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Introduction: Recently, ultrasound (US) imaging has been used to estimate the cross-sectional area of skeletal muscle, but the reliability is uncertain. To improve the reliability of the US, we investigated skeletal muscle thickness measurement using an inertial measurement unit (IMU) to determine the direction of US beam incidence based on posture angle information. In addition, we examined whether the anatomical cross-sectional area (ACSA) of muscle can be estimated from the muscle thickness measured using the US with the IMU. Methods: In Experiment 1, two examiners measured the right psoas major at the fourth lumbar vertebra level in 10 university students using the US with and without an IMU. The intraclass correlation coefficient (ICC) was used to examine intra- and inter-rater variability. In Experiment 2, the two examiners measured the muscle thickness of the right psoas major in 31 male subjects using the US with an IMU. In addition, the ACSA of this muscle was measured using MRI. Pearson's correlation coefficient was used to examine the relationship between muscle thickness and ACSA, and a single regression analysis was performed. Results: Both intrarater reliability ICC (1, 2) and inter-rater reliability ICC (2, 2) were higher when US was used with IMU compared to without IMU (Experiment 1). A significant positive correlation ( r  = 0.84, p < 0.01) was observed between muscle thickness and ACSA (Experiment 2). The regression equation was significant at R 2  = 0.71 ( p < 0.01). Conclusion: Using an IMU during US measurement of the psoas major improves intra- and interexaminer reliability and can be used to estimate the ACSA of the muscle., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Kazuhiro Ito et al.)

Background: It is unclear whether the dementia patients with Alzheimer's disease (AD) and vascular dementia (VaD) and mixed dementia (MIX, including AD and VaD) would have more developed arterial stiffness as compared with local residents without dementia. The aim of this study was to assess arterial stiffness and cognitive function in different types of dementia patients [AD, VaD, MIX and mild cognitive impairment (MCI)] and community residents without dementia., Methods: This was a single-center, cross-sectional observational study. We studied a cohort of 600 elderly outpatients with a complaint of memory loss, who were divided into four groups (AD, VaD, MIX and MCI). In addition, they were compared with 55 age-matched local residents without dementia (Controls). We assessed arterial stiffness by brachial-ankle pulse wave velocity (baPWV) and the global cognitive function by the Mini-Mental State Examination (MMSE)., Results: The baPWV was higher in AD, VaD and MIX than in MCI and in Controls ( P < 0.05). The baPWV was higher in MCI than in Controls ( P = 0.021), while MMSE were compatible between them ( P = 0.119). The higher baPWV predicted the presence of AD, VaD, MIX and MCI with the odds ratio of 6.46, 8.74, 6.16 and 6.19, respectively. In contrast, there were no difference in baPWV among three different types of dementia ( P = 0.191). The linear relationship between baPWV and MMSE was observed in the elderly with MMSE ≥ 23 (R = 0.452, P = 0.033), while it was not in dementia patients (MMSE < 23)., Conclusions: The findings suggest that MCI and dementia patients have stiffer arteries as compared with age-matched local residents, although global cognitive function may be comparable between MCI and the local residents., (© 2022 JGC All rights reserved; www.jgc301.com.)

Background: There is limited research regarding the use of glaucoma medicines during pregnancy. Prostaglandins contract uterine smooth muscle; however, it is not clear whether prostaglandin eye drops are associated with pregnancy loss in pregnant women., Objectives: We conducted a pharmacovigilance study using spontaneous report databases from Japan and the USA to evaluate the association between pregnancy loss and the use of prostaglandin eye drops during pregnancy., Methods: The Japanese Adverse Drug Event Report database and the Food and Drug Administration Adverse Event Reporting System were used for analysis. Disproportionality analyses and a review of individual case safety reports were conducted., Results: As for prostaglandin eye drops in pregnancy-related reports, there were eight reports involving latanoprost in the Japanese Adverse Drug Event Report database and no reports of pregnant women using other prostaglandin eye drops. In the Food and Drug Administration Adverse Event Reporting System, there were 25 reports involving latanoprost, 23 involving bimatoprost, 13 involving travoprost, and three involving tafluprost. The drug safety signal was detected during latanoprost usage and pregnancy loss. In the Japanese Adverse Drug Event Report database, there were five reports of pregnancy loss related to latanoprost, with a reporting odds ratio of 12.84 (95% confidence interval 3.06-53.86), and in the Food and Drug Administration Adverse Event Reporting System, pregnancy loss was reported in 12 cases of latanoprost usage with a reporting odds ratio of 4.35 (95% confidence interval 1.98-9.54). Uterine contractions were observed as concomitant adverse events in one case., Conclusions: Although a disproportionality analysis cannot determine causality, we need to keep an eye on the signal detected in this study. This signal should be validated using a causal design study., (© 2021. The Author(s).)

Background: Endothelial cells play an important role in the prevention of cardiovascular disease., Objective: In this study, we examined the effects of transient aerobic exercise on peripheral endothelial function., Methods: Twenty-seven healthy male college students were selected as subjects and randomly divided into two groups: 13 in the control group and 14 in the exercise group. The subjects in the exercise group had a 15-minute supine rest, followed by 30 minutes of cycling exercise at moderate intensity, while measuring the reactive hyperemia index (RHI), an indicator of endothelial function, before and after exercise. The subjects in the control group had a 40-minute rest, during which RHI was measured with the same timing as in the exercise group., Results: Two-factor analysis of variance revealed a statistically significant interaction effect. In the exercise group, RHI increased significantly after exercise. However, no significant change was observed in the control group. When RHI before exercise was compared between the two groups, no significant difference was found. However, RHI after exercise was significantly higher in the exercise group., Conclusions: The results of this study suggest that 30 minutes of moderate-intensity exercise may have a favorable impact on peripheral endothelial function.

[Purpose] Brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are simple, accurate, and reproducible indices of arterial stiffness. However, only a few studies have evaluated the influence of exercise-training baPWV and CAVI on arterial stiffness. Thus, this study aimed to examine the influence of aerobic-training baPWV and CAVI on arterial stiffness. [Participants and Methods] The participants were 20 middle-aged females (age, 60.1 ± 1.6 years) who were sedentary non-smokers. The participants underwent an exercise intervention, including a 50-min session of moderate-intensity exercises two or three times a week for 12 weeks. Blood pressure (BP), baPWV, and CAVI were measured before and after exercise. Blood nitrite/nitrate (NOx) was also measured as an index of vascular endothelial function. [Results] BaPWV significantly decreased after exercise, whereas CAVI and blood NOx did not change significantly after exercise. A significant correlation was observed between the decrease in baPWV and systolic BP after exercise. In addition, the participants with higher systolic BP before exercise showed a greater decrease in baPWV after exercise. [Conclusion] These results suggest that BP has a significant role in decreasing arterial stiffness after exercise. Further studies are required to elucidate the similarities and differences between baPWV and CAVI to use them more effectively as assessment parameters for arterial stiffness.

