Combined use of deoxyspergualin and FK 506 for temporary circulatory assist.
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Animals↗
Biomedical subjects
M Nonoyama
Publications and source records attributed to M Nonoyama.
[Management of patient with acute myocardial infarction due to left main trunk obstruction].
Between April 1995 and March 1998, we experienced 13 cases of Acute Myocardial Infarction due to Left Main Trunk Obstruction (LMT-AMI). Two cases died before emergent intervention. Eight cases underwent emergent intervention (Plain Old Balloon Angioplasty (POBA) in five cases, Stenting in 3 cases); 2 cases died of acute occlusion of POBA site, 1 case survived by only POBA, and the other 5 cases underwent following Coronary Artery Bypass Grafting (CABG). 3 cases underwent only CABG with stable hemodynamics condition by Intraaortic balloon pumping (IABP) support. In a result, seven of eight CABG cases survived. Emergent stenting made the hemodynamics before CABG stable, and six-month's follow up angiogram showed occluded bypass grafts and patent stented sites in two of three cases. The combination therapy of emergent stenting and CABG will have to be evaluated in future.
Adult↗
Histologic findings and rejection therapies for acute rejection in Japanese patients receiving heart transplants overseas.
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Adolescent↗
Serial hemodynamic study after aortic valve replacement in patients with narrow aortic roots.
BACKGROUND AND AIMS OF THE STUDY: The purpose of this study was to evaluate the hemodynamic performance after aortic valve replacement using different surgical options in small (19-mm diameter) annuli. METHODS: Postoperative hemodynamics were assessed in three groups according to the surgical method. A 19-mm St. Jude Medical (SJM) valve was used in nine patients (group A), a 19-mm SJM HP in nine patients (group B), and annular enlargement was performed in eight patients (group C). Echocardiography was performed and percent fraction shortening, peak pressure gradient, effective orifice area and left ventricular mass were measured. RESULTS: Postoperative peak systolic pressure gradient was decreased to 31.1+/-8.7 mmHg in group B, and to 22.3+/-11.7 mmHg in group C, but was 42.9+/-16.5 mmHg in group A (p <0.01). Percent fraction shortening and left ventricular mass index were improved in groups B and C, soon after surgery compared with group A (p <0.01). The effective orifice area significantly increased during exercise in group C, from 1.59 to 1.87 cm2 (p <0.01), but was not increased in groups A and B (N.S.). CONCLUSIONS: The small SJM HP provides a better hemodynamic performance than the standard 19 mm SJM. However, annular enlargement may be beneficial in patients with poor ejection fraction and severe ventricular hypertrophy.
Adult↗
Clinical assessment of prolonged myocardial preservation for patients with a severely dilated heart.
BACKGROUND: The purpose of this study was to compare the myocardial protective effect of histidine-tryptophan-potassium and glucose-insulin-potassium cardioplegic solutions in patients with a dilated heart (left ventricular diastolic diameter > 55 mm, left ventricular systolic diameter > 45 mm) associated with prolonged cross-clamp time (longer than 200 minutes). METHODS: We selected 20 patients with dilated hearts due to severe aortic regurgitation. Glucose-insulin-potassium cardioplegia was used in 11 patients and histidine-tryptophan-potassium cardioplegia was used in 9 patients. RESULTS: After operation, the cardiac index was significantly increased in the histidine-tryptophan-potassium group (p < 0.05). Postoperative percent fractional shortening was 13.4% +/- 3.1% in the glucose-insulin-potassium group and 23.6% +/- 2.6% in the histidine-tryptophan-potassium group (p < 0.05). Creatine kinase levels were significantly lower in the histidine-tryptophan-potassium group than that in the glucose-insulin-potassium group (p < 0.05). The incidence of ventricular arrhythmia (higher than Lown's grade 2) was lower in the histidine-tryptophan-potassium group. CONCLUSIONS: These data support the superiority of the histidine-tryptophan-potassium method over the glucose-insulin-potassium method for protection of the dilated heart during prolonged ischemia in open heart operations.
Aortic Valve Insufficiency↗
Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.
BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.
Adenoviridae↗
Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts: method and efficacy of adenovirus-mediated transduction.
