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Biomedical subjects

Motonobu Nishimura

Publications and source records attributed to Motonobu Nishimura.

At least 19 recordsLinked to original sources

Importance of luxury flow for critically ill patients receiving a left ventricular assist system.

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m2 had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m2 or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.

Cardiac Output↗

A case of "pure" preeclampsia with nephrotic syndrome before 15 weeks of gestation in a patient whose renal biopsy showed glomerular capillary endotheliosis.

A 35-year-old Japanese woman for whom a previous health checkup showed normal blood pressure and urinalysis results without serological abnormalities developed nephrotic syndrome with severe hypertension at 15 gestational weeks. The renal biopsy performed at 17 weeks of gestation showed severe glomerular capillary endotheliosis. By means of electron microscopy, no electron-dense deposits were observed in glomeruli, and foot-process arrangement was normal. Histological findings indicated the patient's glomerular damage was caused by the mechanisms of preeclampsia. The patient underwent an elective abortion at 18 weeks of gestation. Clinical abnormalities vanished completely within 3 months after the elective abortion, which provided additional evidence that proteinuria and hypertension were caused purely by pregnancy. In general, the term preeclampsia refers to new onset of hypertension and proteinuria after 20 weeks of gestation. When proteinuria or hypertension is newly observed before 20 weeks of gestation, they are practically associated with triploidy, trophoblastic disease, or antiphospholipid syndrome. However, our case was not associated with them. Therefore, we called this case "pure" preeclampsia. We confirm the notion for the first time that preeclampsia associated with glomerular capillary endotheliosis can occur before 20 weeks of gestation. In addition, this report describes the earliest onset of preeclampsia compared with previously published reports. We also discuss causes of preeclampsia in early gestation and refer to the issue of the application of renal biopsies during pregnancy.

Abortion, Induced↗

[Successful salvage of a patient with cardiac arrest caused by multiple pulmonary emboli and lung abscesses due to infective endocarditis of the tricuspid valve: a case report].

A 28-year-old female developed infective endocarditis in the tricuspid valve and multiple lung abscesses due to septic pulmonary emboli early after intensive therapy for ulcerative colitis. The pathogen was methicillin-resistant Staphylococcus aureus. Usual antibiotic agents and linezolid were administered. Three weeks later, she fell into cardiopulmonary arrest due to further pulmonary emboli and required mechanical circulatory assist. Fatal brain damage was suggested at first. Two days later, she fully regained consciousness and underwent tricuspid valve replacement using mechanical valve and extirpation of septic pulmonary embolus. Mechanical circulatory assist was discontinued on the next day. After strenuous administration of linezolid and other drugs for 9 weeks, she was discharged from hospital on foot. We believe that early surgical intervention should be considered in patients with infective endocarditis in the right heart and subsequent septic pulmonary emboli. Linezolid was very useful in this patient.

Acetamides↗

Paraplegia and paraparesis after descending thoracic aortic aneurysm repair: a risk factor analysis.

BACKGROUND: The risk factors of paraplegia and paraparesis (P/P) after surgical repair of descending thoracic aortic aneurysm (TAA) are controversial. PATIENTS AND METHODS: Seventy five patients underwent surgical repair of descending TAA from 2001 through 2002. The mean age was 64.2+/-5.2 years old (range; 26-81) and 58 patients (77.3%) are male. There were 47 patients (62.7%) with nondissecting aortic aneurysm and 28 patients (37.3%) with chronic dissecting aortic aneurysm. Emergent operation was performed in 13 cases (17.3%). Retrospective analysis based on data of these 75 patients was performed to determine the risk factors of P/P. RESULTS: 30-days hospital mortality was 2.7%. The overall incidence of P/P was 12.0% (9/75) overall (immediate paraplegia; 4 (5.3%), delayed paraplegia; 1 (1.3%), immediate paraparesis; 3 (4.0%), delayed paraparesis; 1 (1.3%)). Logistic regression analysis revealed that predictive factors of the development of P/P were; cases in which the distal part (below Th9) of the descending thoracic aorta was included in the extent of graft replacement (P=0.020; odds ratio (OR), 7.981) and nondissecting aneurysm (P=0.029; OR, 12.109). CONCLUSION: There was an increased risk of P/P after descending TAA repair in cases in which the extent of graft replacement included below the Th9 or in cases with nondissecting aortic aneurysm.

