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1.
Mod Rheumatol ; 33(3): 496-502, 2023 Apr 13.
Article En | MEDLINE | ID: mdl-35652691

OBJECTIVES: To explore patient-reported outcomes (PROs) related to quality of life (QOL) in patients with rheumatoid arthritis (RA) who achieved clinical remission. METHODS: In the Institute of Rheumatology, Rheumatoid Arthritis dataset, RA patients >18 years old who met the simplified disease activity index (SDAI) remission criteria in April 2017 were enrolled in this analysis. Pain-visual analogue scale (pain-VAS) (0-100 mm), patient's global assessment of disease activity (Pt-GA; 0-100 mm), Japanese version of the Health Assessment Questionnaire, duration of morning joint stiffness, and fatigue [Checklist Individual Strength 8R (CIS)] were the tools used to evaluate PROs. To assess the contribution of each PRO to the European QOL-5 Dimensions-5 Level (EQ-5D-5L) score, an analysis of variance was conducted. RESULTS: Among the 2443 patients with remission, the mean EQ-5D-5L was 0.9. The mean pain-VAS and Pt-GA were 7.2 and 7.4, respectively. Factors that significantly contributed to the EQ-5D-5L were pain-VAS (48.8%), CIS score (18.1%), and Pt-GA (15.6%). Around 82.5% of the variance in EQ-5D-5L was explained by the three PROs. CONCLUSIONS: This study demonstrated that pain-VAS, CIS, and Pt-GA were significant contributors to the EQ-5D-5L score in patients with RA who achieved the simplified disease activity index remission criteria.


Arthritis, Rheumatoid , Quality of Life , Humans , Adolescent , Arthritis, Rheumatoid/diagnosis , Patient Reported Outcome Measures , Databases, Factual , Pain , Surveys and Questionnaires
2.
Mod Rheumatol ; 33(5): 899-905, 2023 Aug 25.
Article En | MEDLINE | ID: mdl-36094815

OBJECTIVES: To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. RESULTS: The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). CONCLUSIONS: The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.


Arthritis, Rheumatoid , Humans , Female , Middle Aged , Male , Retrospective Studies , Patient Reported Outcome Measures , Surveys and Questionnaires , Pain , Quality of Life
3.
Mod Rheumatol ; 31(2): 326-333, 2021 Mar.
Article En | MEDLINE | ID: mdl-32475196

OBJECTIVES: To assess discordance in overall treatment satisfaction between patients with rheumatoid arthritis (RA) and their physicians. METHODS: This was a multicenter, cross-sectional, observational study of patients with RA (in low disease activity or remission) and their board-certified treating physicians in Japan; 202 patient-physician pairs were analyzed. Treatment satisfaction and perceptions were assessed using a structured questionnaire. RESULTS: Using a two-level ('satisfied' or 'unsatisfied') assessment of satisfaction, 195 patients (96.5%) and 190 physicians (94.1%) answered 'satisfied' with a high level of concordance (184 pairs, 91.1%). Using a four-level assessment, the ratio of 'satisfied' to 'somewhat satisfied' was higher in patients (66.3%/30.2%) than physicians (43.6%/50.5%). Satisfaction with treatment outcomes (e.g. joint conditions, subjective symptoms) was generally high in patients and physicians; relatively less satisfaction was reported for medication cost, especially among patients. Shared treatment decision-making was reported in ≥96% of patient-physician pairs. The most common 'most important' treatment target differed between patients ('Have a social life without worrying about RA') and physicians ('Prevent joint damage, deformity, and joint swelling'). CONCLUSIONS: Treatment satisfaction and concordance were high between patients in low activity/remission and physicians. Some differences between patients and physicians were reported in satisfaction for specific treatment outcomes and important treatment targets.


