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Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted.A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry.TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC)The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

BACKGROUND The impact of the striking perinatal circulatory changes on blood flow distribution have not to date been well examined in hypoplastic left heart syndrome (HLHS). This study aimed to document perinatal redistribution of cardiac output in HLHS compared with healthy control subjects, to further understand the impact of the perinatal transition on cerebral and systemic blood flow. METHODS Prospectively recruited HLHS case subjects (n = 31) and healthy control subjects (n = 19) underwent serial echocardiography from late fetal stages to 96 hours after birth. Combined cardiac output (CCO), systemic, pulmonary, cerebrovascular, and splanchnic flow data were compared between neonates with HLHS and control subjects, and the impact of vasoactive support and positive pressure ventilation in HLHS patients was examined. RESULTS In late gestation, CCO was similar between HLHS and control subjects, whereas middle cerebral artery (MCA) pulsatility index (PI) in HLHS was consistent with low cerebral vascular resistance. In the 96 hours after birth, CCO and pulmonary blood flow progressively increased in HLHS compared with control subjects (P < 0.001), and CCO was further increased in neonates with HLHS receiving vasoactive support (P = 0.01). Neonates with HLHS had reduced systemic and 6-24-hour superior vena cava (SVC) flow compared with control subjects (P < 0.001). Low systemic flow was further suggested by increased MCA and celiac artery PI at 6-48 hours in neonates with HLHS (P < 0.001). Systemic and SVC flow did not differ between those with and without vasoactive support. CONCLUSIONS We provide quantitative echocardiographic evidence associating impaired cerebral and systemic blood flow with perinatal hemodynamic changes in the preoperative neonate with HLHS.

Aim The purpose of this study was to establish a simple method to distinguish premature ventricular contractions (PVC) from premature atrial contractions (PAC) using a fetal Doppler ultrasound arterial pulse waveform to measure time intervals between sinus node restarting. Methods We retrospectively identified 14 fetuses with premature contraction (8 with PAC, 6 with PVC). We measured two distinct parts of time intervals using an arterial pulsed‐wave Doppler: the two consecutive waveforms just before the premature contraction (2‐V interval) and two consecutive waveforms including the premature contraction (XV interval) to measure time intervals between sinus node restarting. We then evaluated the time difference between the 2‐V and XV intervals in PVC compared to PAC. Results For PVC, the difference between the 2‐V interval and the XV interval was significantly shorter than that for PAC. A cut‐off point of 33 ms, where a difference ≤33 ms was clearly shown to be associated with a PVC and a difference more than 33 ms signified a PAC was demonstrated. Conclusion The 2‐V and XV interval measurements, used to measure time intervals between sinus node restarting, could easily distinguish PVC from PAC in utero. Therefore, this study could potentially be a feasible and effective method for obstetricians or sonographers to employ usefully.

Background Preterm premature rupture of membrane (pPROM) leads to high neonatal mortality due in part to severe lung hypoplasia (LH). In other causes of severe LH, fetal echo-based parameters of smaller branch pulmonary arteries (PA), shorter acceleration to ejection time ratio (AT/ET), increased peak early diastolic reverse flow (PEDRF), and higher pulsatility index (PI) are predictive of worse neonatal outcome. We sought to determine whether these parameters correlated with worse clinical outcome in pPROM. Methods Twenty-five pregnancies complicated by pPROM were prospectively recruited. Fetal echocardiography was used to evaluate branch PA diameters and Doppler parameters. Clinical records were reviewed. Fetal echo findings were compared between early survivors and non-survivors. Results Of 25 pPROM cases, 5 had early neonatal demise (≤3 days) due to respiratory insufficiency. While gestational age at pPROM, fetal echo, and at birth did not differ, amniotic fluid index (AFI) was significantly lower in early non-survivors compared to survivors (p = 0.05). No difference was observed in PA diameter, PEDRF, or PI; however, branch PA AT/ET was significantly shorter in non-survivors (right PA median 0.12 (0.11-0.16) vs. survivors 0.17 (0.14-0.21), p = 0.046 and left PA 0.12 (0.09-0.13) vs. survivors 0.16 (0.11-0.21), p = 0.042). Conclusions We found a significantly lower AFI and shorter fetal bilateral branch PA AT/ET to be associated with early neonatal demise following pPROM.