Transcranial Doppler (TCD) ultrasonography is a noninvasive technique allowing continuous recording of cerebral blood flow (CBF) velocity. However, it is unclear whether the CBF estimated by TCD would be reliable for the comparison between individuals. The present study aimed to clarify the relationship between middle cerebral artery blood flow (MCA BF) measured by TCD and regional and total CBF measured by single-photon emission computed tomography (SPECT-CBF) with a quantification software program, a three-dimensional stereotaxic region of interest template. We recruited 91 elderly subjects with and without dementia. MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area (A M ) were measured by TCD and magnetic resonance angiography, respectively. MCA BF was calculated by the product of MCA V and A M . Diastolic or mean MCA V and MCA BF were significantly correlated with SPECT-CBF in several segments. Interestingly, the correlation coefficient in the temporal segment of SPECT-CBF was higher than those of the other segments. Moreover, correlations between MCA BF and SPECT-CBF were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF with TCD ultrasonography would be useful for CBF comparison between individuals especially in the temporal region, although estimated blood flow with arterial area seems to be better than using simple flow velocity. NEW & NOTEWORTHY Correlations between middle cerebral artery blood flow (MCA BF) calculated by the product of MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area and regional and total cerebral blood flow (CBF) measured by single-photon emission computed tomography (SPECT-CBF) were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF would be useful for CBF comparison between individuals although estimated blood flow with arterial area seems to be better than using simple flow velocity.

Background: Although research indicates that a physically active lifestyle has the potential to prevent cognitive decline and dementia, the optimal type of physical activity/exercise remains unclear. The present study aimed to determine the cognitive benefits of a golf-training programme in community-dwelling older adults., Methods: We conducted a randomised controlled trial between August 2016 and June 2017 at a general golf course. Participants included 106 Japanese adults aged 65 and older. Participants were randomly assigned to either a 24-week (90-120 min sessions/week) golf-training group or a health education control group. Postintervention changes in Mini-mental State Examination (MMSE) and National Centre for Geriatrics and Gerontology-Functional Assessment Tool scores were regarded as primary outcome measures. Secondary outcome measures included changes in physical performance and Geriatric Depression Scale (GDS) scores., Results: A total of 100 participants (golf training, n=53; control, n=47) completed the assessments after the 24-week intervention period. The adherence to the golf programme was 96.2% (51/53 participants). Analysis using linear mixed models revealed that the golf training group exhibited significantly greater improvements in immediate logical memory (p=0.033), delayed logical memory (p=0.009) and composite logical memory (p=0.013) scores than the control group. However, no significant changes in MMSE, word memory, Trail Making Test or Symbol Digital Substitution Test scores were observed. In addition, no significant changes in grip strength, walking speed or GDS were observed., Conclusions: Golf-based exercise interventions may improve logical memory in older adults, but no significant changes in other cognitive tests. Further follow-up investigations are required to determine whether the observed effects are associated with delayed onset of mild cognitive impairment or Alzheimer's disease in older adults., Trial Registration Number: UMIN-CTR UMIN000024797; Pre-results., Competing Interests: Competing interests: HS reports receiving institutional grants from the National Center for Geriatrics and Gerontology during the study period (28–29). Kanto Golf Association and Japan Ladies Professional Golf Association supported the intervention by providing golf instructors and support staff. There are no other disclosures to report., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: White matter hyperintensities (WMH), visualized on brain magnetic resonance imaging, represent an abnormality related to the development of geriatric syndromes. Recently, it has been found that low sympathetic nervous activity might be associated with physical and cognitive dysfunction in older adults. Therefore, we investigated the relationship between the severity of cerebral WMH and sympathetic nervous activity, measured by the heart rate variability., Methods: We carried out a cross-sectional study of 39 older patients. Holter recording was carried out for 30 min. From the RR intervals on the electrocardiogram, the standard deviation of the normal-to-normal intervals, the standard deviation of all normal-to-normal intervals in all the five segments of the entire recording, low frequency (LF), high frequency (HF) and LF/HF were calculated. In regard to the WMH, periventricular hyperintensities and deep white matter hyperintensities (DWMH) were rated according to the Fazekas classification. The WMH were also rated semiquantitatively according to the methods developed by Junque (periventricular hyperintensities) and de Groot (DWMH)., Results: The LF/HF showed significant negative correlations with the total and regional periventricular hyperintensities, as well as DWMH. Multiple regression analysis showed that the negative associations remained significant between the LF/HF and DWMH (total, temporal, occipital). Furthermore, fall risk index significantly correlated with the LF/HF, total and the occipital DWMH., Conclusions: The severity of the DWMH was associated with the LF/HF and the fall risk, one of the important geriatric syndromes, suggesting that WMH, sympathetic nervous dysfunction and geriatric syndrome are interrelated to each other. Geriatr Gerontol Int 2018; 18: 569-575., (© 2017 Japan Geriatrics Society.)

This study investigated the relationship between changes in arterial stiffness and the lifestyle habits of endurance athletes after retiring from competition. The subjects were 10 female university endurance athletes. We used formPWV/ABI ® as an index for arterial stiffness and measured brachial-ankle pulse-wave velocity (baPWV) directly before subjects retired (0Y) and at 2 years after retirement (2Y). Furthermore, to investigate the relationship between arterial stiffness and lifestyle habits 2 years later, Lifecorder ® PLUS was used to measure physical activity levels, hours of sleep were surveyed using a questionnaire, and a food intake survey was conducted using Excel Eiyoukun Food Frequency Questionnaire Based on Food Group, FFQg Ver. 3.5. We found that baPWV increased significantly from 0Y to 2Y (P<0·05). Furthermore, negative correlations were observed between 2Y baPWV and step count as the physical activity index (r = -0·653, P<0·05) and moderate physical activity (r = -0·663, P<0·05). With regard to lifestyle habits that affected the amount of increase in baPWV from 0Y to 2Y (ΔbaPWV), negative correlations were noted between the step count (r = -0·690, P<0·05) and total physical activity (r = -0·657, P<0·05). However, no significant correlations were observed between 2Y baPWV and ΔbaPWV with food intake or hours of sleep. The results of this study suggested that physical activity was a lifestyle habit that inhibited an increase in arterial stiffness after retirement from competition and that having a high step count or engaging in physical activity for long periods of time in particular was useful in this regard., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: Gait disturbance and falls are serious events that can impair activities of daily living (ADL) in the elderly. On the other hand, carnitine plays essential roles in energy production, and carnitine deficiency leads to low activity levels., Objectives: We examined whether a lower serum carnitine concentration was correlated with falls and gait disturbances in the elderly., Design, Setting, and Participants: We performed a cross-sectional study. One hundred and ninety-eight elderly patients (male, 83; female, 115; 81 ± 6 years old) were enrolled in this study., Measurements: Physical performance (hand grip strength, leg strength, walking speed, one-leg standing time, and tandem gait steps) and frailty status (The Edmonton Frail Scale: EFS) were evaluated. The serum total, free, and acylated carnitine levels were measured using an enzyme cycling method. We then investigated the associations between the serum carnitine level, history of falls, and the results of these physical examinations., Results: Of the 198 subjects, 56 (28%) had a history of falls within the past one year. The patients with a history of falls had lower serum total carnitine and free carnitine levels than those without a history of falls. Regarding the physical performance results, the patients with a history of falls had higher EFS scores, a weaker hand grip strength, a slower walking speed, a shorter one-leg standing time, and a smaller number of tandem gait steps than those without a history of falls. A logistic regression analysis showed that the low serum total carnitine concentration was identified as an independent factor associated with a history of falls, a slow walking speed after adjustments for age, sex and modified EFS., Conclusions: A low serum carnitine level is associated with a history of falls and gait disturbances in elderly people., Competing Interests: No potential conflicts of interest were disclosed.

