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Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 19 recordsLinked to original sources

Mid-term surgical results after valve replacement with the CarboMedics valve prosthesis.

We present herein a review of 95 patients who underwent valve replacement with the CarboMedics (CM) valve prosthesis between April 1990 and December 1992. The operative mortality for the entire group was 4.2%: 0% following aortic valve replacement (AVR), 2.7% following double valve replacement (DVR). All patients were prescribed warfarin and bucolome for anticoagulation, and were followed up for a mean period of 29.9 months. Late mortality was 8.4%; 3.1% following AVR, 10.8% following MVR, and 12.5% following DVR. There were no cases of mechanical prosthetic valve failure, significant hemolysis, infective prosthetic valve endocarditis, or bleeding complications. After 44 months of follow-up, the actuarial freedom from complications was calculated as: thromboembolism, 97.8 +/- 1.6%; valve thrombosis, 97.8 +/- 1.1%; paravalvular leak, 96.7 +/- 1.9%; and reoperation, 98.9 +/- 1.1%. The overall survival rate was 84.3 +/- 6.3% and all survivors showed a significant improvement in NYHA functional class, from 81% in classes III and IV preoperatively to 99% in classes I and II postoperatively. The CM valve exhibited no significant differences in hemolytic parameters or hemodynamic performance after isolated AVR or MVR compared with the similar type of St. Jude Medical bileaflet valve. The evidence provided by the present study therefore suggests that the CM valve prosthesis can achieve excellent mid-term clinical results and hemodynamic performance with a low incidence of thromboembolism and valve thrombosis.

Adolescent

Hst-1 (FGF-4) antisense oligonucleotides block murine limb development.

The initiation of limb development depends on the site specific proliferation of the mesenchyme by the signals from the apical ectodermal ridge (AER) in embryonic mouse. We have previously reported that the local expression of Hst-1/Fgf-4 transcripts in AER of the mouse limb bud is developmentally regulated, expressed at 11 and 12 days post coitus (p.c.) embryo. In an effort to further understand the role of Hst-1/FGF-4 in mouse limb development, an antisense oligodeoxynucleotides (ODNs) study was performed. We first established a novel organ culture system to study mouse limb development in vitro. This system allows mouse limb bud at 9.5-10-d p.c. embryo, when placed on a sheet of extracellular matrix in a defined medium, to differentiate into a limb at 12.5-d p.c. embryo within 4.5 d. Using this organ culture system, we have shown that exposure of 9.5-10-d p.c. embryonal limb bud explants to antisense ODNs of Hst-1/FGF-4 blocks limb development. In contrast, sense and scrambled ODNs have no inhibitory effect on limb outgrowth, suggesting that Hst-1/FGF-4 may work as a potent inducing factor for mouse limb development.

Animals

Effective prevention of thrombocytopenia in mice using adenovirus-mediated transfer of HST-1 (FGF-4) gene.

HST-1 (FGF-4) gene product is a member of the fibroblast growth factor family with a signal peptide and plays a crucial role in limb development. We showed previously that an intraperitoneal injection of replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into normal mice caused a twofold increase in peripheral platelet count. To investigate whether Adex1HST-1 could effectively prevent experimentally induced thrombocytopenia in mice, we injected Adex1HST-1 intraperitoneally into thrombocytopenic mice induced by administration of a chemotherapeutic agent and/or by irradiation. A single Adex1HST-1 injection caused continuously increased levels of serum HST-1 protein for at least 30 d and increased the count of large megakaryocytes in bone marrow, which specifically recovered platelet counts and more efficiently diminished the extent and duration of thrombocytopenia than any other reported cytokine or any combination of cytokines so far. In the other peripheral hematological parameters, no discernible differences were detected. No other apparent side effects were observed. Therefore, this method could be useful for treatment and/or prevention of thrombocytopenia induced by chemotherapy and/or irradiation for cancer treatment.

Adenoviruses, Human

High prevalence of anti-phospholipid antibodies and anti-thyroglobulin antibody in patients with hepatitis C virus infection treated with interferon-alpha.

