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Biomedical subjects

H Ohta

Publications and source records attributed to H Ohta.

At least 91 records · Page 5Linked to original sources

Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.

The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E-3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/-10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E-3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan.

Angiotensin Receptor Antagonists↗

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

Aged↗

Dr. Soju Kurihara: increased awareness of cytologic diagnosis.

Cytopathology is now regarded as an important tool for detecting cancer, especially uterine cervical cancer. There was, however, a hard way to acquire the current status. This technique, the diagnosis of cancer by light microscopic examination of exfoliated cells, was first established by Dr. Papanicolaou in the 1940's. For spreading this technique and acknowledgement of this clinical field by conservative pathologists, many doctors including Dr. Kurihara, Professor emeritus of Department of Obstetrics and Gynecology, School of Medicine, Keio University, have made efforts for about fifty years. Dr. Kurihara and his colleagues made a clinical study and revealed the natural history of uterine cervical cancer from dysplastic lesions. Based on these results, he supported the establishment of the new screening system for uterine cervical cancer, "Tohbo-Hoshiki", which is now widely employed in Japan. This system has played an important role to decrease the mortality from uterine cervical cancer. Dr. Kurihara is one of the founders of the Japanese Society of Clinical Cytology, which has played a central role in the development of cytologic diagnosis in Japan, and he also contributed to bring up many gynecologic oncologists specializing in cytopathology and the treatment of cancer. Although remarkable progress has been made in computer-related technology and the automation of cytologic diagnosis is no longer a dream, the results of the untiring efforts of Dr. Kurihara and his colleagues will continue to play an instrumental role in the future advancement of cytologic diagnosis.

Cytodiagnosis↗

[Comparison of carotenoid components between GM and non-GM papaya].

We compared the carotenoid profile in GM papaya (Sunup) line to that of a non-GM one (Sunset). First, to identify major carotenoids in papaya, large-scale extraction was carried out with methanol. HPLC analyses of the methanol extracts revealed that both papayas mainly contained 5 pigments and no apparent difference was observed in the HPLC profiles. On the basis of LC/MS data and photodiode-array spectra, beta-carotene (3), lycopene (2), beta-cryptoxanthin (1), and beta-cryptoxanthin myristoyl and lauroyl esters (4 and 5) were identified as major carotenoids. It is well known that most carotenoids are labile, so a rapid analysis with precautions to avoid decomposition was developed to quantify their contents in the original fruits. Frozen samples of the fruits were sliced and a piece (about 2 g) of fruit was cut out and lyophilized. After extraction of the piece with methanol containing an anti-oxidant, BHT, the extract was further partitioned with hexane and methanol. Finally the contents of the main carotenoids in the hexane fraction were analyzed by HPLC. The contents of total carotenoids (sum of 1-5) and beta-cryptoxanthin (1, 4 and 5) in GM papaya fruit were estimated to be 0.764 +/- 0.056 and 0.604 +/- 0.051 (mumol/g), respectively and those in non-GM fruit were 0.883 +/- 0.145 and 0.705 +/- 0.098 (mumol/g), respectively. These differences are not statistically significant.

Carica↗

[A case of the spinal subdural hematoma formation following ventriculoperitoneal shunting for von Recklinghausen's disease associated with aqueductal stenosis].

Von Recklinghausen's disease associated with hydrocephalus due to non-tumoral aqueductal stenosis is rare. Furthermore the formation of subdural hematoma within the spinal canal is also a very rare complication of ventriculoperitoneal shunt. We presented a case of spinal subdural hematoma formation following ventriculoperitoneal shunting for von Recklinghausen's disease associated with aqueductal stenosis. A 10-year-old girl with von Recklinghausen's disease was referred to our hospital for gait disturbance during the previous 8 months. Magnetic resonance imaging (MRI) revealed hydrocephalus due to non-tumoral aqueductal stenosis, and ventriculoperitoneal shunt was instituted. Three months later, the patient developed lumbar pain and paraplegia. MRI revealed subdural hematoma in the lumbosacral spinal canal, and bilateral intracranial subdural hematoma were shown on computerized tomography (CT) scans. Subdural hematoma in the lumbosacral spinal canal was evacuated by laminectomy. Improvement of her neurological deficit was obtained postoperatively, and intracranial subdural hematomas disappeared spontaneously. Spinal subdural hematoma is assumed to be formed by the migratory movement of intracranial subdural hematoma under the influence of gravity. A characteristic finding of MRI is that such a subdural hematoma in the lumbosacral canal is located around the cauda equina.

Cerebral Aqueduct↗

[Persistent primitive hypoglossal artery aneurysm--case report].

