Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.

We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.     

Case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain]

We reported a case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain and lungs. A 21-year-old man was admitted because of one month history of low grade fever, headache, nausea, and amnesia. He developed agammaglobulinemia following Epstein-Barr virus infection at 3-year-old, and thereafter was administered 7.5g of immunoglobulin every 3 weeks with a diagnosis of XLP. Physical examination was unremarkable on admission. Neurological examination revealed disorientation of time, and bilateral gaze-evoked nystagmus. Neuropsychological tests demonstrated impairment of recent memory and calculation. Pleocytosis (83/microl) and increase of protein (1269 mg/dl) and IgG (141 mg/dl) in the CSF were observed. Brain MRI showed multiple nodular lesions with high intense signal on T2-weighted images and Gd-DTPA enhancement on T1-weighted images. Chest CT showed multiple nodular lesions in the bilateral lungs. The needle lung biopsy was performed, which showed infiltration of lymphocytes around the vessels. An immunohistochemical study showed that the infiltrating cells were mainly CD8 positive T lymphocytes. B lymphocyte and plasma cells were not seen. The histological findings excluded intravascular malignant lymphoma and lymphomatoid granulomatosis. Therefore we diagnosed lymphoid vasculitis. The patient developed pancytopenia caused by hemophagocytic syndrome 48 days after admission and was treated with 1 g of methylprednisolone per day for 3 days and a tapered dose of steroid (500 mg to 125 mg of methylprednisolone and 60 mg to 10mg of predonisolone) for 21 days, which resulted in the improvement of clinical features (hemophagocytic syndrome and central nervous system symptoms) and the abnormal CSF findings. The multple nodular lesions in the brain and the lungs shrank 1 month after treatment and disappeared 11 months later. There are few reports concerning lymphoid vasculitis with XLP, and no effective treatment has been described. Our case suggests that steroid therapy may be useful for the treatment of lymphoid vasculitis in XLP.     

Long-term follow up studies of bronchial asthma in children. II. Prognosis and complications, treatment and allergic evaluations

A questionnaire on the prognosis of bronchial asthma was sent in 1988 to 1592 patients (1038 males, 554 females) averaging 20 years of age after 12 years' follow up. We reported on the prognosis and risk factors associated with asthmatic children in part I. The relation between prognosis and other allergic complications, treatment and laboratory data were investigated in this study. Eosinophil counts of more than 1000/mm3 and/or total serum IgE levels of more than 500 IU/ml (100 IU/ml in infants) indicated poor prognosis. However, the prognosis was not affected either by the allergens themselves or by the number of allergens determined by skin test and RAST. The prognosis was worse for patients with multiple allergic complications than for those without complications. Treatment may after the natural course of childhood asthma, but it has been difficult to evaluate the effect of each regimen over a long period. We compared the effect of hyposensitization (specific immunization) and non-bronchodilator antiasthmatic drugs (NBAAD), and found that hyposensitization alone gave better results than NBAAD and its combination. We had better results from hyposensitization over a period of 1 to 5 years than for less than 1 year or more than 5 years. We conclude that asthmatic children with risk factors should be kept under strict environmental control and given suitable therapeutic regimens to avoid the development of allergic diseases, the slow down of "allergic march", and to avoid intractable asthma.     

The early hemorrhage and development of a bacterial aneurysm after a cerebral ischemic attack caused by a septic embolism--a case report]

A 71-year-old female was admitted with the complaints of dysarthria and right hemiparesis. CT scan revealed subarachnoid hemorrhage in the left cerebral sulcus. The first angiography was performed 3 days after the onset and left carotid angiography revealed a small aneurysm arising from the left middle cerebral artery. After 3 weeks of antibiotic therapy, the second angiography showed the aneurysm to be clearly enlarged, so it was resected. The patient complained of marked dysarthria a day after the operation and CT scan revealed a new infarction in the right frontal lobe. The third angiography showed an aneurysm arising from the right middle cerebral artery and the fact that two peripheral arteries of the aneurysm had disappeared 3 weeks after the first operation. The second operation was performed and a bacterial aneurysm was resected. The patient left the hospital without any neurological deficits. Septic embolism is the most important complication of infective endocarditis and it is usually presented with subarachnoid hemorrhage and intracerebral hemorrhage caused by ruptured bacterial aneurysms. In this case the septic embolism occurred two times. At each time cerebral ischemic attacks were presented. The reason why this case presented with ischemic symptoms was suspected to be that embolisms occurred at the trifurcation of the distal middle cerebral arteries. We were able to detect a bacterial aneurysm angiographically 3 days after the ischemic attack and we suspected that a bacterial aneurysm had been able to develop within 3 days after the septic embolism.     

