Biomedical subjects

H Hayakawa

Publications and source records attributed to H Hayakawa.

At least 145 records · Page 8Linked to original sources

PubMed1996

Possible involvement of an environmental agent in the development of acute eosinophilic pneumonia.

BACKGROUND: Although the pathogenesis of acute eosinophilic pneumonia remains largely unknown, it has been suggested that it may include a hypersensitivity phenomenon induced by inhaled environmental antigens. METHODS: To investigate this possibility, we studied the effect of environmental challenges in three patients with acute eosinophilic pneumonia. Symptoms and laboratory findings were evaluated before and after the challenge tests in the patient's homes and their places of work. RESULTS: After the provocation challenges to their homes, all three patients developed fever, cough, and fatigue and two of them presented with dyspnea. Inspiratory crackles became audible in all cases, and there was a decreased Pao2 level in two. Similar challenges at their workplaces were negative. After moving out of their homes, the patients engaged in their usual work but had no recurrent episodes. CONCLUSIONS: These results suggest that environmental factors in the home can be the cause of acute eosinophilic pneumonia. In order to elucidate the pathogenesis of the disease, it is important to further investigate environmental factors.

Acute Disease↗

PubMed1996

Multicenter, double-blind study of intravenous milrinone for patients with acute heart failure in Japan. Japan Intravenous Milrinone Investigators.

OBJECTIVES: Milrinone is a phosphodiesterase F-III inhibitor with positive inotropic and vasodilating activities. We investigated the hemodynamic response and pharmacokinetics of intravenous milrinone in patients with acute heart failure. DESIGN: Double-blind studies: a prospective, multicenter, double-blind, dose-finding study and a placebo-controlled, double-blind, comparative study. SETTING: Patients with acute heart failure (pulmonary artery occlusion pressure of > or = 18 mm Hg), who were hospitalized in the cardiac care units of 33 institutes in Japan, were entered into the study. PATIENTS: Fifty-four patients with acute or decompensated heart failure in the dose-finding study and 52 patients in the placebo-controlled, double-blind, comparative study. INTERVENTIONS: The present multicenter study consisted of a double-blind, dose-finding study (50-micrograms/kg intravenous loading dose, followed by 0.25, 0.5, or 0.75 microgram/kg/min of a continuous infusion of milrinone for 6 hrs, n = 54), and a placebo-controlled, double-blind, comparative study (50-micrograms/kg loading dose, followed by 0.5 microgram/kg/min of a continuous infusion of milrinone vs. placebo treatment, n = 52). We investigated the effects on cardiovascular hemodynamics, subjective symptoms, physical findings, and the pharmacokinetics of intravenous milrinone in a total of 106 patients with acute heart failure. MEASUREMENTS AND MAIN RESULTS: In the double-blind, dose-finding study, dose-dependent inotropic/vasodilating hemodynamic effects were documented for percent changes in cardiac index (+21.2%, +25.8%, and +30.9%, respectively) and pulmonary artery occlusion pressure (-12.8%, -17.0%, -41.3%, respectively) vs. plasma drug concentration at the equilibrium state (6 hrs after starting continuous infusion; 97 +/- 13, 197 +/- 22, and 284 +/- 28 ng/mL, respectively). Throughout the 6-hr infusion period, subjective symptoms were improved in 40%, 46.2%, and 70% of patients, respectively, for the three continuous infusion rates (0.25, 0.5, and 0.75 microgram/kg/min). In the placebo-controlled, double-blind, comparative study, the milrinone group exhibited marked improvement in cardiovascular hemodynamics (pulmonary artery occlusion pressure: from 26 +/- 6 to 15 +/- 3 mm Hg; cardiac index: from 2.6 +/- 0.9 to 3.3 +/- 1.1 L/min/m2) within 15 mins after starting drug administration. However, the placebo group showed no significant hemodynamic changes. Subjective symptoms and physical findings of acute heart failure improved in 47.6% and 40%, respectively, of patients within 60 mins after starting milrinone. The placebo group, however, showed no improvement providing inotropic/vasodilating (both 0%). CONCLUSION: Continuous infusion of milrinone (0.25 to 0.75 microgram/kg/min) after a 50-micrograms/kg loading dose is effective for inotropic/vasodilating hemodynamic support in patients with acute or decompensated heart failure.