Aim: The aim of the present study was to investigate the prevalence of sarcopenia in outpatients attending a geriatric and memory clinic and to investigate its relationship with falling., Methods: We investigated the prevalence of sarcopenia (according to the EWGSOP criteria) among 283 outpatients that were all ≥65 years of age, and who attended the geriatric and memory clinic at Kyorin University Hospital. We also examined comorbidities, CGA items, and fall-related measures, and analyzed the relationships between these factors and sarcopenia., Results: Seventy men (60.9%) and 88 women (52.4%) were diagnosed with sarcopenia. The sarcopenic men were older, had lower BMI values, and had a higher prevalence of dementia. The sarcopenic women had lower BMI values, and a higher prevalence of dyslipidemia. ASMI was not associated with walking speed or fall-related measures, whereas grip strength and walking speed were associated with each other and both were associated with fall-related measures. Ninety-one patients (32.2%) experienced a fall in the previous year. The prevalence of sarcopenia and ASMI among fallers and non-fallers did not differ to a statistically significant extent, whereas the fallers had lower grip strength and walking speed. A multiple logistic regression analysis revealed that weak grip strength in men and slow walking speed and the presence of diabetes in women were significant risk factors for falling., Conclusions: The frequency of sarcopenia in outpatients attending the geriatric and memory clinic was higher than that in the community-dwelling elderly individuals. Falls were more related to the patients' muscle strength and walking speed than their muscle mass or the presence of sarcopenia itself.

[Purpose] The purpose of the present study was to establish the intra- and inter-rater reliability of measurement of extensor strength in the maximum shoulder abducted position and internal rotator strength in the 90° abducted and the 90° external rotated position using a hand-held dynamometer. [Subjects and Methods] Twelve healthy volunteers (12 male; mean ± SD: age 19.0 ± 1.1 years) participated in the study. The examiners were two students who had nonclinical experience with a hand-held dynamometer measurement. The examiners and participants were blinded to measurement results by the recorder. Participants in the prone position were instructed to hold the contraction against the ground reaction force, and peak isometric force was recorded using the hand-held dynamometer on the floor. Reliability was determined using intraclass correlation coefficients. [Results] The intra- and inter-rater reliability data were found to be "almost perfect". [Conclusion] This study investigated intra- and inter-rater reliability and reveald high reliability. Thus, the measurement method used in the present study can evaluate muscle strength by a simple measurement technique.

[Purpose] The purpose of present study was to establish the same-session and between-day intra-rater reliability of measurements of extensor strength in the maximum abducted position (MABP) using hand-held dynamometer (HHD). [Subjects] Thirteen healthy volunteers (10 male, 3 female; mean ± SD: age 19.8 ± 0.8 y) participated in the study. [Methods] Participants in the prone position with maximum abduction of shoulder were instructed to hold the contraction against the ground reaction force, and peak isometric force was recorded using the HHD on the floor. Participants performed maximum isometric contractions lasting 3 s, with 3 trials in one session. Between-day measurements were performed in 2 sessions separated by a 1-week interval. Intra-rater reliability was determined using intraclass correlation coefficients (ICC). Systematic errors were assessed using Bland-Altman analysis for between-day data. [Results] ICC values for same-session data and between-day data were found to be "almost perfect". Systematic errors not existed and only random error existed. [Conclusion] The measurement method used in this study can easily control for experimental conditions and allow precise measurement because the lack of stabilization and the impact of tester strength are removed. Thus, extensor strength in MABP measurement is beneficial for muscle strength assessment.

[Purpose] We examined the effects of detraining on temporal changes in arterial stiffness in endurance athletes. [Subjects] Eighteen female university athletes requiring high endurance exercise capabilities were classified into 2 groups: 10 retired players (detraining group) and 8 active players (training group). [Methods] Brachial-ankle pulse wave velocity, an index of arterial stiffness, was measured a total of 6 times: immediately before retirement of the detraining group and at 1, 2, 3, 6, and 12 months after retirement. [Results] Brachial-ankle pulse wave velocity was measured in the training group at the same 6 points to allow comparison with the detraining group. The brachial-ankle pulse wave velocity in the detraining group increased significantly at 3 and 12 months as compared with that at 0 months and showed a significant increase at 12 months compared with that at 1 month. Moreover, the brachial-ankle pulse wave velocity in the detraining group was significantly higher at 3, 6, and 12 months than in the training group. [Conclusion] These results revealed that detraining may result in increased arterial stiffness from 3 months onward in endurance athletes.

Aim: The relationships of n-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid (EPA), to stroke and cardiovascular events have been studied extensively. The present study was undertaken to analyze the relationships of the severity of cerebral white matter hyperintensities (WMH) to the blood polyunsaturated fatty acids level and the ratio of serum EPA level to the serum arachidonic acid (AA) level (EPA/AA ratio) among older adults., Methods: A total of 150 patients underwent diagnostic magnetic resonance imaging and blood sampling under the fasting state. In regard to WMH, the periventricular hyperintensities and deep white matter hyperintensities were rated according to the Fazekas classification. The serum docosahexaenoic acid, EPA, AA, dihomo-γ-linolenic acid and EPA/AA ratio were compared in relation to the grade of severity of WMH. Furthermore, multiple regression analysis was carried out with age, sex and atherosclerosis risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking status) as the covariables, serum polyunsaturated fatty acids level as an independent variable and Fazekas grade as the dependent variable., Results: A rise of the periventricular hyperintensities grade was associated with a significant reduction of the mean EPA level (P < 0.05) and EPA/AA ratio (P < 0.05). The multiple regression analysis identified a significant negative correlation between the periventricular hyperintensities grade and the serum EPA/AA ratio (β = -0.215, P < 0.05)., Conclusion: These results suggest that the serum EPA/AA ratio have an important role in the formation and progression of WMH., (© 2015 Japan Geriatrics Society.)

