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Biomedical subjects

H Hayakawa

Publications and source records attributed to H Hayakawa.

At least 127 records · Page 7Linked to original sources
PubMed1997

Clinical and electrophysiologic effects of dofetilide in patients with supraventricular tachyarrhythmias.

The clinical and electrophysiologic effect of intravenous dofetilide was evaluated in patients with paroxysmal atrial fibrillation (AF) of recent onset (< 7 days) and paroxysmal supraventricular tachycardia (PSVT). From 2.5 to 5.0 micrograms/kg of dofetilide was administered intravenously for the termination of arrhythmias. For the electrophysiologic study (EPS), 3.0 micrograms for loading and subsequently 2 micrograms/kg was injected for 45 min as a maintenance dose. The EPSs were performed before the loading and during the maintenance dose. AF was successfully converted to sinus rhythm in seven (54%) of 13 patients. The duration of AF from its onset was significantly shorter in responders than that of nonresponders (p < 0.05). Dofetilide also terminated PSVT in four of six patients. In the EPS, dofetilide proportionately lengthened the effective refractory period of the atrium, ventricle, and the accessory pathways without slowing of the intracardiac conduction. Dofetilide completely suppressed the induction of PSVT in seven of 13 patients, restricted the induction zone in five, and inhibited perpetuation of the arrhythmia in the remaining one. The cycle length of PSVT remained unchanged after dofetilide. These results imply that the suppression of the development and maintenance of reentrant arrhythmias may result from the lengthening effect of dofetilide on the refractoriness and the consequent elimination of the excitable gap at the critical part of the reentrant loop.

Adult↗
PubMed1997

T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use.

Animals↗
PubMed1997

Nitric oxide production during Vibrio cholerae infection.

Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites (NO2-/NO3-) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of NO2-/NO3- in the fluid (P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues (P < 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+ dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca(2+)-dependent NOS activity in the tissues.

Adult↗
PubMed1997

The link among nitric oxide synthase activity, endothelial function, and aortic and ventricular hypertrophy in hypertension.

The adaptive changes that occur in the left ventricle (LV) and vessels in response to hypertension, namely, muscle hypertrophy/hyperplasia, endothelial dysfunction, and extracellular matrix increase, do not depend solely on blood pressure elevation. These changes are in fact, maladaptive since they are forerunners of cardiac failure, stroke, and renal failure. Nitric oxide, an endogenous vasodilator and inhibitor of vascular smooth muscle cell growth, is synthesized in the endothelium by constitutive nitric oxide synthase (cNOS). We investigated the relationships among LV and aortic cNOS activity (conversion of [14C] L-arginine to [14C] L-citrulline), with LV hypertrophy (LV weight/body weight), and (2) aortic hypertrophy (aortic weight/ length) in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats matched for blood pressure (219 +/- 12 versus 211 +/- 7 mm Hg, P = NS) and age. Compared with their normotensive counterparts, aortic cNOS activity was increased 106% in SHR but reduced by 73% in DS rats. The correlation between blood pressure and aortic cNOS activity was positive (r = .74, P < .01) in SHR and negative (r = -.82, P < .01) in DS rats, LV cNOS activity was increased 73% in SHR compared with normotensive Wistar-Kyoto rats (P < .01). On the other hand, LV cNOS activity was not increased in hypertensive DS rats compared with normotensive DS rats. In SHR, aortic hypertrophy did not increase significantly and LV hypertrophy increased only 15%, whereas in hypertensive DS rats the aorta and LV hypertrophied 36% and 88%, respectively (both P < .01). Moreover, in DS rats there was a negative correlation between cNOS activity and aortic hypertrophy (r = -.70, P < .01). In DS rats, antihypertensive therapy consisting of an angiotensin-converting enzyme inhibitor, perindopril, and a diuretic, indapamide, normalized blood pressure, aortic cNOS activity, and LV hypertrophy and reduced aortic hypertrophy. Our studies imply that upregulation of vascular cNOS activity has a protective cardiovascular homeostatic role in hypertension. Clinically, the variable end-organ disease observed in individuals with similar severity of hypertension may be explained, at least in part, by genetically conditioned differences in vascular cNOS activity in response to hypertension.

