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Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

SummaryA 69-year-old woman underwent percutaneous coronary intervention for a severe stenotic lesion in the bifurcation of the mid-left anterior descending artery and first diagonal branch. A single stent was implanted into the left anterior descending artery. After the stent strut was dilated by balloon inflation in the diagonal branch, dissection occurred at the ostium of the diagonal branch and resulted in side branch occlusion due to hematoma. Bailout stenting was performed in the diagonal branch, but thrombus projection occurred in the left anterior descending artery. Aspiration, balloon inflation and thrombolytic therapy were performed, but distal embolism developed. This case illustrates that thrombus projection caused by stenting in a side branch may occur as a rare complication in percutaneous coronary intervention.

Determining the type of cardiac dysfunction is important for implementing therapeutic strategies and for prognostic insights. We characterized systolic dysfunction (SD) and isolated diastolic dysfunction (IDD) in adults referred for echocardiographic evaluation, and compared their clinical and other characteristics. In the present work, we studied 218 patients (137 males) with cardiac dysfunction (mean age, 66.3 +/- 8.3 years). SD was defined as a left ventricular ejection fraction (LVEF) of or= 45% in addition to the standard Doppler-echocardiography diagnostic criteria for IDD. Approximately 68% of subjects had SD (70% males). The proportions of hypertension, diabetes, and dyslipidemia were 44%, 26%, and 22%, respectively, without significant association with the type of dysfunction. Myocardial infarction (MI) was found in 31% of patients, and was significantly (P < 0.001) more prevalent among SD compared with IDD cases. Cerebral stroke (18%) and malignancy (16%) were significantly associated with IDD (29% versus 13% for SD in the case of stroke, and 26% versus 11% for SD in the case of malignancy; P = 0.008 for each). In multivariately-adjusted logistic regression analysis, the following variables were found to be significantly (P < 0.05) and independently associated with IDD: female gender (odds ratio [OR] = 2.207 [95% CI = 1.302-4.608]), stroke (OR = 2.009 [1.119-3.980]), and malignancy (OR = 2.016 [1.230-4.010]). On the other hand, previous MI (OR = 2.075 [1.769-4.808]) was independently associated with SD. In conclusion, some factors/comorbidities were more likely to associate with IDD (female gender, stroke, and malignancy) or SD (previous MI) when IDD and SD were compared with each other.

Background The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. Methods and Results To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60‐84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. Conclusions Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure. (Circ J 2008; 72: 1436 ‐ 1442)

Background Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado). Methods and Results Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fraction ≤50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend

Background The prevalence of congestive heart failure (CHF) is increasing with the aging of the community. Management of patients with systolic dysfunction (SD) is important for prevention of CHF, but there is little information regarding the burden of SD on Japanese communities. Methods and Results In order to delineate the epidemiological and clinical characteristics of SD patients, the medical records of patients from Sado Island were collected and summarized in 2003. From the 5 years prior to 2003, data for 497 patients were extracted. The mortality rate was significantly higher compared with the general population; and the total number of survivors had decreased to 410 by 2003. The proportion of SD patients in the general population increased sharply after the age of 65 years in males and 70 years in females, reaching 3.3% and 1.7% for men and women, respectively, in their 80 s. In 49% of the patients, the Charlson comorbidity index was ≥2, whereas 24% of females led a solitary life. Conclusions The total count of outpatients with SD is progressively increasing with age. These patients have multiple comorbidities, making the outcome of SD a poor one. The gender difference in disease characteristics and living conditions should be taken into consideration when establishing preventive strategies for CHF in Japanese communities. (Circ J 2007; 71: 1004 - 1012)

Background The incidence of diastolic heart failure (DHF) is increasing with the aging of the community and identifying patients with isolated diastolic dysfunction (IDD) is important for preventing DHF. However, very little information is available about such patients in the Japanese community. Methods and Results The medical information of all outpatients with moderate to severe IDD was extracted from the records of approximately 6,948 individuals who underwent echocardiographic (Echo) examinations during the past 5 years in Sado Island. Of the 284 patients extracted, 272 survived until 2003. In January 2003 the proportion of patients with moderate to severe IDD in the general population sector aged 45-84 years was 0.9% for males and 0.5% for females, and this proportion increased sharply after the age of 65 in both genders, reaching 1.6% for men in their 70 s and 0.8% for women in their 80 s. On Echo, 165 patients (61%) showed hypertrophic left ventricular geometry. The Charlson comorbidity index score was ≤1 in 63% of patients. The cumulative survival of IDD patients, irrespective of a history of congestive heart failure (HF), was significantly lower than in the general population. Conclusions Moderate to severe IDD is not uncommon in the elderly and has a poor prognosis. Characteristics of outpatients with IDD should be taken into consideration when establishing a preventive strategy for HF in the Japanese community. (Circ J 2007; 71: 1013 - 1021)