OBJECTIVE: Allograft-targeted immunosuppressive gene therapy may inhibit recipient immune activation and provide an alternative to systemic immunosuppression. We studied the optimal technique and efficacy of intracoronary gene transfer of viral interleukin-10 and human transforming growth factor-beta 1 in a rabbit model of heterotopic heart transplantation. METHODS: Replication-defective adenoviral vectors were constructed, expressing viral interleukin-10 (AdSvIL10) or transforming growth factor-beta 1 (AdCMVTGF-beta 1). Intracoronary delivery of vectors was accomplished ex vivo by either bolus injection or slow infusion. The allografts were implanted heterotopically in recipient rabbits and collected 4 days after the operation. Vector dose was 4 x 10(9) to 6 x 10(10) pfu/gm of donor heart. Transfer was confirmed by DNA amplification for both genes. Gene product expression in tissue was quantified by immunoassay and visualized by immunohistochemical staining. RESULTS: Allograft viral uptake was only 9.9% +/- 2.4% with bolus injection, but increased to 80.5% +/- 6.8% at 1 ml/min infusion rate (p = 5 x 10(-14)). Uptake ratio was not affected by vector quantity or slower infusion rates. Transforming growth factor-beta 1 was consistently detected in allografts infected with AdCMVTGF-beta 1, but not with control adenovirus or AdSvIL10. Expression was proportional to infused vector quantity and reached 10 ng/gm of allograft at infused 10(10) pfu/gm. Transforming growth factor-beta 1 was also detected in recipient's serum at less than 1 ng/ml. Viral interleukin-10 was detected in minor amounts only (< 1 ng/gm) in allografts infected with AdvIL10 up to 5 x 10(10) pfu/gm. Nevertheless, it was detected in recipient serum at concentrations up to 0.4 ng/ml. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts during cold preservation is feasible. Slow infusion is superior to bolus injection. In vivo effects on allograft rejection remain to be determined.
Adenoviridae↗
[A case report of sudden death after Bentall's operation (Piehler's modification) due to left coronary occlusion].
We encountered a rare complication after Bentall's operation (Piehler's modification) with the left coronary artery occlusion. A 56-year-old man admitted to our hospital to get the aortic reconstruction operation for the chronic dissecting aortic aneurysm (DeBakey type I) with 7 cm in diameter. We performed Piehler's modification procedure using a 26 mm and 8 mm woven Dacron tubes coated with gelatin, and 23 mm prosthetic valve (St. Jude Medical). He got well after 6-day intubation until he complained anterior chest pain suddenly on 22 postoperative day. He showed ventricular fibrillation on the second attack requiring resuscitation procedures. Emergent angiogram showed total occlusion of the left coronary artery. The percutaneous transluminal coronary angioplasty was performed only with temporal success. Autopsy revealed no thrombus in the grafts and no kinking of the tubes. We might have to use more anticoagulants during the respirator assisted period when the APTT was naturally prolonged from 120 to 160 seconds.
Aortic Dissection↗
Experience of patients with end-stage heart failure who underwent heart transplant at UCLA.
From 1993 to 1997, nine Japanese heart transplant candidates were accepted by the University of California at Los Angeles (UCLA) Medical Center, because no donor heart was available in Japan from a brain-dead patient. In all nine heart transplant patients described in this investigation, the preoperative diagnosis was dilated cardiomyopathy. One patient underwent implantation with a Novacor left ventricular assist device (Baxter Japan, Tokyo, Japan) as a bridge to heart transplant. All patients survived surgery and for a long-term period. The actuarial 1-year and 3-year survival curves of these patients were both 100%. The postoperative functional status was New York Heart Association Class 1 in all patients (100%). Immunosuppressive triple drug therapy (azathioprine, steroids, and cyclosporine) was given in seven patients; in two patients, cyclosporine was withdrawn and replaced by FK506 due to refractory rejection. The incidence of acute rejection per patient of more than grade 3 according to the International Society for Heart and Lung Transplantation was 6% within 3 months and 4.5% in 3-6 months; there was no rejection episode more than 6 months after transplantation. Post-transplant coronary artery disease was seen in two patients. However, no disease progression was seen after diltiazem therapy. These results may encourage heart transplantation in Japan.
Adult↗
Combined aortic and mitral valve replacement in an adult with mucopolysaccharidosis (Maroteaux-Lamy syndrome).
A 41-year-old man with aortic stenosis, mitral stenosis, and tricuspid regurgitation due to Maroteaux-Lamy syndrome underwent aortic and mitral valve replacement with tricuspid annuloplasty. The annular diameter of the aortic and mitral valves was extremely small. The valve prostheses were 19 mm in diameter in the aortic position and 25 mm in the mitral position. Histologically, the valves showed thickening and hyalinization of the collagen fibers, and the presence of foamy cells that contained a large quantity of pure acid mucopolysaccharide. On an echocardiographic examination performed 2 years after the surgery, the peak systolic gradient of the trans-aortic valve was 18 mmHg at rest, and 26 mmHg during exercise. Careful observation of the residual pressure gradient will be needed. The patient's present New York Heart Association (NYHA) status is grade I and he has returned to work.