Animals↗
PubMed1997

Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney.

The vasopressin receptor subtype that causes nitric oxide (NO) release remains controversial. To elucidate this receptor-ligand interaction, we examined the effects of vasopressin receptor antagonists on vasopressin-induced release of NO from isolated perfused rat kidneys by using a sensitive chemiluminescence assay. Vasopressin increased renal perfusion pressure and NO signals in the perfusate in a dose-dependent manner. N omega-Monomethyl-L-arginine abolished this increase in NO release; however, a similar increase in renal perfusion pressure induced by prostaglandin F2 alpha was not associated with the increase in NO release. OPC-21268, a V1 receptor antagonist, significantly reduced the vasopressin-evoked renal vasoconstriction and NO release, whereas OPC-31260, a V2 receptor antagonist, had no effects. Moreover, desmopressin, a selective V2 receptor agonist, did not increase the NO signal. NO release by vasopressin was markedly attenuated in deoxycorticosterone acetate (DOCA)-salt hypertensive rat kidneys compared with control kidneys (10(-10) mol/L vasopressin: +0.8 +/- 0.3 versus +6.9 +/- 1.4 fmol/min per gram kidney, DOCA versus control; P < .001). Histochemical analysis for renal NO synthase revealed a substantial attenuation of the staining of endothelial NO synthase in DOCA-salt rats. These results directly demonstrate that vasopressin stimulates NO release via the endothelial V1 receptor in the rat kidney.

Animals↗
PubMed1997

Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis.

Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohistochemistry and compared the results with those from patients who had interstitial pneumonia associated with systemic sclerosis (IP-SSc) and idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP). Expression of TF-mRNA was also assessed, using in situ hybridization with a digoxigenin-labeled cRNA probe. In patients with IPF, IP-SSc, and idiopathic BOOP, the TF antigen was positively stained in type II pneumocytes and in some alveolar macrophages. The fibrin antigen was stained in the type II pneumocytes and the adjacent area. Tissue factor-mRNA was expressed in the type II pneumocytes and in some alveolar macrophages. Neither TF antigens nor TF-mRNA were detected in the normal lung. These results indicate that type II pneumocytes are a major source of TF, suggesting that TF production in these cells is closely related to fibrin deposition in the lungs of people with these diseases.

Base Sequence↗
PubMed1997

Mitral insufficiency as a complication of acute myocardial infarction and left ventricular remodeling.

The presence of mitral insufficiency after acute myocardial infarction (AMI) often leads to hemodynamic impairment and heart failure. This study was designed to examine the relationship between mitral regurgitation (MR), an indicator of mitral insufficiency, and the course of recovery from AMI. We evaluated the course of MR after AMI in 223 patients by color Doppler echocardiography. MR was detected in 21% (47/223) of patients at the onset of AMI, and developed in 18% (40/223) of patients during follow-up. Patients were grouped according to the course of MR as well as the success of acute recanalization therapy. No correlation was observed between the presence or course of MR and the site of infarction. The incidence of successful recanalization was higher in patients with MR that improved during follow-up than in patients with MR that was unchanged or that worsened during follow-up. Although no significant differences in hemodynamic variables were noted among the groups at admission, the group with unsuccessful recanalization and unimproved MR (BS-) showed a significantly greater left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter, and left ventricular end-diastolic volume (LVEDV) as well as a lower left ventricular ejection fraction than patients with successful recanalization and no MR (CS+) during the convalescent period. The extent of change in LVDd and LVEDV between admission and convalescence was significantly greater in the BS(-) group than in the CS(+) group. The results suggest that successful recanalization after AMI reduces the incidence of MR. Acute recanalization therapy after AMI may prevent left ventricular remodeling, resulting in a secondary improvement of MR.

Aged↗
PubMed1997

Curative percutaneous catheter ablation for various supraventricular and ventricular tachyarrhythmias. Results in 187 consecutive patients during the first five years.

