A retrospective observational study to assess adverse transfusion reactions of patients with and without prior transfusion history.

BACKGROUND AND OBJECTIVES: This study compares the frequency of adverse transfusion reactions (ATRs) after first transfusions with the frequency of ATRs for subsequent (non-first) transfusions. MATERIALS AND METHODS: Five hospitals agreed to systematically collect and share 2 years of data. This was a retrospective observational analysis of data including the number of transfusion episodes and ATRs for red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrates (PCs) given to first-time transfusion recipients and to those previously transfused. RESULTS: First transfusion ATRs to RBCs, FFP and PCs were 1.08%, 2.84% and 3.34%, respectively. These are higher than ATR incidences to RBCs (0.69%), FFP (1.91%) and PCs (2.75%) on subsequent transfusions. Specifically, first transfusion incidences of febrile non-haemolytic transfusion reactions (FNHTRs) to RBCs (0.43%) and allergic reactions to FFP (2.51%) were higher than on subsequent transfusions (RBCs: 0.23%, FFP: 1.65%). CONCLUSION: There are risks of ATRs on the first transfusion as well as transfusions of patients with transfusion history.

Cardiac intervention using high-intensity focused ultrasound: creation of interatrial communication in beating heart of an anesthetized rabbit.

OBJECTIVE: Current fetal cardiac intervention for restrictive atrial septum is invasive and technically demanding. We investigated the feasibility of computer-assisted high-intensity focused ultrasound (HIFU) for cardiac intervention on the atrial septum of a beating heart. METHODS: To create an interatrial communication in the beating heart of nine anesthetized rabbits, the heart was exposed surgically and placed under a water-filled tank, in contact with the tank's membranous base. A HIFU transducer (3.3 MHz) coupled with a diagnostic ultrasound probe (10.0 MHz) was placed in the tank over the beating heart. The focus of the HIFU transducer was set so that it could create a hole in the target area on the atrial septum during the early diastolic phase. HIFU delivery was controlled based on ultrasound images captured with real-time image-recognition software. We attempted to create interatrial communication using HIFU and assessed the cardiac tissue specimen pathologically. RESULTS: In eight of nine rabbits, small holes in the atrial septum were successfully created. Serious complications occurred in two animals: a fatal atrioventricular block in one and a cardiac tamponade in the other. CONCLUSION: HIFU combined with a computer-assisted imaging system might be useful to create interatrial communication in beating hearts. This procedure may be helpful for making current fetal cardiac intervention less invasive.

[Lung cancer operation in situs inversus totalis patient].

Situs inversus totalis represents a complete mirror image anatomy of the normal arrangement of the thoracic and abdominal viscera. This rare condition may pose possible surgical problems due to anatomical abnormality. There were few reports of surgical treatment for lung cancer patient with situs inversus totalis. In this case report, we describe a 74-year-old patient with situs inversus totalis and primary lung cancer who underwent successful left upper lobectomy and systemic lymph node dissection. For this rare condition, detail preoperative evaluation of mirror image anatomy with computed tomography and bronchofiber optic examination was thought to be a key to carry out safe operative procedure.

Dosimetric evaluation of neutron capture therapy for local advanced breast cancer.

Local recurrence breast cancer is one of the most difficult conditions to cure and there is a need for new therapy. If sufficient boron compound can be targeted to the tumor, boron neutron capture therapy (BNCT) can be applied to local recurrent breast cancer. In this study, we performed a preliminary dosimetry with a phantom model of the mammary gland at Kyoto University Research Reactor (KUR), and a feasibility dosimetry with JAERI Computational Dosimetry System (JCDS) at JRR4 reactor of Japan Atomic Research Institute. We performed preliminary dosimetry of a phantom model of the mammary gland with thermal neutron irradiation (OO-0011 mode) on LiF collimation at KUR. The thermal neutron flux was 5.16 E+08 cm(-2)s(-1) at the surface of phantom. The blood boron concentration is estimated to be 30 ppm; tumor boron concentration is also estimated to be 90 ppm according to tumor/blood ratio 3 and skin/blood ratio 1.2. Tumor RBE dose is estimated to be 47 Gy/h, and skin RBE dose is 12.4 Gy/h. In case of advanced breast cancer, we performed the feasibility estimation of 3D construction of tumor according to the MRI imaging of a patient with epithermal neutron mode at JRR4. The blood boron concentration (ppm) and tumor/normal tissue ratio are estimated to be 24 and 3.5, respectively. Skin RBE dose is restricted to 10 Gy/h, the maximum tumor RBE dose, minimum tumor RBE dose, and mean tumor RBE dose are 42.2, 11.3, and 28.9 Gy-Eq, respectively, in half hour irradiation. In this study, we showed the possibility to apply BNCT to local recurrent breast cancer. We can irradiate tumors selectively and as safely as possible, reducing the effects on neighboring healthy tissues.

