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Biomedical subjects

H Mizuhara

Publications and source records attributed to H Mizuhara.

At least 19 recordsLinked to original sources

Evaluation of a compressive-type skeletal muscle pump for cardiac assistance.

BACKGROUND: Recent investigations have focused on using the latissimus dorsi muscle for cardiac assistance. Although cardiomyoplasty has been applied clinically, other procedures remain experimental, but promising, modes of cardiac assistance. We assessed the latissimus dorsi muscle as an in situ energy source for circulatory assist devices. METHODS: We developed a pneumatic chamber as a compressive-type muscle actuator. The chamber was implanted under the latissimus dorsi muscle and converted contractile power into pneumatic pressure. The effect of chamber position and size and the influence on muscle blood flow were examined. After muscle conditioning, the pump performance of a circulatory assist device driven by the chamber was evaluated. RESULTS: The chamber functioned better when placed in the proximal position of the latissimus dorsi muscle. The size affected the generated pneumatic pressure, and the higher resting pressure of the chamber reduced the muscle blood flow. The maximum stroke work of the circulatory assist device was greater than that of the right ventricle but less than that of the left ventricle. The chamber could drive the circulatory assist device against the systemic range of afterload in which a high preload was available. Long-term adhesion surrounding the chamber reduced the pressure generation capability. CONCLUSIONS: The compressive-type muscle actuator using the latissimus dorsi muscle generated acceptable hemodynamic work for right ventricular bypass or aortic counterpulsation.

Animals

Involvement of intrasinusoidal hemostasis in the development of concanavalin A-induced hepatic injury in mice.

Concanavalin A (Con A) stimulation induces T-cell activation-associated hepatic injury. This study is designed to show the involvement of microcirculatory disturbance in the pathogenesis. Con A administration led to prominent intrasinusoidal hemostasis, which consisted of erythrocyte agglutination, lymphocyte/neutrophil sticking to endothelial cells, and platelet aggregation and degranulation, resulting in a marked decrease in the intrahepatic blood flow and elevation of portal perfusion pressure. After hemostasis, confluent hepatic necrosis occurred within the congested area of liver parenchyma. Reduction in the extent of hemostasis by the treatment with heparin (thrombin inhibitor) or cyproheptadine (serotonin inhibitor) decreased hepatic injury. Pretreatment with either anti-tumor necrosis factor alfa (TNF-alpha) or anti-interferon gamma (IFN-gamma) monoclonal antibody (MAb) moderately decreased hemostasis and hepatic injury, whereas combined use of two MAbs almost perfectly protected mice from these disorders. Complete obliteration of hemostasis and hepatic injury was also accomplished by the pretreatment with FK506 which suppressed TNF-alpha and IFN-gamma production. Intrasinusoidal accumulation of leukocytes and platelets was, however, not blocked by FK506, indicating that Con A activities other than the stimulation of cytokine production are responsible for this event. The administration of anti-CD3 MAb, a T-cell stimulant without agglutination activities, which elevated plasma cytokine levels in a comparable degree without inducing prominent leukocyte infiltration, did not induce hepatic congestion and injury. These findings indicate that the agglutination activities of Con A and T-cell activation mediated TNF-alpha/IFN-gamma production are both required for the induction of intrasinusoidal hemostasis, which is indispensable for the development of hepatic injury.

Animals

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.

Alanine Transaminase

[Clinical and bacteriological studies on panipenem/betamipron in pediatrics. Kanagawa Research Group for Infectious Diseases of Children].

Following its introduction into the market, PAPM/BP (panipenem/betamipron) was clinically studied in 188 evaluable cases out of 207 cases primarily of respiratory infectious diseases treated at the pediatric departments of 15 hospitals. In the clinical evaluation, the drug proved effective in three of three cases of sepsis; three of three cases of suppurative meningitis; nine of ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63 cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of phyothorax, all of which are respiratory infectious diseases; one of one case of secondary infection of a chronic respiratory disease; and two of two cases of lymphadenitis, which is a disease of the soft dermal structure. The overall efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram-positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31 strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes. Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae (88.2%), three of four strains of M. catarrhalis, and two of two strains of K. pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23 strains of S. pneumoniae that were examined, penicillin-resistant strains accounted for 56.5%, showing an elimination rate of 100%. No serious adverse effects were observed, and the incidence of adverse effects was 1.45%. As for abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case (0.51%). These results suggest that PAMP/BP could be considered the first choice in the treatment of infectious diseases in pediatrics, due to its effectiveness and high level of safety.