OBJECTIVES AND METHODS: We investigated the prevalence rate of beta 2-glycoprotein I (beta 2-GPI)-dependent antiphospholipid antibodies (aPL)[anti-cardiolipin antibody (aCL), anti-phosphadidylserine antibody (aPS), and anti-phosphatidic acid antibody (aPA)], antinuclear antibody (ANA), anti-deoxyribonucleic acid antibody (aDNA), anti-thyroglobulin antibody (aTG), and anti-thyroid peroxidase antibody (aTPO) in 56 patients with hepatitis C virus (HCV) infection and correlated the results with inteferon-alpha (IFN) treatment. RESULTS: aCL, aPS, and aPA were positive in, respectively, 7/56 (13%), 12/56 (21%), and 13/56 (23%) patients before treatment. aPS and aPA appeared in 6/44 and 9/43 and disappeared in 6/12 and 2/13 patients, respectively, after IFN treatment; the differences were statistically significant. The changes in OD readings were higher in the group of patients who became positive for aPS and aPA than in those who became negative after treatment. The positive rates of aTG and aTPO in the patient group were statistically higher than in the healthy controls, and aTG developed in four patients and disappeared in two. No obvious changes in aTPO were observed; however, the aTPO titer was increased in four previously positive patients. None of the patients positive for any antibodies developed an abnormality associated with these antibodies during an observation period of up to 1 yr. CONCLUSIONS: The pathogenesis of production and clinical significance of aPL, ATG/aTPO in this clinical setting are unclear, but immunological disturbances, such as the effects of HCV infection and/or IFN treatment, were considered to be a possibility. Further investigation is needed to clarify whether HCV/aPL- and/or aTG/aTPO-positive patients treated with IFN might develop aPL-associated complications and/or autoimmune disease(es), in the future and to confirm whether IFN treatment justifies the outcome in this clinical setting.

Adult

GSH-independent denitration of organic nitrate esters in rabbit hepatic and vascular cytosol.

The denitration of organic nitrate esters in rabbit hepatic cytosol was characterized. Sephadex G-200 chromatography of ammonium sulfate precipitate (40-80%) from hepatic cytosol demonstrated the presence of two distinct activities (peak I and peak II) responsible for the denitration of nitroglycerin (NTG) and isosorbide dinitrate (ISDN). The denitration of peak I required dithiothreitol (DTT), but not glutathione (GSH), and was not inhibited by S-alkyl GSH, an inhibitor of glutathione S-transferase (GST). Whereas, the denitration activity of peak II was potentiated by GSH, and was inhibited by S-alkyl GSH. These results strongly suggest that the denitration of organic nitrate esters, such as NTG and ISDN, can be catalyzed by at least two enzymes, GSH-independent denitration (peak I) and the GSH-dependent denitration (peak II, GST), in rabbit hepatic cytosol. The denitration activity of peak I was inhibited by SH-modified reagent, indicating that free thiol(s) is (are) critical for expression of the denitration activity. Also, in rabbit vascular cytosol, the cofactor requirement for denitration and response to S-hexyl GSH suggest the participation of GSH-independent enzyme which is responsible for the denitration of organic nitrate esters.

Animals

Clinical significance of serum 2,5-oligoadenylate synthetase and soluble interleukin-2 receptor in hemophiliacs positive and negative for human immunodeficiency virus type 1.

We measured serum 2,5-oligoadenylate synthetase (2,5-AS) levels and soluble interleukin-2 receptor (sIL-2R) levels in human immune deficiency virus type 1 (HIV-1)-positive and HIV-1-negative hemophiliacs in order to clarify the clinical significance of these parameters in hemophiliacs. Serum 2,5-AS levels were measured by a radioimmunosorbent assay, and sIL-2R levels were measured by an enzyme-linked immunosorbent assay. The mean serum 2,5-AS levels were higher in AIDS-related-complex and AIDS patients, asymptomatic carriers, and HIV-1-negative hemophiliacs than in hepatitis C virus-positive patients and healthy controls. Serial determinations showed that the 2,5-AS levels tended to increase in HIV-1-positive patients, especially those with AIDS-related complex or AIDS, although it showed a substantial decrease in the terminal stage. The serum sIL-2R levels were higher in HIV-1-positive patients, HIV-1-negative patients, and hepatitis C virus-positive patients than in controls. Serial studies showed little change in the HIV-1-positive and HIV-1-negative groups, although sIL-2R levels showed a tendency to decrease with zidovudine treatment. On the basis of the present results, we may well conclude that 2,5-AS and sIL-2R are not specific markers for hemophiliacs with HIV-1 infection. However, serial measurement of these markers can still be useful for assessing the progression of AIDS and the prognosis for patients with AIDS, as well as for monitoring the response to zidovudine.