Arthritis, Rheumatoid/drug therapy , Patient Satisfaction , Physician-Patient Relations , Physicians/psychology , Adult , Female , Humans , Japan , Male , Middle Aged , Surveys and Questionnaires , Treatment Outcome
4.
Am J Respir Cell Mol Biol ; 63(3): 293-305, 2020 09.
Article En | MEDLINE | ID: mdl-32338993

Chronic exposure to cigarette smoke (CS) causes chronic inflammation, oxidative stress, and apoptosis of epithelial cells, which results in destruction of the lung matrix. However, the mechanism by which the lung fails to repair the CS-induced damage, thereby succumbing to emphysema, remains unclear. Alveolar type 2 (AT2) cells comprise the stem cells of the alveolar compartments and are responsible for repairing and maintaining lung tissues. In this study, we examined the effect of chronic CS on AT2 stem cells. Adult mice expressing GFP in their AT2 cells were exposed to CS for > 3 months. Histological assessment showed that CS not only induced emphysematous changes but also increased the number of AT2 cells compared with that of air-exposed lungs. Assessment of sorted GFP+/AT2 cells via the stem cell three-dimensional organoid/colony-forming assay revealed that the number and size of the colonies formed by the CS-exposed AT2 stem cells were significantly higher than those of air-exposed control AT2 cells. Although CS-exposed lungs had more apoptotic cells, examination of the surviving AT2 stem cells in two-dimensional in vitro culture revealed that they developed a higher ability to resist apoptosis. Microarray analysis of CS-exposed AT2 stem cells revealed the upregulation of genes related to circadian rhythm and inflammatory pathways. In conclusion, we provide evidence that AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes.


Alveolar Epithelial Cells/drug effects , Nicotiana/toxicity , Pulmonary Emphysema/pathology , Smoke/adverse effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Animals , Apoptosis/drug effects , Lung/pathology , Mice, Inbred C57BL , Oxidative Stress/drug effects , Pulmonary Disease, Chronic Obstructive/pathology , Smoking
5.
Surg Radiol Anat ; 42(7): 761-770, 2020 Jul.
Article En | MEDLINE | ID: mdl-32112281

A long tortuous course of the abducens nerve (ABN) crossing a highly curved siphon of the internal carotid artery is of interest to neurosurgeons for cavernous sinus surgery. Although a "straight" intracavernous carotid artery in fetuses can change into an adult-like siphon in infants, there is no information on when or how the unique course of ABN is established. Histological observations of 18 near-term fetuses (12 specimens of frontal sections and 6 specimens of sagittal sections) demonstrated the following: (I) the ABN consistently took a straight course crossing the lateral side of an almost straight intracavernous carotid artery; (II) the straight course was maintained when sympathetic nerves joined; (III) few parasellar veins of the developing cavernous sinus separated the ABN from the ophthalmic nerve; and (IV) immediately before the developing tendinous annulus for a common origin of extraocular recti, the ABN bent laterally to avoid a passage of the thick oculomotor nerve. Since the present observations strongly suggested morphologies at birth and in infants, major angulations of the ABN as well as the well-known course independent of the other nerves in the cavernous sinus seemed to be established during childhood. In the human body, the ABN might be a limited example showing a drastic postnatal change in course. Consequently, it might be important to know the unique course of ABN before performing endovascular interventions and skull base surgery for petroclival and cavernous sinus lesions without causing inadvertent neurovascular injuries to neonates or infants.


Abducens Nerve/embryology , Aborted Fetus/anatomy & histology , Cavernous Sinus/innervation , Carotid Artery, Internal/embryology , Cavernous Sinus/embryology , Gestational Age , Humans , Oculomotor Nerve/embryology
6.
PLoS One ; 13(1): e0191611, 2018.
Article En | MEDLINE | ID: mdl-29381718

Smoking is a common risk factor for both chronic obstructive pulmonary disease (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor for vertebral fracture; however, the effects of smoking or emphysema on bone health remain largely unknown. We report bone deterioration in a mouse model of emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short-term exposure for 4-weeks decreased bone turnover and increased bone volume in mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from suppression to promotion of bone resorption. This long-term CS exposure increased osteoclast number and impaired bone growth, while it increased bone volume. Strikingly, long-term CS exposure deteriorated bone quality of the lumbar vertebrae as illustrated by disorientation of collagen fibers and the biological apatite c-axis. This animal model may provide a better understanding of the mechanisms underlying the deterioration of bone quality in pulmonary emphysema caused by smoking.