Adult↗
Surgical treatment of ischaemic valve disease.
Mitral valve regurgitation secondary to ischaemic heart disease carries a significant mortality even after open-heart surgery. In this study, 21 patients with mitral regurgitation associated with ischaemic heart disease were evaluated with respect to valvular pathology. Pathological examination of the mitral valve revealed chorda elongation or rupture in seven patients (group 1), papillary muscle dysfunction in 10 (group 2), and papillary muscle rupture in four (group 3). Significant preoperative characteristics in each group were subacute haemodynamic deterioration in group 1, chronic severe left ventricular failure in group 2, and a high incidence of acute renal failure associated with haemodynamic shock in group 3. Mitral valve plasty was performed in six patients and mitral valve replacement, using the St Jude Medical valve, in 15. Fourteen patients underwent mitral valve surgery combined with coronary artery bypass grafting. Mitral plasty was applied to the patients with low left ventricular function with mean(s.d.) fraction shortening of 19.2(6.2)% compared with 30.2(8.4)% in patients with mitral valve replacement. There were no operative deaths. Of four late deaths, two in group 1 resulted from infection and myocardial infarction, respectively and one in group 2 resulted from arrhythmia. One patient in group 3 died from renal failure. It is suggested that incorporation of these therapeutic concepts may lead to satisfactory results in the surgical treatment of ischaemic mitral regurgitation.
Coronary Artery Bypass↗
Detection of tet(K) and tet(M) in Staphylococcus aureus of Asian countries by the polymerase chain reaction.
This study describes the use of the polymerase chain reaction (PCR) to detect the tet(K) and tet(M) tetracycline resistance genes in Staphylococcus aureus. Primers based on the DNA sequence of the tet(K) and tet(M) genes from S. aureus were used as primers in the PCR assay to detect the presence of genes for resistance to tetracycline and minocycline. Two-hundred and fifteen isolates of S. aureus from Asian countries as Japan, Indonesia, China, Korea and Thailand were examined, and the results confirm that tet(K) specifies resistance to tetracycline but not to minocycline and tet(M) specifies resistance to both tetracycline and minocycline. We observed two different types of clinical isolates of S. aureus strains resistant to minocycline and tetracycline: the first carried only the tet(M) gene, while the second carried both the tet(M) and the tet(K) genes. Almost all of the clinical isolates of S. aureus resistant to minocycline and tetracycline from Indonesia, China and Thailand carried both tet(M) and tet(K) genes, while most of clinical isolates of S. aureuss from Japan and Korea carried only tet(M) gene.
Anti-Bacterial Agents↗
Effect of HTK solution for myocardial preservation.
The aim of this study was to investigate the efficacy of HTK solution for cardioplegia in the continuous 120-minute cross-clamping method in comparison with the conventional GIK method. In an experimental model, the efficacy of ketoglutarate and tryptophan in recovering cardiac function after 6 hours' preservation was evaluated. In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed. In Group B, in which tryptophan was excluded from the HTK solution, a significant decrease in percent developed pressure and coronary flow was seen (p<0.01). This indicated that ketoglutarate and tryptophan were effective in protecting the myocardium during the ischemia. In the clinical study, 54 open heart operations were performed with cardioplegic solution, using either HTK solution or GIK solution. In the HTK Group, the heart was exposed to 120 minutes' of ischemia after the infusion of HTK solution (3L). In the GIK group, intermittent GIK perfusion was performed every 30 minutes in association with continuous cold blood perfusion. Percent fraction shortening and cardiac index were not significantly different. However, CK-MB and HBDH were increased in the GIK group, postoperatively. Histological findings showed deterioration of the mitochondria and myocytes during ischemia in the GIK group. These data suggest that the effect of the cardioplegias in heart preservation was satisfactory in both groups, although the interval of intermittent perfusion was prolonged to 120 minutes in the HTK solution.
Animals↗
[A case report of a successful Redo Bentall operation].
An initial Bentall operation was performed on a patient aged 38 years with annuloaortic ectasia and aortic regurgitation. An echocardiogram and RI angiogram revealed a perigraft aortic aneurysm on the same patient aged 45 years. The aneurysm gradually developed and the maximum diameter reached 90 mm in size. The Redo-Bentall operation (Piehler modification) was successfully done once again on the same patient aged 56 years. The anastmosis between the right coronary orifice and the graft was detached on all sides. The anastmosis between the left coronary orifice and the graft was detached two thirds of all sides.