2',5'-Oligoadenylate Synthetase

Effects of bile acids and bilirubin on bicarbonate secretion of isolated guinea pig antrum.

The effects of bile acids and bilirubin, which increase in blood in obstructive jaundice, on bicarbonate secretion were studied experimentally using isolated antral mucosa of the guinea pig. Antral mucosal preparations were mounted between Ussing chambers. Basal and bethanechol-stimulated secretion were measured by a pH stat device using 5 mM HCl. After 10(-4), 10(-3), and 5 x 10(-3) M taurocholic acid, 10(-4) and 10(-3) M cholic acid, and 1.2 x 10(-4) and 2.4 x 10(-4) M bilirubin conjugate were added to the serosal solution, basal and bethanechol-stimulated secretion were also measured. Taurocholic acid, at any dose, did not affect basal secretion, but bethanechol-stimulated secretion was inhibited dose dependently. Cholic acid and bilirubin conjugate did not affect basal secretion, but bethanechol-stimulated secretion was significantly inhibited. Although the addition of bile acid or bilirubin into the serosal solution under experimental conditions is not the same as obstructive jaundice, these studies suggest that the inhibition of bicarbonate secretion in the gastric mucosa may have an important role in the formation of acute gastric mucosal lesions in obstructive jaundice.

Animals

Clinical significance of the venous occlusion test on systemic lupus erythematosus patients with a focus on changes in blood levels of tissue plasminogen activator, von Willebrand factor antigen, and thrombomodulin.

We investigated the clinical significance of the venous occlusion (VO) test on patients with systemic lupus erythematosus (SLE) with or without circulating lupus anticoagulant (LA) concerning whether changes in the blood coagulation and fibrinolysis system in vivo subsequent to VO reflect mechanical stimulation of the endothelium or presence/development of endothelial damage. The tissue plasminogen activator antigen (tPA:Ag) before VO was much lower in the LA-positive patients than in the LA-negative ones (p < 0.01) and the von Willebrand factor antigen (VWF:Ag) pre-VO was significantly higher in the patient group, regardless of LA status, than in the control group (p < 0.01). But the mean increment in tPA:Ag and VWF:Ag post-VO, when expressed as the percentage of the baseline level, showed no appreciable difference between LA-positive and -negative groups. Thrombomodulin (TM) basically, on the other hand, was higher in the patients of either LA status than in the controls (p < 0.01) with a significant post-VO increase in the SLE group, which was more marked in the LA-positive patients, against no substantial change in the controls (p < 0.01). It is known that tPA and VWF:Ag are released simply as a result of endothelial stimulation and that the release of TM is preceded by endothelial damage. Based on the present results, we may well conclude that (1) the endothelium is functionally intact in SLE patients, (2) an injury of the endothelium, possibly as a consequence of vasculitis, preexists in LA-positive patients, and thus to measure the TM response to VO would offer a helpful tool in diagnosing the preexisting endothelial damage in these clinical settings.

Adult

Effect of total-body cold exposure on plasma concentrations of von Willebrand factor, endothelin-1 and thrombomodulin in systemic lupus erythematosus patients with or without Raynaud's phenomenon.

The effect of total-body cold exposure on plasma concentrations of von Willebrand factor (vWF), endothelin-1 (ET) and thrombomodulin (TM), all of which are considered to be generated from the endothelium, was studied in systemic lupus erythematosus (SLE) patients with and without Raynaud's phenomenon. The plasma levels of vWF, ET and TM in SLE patients, irrespective of the presence of Raynaud's phenomenon, were significantly higher than in normal controls even before the cold provocation test. After the cold provocation test, plasma levels of vWF and ET were significantly higher in SLE patients with Raynaud's phenomenon than in those without and in normal controls. No significant increase in TM was observed in either the SLE patients or the controls. These results suggest that SLE patients, regardless of the presence of Raynaud's phenomenon, are in a hypercoagulable state and that this state may be further intensified by cold exposure. Hence, it is concluded that we should consider antithrombotic therapy for SLE patients, especially those with Raynaud's phenomenon, to prevent unwanted activation of the coagulation system and possible endothelial damage.