[Ventricular assist device].

There are 2 kinds of artificial heart used for clinical patients with end-stage heart failure. One is a ventricular assist device (VAD) and the other is a total artificial heart (TAH). Only paracorporeal VADs are commercially available currently in Japan, such as Toyobo VAD and BVS 5000. Paracorporeal Zeon VAD and implantable Novacor LVAD were approved by the MHLW in the past but already disappeared from the Japanese market in 2005 and 2006. A little more than 1,000 LVADs had been implanted since 1980 in Japan until last autumn, while no TAH has been implanted in patients. In the world 1st generation pulsatile implantable LVADs have been taken over by the 2nd and 3rd generation non-pulsatile implantable LVADs in the past 10 years. In Japan 4 kinds of implantable LVADs are under clinical evaluation, HeartMate XVE (1st generation, HeartMate VE was used in the Japanese clinical trial), Jarvik 2000 (2nd generation), Evaheart (2nd generation), and DuraHeart (3rd generation). All 5 patients with HeartMate VE survived more than 1 year during the clinical trial, 13 patients with Evaheart were long survivors or successfully heart-transplanted. Although follow-up interval is relatively short, all 6 patients with DuraHeart and 5 of the 6 patients with Jarvik 2000 recovered from end-stage heart failure and are keeping very good condition. Most of them returned to their home and are waiting for heart transplantation. Especially the 3rd generation of non-pulsatile LVADs is expected to have long-term durability and less frequency of thromboembolic episode.

Vascular allografts are resistant to methicillin-resistant Staphylococcus aureus through indoleamine 2,3-dioxygenase in a murine model.

OBJECTIVE: Surgical results have shown the superiority of human heart valve and vascular allografts over artificial prostheses when used for the treatment of infectious cardiovascular diseases. However, the mechanism of infection resistance in these allografts has not been determined. In this study the contribution of the inflammatory response after allogeneic transplantation to the antimicrobial mechanism was assessed, focusing on the induction of indoleamine 2,3-dioxygenase, a tryptophan-metabolizing enzyme. METHODS: Aortic transplantation was performed with inbred rats, and aortic allografts, isografts, and control grafts were obtained for the following analyses. The extent of inflammatory-related and indoleamine 2,3-dioxygenase gene expression was measured by means of quantitative reverse transcriptase-polymerase chain reaction, and tryptophan metabolite production in the graft was measured by means of liquid chromatographic/tandem mass spectrometric analysis. The bacteriostatic effect of each graft and tryptophan metabolites was determined by using the methicillin-resistant Staphylococcus aureus proliferation assay. RESULTS: The inflammatory response, including interferon gamma, tumor necrosis factor alpha, and indoleamine 2,3-dioxygenase gene expression, was significant in the allografts but minimal in the isografts and control grafts. Methicillin-resistant S. aureus proliferation was remarkably suppressed when cultured with the allografts but not with the control grafts. Among tryptophan metabolites, the bacteriostatic effect against methicillin-resistant S. aureus was remarkable with 3-hydroxykynurenine, with a minimum inhibitory concentration of 32 mg/L. The 3-hydroxykynurenine level in the allografts was 9-fold greater than that in the control grafts. CONCLUSION: The bacteriostatic effect of the allografts was acquired by inducing indoleamine 2,3-dioxygenase, which resulted in local production of 3-hydroxykynurenine as an antimicrobial agent. This is the first report to document a mechanism of the allograft's infection-resistant property against methicillin-resistant S. aureus growth.

Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models.