Closed-chest transcatheter electrical ablation (catheter ablation) has been applied to various supraventricular and ventricular tachyarrhythmias as a radical therapeutic technique since its introduction in 1982. Currently, it has become a first line therapy for supraventricular tachyarrhythmias except atrial fibrillation and uncommon types of atrial flutter. We first carried out the ablation procedure in 1991 for the treatment of ventricular tachycardia. Up to February 1997, a total of 187 patients underwent catheter ablation in our institution. The aims of this study are to demonstrate our results of catheter ablation in the early 5 years and to show the usefulness of this new curative method. Successful results were obtained in 168 of 187 patients (overall final success rate: 89.8%). The success rates of each category of tachyarrhythmias were 100/105 patients (95%) with WPW syndrome, 41/46 (89%) with atrioventricular nodal reentrant tachycardia, 7/10 (70%) with atrial flutter, 4/4 (100%) with atrial tachycardia, 2/2 (100%) with medically refractory atrial fibrillation, 13/15 (85%) with idiopathic ventricular tachycardia and 3/7 (43%) with sustained ventricular tachycardia associated with structural heart disease, respectively. Complications that required invasive treatments were observed in 3 patients (2 hemopericardium and 1 complete atrioventricular block). Our results indicate that catheter ablation is highly effective in most categories of tachyarrhythmias and can be applied safely without lethal complications.

Adult↗
PubMed1997

[Clinicopathological features of interstitial pneumonia associated with amyopathic dermatomyositis].

We studied clinicopathological characteristics of interstitial pneumonia associated with amyopathic dermatomyositis. The subjects comprised two men and three women, and their mean age was 58.2 years. All subjects had cruptions specific for dermatomyositis, but had no signs of myositis. They all presented with acutely or subacutely developed coughing and dyspnea. Results of tests for anti-Jo-1 antibody were negative in all cases. Chest X-ray films showed infiltrations or streaky shadows, or both in the middle and lower lung fields. Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of lymphocytes and neutrophils. In one patients a specimen obtained by open lung biopsy showed homogeneous cell infiltrations in alveolar septa and regional alveolar damage. That patient was successfully treated with cyclosporin and corticosteroids in early phase of the disease. The other four patients received immunosuppressive agents after respiratory failure developed. All four died despite having received high-dose corticosteroid and immunosuppressive therapy. Examination of autopsy specimens showed diffuse alveolar damage.

Acute Disease↗
PubMed1997

[Prediction of outcome after acute exacerbation of idiopathic interstitial pneumonia].

Some patients with chronic idiopathic interstitial pneumonia (IIP) experience acute exacerbations (AE). Because the precise mechanisms of AE in patients with IIP remain unclear, the treatment for AE is not established and the efficacy of steroids is controversial. Consequently, it is difficult to predict outcomes in patients with AE of IIP. We therefore studied the relationship between clinical findings, efficacy of treatment, and clinical outcome in patients with AE of IIP. Thirty-two patients were enrolled, and were divided into two groups: 10 who were alive more than one year after the onset of the AE survivors, 8 men and 2 women, and 22 who died within one year of the AE (non-survivors, 17 men and 5 women). Survivors were significantly younger than non-survivors (59.7 +/- 9.9 vs 67.5 +/- 8.2 years, respectively, p < 0.05). The values of PaCO2 measured before the AE were higher in survivors than in non-survivors (43.0 +/- 3.7 vs 38.4 +/- 4.0 torr, respectively, p < 0.05). At the onset of the AE the levels of C-reactive protein in serum were higher in survivors than in non-survivors (13.9 +/- 7.9 vs 7.3 +/- 5.8 mg/dl, respectively, p < 0.05). Chest X-ray films showed progression of ground-glass shadows in both groups when the AE occurred; the radiographic findings did not differ markedly between groups. Of the 22 non-survivors, 7 had received medication before the AE; none of the survivors had received medication before the AE. At the time of the AE all patients were treated with steroid pulse therapy, and the dose of methylprednisolone used, did not differ significantly between groups. These data suggest that three factors are closely related to responsiveness to steroid therapy and to clinical outcomes after AE in patients with IIP: 1) age at the onset on IIP, 2) respiratory status before the AE, and 3) disease activity as reflected by inflammatory reactions.