Development of efficient screening method coupled with cell functionality evaluation is highly needed in contemporary microbiology. The presented novel concept and fast non-destructive method brings in to play the water spectral pattern of the solution as a molecular fingerprint of the cell culture system. To elucidate the concept, NIR spectroscopy with Aquaphotomics were applied to monitor the growth of sixteen Lactobacillus bulgaricus one Lactobacillus pentosus and one Lactobacillus gasseri bacteria strains. Their growth rate, maximal optical density, low pH and bile tolerances were measured and further used as a reference data for analysis of the simultaneously acquired spectral data. The acquired spectral data in the region of 1100-1850nm was subjected to various multivariate data analyses - PCA, OPLS-DA, PLSR. The results showed high accuracy of bacteria strains classification according to their probiotic strength. Most informative spectral fingerprints covered the first overtone of water, emphasizing the relation of water molecular system to cell functionality.

Aim: Vascular dementia may be referred to as "treatable dementia" because its development and progress can be inhibited by intervention in the early stage. In particular, cerebral white matter lesions are readily encountered the clinical setting. In this study, we aimed to clarify the phenomenon and symptoms of patients with mild cognitive impairment (MCI) with cerebral white matter lesions prior to the onset of dementia., Methods: The subjects included 181 cases diagnosed with MCI among 643 consecutive new patients of the Center for Comprehensive Care on Memory Disorder at Kyorin University Hospital from January 1, 2013 to January 31, 2014. Patients with particular diseases were excluded. An interview, physical examination, comprehensive geriatric assessment, brain MRI and SPECT were performed for all subjects. The cerebral white matter lesions were evaluated using the modified Fazekas scale. We defined Grades 0 and 1 as the group without apparent cerebral white matter lesions and Grades 2 and 3 as the group with apparent cerebral white matter lesions. We compared the laboratory findings and outcomes of these two groups., Results: The age of the group with apparent cerebral white matter lesions was significantly higher than the group without apparent cerebral white matter lesions (P<0.05). No significant difference was observed regarding gender, MMSE, or "vegetable" term retrieval. A significant difference was observed in the total score and the subordinate component of the 21-item fall risk index and geriatric depression scale between the groups (P<0.05). Additionally, a significant difference was observed regarding the subordinate component of the instrumental ADL, the Dementia Behavior Disturbance Scale and the Zarit Care Burden Scale between the groups (P<0.05)., Conclusions: Our results suggest that the presence of white matter lesions at the stage of MCI has a significant relationship to care burden due to the deterioration of ADL, risk of falling, and the presence of depression and behavior disorders. We speculate that our results are useful for the explanation of the characteristics of MCI with white matter lesion to the patients and the care givers. Furthermore, these results may lead to improvements in the appropriate approach, intervention and appropriate nursing of such patients.

Background: We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS). In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases., Materials and Methods: Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group), patients with systemic sclerosis not complicated by SjS (SSc group), and patients with other autoimmune diseases (non-SjS/non-SSc group). Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates., Results: Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups., Conclusion: Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases.

Aim: To assess the validity and reliability of a pre-visit questionnaire newly developed to identify geriatric conditions in older adults in an outpatient clinical setting., Methods: A new self-administered questionnaire consisting of 17 items was distributed to 277 patients or their caregivers visiting a memory clinic. The questionnaire was designed to address common symptoms associated with an increasing age based on yes/no responses with symptom-oriented questions avoiding the use of 'jargon'. The patients also underwent comprehensive geriatric assessments (CGAs), as well as tests of the Barthel index, Lawton instrumental activities of daily living, mini-mental state examination (MMSE), geriatric depression scale and vitality index to assess construct validity in a factor analysis. The differences in the prevalence of symptoms between the patients and their caregivers were also assessed., Results: The factor analysis detected eight components that included symptoms referring to gait disturbance, numbness, urinary incontinence, insomnia or body weight loss and were significantly correlated with the measurements of the CGA. Cronbach's alpha coefficient for the internal consistency of the questionnaire was 0.729. The caregivers tended to respond to the questionnaire for older patients (81.6±5.5 vs. 76±9.7 years of age for patients with caregivers as responders versus patients as responders respectively, p<0.001) and those with lower MMSE scores (19.4±5.8 vs. 24.8±4.2 points, p<0.001). A higher prevalence of falls and episodes of delusions was observed among the patients with caregivers as responders., Conclusions: These results demonstrate that the current questionnaire is a valid and reliable instrument for use in clinical practice and that obtaining collateral source information is essential for assessing significant geriatric symptoms. Such information also provides clinicians with a guide to conducting more detailed evaluations of geriatric conditions and aids in the diagnostic process in older patients with multidisciplinary complications.

We have investigated the prevalence of dry mouth among patients with autoimmune diseases other than Sjögren's syndrome. One hundred and forty-four patients, excluding patients with primary Sjögren's syndrome, were enrolled in this study. The volume of saliva secreted was measured with the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth. Disturbed salivary secretion was observed in 84 (58.3 %) of the 144 patients. In the case of patients free of Sjögren's syndrome, the prevalence of disturbed salivary secretion differed significantly among the disease groups (P < 0.05), with the prevalence being over 50 % in all disease groups other than the rheumatoid arthritis group and the highest in the systemic sclerosis group. There was significant positive correlation between the number of colored spots and oral visual analog scale score (r = 0.45, P < 0.0001). Autoimmune diseases can be accompanied by salivary gland dysfunction, regardless of the presence/absence of complication by Sjögren's syndrome. In the present study, the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth, was shown to be a useful means of detecting salivary gland dysfunction.

Introduction: To determine the long-term effect of neoadjuvant chemotherapy with paclitaxel and carboplatin on a weekly schedule followed by radical surgery for patients with locally advanced cervical cancer., Materials and Methods: Thirty patients with stage IB2 to IIIB uterine cervical cancer were treated with paclitaxel (60 mg/m) and carboplatin (area under the curve, 2-an area under the time-concentration curve of 2 mg x min/mL based on creatinine clearance) every week for 6 cycles. A radical hysterectomy was performed 6 days after the final administration of neoadjuvant chemotherapy. The patients were followed up, and 5-year progression-free survival (PFS) and overall survival (OS) were evaluated., Results: Of 30 patients, 28 were followed up. The median follow-up period was 55.6 months (range, 26-83 months). An objective response (complete response + partial response) to the treatment was observed in 26 patients (87%; 95% confidence interval, 70%-95%). Two had complete response, 4 had stable disease, and the remaining patients had partial response; progressive disease was not seen in this study. A radical hysterectomy was performed in 28 patients without delay. Thirteen patients with high-risk factors received radiotherapy after surgery. The 5-year PFS and OS rates were 78.6% and 81.8%, respectively. The 5-year PFS and OS for patients with stage IB2 to IIB cervical cancer were 79.2% and 83.1%, respectively, which were comparable with those in the concurrent chemoradiation therapy study previously reported. There was no significant correlation in survival between preoperative staging and cell type, whereas larger initial tumor size and lymph node metastasis tended to be negatively correlated with survival., Conclusions: Neoadjuvant chemotherapy with paclitaxel and carboplatin on a weekly schedule followed by radical surgery for patients with locally advanced cervical cancer is a promising mode of therapy that may improve the prognosis. It would be worthwhile to conduct larger-scale trials for comparison with the results of the chemoradiation therapy study.

