortic aneurysm induced by thrombosed-type acute aortic dissection (Stanford type A)].

Impending rupture of the true aneurysm of the thoraco-abdominal aorta induced by acute aortic dissection (Stanford type A) is very rare, and decision making of the therapeutic plain is difficult. A 88-year-old woman manifested severe back pain with hypotension. Chest computed tomographic examination revealed a true aneurysm of the thoraco-abdominal aorta and acute thrombosed-type aortic dissection (Stanford type A) with cardiac tamponade. Under the diagnosis of impending rupture of the thoraco-abdominal aortic aneurysm induced by acute aortic dissection (Stanford type A), graft replacement of the thoraco-abdominal aortic aneurysm and pericardial drainage were successfully performed. Two months later, computed tomographic examination revealed disappearance of the thrombosed false lumen in the ascending aorta.

[Re-operation for Budd-Chiari syndrome].

A 42-year-old man, who underwent a radical operation for Budd-Chiari syndrome under femoro-femoral bypass in our hospital 5 years ago, was re-admitted for evaluation of progressive liver dysfunction and dilatation of superficial veins of scrotum and lower extremities. Cavography revealed complete obstruction at the portion of previous patch dilatation. We performed re-do operation by the same method except we chose this time the heparin-coated circulatory system including centrifugal pump and ringed ePTFE graft as a material of patch dilatation. Cavography after the re-do operation revealed widely patent IVC-RA junction and he has been doing well.

Pathology of bovine abortion and newborn calf death caused by dual infection with Chlamydia psittaci and infectious bovine rhinotracheitis virus.

Nine aborted fetuses and one newborn calf, diagnosed as Chlamydia psittaci (C. psittaci) infection, were pathologically examined. The characteristic lesions in the liver were focal necrosis in 9 aborted fetuses and granulomatous necrotic foci in the newborn calf. Moderate numbers of intranuclear inclusion bodies were found in necrotic foci of the liver, spleen, thymus, lymph nodes, adrenal gland, kidney, lung and forestomach. Immunohistologically, a small number of C. psittaci antigens was demonstrated in necrotic foci of the liver and correlated with distribution of elementary bodies. Moderate numbers of infectious bovine rhinotracheitis (IBR) virus antigens were also detected in degenerating and necrotizing parenchymal cells in various organs and correlated with distribution of intranuclear inclusion bodies. Thus, these aborted bovine fetuses and newborn calf were interpreted as being dually infected with C. psittaci and IBR virus during pregnancy.