Laryngeal stenosis associated with chronic graft-versus-host disease following unrelated bone marrow transplantation.
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Biomedical subjects
Publications and source records attributed to M Kume.
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From 1989 to 2002, 9 patients with metastatic renal cell carcinoma to lung underwent lung resections for curative removal of metastatic disease in our department. Disease free interval (DFI), number and size of metastases resected (at first metastasectomy), and number of metastasized regional lymph nodes were studied after resection of pulmonary metastases. DFI were 0 to 60 months with mean value of 23 months. At first operation, single metastases accounted for 4 cases and multiple lesions more than 2 metastases accounted for 5 cases with mean value of 2.1. Maximal diameter of metastases was 10 to 50 mm with mean value of 24 mm. Regional lymph nodes metastases were demonstrated only 1 patient in 2 of No. 12 lymph nodes adjacent to metastases. At subsequent relapse, 1 patient had second-stage metastasectomy, 2 patients went on to a third phase. Four patients were lost, 2 are under treatment for newly relapsed lesions, and 3 are now free of metastases. Analysis was performed by Cox proportional hazards model of survival using these factors. Though lacking the statistical significance, only maximal diameter of metastases was prone to have influencing factor on prognosis. Survival was not related to DFI between 0 to 21 months and more than 21 months and numerous lung metastases between single metastasis and with 2 or more. In general, estimated survival rate of these patients according to Kaplan-Meier was 0% at 67 months. Considering the above results, surgical treatment for patients with metastatic renal cell carcinoma to lung should be planned carefully.
Conventional surgical treatment of patients with an anastomotic aneurysm can be a surgical challenge if severe adhesions are present. We report here effective treatment of an anastomotic aneurysm using an endoluminal stent graft. A 71-year-old man had undergone an aorto-bifemoral bypass for Leriche's syndrome in 1989 and partial gastrectomy for cancer in 1996. He was admitted to our department with a pseudoaneurysm of a proximal anastomosis located at the aorta below both renal arteries. Based on his medico-surgical history, we considered that an endovascular stent should be placed. This graft composed of an UBE(UBE-WOVEN GRAFT) graft and self-expandable Z stents were introduced through the right limb of the bifurcated graft previously implanted, then were placed using the delivery system while advancing under fluoroscopic control, using a pusher rod. Endoleakage was not evident and the postoperative course was uneventful. An endovascular graft is one alternative approach for treating patients with an anastomotic aneurysm as it is less invasive. This procedure proved satisfactory for this patient.
Heat shock protein (hsp), including hsp70, has been reported to restore the glucose-induced insulin release suppressed by nitric oxide (NO). However, the mechanism underlying this recovery remains unclear. In the present study, we examine the effects, in rat islets, of heat shock on insulin secretion inhibited by a small amount of NO and also on glucose metabolism, the crucial factor in insulin release. Exposure to a higher dose (15 U/ml) of interleukin-1beta (IL-1beta) abolished the insulin release by stimulation of glucose or KCl in both control and heat shocked islets. In rat islets exposed to a lower dose (1.5 U/ml) of IL-1beta, insulin secretion in response to glucose, but not to glyceraldehydes (GA), ketoisocaproate (KIC), or KCl, was selectively impaired, concomitantly with lower ATP concentrations in the presence of 16.7 mM glucose, while such suppression of insulin secretion and ATP content was not observed in heat shock-treated islets. NO production in islets exposed to 1.5 U/ml IL-1beta was significantly, but only partly, decreased by heat shock treatment. The glucose utilization rate measurement using [5-3H]-glucose and [2-3H]-glucose and the glucokinase activity in vitro were reduced in islets treated with 1.5 U/ml IL-1beta. In heat shock-treated islets, glucose utilization and glucokinase activity were not affected by 1.5 U/ml IL-1beta. These data suggest that heat shock restores glucose-induced insulin release inhibited by NO by maintaining glucokinase activity and the glucose utilization rate in islets in addition to reducing endogenous NO production.