Bone and Bones/metabolism , Disease Models, Animal , Emphysema/metabolism , Smoke , Tobacco Products , Animals , Bone Remodeling , Mice , Mice, Inbred C57BL
7.
Chron Respir Dis ; 15(4): 329-338, 2018 11.
Article En | MEDLINE | ID: mdl-29232989

Cigarette smoking increases the risk of developing both cataract and chronic obstructive pulmonary disease (COPD). The prevalence of cataract and the clinical characteristics of COPD patients with cataract were retrospectively investigated in a 2-year observational COPD cohort. We analyzed 395 patients with complete data on ophthalmologic evaluation (319 subjects with COPD and 76 subjects at risk of COPD). There was no difference in the prevalence of cataract between COPD patients and those at risk (47.0% vs. 42.1%, p = 0.44). Age ≥ 75 years, low body mass index, and hypertension were independently associated with cataract as a comorbidity in COPD. The incidence of exacerbation within 2 years was significantly higher in COPD patients with cataract than those without cataract (36.6% vs. 18.3%, p = 0.0019). COPD patients with cataract exhibited significantly higher COPD assessment test score compared to those without cataract (13.7 ± 8.9 vs. 11.5 ± 7.2, p = 0.0240). Overall St George's Respiratory Questionnaire score and each component were significantly worse in COPD patients with cataract compared to those without cataract. COPD patients with cataract exhibited poor health-related quality of life and frequent exacerbations. The association between cataract and exacerbations of COPD deserves further attention.


Cataract/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Quality of Life , Age Factors , Aged , Aged, 80 and over , Body Mass Index , Comorbidity , Disease Progression , Female , Health Status , Humans , Hypertension/epidemiology , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Prevalence , Retrospective Studies , Surveys and Questionnaires
8.
Okajimas Folia Anat Jpn ; 94(1): 17-25, 2017.
Article En | MEDLINE | ID: mdl-29213015

The origin of the posterior scrotal nerve is considered to be the bilateral pudendal nerves but the course to the midline is still obscure. Using 5 late-stage human male fetuses, we identified the single nerve through the intramuscular midline septum of the bulbospongiosus and the bilateral nerves along the left and right sides of the septum. Thus, the posterior scrotal nerve showed a variation: a single midline trunk or bilateral nerves. Branches of the bilateral pudendal nerves ran medially between the muscle and Cowper's gland and, at the midline area, they joined or associated closely. During the proximal course, much or less, the nerve penetrated the superior part of the muscle. The nerve entered the subcutaneous tissue at and near the perineal raphe. The communication with intrapelvic autonomic nerves were suggested behind Cowper's gland. Notably, the midline skin immediately anterior to the anus carried a considerable dense supply of thin sensory nerves. However, these nerves seemed to come from a space between the rectal smooth muscle and the external anal sphincter, not from the posterior scrotal nerve. Therefore, surgical treatment of the intersphincteric layer was likely to injure the original sensory nerve supply to the anterior anal skin.


