Suppressive effects of combination therapy with mizoribine and FK 506 on the development of accelerated coronary artery disease and myocardial rejection after heart transplantation.
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Biomedical subjects
Publications and source records attributed to T Shibata.
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Late pericardial effusion (PE) after open heart surgery has a potential for serious complications, including tamponade necessitating urgent drainage. From October 1990 to March 1995 moderate to massive PE developed following 9 of 359 (2.5%) cardiac procedures between 11 and 55 days postoperatively (mean, 18.6 days). Only one of these nine patients had evidence of cardiac tamponade; the other 8 patients had moderate symptoms including malaise, weight gain, and dyspnea on exertion. All patients except one were being treated with warfarin and anti-platelet agents. Echocardiography detected posterior PE of variable magnitude in all 9 patients; anterior PE was present in only one of these patients. Pericardiocentesis under echocardiographic guidance using an echo transducer with a built in puncture needle was performed in all patients. A flexible catheter was left in place for 24 to 72 hours for suction. In each case, 300 to 712 ml of old bloody fluid (mean, 475 ml) was evacuated, with relief of symptoms. Despite continuing anticoagulant therapy, there was no recurrence of pericardial effusion. The technique we have described simplifies pericardiocentesis and helps to avoid complications in this procedure.
A 14-year-old girl with severe coronary artery disease due to mucocutaneous lymph node syndrome, "Kawasaki disease", admitted to our hospital. Though she had no angina on any effort in her daily life, coronary angiography (CAG) demonstrated 90% stenosis and a large aneurysm of left main trunk. Based on the CAG findings, we determined to do the coronary artery bypass grafting (CABG) to left anterior descending artery (LAD) and 1st diagonal branch (D1) to prevent the occurrance of fatal acute myocardial infarction. We attempted to use bilateral internal thoracic arteries (ITAs) at the beginning of this surgery. While LAD was grafted with left one, D1 was done with saphenous vein (SV) because of difficulty of harvesting right one. The weaning from cardiopulmonary bypass was easy and the postoperative course was of no event. A month later, CAG showed the good patency of both left ITA and SV graft.
To elucidate the cause of anterior displacement of the disc, we evaluated the relation between anterior displacement and the size of the condyle from MR images in 301 patients (602 TMJs) with clinical diagnosis of internal derangement. We found that the size of condyles with anterior displacement of the disc was significantly smaller than that of condyles without anterior displacement. This result suggests that small condyles may give rise to anterior displacement of the disc.
We encountered three cases of hyperkalemia after the reperfusion of ischemic limbs associated with revascularization surgery for acute arterial occlusions. Two patients died because of uncontrollable hyperkalemia in spite of intravenous insulin and forced diuresis. Careful attention should be paid to hyperkalemia and metabolic acidosis for several hours after the reperfusion in cases of ischemia and/or extensive ischemia of long duration. The aggressive prophylaxis and treatment for MNMS are vital to the anesthetic management of revascularization for acute arterial occlusions.
We investigated the cytotoxicity and the interaction with low-dose radiation (1-4Gy) of tirapazamine by the in vitro cytokinesis-block micronucleus (MN) assay. Murine SCCVII and human melanoma (G-361) cells were treated with tirapazamine under aerobic or hypoxic conditions for 1 h and the MN frequency was determined using cytochalasin-B. The cells were also treated with or without tirapazamine or KU-2285 (hypoxic cell sensitiser) under hypoxic conditions and irradiated with or without reaeration of the cell suspensions. A dose-dependent increase of MN frequency was observed by tirapazamine treatment and the hypoxic toxicity ratio was about 130 for SCCVII and 37 for G-361. The radiation dose-response curves of MN frequency suggested that the interaction of tirapazamine with irradiation appeared to be essentially additive in both cell lines. In contrast, the dose-response curve became steeper by KU-2285 treatment. Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation. In conclusion, tirapazamine appeared to be superior to hypoxic radiosensitisers at clinically relevant doses, not because of aerobic radiosensitisation but because of its potent hypoxic cytotoxicity additive to radiation effect.
A 50-year-old man who had undergone successful aortic valve replacement for fungal endocarditis was presented. He had been doing well until October 1993, when he suddenly developed shock with high fever. In two weeks he recovered from septic shock with vigorous medical treatment including intravenous administration of antibiotics. The infecting organism was not detected on repeated blood cultures. Four months later he was admitted to our hospital because of left heart failure. Although he was afebrile on admission, a two dimensional echocardiogram revealed vegetation on the aortic valve and massive aortic regurgitation. Inflammatory signs persisted and the vegetation increased in size, and therefore an aortic valve replacement was performed. A surgical specimen of the aortic valve revealed perforation in each of three cusps and vegetation on the non-coronary cusp. Pathological exploration revealed typical colonies of fungi. Following the diagnosis of fungal endocarditis, administration of an anti-fungal drug was started. His post-operative course was uneventful, and there was no evidence of recurrence with the anti-fungal medication for one year postoperatively.