We retrospectively analyzed 52 adult patients with hemophagocytic syndrome (HPS). The underlying diseases were heterogeneous, including malignant lymphoma (lymphoma-associated hemophagocytic syndrome [LAHS]) in 26 patients, systemic lupus erythematosus in 3 patients, viral infections in 7 patients, and bacteria] or fungal infections in 6 patients. More than 83% of patients received prednisolone as an initial treatment. Multiple-agent chemotherapies (cyclophosphamide, doxorubicin, and vincristine) were administered to 96% of LAHS patients after a histopathological diagnosis of lymphoma. HPSs were controllable and remissions were achieved except for those patients with LAHS, fulminant Epstein-Barr virus-associated HPS, and an immunosuppressive state. Twenty-one (81%) of the LAHS patients had uncontrollable HPS and died of multiple organ failure and disseminated intravascular coagulation. The median survival time of LAHS patients was 83 days. In contrast, 3 (12%) of the other HPS patients died of multiple organ failure within 44 days.The clinical manifestations and the laboratory findings of LAHS and the other HPSs were too variable to establish the prognosis based only on the findings at the onset of HPS. The prognostic factors of adult HPS were found to be the underlying diseases, notably malignant lymphoma and infections, accompanied by the immunosuppressive state.
Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: P(on)time 20 ms, the pulse interval: P(off) time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature.
BACKGROUND AND OBJECTIVE: To investigate whether the administration of ketamine before induction with propofol produces a smaller decrease in arterial pressure. METHODS: Twenty-two patients were assigned to one of two groups to receive either propofol with ketamine (n = 11) or propofol alone (n = 11, control). Anaesthesia was induced with 2 mg kg-1 propofol and 0.5 mg kg-1 ketamine or 2 mg kg-1 propofol alone. Ketamine was administered 1 min prior to induction with propofol. Immediately after induction with propofol, vecuronium (0.15 mg kg-1) was administered. Four minutes after administration of vecuronium, tracheal intubation was performed. Anaesthesia was maintained using sevoflurane (0.5%) in 66% nitrous oxide until 3 min after intubation. Systolic, diastolic and mean arterial pressure and heart rate were recorded on arrival, directly before induction with propofol, prior to tracheal intubation, immediately after intubation and at 3 min after intubation. RESULTS AND CONCLUSIONS: Administration of ketamine before induction with propofol preserved haemodynamic stability compared with induction with propofol alone.
BACKGROUND AND OBJECTIVE: Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhythmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. METHODS: Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ng mL(-1). The cibenzoline was administered into the perfusate 5 min after the start of perfusion. Heart rates in the 3000 ng mL(-1) group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL(-1) group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/dt max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5 min. Myocardial adenosine triphosphate concentration in the 3000 ng mL(-1) group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio. CONCLUSION: The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.
BACKGROUND AND OBJECTIVE: We investigated whether glibenclamide (glyburide) affects myocardial metabolism and hydroxyl radical formation in the rat heart-lung preparation with or without inhalation anaesthetics. METHODS: Thirty-seven male Wistar rats were allocated to four groups: (a) control group (C), received vehicle only; (b) group G, received glibenclamide 10 microM L-1; (c) group I, received glibenclamide 10 microM L-1 and 1.4% isoflurane during perfusion; (d) group S, received glibenclamide 10 microM L-1 and 2.7% sevoflurane during perfusion. Glibenclamide was administered 7 min after the start of perfusion. Ten minutes later, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero, and then the heart was reperfused for 10 min. The formation of hydroxyl radicals in perfusate blood and heart was measured with high performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acids. RESULTS: The recovery time from ischaemia in group G was significantly longer than the other groups. However, there were no differences in myocardial metabolites and dihydroxybenzoic acids concentrations in the perfusate and heart among the four groups. CONCLUSIONS: Glibenclamide prolonged recovery time from ischaemia, but did not affect hydroxyl radical formation in the postischaemic reperfused heart. In addition, isoflurane and sevoflurane shortened this time. These facts suggest that mechanisms other than effects of volatile anaesthetics on hydroxyl radical formation are responsible for their protective effects in this model.
The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E 1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction.