The aneurysm arising from a persistent primitive hypoglossal artery (PHA) is rare, and only 13 such cases have been reported in literature. We present a 62-year-old woman with an aneurysm of PHA at its junction with the basilar artery. The patient consulted our hospital for a transient loss of consciousness and headaches. No neurological deficit was found, but MRI and MRA showed an aneurysm of the vertebrobasilar junction. Cerebral angiogram after admission showed the aneurysm of PHA at its junction with the basilar artery. Perspective 3D-CTA and 3D-T2 weighted MR images were composed to simulate the condition and aneurysmal surgery via the transcondylar approach was carried out. The aneurysm was successfully clipped and the patient was discharged with no neurological deficits. Perspective 3 D-CTA and MRI simulation were very useful for this operation.

Cerebral Arteries↗

[Incidence and severity of coronary artery disease in patients with acute aortic dissection: comparison with abdominal aortic aneurysm and arteriosclerosis obliterans].

OBJECTIVES: The incidence and severity of coronary artery disease were studied in patients with acute aortic dissection (AAD), and compared with coronary artery disease in patients with abdominal aortic aneurysm (AAA) or arteriosclerosis obliterans (ASO). METHODS: A total of 71 patients(42 males, 29 females, mean age 61.4 +/- 10.0 years) with AAD, undergoing coronary angiography between 1988 and 1999, were studied including 38 patients with open communication type and 33 patients with thrombosed type. According to the Stanford classification, 18 patients were type A and 53 patients were type B. Patients with AAD following Marfan syndrome or chest trauma were excluded from the study. Selective coronary angiography was performed in age- and sex-matched patients with AAA(n = 57; 42 males, 15 females, mean age 63.9 +/- 4.6 years) or ASO (n = 95; 66 males, 29 females, mean age 62.4 +/- 9.4 years). Coronary artery disease was defined as > or = 75% stenosis (left main trunk lesion of > or = 50% stenosis) by multidirectional imaging. RESULTS: Significant coronary artery disease was demonstrated in 14 patients with AAD (19.7%), 25 patients with AAA (43.9%), and 49 patients with ASO (51.5%). The incidence of coronary artery disease was significantly lower in the AAD group than in the other two groups (p < 0.05). One-vessel disease was present in approximately 70% of the patients with AAD and coronary artery disease. In contrast, multivessel disease was observed in approximately 50% of patients with AAA and ASO. Classification of the patients with AAD according to the blood flow in the false lumen showed coronary artery disease was more highly associated with the thrombosed type [10 (30.3%) of 33 patients] than the open communication type [4 (10.5%) of 38 patients]. Multivariate logistic regression analysis of the patients with AAD showed coronary artery disease was associated with a high serum total cholesterol level (p = 0.025) and the thrombosed type (p = 0.043). CONCLUSIONS: The incidence of coronary artery disease was significantly lower among patients with AAD than among age- and sex-matched patients with AAA or ASO. Coronary artery disease developed in 30% of the patients with the thrombosed type of AAD, although the prognosis seemed to be good.

Acute Disease↗

[Bilateral carotid stenting for radiation-induced arterial stenosis].

We report a case of bilateral radiation-induced internal carotid artery (ICA) stenosis treated with stenting. A 67-year-old man experienced transient left hemiparesis several times, and it was diagnosed as a bilateral ICA stenosis by magnetic resonance angiogram (MRA) and cervical ultrasound sonogram (US). Ten years before, the patient had received radiation therapy (66 Gy) and radical resection for a squamous cell carcinoma (SCC) in the right infrapharyngeal space. A cerebral angiogram showed bilateral severe ICA stenosis (right; 90%, left; 99%). We diagnosed this as radiation-induced ICA stenosis, and performed carotid angioplasty with a self-expanding stent. The post-operative course was uneventful and the patient was discharged without neurological deficits. Carotid endarterectomy (CEA) is difficult in the case of carotid artery stenosis due to radiation-induced arterial injury. Carotid stenting may be an alternative treatment for such a patient.

Aged↗

Pathophysiological roles of endogenous endothelin-1 in dogs with chronic heart failure produced by rapid right ventricular pacing.