Objective Prematurity and bronchopulmonary dysplasia (BPD) are associated with poorly understood abnormalities of ventricular function. We therefore comprehensively compared biventricular function in infants with and without BPD. Methods Prospective observational study in extremely preterm infants with (n = 20) and without (n = 38) BPD using conventional and advanced echocardiography at 28 days (T1) and near-term (T2). Results Infants with BPD had lower birth gestational age (26.7±1.9 vs 27.4±1.1 weeks, p = 0.047) and weight (884±207 vs 1108±190 g, p = 0.0001). BPD was associated with larger right ventricles (RV) and reduced RV systolic strain rate at T1 and pulmonary hypertensive indicators at T2 (pulmonary artery acceleration time BPD 51±17 vs no BPD 63±12 ms, p = 0.017). At T1/T2, infants with BPD had lower RV tissue Doppler velocities (e', a' and s) and higher E/e' ratios (T1: BPD 10.4±2.4 vs no BPD 6.2±3.1 cm/sec, p = 0.001; T2: BPD 8.0±3.1 vs no BPD 5.6±2.6 cm/sec, p = 0.02), altered LV diastolic function (apical circumferential T1 early diastolic strain rate BPD 2.8±0.8 vs no BPD 3.6±1.0 /sec, p = 0.04; T2 late diastolic strain rate, BPD 2.29 ± 0.99 vs no BPD 1.67±0.84 /sec, p = 0.03) and LV rotational mechanics (T1: twist rate BPD 90±16 vs no BPD 130±48 deg/sec, p = 0.008; untwist rate (UTR) BPD -69±90 vs no BPD -147±68 deg/sec, p = 0.008; torsion BPD 2.78±0.56 vs no BPD 4.48±1.74 deg/cm, p = 0.009; and T2: UTR BPD -132±69 vs no BPD -179±57 deg/sec, p = 0.013). Conclusion BPD is associated with altered RV diastolic function that persists near term, with elevated pulmonary vascular resistance, and with persistent alterations in LV apical strain rate and rotational mechanics.

The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment.We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy.The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy.The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo.Level I, double-blinded, placebo-controlled, prospective study.

This article explores the issue of how cultural backgrounds influence the way readers construct mental images of fictional characters. In an experiment conducted in 2008 in Germany, we found evidence suggesting that readers of fictional narratives draw on their stereotypes when evaluating the personality of a fictional character. Moreover, results of this experiment also suggest that this tendency to focus on (stereo-)typical attributes in the evaluation of characters increases rather than decreases with knowledge about the respective culture. Here, we discuss what cognitive processes presumably underlie these findings and what conclusions can be drawn for the reading process from these theoretical considerations on the influence of readers' cultural beliefs, values, norms, and so on. We further report the results of a second experiment conducted in Japan, which corroborates our previous findings. Finally, we outline suggestions for future endeavors that could make use of our research to address further questions.

This cross-sectional study investigated the relationship between eating speed and fat accumulation in Japanese non-obese adults.In total, 381 non-obese participants aged 35-74 years underwent a health checkup including fat distribution. All participants underwent magnetic resonance imaging to quantify visceral fat area (VFA) and subcutaneous fat area (SFA). Information on eating speed was obtained using a self-administrated questionnaire.The numbers of participants with self-reported behavior of eating slowly, medium, or quickly were 24 (6.3%), 180 (47.2%), and 177 (46.5%), respectively. The prevalence of VFA ≥100 cm2 was higher in the eating quickly group than in the eating slowly (p0.05) or medium groups (p0.05). On the other hand, no significant differences in SFA ≥100 cm2 were observed between groups. In addition, multiple stepwise regression analysis showed that eating quickly was positively correlated with VFA (standard β=0.068, p0.05), but not with SFA.Although eating quickly was positively correlated with bigger VFA in Japanese non-obese adults, no associations were found between eating speed and SFA.