Adolescent

Critical involvement of interferon gamma in the pathogenesis of T-cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation and an acute hepatitis in mice. This study investigated the role of interferon gamma (IFN-gamma) in the pathogenesis of this hepatitis model. Striking increases in the plasma levels of various cytokines, including tumor necrosis factor (TNF), interleukin-2 (IL-2), and IFN-gamma, were detected before the increase in plasma aminotransferase levels induced by Con A injection. TNF levels peaked within 2 hours, whereas IFN-gamma levels peaked at 6 hours after Con A injection. In contrast to a sharp peak of TNF levels, high IFN-gamma levels were detected for a more prolonged period. Passive immunization with anti-IFN-gamma monoclonal antibody (MAb) conferred a dose-dependent protection against liver injury in this model. This protection was observed when anti-IFN-gamma MAb was administered at least 30 minutes before Con A injection but not when given 1 hour after Con A injection. The protection from Con A-induced hepatitis was also induced by administration of rIL-6 before Con A injection. rIL-6 treatment induced significant albeit incomplete inhibition of IFN-gamma and TNF production, whereas this regimen did not affect IL-2 production. Despite striking protective effects of rIL-6 or anti-IFN-gamma MAb, comparable levels of cellular (both T cell and polymorphonuclear cell) infiltration were detected in liver sections from animals untreated, or treated with either rIL-6 or anti-IFN-gamma MAb. Moreover, electron microscopic examination showed that infiltrating T cells exhibited a blastoid appearance in all groups. These results indicate that IFN-gamma plays a critical role in the development of Con A-induced acute hepatitis and suggest that IL-6 administration can regulate the manifestation of hepatitis through mechanisms including the reduced production of inflammatory cytokines such as IFN-gamma.

Animals

[Surgical treatment of congenital aortic stenosis by aortoseptal approach].

Between 1975 and 1994, six patients under 15 years old with congenital aortic stenosis underwent relief of left ventricular outflow tract obstruction (LVOTO) by aortoseptal approach. Although we got satisfactory relief of LVOTO in all patients, there were two late deaths. In one patient with residual ventricular septal defect (VSD), intractable ventricular arrhythmia developed 12 years postoperatively. Although the residual VSD closure was performed, the patient died of the arrhythmia. The another one who was the youngest 4-year-old boy suddenly died 4 months postoperatively. The detail about his death was unknown, but we presumed ischemic heart attack as the cause of his death. In 3 of remaining survived 4 patients, we encountered a few complications. They were right ventricular outflow obstruction, coronary artery injury and conduction system injury. All complications and problems we encountered in this series were related to the incision and the reconstruction of aortoseptal approach. In conclusion, the aortoseptal approach is effective technique for relief of LVOTO, but on the other hand it is invasive and not so safe operation. So we should be cautious about these complications and problems.

Adolescent

T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6.

This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.

Animals

[Extended aortic arch anastomosis for coarctation of the aorta and interruption of the aortic arch in early infancy].

We performed extended aortic arch anastomosis, which was so called EAA procedure, for Coarctation of the Aorta (CoA) with hypoplastic aortic arch (HAA) and interruption of the aortic arch (IAA) in 17 infants under three months of age. The proximal anastomosis site was extended into ascending aorta in order that we could make non-obstructive pathway of systemic flow. During anastomosis, we employed mild systemic hypothermia and topical cooling of head and lumber lesion. Satisfactory anastomoses were performed without any neurological and renal complications except one case. Postoperative Doppler echographic evaluation revealed that the mean peak flow velocities at anastomotic site were under 2.0 m/sec at 1 and 2 years after surgery. We concluded that EAA procedure was useful for CoA with HAA and IAA in early infancy.

Anastomosis, Surgical

[Relief of pulmonary venous obstruction for asplenia syndrome associated with total anomalous pulmonary venous connection in neonates and infants].

Five patients of asplenia syndrome with pulmonary venous obstruction underwent TAPVC repair in the period of neonates (4 patients) and infant (1 patient). They also underwent associated procedures to reconstruct or adjust pulmonary blood flow (systemic-pulmonary shunts in 2, bilateral PDA banding in 1, pulmonary artery banding in 1) in accordance with individual anatomy of the pulmonary arteries. In four of them, they required subsequent surgical procedures for reduction of pulmonary blood flow because of intractable heart failure due to increase in pulmonary blood flow mostly at the early postoperative period. The increasing pulmonary blood flow was successfully controlled by early reduction procedures (1 patient: extrathoracically adjustable PA banding, 1 patient: tightening of shunt graft) in two patients. However, one patient died in the early postoperative period because of moribund preoperative condition. The remaining one patient underwent PA banding three month after the first operation, but died in late period due to heart failure. These results suggest that the adjustment of pulmonary blood flow is critically important for management of the patients of asplenia syndrome with TAPVC after the operation, and early decision of PA band re-adjustment (or other procedures to decrease pulmonary blood flow) is mandatory to improve the results.