This study was designed to analyze the pathophysiological role of the endogenous endothelin (ET) system and the therapeutic approach to congestive heart failure (CHF) with ET(A)/ET(B) receptor antagonists in a canine CHF model. After 3 weeks of rapid right ventricular pacing (240 beats/min), concentrations of immunoreactive ET-1 in dogs increased approximately 2-fold in plasma and in the left and right ventricles but not in the lung. There were no meaningful changes in the density and affinity of total ET receptors, or in the ratio of ET(A) to ET(B) receptors. To clarify the functional role of endogenous ET, we examined the effects of acute injection of J-104132 (1 and 3 mg/kg i.v.), an ET(A)/ET(B) receptor antagonist, on cardiovascular and renal function in dogs with CHF. Compared with vehicle, J-104132 at both doses significantly decreased pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP), and increased cardiac output (CO) and renal blood flow. J-104132 had no effects on heart rate and cardiac contractility. In addition, we examined whether J-104132 has an additive effect in the presence of enalaprilat. J-104132 (1 mg/kg i.v.) administered after enalaprilat (0.05 mg/kg i.v.) induced further decreases in MAP, PCWP and PAP, and further increases in CO, resulting in further decreases in total peripheral resistance. These results indicate that the endogenous ET system is exaggerated in CHF and has a detrimental effect on cardiac function. Therefore, J-104132 given alone or as combination therapy may play a beneficial role in the treatment of CHF in humans.

Angiotensin-Converting Enzyme Inhibitors↗

[Stenting for proximal subclavian and brachiocephalic artery occlusion--preliminary results].

The authors report the initial results, between January 1998 and February 2001, of stenting utilizing the brachial approach in seven patients for total occlusions at the following locations: two right subclavian, one brachiocephalic, and five left subclavian arteries. All lesions were associated with subclavian steal syndrome. Indications for the treatment included ischemic symptoms in the affected arm (seven patients), and vertebrobasilar insufficiency (five patients). A total of eight stents were implanted in six occluded arteries, resulting in a 75% procedural success rate. Procedural complications encountered were two subintimal dissections by a 0.035-inch guide wire during recanalization, and one stent dislodgement with migration. There was no stroke, presumably because of the previously reported preventive effect of delayed reversal of a stealing vertebral artery. Follow-up over a mean duration of 11 months revealed no sign or symptom of recurrence in cases with initial technical success. The results of the current study, with a literature survey, indicated that percutaneous transluminal angioplasty with primary stent deployment in an occluded prevertebral segment of the subclavian or the brachiocephalic artery should be considered as an available choice for treatment. Further points, such as some remaining technical and clinical problems, will require more experience and consideration.

Adult↗

[Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis].

The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.

Adult↗

Postmenopausal hormone replacement therapy use and risk of endometrial cancer in Japanese women.

The relationship between the risk of endometrial cancer and the use of noncontraceptive estrogens by Japanese postmenopausal women was investigated in a hospital-based case-control study of 1025 women with endometrial cancer and 1267 with other conditions. The overall odds ratio (OR) for estrogen use with or without progestins, compared with never use of any type of estrogens, was 0.917 (95% confidence interval (CI) 0.622-1.353), suggesting that hormone replacement therapy is not a causative agent for endometrial cancer in Japanese women, and that a recent increase in the incidence of endometrial cancer in Japanese women may be related to changes in their life-style. However, although not statistically significant, women who used estrogen without progestin for 12 or more months had an OR of 2.552 (CI 0.231-28.192), while those who used estrogen with progestin for 12 or more months had an OR of 0.425 (CI 0.086-2.113). These results indicate that the addition of a progestin should be considered for reducing the risk of endometrial cancer in Japanese women.

Asian People↗

Vaginal symptoms in Japanese postmenopausal women: comparison with other climacteric symptoms.

OBJECTIVES: This study was designed to investigate the current status of vaginal symptoms in Japanese postmenopausal women, and to clarify the significance of vaginal symptoms by analyzing their relationship to other climacteric symptoms. METHODS: The complaints of 613 women attending a menopause clinic (mean age +/- standard deviation 53.5 +/- 7.2 years; time since menopause or bilateral oophorectomy 6.4 +/- 6.5 years) were evaluated according to the Keio modified menopause index. RESULTS: In total, 56.4% of subjects had at least one vaginal symptom. The most frequent vaginal symptom was dyspareunia, followed by vaginal dryness, discharge and itching, and the mean prevalence of the four symptoms was 31.7%. The peak intensity of vaginal symptoms occurred in the sixth decade, or 3-5 years after menopause or oophorectomy. Vaginal symptoms were usually associated with other climacteric symptoms, but some occurred independently. CONCLUSIONS: A moderate proportion of Japanese postmenopausal women experience vaginal symptoms, which can occur independently of other climacteric symptoms. Vaginal symptoms therefore warrant careful attention during the treatment of postmenopausal women.

Adult↗

[Differences between gynecological cancer patients taken care for at home and those taken care for at the hospital].