Acute Disease↗

PubMed1996

Inhibition of nitric oxide synthesis reduces coronary blood flow response but does not increase cardiac contractile response to beta-adrenergic stimulation in normal dogs.

Whether the nitric oxide (NO) system constitutively present in the normal myocardium and resistance coronary vessels regulates basal cardiac contractility and coronary blood flow (CBF), as well as their responses to beta-adrenergic stimulation in intact heart, remains controversial. We examined the effects of low and high doses of NG-nitro-L-arginine methyl ester (L-NAME) (10 and 100 mu g/kg/min for 10 min), an NO synthase inhibitor, as well as D-enantiomer administered into left circumflex (LCX) artery on responses of left ventricular (LV) dP/dt, regional wall thickening in LCX region and LCX blood flow to graded intracoronary doses of isoproterenol (ISO 0.002-0.016 mu g/kg/min) in normal dogs. Intracoronary L-NAME, which was associated with dose-related reductions in acetylcholine (ACh)-induced coronary vasodilation, significantly reduced baseline LCX blood flow and its response to ISO. However, L-NAME did not change baseline LV contractility as assessed by LV dP/dt and regional wall thickening, nor did it increase its response to ISO. D-Enantiomer was ineffective in reducing baseline LCX blood flow as well as its response to ISO. These results indicate that constitutive NO formation in the vasculature contributes to basal coronary vascular tone as well as resistance adjustments during beta-adrenergic stimulation. However, NO formation in the normal myocardium did not influence basal cardiac contractility; nor did it increase cardiac response to beta-adrenergic stimulation.

Acetylcholine↗

PubMed1996

Clinical effects and pharmacokinetics of a single oral dose of pirmenol hydrochloride.

To establish the clinical efficacy of a single oral dose of pirmenol, we evaluated electrophysiologic and hemodynamic effects simultaneously after drug administration, performing electrophysiologic testing in 20 patients with ECG-documented paroxysmal supraventricular tachycardia (PSVT) before and after a single oral 200-mg dose of pirmenol. Hemodynamic measurements were made with a Swan-Ganz catheter in the first 10 consecutive patients. In a different series of patients, we administered a single 200-mg oral dose of pirmenol to evaluate its acute termination effect in 7 patients with PSVT and 9 with paroxysmal atrial fibrillation. Pirmenol prolonged the refractory period of the retrograde conduction system in patients with or without an accessory pathway, and supraventricular tachycardia was no longer inducible at 60 min in 11 patients [8 of 11 with atrioventricular (AV) reentrant tachycardia and 3 of 5 with AV nodal reentrant tachycardia]. Pirmenol increased the heart rate (p < 0.01) and total systemic resistance (p < 0.05), and reduced the stroke volume index (p < 0.01), all significantly. The plasma concentration of pirmenol at 1 h after administration was 0.75 +/- 0.48 microgram/ml. A single oral dose of pirmenol during tachyarrhythmia successfully restored sinus rhythm in 4 of 7 (57%) patients with PSVT and 4 of 9 (44%) patients with paroxysmal atrial fibrillation. A single oral dose of pirmenol was well tolerated as episodic treatment in patients with supraventricular tachyarrhythmias.

Administration, Oral↗

PubMed1996

Changes in autonomic activity preceding onset of nonsustained ventricular tachycardia.