Aneurysm, False↗
[A surgical case report of an atrial septal defect combined with stenosis of the left main coronary artery caused by a dilated pulmonary artery in adult].
We encountered a 40-year-old male patient diagnosed to have an atrial septal defect combined with pulmonary hypertension and left main coronary artery stenosis of 50% caused by a dilated pulmonary artery. Preoperative Trazoline tolerance test revealed an increase in pulmonary artery pressure from 77/22(40) to 85/24(42), and a decrease in pulmonary vascular resistance from 4.2 U.m2 to 3.6 U.m2. Moreover, his treadmill exercise test was positive. We performed only a patch closure of the atrial septal defect. The postoperative catheterization examination showed normal pulmonary artery pressure, mild mitral valve regurgitation, and improvement of the left main coronary artery stenosis from 50% to 41%. After 6 months, his treadmill exercise test was negative. We believe that it is important to estimate preoperatively for the possible reversibility of pulmonary hypertension in a patient with an atrial septal defect combined with a left main coronary artery stenosis caused by a dilated pulmonary artery.
Adult↗
Isolation and characterization of Marek's disease virus (MDV) cDNAs mapping to the BamHI-I2, BamHI-Q2, and BamHI-L fragments of the MDV genome from lymphoblastoid cells transformed and persistently infected with MDV.
We have isolated and sequenced two cDNAs of sizes 2674 and 677 bp from a cDNA library derived from MKT-1, a lymphoblastoid cell line transformed and latently infected with Marek's disease virus (MDV) using probes corresponding to the right-hand end of the BamHI-I2 fragment of the MDV genome. The larger cDNA clone represents an abundant transcript, which extends from the right-hand end of BamHI-I2 to the adjacent BamHI-Q2 and BamHI-L fragments of the MDV genome and contains the Meq (MDV Eco-Q) open reading frame. The smaller cDNA clone represents a spliced transcript containing the putative DNA binding domain of Meq as well as sequences in the BamHI-L region. We prepared a polyclonal antibody against part of the protein sequence of Meq and detected a 44-kDa protein in MKT-1 cells and in cells lytically infected with MDV. In addition, riboprobes corresponding to sequences specific to each cDNA as well as shared sequences between cDNAs detected a number of transcripts in cells either lytically or latently infected with MDV. Our results indicate that the Meq transcriptional unit extends to the BamHI-L fragment and that the transcripts mapping to the right-hand end of the BamHI-I2 and adjacent BamHI-Q2 and BamHI-L fragments are not preferentially expressed during latency.
Amino Acid Sequence↗
Common antigenic epitopes are present on heat-labile oligomers of MDV glycoprotein B and on HSV glycoprotein B.
The antigenic cross-reactivity between the Marek's disease virus glycoprotein B (MDV gB) and glycoprotein B (gB) of herpes simplex virus type 1 and 2 (HSV1 and HSV2) was analysed by the immunoblotting method. We studied cell lysates in both denatured and in undenatured form (i.e., unheated) and reacted them with convalescent sera from chickens infected with the RBIB MDV strain and with human anti-HSV1 gB. Both sera detected the heat-labile MDV gB and the HSV gB oligomers. In addition, monospecific antibodies to the MDV gB 230 kDa oligomer (strain CVI988) were immunoaffinity purified from both the chicken and the human sera. The chicken and human monospecific antibodies detected the homologous and the heterologous gB oligomers in native MDV- and HSV1-infected cell lysates. 15 human sera were tested by immunoblotting and by immunofluorescence on HSV1-, CVI988-and herpes virus of turkeys (HVT)-infected cells. By both assays about half of the human sera reacted with MDV-infected cells. This study demonstrates that the MDV gB heat-labile oligomers possess conformational epitopes shared with the human alpha-herpes virus HSV1 and HSV2 gB heat-labile oligomers.
Animals↗
Superinfection of a defective human immunodeficiency virus type 1 provirus-carrying T cell clone with vif or vpu mutants gives cytopathic virus particles by homologous recombination.
The partially CD4-expressing T cell clone, Vpr-1, which carries a latent vpr-defective HIV-1 genome and expresses HIV-1 Nef protein only, was permissive to superinfection by HIV-1. Superinfection of Vpr-1 with vif- or vpu-defective mutants, which were noncytopathic, reactivated the vpr-defective virus and led to homologous recombination and cytopathogenesis. The data provide an experimental model for homologous recombination being an important mechanism whereby HIV-1 acquires genetic heterogeneity, and when occurring among defective virus in vivo bestows novel biological activities and virulence.
CD4-Positive T-Lymphocytes↗