Abnormalities, Multiple

Effects of adenosine A2 receptor agonists on the excitation of capsaicin-sensitive afferent sensory nerves in airway tissues.

We examined the effects of adenosine analogues on the asthmatic reactions induced by the stimulation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of adenosine A2 receptor agonists, 5'-(N-ethylcarboxamido)-adenosine (NECA) and 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamido-adenos ine (CGS 21,680), dose dependently inhibited capsaicin-induced guinea-pig bronchoconstriction (1-1000 nmol kg-1), whereas i.v. administration of the adenosine A1 receptor agonist, N6-cyclo-hexyladenosine (CHA), did not affect it (1000 nmol kg-1). Intratracheal injection of NECA (0.05-5 nmol site-1) and CGS 21,680 (0.05-5 nmol site-1) also reduced capsaicin-induced constriction in a dose-dependent manner. However, NECA (1000 nmol kg-1) failed to inhibit substance P-induced guinea-pig bronchoconstriction. NECA (1-1000 nmol kg-1) dose-dependently inhibited cigarette smoke-induced rat tracheal plasma extravasation, but not substance P-induced reaction. NECA (0.1-10 microM) and CGS 21,680 (10 microM) significantly blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea-pig lung, whereas CHA (10 microM) had no effect. This evidence suggests that adenosine A2 receptors modulate negatively the excitation of capsaicin-sensitive afferent sensory nerves and substance P release from their endings in airway tissues.

Adenosine

Type II collagen-induced murine arthritis: induction of arthritis depends on antigen-presenting cell function as well as susceptibility of host to an anticollagen immune response.

Two sets of ((resistant x susceptible) F1----parent) and (parent----F1) chimeric mice were prepared. In the chimeric combinations involving BALB/c and DBA/1 mice, all (F1----F1) chimeras developed arthritis as well as potent anticollagen responses after immunization with collagen, whereas all (F1----BALB/c) and (BALB/c----F1) chimeras induced neither arthritis nor immune responses. This type of F1 T cells could be activated with APC from DBA/1 but not from BALB/c mice. Thus, the failure of the [F1 in equilibrium with BALB/c] chimeras to mount anticollagen responses was due to a defect at the APC level. Another arthritis-resistant strain, C57BL/6, exhibited adequate APC function, but reduced T cell responsiveness, representing an intermediate responder. In the chimeric combinations involving C57BL/6 and DBA/1 mice, (F1----F1) and (C57BL/6----C57BL/6) chimeras developed very high and very low incidence of arthritis, respectively. (C57BL/6----F1) chimeras developed an appreciable incidence of arthritis under conditions in which this group of chimeras generated intermediate levels of anticollagen responses. In contrast, (F1----C57BL/6) chimeras developed low incidence of disease despite induction of strong responses. Moreover, cells from collagen-immunized (F1----C57BL/6) chimeras, when transferred into T cell-depleted B cell mice of F1 or C57BL/6 strain, produced comparable immune responses in both groups but induced much more severe arthritis in F1 than in C57BL/6 recipients. These results indicate that: i) two types of arthritis-resistant strains can be identified, each of which has anticollagen APC defect as a low responder and reduced T cell responsiveness as an intermediate responder and ii) a discrepancy between the degree of anticollagen responses and clinical arthritis is attributed to the differential susceptibility to anticollagen immune responses.

Animals

[Postoperative management in neonate after open cardiac surgery].

Recent advances in diagnostic method and preoperative care have allowed us to perform surgical repair in neonate. Important to the successful outcome of open cardiac surgery in neonate is cautious management in postoperative period. So we investigated the hemodynamics in the first 72 hours following open heart surgery for TAPVC, TGA and PAIVS. The hemodynamics in acute period are different according to patient age. Especially, early neonates under 14 days present low systemic blood pressure and high central venous pressure. So we must manage them according to their hemodynamic characteristics.

