[Show abstract][Hide abstract] ABSTRACT: We have demonstrated photosensitization reaction-induced electrical conduction block of myocardial tissue. Subcellular distribution
of photosensitizer and electrophysiological cell response to this photosensitization reaction were studied with rat myocardial
cells, in order to clarify the mechanism of the myocardial electrical conduction block with photodynamic therapy (PDT). Photofrin®
was used as photo sensitizer in this study. The subcellular distribution of the photosensitizer was obtained by microscopic
fluorescent observation. The sites of photosensitizer localization were deter mined by organelle fluorescent probe, Rhodamine®
123, to specify the mitochondria location. The myocardial cell response to the photosensitization reaction was studied by
the observation of intracellular Ca2 + dynamics. Intracellular free Ca2 + concentration in the myocardial cells was measured with fluorescent Ca2 + indicator, Fluo-4 AM, by a high-speed Nipkow type confocal laser microscope during the PDT when the photosensitizer was distributed
outside the cells or localized to intracellular compartments. We concluded that the Ca2 + influx accompanied by cell membrane damage when the photosensitizer was distributed outside the cells or on the cell membrane
was the possible mechanism of the myocardial electrical conduction block with the photosensitization reaction.
KeywordsPhotodynamic therapy-photosensitization reaction-Photofrin®-electrical conduction block-Ca2 +
[Show abstract][Hide abstract] ABSTRACT: Infertility patients are known to be at increased risk of endometrial carcinoma (EC) and atypical hyperplasia (AH). However, the incidence and clinical features of EC and AH in these patients remain to be clarified. In this study, we examined the rate at which a routine infertility workup revealed EC/AH and investigated the clinicopathological features of EC/AH detected in this way. Among patients diagnosed with EC or AH at the Jichi Medical University Hospital between the 10-year period from 1997 to 2006, six patients were referred from Tochigi Central Clinic, a specialized infertility facility. We report the clinicopathological features of these patients and calculate the incidence of EC/AH in patients who underwent infertility investigations at Tochigi Central Clinic. All six patients were younger than 40 and had early stage disease (final diagnosis: EC stage IA: 3, EC stage IB: 1, AH: 2). A total of 19 826 patients underwent routine infertility investigations at Tochigi Central Clinic during the same period. The incidence of EC/AH detected from these investigations was 0.03% (6/19 826) and that of EC was 0.02% (4/19 826): 5-10 times higher than the overall incidence in Japanese women of the same age. Routine infertility investigations may provide an opportunity to examine the corpus uteri of young women in whom examination is otherwise limited, contributing to the early detection of EC/AH.
Human Reproduction 03/2009; 24(5):1045-50. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diode laser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca2+ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca2+ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca2+ concentration during the PDT was examined with a fluorescent Ca2+ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca2+ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca2+ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT.
Proceedings of SPIE - The International Society for Optical Engineering 02/2009; · 0.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dopamine treatment constitutes a major advance towards the management of severe ovarian hyperstimulation syndrome (OHSS) by causing renal and mesenteric vasodilatation as well as diuretic and positive inotropic actions. Docarpamine, an oral dopamine prodrug, is converted into dopamine after enteral administration, and the generated dopamine causes renal vasodilatation and diuresis. The purpose of this study was to assess whether docarpamine had beneficial effects in patients with OHSS. Twenty-seven patients, hospitalized because of OHSS and refractory to the initial therapy with intravenous albumin, were treated by docarpamine, after informed consent had been obtained. A 750-mg tablet of docarpamine was taken every 8 h. In some cases, the plasma levels of free dopamine were measured. The daily urinary outputs before and 1, 2, 3 and 4 days after the docarpamine treatment were 839 +/- 424 ml, 1121 +/- 608 ml, 1168 +/- 504 ml, 1325 +/- 815 ml and 1133 +/- 509 ml, respectively. There were significant differences between the first and each of the others (p < 0.05). In 19 (86.4%) of 22 patients treated, clinical symptoms associated with ascites were gradually improved after administrating docarpamine. The plasma free dopamine concentration rose to as high as 55.9 +/- 33.2 mg/ml during the first hour, which corresponded to the usual intravenous drip infusion treatment with dopamine. Moreover, there were no major adverse effects of docarpamine in this study. This was the first demonstration of docarpamine treatment in patients with intravenous albumin-resistant OHSS. Although no effect was seen in pregnant women, diuresis was increased in some women, and ascites decreased. These findings indicate that oral docarpamine administration could be one of the options in the management of patients with OHSS using dopamine therapy.