BACKGROUND: The triggering role of the autonomic nervous system in the initiation of ventricular tachycardia has not been established. To investigate the relationship between changes in autonomic activity and the occurrence of nonsustained ventricular tachycardia (NSVT) we examined heart rate variability (HRV) during the 2-hour period preceding spontaneous episodes of NSVT. Twenty-four subjects were identified retrospectively as having had one episode of NSVT during 24-hour Holter ECC recording. METHODS: We measured the mean interval between normal heats (meanRR), the standard deviation of the intervals between beats (SD), the percentage of counts of sequential intervals between normal beats with a change of >50 ms (%RR50), the logarithms of low- and high-frequency spectral components (lnLF, lnHF) of HRV for sequential 10-minute segments preceding NSVT. The correlation dimension (CDim) of HRV was calculated similarly for sequential 20-minute segments. We assessed the significance of the time-course change of each marker over the 120-minute period prior to NSVT onset. RESULTS: MeanRR (P < 0.05), lnLF (P < 0.0001), lnHF (P < 0.0001), the natural logarithm of the ratio of LF to HF (ln[LF/HF]; P < 0.05), and CDim (P < 0.05) showed significant time-course changes during that period, while SD and %RR50 did not. MeanRR, lnLF, lnHF, and CDim all decreased prior to the onset of NSVT, whereas ln(LF/HF) increased. We divided the subjects into two groups: one consisting of 12 patients with coronary artery disease; and the second group of 12 patients without known coronary artery disease. Both groups showed significant changes (P < 0.05) of CDim, lnLF, and lnHF preceding the episodes of NSVT. CONCLUSIONS: Changes in the pattern of HRV prior to the onset of episodes of NSVT suggest that changes in autonomic activity may commonly play a role in the triggering of spontaneous episodes of NSVT in susceptible patients. The measured changes suggest a reduction in parasympathetic activity, perhaps in conjunction with an increase in sympathetic activity, may trigger NSVT.

Adult↗

PubMed1996

Addition of lithium to chronic antidepressant treatment potentiates presynaptic serotonergic function without changes in serotonergic receptors in the rat cerebral cortex.

The effects of the addition of short-term lithium to long-term administration of antidepressants (clomipramine or citalopram) on the levels of 5-HT and 5-HIAA and serotonergic receptors were studied in the rat cortex. The addition of short-term Li to long-term antidepressant treatment potentiated an increase in 5-HIAA, although Li alone had no effect. On the serotonergic receptors, the addition of short-term Li had no effect. It is speculated that the therapeutic action of Li when added to antidepressants in the treatment of refractory depression may partly have its basis in the further activation of the presynaptic serotonergic system.

Animals↗

PubMed1996

Nitric oxide release from kidneys of hypertensive rats treated with imidapril.

To examine whether endothelial dysfunction in hypertension is reversible or not, we studied the effects of imidapril, an angiotensin-converting enzyme inhibitor, on nitric oxide release in stroke-prone spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 4-week treatment with imidapril (1 or 10 mg/d SC) or vehicle, acetylcholine-induced vasodilation and nitric oxide release in the isolated kidneys were determined. Nitric oxide release was measured by a chemiluminescense assay. Imidapril lowered blood pressure in stroke-prone SHR in a dose-dependent manner. Untreated stroke-prone SHR exhibited significantly attenuated responses to acetylcholine (10(-8) mol/L) of both renal perfusion pressure (stroke-prone SHE 42 +/- 4% versus Wistar-Kyoto rats [WKY] 58 +/- 4% [mean +/- SE], P < .01) and nitric oxide release (stroke-prone SHR +7.6 +/- 2.1 versus WKY +29.7 +/- 9.7 fmol/min per gram of kidney wt, P < .01). Imidapril at 10 mg/d significantly increased acetylcholine-induced renal vasodilation and nitric oxide release in stroke-prone SHR (renal perfusion pressure, 56 +/- 3%; nitric oxide release, +27.1 +/- 6.4 fmol/min per gram of kidney wt; both P < .01 versus stroke-prone SHR treated with vehicle). On the other hand, imidapril neither decreased blood pressure nor changed nitric oxide release induced by acetylcholine in DOCA-salt hypertensive rats. Staining for endothelial nitric oxide synthase and brain nitric oxide synthase was clearly detected in the kidneys of both stroke-prone SHR and WKY, whereas staining intensity was weaker in DOCA-salt hypertensive rats. Inducible nitric oxide synthase immunoreactivity was barely noticeable in any type of rat. Thus, imidapril restored endothelial damage by pressure-dependent mechanisms. Most of the nitric oxide detected in the perfusate seemed to be derived from constitutive nitric oxide synthase.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Bronchiolar disease in rheumatoid arthritis.