Paclitaxel and carboplatin are commonly used and well-tolerated agents for gynecologic malignancies. The persistence of platinum in human tissues for 14 days and the long-term retention of platinum in tissues for up to 17 months have been reported. Paclitaxel remains in human uterine cervical cancer tissues for 6 days. These findings prompted us to determine the retention of paclitaxel and carboplatin in human uterine cervical carcinoma, endometrial carcinoma, ovarian carcinoma, and pelvic lymph nodes to establish baseline parameters and guide the development of more effective treatment interventions. Thirty patients with uterine or ovarian carcinomas were treated with intravenous weekly paclitaxel-carboplatin chemotherapy before surgery. The concentrations of these agents in carcinoma tissue, normal cervical, myometrial and ovarian tissues, and pelvic lymph nodes were measured 5 days after the final administration. Paclitaxel was specifically retained in cervical, endometrial, and ovarian carcinoma tissues but was not detected in lymph nodes. In contrast to paclitaxel, carboplatin was readily detectable with similar levels in all tumor-associated and normal host tissues. In addition, a low paclitaxel concentration in cervical carcinoma tissue was significantly associated with short progression-free survival and overall survival. Further studies are needed to clarify the tissue distribution of anticancer drugs in humans and promote optimal treatment strategies enhancing paclitaxel lymphatic targeting.

Carboplatin is one of the most commonly used and well-tolerated agents for gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the overall population of patients receiving carboplatin has been reported to increase after multiple doses of the agent. We retrospectively analyzed the incidence, clinical features, management, or outcome of carboplatin-related HSRs in 113 Japanese patients with gynecologic malignancies and the possibility of rechallenge with the drug. We intravenously administered carboplatin after paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs, with an overall incidence of 8.85%. The first HSR episode was mild in all cases. When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles and/or more than 5000 mg of carboplatin administration significantly increased the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles and/or 8000 mg increased the risk of severe HSRs (P < 0.0001). The incidence of HSRs in the ovarian carcinoma group was significantly greater than that in the uterine carcinoma group (P = 0.0046). Careful attention should be paid to HSRs during carboplatin treatment beyond 9 cycles and/or 5000 mg. The rate of severe HSRs greatly increases beyond 15 cycles and/or 8000 mg. Further studies are needed to identify potential risk factors that may contribute to the development of carboplatin HSRs and to decrease the risk of reactions.

Junctional adhesion molecule A (JAM-A) is involved in cell-cell contact and tight junction formation. Loss of cell adhesion molecules may be associated with high histologic grade and invasiveness of endometrial carcinoma. We attempted to determine JAM-A expression in human endometrial carcinoma and its correlations with pathologic features, stage, and survival. Junctional adhesion molecule A expression in human endometrial carcinoma was evaluated by immunohistochemistry. In addition, we cultured human well and poorly differentiated endometrial adenocarcinoma cell lines, Ishikawa cells, and KLE in 3-dimensional basement membrane preparation, and JAM-A expression in these cells was assessed by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Junctional adhesion molecule A immunostaining intensity was negatively correlated with histologic grade (tau = -0.420, P < 0.0001), myometrial invasion (tau = -0.306, P < 0.01), and stage (tau = -0.383, P < 0.0001). Low JAM-A immunostaining intensity was associated with positive vascular space involvement (P < 0.01). Moreover, low immunostain intensity was significantly (P < 0.0001) related to low overall survival rate and progression-free survival rate. Additionally, in our 3-dimensional epithelial cell culture, JAM-A expression in poorly differentiated adenocarcinoma was significantly lower than that in well-differentiated adenocarcinoma (P < 0.001). Junctional adhesion molecule A expression seems to be reduced in high-grade or advanced endometrial carcinoma and may be a prognostic factor.

Background: Rupture of an ovarian cyst may cause chemical peritonitis. When an ovarian cyst ruptures spontaneously, an emergency operation is usually performed, and the chemical peritonitis is alleviated by irrigating the abdominal cavity. This appears to be the only report of prolonged chemical peritonitis., Case: A spontaneously ruptured ovarian mature cystic teratoma was left untreated for >2 weeks, and chemical peritonitis lasted for 1 year. The peritonitis required administration of a synthetic adrenal corticosteroid and an immunosuppressive antimetabolite., Conclusion: It is important to perform an operation immediately when spontaneous rupture of an ovarian cyst is suspected. For therapeutic purposes, spilled ovarian cyst fluid should be eliminated as soon as possible to prevent prolonged chemical peritonitis.

Objectives: To investigate the in vitro effects of five progestogens commonly used in hormone replacement therapy (HRT) on estrogen-metabolizing enzymes in human breast cancer cells., Methods: The human hormone-dependent breast cancer cell lines T47D, MCF-7, and MCF-7aro were cultured with estradiol (E(2)) and progestogens. The mRNA levels of estrogen-metabolizing enzymes were determined by RT-PCR or Northern blot, and enzyme activities by radiolabeled substrates. Cell proliferation was measured by bromodeoxyuridine incorporation. In vitro models for continuous combined regimen (CCR) and sequential combined regimen (SCR) were established to mimic the in vivo conditions of HRT., Results: Medroxyprogesterone acetate (MPA) plus E(2) (10(-8)M) stimulated the mRNA levels and activities of estrogen-activating enzymes aromatase (at 10(-8)M MPA), 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1) (at 10(-6)M), and sulfatase (at 10(-8) to 10(-6)M) compared to E(2) only. Progesterone also stimulated enzyme activity, but to a lower magnitude. Levonorgestrel, norethindrone, and dienogest showed no enzyme stimulation. The estrogen-inactivating enzymes 17beta-hydroxysteroid dehydrogenase type 2 and sulfotransferase were not affected by any of the progestogens tested. However, all the progestogens (at 10(-8) to 10(-6)M) inhibited E(2)-stimulated cell proliferation. While increased aromatase and 17betaHSD1 activities were observed in the CCR model, no significant enzyme stimulation was observed in the SCR model., Conclusions: The present study suggested that progestogens exert different actions on estrogen-metabolizing enzymes in breast cancer cells dependent on the specific progestogen and regimen used. Further studies are needed to elucidate whether MPA, a progestogen currently used in HRT, leads to a higher risk of breast cancer development than other progestogens.