[Show abstract][Hide abstract] ABSTRACT: Clinical experience suggests that sodium channel blockers are effective in converting atrial fibrillation of recent onset but not chronic atrial fibrillation. We investigated changes in the electrophysiologic effects of pilsicainide, a pure sodium channel blocker, on the canine atrium during chronic rapid pacing (400/min). Three pairs of bipolar electrodes were sutured to the right atrial appendage in six dogs. Five days later, rapid atrial pacing was started after baseline measurements of the effective refractory period (ERP), the intra-atrial conduction velocity, the atrial wavelength, and the inducibility of atrial fibrillation. These studies were repeated at 2, 7, and 14 days of pacing, both before and after pilsicainide administration. Before pacing, pilsicainide increased ERP more than it decreased conduction velocity, causing an increase of wavelength, particularly at faster rates. However, this use-dependent prolongation of ERP disappeared after 2 days of pacing. Thus, pilsicainide failed to prolong ERP during chronic pacing, allowing progressive shortening of wavelength in the remodeled atrium. The effect of sodium channel blockers on atrial refractoriness may decline as rapid atrial excitation persists, limiting the usefulness of these agents for the treatment of chronic atrial fibrillation.
Journal of Cardiovascular Pharmacology 01/2002; 38(6):812-20. · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.
Japanese Circulation Journal 11/2001; 65(10):867-73.
[Show abstract][Hide abstract] ABSTRACT: We investigated the recovery of electrophysiological parameters from electrical remodeling after conversion of chronic lone atrial fibrillation in humans. Clinical studies have shown that the longer atrial fibrillation lasts, the more difficult it becomes to maintain the sinus rhythm after cardioversion. To explore the effects of the duration of atrial fibrillation on changes of electrophysiological parameters after conversion, we determined the atrial effective refractory period and P wave duration during right atrial pacing at 1 and 24 h after electrical cardioversion in 15 patients with chronic lone atrial fibrillation (median duration, 6 months). By 24 h after cardioversion, the effective refractory period at a pacing cycle length of 600 ms increased from 225+/-19 to 254+/-27 ms. However, the P wave duration did not decrease significantly 24 h after conversion. As the duration of atrial fibrillation became longer, the prolongation of effective refractory period was more delayed (P<0. 001, r=0.82), and the shortening of P wave duration was significantly smaller within 24 h after cardioversion (P<0. 001, r=0.67). After cardioversion of chronic lone atrial fibrillation, the recovery of shortened atrial refractoriness and prolonged intraatrial conduction time is dependent on the duration of preexisting atrial fibrillation.
International Journal of Cardiology 08/2001; 79(2-3):183-9. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 62 year old man was admitted for evaluation of recurrent episodes of syncope. A surface ECG showed frequent repetitive premature ventricular complexes of right ventricular outflow tract origin. Ventricular fibrillation was inducible by programmed electrical stimulation but otherwise cardiac evaluation was unremarkable. A diagnosis of idiopathic ventricular fibrillation was made and an implantable cardioverter-defibrillator (ICD) was installed. However, spontaneous ventricular fibrillation recurred, requiring repeated ICD discharges. The ventricular fibrillation was reproducibly triggered by a single premature ventricular complex with a specific QRS morphology. Radiofrequency catheter ablation was carried out to eradicate this complex. No ventricular fibrillation has developed after this procedure, and the patient does not require drug treatment.