This study investigated the relationship between eating behavior and poor glycemic control in 5,479 Japanese adults with hemoglobin A1c (HbA1c) p p p p p

Objective: To evaluate the effects of the eight-week consumption of Theracurmin® on liver function, fatigue, and sleep. Methods: This was a randomized, double-blind, placebo-controlled, parallel-comparison study involving 68 healthy Japanese adults. Subjects were allocated into either the active (Theracurmin®) or placebo group ( n = 34 each) using a random number generator. Subjects consumed two capsules per day of either the active or placebo food for eight weeks. The primary outcome was the serum alanine aminotransferase (ALT) levels at eight weeks, whereas the secondary outcomes were the biomarkers of liver function, comparison of the percentages of improvement in liver function based on the decision criteria, OSA sleep inventory MA version (OSA-MA), and visual analog scale of fatigue. Results: Each group included 33 subjects in the full analysis set. ALT levels in the per protocol set analysis, except for subjects drinking quantities of alcohol that increase the risk of lifestyle-related disease onset, showed a significant decrease in ALT compared to the placebo group ( P < 0.05). The subjective symptom in the fatigue recovery factor of OSA-MA was significantly improved through the intervention ( P < 0.05). The fatigue recovery effect of Theracurmin® was prominent in the subjects aged ≤ 45 years, the age group defined by the Ministry of Health, Labour and Welfare as middle-aged and older persons in the Act on Stabilization of Employment of Elderly. No adverse event was observed. Conclusions: These results suggest that the consumption of Theracurmin® or eight weeks improved liver function and fatigue recovery at awakening in healthy Japanese adults. Trial registration: UMIN-CTR: UMIN000039319. Foundation: Theravalues Corporation Keywords: highly bioavailable curcumin, liver function, alanine aminotransferase (ALT), OSA sleep inventory MA version, fatigue recovery

This cross-sectional study investigated the relationship between periodontal condition and ultrasound-diagnosed non-alcoholic fatty liver disease (NAFLD) in a Japanese oral health check population. A total of 1226 consecutive participant were enrolled in the study. Abdominal ultrasonography was applied to diagnose NAFLD. Of the study participants, 339 (27.7%) had ultrasonography-diagnosed NAFLD. The participants with NAFLD had a significantly higher prevalence of probing pocket depth (PPD) ≥ 4 mm (86.7%) than those without NAFLD (72.9%) (p p

The aim of this study was to evaluate left ventricular function in preterm infants from 28 days to near term using echocardiography.Thirty clinically stable preterm infants delivered at30 weeks' gestational age were prospectively enrolled. At 28 days, conventional, tissue Doppler, and speckle-tracking echocardiography evaluations of left ventricular function were performed, with comparison made to findings in 30 healthy term infants of similar postnatal age. Sixteen preterm infants underwent repeat examinations near term.Compared with controls, preterm infants at 28 days had decreased peak mitral valve (MV) E-wave velocities (P.01), E/A ratios (P.0001), annular e' velocities (P.0001), and e'/a' ratios (P.0001); increased MV E/e' ratios (P.01); and lower basal circumferential early diastolic and higher late diastolic strain rates. No significant differences were found in fractional shortening, ejection fraction, and longitudinal or circumferential strain and strain rate between preterm infants and controls. Although preterm infants at 28 days had higher heart rates compared with controls (161 ± 15 vs 142 ± 16 beats/min), no significant correlations existed between heart rate and MV E, E/A ratio, e', e'/a' ratio, and E/e' ratio. Near term, the differences in diastolic function persisted, including decreased MV e'/a' ratio (P.05), increased E/e' ratio (P.01), and increased late diastolic strain rate.Clinically stable preterm infants have normal left ventricular systolic function but altered diastolic function, with greater dependence on atrial contraction, the latter of which persists despite nearing term. These findings may be relevant to the management of preterm infants and may relate to the longer term myocardial dysfunction observed in affected adults.