Polyoxomolybdates (PMs) as discrete molybdenum-oxide cluster anions have been investigated in the course of study of their medical applications. Here, we show the significant antitumour potency of the polyoxomolybdate [Me(3)NH](6)[H(2)Mo(V)(12)O(28)(OH)(12)(Mo(VI)O(3))(4)].2H(2)O (PM-17), which is a photo-reduced compound of [NH(3)Pr(i)](6)[Mo(7)O(24)].3H(2)O. The effect of PM-17 on the growth of cancer cell lines and xenografts was assessed by a cell viability test and analysis of tumour expansion rate. Morphological analysis was carried out by Hoechst staining, flow-cytometric analysis of Annexin V staining, terminal deoxynucleotidyl transferase-mediated 'nick-end' labelling staining, and electron-microscopic analysis. Activation of autophagy was detected by western blotting and fluorescence-microscopic analysis of the localisation of GFP-LC3 in transfected tumour cells. PM-17 inhibited the growth of human pancreatic cancer (AsPC-1) xenografts in a nude mice model, and induced morphological alterations in tumour cells. Correspondingly, PM-17 repressed the proliferation of AsPC-1 cells and human gastric cancer cells (MKN45) depending on the dose in vitro. We observed apoptotic patterns as the formation of apoptotic small bodies and translocation of phosphatidylserine by Hoechst staining and flow-cytometric analysis following Annexin V staining, and in parallel, autophagic conformation by the formulation of autophagosomes and localisation of GFP-LC3 by electron- and fluorescence-microscopic analysis.

[Safety measures of extracorporeal circulation by heart surgeons and perfusionists].

In the past, heart surgeons often set up the extracorporeal circulation (ECC) system, primed the circuit, and operated the ECC in Japan. As works of perfusionists recently became specialized, young Japanese heart surgeons seldom receive education on ECC, and rarely operate ECC. ECC accidents are rare, but once it occurs, even a well experienced perfusionist often becomes too upset to think of the next action, while surgeons at the operative table have little knowledge of the ECC system. Reconsideration of ECC education for heart surgeons is still rare. As a medical team, tragedies such as death and life-threatening complication due to an ECC accident are to be prevented at all costs. At an on-site training session for ECC troubles at the 59th annual meeting of Japanese Association for Thoracic Surgery, the basic ECC operations, recovering procedures after an accident, and the use of safety devices were taught to 30 teams of young heart surgeons and perfusionists as a measure to ensure safety of ECC. A questionnaire survey was conducted at the end and satisfactory results were obtained.

[Posterior mediastinal hemangioma successfully resected with cardiopulmonary bypass; report of a case].

Mediastinal hemangioma is a rare tumor. We report a case of a 62-year-old woman with a posterior mediastinal hemangioma. She had a history of right breast cancer and a follow-up chest radiography revealed a mass located in the left posterior mediastinum. The size was about 80 mm in diameter. The tumor surrounded the descending thoracic aorta and involved intercostal arteries. Complete excision could be achieved by decompressing the descending aorta with the aid of partial cardiopulmonary bypass and the aortic cross-clamp. Histologically, the tumor was diagnosed as a benign hemangioma. It was reported that hemangioma would reccur after subtotal excision. To employ cardiopulmonary bypass was a very effective approach for the purpose of complete excision in our case.

Selective expansion of the CD14(+)/CD16(bright) subpopulation of circulating monocytes in patients with hemophagocytic syndrome.

Overproduction of proinflammatory cytokines is characteristic of hemophagocytic syndrome (HPS), a highly lethal inflammatory disease. Peripheral blood monocytes include two distinct subpopulations according to surface antigen expression: a major type, CD14(+)/CD16(-) (classical monocytes), and a minor type, CD14(+)/CD16(bright) (proinflammatory monocytes). Among peripheral blood monocytes from HPS patients, CD14(+)/CD16(bright) cells were increased, together with lipopolysaccharide-induced production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. By three-color immunofluorescence, CD14(+)/CD16(bright) monocytes exhibited more intense human leukocytic antigen DR than CD14(+)/CD16(-) monocytes, consistent with greater maturity. Serum IL-6, TNF-alpha, and IL-8 were increased in HPS patients. A sensitive inflammatory marker, neutrophil CD64 expression, also was significantly elevated in HPS patients. In conclusion, expansion of proinflammatory monocytes and increased expression of neutrophil CD64 appeared to be important in the pathophysiology of HPS. Expansion of CD14(+)/CD16(bright) monocytes and neutrophil CD64 expression could serve as indicators of the inflammatory state in HPS.

A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer.