The pulmonary manifestations of rheumatoid arthritis (RA) include bronchiolar diseases such as follicular bronchiolitis (FB) and bronchiolitis obliterans (BO). In this study, we investigated the clinical and pathologic features of FB and BO, as well as the effect of erythromycin (EM) on these diseases. The subjects included 15 RA patients with biopsy-proven bronchiolar disease (eight with FB, seven with BO). None of the patients had Sjögren's syndrome. Eleven patients (73%) had chronic sinusitis, and 14 (93%) had a chronic cough with sputum. Bacterial culture of sputum was positive in 50% and 71% of the FB and BO patients, respectively. High-resolution computed tomography (HRCT) revealed small nodular shadows in the centrilobular regions (FB and BO), patchy areas of low attenuation (BO), and peribronchial thickening (FB and BO). Eleven patients who received EM therapy showed a significant improvement of symptoms. In addition, none of the 15 patients died of the bronchiolar disease during follow-up. In conclusion, RA patients with FB or BO basically have a chronic clinical course with main complaint of productive cough, and EM may be useful for the management of these diseases.

Anti-Bacterial Agents↗

PubMed1996

Cellular distribution of bronchus-associated lymphoid tissue in rheumatoid arthritis.

Bronchus-associated Lymphoid tissue (BALT) has been reported to be present in the lungs of patients with rheumatoid arthritis (RA). However, little is known about the structure and cellular distribution of BALT in this disease, so we investigated these points using immunohistochemical methods. The subjects were eight RA patients with BALT in biopsy specimens and a histologic diagnosis of follicular bronchiolitis. Seven patients had cough and purulent sputum, and four patients had positive sputum cultures. BALT was histologically composed of four distinct regions, which were the lymphoepithelium, the dome area, the follicular area, and the parafollicular area. Surface IgM+ B cells were predominant in the follicular area, whereas IgA+ cells were scattered in the dome and parafollicular areas. T cells were mainly found in the parafollicular area (CD4+ > CD8+), and most of them expressed the T Cell receptor alpha beta (alpha beta TCR). These findings were similar to those described previously for BALT in diffuse panbronchiolitis, which manifests as a chronic respiratory infection. The present study indicated that extrinsic stimulation as well as alterations of the immune response are involved in the development of BALT in RA, although the exact mechanism requires further clarification.

Adult↗

PubMed1996

Pathophysiological analysis of serum troponin T release kinetics in evolving ischemic myocardial injury.

The present study measured cardiac troponin T(TnT) for the pathophysiological analysis of evolving ischemic myocardial injury in 35 patients with unstable angina (3: Class IB, 32: Class IIIB) and in 40 patients undergoing coronary reperfusion therapy for acute myocardial infarction. Serum TnT, creatine kinase (CK), CKMB, myoglobin (Mb), and myosin light chain 1 (MLC1) were measured every 2-24 h for 10 days after admission to the CCU. In patients with unstable angina, positive test results were detected in 65.7% for TnT, 20% for CK, 37.1% for CKMB, 60.9% for Mb, and 26% for MLC1. Of the 23 patients with positive TnT, 12 (52.2%) had cardiac events. Of the 12 patients with negative TnT, 11 (91.6%) were event-free. All of the patients who developed cardiac events showed a persistent (n = 10) or delayed elevation (n = 2) pattern 28-120 h beforehand. The sensitivity for predicting cardiac events was 92.3% for TnT, 80% for Mb, 53.8% for CKMB, and 50% for MLC1. In patients with acute myocardial infarction, TnT release kinetics showed 2 peaks after coronary reperfusion therapy. TnT values at the 1st peak significantly correlated with maximum CKMB (r = 0.70, p < 0.05) and early-stage left ventricular wall motion score (r = 0.60, p < 0.05), while 2nd-peak TnT values significantly correlated with maximum MLC1 (r = 0.59, p < 0.05), the T1-SPECT score (r = 0.78, p < 0.05) and left ventricular ejection fraction (r = -0.74, p < 0.05) in the convalescent stage. The 2nd/1st-peak TnT ratio significantly correlated with the nQ/nST elevation index (ratio of the number of leads developing abnormal Q-wave 1 week after the onset to the number of leads showing ST elevation of more than 1 mm at admission) (r = 0.63, p < 0.05) in patients with anterior myocardial infarction. These data indicate that persistent release of TnT reflects progressive irreversible myocardial damage in unstable angina and indicates a risk of future cardiac events. In acute myocardial infarction, the 2nd/1st-peak TnT ratio in patients undergoing coronary reperfusion therapy may be useful for the quantitative evaluation of myocardial salvage.