Oral health-related quality of life (OHRQoL) is a multidimensional construct that involves subjective evaluation of an individual’s oral health. Although it is difficult to evaluate OHRQoL biologically, recently, it has been reported that circulating microRNAs (miRNAs) in several body fluids could reflect various health conditions. The aim of this pilot study was to investigate whether salivary miRNAs expression differs according to OHRQoL in healthy volunteers. Forty-six volunteers (median age, 23.0 years) were recruited, and their OHRQoL was assessed using the Japanese version of the Oral Health Impact Profile (OHIP-J). Then, we compared salivary microRNA profiles of the high-OHRQoL group (≤25th percentile score of OHIP-J) and the low-OHRQoL group (≥75th percentile score of OHIP-J) using the polymerase chain reaction (PCR) array and the quantitative real-time PCR. There were no significant differences between the two groups in terms of oral health status. In the PCR array, miR-203a-3p and miR-30b-5p were significantly more expressed in the low-OHRQoL group (p < 0.05). Quantitative real-time PCR assay also showed that miR-203a-3p was more highly expressed in the low-OHRQoL group than in the high-OHRQoL group (p < 0.05). These observations suggest that expression of salivary miR-203a-3p was related with OHRQoL in healthy volunteers.

Objectives To document changes in the normal embryonic/fetal cardiac axis in the late first and early second trimesters of pregnancy. Methods Images from 188 fetal echocardiograms performed prospectively between 8 and 15 weeks' gestation in 166 healthy pregnancies and in 10 pregnancies with severe fetal heart disease were reviewed. For each echocardiogram, three measurements of the cardiac axis were taken in the axial plane at the level of the four-chamber view. Differences in mean embryonic/fetal cardiac axis at different gestational ages in the healthy pregnancies were compared. Results The mean ± SD embryonic/fetal cardiac axis was 25.5 ± 11.5° from 8 + 0 to 9 + 6 weeks (Group 1), 40.4 ± 9.2° from 10 + 0 to 11 + 6 weeks (Group 2), 49.2 ± 7.4° from 12 + 0 to 12 + 6 weeks (Group 3), 50.6 ± 5.7° from 13 + 0 to 13 + 6 weeks (Group 4) and 48.6 ± 7.3° from 14 + 0 to 14 + 6 weeks (Group 5). Groups 1 and 2 were significantly different from each other and all other groups (P 90th centile in four cases and

Objective Decreased middle cerebral artery (MCA) pulsatility index (PI) is a marker of fetal brain-sparing in placental insufficiency and it is also found in fetuses with severe congenital heart disease. This study sought to explore the impact of anatomical subtypes in fetal heart disease on MCA-PI and head growth. Methods We retrospectively reviewed fetal echocardiograms of pregnancies complicated by fetal hypoplastic left heart syndrome (HLHS; n = 42) with and without anatomic coarctation (n = 28 and n = 10, respectively), isolated severe aortic coarctation (n = 21), D-transposition of the great arteries (TGA; n = 11) and pulmonary outflow tract obstruction without forward flow across the pulmonary valve (POTO; n = 15), comparing observations with gestational age-matched controls (n = 89). No fetus had major extracardiac pathology or aneuploidy. MCA and umbilical artery (UA) PI, the cerebral placental ratio (CPR = MCA-PI/ UA-PI) and neonatal head circumference were obtained and expressed as Z-scores. Results Lower MCA-PI, higher UA-PI and lower CPR were observed in fetal HLHS and isolated coarctation with reversed arch flow (n = 6) (P

Objectives Several parameters, including branch pulmonary artery (PA) diameter and Doppler-derived PA acceleration-to-ejection time ratio (AT/ET), peak late-systolic/early-diastolic reversed flow (PEDRF) and pulsatility index (PI) response to maternal hyperoxia, have been used to investigate fetal pulmonary health. Lower AT/ET, increased PEDRF and lack of PI response to hyperoxia have been observed in fetuses with severe lung hypoplasia and are considered markers of pulmonary vascular resistance. We sought to further define the evolution of PA diameter and Doppler parameters and their response to maternal hyperoxia in healthy fetuses. Methods Fifty-four prospectively recruited women with healthy pregnancy underwent fetal echocardiography from 18–36 weeks of gestation. After baseline branch PA diameter and Doppler assessment, oxygen (8–10 L/min) was administered by non-reservoir facemask for 10 min and PA Doppler parameters were reassessed. Results Branch PA diameters and AT/ET increased linearly with gestational age, while PEDRF increased quadratically (P

