Biomedical subjects
Publications and source records attributed to Y Shimazaki.
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We report a successful resection of an osteosarcoma in the chest wall developed 25 years after irradiation. A 74-year-old woman was admitted to our hospital for her swelling in the left chest wall at August 24, 1995. At 49-year-old, she had undergone an operation and postoperative irradiation for left breast cancer. A computed tomography demonstrated a mass in the left chest wall that destructed the first rib, extending into the pleural space and invaded into the left common carotid and subclavian arteries. We planned a radical resection of the mass after repeated CT scannings, since it was histopathologically diagnosed as a chondrosarcoma and showed a rapid growth. The tumor was completely removed with radical transmediastinal forequarter amputation of the partial chest wall and total left upper extremity. The left common carotid artery was partially replaced with 6 mm EPTFE vascular prosthesis. The chest wall was reconstructed with Marlex-mesh prosthesis and a myocutaneous flap. She was discharged uneventfully and has not shown any evidence of recurrence.
Azithromycin (AZM), an oral macrolide antibiotic drug, was studied for its efficacy and pharmacokinetics in the treatment of pediatric patients with respiratory tract infections. The results of the study are presented. Fifteen pediatric patients in an age range between 1 and 10 years were given 8.9 to 14.7 mg/ kg body weight of AZM once daily for 3 to 4 days. Pharmacokinetics of AZM in three patients were examined. AZM concentration in plasma was 0.037 microgram/ml at 72 hours after final dosing, while urine concentration was 10.9 micrograms/ml measured during a period between 72 and 96 hours post-dosing. Fourteen patient cases were included in analysis of drug efficacy for AZM. AZM was found "markedly effective" in all seven patients with pneumonia, and "effective" in all three patients with acute bronchitis, two patients with mycoplasmal pneumonia, and one patient with tonsillitis. In one patient with mycoplasmal bronchitis, AZM was found slightly effective. The efficacy rate was 92.9% (13/14). The study found one case of side effect, moderate diarrhea. No laboratory abnormality was documented. In conclusion, an antibiotic AZM was found useful in a treatment of pediatric respiratory tract infections.
The histopathological features of chronic rejection and its initiation were assessed using rat heterotopic heart transplantation and retransplantation models. Fully allogeneic or minor, non-MHC antigen-mismatch heart grafts transplanted into recipient rats treated with a short course of FK506 showed long-term survival but developed graft atherosclerosis after 40 days posttransplantation. Retransplantation of allografts back into the original donor strain did not prevent graft atherosclerosis if the grafts had resided in the primary recipient for up to 5 days; residence in the primary allogeneic recipient for less than 4 days did not result in graft atherosclerosis in the secondary recipient. Short-course administration of FK506 did not affect the production of these changes. Graft coronary arteriosclerosis begins between 3 and 5 days posttransplantation and progresses without continuous allogeneic immunological drive. The present findings will provide a new means by which to approach the analysis of development of chronic allograft rejection.
BACKGROUND: Nitric oxide (NO) derived from the endothelial cell has been identified as a constitutive chemical mediator that regulates the function of the endothelial cell in association with neutrophil (PMN) adhesion and activation. However, its role in the pathogenesis of myocardial reperfusion injury is not clear. METHODS AND RESULTS: Fifteen isolated rat hearts were perfused with modified Krebs-Henseleit solution and subjected to 20 minutes of global and normothermic ischemia. Then the hearts were reperfused for 45 minutes with different protocols: the control (C) group was reperfused without PMNs, the P group was reperfused with PMNs, and the N group was reperfused with PMNs and nitroprusside (10(-5) mol/L). The ozone chemiluminescence method was used for direct measurement of NO in the coronary effluent during reperfusion. NO in the coronary effluent in the C group decreased at reperfusion after normoxic perfusion, and this decrease in NO continued for the first 15 minutes of reperfusion. Percentage recovery of left ventricular developed pressure and coronary flow was significantly lower in the P group than that in the N group. Also, the N group had a significantly lesser Luminol-elicited chemiluminescence of the coronary effluent and ratio of PMN adherence to myocardial vasculature compared with the P group. CONCLUSIONS: This study demonstrated directly the decrease in NO production during reperfusion and showed that supplement of NO with NO donor attenuated the injury in which PMNs were involved. The results suggest that NO plays a significant role in reperfusion injury and that supplement of NO during reperfusion appears to be useful to attenuate this injury.