Adult↗

Japanese multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system.

Implantable left ventricular assist device systems (LVAS) are increasingly being used to bridge patients to heart transplantation because of the limited number of available donor hearts. This prospective, multicenter trial was designed to evaluate the usefulness of the HeartMate vented electric (VE) LVAS as a bridge to transplantation in Japan. Between November 2001 and June 2003, six patients with end-stage heart failure [New York Heart Association (NYHA) class IV] were supported with the LVAS and five of the six were able to implement the evaluation (one dropped out). The five were men with an average age of 38.6 years and were supported for 2390 cumulative days (6.6 years). Average preimplant cardiac index improved from 1.93 l/min/m(2) to a 3.79 l/min/m(2) VAD flow index at the end of the clinical trial. All five patients improved to NYHA class I or II, survived more than 1 year, and one patient was discharged from the hospital. Mean LVAS support duration was 478 days (range 390-575 days) and four patients remain supported. One patient died from cardiac failure and sepsis. Device-related complications included: infections (four patients), thromboembolism (one patient), hemolysis (two patients), and repeat operation for bleeding (two patients). There was one case of inflow valve incompetence and two pump motor malfunctions. We conclude that the LVAS can effectively support patients as they await cardiac transplantation and offers improvement to the patient's quality of life.

Adult↗

Successful bridge to resynchronization therapy with a left ventricular assist system in a patient with idiopathic dilated cardiomyopathy.

Implantation of a left ventricular assist system (LVAS) in patients with idiopathic dilated cardiomyopathy (DCM) may improve cardiac function and allow explantation of the device. Generally, an ejection fraction of more than 40% is considered necessary for successful weaning from an LVAS, but less than 10% of DCM patients with an LVAS can achieve such a significant recovery of cardiac function. Cardiac resynchronization therapy, or atrial-synchronized biventricular pacing, has been found to treat congestive heart failure and ventricular dyssynchrony effectively. Here we report on a patient with an LVAS, in whom enough functional recovery could be obtained with resynchronization therapy for the device to be explanted successfully. A 32-year-old man was implanted with a Toyobo-NCVC paracorporeal LVAS to treat his intractable heart failure caused by idiopathic dilated cardiomyopathy. While on the LVAS for 8 months, his cardiac function recovered to some extent. The ejection fraction of his left ventricle (LVEF) improved from 9% to 41%. He chose explantation of the device rather than heart transplantation. Because he occasionally showed a wide QRS pattern on his ECG, epicardial biventricular pacing leads as well as a biventricular pacemaker were implanted on LVAS explantation surgery. An echocardiogram 2 weeks after explantation showed a marked difference in his LVEF by switching his biventricular pacing on and off (40% with biventricular pacing on and 29% with it off). Biventricular pacing may help recovery of cardiac function in selected LVAS patients and contribute to the increase in bridge to recovery cases.

Adult↗

[Coronary artery bypass grafting in patients undergoing chronic hemodialysis: importance of wound healing and hypoproteinemia].