Screening of the congenital heart disease (CHD) is one of the most important techniques in prenatal ultrasonographic examination. Step by step screening methods for taking account for the level of screener, especially in the area with poor detection rate, is needed for starting effective fetal CHD screening. In this review, the fetal cardiac screening is divided into two methods accounting for steps for learning screening technique; the basic screening and the advanced screening. Basic screening is a simple method even for the one who is not familiar to the cardiac anatomy. The goal of this basic screening is to detect most of the ductal dependent lesions including transposition of the great arteries. For the basic screening, ‘location’ and ‘size’ of the heart and vessels are checked in standard fourchamber view and three-vessel view. Advanced screening is a screening for detecting all fetal CHDs, including total anomalous pulmonary venous return. For the advanced screening, the side of the heart is defined, and then the ‘detail anatomy’ and the ‘function and blood flow’ are assessed in all standard screening views, including one fetal abdominal transverse view and three fetal chest transverse views, such as four-chamber, three-vessel and three-vessel and trachea view.

P>BackgroundRecent studies suggest that refractory hypotension from causes other than septicaemia or cardiac failure is common in extremely preterm infants even out of the transitional period. Marked response to low-dose cortisol suggests underlying adrenal insufficiency, although the exact mechanism remains unknown.MethodsTo investigate potential triggers for and related short-term outcomes of early-onset ( = Day 7) refractory hypotension, clinical data for 70 infants < 30 weeks gestation were assessed.ResultsThe incidence of early-onset refractory hypotension (n = 7) was correlated with younger gestational ages < 26 weeks (P < 0 center dot 05), whereas the incidence of late-onset refractory hypotension (n = 14) was correlated with younger gestational ages and levothyroxine supplementation (P < 0 center dot 05 and 0 center dot 01, respectively). The incidence of both early- and late-onset refractory hypotension was correlated with risks of short-term adverse outcomes such as prolonged mechanical ventilation and hospital stay.ConclusionsLevothyroxine supplementation was identified as an independent variable correlated with an increased incidence of refractory hypotension out of the transitional period; as seen in hypothyroidism with Addison's disease, the immature hypothalamic-pituitary-adrenal axis may not respond properly to the increased demand for cortisol, which may precipitate premature infants into refractory hypotension. Following the administration of levothyroxine, preterm infants may have to be carefully monitored for early signs of refractory hypotension.

Aim:Antenatal stress, maturation and other foetal conditions affect the postnatal cardiovascular function. Atrial- (ANP) and brain-type natriuretic peptide (BNP) play important roles in regulating extracellular fluid volume and blood pressure, which may surrogate the foetal cardiovascular condition. The aim of this study was to investigate the dependence of serum ANP and BNP at birth on antenatal variables in high-risk infants.Methods:Plasma ANP and BNP levels in the umbilical cord blood were compared with antenatal clinical information in 280 infants.Results:High levels of ANP and BNP were associated with multiple pregnancy, antenatal magnesium sulphate and foetal distress. Caesarean section (CS) was paradoxically associated with low ANP and high BNP; low ANP was related with CS before labour whereas high BNP was related with CS after the commencement of labour. High BNP levels further correlated with younger gestational age and intrauteral growth restriction. With regard to short-term postnatal variables, high BNP levels were associated with low Apgar scores and respiratory failure whereas high ANP only correlated with the latter.Conclusion:High natriuretic peptide levels were associated with prematurity at birth, uteral contraction and antenatal stress: cord blood ANP and BNP may be a useful surrogate marker for hidden antenatal stress.