Thirty-five patients with end-stage gynecological cancer, twelve taken care for at home care and 23 taken care for at our hospital, were compared. The life span after recurrence was significantly (p < 0.05) longer in the group taken care for at home. The number of persons living with the patient was also significantly (p < 0.01) larger in the group taken care for at home. Moreover, the hospitalization in the end stage of the disease was significantly (p < 0.01) shorter in the group taken care for at home. The average hospitalization in the end was for 6.5 days. Four patients died at their home. Average period the 12 patients stayed at home was 52.7 days. Following matters are important in order to provide home care. 1. We must know the biological characteristics of the cancer. 2. It is important that it does not lose the timing to which shift to the home care, keeping good doctor-patient relationship. 3. Limit of the therapy against cancer and importance of treatment at home should be carefully and clearly explained to the patient.

Adult↗

[Expectations for alendronate in gynecology].

Although the effect of alendronate is slightly less effective than that of hormone replacement therapy in terms of the short-term increase in bone mineral density, alendronate excels with respect to long-term benefits, often persisting after discontinuation of treatment. Alendronate is more effective than hormone replacement therapy in preventing femoral neck fractures and is thus indicated for the long-term prophylaxis of postmenopausal decreases in bone mineral density and for the management of osteoporosis in women who have fractures or an increased fracture risk. Alendronate may become a treatment of first choice for osteoporosis in postmenopausal women. As further evidence of cardiovascular benefits of alendronate becomes available, alendronate is expected to contribute to the overall health care of middle aged and elderly women.

English Abstract↗

[Drug therapy for osteoporosis associated with rheumatoid arthritis (estrogen replacement therapy)].

Various types of drug therapy are available for the management of osteoporosis associated with rheumatoid arthritis. Hormone replacement therapy plays an especially important part in the management of this condition. Although hormone replacement therapy increases lumbar bone mineral density in patients who have osteoporosis and rheumatoid arthritis, similar to those with primary osteoporosis, its effect on femoral bone mineral density remains controversial. Since hormone replacement therapy is also effective for rheumatoid arthritis, it is an important treatment option in patients who also have osteoporosis. Evidence is awaited from studies with new designs, including assessment of fracture risk.

English Abstract↗

In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist.

1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl -1, 3-dihydro-2H-benzimidazol-2-one (J-113397) was found to be the first potent nonpeptidyl ORL1 receptor antagonist (K(i): cloned human ORL1=1.8 nM) with high selectivity over other opioid receptors (K(i): 1000 nM for human mu-opioid receptor, >10,000 nM for human delta-opioid receptor, and 640 nM for human kappa-opioid receptor). In vitro, J-113397 inhibited nociceptin/orphanin FQ-stimulated [35S]guanosine 5'-O-(gamma-thio)triphosphate (GTP gamma S) binding to Chinese Hamster Ovary (CHO) cells expressing ORL1 (CHO-ORL1) with an IC(50) value of 5.3 nM but had no effect on [35S]GTP gamma S binding by itself. Schild plot analysis of the [35S]GTP gamma S binding assay and cAMP assay using CHO-ORL1 indicated competitive antagonism of J-113397 on the ORL1 receptor. In CHO cells expressing mu-, delta- or kappa-opioid receptors, J-113397 had no effects on [35S]GTP gamma S binding up to a concentration of 100 nM, indicating selective antagonism of the compound on the ORL1 receptor. In vivo, J-113397, when administered subcutaneously (s.c.), dose-dependently inhibited hyperalgesia elicited by intracerebroventricular (i.c.v.) administration of nociceptin/orphanin FQ in a tail-flick test with mice. An in vitro binding study using mouse brains indicated that J-113397 possesses high affinity for the mouse ORL1 receptor (K(i): 1.1 nM) as well as the human receptor. In summary, J-113397 is the first potent, selective ORL1 receptor antagonist that may be useful in elucidating the physiological roles of nociceptin/orphanin FQ.

Analgesics, Opioid↗

Wave dispersion relations in Yukawa fluids.

The wave dispersion relations in the fluid phase of Yukawa systems are obtained from molecular dynamics (MD) simulations for a wide range of the parameters. The Yukawa system is a collection of particles interacting through Yukawa (i.e., screened Coulomb) potentials, which can serve as a simple model for dusty plasmas. Our simulations have clearly shown that the transverse wave dispersion has a cutoff at a long wavelength even in the case of weak screening. The MD simulation data are compared with earlier theoretical predictions of the Yukawa dispersion relations and the validity of these theories is clarified.

Journal Article↗