OBJECTIVES: Outcome of coronary artery bypass grafting (CABG) in patients undergoing chronic hemodialysis was studied. METHODS: Between January 1996 and August 2004, 49 consecutive hemodialysis patients [38 males and 11 females, mean age 60.0 years (range 47-74 years)] underwent CABG using cardiopulmonary bypass. Duration of hemodialysis was 5.2 years (range 1 month-21 years), and 32 patients were diabetics. Surgery was conducted on the emergency/urgency basis in 12 patients, and intraaortic balloon pumping was placed in 7. Left ventricular ejection fraction was 57.7 +/- 16.3% (range 27-84%). Nine patients underwent concomitant valve surgery. CABG was performed under hypothermic cardiopulmonary bypass and ventricular fibrillation except in one patient, and intraoperative hemodialysis was also performed. Continuous hemodiafiltration was used in the early period after surgery. RESULTS: Number of bypass grafts was 3.0 +/- 1.0 (range 1-6), and the unilateral internal thoracic artery was used in 29 patients. Operation time, cardiopulmonary bypass time, and aorta clamp time were 313 +/- 87, 145 +/- 63, and 49 +/- 43 min, respectively. Diffuse pericardial adhesion was present in five patients. Severely atheromatous ascending aorta precluded manipulation in seven patients. Although the 30-day mortality was 2.0% (one case), all in-hospital mortality over 9 months was 14.3% (seven cases). The morbid events were mediastinitis in seven cases, reexploration for hemorrhage in seven, pneumonia in two, abdominal complication in three, and stroke in one. Delayed onset mediastinitis was common. Risk factors for death were mediastinitis and serum albumin levels < 3.5 g/dl (both p < 0.05), both of which were wound healing-related factors. CONCLUSIONS: CABG in hemodialysis patients carries a high risk. Patients with hypoalbuminemia appear to require special consideration.

Aged↗

[Active infective endocarditis remaining latent for six weeks after discontinuation of antibiotic therapy: a case report].

A 75-year-old man was treated for 4 weeks with penicillin administration for infective endocarditis in the mitral valve caused by Enterococcus faecalis. The infection recurred, so he received penicillin administration for a further 6 weeks. He remained afebrile and all laboratory examinations were within normal limits for 6 weeks after the antibiotic treatment was discontinued, but the vegetation remained large and highly mobile. Since the onset, possible embolic episodes had occurred three times. He underwent mitral valve repair with annuloplasty. Although the infection appeared to have healed by antibiotic therapy, resected tissue was strongly positive for Enterococcus faecalis. This case suggests that surgery should be aggressively considered if the vegetation does not shrink markedly.

Aged↗

Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response.

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce post-bypass systemic inflammatory response. Peroxynitrite (ONOO-) is a potent oxidant formed by a rapid reaction between nitric oxide (NO) and superoxide anion. We hypothesized that ONOO- plays a role in the development of post-bypass systemic inflammatory response and examined the efficacy of ONOO- scavenger in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 min of CPB (100 ml/kg per min, 34 degrees C). Group-P (n = 10) received 50 mg/kg of ONOO- scavenger, quercetin, intraperitoneally 24 h before the initiation of CPB, and Group-C (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma nitrate+nitrite (NOx), the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr: an indicator of ONOO- formation), interleukin (IL)-6, IL-8, and respiratory index (RI). There were significant differences in %NO2-Tyr between the groups both at CPB termination (Group-P vs C; 0.26+/-0.07 vs 0.55+/-0.11%, P < 0.01) and 3 h after CPB termination (0.65+/-0.14 vs 1.46+/-0.25%, P < 0.01); whereas there were no significant differences in NOx between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6+/-4.3 vs 32.7+/-4.1 micromol/l, (3 h after CPB termination) Group-P vs C; 47.8+/-4.9 vs 51.7+/-5.3 micromol/l). Group-P showed significantly lower plasma IL-6 (176.8+/-44.3 vs 302.4+/-78.1 pg/ml, P < 0.01), IL-8 (9.45+/-1.78 vs 16.42+/-2.53 ng/ml, P < 0.01) and RI (1.07+/-0.19 vs 1.54+/-0.25, P < 0.01) 3 h after CPB termination, though there were no significant differences between the groups at CPB termination. CONCLUSIONS: These results suggest that ONOO- plays a crucial role in the development of post-bypass systemic inflammatory response and the pretreatment with quercetin has a potential benefit to avoid deleterious effects of ONOO-.