[Show abstract][Hide abstract] ABSTRACT: Although immunoapheresis removing autoantibodies against the second extracellular domain of beta(1)-adrenergic receptors (ARs) improves cardiac function in patients with cardiomyopathy, the underlying mechanisms have not been defined. We examined the role of autoimmunity against the domain in the development of cardiac dysfunction in vivo. Japanese white rabbits were immunized with a synthetic peptide corresponding to the second extracellular loop of beta(1)-AR once a month with (beta+biso rabbits, n=10) or without (beta rabbits, n=13) bisoprolol treatment (2 mg/kg per day). Control rabbits received vehicle without bisoprolol treatment (n=13). Autoantibodies of IgG isotype against the domain were persistently detected in beta and beta+biso rabbits. Purified IgG from sera of beta and beta+biso rabbits increased cAMP production in a rabbit cardiac membrane preparation, which was blocked by bisoprolol. At 3 months, beta-AR uncoupling with increased G protein-coupled receptor kinase 5 (GRK5) expression was found in beta rabbits. At 6 months, left ventricular hypertrophy was noted with hemodynamic derangements in beta rabbits. This was accompanied by decreased beta(1)-AR density and increased inhibitory G protein and GRK5 expression, which were related to marked decrease in membrane cAMP production. These changes in beta rabbits at 6 months were prevented in beta+biso rabbits. There was no difference in the plasma norepinephrine concentration in the 3 groups over the observation period. Thus, autoimmunity against the second extracellular loop of beta(1)-ARs induced profound beta-AR desensitization and myocardial hypertrophy in vivo, associated with cardiac dysfunction. Sustained sympathomimetic-like actions of autoantibodies against the domain may be partly responsible for these changes.
Circulation Research 04/2001; 88(6):578-86. · 11.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Based on the results of the Cardiac Arrhythmia Suppression Trial (CAST), strategies for the treatment of tachyarrhythmias have changed rapidly. The Japanese Antiarrhythmics Long-Term (JALT) study was planned to investigate the present methods for choosing antiarrhythmic drugs, and the effects on long-term prognosis in patients with tachyarrhythmias in Japan. Following a 6-month preliminary study (JALT-1), there was a multicenter nonrandomized prospective study (JALT-2), with a 2-year follow-up, of patients with paroxysmal atrial fibrillation (PAF), sustained ventricular tachycardia (SVT) and nonsustained VT (NSVT). Four hundred fifty-five patients were registered, and 361 of them (79%) were analyzed. Cerebral infarction occurred in 10 of 193 patients (5.2%) with PAF. Transition to chronic AF was observed in 21 patients (10.9%), but in none of the patients receiving Ca antagonist therapy. Twenty-five patients died: 5 deaths were arrhythmic, 10 were because of pump failure, and 9 were noncardiac. The most significant difference in drug selection between JALT-1 and JALT-2 was the increase in the use of slow kinetic Na channel blockers for PAF and the decrease in the use of the same agents for VT in the JALT-2 study. A marked change of therapeutic strategy occurred in JALT-2 compared with JALT-1. Most patients with a poor prognosis had underlying heart diseases and heart failure, but the per annum rate of death by arrhythmia and pump failure in JALT-2 was less than that in JALT-1.
Japanese Circulation Journal 04/2001; 65(4):275-8.
[Show abstract][Hide abstract] ABSTRACT: Ovarian hyperstimulation syndrome (OHSS) appears to be caused by increased capillary permeability in the vascular endothelial cells. Such cells secrete excess amounts of von Willebrand factor (vWF), a large adhesive glycoprotein.
We retrospectively evaluated the circulating levels of vWF and of vascular endothelial growth factor (VEGF) twice, on the days of oocyte retrieval and embryo transfer, in 46 women who developed early-onset OHSS.