Fetus/innervation , Perineum/innervation , Humans , Male
9.
Okajimas Folia Anat Jpn ; 94(1): 37-44, 2017.
Article En | MEDLINE | ID: mdl-29213017

The median nerve passes through the humeral and ulnar heads of the pronator teres muscle (PT), although variations such as absence of the ulnar head may exist. We observed histological sections of the upper extremity from 24 embryos and fetuses. In the early stage, the PT extended between the radius and the medial epicondyle of the humerus, but no candidate for the ulnar head was found. In mid-term fetuses, the ulnar margin of the PT was attached to the elbow joint capsule. Moreover, in late-stage fetuses, a small deep part of the PT arose from the thick joint capsule of the humero-ulnar joint near the coronoid process of the ulna. This joint capsule also provided the most proximal origin of the flexor digitorum profundus muscle. Therefore, we considered fetal PT origin from the capsule as a likely candidate for the ulnar head. Consequently, the PT seemed to develop from a single anlage through which the median nerve passed, but later - possibly after birth - a small PT origin from the joint capsule appeared to obtain an aponeurosis connecting the muscle fiber to the ulna. This secondary change in PT morphology might explain the muscle variation seen in adults.


Fetus/anatomy & histology , Forearm/embryology , Median Nerve/embryology , Muscle, Skeletal/embryology , Embryonic Development , Fetal Development , Humans
10.
Respir Med ; 131: 101-108, 2017 10.
Article En | MEDLINE | ID: mdl-28947014

BACKGROUND: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a subjective measure of quality of life. The aim of this study was to examine the characteristics of COPD patients with increasing CAT scores within 3 years. METHODS: Keio University and its affiliate hospitals conducted an observational COPD cohort study over 3 years. St. George's Respiratory Questionnaire (SGRQ) and CAT were completed at baseline and annually thereafter. Patients who had at least 3 CAT scores were included (n = 315). The ΔCAT score/year and ΔSGRQ score/year were calculated by the slope between each of the measures and the date of measurement. RESULTS: The median ΔCAT score/year was 0.4, and ΔCAT score/year was significantly correlated with ΔSGRQ total score/year. Using an annual cut-off CAT score of +2 points, patients who deteriorated (n = 79) were older, had lower %FEV1, and more severe emphysema on computed tomography scan at baseline than patients who did not deteriorate. The baseline value was not a determinant of subsequent changes in the CAT score. Longitudinal changes in the CAT score were positively correlated with those in the SGRQ score. CONCLUSIONS: Old age and severe COPD, not the CAT score at one time point, predicted worsening quality of life.


Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/physiopathology , Quality of Life , Adult , Age Factors , Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Severity of Illness Index , Tomography, X-Ray Computed
11.
Int J Psychiatry Clin Pract ; 20(4): 260-4, 2016 Nov.
Article En | MEDLINE | ID: mdl-27541857

OBJECTIVE: The study aimed to identify the predictors for readmission after a successful electroconvulsive therapy (ECT) course. METHODS: Medical charts of patients who received ECT for major depressive episodes were reviewed. Patients' demographic characteristics and treatment parameters, such as ECT charge, seizure duration, the number of ECT sessions and pharmacotherapy, were extracted. We compared differences between those who were readmitted after successful ECT within 6 and 12 months, versus those not readmitted. We also conducted a multivariate logistic regression analysis to identify the predictors for readmission. RESULTS: Out of 51 patients who were discharged after ECT, 27 patients met the inclusion criteria and were included in the analysis. Eight patients were readmitted within 6 months after discharge, and four more patients were readmitted during the next 6-month follow up. Comparing patients who were and were not readmitted, we found no significant differences between groups, including ECT parameters such as the number of ECT sessions, average charge and final charge. No predictors for readmission were found through multivariate analysis. CONCLUSIONS: Although patients who require higher ECT charge and more sessions seem to be prone to readmission, our dataset suggested that none of these types of ECT parameters were risk factors for readmission.