The surgical management of patients with concomitant critical coronary artery disease (CAD) and surgically resectable cancer is controversial. We evaluated 19 patients who underwent concomitant coronary artery bypass grafting (CABG) and curative operation for cancer of the stomach in 9 patients, the colon in 4, the lung in 4, and the breast in 2. Each cancer operation was performed under stable hemodynamics without any serious bleeding tendency, immediately after CABG with an average of 2.5 +/- 0.8 grafts. There were no operative deaths and no incidences of perioperative myocardial infarction. Postoperative complications developed in three of the patients with lung cancer: respiratory dysfunction caused by phrenic nerve paralysis in two and mediastinitis in one. During the mean follow-up period of 33 +/- 23 months, 5 patients died of recurrent cancer or non-cardiac disease; however, all 19 patients remained free from any postoperative cardiac events and their quality of life apparently improved. This experience suggests that such simultaneous correction would be safe and beneficial in carefully selected patients who have surgically correctable CAD and potentially curable cancer.
A percutaneous left ventricular assist system (PLVAS) using a modification of the Dennis method was developed and implemented in 8 patients. Transseptal cannulation was performed under biplane fluoroscopy and/or transesophageal echocardiogram without encountering any problems. All the patients were in a state of severe cardiogenic shock, caused by acute myocardial infarction in 5, cardiomyopathy in 2, and postcardiotomy in 1, and were on intraaortic balloon pump support and/or percutaneous cardiopulmonary support (PCPS), in the form of partial cardiopulmonary bypass. Three patients who developed concomitant right heart failure required additional PCPS. All the patients were supported at 3.0 to 4.0 l/min for 76-284h for an average time of 159h. Three patients were successfully weaned from PLVAS and one of these patients, who had suffered an acute myocardial infarction, was discharged from hospital. The complications directly related to this system were minimal. Our observations led to the conclusion that PLVAS using our modification of the Dennis method is a simple, easy, and safe means of maintaining adequate systemic circulation in severely ill patients. As PLVAS is particularly effective for patients in cardiogenic shock following acute myocardial infarction, we believe that it will be applied routinely by many cardiac surgeons and cardiologists in the future.
BACKGROUND: The effect of Na+/H+ exchange inhibition in neutrophil-induced reperfusion injury was investigated using a new amiloride analogue, 5-methyl-N-isobutyl amiloride (MIA). METHODS: Rat neutrophils were separated using Percoll gradient. Luminol chemiluminescence intensity of isolated neutrophils was depressed by MIA in a dose-dependent manner. RESULTS: The effect of MIA on neutrophil-induced reperfusion injury was evaluated in Langendorff-perfused rat hearts subjected to 30 minutes of normothermic ischemia. Postischemic left ventricular developed pressure recovery was depressed by the reperfusion with neutrophils (60% +/- 7% to 33% +/- 26%) and was reverted by MIA pretreatment (86% +/- 17%, p < 0.05). MIA also improved percent recovery of coronary flow (51% +/- 2% to 70% +/- 13%), reduced creatine kinase (0.28 +/- 0.1 to 0.085 +/- 0.03 IU.L-1.g-1 dry wt), and lactate dehydrogenase leakage (10.6 +/- 3.8 to 5.16 +/- 1.3 IU.L-1.g-1 dry wt) significantly. The incidence of reperfusion-induced ventricular fibrillation also was reduced by MIA. CONCLUSIONS: The inhibition of Na+/H+ exchange shows a protective effect against neutrophil-induced reperfusion injury possibly by inhibiting the activation of neutrophils.
Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 +/- 3.6) in group 1 and 0.8 to 15.8 years (4.3 +/- 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 +/- 3.0) in group 1 and 9 to 22 years (13.5 +/- 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 +/- 2) and 10 to 26 mm Hg (20 +/- 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 +/- 3) and 14 to 39 mm Hg (27 +/- 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U.m2 (1.93 +/- 0.63) and 0.79 to 3.31 U.m2 (2.05 +/- 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U.m2 (1.36 +/- 0.57) and 0.81 to 3.85 U.m2 (2.18 +/- 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years.
We have recently reported that 4-[2-(4-substituted phenylsulfonylamino) ethylthio]phenoxyacetic acids and related compounds showed potent thromboxane A2 (TXA2) receptor antagonist activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) was analyzed by using the Hansch-Fujita method for 36 compounds, including newly synthesized compounds. The positive coefficient for pi R and FR in the results of the QSAR study suggested that a hydrophobic an sigma electron-withdrawing substituent R at the para-position of the phenylsulfonyl moiety is required to improve the activity. Further, a substituent R which is long and moderately wide, was suggested to be preferable for the activity. The positive coefficients for pi X,Y,W-COOH and sigma Q(1)-(6) may indicate that the introduction of a hydrophobic and electron-withdrawing group on the benzene ring of the phenoxy acetic acid moiety enhances the activity. The length of the W-COOH moiety may also be important. On the other hand, the effect of the presence of methylene (n = 1) was not clear.
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We describe a 22-month-old Japanese girl with severe microcephaly with a prominent nose and a receding chin, developmental delay, marked intrauterine and postnatal dwarfism with limb shortening and brachydactyly, and distinctive radiological changes of the skeleton. The radiological findings include hypoplasia of the short tubular bones, multiple pseudoepiphyses in the bases of the metacarpals, coxa valga, a wide pelvis with iliac flaring, thoracolumbar scoliosis, and disharmonious ossification delay. The clinical and radiological features are somewhat different from those of previously reported cases with osteodysplastic primordial dwarfism. The clinical and radiological manifestations of osteodysplastic primordial dwarfism are reviewed and compared with those in our patient.
To reevaluate the postoperative contractile state and survival, 34 patients (19 men and 15 women; average age 45 years, range 23 to 65) undergoing conventional mitral valve replacement between 1980 and 1990 were studied. There were 5 cardiac deaths (2 early and 3 late). Four of 5 deaths occurred in patients who had a preoperative left ventricular end-systolic volume index > 100 ml/m2. Sixteen patients with an end-systolic volume index < 100 ml/m2 (group I), and 5 with an index > 100 ml/m2 (group II) underwent repeat catheterization 8 months (range 4 to 17) after surgery. The ratio of end-systolic wall stress to end-systolic volume index increased significantly after surgery in group I, whereas it remained reduced in group II. The postoperative end-systolic wall stress/volume index ratio correlated significantly with the preoperative end-systolic volume index (p < 0.001). In the relation between end-systolic wall stress and ejection fraction, all patients in group II had values that were less than the 95% confidence limits for the normal relation. In conclusion, patients with a preoperative end-systolic volume index > 100 ml/m2 appeared to be at high risk of incurring irreversible depressed myocardial contractility, with a high postoperative mortality.
Using an isolated perfusion model of neonatal rabbit hearts aged 3 to 6 days, cardioplegic arrest (CPA) using crystalloid cold cardioplegia with aortic cross clamp (AXC: 60 min, n = 15) and continuous deep hypothermic perfusion (DHP) at 15 degrees C without AXC (n = 15) were compared. The hearts were divided into two subgroups: intact hearts (n = 18) and with preceding 40 min warm ischemia (stressed hearts, n = 22). In the intact hearts, there were no significant differences between the CPA and DHP groups in left ventricular function, myocardial water content, and myocardial mitochondrial score after reperfusion. In the stressed hearts, recovery of cardiac output and left ventricular work was significantly higher in the DHP group than in the CPA group. The post-reperfusion myocardial mitochondrial score was significantly better in the DHP group than in the CPA group. These results suggest that non-AXC DHP may be advantageous in the setting of stressed hearts with preceding ischemic injury where conventional CPA cannot provide adequate myocardial protection.