Nineteen, 14, and 13 women developed mild, moderate, and severe OHSS, respectively. Inconsistent changes were observed in the VEGF during oocyte retrieval and embryo transfer. However, the net increase in serum vWF during that period showed an increase in absolute value at the time of embryo transfer that paralleled an increase in the severity of OHSS. That is, in mild OHSS, the serum vWF increased from 140 +/- 44 to 164 +/- 28%; in moderate OHSS, it increased from 113 +/- 47 to 186 +/- 22%; and in severe OHSS, it increased from 120 +/- 35 to 274 +/- 63%. All 9 women with a vWF level > 230% at embryo transfer developed severe OHSS, while 9 of 13 women with severe OHSS exhibited a vWF > 230% at embryo transfer.
The results suggest that a rise of the serum level of vWF occurs prior to clinical manifestation of OHSS in patients with severe OHSS but not in patients with mild OHSS.
Journal of Assisted Reproduction and Genetics 02/2001; 18(2):114-9. · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.
Journal of Human Genetics 02/2001; 46(1):38-40. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this retrospective study was to determine the efficacy and safety of percutaneous T-tube placement for malignant hilar obstruction. Results were compared with self-expanding metal stents.
Between June 1989 and April 1999, 24 consecutive patients with type II, III, IV hilar obstructions underwent T-tube (n = 12) and metal stent placement (n = 12). A 9-F T-tube was placed percutaneously into the right and left hepatic ducts. Metal stents (diameter: 6-10 mm) were placed in both ducts.
Stent placement was successful in all patients. Early complications occurred in 2 patients in the metal stent group (arterio-biliary fistula and cholangitis). In the T-tube group, the 30-day mortality rate were 25%. These were not procedure related. The median patency period in the metal stent group (365.0 +/- 113.3 days) was longer than in the T-tube group (167.0 +/- 71.1 days). There were no significant differences in the median survival rates (224.0 +/- 39.0 days vs. 197.0 +/- 104.8 days).
Internal T-tube placement for drainage of malignant hilar obstruction is safe and associated with few complications. The advantage of this procedure is removability of the T-tube stents.
[Show abstract][Hide abstract] ABSTRACT: The patient was a 74-year-old man, a physician, whose chief complaint was an unproductive cough. The shadow of a mass was seen at the hilum of the left lung, and the mediastinal lymph nodes on both sides were swollen. No histological diagnosis was obtained even after bronchoscopy, including transbronchial needle aspiration biopsy, but large-cell carcinoma of the lung was diagnosed on the basis of ultrasound-guided biopsy of a shadow in the liver suspected of being a metastatic tumor (T2N3M1, Stage IV). Two courses of chemotherapy (CBCDA + VDS) failed to gain any improvement, and the pain resulting from recurrent bone metastases was managed mainly by the administration of the best supportive care. The patient was readmitted to the hospital after development of numbness in the right upper extremity followed by complication of pneumonia and heart failure, and he passed away. Autopsy revealed a primary hilar lung tumor with a histological diagnosis of poorly differentiated adenocarcinoma.
The Keio Journal of Medicine 01/2001; 49(4):162-72.
[Show abstract][Hide abstract] ABSTRACT: To re-evaluate outcomes of stenting in small vessels, we studied 176 patients successfully treated with several types of stent by way of intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). These lesions were divided into 3 subgroups according to reference diameter (RD) by QCA, and vessel diameter (VD) by IVUS (group I: pre-RD 2.5 mm; group II: pre-RD < 2.5 mm and pre-VD 4.0 mm; group III: pre-RD < 2.5 mm and pre-VD < 4.0 mm). Post-procedure percent diameter stenosis (4 +/- 3%), post-procedure percent plaque area (42 +/- 3%), and loss index (39 +/- 11%) in group II were not significantly different from those in group I (7 +/- 2%, 37 +/- 2%, 45 +/- 5%, respectively). The rates of restenosis and target lesion revascularization in group II (24.0% and 16.0%, respectively) were not different from those in group I (25.9% and 21. 2%, respectively), and were significantly favorable compared to group III (66.7% and 39.4%, respectively; p < 0.05). By the use of IVUS, we not only identified those vessels which would normally go unstented when only using QCA, but also documented excellent long-term outcome in these patients.
The Journal of invasive cardiology 01/2001; 12(12):625-30. · 0.82 Impact Factor