Acute Disease↗

PubMed1996

Adenosine mediates the antiarrhythmic effect of ischemic preconditioning in isolated rat hearts.

Adenosine appears to mediate the preconditioning-induced reduction in infarct size in rabbits and dogs, but little is known about the role of adenosine in preconditioning-induced protection against ischemia-induced arrhythmias. We compared the effects of preconditioning induced by 2 cycles of 5 min of global ischemia and 2 cycles of 5 min of perfusion with either adenosine (100 mumol/L) or the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 100 nmol/L) in protecting against ischemia-induced arrhythmias in Langendorff-perfused rat hearts. Preconditioning reduced the incidence of ventricular tachycardia (VT) from 100 to 58% and the incidence of sustained VT or ventricular fibrillation (VF) from 92 to 33%. Perfusion with adenosine reduced the incidence of VT from 100 to 55%, the incidence of VF from 67 to 9% and the incidence of sustained VT or VF from 92 to 9%. CCPA reduced the incidence of sustained VT or VF from 92 to 25%. These interventions provided a true reduction in the severity of arrhythmias, rather than merely a delay in the onset. Our results suggest that the stimulation of A1 receptor by adenosine is involved in triggering ischemic preconditioning-induced protection against ischemia-induced arrhythmias in rats.

Adenosine↗

PubMed1996

Use of intravenous dofetilide in atrial flutter with hemodynamic instability.

Paroxysmal atrial flutter is a drug-resistant supraventricular tachyarrhythmia that is often accompanied by hemodynamic instability due to an excessive ventricular response. We report here a case of atrial flutter with 1:1 atrioventricular conduction, in which we were able to rescue the patient from a state of cardiogenic shock by using intravenous dofetilide, a new class III antiarrhythmic agent. Dofetilide was suitable for the treatment because it immediately increased atrioventricular nodal refractoriness without any negative inotropic action.

Adult↗

PubMed1996

Does inhibition of coronary nitric oxide synthesis alter coronary vascular tone in normal dogs?

To examine whether endothelial nitric oxide formation contributes to the vascular tone of resistance coronary vessels in vivo, we administered NG-nitro-L-arginine methyl ester (L-NAME) (10 and 100 micrograms/kg/min), a nitric oxide synthase inhibitor, as well as D-enantiomer into the left circumflex artery in normal dogs. Intracoronary L-NAME, which was associated with dose-related reductions in acetylcholine-induced coronary vasodilation, significantly reduced the baseline left circumflex blood flow by 6% and increased coronary vascular resistance of the left circumflex artery by 6%. D-enantiomer was ineffective in altering baseline coronary blood flow and vascular resistance of the left circumflex artery. These results indicate that continuous nitric oxide formation in the vasculature is important in the regulation of the coronary vascular tone of resistance vessels in vivo, and serves to maintain the vessels in a dilated state.

Animals↗

PubMed1996

[Analysis of initial potential of signal-averaged QRS complex in patients with acute myocardial infarction].

Non-invasive recording of the late potential (LP) by signal-averaging technique is useful in predicting ventricular tachycardia (VT), especially in patients with myocardial infarction (MI). However, the rate of positive LP is LOW in anterior or anteroseptal MI, since the LP is masked by QRS complex. The purpose of the present study is first, to detect local conduction delay in initial portion of QRS complex and secondly, to evaluate the clinical significance of the initial delay in patients with MI. Eighty patients with MI were analyzed; AS: anteroseptal, n = 18, including 6 VT, A: anterior, n = 22, 7 VT, I: inferior, n = 28, 9 VT, and P: posterior, n = 12, no VT. Twenty non-MI patients were used as normal controls (N). A signal processor (NEC 7 T 18) was used to record signal-averaged electrocardiograms and each 10 msec integral value of filtered QRS complex from the initial upstroke to the 60 msec point was automatically measured. The integral values of groups AS and A were lower than those of groups I, P, and N. AS with VT showed a lower integral value than AS without VT, but no differences were observed between A with VT and A without VT. We conclude that there is a much lower upstroke of signal-averaged initial QRS complex in patients with anteroseptal MI with VT, suggesting that the local conduction delay at the ventricular septum plays an important role in the mechanism of VT in these patients.