Animals↗

Lethal thrombus in the carotid artery during operation for acute aortic dissection with cerebral malperfusion.

A drowsy patient with acute type A aortic dissection and cerebral malperfusion required emergency operation. Because the right carotid artery was totally obstructed, cerebral perfusion was first restored by cannulating it and the left femoral artery before midline sternotomy. However, a long fresh thrombus was found flowing backward from the obstructed carotid artery. This thrombus was removed, and both arteries were connected through a Y-shaped extracorporeal circulation circuit to reperfuse the brain. During the subsequent aortic procedure, both arteries were used for arterial inflow. Such thrombi can cause grave postoperative neurologic dysfunction. Carotid artery cannulation is mandatory in such cases.

Acute Disease↗

Early result of heart transplantation in Japan: Osaka University experience.

Since the new organ transplantation law was established in 1997, 17 heart transplantations have been performed in Japan, 7 of which were carried out at Osaka University Hospital. Recipient diagnosis was dilated cardiomyopathy in 2, dilated phase of hypertrophic cardiomyopathy in 4, and post-myocarditis cardiomyopathy in 1. Ages ranged from 8 to 49 years with a mean of 35.3 years. Five patients were bridged with a left ventricular assist device. The waiting period was 182-977 days (mean, 643 days). There was no early or late death during follow-up of 1-4.8 years. Under a standard triple-drug regimen using mycophenolate, there were 3 rejection episodes greater than grade 3 in 2 patients, and humoral rejection requiring plasmapheresis in one. A young boy whose donor was a hemodynamically compromised adult developed neurological sequelae after resuscitation following ventricular tachycardia. All patients were discharged and went back to work or their regular daily life. Although the donor shortage is still severe in Japan, the resumption of heart transplantation has been satisfactory, and left ventricular assist devices have played a crucial role.

Adult↗

[Aortic root replacement using an allograft for active infective endocarditis with periannular abscess: single center experience].

OBJECTIVES: Results of aortic root replacement using an allograft for active infective endocarditis in the aortic position and periannular abscess were studied. METHODS: Aortic root replacement using a cryopreserved aortic allograft was performed 13 times in 12 patients (9 men, 3 women, mean age 52.8 years) at Saitama Medical School. Allografts were obtained from the Tokyo University Tissue Bank. Infection affected the prosthetic valve in 6 patients and the native valve in 7. Causative organisms were Staphylococci in 7 patients, Streptococci in 2, and unknown in 4. New York Heart Association functional class was II in 2 patients, III in 3, and IV in 8. Six patients required inotropic support. Four were mechanically ventilated. Two were in a state of profound shock. Four had multiple organ failure. Surgery was conducted under hypothermic cardiopulmonary bypass and cardioplegic arrest. Allograft was sewn into place by monofilament continuous sutures. Carrel patch technique was used for coronary artery reconstruction. Five patients underwent concomitant procedures (replacement of the ascending aorta in 2 patients, coronary artery bypass grafting in 1, mitral valve repair in 1, pulmonary artery reconstruction in 1). RESULTS: Duration of surgery, cardiopulmonary bypass, and aortic clamping were 507 +/- 154, 307 +/- 111, and 189 +/- 49 min, respectively. Two patients required intraaortic balloon pumping, and one required percutaneous cardiopulmonary support. Two patients in a state of shock died(hospital mortality: 15.4%). Duration of mechanical ventilation was 2.9 +/- 3.7 days. Intensive care unit stay was 4.6 +/- 5.5 days, and hospital stay was 61 +/- 26 days. One patient died of cancer 18 months later. One patient required reoperation 11 months later. Including operative death cases, cumulative survival at 2 years was 66.5% and freedom from cardiac events was 72.7%. CONCLUSIONS: Aortic root replacement with an allograft yielded acceptable clinical results.