Shakuyaku-kanzo-to (SK), a Chinese herb medicine consisting of Shakuyaku (Paeoniae Radix) and Kanzo (Glycyrrhizae Radix) has been used for the treatment of dysmenorrhea. It is reported that prostaglandin (PG) production increased during menstruation in uterine myometrium. To know the effect of SK on PG production in the uterine myometrium, the following in vitro study was undertaken. Human uterine myometrium was obtained from patients who underwent hysterectomy. 1. Myometrial cells were cultured and, SK, Shakuyaku (S), Kanzo (K), or glycyrrhetinic acid (GA), which is the major component of K, were added to the culture medium. Concentrations of PGE2, PGF2 alpha, and 6-ketoPGF1 alpha in the medium measured by RIA were significantly decreased by the addition of SK, K or GA but no effect was observed when S. 2. [3H]-arachidonic acid (AA) was added to culture medium and incorporated into the Sn-2 of phospholipids. [3H]-AA release and PG production in the medium were determined. PG were extracted and the radioactivity of PG was measured. The production of PGE2, PGE2 alpha and 6-ketoPGF1 alpha from labeled cells was significantly reduced by the addition of SK, K and GA. 3. Phosphatidylcholine containing [14C]-AA in Sn-2 (150,000 dpm) was incubated with cytosol of uterine myometrium and the amounts of [14C]-AA released were calculated as Phospholipase A2 activity. The amount of [14C]-AA release was inhibited dose-dependently by SK, K and GA. It is the first time that SK has been shown to suppress PG production in the myometrium by inhibiting cPLA2 activity.
To identify appropriate candidates with rectal cancer for preoperative chemoradiation therapy, the local recurrence rate and clinicopathological characteristics of 232 patients with rectal cancer undergoing curative resection in our department were investigated. The local recurrence rates were 3.8%, 10.8% and 16.5% in the Rs, Ra and Rb lesions, respectively. Regarding lower (Rb) rectal cancer, depth of lesion (> a1) and nodal metastasis consisted of high factors for local recurrence. Basing on these results, entry criteria for preoperative chemoradiation therapy were established, and concurrent chemoradiation therapy with fluorouracil and cisplatin was delivered preoperatively in 9 primary cases of locally advanced rectal cancer and 3 cases with local recurrence. A partial response was obtained in 7 of 12 cases with a response rate of 58%, size-reduction of the distant metastatic lesions was found in 2 cases, and clinical symptoms were improved in all cases. The histological responses of the 6 resected cases were Grade 2 in 2 cases and Grade 1b in 4 cases. The toxicities of this chemoradiation regimen were well tolerable. As a postoperative complication, infection of the perineal wound was most frequent. Preoperative chemoradiation therapy with the present regimen would be a useful adjuvant treatment for advanced lower rectal cancer.
It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.
We evaluated clinical benefits (QOL and local control rate) of percutaneous microwave coagulation therapy conducted with general anesthesia. Five cases with hepatic tumor (3 cases with hepatocellular carcinoma, 2 cases with metastatic hepatic tumor) were enrolled. The day following treatment all patients were virtually free of complaints with performance status ranging 0 to 1, and they were discharged from the hospital within 1 week. Four of five cases could be controlled solely with this treatment: one case showed local relapse, the tumor size of which exceeded 3 cm. PMTC may be one of the most beneficial local treatments for malignant hepatic tumor, since it shortens hospital stay with a good QOL status, and is applicable to metastatic tumor.
Wood creosote suppresses intestinal fluid secretion induced by heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC). When rabbit jejunum is ligated into a 5-cm segment and LT is administered locally, it actively induces intestinal fluid secretion in a dose-dependent manner. Local administration of wood creosote together with a fixed dose of LT suppressed the LT-induced fluid secretion in a dose-dependent manner. At a 50-ng/segment dose of LT, 7.4 +/- 1.1 ml (n = 5) of fluid is secreted into an intestinal segment; coadministration of wood creosote (150 micrograms/segment) significantly (p < 0.01) suppressed the fluid secretion to 2.4 +/- 2.3 ml. Based on these results, we conclude that the antidiarrheal activity of wood creosote is attributable to its antisecretory or proabsorptive effect (or both) on the intestine.
An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis and glomerulone phritis in the same individual, and both have been thought to be associated with an increase in circulating immune complexes and autoantibodies. However, the genetic basis of these diseases is poorly understood. A novel recombinant congenic mouse strain, McH5-lpr/lpr, which was established by rearrangement of the genetic background of MRL/lpr mice by hybridization with C3H/HeJ-lpr/lpr mice, developed severe granulomatous polyarteritis, as did the MRL/lpr strain, but not glomerulonephritis. Serum levels of anti-DNA and anti-myeloperoxidase antibodies in these mice were significantly reduced, as compared with MRL/lpr mice, although rheumatoid factors were not. These results indicate that each of these two diseases, arteritis and glomerulonephritis, is under the control of different background gene(s), suggesting a different pathological basis of these diseases, and that anti-DNA and anti-myeloperoxidase autoantibodies appear to have a limited pathogenic role in granulomatous arteritis in the mouse strain described.