Objective: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor that plays an important role in many diseases. This study investigated whether two polymorphisms (Pro12Ala in exon B and C161T in exon 6) of the PPAR-gamma2 gene are related to adenomyosis, endometriosis, or leiomyomata., Methods: A total of 390 patients with adenomyosis, endometriosis, and/or leiomyomata were classified into four groups: 103 patients with adenomyosis (21 adenomyosis only and 82 adenomyosis with endometriosis and/or leiomyomata), 95 patients with endometriosis only, 100 patients with leiomyomata only, and 92 patients with endometriosis and leiomyomata., Results: There was no association between distribution of genotype or allele frequencies for the PPAR-gamma Pro12Ala polymorphism and the presence of adenomyosis, endometriosis, and/or leiomyomata. However, compared with results for controls, the PPAR-gamma 161CC genotype and 161C allele frequencies were significantly increased in patients with adenomyosis (genotype: chi2 = 8.185, corrected P value [Pc] = .0169; allele: chi2 = 8.337, Pc = .0155) and in patients with endometriosis (genotype: chi2 = 6.748, Pc = .0375; allele: chi2 = 6.413, Pc = .0453)., Conclusion: The results suggest that the PPAR-gamma 161CC genotype could be a genetic risk factor for adenomyosis and endometriosis, whereas the Pro12Ala polymorphism was not associated with these estrogen-dependent benign uterine diseases in a Japanese population.

Background: The aim of this study was to evaluate the diagnostic significance of CA-125 for endometriosis without ovarian endometriomas., Methods: Preoperative serum CA-125 levels were measured in 775 consecutive women diagnosed by laparoscopy or laparotomy with endometriosis, adenomyosis, leiomyomas, or normal pelvis., Results: Receiver operating characteristic curve analysis revealed that the area under the curve for endometriosis without endometriomas was 0.788, significantly smaller than that for endometriosis with endometriomas (0.935, P < 0.05). In diagnosis of endometriosis without endometriomas, both the maximal accuracy of 78.8% and the maximal diagnostic value of 61.2% were obtained at the cutoff value of 20 U/mL. Negative predictive value was 78.0% at the cutoff value of 20 U/mL, whereas positive predictive value was 92.9% at the cutoff value of 30 U/mL. This range is clearly superior to the empirical single cutoff of 35 U/mL., Conclusions: In the diagnosis of endometriosis without endometriomas, combined use of two cutoff values for CA-125, 20 and 30 U/mL, provides improved diagnostic performance. However, the accuracy of using only CA-125 testing for diagnosis is still limited. Serum CA-125 testing can be done during initial screenings of women with possible endometriosis.

Allograft inflammatory factor-1 (AIF-1) is a cytokine originally identified in rat cardiac allografts with chronic rejection. AIF-1 is expressed in various human immune-related tissues and is thought to play a role in inflammatory responses and the immune activation and function of macrophages. Expression has also been shown in human placentas and bovine embryos, suggesting that AIF-1 may be involved in reproductive function. Immune factors are thought to be involved in the pathogenesis of endometriosis. High concentrations of activated macrophages and various cytokines have been found in the peritoneal fluid of patients with endometriosis. In the current work we examined the expression of AIF-1 in human eutopic endometrium and endometriosis, and measured AIF-1 in peritoneal fluid samples from women with and without endometriosis. RT-PCR, Western blot analysis, and immunohistochemistry showed that AIF-1 mRNA and protein were expressed both in eutopic endometrium and in endometriotic tissue. In eutopic endometrium, expression was greater in the late secretory and menstrual phases than in other phases of the menstrual cycle (P < 0.01). AIF-1 protein was present in greater amounts in peritoneal fluid from patients with endometriosis than in women without it (P < 0.01), and its concentration correlated with the Revised American Society for Reproductive Medicine score (rs = 0.693; P < 0.0001). Peritoneal macrophages from endometriosis patients secreted more AIF-1 than those from unaffected women (P < 0.05). AIF-1 release from macrophages was stimulated by IL-1beta (P < 0.01) and interferon-gamma (P < 0.05). These results demonstrate for the first time that AIF-1 is expressed in eutopic endometrium and endometriotic tissue, suggesting that AIF-1 is one cytokine in the local network involved in the onset of menstruation. AIF-1 derived from peritoneal macrophages may also possibly play a significant role in the pathophysiology and progression of endometriosis.

Background: Endometriosis is a multifactorial disease with possible genetic predisposition and involvement of environmental factors in its pathogenesis. Cytokines may play important roles in the pathogenesis of endometriosis. The aim of this study was to investigate whether the interferon-gamma gene (IFNG) CA-repeat and interleukin-4 (IL-4) promoter region (-590C/T) polymorphisms may be responsible in part for genetic susceptibility to endometriosis., Methods: IFNG CA-repeat and IL-4 -590C/T polymorphisms were determined for 185 patients with endometriosis and 176 healthy fertile women by quantitative genescan technology and PCR-restriction fragment length polymorphism analysis, respectively. Patients with endometriosis were analysed further according to their stage of disease, the presence or absence of chocolate cysts and whether or not their disease was associated with adenomyosis and/or lyomyomata., Results: The global IFNG allele frequencies in the patients with endometriosis were significantly different from those in the control women (chi2 = 12.964, 6 df, P = 0.0436). The difference was due to an increase of the a13 (114 bp) allele in patients with endometriosis (chi2 = 10.222, P = 0.0088, corrected P = 0.0352, odds ratio = 1.48, 95% confidence interval = 1.10-1.98). There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and all patients with endometriosis or between control women and each subgroup of patients with endometriosis., Conclusion: The results suggest that the IFNG CA-repeat polymorphism is associated with susceptibility to endometriosis in a Japanese population., (Copyright 2004 European Society of Human Reproduction and Embryology)

Problem: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis., Methods of Study: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) - preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively., Results: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls., Conclusion: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms.

We examined the immunohistochemical expression of aromatase cytochrome P450 (P450arom), estrogen receptor (ER), progesterone receptor (PR), and Ki-67 in postoperative uterine sarcomas (n = 31) and the corresponding eutopic endometria (n = 20) to evaluate the relationships between the endocrine character of uterine sarcomas and the clinical features. In sarcoma tissues, P450arom was detected in 55% of cases, ER in 42%, PR in 42%, and Ki-67 in 90%. In eutopic endometria, P450arom was detected in 60% of cases, ER in 60%, and PR in 35%. There were correlations in the steroid-related proteins between the tumors and endometria (P = 0.001-0.026). The positivity of endometrial P450arom (P = 0.04) and ER (P = 0.006) was higher in surviving patients than dead patients regardless of the menstrual state. The results demonstrate correlation between the expression of P450arom, ER, and PR in tumors and eutopic endometria. Intense expression of the steroid-related proteins was associated with better survival.