A number of bioassays for screening the compounds for estrogenic activity have been proposed so far, however, a yeast two-hybrid system appears more simple and inexpensive assay with high repeatability. The biggest problem of this bioassay is that it cannot measure estrogenic activity in some of the environmental samples. At is was assumed that the co-existing compounds were responsible for these false negatives, two methods were tested:1. Separation of such co-existing chemical interferences by use of liquid chromatographic method.2. Masking the retarding effect of such co-existing chemicals interferences by the addition of S9mix.The results indicated that both methods were effective to identify the estrogenic activity, however, the addition of S9mix was much more simple to conduct and more effective to determine the estrogenic activity in environmental samples.

Background The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. Methods and results The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. Conclusion LVD is expected to precipitate a future epidemic of heart failure in Japan.

Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration. The shell of the selected suppository is composed of VOSCO S-55 and progesterone for rapid release. The molded progesterone tablets for sustained release were embedded inside. The distribution of the weight and content of the suppository was limited, and the release rate of progesterone was significantly slower than that of a conventional progesterone suppository prepared in our hospital. The single-dose administration of the selected suppository to five healthy volunteers led to significant extension of the blood concentration. We also confirmed the rise of the basic value by multiple administration. The simulation comparison suggested that the blood progesterone concentration is controlled by once-a-day administration of the selected suppository better than twice-a-day administration of the conventional suppository. In conclusion, the sustained-release vaginal suppository prepared in this study was considered to be useful for clinical treatment.

本研究は道路植栽による騒音感の緩和効果をより確実に評価することを目的に心理的快適さの度合を検討した。一般に人がリラックスした状態のときに脳波のα波が出現することから,心理的快適さの度合をみるにはこの脳波が適していると考えた。緑量の異なる道路植栽のビデオ映像と騒音を刺激とし,国際電極配置法に従って脳波測定を行った。その結果以下のことが明らかとなった。(1)緑量が増大するのに従ってα2波が増大し,緑視率が高い状態のときリラックスした状態になることが明らかとなった。(2)道路植栽による騒音感の緩和は緑視率が高いとき認められた。(3)道路植栽による騒音感の緩和効果は騒音レベルが高いときの方が大きくなることが明らかとなった。

A measuring system was constructed with a horizontal platinum plate, a piezoelectric quartz crystal (quartz plate) on the platinum plate and a platinum wire set vertically above the centre of the platinum plate and at a distance of 0.8 mm from it in the same housing. The platinum plate and the wire were connected to an oscillator. The procedure is as follows: set the quartz plate on the platinum plate, set the recorder to record the frequency, place a single drop of reagent solution containing buffer and electrolyte on the quartz plate, leave for about 7 min to obtain a constant frequency, place a single drop of the ion sample solution containing electrolyte and buffer on the quartz plate along with a platinum wire using a micropipette, read off the frequency shift (ΔF, Hz) between the frequency at the start (when the single drop of the sample solution was placed, F1) and that at 100 s later (F2), ΔF = F1 – F2, and calculate the concentration of the ion from a calibration graph constructed with a standard solution. Sulphate and potassium ions at levels of 50 μM-0.5 mM can be determined using the barium salt or tetraphenylborate, respectively, with good reproducibility.

Determining the type of cardiac dysfunction is important for implementing therapeutic strategies and for prognostic insights. We characterized systolic dysfunction (SD) and isolated diastolic dysfunction (IDD) in adults referred for echocardiographic evaluation, and compared their clinical and other characteristics. In the present work, we studied 218 patients (137 males) with cardiac dysfunction (mean age, 66.3 +/- 8.3 years). SD was defined as a left ventricular ejection fraction (LVEF) of45%, whereas IDD was defined as a LVEFor= 45% in addition to the standard Doppler-echocardiography diagnostic criteria for IDD. Approximately 68% of subjects had SD (70% males). The proportions of hypertension, diabetes, and dyslipidemia were 44%, 26%, and 22%, respectively, without significant association with the type of dysfunction. Myocardial infarction (MI) was found in 31% of patients, and was significantly (P0.001) more prevalent among SD compared with IDD cases. Cerebral stroke (18%) and malignancy (16%) were significantly associated with IDD (29% versus 13% for SD in the case of stroke, and 26% versus 11% for SD in the case of malignancy; P = 0.008 for each). In multivariately-adjusted logistic regression analysis, the following variables were found to be significantly (P0.05) and independently associated with IDD: female gender (odds ratio [OR] = 2.207 [95% CI = 1.302-4.608]), stroke (OR = 2.009 [1.119-3.980]), and malignancy (OR = 2.016 [1.230-4.010]). On the other hand, previous MI (OR = 2.075 [1.769-4.808]) was independently associated with SD. In conclusion, some factors/comorbidities were more likely to associate with IDD (female gender, stroke, and malignancy) or SD (previous MI) when IDD and SD were compared with each other.