Blood Pressure

[An experience of rapid, two-stage arterial switch operation for transposition of the great arteries and intact ventricular septum beyond the neonatal period].

A 2-month-old girl with transposition of the great arteries and intact ventricular septum was successfully repaired by rapid, two-stage arterial switch operation. Balloon atrioseptostomy and ligation of the ductus arteriosus was done elsewhere on 14th and 29th day after birth. On her first admission to our hospital at 2 months of age, left ventricular-right ventricular pressure ratio (LVp/RVp) was almost 0.5 and left ventricular posterior wall thickness (LVPWT) by echo cardiography was 3.5 mm. Because of these date, we selected rapid, two-stage arterial switch operation. On 74 days, the first-stage preparatory operation (pulmonary arterial banding and right modified Blalock-Taussig shunt) was undergone with the resultant LVp/RVp of 0.97. During a few days after the first-stage operation, left ventricular ejection fraction (LVEF) by echocardiography was reduced to nearly 30%. But after this phase left ventricular function recovered rapidly and LVp/RVp, LVPWT and LVEF was 1.18, 6.3 mm and 66% on the 7th day. On the 9th day, the second-stage arterial switch operation was undergone as usual as in neonatal period without hard adhesion. Her postoperative course was uneventful.

Cardiac Surgical Procedures

[Fundamental study on levofloxacin in the field of obstetrics and gynecology].

We performed a fundamental study on levofloxacin (LVFX, DR-3355), a new synthetic antimicrobial agent, in the field of obstetrics and gynecology. Concentrations in serum and intrapelvic genital organs (various regions in the uterus, ovary and oviduct) were determined following single oral administration. The transport of LVFX into genital tissues was found to be good, with the tissue levels of 0.64-2.13 micrograms/g after oral administration of 100 mg and 0.77-4.86 micrograms/g after administration of 200 mg. These tissue levels of LVFX were higher than those in serum and exceeded the MIC90 values against most causative organisms isolated from the lesions of obstetric and gynecological infections. These data indicate that LVFX should be useful in the field of obstetrics and gynecology.

Administration, Oral

[Absent pulmonary valve syndrome: surgical approach for the worst group included in symptomatic neonates].

Absent pulmonary valve syndrome (APVS) has been classified to two groups. One is severely symptomatic infant group and the other no or slightly symptomatic. But we think that severely symptomatic group should be divided into the worst neonate group and the other. This worst group, that contains neonates who can not be weaned from the respirator after surgical intervention including corrective surgery because of severe bronchomalacia and/or peripheral bronchial stenosis, has already severe respiratory distress and needs ventilatory support while high pulmonary vascular resistance is maintained. Three patients of this group were operated on at 2, 13 and 2 days of age and there were two late hospital death. The last patient underwent ligation of main pulmonary artery (mPA) and left modified Blalock-Taussig shunt (MBTS) with phi 4 mm polytetrafluoroethylene graft and was extubated on the next day. The management of this group should aim at controlling the pulmonary regurgitation as early as possible to decrease the progressive airway obstruction and minimize pulmonary tissue damage. Ligation of mPA and MBTS can be performed without cardiopulmonary bypass and eliminates pulmonary regurgitation and controls the pulmonary blood flow less than the total correction. In the point of protecting bronchi and lung and reducing the risk of surgical intervention in critical neonatal period, ligation of mPA and MBTS can be safer and more effective operation for the worst APVS neonate than the total correction with insertion of artificial valve.

Blood Vessel Prosthesis

[Successful treatment by using a pedicled omental flap for mediastinal infection in the presence of a external valved conduit].

Mediastinal infection is one of serve and fatal complications after cardiac surgery, especially in the presence of an artificial graft. A case of successful treatment by using a pedicled omental flap for mediastinal infection in the presence of an external valved conduit is reported. a 10-year-old girl who had implanted the 12 mm porcine valved conduit for truncus arteriosus at age 9 months, underwent replacement of the old conduit with a 18 mm valved conduit. On the 9th postoperative day, as soon as mediastinal infection was proved by positive culture of the drainage from the chest tube, a reoperation was performed to debride and irrigate the mediastinum. Irrigation with povidone-iodine and antibiotics was continued for 3 weeks until improvement of CRP levels and negative drainage cultures. Then the heart and the valved conduit were wrapped with the pedicled omental flap and the skin was closed. She was without any evidence of infection for 3 months after operation. Use of a pedicled omental flap might be an effective method for treatment of mediastinal infection in the presence of an external conduit.

Blood Vessel Prosthesis