Bulk metallic glasses--formed by supercooling the liquid state of certain metallic alloys--have potentially superior mechanical properties to crystalline materials. Here, we report a Co(43)Fe(20)Ta(5.5)B(31.5) glassy alloy exhibiting ultrahigh fracture strength of 5,185 MPa, high Young's modulus of 268 GPa, high specific strength of 6.0 x 10(5) Nm kg(-1) and high specific Young's modulus of 31 x 10(6) Nm kg(-1). The strength, specific strength and specific Young's modulus are higher than previous values reported for any bulk crystalline or glassy alloys. Excellent formability is manifested by large tensile elongation of 1,400% and large reduction ratio in thickness above 90% in the supercooled liquid region. The ultrahigh-strength alloy also exhibited soft magnetic properties with extremely high permeability of 550,000. This alloy is promising as a new ultrahigh-strength material with good deformability and soft magnetic properties.

Background: Giant ovarian tumors are rarely seen in modern surgical practice. Cardiopulmonary complications associated with the removal of such tumors are serious problems., Case: An ovarian tumor weighing 55 kg was removed from a 33-year-old woman without cardiorespiratory complications using preoperative drainage and abdominoplasty by excision of the excess skin., Conclusion: Preoperative drainage before and abdominoplasty after removal of giant ovarian tumors are effective.

Background: The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor (SLEPR), and total, free and bound leptin, and the change in the serum SLEPR level during an IVF cycle., Methods: Serum concentrations of leptin and SLEPR were measured in 50 Japanese women of reproductive age, and 20 patients participating in an IVF programme. The total leptin was fractionated into free and bound portions by gel filtration chromatography., Results: The SLEPR level was negatively correlated with the body mass index (BMI) (r = -0.548, P < 0.0001), total leptin (r = -0.433, P < 0.0001), the percentage of free leptin (r = -0.732, P < 0.0001) and the absolute free leptin concentration (r = -0.506, P < 0.0001). The SLEPR level was positively correlated with the percentage of bound leptin (r = 0.730, P < 0.0001), whereas there was little variation in the absolute bound leptin concentration, regardless of the BMI or SLEPR concentration. During the IVF cycle, total and free leptin elevated during maximal ovarian stimulation, whereas there was no significant difference in the SLEPR concentration., Conclusions: The results demonstrate a skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation.

Objective: To investigate whether GnRH agonists or danazol therapy normalizes estrogen metabolism in the eutopic endometrium of women with endometriosis, adenomyosis, or leiomyomas., Design: Prospective clinical study., Setting: University hospital., Patient(s): Fifty-three women with endometriosis, adenomyosis, or leiomyomas., Intervention(s): Patients received GnRH agonist or danazol. Biopsy samples of the endometrium were obtained before and after endocrine therapy. Nontreated endometrial explants were cultured in the presence of either drug., Main Outcome Measure(s): Reverse transcription polymerase chain reaction-Southern blot and immunohistochemical analyses of the endometrial expression of aromatase cytochrome P450, estrogen receptor, progesterone receptor, and Ki-67. Nontreated endometrial explants were cultured in the presence of either drug., Result(s): Messenger RNA and protein of aromatase cytochrome P450 were greatly reduced in the eutopic endometrium of patients treated with GnRH agonist for 2 months or more or with danazol for 1 month or more. Culture of endometrial explants with GnRH agonist (10(-9)-10(-7) M) did not change the amount of aromatase cytochrome P450, whereas danazol (10(-7)-10(-6) M) efficiently reduced aromatase cytochrome P450 expression., Conclusion(s): Therapy with GnRH agonist or danazol decreases expression of aromatase cytochrome P450 in diseased eutopic endometrium. Endocrine therapy normalized in part the impaired hormonal expression of the eutopic endometrium. GnRH agonist reduced aromatase cytochrome P450 expression mainly by promoting a hypoestrogenic state, whereas danazol reduced aromatase cytochrome P450 in part by direct action on the eutopic endometrium.

Endometriosis, defined as the presence of endometrial glands and stroma outside of the uterine cavity, develops mostly in women of reproductive age and regresses after menopause or ovariectomy, suggesting that the growth is estrogen-dependent. Indeed, the lesions contain estrogen receptors (ER) as well as aromatase, an enzyme that catalyses the conversion of androgens to estrogens, suggesting that local estrogen production may stimulate the growth of lesions. The expression patterns of ER and progesterone receptors in endometriotic lesions are different from those in the eutopic endometrium. Moreover, estrogen metabolism, including the expression pattern of aromatase and the regulation of 17 beta-hydroxysteroid dehydrogenase type 2 (an enzyme responsible for the inactivation of estradiol to estrone), is altered in the eutopic endometrium of women with endometriosis, adenomyosis, and/or leiomyomas compared to that in the eutopic endometrium of women without disease. Immunostaining for P450arom in endometrial biopsy specimens diagnosed these diseases with sensitivity and specificity of 91 and 100%, respectively. This is applicable to the clinical diagnosis of endometriosis. The polymorphisms in the ER-alpha gene, the CYP19 gene encoding aromatase, and several other genes are associated with the risk of endometriosis. Studies of these will lead to better understandings of the etiology and pathophysiology of endometriosis.

Although the exact etiology of endometriosis is unclear, several lines of evidence support roles for both cell-mediated and humoral immunity in its pathogenesis. To assess the association between HLA genotypes and endometriosis, we investigated the frequencies of HLA-A, -B, -C, and -DRB1 antigens or alleles in 123 Japanese patients with endometriosis and 165 healthy women as controls. Significant positive association with endometriosis was observed for HLA-B7 (OR = 2.7, 95% CI = 1.5-5.1, p(u) = 0.0022, p(c) = 0.0440) and for Cw*0702 (OR = 2.1, 95% CI = 1.2-3.3, p(u) = 0.0026, p(c) = 0.0398). An increased frequency of DRB1*0101 was observed in endometriosis patients compared with control subjects (OR = 2.3, 95% CI = 1.2-4.4, p(u) = 0.0143), but was not statistically significant after correction for multiple comparisons. Two-locus analysis indicated that the susceptibility to endometriosis was primarily associated with B7, and that the increased frequencies of Cw*0702 and DRB1*0101 in patients reflected the linkage disequilibrium between B7 and Cw*0702 and DRB1*0101. Most of the B7 antigens were encoded by the B*0702 allele, which was in complete linkage disequilibrium with A24, Cw*0702, and DRB1*0101. Therefore, our results indicated that the HLA-A24-B*0702-Cw*0702-DRB1*0101 haplotype was associated with endometriosis susceptibility. Our findings may provide an important clue to elucidating the pathogenesis of endometriosis.