The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown.To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD.Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure.

The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients.The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030.LVD is expected to precipitate a future epidemic of heart failure in Japan.

Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado).Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fractionor =50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend0.0001), reaching 1-2% in those agedor =75 years. The prevalence of comorbidities was noticeable (47% had hypertension, 41% myocardial ischemia, 34% atrial fibrillation, 33% previous hospitalization because of congestive HF, 27% cerebral stroke). In comparison with Sado, Niigata patients were younger, with a higher prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and cerebral stroke).As the proportion of LVSD cases increases progressively with age, it is expected to simulate a future epidemic. The differences between patients' characteristics and disease patterns in urban and rural communities may favor individually tailoring preventive strategies for HF in these areas.

The incidence of diastolic heart failure (DHF) is increasing with the aging of the community and identifying patients with isolated diastolic dysfunction (IDD) is important for preventing DHF. However, very little information is available about such patients in the Japanese community.The medical information of all outpatients with moderate to severe IDD was extracted from the records of approximately 6,948 individuals who underwent echocardiographic (Echo) examinations during the past 5 years in Sado Island. Of the 284 patients extracted, 272 survived until 2003. In January 2003 the proportion of patients with moderate to severe IDD in the general population sector aged 45-84 years was 0.9% for males and 0.5% for females, and this proportion increased sharply after the age of 65 in both genders, reaching 1.6% for men in their 70 s and 0.8% for women in their 80 s. On Echo, 165 patients (61%) showed hypertrophic left ventricular geometry. The Charlson comorbidity index score wasor = 1 in 63% of patients. The cumulative survival of IDD patients, irrespective of a history of congestive heart failure (HF), was significantly lower than in the general population.Moderate to severe IDD is not uncommon in the elderly and has a poor prognosis. Characteristics of outpatients with IDD should be taken into consideration when establishing a preventive strategy for HF in the Japanese community.

The role of neural factors in experimental renal hypertension was studied from the points of peripheral vascular reactivity, function of baroceptors and sympathetic activity in renal hypertensive dogs and the isolated smooth muscle strips of hypertensive rats. (1) The hypotensive responses to pentobarbital was more marked and continued longer in chronic renal hypertensive dogs than the controls. (2) The pressor responses to noradrenaline was remarkably augmented in renal hypertensive dogs, while the changes in those to angiotensin and Pitressin were not so marked. (3) The threshold for adrenaline or noradrenaline of isolated smooth muscle strips of intestine, rectum and uterus of rats was lower in hypertensive rats than in the operated normotensive and control groups. But the threshold for angiotensin and acetylcholine was rather higher in the hypertensive group. (4) The sensitivity of baroceptors examined by using the isolated perfusion method was unchanged and the baroceptors were resetted to the higher blood pressure level in chronic renal hypertension. (5) The influence of sympathetic innervation on carotid sinus activity was not different between the normotensive and renal hypertensive dogs. (6) The depressor responses to the sufficient amounts of ganglioplegics were not significantly changed in hypertensive dogs compared with the normotensives. (7) After the extensive sympathectomy the direct blood pressure fall was not significantly different between the normotensive and renal hypertensive dogs and the final blood pressure level was higher in renal hypertension than the control level. (8) The urinary excretion of adrenaline and noradrenaline was not significantly changed in chronic renal hypertensive dogs except the slight increase in the stage of blood pressure rising. Thus, increased sensitivity of peripheral blood vessels to noradrenaline was demonstrated in vivo and in vitro experiments in hypertensive animals. The baroceptors were resetted to the higher blood pressure level, and their sensitivity itself remained unchanged in renal hypertension. The sympathetic overactivity was not recognized in hypertension. Therefore, only the increased sensitivity of peripheral vessels to noradrenaline contributes to a part of the pressor mechanism in renal hypertension, while the baroceptors and sympathetic activities are passively adjusted to the higher blood pressure levels in hypertension.