To elucidate factors influencing responses of right ventricular systolic function to exercise stress, we evaluated the right ventricular ejection fraction and peak ejection rate with two different loading conditions, atrial septal defect and mitral stenosis, at rest and during exercise by means of gated equilibrium blood pool radionuclide ventriculography. In both atrial septal defect and mitral stenosis, strong correlations between changes in the right ventricular ejection fraction with exercise and pulmonary vascular resistance at rest (r = -0.97, p < 0.001; r = -0.86, p < 0.005: respectively) were found. Significant correlations between changes in the right ventricular peak ejection rate with exercise and pulmonary vascular resistance at rest (r = -0.85, p < 0.05; r = -0.75, p < 0.01: respectively) were found in atrial septal defect and mitral stenosis. Both the right ventricular ejection fraction and peak ejection rate were lower during exercise than at rest when pulmonary vascular resistance at rest was more than 200 dynes.sec.cm-5.m2 in both atrial septal defect and mitral stenosis. In conclusion, right ventricular systolic function responding to exercise stress was influenced by the pulmonary vascular resistance in both atrial septal defect and mitral stenosis.
Thirty-six isolated blood-perfused hearts from newborn rabbits (age range, birth to 2 days) were subjected to 2 hours of cold global ischemia (15 degrees C), with an initial infusion of cold crystalloid cardioplegic solution, followed by 30 minutes of reperfusion (37 degrees C). The hearts were divided into two groups: those reperfused with whole blood (n = 18) and those reperfused with leukocyte-depleted blood (n = 18) obtained by the passage of blood through a leukocyte removal filter. At 30 minutes of reperfusion, the group of hearts reperfused with leukocyte-depleted blood showed significantly higher percentages of recovery in terms of the left ventricular developed pressure, the maximum rate of increase of left ventricular pressure, the rate pressure product, coronary sinus flow, and the adenosine triphosphate content in myocardium than did the group of hearts reperfused with whole blood. The hearts reperfused with leukocyte-depleted blood also showed significantly lower levels of malondialdehyde, chemiluminescence in the coronary sinus effluent, and counts of intracapillary neutrophils in myocardium than did the group of hearts reperfused with whole blood. The ultrastructural semiquantitative assessment in the myocardium showed that the mitochondrial and endothelial cell damages after 30 minutes of reperfusion were significantly less in the hearts reperfused with leukocyte-depleted blood than those in the hearts reperfused with whole blood.(ABSTRACT TRUNCATED AT 250 WORDS)
T cell subsets involved in rejection of xenografts were analyzed using a rat to mouse cardiac xenotransplant model. Proliferating response and interleulin-2 (IL-2) production in recipients' spleen cells were almost completely abrogated by elimination of L3T4+ T cells, but not by elimination of Lyt2.1+ T cells. Cytotoxic T lymphocyte (CTL) activities were mediated by both L3T4+ and Lyt2.1+ T cells with the help of IL-2-producing L3T4+ T cells. Administration of anti-L3T4 monoclonal antibody (mAb) into recipient mice resulted in a significant prolongation of graft survival (mean graft survival was 29.2 days). Moreover, anti-L3T4 mAb treatment plus thymectomy led to indefinite graft survival. Anti-rat endothelial cell (EC) antibody production in the grafted mice was remarkably suppressed by anti-L3T4 mAb treatment. In contrast, Lyt2.1 mAb treatment did not prolong the graft survival and did not suppress anti-EC antibody production. These results indicated the absolute requirement of L3T4+ T cells in the rejection of rat to mouse cardiac xenografts.