Age Factors↗
PubMed1997

Nonlinear pattern analysis of ventricular premature beats by mutual information.

The frequency of ventricular premature beats (VPBs) has been related to the risk of mortality. However, little is known about the temporal pattern of occurrence of VPBs and its relationship to autonomic activity. Hence, we applied a general correlation measure, mutual information, to quantify how VPBs are generated over time. We also used mutual information to determine the correlation between VPB production and heart rate in order to evaluate effects of autonomic activity on VPB production. We examined twenty subjects with more than 3000 VPBs/day and simulated random time series of VPB occurrence. We found that mutual information values could be used to characterize quantitatively the temporal patterns of VPB generation. Our data suggest that VPB production is not random and VPBs generated with a higher value of mutual information may be more greatly affected by autonomic activity.

Adult↗
PubMed1997

Recent therapeutic strategy for sustained ventricular tachycardia in Japan.

We investigated the therapeutic principles and strategies to treat sustained ventricular tachycardia (SVT) as five leading medical institutions in the Tokyo area and summarized the present situation of SVT treatment in Japan. Catheter ablation (ABL) has been almost established to be effective in idiopathic ventricular tachycardia (IVT) and was used as the last treatment in 60.3% of IVTs in this series. ABL may be the first option of therapy for IVT. In patients with SVT who have underlying cardiac diseases, the last treatment was class I drugs in 8.3%, class III drugs in 34.3%, combination drug therapy in 24.0%, ABL in 33.3%, surgical therapy (SUR) in 7.3%, and implantable cardioverter defibrillator (ICD) in 12.5% (nonpharmacological therapy in combination with other therapy). The use of class I drugs was not common, whereas class III drugs were used more frequently in patients with a low left ventricular ejection fraction. In some patients with reduced cardiac function, a combination of class III drugs and non-pharmacological therapy is appropriate.

Adult↗
PubMed1996

Conversion of recent-onset Atrial Fibrillation by a single oral dose of Pilsicainide (Pilsicainide Suppression Trial on atrial fibrillation). The PSTAF Investigators.

The efficacy and safety of a single oral dose of 150-mg pilsicainide, a new class Ic antiarrhythmic drug, in converting recent-onset atrial fibrillation to sinus rhythm were evaluated in 75 patients (51 men, 24 women; age 23 to 74 years). Conversion to sinus rhythm was achieved within 90 minutes in 45% of patients given pilsicainide and in 8.6% of those on placebo (p < 0.01), with no major adverse effects.

Administration, Oral↗
PubMed1996

Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators.

To elucidate the clinical characteristics of patients with right bundle branch block and ST elevation in the right precordial leads, a prospective follow-up study was made in 63 registered patients, including 17 with a history of ventricular fibrillation (VF) and 14 with a history of syncope. The prevalence of coved type ST elevation was significantly higher in patients who had had cardiac events, and during the initial 15-month follow-up, 2 patients in the VF group died suddenly.

Adult↗
PubMed1996

Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan.

Deficiencies of Bruton's tyrosine kinase (Btk) have been implicated in the pathogenesis of human X-linked agammaglobulinemia (XLA). The distinctive phenotype observed in B-cell deficiency indicates the crucial role of Btk in B-cell development. This report describes a nationwide study of Btk deficiency in Japan, covering 51 XLA patients (35 independent families). Along with the identification of mutations, the resulting protein products were characterized by an in vitro kinase assay and a Western blot analysis. Thirty-one of the families were found to have mutations in the coding region of Btk. Although mutations were not found in the cDNA of 4 families, the Btk transcripts of these patients were greatly reduced. The identification of several novel missense mutations, in combination with the result of other studies, clarified the presence of two (missense) mutation hot spots, one in the SH1 and the other in the PH domain. The absence of kinase activity seen in 32 of the families underscored the importance of Btk protein analysis as a diagnostic indicator of XLA. The protein analysis also clarified the different effects of missense mutations on kinase activity and protein stability.

Adolescent↗