Adult

[Intentional hypotension therapy induced by nitroglycerin and the changes in the intracranial pressure for acute hemorrhagic intracranial lesions].

It is reported that nitroglycerin (NTG) induces the elevation of intracranial pressure (ICP). Because of it, the use of NTG in patients exhibiting the increased ICP especially in the neurosurgical field is thought to be avoided. However, these reported cases dealt with normal patients. Few cases under the condition of exactly increased intracranial pressure were studied. Our 31 patients of the hemorrhagic intracranial lesion (subarachnoid hemorrhage and hypertensive intracranial hemorrhage) at the acute stage were treated by NTG infusion as an antihypertensive drug, and the ICP was measured using the epidural pressure transducer. The 31 patients were divided into three groups. Group 1 consists of the 14 patients exhibiting normal ICP (< 15mmHg). Group 2 consists of 9 patients showing elevated ICP (15mmHg < or =). Group 3 consists of 8 patients treated with glycerol before the NTG infusion. Group 1 demonstrates a statistically significant elevation of ICP corresponding with the blood pressure depression. Group 2 showed no significant elevation of it. Group 3 disclosed no remarkable elevation of it both in the elevated ICP cases and the normal ICP cases. As mentioned above, the intravenous NTG caused a remarkable increase of ICP in the normal compliance of the intracranial contents and no elevation of ICP in the poor compliance. We conclude that NTG can be used for blood pressure control at an acute stage even in hemorrhagic intracranial lesion as anti-depressor.

Acute Disease

[Effects of preoperative transcatheter portal embolization (TPE) on prevention of hepatic failure after massive hepatectomy].

Effects of TPE on prevention of hepatic failure after massive hepatectomy were studied experimentally using dogs. A 70% or 85% hepatectomy (Hx) was performed two weeks after TPE. All of the 70%Hx groups with(+)/without(-) TPE were alive for over two weeks after hepatectomy. While all of the 85%Hx group without TPE died, eight of ten in the 85%Hx group with TPE survived. Without TPE, total bilirubin levels in sera were elevated markedly in the 85%Hx group and moderately in the 70%Hx group after hepatectomy. The levels of escaped enzymes in sera, such as GOT or GPT, were also elevated remarkably in the TPE(-) groups. Although the levels of these enzymes were also high in the 85%Hx.TPE(+) group, these values were as same as those of 70%Hx.TPE(-) group. In the 85%Hx.TPE(-) group, critical diminution of functional hepatic cell mass and severe portal hypertension occurred after hepatectomy and coagulopathy and death followed to these phenomena. TPE might prevent the onset of these critical phenomena, and diminish the damage caused by massive hepatectomy. These results suggest that TPE is useful for prevention of postoperative hepatic failure so that we could perform massive hepatectomy safely, and extend the operative indication.

Alanine Transaminase

Localization of blood coagulation factors in the germinal centers of human Peyer's patches.

The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factors XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin III and inactive alpha-thrombin were found, showing a lace-like staining pattern similar to that obtained with a monoclonal antibody, R4/23, specific for follicular dendritic cells (FDCs) in the GCs. By immunoelectron microscopy, positive reactions for factor X and XIIIa were found on the surfaces of FDCs, GC cells, and/or in the intercellular spaces of GCs, being especially marked on the surface of the labyrinth-like structure of FDCs. It is concluded that a majority of coagulation factors are localized in the GCs of human PPs. Furthermore, it is suggested that some of these coagulation factors have a close topographical relationship with FDCs.

Antibodies, Monoclonal

[Surgical treatment of Marfan's syndrome with annulo aortic ectasia and mitral regurgitation].