The importance of managing fetal arrhythmia has increased over the past three decades. Although most fetal arrhythmias are benign, some types cause fetal hydrops and can lead to fetal death. With the aim of improving the outcome in such cases, various studies for prenatal diagnosis and perinatal management have been published. Detailed analysis of the type of arrhythmia in utero is possible using M-mode and Doppler echocardiography. In particular, a simultaneous record of Doppler waveform at the superior venous cava and the ascending aorta has become an important and useful method of assessing the interval between atrial and ventricular contractions. Common causes of fetal tachycardia (ventricular heart rate faster than 180 bpm), are paroxysmal supraventricular tachycardia (SVT) with 1:1 atrioventricular (AV) relation and atrial flutter with 2:1 AV relation. Of fetal SVT, short ventriculo-atrial (VA) interval tachycardia due to atrioventricular reentrant tachycardia is more common than long VA interval. Most fetuses with tachycardia are successfully treated in utero by transplacental administration of antiarrhythmic drugs. Digoxin is widely accepted as a first-line antiarrhythmic drug. Sotalol, flecainide and amiodarone are used as second-line drugs when digoxin fails to achieve conversion to sinus rhythm. Fetal bradycardia is diagnosed when the fetal ventricular heart rate is slower than 100 bpm, mainly due to AV block. Approximately half of all cases are caused by associated congenital heart disease, and the remaining cases that have normal cardiac structure are often caused by maternal SS-A antibody. The efficacy of prenatal treatment for fetal AV block is limited compared with treatment for fetal tachycardia. Beta stimulants and steroids have been reported as effective transplacental treatments for fetal AV block. Perinatal management based on prospective clinical study protocol rather than individual experience is crucial for further improvement of outcome in fetuses with tachycardia and bradycardia.

We report two cases of insulinoma in advanced age patients considered unsuitable for surgery, in whom single daily doses of octreotide successfully improved hypoglycemia and hyperinsulinemia. The biological half-life of octreotide is about 100 min, hence it is customary to use two or three administrations per day to prevent hypoglycemia in insulinoma patients. The first case was a 76-year-old woman who presented with hyperinsulinemic hypoglycemia. Computed tomography (CT) and magnetic resonance imaging did not identify a tumor in the pancreas but a 1.5-cm tumor was found in the pancreatic body on abdominal angiography and selective arterial calcium stimulation and hepatic venous sampling (ASVS) were compatible with insulinoma. The patient refused surgery, but was successfully treated with octreotide at 50 microg subcutaneous injection once daily. Since the treatment was started (1 year), she has not suffered hypoglycemia. Case 2 was an 85-year-old woman who presented with hyperinsulinemic hypoglycemia. CT identified a 1.5-cm tumor in the pancreatic uncus, but she was considered unsuitable for surgery due to advanced age, obesity and cardiopulmonary dysfunction. Octreotide at 100 microg subcutaneous injection once daily prevented further hypoglycemic attacks, but two months later, postprandial plasma glucose was elevated. Octreotide was gradually reduced to 50 microg once daily. Three years have passed since the treatment without any hypoglycemic attack. Successful treatment with octreotide once daily could be due to old-age-related slow metabolism and could be potentially considered as the treatment of choice for elderly patients with insulinoma especially those considered unsuitable for surgery.

Objectives The aims of this study were to elucidate the clinical course of fetal bradycardia with 1 : 1 atrioventricular conduction, and to discuss the optimal management of affected fetuses in the second and third trimesters of pregnancy. Methods The hospital records of five fetuses with the diagnosis of bradycardia (100 bpm) with 1 : 1 atrioventricular conduction between 1981 and 2000 in our institution were reviewed. Atrioventricular conduction was evaluated by simultaneous M-mode echocardiographic tracing of the atria and the ventricles. Results The gestational ages at referral ranged from 19 to 36 (median, 25) weeks, and fetal heart rates ranged from 60 to 80 (median, 80) bpm. Postnatal electrocardiography revealed sinus bradycardia in four (two of which were siblings) of the five cases, and junctional rhythm in the remaining case. Two fetuses with congenital heart defects (CHDs) were delivered by Cesarean section but died postnatally. The three fetuses without CHDs were delivered vaginally and have survived to date for 6, 8 and 15 years. Conclusions Fetal bradycardia with 1 : 1 atrioventricular conduction caused by sustained sinus bradycardia or wandering pacemaker is an important type of fetal arrhythmia. Further investigations with a larger number of cases are required to determine the risk factors for predicting the outcome of affected fetuses. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