Analysis of heat generation of lithium ion rechargeable batteries used in implantable battery systems for driving undulation pump ventricular assist device

We have developed internal battery systems for driving an undulation pump ventricular assist device using two kinds of lithium ion rechargeable batteries. The lithium ion rechargeable batteries have high energy density, long life, and no memory effect; however, rise in temperature of the lithium ion rechargeable battery is a critical issue. Evaluation of temperature rise by means of numerical estimation is required to develop an internal battery system. Temperature of the lithium ion rechargeable batteries is determined by ohmic loss due to internal resistance, chemical loss due to chemical reaction, and heat release. Measurement results of internal resistance (R(cell)) at an ambient temperature of 37 degrees C were 0.1 Omega in the lithium ion (Li-ion) battery and 0.03 Omega in the lithium polymer (Li-po) battery. Entropy change (DeltaS) of each battery, which leads to chemical loss, was -1.6 to -61.1 J/(mol.K) in the Li-ion battery and -9.6 to -67.5 J/(mol.K) in the Li-po battery depending on state of charge (SOC). Temperature of each lithium ion rechargeable battery under a discharge current of 1 A was estimated by finite element method heat transfer analysis at an ambient temperature of 37 degrees C configuring with measured R(cell) and measured DeltaS in each SOC. Results of estimation of time-course change in the surface temperature of each battery coincided with results of measurement results, and the success of the estimation will greatly contribute to the development of an internal battery system using lithium ion rechargeable batteries.     

Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds

Hepatocyte growth factor (HGF) has a number of biological activities, e.g., mitogenic, motogenic, antiapoptotic, antifibrous, and morphogenic. It also has angiogenic and angioprotective activities for endothelial cells. The aim of this study was to characterize the role of HGF in wound healing by administering the HGF gene locally to acute incisional skin wounds created on the backs of rats. To create wounds, the backs of Wistar rats were clipped and three 2-cm-long incisional wounds were made deep to the fascia. The wounds contained pannicrus carnosum and were created at intervals of 2 cm. After suturing, the HGF gene was then administered intradermally. Apoptotic cells in wound lesions were identified by TUNEL method as well as by immunological detection of active caspase-3. In the HGF-treated animals, we found almost complete suppression of apoptosis and well-organized wound healing. Histopathological examination revealed that the proliferation of fibroblasts was suppressed and that scar formation was less apparent in the HGF-treated animals compared to the controls. It is thought that administration of the HGF gene immediately after surgery may enhance the healing process through suppressing apoptosis, which occurred in the controls 1 week after suturing the incisional wound. In addition, locally increased HGF expression due to the introduction of the HGF gene to cells around wounds enhances dermal regeneration, possibly by promoting regeneration of dermal tissue, which results in less scarring due to its antifibrotic effect. Thus, HGF supplementation through gene therapy may be an effective strategy for treating wounds, as it increases the regeneration of the dermis to allow for "scarless wound healing."     

Transplanted mesenchymal stem cells are effective for skin regeneration in acute cutaneous wounds

Mesenchymal stem cells (MSCs) possess the capacity for site-specific differentiation of cell types in response to cues provided by different organs. This phenomenon suggests that MSCs participate in cutaneous wound regeneration. However, there are no prior reports on the influence of the local application of MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound regeneration, we cultured bone marrow cells of the femur of rats and treated the plastic adherent cells with a differentiation medium to induce differentiation. After treatment, we found that the bone marrow-derived plastic adherent cells possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating that these cells are MSCs. The bone marrow-derived plastic adherent cells were injected intradermally into the skin of rats, and linear full-thickness incisional wounds were made immediately through the injected area. At 14 days after operation, wounds transplanted with bone marrow-derived plastic adherent cells had healed with very fine scars. Collagen architecture was thick and appeared to be similar to normal dermis. Histomorphologic scale analysis demonstrated significant differences between the control and the wounds transplanted with bone marrow-derived plastic adherent cells. These results indicate that transplanted MSCs can respond quite normally to wound healing and regenerate dermal structure.     

Thrombus entrapped in a patent foramen ovale of the atrial septum

A 59-year-old women was referred to our hospital due to severe dyspnea and shock status 12 days after intracranial hematoma evacuation for the hypertensive right putaminal hemorrhage. Transthoracic echocardiography revealed right ventricular dilatation and floating structures in the right atrium. Transesophageal echocardiography demonstrated a large, snake-like structure crossing her foramen ovale of the interatrial septum, and impending paradoxical embolism was diagnosed. She did not receive any anticoagulation and surgery due to recent cerebral hemorrhage. Follow-up TEE showed complete disappearance of the thrombus in the atrium two weeks after the onset. Phlebogram of deep vein demonstrated several thrombus in her leg. She underwent placement of inferior vena cava filter and was discharged from our hospital without any symptom of paradoxical embolism.     

Aortobronchial fistula after replacement of descending thoracic aorta with ringed graft; report of a case

A 79-year-old male patient complicated with aortobronchial fistula after replacement of descending thoracic aorta with ringed graft. He underwent replacement of the aortic arch using a four branched vascular graft and open stent grafting to replace the descending thoracic aorta after removing the ringed-graft through median sternotomy. This procedure is useful for patients as the left thoracotomy is risky and the distal anastomotic site of the descending thoracic aorta is too far to anastomose.     

Vacuum-assisted closure system for the treatment of mediastinitis after total aortic arch replacement

A 77-year-old man developed deep sternal wound infection withEnterobacter cloacae 4 days after total aortic arch replacement for distal aortic arch aneurysm. Reexploration and open drainage of the mediastinum was carried out for 4 days, and the vacuum-assisted closure system was applied and continued for 10 days. During the treatment, granulation formation and neovascularization was apparently enhanced which lead us to perform omental transfer and chest closure on the 18^th postoperative day. The patient has been free from recurrent sign of mediastinal infection or graft infection for the 19 months of the follow-up period.