This report is concerned with results of surgical treatment for Marfan's syndrome combined with annulo-aortic ectasia (AAE) and mitral regurgitation (MR). Of the 23 patients with Marfan's syndrome who received Bentall's procedure during 14 year period, seven (30%) of these patients had both AAE and MR. The MR grade of seven patients by cardiac Doppler or left ventriculographic studies were grade 1 in 2, 2 in 1, 3 in 1, and 4 in 3. Atrial fibrillation was present in 4 patients. New York Heart Association Functional Class on admission in these 7 patients were II in 1, III in 4, and IV in 2. The mitral valve was replaced with mechanical valve in 4 patients by left atrial approach whose MR grade were over 3. In the 4 patients the mitral annuli were extremely dilated, both valve leaflets were massively redundant, and all chordae were elongated and turned chordae and vegetation were detected due to infective endocarditis. Only Bentall's procedure was performed in 3 patients whose MR were minimal. There were no early death, but two late deaths. One of them died of cardiac failure 2.3 years after Bentall's procedure because grade 2 MR was increased. Another one died from ventricular arrhythmia 1.6 years after MVR and Bentall's procedure. The remaining 5 patients are doing well for 3 months to 11.5 years after operation. For Marfan's syndrome combined with AAE and MR, early operation is recommended before left ventricular impairment. Mitral valve repair was not performed, both to save time and because anticoagulant therapy was need for aortic valve replacement. Concomitant MVR was to be done for moderate to severe MR.

Adult

[The hemodynamics during hemodilution and its influence on the liver functions after hepatectomy for hepatocellular carcinoma with liver cirrhosis].

The hemodynamics during hemodilution occurred after hepatectomy for hepatocellular carcinoma with liver cirrhosis and its influences on the liver functions were studied. The hematocrit value gradually decreased about 10% until the 4th postoperative day owing to hemodilution after hepatectomy. While anemia progressed, cardiac index inversely increased. Under such a condition, oxygen consumption was maintained so that acidosis did not develop. Arterial blood ketone body ratio was also kept within a normal range except for a case whose hematocrit value decreased to 17.1%. Although the escaped hepatic enzymes such as GOT and GPT increased in the serum after hepatectomy, hemodilution was not responsible for their increase. While total bilirubin increased in the severe hemodiluted group, the increase was not due to hemodilution but caused by blood transfusion. The protein synthesis of the liver measured by rapid turnover protein levels in plasma was depressed after surgery, and this depression prolonged to the 14th postoperative day in the group whose hematocrit value decreased below 20%. These results suggest that it is better to keep hemodynamics without blood transfusion unless the hematocrit value decrease below 20%, and also better to maintain the hematocrit above 20% for liver regeneration after hepatectomy.

Adult

[Reoperation of primary tissue failure of bioprosthesis in the mitral position].

The surgical results of 38 patients who underwent reoperation for primary tissue failure of bioprosthesis in the mitral position between May 1982 and June 1990 were analyzed to determine the risk factors affecting the hospital mortality. The type of bioprostheses requiring reoperation were Hancock valve in 21 patients, Liotta valve in 15 patients and Mitroflow valve in 2 patients. Twenty-five preoperative and perioperative variables were collected and analyzed by univariate statistics using chi 2 test or Student's test. Four of thirty eight patients died postoperatively in the hospital, yielding an overall mortality of 10.5%. The causes of hospital mortality were low output syndrome in 2 patients and multiple organ failure in 2 patients. By univariate analysis, male, NYHA IV class, prosthetic stenosis, hepatic failure, renal failure, and pulmonary failure were risk factors predictive of high hospital mortality. In spite of recent improvement of surgical technique and myocardial protection, the hospital mortality of patients with NYHA IV class and advanced organ failure still remains unacceptable. Therefore, it is essential to perform reoperation for primary tissue failure of bioprosthesis before severe myocardial decompensation occurs. To accomplish this goal, patients with bioprosthesis who survived beyond the certain time should be followed periodically using echocardiogram.

Adult

[Respiratory care with prone position for diffuse atelectasis in critically ill patients].

Diffuse atelectasis often occurs in the dorsal region of the lung of critically ill patients under long term mechanical ventilation. Conventional physical therapies (ex. PEEP, Sigh) have little effect on diffuse dorsal atelectasis. We provided respiratory care with prone position for 7 patients with severe respiratory distress (Two patients were treated twice). Improvement of their Respiratory Indexes (RI, mean 2.97) was obtained in the prone position for 6-163 (mean 35.8) hours. Ventilation efficiency also improved. Static lung compliance didn't change. It was assumed that the prone position was the factor responsible for the improvement of pulmonary V/Q ratio, the change of movement pattern of the diaphragm, and the ease of postural drainage of sputum. There were no complications. We conclude that prone position respiratory care has high utility for critically ill patients with diffuse dorsal atelectasis.

Adult