We examined the change in awareness, both systematically and continuously, after deliver ing education regarding acquired immunodeficiency syndrome (AIDS) by lecture mode. The sur vey subjects were 51 (school A), 49 (school B) and 45 (school C) students who entered one of the three dental hygienist schools in April 1999 and who participated in an investigation on their at titude, behavior and knowledge regarding AIDS in April and February of their first year. We conducted four lectures about AIDS after the first survey at schools A and B (Lecture group). The following results were demonstrated: 1. In the lecture group and non-lecture group, the students differed in their attitude and behavior, and the number of students who recognized AIDS as a common disease increased. 2. By receiving the lecture, students became afraid of the prevalence of AIDS; they considered that they might conduct dental procedures when they had been infected with HIV; and they believed that it was necessary for them to know whether patients were infected with HIV. 3. The students' knowledge about AIDS increased after education. It is necessary to conduct follow-up studies to examine whether the students are able to retain a good command of this education.

To raise the level of AIDS awareness among dental hygienist students, effective teaching methods should be established at training schools, because of the limitations of conventional teaching methods that focus on knowledge acquisition. HIV/AIDS awareness was analyzed in 296 dental hygienist students, with a view to find effective means of increasing their awareness. Our principal component analysis found that HIV/AIDS awareness consists of five principal components extracted from general awareness: (a) degree of acceptance, (b) sense of distance, (c) self-defense, (d) lack of sense of emergency concerning infection, and (e) fear of infection in daily life; and three principal components extracted from the awareness of dentistry: (a) degree of acceptance, (b) fear of infection in clinical practice, and (c) ethics as a dental hygienist. Comparing the principal components of the six distinct groups, we could assume that there is a connection between the degree of acceptance of HIV/AIDS on one hand, and AIDS education and clinical experience on the other. Furthermore, in analyzing the relationship between awareness and knowledge, it is presumed that there is a connection between the degree of acceptance in daily life and clinical practice, and knowledge about infection. This results would suggest that knowledge about infection has priority over other types of knowledge in order to raise the level of HIV/AIDS awareness.

We have investigated whether the Fas-mediated cell death pathway is functional in renal cell carcinoma. The expression of Fas in surgical specimens and cell lines of renal cell carcinoma was examined. Fas expression was positive in six out of 18 tumors measured by flow cytometry and was prominent in advanced tumors. Three out of the six Fas-positive tumors had already metastasized at the time of surgery. A significant correlation was found between the tumor volume and the percentage of Fas-positive cells in a tumor (r = 0.70, P = 0.0007). Fas-positive tumors were larger than Fas-negative tumors [mean tumor volume (ml) +/- SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012]. All human renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accounted for > 50% in all cell lines by flow cytometry. Treatment with anti-Fas antibody caused apoptosis in Fas-positive renal cell carcinoma cell lines. However, the effectiveness of apoptosis induction in individual cell lines was not correlated with the level of Fas expressed. These data suggest that Fas targeting may be a therapeutic option for treatment of advanced renal cell carcinoma which is refractory to either chemotherapy or irradiation.

A 22-week fetus presented with a large left ventricular aneurysm, 24 × 21 × 18 mm in size, detected by abnormal four-chamber view, and severe fetal hydrops with pericardial effusion, ascites and skin edema. The aneurysm was thin-walled, hypokinetic, and had enlarged with gestational age, causing compression of the lung. Although the left ventricular function had progressively impaired as expressed by increase in Tei index, hydrops had resolved by 32 weeks of gestation, probably because of maternal digoxin therapy and successful compensation by the right ventricle, as represented by retrograde blood flow in the distal aortic arch via the patent arterial duct. Because of the significant risk of severe cardiorespiratory failure, we transported the mother to a neonatal cardiac surgical center at 38 weeks of gestation. Indeed, the baby showed severe cardiopulmonary failure after birth, showing 100% of cardiothoracic ratio on the chest X-ray film, but was saved by the successful Dor procedure, including surgical resection of the aneurysm at 10 h of life. In this case, serial echocardiographic evaluation can allow us to monitor the hemodynamics and lead to successful postnatal management.

Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.