Abscess↗

Mice lacking Smad3 are protected against streptozotocin-induced diabetic glomerulopathy.

Transforming growth factor-beta (TGF-beta) has been implicated in the development of diabetic glomerulopathy. In order to evaluate a role of Smad3, one of the major signaling molecules downstream of TGF-beta, in the pathogenesis of diabetic glomerulopathy, Smad3-null mice were made diabetic with streptozotocin injection and analyzed 4 weeks after induction of diabetes. Electron microscopy revealed that the thickness of glomerular basement membrane (GBM) in wild-type diabetic mice was significantly higher than that in non-diabetic mice, whereas no appreciable GBM thickening was found in Smad3-null diabetic mice. Urinary albumin excretion was dramatically increased in wild-type diabetic mice, whereas Smad3-null diabetic mice did not show any overt albuminuria. Northern blotting revealed that mRNA levels of fibronectin and alpha 3 chain of type IV collagen (alpha 3Col4) in renal cortex of wild-type diabetic mice were approximately twice as much as those of non-diabetic mice, whereas their mRNA levels were not increased in Smad3-null diabetic mice. Real-time polymerase chain reaction (PCR) also confirmed diabetes-induced upregulation of fibronectin and alpha 3Col4 in glomeruli of wild-type mice. Glomerular expression of TGF-beta 1, as assessed by real-time PCR, was enhanced to a similar degree in wild-type and smad3-null diabetic mice, indicating that the observed differences between wild-type and Smad3-null mice are not attributable to difference in the expression of TGF-beta 1. These data clearly demonstrate a critical role of Smad3 in the early phase of diabetic glomerulopathy. This may be due at least partly to the present findings that diabetes-induced upregulation of fibronectin and alpha 3Col4 is dependent on Smad3 function.

Albuminuria↗

Successful treatment of Novacor pump pocket infection by omental transposition.

Device-related infection remains a major factor restricting the long-term use of left ventricular assist systems. Severe pocket infection is especially difficult to manage and removal of the device has been the only curative treatment in most cases. We report a case of a Novacor device pocket infection treated successfully with continuous local irrigation and transposition of omental flap. This procedure provides another option for the management of pocket infection, which is mandatory for destination therapy the permanent usage of LVAS for the purpose of circulatory supports in patients with end-stage heart failure, who are not indicated for heart transplantation.

Adult↗

Participation of caspase-3-like protease in necrotic cell death of myocardium during ischemia-reperfusion injury in rat hearts.

This experimental study was designed to determine if caspase-3-like protease is activated during a short period of ischemia - reperfusion (I-R) that did not induce apoptosis, and whether protease-3-protease inhibitor could prevent myocardial I-R injury, especially necrotic cell death. The subjects were 20 isolated rat hearts; 10 were pretreated for 20 min with 100 micromol/L of the protease-3-protease inhibitor, peptide antagonist Asp-Glu-Val-Asp-CHO (DEVD) (Group D), and compared with the 10 no-pretreated hearts (Group C). The hearts were then subjected to 20, 30, 45, and 60 min of normothermic global ischemia followed by 30 min of reperfusion. Caspase-3-like protease was significantly elevated after 45 min and 60 min in ischemic hearts. Group D had reduced levels of caspase-3-like protease activity after 45 min and 60 min (302+/-58%, 378+/-69% of pre-ischemic control, respectively), as compared with Group C (542+/-74%, 689+/-85%, respectively) (p<0.05, p<0.05, respectively). Histological analysis also demonstrated a decrease in cellular damage in Group D, as the count ratio of necrotic cells with total cardiomyocytes was 38%, as compared with 78% in the control group (p<0.05). Caspase-3-like protease participated in I-R injury in rat hearts and inhibition of this protease resulted in a reduction of necrotic cell death.

Animals↗

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation.

BACKGROUND: In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS: Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS: Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS: Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Adult↗