BACKGROUND: We examined the time course of endothelium-dependent and -independent responses in reversed autogenous arterial grafts during regeneration and tissue repair processes after arterial grafting in dogs. MATERIALS AND METHODS: Autogenous arterial grafts implanted in the canine femoral artery were removed, cut into rings and suspended in organ chambers for isometric tension recording on the 1st, 3rd, 7th, 14th and 28th days after implantation. Electron-microscopic examination on the 1st, 3rd,7th, 14th and 28th days after transplantation was also performed. Control arteries were taken from nonsurgically treated femoral arteries. RESULTS: Acetylcholine (ACh) and A23187 caused endothelium-dependent relaxations in arterial grafts throughout the study. Although endothelium-dependent relaxations to ACh and A23187 on the 3rd day after transplantation were only significantly impaired compared to those of control, they were similar to the control within 1 week after grafting. Smooth muscle relaxations in response to sodium nitroprusside in arterial grafts throughout the study were comparable with those of control arteries. No apparent intimal thickening of the arterial grafts was observed. Electron microscopy scanning revealed mild endothelial cell damage in implanted autogenous arterial grafts on the 1st or 3rd day after grafting. Seven to 14 days after grafting, the endothelial cell layer appeared to be normal. CONCLUSIONS: It was observed that the endothelial function remained intact and there was an absence of intimal thickening in the arterial grafts. These observations may explain the improved patency of autogenous arterial grafts compared to the vein grafts in aortocoronary revascularization.
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N-nitro-L-arginine methyl ester (L-NAME) has been reported to have protective action against hydroxyl free radicals. We have investigated whether L-NAME influences free radical formation in the post-ischemic reperfused heart of anesthetized rats. An isolated rat heart-lung preparation was used. Forty male Wistar rats were allocated into D (D-NAME 100 microMol.l-1), L (L-NAME 100 microMol.l-1), LH (L-NAME 100 microMol.l-1 and 1MAC halothane), LI (L-NAME 100 microMol.l-1 and 1MAC isoflurane), and LS (L-NAME 100 microMol.l-1 and 1MAC sevoflurane) groups. The heart was perfused initially at the cardiac output of 30 ml.min-1 and the atrial pressure of 70 mmHg. Drugs were administered into the reservor 7 min after the start of perfusion. Ten minutes after the start of perfusion, the heart was rendered globally ischemic for 10 min by reducing the preload and afterload to zero and then reperfused for 10 min. At the end of reperfusion, the heart was freeze-dried for 4 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in the perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acid (DHBA). Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. DHBAs in the heart of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups. The concentrations of DHBA in the perfusate blood after ischemia and reperfusion were significantly higher than those before ischemia in all groups. DHBAs in the perfusate blood after ischemia and reperfusion of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups administered L-NAME. This study indicates that L-NAME reduces hydroxyl free radical formation in the post-ischemic reperfused heart in anesthetized rats and volatile anesthetics do not influence the depressant effect of hydroxyl free radical formation by L-NAME.
We describe a patient with acute promyelocytic leukemia (APL) carrying a new complex variant translocation of t(2;15;17)(q21;q22;q21). The karyotypic interpretation was confirmed by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 2, 15, and 17 and a PML/RARA dual color DNA probe. FISH showed a PML/RARA fusion gene on the der(2) instead of the der(15). These results suggest that the critical event in the development of APL is the formation of a PML/RARA chimeric gene, regardless of its locus in the genome.
Membrane lipids and cytosolic proteins are major targets of oxidative injury. This study examined the effect of heat-shock preconditioning associated with the induction of heat-shock protein 72 on liver injury, from the aspect of lipid peroxidation and protein denaturation after carbon tetrachloride (CCl4) administration in rats--one of the representative oxidative injuries. Male Wistar rats were divided into two groups, group HS (preconditioned by heat exposure) and group C (not preconditioned). Expression of HSP72 in the liver tissue was confirmed by Western blot analysis. After a 48-h recovery period, all rats were given CCl4 intragastrically. Liver damage was assessed by measuring serum liver-related enzyme levels and adenine nucleotide concentration in the liver tissue. Lipid peroxidation and protein denaturation were evaluated by measuring tiobarbituric acid reactive substances (TBARS) and by immunohistochemical staining of 4-hydroxy-2-nonenal(HNE)-modified proteins in the liver. Survival rates of the rats after CCl4 administration were also compared. Expression of HSP72 was clearly detected in group HS, but not in group C. Heat-shock preconditioning significantly improved the survival rate, suppressed the increase in liver-related enzyme levels and maintained adenosine triphosphate levels (P<0.01 each). HNE-modified proteins--denatured proteins by free radical attack--were significantly less stained in group HS than in group C (P<0.05). However, TBARS levels did not differ between groups. Because heat-shock preconditioning did not alter TBARS levels but reduced HNE-modified proteins in association with the expression of HSP72, it is suggested that HSP72 did not prevent lipid peroxidation but decreased the lipid peroxidation-induced denaturation of proteins. This seemed to be a mechanism of heat-shock preconditioning to ameliorate oxidative liver injury.