Cancer-specific gene promoter methylation has been described in many types of cancers, and various semi-quantified results have shown their usefulness. Here, we show a more sensitive and specific second-generation system for profiling the DNA methylation status. This method is based on bisulfite reaction of DNA and real-time PCR using two TaqMan MGB probes labeled with different fluorescence, followed by clustering analysis. Primers were designed with CpG-less sequences, and TaqMan MGB probes were designed to contain three or four CpG sites and to be shorter than conventional TaqMan probes. We have added new criteria for primer and probe design for further specificity. We confirmed the reliability of this system and applied it to analysis of lung cancers. Using 10 promoters, 90 primary lung cancers were clustered into six groups consisting of cases having similar smoking status and pathological findings. EGFR mutation and p16 promoter DNA methylation were exclusive, as previously reported; however, DNA methylation in other genes was unrelated to EGFR mutation. This system was also useful to distinguish double primary lung cancers from a single cancer with intrapulmonary metastasis. As above, our system has widespread availability in clinical use and biological research.

[Pulmonary thromboembolism after lung resection in patients with schizophrenia; report of 2 cases].

We report 2 cases of pulmonary thromboembolism after lung resection in patients with schizophrenia. The first case is a 67-year-old woman. She underwent right lower lobectomy for primary lung cancer and suddenly felt dyspnea 2 days after the operation. She was diagnosed pulmonary thromboembolism by computed tomography (CT) and lung perfusion scintigram, and recoverd soon. The second case is a 42-year-old man. He underwent partial resection of the right lung for metastatic germ cell tumor. Six days after the operation, he fell into acute respiratory failure and died in spite of resuscitation. The autopsy showed that the cause of death was pulmonary thromboembolism. Because patients with schizophrenia have high-risk of pulmonary thromboembolism, extreme care must be exercised to avoid it.

Automated diagnosis of heart disease in patients with heart murmurs: application of a neural network technique.

This study was conducted to test a three-layered artificial neural network analysis of phonocardiogram recordings to diagnose, automatically and objectively, the condition of the heart in patients with heart murmurs. The data were recorded simultaneously in each of 49 patients with a heart murmur through eight microphones attached to the skin surface with adhesive tape, and were analysed by computer. The diagnosis was automated using a three-layered neural network technique. The neural network generated correct answers in over 70% of cases. Furthermore, about 80% of cases of two concurrent diseases were identified correctly. However, ventricular septal defects were incorrectly classified as aortic stenosis or aortic regurgitation, and patent ductus arteriosus was not diagnosed correctly. Accurate diagnoses can frequently be obtained using a neural network, but accuracy can be improved with further data accumulation.

Graft insertion technique for distal anastomosis in cases of ascending aortic aneurysm.

We describe a simple and reliable technique of making a secure graft for aorta anastomosis, involving sandwiching the friable aortic wall between the graft and a Teflon strip. This technique makes possible a secure anastomosis with the distal friable tissue and prevents bleeding from the junction.

Usefulness of intraoperative color doppler ultrasonography in decision making regarding conversion of an accessory hepatic vein after a Fontan-type operation.

An accessory hepatic vein (AHV) after a Fontan-type operation will result in progressive desaturation if left intact. We report a case in which intraoperative color Doppler ultrasonography revealed the absence of AHV flow and reversed portal vein flow when the AHV was clamped, suggesting that simple ligation of the AHV would lead to liver dysfunction in the area affected. Based on the results of the ultrasonography evaluations, diversion of the AHV into the pulmonary circulation was performed without cardiopulmonary bypass, and the clinical outcome has been favorable.

[Novel strategy for spinal cord protection during thoracoabdominal aortic aneurysm surgery using Doppler ultrasonography].

Paraplegia remains one of the most serious complications after thoracoabdominal aortic aneurysm surgery. Spinal cord ischemia during the operation is thought to be the most important contributor to the development of this neurological deficit. So, it is important to preserve or reconstruct the critical segmental arteries for spinal cord protection. In order to identify the critical segmental arteries, we evaluate the segmental arteries by measuring the flow velocities using Doppler ultrasonography. The flow velocities are different among segmental arteries and some segmental arteries have no flow even though they are patent. Because we think that the segmental arteries with high flow velocities have much contribution to the spinal cord perfusion, we reconstruct or preserve such segmental arteries during the operation. We hope that this method would be clinically useful for spinal cord protection during thoracoabdominal aortic aneurysm surgery.