The tolerability and feasibility of combination therapy with paclitaxel (TXL) and carboplatin (CBDCA) against small residual disease following first-line optimal debulking of stage I c-IV ovarian cancer were evaluated in a multicenter dose-finding study. Eligibility criteria included histologically diagnosed stage I c-IV epithelial ovarian cancer with a postoperative residual lesion < or = 10 mm in diameter, no prior chemotherapy, and written informed consent of the patient and his/her family members to the chemotherapy. Twenty-two patients were enrolled and 20 of them were eligible. The patients were to receive 5 courses of TXL (175 mg/m2) and CBDCA (AUC 5) every 3 weeks. Hematological toxicities occurred in the form of grade 3 leukopenia during 25.7% of all courses, grade 3 neutropenia during 32.0% of all courses, and grade 4 neutropenia during 56.0% of all courses. No courses were associated with grade 4 leukopenia. G-CSF support was needed during 48 of 109 courses (44%) and caused normalization of the leukocyte count from a nadir of 1,921 +/- 434/mm3 after a mean time of 6 +/- 3.1 days, compared with 6 +/- 3.6 days needed for recovery from a nadir of 2, 357 +/- 360/mm3 without G-CSF support. This indicates similarly rapid recovery from severe leukopenia with the use of G-CSF. All eligible patients completed at least 5 courses of the chemotherapy. Some courses were given at a reduced dose or delayed due to toxicity but these dosage modifications were thought to be acceptable for both TXL and CBDCA. Five courses of TXL combined with CBDCA were tolerated well in this patient population.

Background: To investigate whether polymorphisms of CYP17 and CYP19 genes are associated with the risk of endometriosis, we analysed the frequency and distribution of a single nucleotide polymorphism at the 5' untranslated region of the CYP17 gene, and a tetranucleotide (TTTA) tandem repeat polymorphism and a 3 bp insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene., Methods: We studied 140 patients with endometriosis, 67 with adenomyosis and/or leiomyomas and 177 healthy control women., Results: The distribution of the genotypes of CYP17 and alleles of the TTTA repeat polymorphism of CYP19 were not significantly different between the groups. In contrast, an increased frequency of the D/D genotype was observed in the endometriosis group as compared with the control group (D/D genotype versus I/I plus I/D genotypes; corrected P = 0.024). This was more evident in the endometriosis subgroups with chocolate cysts (corrected P = 0.043) and at severe clinical stages (corrected P = 0.035)., Conclusions: The results suggest that the 3 bp I/D polymorphism of the CYP19 gene may be weakly associated with the susceptibility of endometriosis in a Japanese population.

Problem: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The aim of this study was to investigate whether polymorphisms of the IL-10 gene promoter polymorphisms may be responsible in part for genetic susceptibility to endometriosis., Methods of Study: Polymorphisms at position -1082 and -592 in the IL-10 promoter region were determined in 196 patients with endometriosis and 160 fertile healthy women by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)., Results: There were no statistically significant differences in the genotype and allele frequencies of IL-10 promoter polymorphism between the endometriosis and control groups. However, when subgrouped according to clinical features, the frequencies of the -592*CC genotype and -592*C allele were significantly increased in patients with autoantibodies to carbonic anhydrase II (anti-CA II ab) compared with controls., Conclusion: IL-10 promoter polymorphisms were associated with the production of anti-CA II ab in patients with endometriosis, suggesting a role in the genetic susceptibility for endometriosis.

An immunohistochemical study was made of a case of serous cystadenocarcinoma that had been shown to have arisen from ovarian endometriosis. Aromatase cytochrome P450 (P450arom), an enzyme responsible for estrogen biosynthesis, was localized in the epithelial linings of the endometriosis and faintly in the transitional part, whereas it was not expressed in the carcinoma tissue. In contrast, estrogen receptors, progesterone receptors, and apoptosis-associated proteins, Fas, Fas ligand, and Bax were expressed in both endometriosis and carcinoma tissues of the tumor, whereas Bcl-2 was not expressed in either tissue of the tumor. It was suggested that the undifferentiated shift of the histologic grade might result in the loss of P450arom and that the malignant transformation was not caused by an altered balance of apoptosis-associated proteins. Accumulation of these studies may lead to a better understanding of the nature of malignant transformation of ovarian endometriosis.

Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Leptin is involved in the stimulation of reproductive functions, and local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta might play a role in early development. The mRNA and protein of the long form leptin receptor (OB-R(L)) but not of leptin are expressed in the human endometrium and the abundance of OB-R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase. We examined the steroidal regulation of OB-R(L) mRNA expression. Northern blot analyses showed that in organ-cultured proliferative endometrial specimens, oestradiol (10(-9) and 10(-8) mol/l) had no acute effect on the OB-R(L) mRNA expression, whereas oestradiol plus progesterone (10(-8), 10(-7) and 10(-6) mol/l) or medroxyprogesterone acetate (10(-8) and 10(-7) mol/l) suppressed the expression by approximately 50%. This progestin-induced suppression was blocked by a concomitant addition of mifepristone. Additionally, incubation of endometrial specimens in the presence of leptin resulted in the phosphorylation of its intracellular target, STAT3 (signal transducer and activator of transcription 3). These results indicate that, in the human endometrium, progestins act via the progesterone receptors to suppress functional OB-R(L) mRNA expression, and may thereby alter the sensitivity of the endometrium to leptin.

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.

Endometriosis, adenomyosis and leiomyomata develop in women of reproductive age and regress after menopause or ovariectomy, suggesting that they grow in an oestrogen-dependent fashion. We investigated whether polymorphism in the oestrogen receptor-alpha (ERalpha) gene is related to oestrogen-dependent benign uterine disease. A total of 203 women with regular menstrual cycles underwent laparotomy or laparoscopy and were diagnosed histologically with endometriosis, adenomyosis and/or leiomyomata. Patients with cervical carcinoma in situ, tubal occlusion or adhesion but no other gynaecological disease were considered to be disease-free. A total of 179 women undergoing annual health examination were grouped as reference population. The distribution of PVUII genotypes (PP, Pp, and pp) of the ERalpha gene was different between each pair of the four groups of endometriosis, adenomyosis/leiomyomata, disease-free, and reference population (P = 0.022-0.0005), except between the former two groups. The PP genotype was less frequent in the groups of endometriosis (P = 0.0002) and adenomyosis/leiomyomata (P = 0.002) as compared to that in the disease-free group. In the endometriosis group, there was no difference in the distribution of PVUII genotypes due to complicating diseases (adenomyosis and/or leiomyomata) or severity of the clinical stages. These results suggest that the PVUII polymorphism of the ERalpha gene is associated with the risk for endometriosis, adenomyosis, and leiomyomata.