We describe a case of an acute myelogenous leukemia (AML) associated with t(1;11) (q23;p15), which is a novel simple variant translocation of t(7;11)(p15;p15). The patient was a Japanese man who had a history of non-Hodgkin lymphoma (NHL) and received MACOP-B combination chemotherapy. Fifteen months after the completion of the treatment, the patient developed AML (M2), which was regarded as a therapy-related leukemia. Cytogenetic study of bone marrow cells showed t(1;11). Although he achieved complete remission by combination chemotherapy, a relapse of NHL and gastric cancer were revealed in the course of the consolidation chemotherapy for AML. The NHL was considered a histological conversion from follicular lymphoma because lymphoma cells carried t(14;18) (q32;q21) and were strongly positive for BCL2 protein. Translocation (1;11), together with AML having t(7;11) or inv(11) involving 11p15, shows that 11p15 is a common acceptor site of these chromosome aberrations and suggests the significance of the NUP98 gene located in 11p15 in therapy-related leukemia.
BACKGROUND: Cardiovascular disease such as coronary artery disease is a major cause of late death after repair of abdominal aortic aneurysm (AAA). But risk factors are not well known. So, we investigated the incidence of cardiovascular events after surgery and examined the prognostic factors. STUDY DESIGN: We retrospectively reviewed 270 patients who underwent elective surgery for AAA from 1985 to 1995. Kaplan-Meier survival analysis was used to estimate survival rates and the probability of coronary, cerebrovascular, and cardiovascular events. The risk factors for each endpoint were investigated using multivariate analysis. RESULTS: The overall survival rate was 87.3% at 3 years, 76.4% at 5 years, and 52.3% at 10 years. Current cigarette use, renal insufficiency, advanced age (> or = 70 years old), and higher plasma fibrinogen level (> or = 300 mg/dL) were significant factors influencing survival. The probability of a coronary event was 4.9% at 3 years, 7.1% at 5 years, and 20.7% at 10 years. Plasma fibrinogen level and cerebrovascular disease were significant prognostic factors for coronary events. The probability of a cerebrovascular event was 5.3% at 3 years, 7.6% at 5 years, and 18.0% at 10 years. No significant prognostic factors for cerebrovascular events existed. The probability of a cardiovascular event was 10.3% at 3 years, 14.9% at 5 years, and 33.6% at 10 years. Plasma fibrinogen level was a significant risk factor for cardiovascular events. But the presence of coronary artery disease did not affect survival or the incidence of coronary, cerebrovascular, or cardiovascular events. CONCLUSIONS: Plasma fibrinogen level is an independent risk factor of future coronary events after surgery for AAA, and the increased risk of coronary artery events contributes to the impaired survival. Patients with higher plasma fibrinogen level need careful surveillance for cardiovascular disease after surgery.
BACKGROUND: Pharmacological preconditioning may induce a stress response which protects liver against ischaemia-reperfusion injury (IRI). The aim of this study was to determine, in an animal model, whether intravenous administration of doxorubicin induces heat shock proteins (HSPs) in liver tissue and facilitates liver tolerance to subsequent warm IRI. METHODS: Male Wistar rats were used. Production of HSPs was determined in liver tissue sequentially after the injection of doxorubicin 1 mg/kg body-weight. Acquisition of tolerance for 30 min warm ischaemia and reperfusion of the liver was determined in animals pretreated (48 h beforehand) with doxorubicin, and in controls. Biochemical liver function and liver adenine nucleotide concentration 40 min after reperfusion and survival rate at 7 days after the ischaemic insult were recorded. RESULTS: Expression of HSP72 and HSP73 in the liver was confirmed 48 h after doxorubicin administration. Biochemical parameters and survival rates were significantly better in pretreated animals than in controls. CONCLUSION: These results indicate that doxorubicin has the potential to provide the liver with tolerance against IRI. A simultaneous increase of both HSP72 and HSP73 in liver tissue may explain the acquisition of tolerance following the administration of doxorubicin.