Action Potentials↗

PubMed1996

Induction and involvement of endogenous IGF-I in pancreas regeneration after partial pancreatectomy in the dog.

To elucidate whether and how IGF-I is involved in the regeneration of the pancreas after partial pancreatectomy, IGF-I mRNA expression, IGF-I protein synthesis, ornithine decarboxylase (ODC) activity and DNA replication in the remnant pancreas were determined in the dog. After pancreatectomy, IGF-I mRNA expression was remarkably enhanced in the remnant pancreas, showing the maximal value at post-operative day (POD) 1. Subsequently, IGF-I synthesis in the tissue was significantly stimulated at POD 2, and its maximal concentration was observed at POD 3. Following IGF-I synthesis, ODC activity was induced and its maximal activity was also obtained at POD 3. Finally, DNA replication was induced in the remnant pancreas, and its maximal level was observed at POD 5. These responses in the remnant pancreatic tissue to partial pancreatectomy were greatly enhanced as the resection rate was increased up to 95%. Positive correlations were observed between IGF-I concentrations in the remnant pancreas and the activities of ODC and DNA synthesis in the tissue after 95% pancreatectomy. These results suggest that the gene expression of IGF-I is rapidly induced in the remnant pancreas after partial pancreatectomy, and subsequently synthesized endogenous IGF-I peptides may stimulate ODC and other cell growth-related activities in the tissue in paracrine and/or autocrine manners eventually to induce DNA replication and tissue regeneration.

Animals↗

PubMed1996

A clinical study of minocycline-induced pneumonitis.

We studied the clinical features of minocycline-induced pneumonitis in seven patients. Acute symptoms included fever, dry cough and dyspnea, indicating acute respiratory failure. Diffuse ground glass shadows with Kerley's B lines, bronchial wall thickening, swelling of vascular bundles and pleural effusion were visible on radiography. Bronchoalveolar lavage or transbronchial lung biopsy confirmed pulmonary eosinophilia. Cessation of minocycline led to rapid remission with no treatment or only short-term steroid therapy. The lymphocyte stimulation test for minocycline with peripheral blood lymphocytes was not found to be useful for diagnosis.

Acute Disease↗

PubMed1996

Serum carnitine concentrations in different glomerular diseases with normal renal function.

Serum carnitine concentrations are known to decrease in patients on regular hemodialysis and to increase in chronic renal failure. However, there is little information available concerning serum levels of carnitine in different glomerular diseases in patients whose renal functions have not yet deteriorated. In this study, we measured serum carnitine concentrations in 40 pediatric patients with idiopathic nephrotic syndrome, IgA nephropathy, non-IgA glomerulonephritis, focal segmental glomerular sclerosis, and normal controls. The results showed that there were no significant differences in the serum-free and total carnitine concentrations (S-FCC and S-TCC, respectively) between patients with different glomerular diseases and the controls. Of interest was the statistically weak correlations of both S-TCC and S-FCC with BUN in these patients, despite their normal renal functions. The ratio of S-FCC to S-TCC was significantly higher as compared with that of the controls. These findings suggest that serum carnitine concentrations are not affected by the types of glomerular lesions and that serum levels of carnitine depend mostly on the glomerular excretory capacity of urea nitrogens, even when the renal functions have not yet deteriorated. The increase in the ratio of S-FCC to S-TCC may be an early reflection of changes in the serum carnitine profiles of these patients.

Adolescent↗

PubMed1996

[Etiology and classification of cardiac arrhythmias].

The presence of cardiac arrhythmias may at times suggest a specific underlying heart disease or even noncardiac disease. The most common and important cause of cardiac arrhythmias is coronary artery disease. In the past three decades, according to decrease in the incidence of rheumatic heart disease, the cause of atrial fibrillation is also going to change. Various classification of arrhythmias are available, however, a simple one is related anatomical portion of the heart in which they arise. Recently, the Sicilian gambit has introduced a classification which is based on there electrophysiologic mechanism. This classification is valuable for the clinician, because it makes easy to understand the strategy for suppression of the arrhythmias.

Arrhythmias, Cardiac↗