The purpose of this study was to evaluate the relationship between exercise induced ischemia and left ventricular dysfunction, ergometer exercise 99mTc-tetrofosmin myocardial scintigraphy was performed using one day protocol (exercise/rest). Subjects consisted of 68 patients without previous myocardial infarction; without coronary artery disease (CAD) (n = 36) and with CAD (n = 32). Perfusion and function images were evaluated simultaneously. Perfusion image was taken by single photon emission tomography (SPECT). Quantitative analysis was performed with normal data-base. The area of abnormal perfusion, less than normal lower limits, was named as extent score (ES). Left ventricular ejection fraction (LVEF) was measured by first-pass study. According to ES on stress image, 32 patients with CAD were divided into 3 groups; ES < 10% (n = 15), ES = 10-20% (n = 7) and ES > 20% (n = 10). LVEF at rest among 4 groups were not different. LVEF at peak exercise was 61.7+/ -5.3% in CAD (-), 59.0 +/- 5.8% in ES < 10%, 57.4 +/- 6.6% in ES = 10-20% and 47.4 +/- 10.5% in ES > 20%. LVEF in ES > 20% at peak exercise was lowest significantly. Thus, simultaneous perfusion and function images were evaluated for the relationship between exercise induced ischemia and left ventricular dysfunction. If extent score on stress image was more than 20% of left ventricle, significant left ventricular dysfunction was observed.
This study was conducted to evaluate the hemodynamic effects of amrinone early after open-heart surgery. Eighteen patients who underwent coronary artery bypass grafting were randomly divided into two groups: ten patients (group A) were administered 5 micrograms/kg/min of amrinone, and eight patients (group B) were administered 10 micrograms/kg/min. No bolus of amrinone was administered before continuous infusion. The mean and systolic arterial pressure and systemic vascular resistance index were significantly decreased (p < 0.05) after infusion of amrinone in both groups. Cardiac index was not increased in group A, but was significantly increased in group B without increase in the double product. There were no significant changes in heart rate, mean pulmonary arterial pressure or pulmonary capillary wedge pressure in either group. Pulmonary vascular resistance index tended to decrease in either group. Transient hypotension after infusion of amrinone was a serious clinical problem. Of the eight patients with systemic vascular resistance index less than 2000 dyne*sec*cm-5*m2 before infusion, blood pressure decreased below 100 mmHg in five patients. Administration of amrinone was discontinued in two patients in group B and one patient in group A because of transient hypotension. In this study, continuous infusion of amrinone (10 micrograms/kg/min) had both positive inotropic and vasodilating properties; however, transient hypotension must be monitored carefully.
A 79-year-old man was admitted to our hospital with heart failure following acute inferior myocardial infarction. An echocardiogram demonstrated severe mitral insufficiency, and coronary arteriography revealed double vesel disease. Following diagnosis of ischemic papillary muscle dysfunction, PTCA was performed, but the mitral insufficiency was not eliminated. Follow-up echocardiography disclosed rupture of the posterior papillary muscle. He underwent surgery on the 30th day after onset of acute myocardial infarction. Partial rupture of the posterior papillary muscle was found at surgery, and mitral valve replacement and single coronary artery bypass to Lcx were performed. His postoperative course was uneventful, and he was discharged on the 46th day after operation.
A successful closure of patent ductus arteriosus (PDA) in a 70-year-old women is described. The patient had poor pulmonary function and calcification of the aortic arch and the descending aorta, as well as arteriosclerosis obliterans bilaterally in the iliac arteries. We therefore performed trans-pulmonary artery direct closure of the ductus arteriosus via a median strenotomy. In surgery, we used a Foley balloon catheter inserted into the aorta through the ductus to prevent backflow. Leakage of blood from the ductus, even with use of balloon occlusion, required the reduction of perfusion flow to 500 ml/min and temporary circulatory arrest. Rectal temperature was 27 degrees C when the aorta was cross-clamped. The ductus orifice was primarily closed with three mattress sutures with pledgets, and this sutured orifice was secondarily covered with a bovine pericardial patch. The postoperative course was satisfactory. Trans-pulmonary artery direct closure of the PDA using cardiopulmonary bypass is useful for aged patients. This patient is, as far as our knowledge, the oldest surgical report in Japan.
The number of official inspection of coal-tar dyes and their lakes from April in 1995 till March in 1996 were 580 in total. The quantity which passed inspection amounted to 166.4 ton in Japan. The production of color in each month was summarised in Table 1, and by each producing company in Table 2. The food coal-tar dye produced in the largest quantity was Food Yellow No.4, occupying 43.9% in this period.