Depressive Disorder, Major/therapy , Electroconvulsive Therapy/statistics & numerical data , Patient Readmission/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Risk Factors
12.
Respir Med ; 117: 272-9, 2016 08.
Article En | MEDLINE | ID: mdl-27492541

BACKGROUND AND OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from various comorbidities. Recently, cluster analysis has been proposed to examine the phenotypic heterogeneity in COPD. In order to comprehensively understand the comorbidities of COPD in Japan, we conducted multicenter, longitudinal cohort study, called the Keio COPD Comorbidity Research (K-CCR). In this cohort, comorbid diagnoses were established by both objective examination and review of clinical records, in addition to self-report. We aimed to investigate the clustering of nineteen clinically relevant comorbidities and the meaningful outcomes of the clusters over a two-year follow-up period. MATERIAL AND METHODS: The present study analyzed data from COPD patients whose data of comorbidities were completed (n = 311). Cluster analysis was performed using Ward's minimum-variance method. RESULTS: Five comorbidity clusters were identified: less comorbidity; malignancy; metabolic and cardiovascular; gastroesophageal reflux disease (GERD) and psychological; and underweight and anemic. FEV1 did not differ among the clusters. GERD and psychological cluster had worse COPD assessment test (CAT) and Saint George's respiratory questionnaire (SGRQ) at baseline compared to the other clusters (CAT: p = 0.0003 and SGRQ: p = 0.00046). The rate of change in these scores did not differ within 2 years. The underweight and anemic cluster included subjects with lower baseline ratio of predicted diffusing capacity (DLco/VA) compared to the malignancy cluster (p = 0.036). CONCLUSIONS: Five clusters of comorbidities were identified in Japanese COPD patients. The clinical characteristics and health-related quality of life were different among these clusters during a follow-up of two years.


Cluster Analysis , Comorbidity/trends , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Aged, 80 and over , Anemia/epidemiology , Cardiovascular Diseases/epidemiology , Cohort Studies , Female , Follow-Up Studies , Forced Expiratory Volume/physiology , Gastroesophageal Reflux/epidemiology , Humans , Japan/epidemiology , Longitudinal Studies , Male , Neoplasms/epidemiology , Phenotype , Prospective Studies , Pulmonary Diffusing Capacity/methods , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/epidemiology , Quality of Life , Self Report , Smoking/epidemiology , Thinness/epidemiology , Tomography, X-Ray Computed
13.
Article En | MEDLINE | ID: mdl-27354785

BACKGROUND: Patients with COPD might not report mild exacerbation. The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown. OBJECTIVES: The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD. PATIENTS AND METHODS: An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities. This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311). RESULTS: Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year. Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year. Findings of the COPD assessment test and the symptom component of the St George's Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them. Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year. CONCLUSION: The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD.


Pulmonary Disease, Chronic Obstructive/diagnosis , Aged , Aged, 80 and over , Comorbidity , Disease Progression , Female , Forced Expiratory Volume , Humans , Japan/epidemiology , Lung/physiopathology , Male , Middle Aged , Prevalence , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Registries , Retrospective Studies , Risk Factors , Severity of Illness Index , Surveys and Questionnaires , Time Factors
14.
J Infect Dis ; 213(6): 1018-30, 2016 Mar 15.
Article En | MEDLINE | ID: mdl-26563237

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD)--typically caused by bacterial or viral infection--is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. METHODS: We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. RESULTS: In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, an increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly owing to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and emphysema progression. CONCLUSIONS: These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD.


Matrix Metalloproteinase 12/metabolism , Pancreatic Elastase/toxicity , Pneumococcal Infections/complications , Pulmonary Emphysema/chemically induced , Animals , Bronchoalveolar Lavage Fluid/cytology , Cytokines/genetics , Cytokines/metabolism , Dexamethasone/therapeutic use , Female , Gene Expression Regulation/physiology , Lymphocytes/physiology , Macrophages/physiology , Matrix Metalloproteinase 12/genetics , Mice , Mice, Inbred C57BL , Neutrophils/physiology , Phenyl Ethers/pharmacology , Pneumococcal Infections/metabolism , Pulmonary Emphysema/complications , Pulmonary Emphysema/pathology , Streptococcus pneumoniae
15.
Am J Physiol Lung Cell Mol Physiol ; 308(10): L1039-45, 2015 May 15.
Article En | MEDLINE | ID: mdl-25820526

Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few studies evaluated the dynamic structural changes in a CS-induced emphysema mouse model. A novel micro-CT technique with respiratory and cardiac gating has resulted in high-quality images that enable processing for further quantitative and qualitative analyses. Adult female C57BL/6J mice were repeatedly exposed to mainstream CS, and micro-CT scans were performed at 0, 4, 12, and 20 wk. Emphysema was also histologically quantified at each time point. Air-exposed mice and mice treated with intratracheal elastase served as controls and comparisons, respectively. End-expiratory lung volume, corresponding to functional residual volume, was defined as the calculated volume at the phase of end-expiration, and it evaluated air trapping. The end-expiratory lung volumes of CS-exposed mice were significantly larger than those of air controls at 12 and 20 wk, which was in line with alveolar enlargement and destruction by histological quantification. However, CS exposure neither increased low attenuation volume nor decreased the average lung CT value at any time point, unlike the elastase-instilled emphysema model. CS-exposed mice had rather higher average lung CT values at 4 and 12 wk. This is the first study characterizing a CS-induced emphysema model on micro-CT over time in mice. Moreover, these findings extend our understanding of the distinct pathophysiology of CS-induced emphysema in mice.


Pulmonary Alveoli/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Smoking/adverse effects , Animals , Disease Models, Animal , Female , Forced Expiratory Volume , Humans , Mice , Pulmonary Alveoli/physiopathology , Pulmonary Emphysema/physiopathology , X-Ray Microtomography
16.
J Med Invest ; 57(3-4): 314-20, 2010 Aug.
Article En | MEDLINE | ID: mdl-20847532

Glycoglycerolipids are mostly found in plants, however the beneficial effects of the glycoglycerolipids on mammalian body have not been understood. In this study, we investigated the effects of glycolipid extracts from spinach, which highly contained glycoglycerolipids, on mucosal injury induced by 5-fluorouracil (5-FU) in rats. Preadministration of glycolipid extracts from spinach (20 mg/kg body weight) prevented villous atrophy, misaligned crypts, and increased inflammatory cytokines in rat jejunum treated with 5-FU (300 mg/kg body weight) compared with the extracts from soybean. The glycolipid extracts from spinach highly contained monogalactosyl-diacylglycerol (MGDG) and diglactosyl-diacylglycerol (DGDG). In Caco-2 cells, MGDG and DGDG inhibited the production of reactive oxygen species induced by phorbol ester. We concluded that glycolipid extracts from spinach has anti-oxidative and anti-inflammatory effects, and the extract may be useful for prevention of drug-induced mucosal injury and other inflammatory diseases. Tokushima


Fluorouracil/antagonists & inhibitors , Fluorouracil/toxicity , Glycolipids/pharmacology , Intestinal Mucosa/drug effects , Alkaline Phosphatase/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Caco-2 Cells , Cytokines/genetics , Galactolipids/pharmacology , Glycolipids/isolation & purification , Humans , Intestinal Mucosa/injuries , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mucositis/chemically induced , Mucositis/prevention & control , Plant Extracts/chemistry , Plant Extracts/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Glycine max/chemistry , Spinacia oleracea/chemistry
17.
Masui ; 58(6): 700-7, 2009 Jun.
Article Ja | MEDLINE | ID: mdl-19522260

BACKGROUND: Transient postoperative neurological disorders are common in patients undergoing aortic surgery with retrograde cerebral perfusion (RCP). We evaluated the relationship between transient postoperative neurological disorders and regional cerebral oxygen saturation (rSO2) during RCP. METHODS: Thirty-seven patients with aortic aneurysm dissection were enrolled in the study. They underwent the ascending aorta or hemi-arch replacement. The postoperative neurological complications occurred in 17 patients, including 2 strokes, 1 hypoxic encephalopathy, 6 delay of awareness, and 8 disorientations. Strokes and a hypoxic encephalopathy were excluded because they could result from embolic episodes. Changes in rSO2 during RCP in 14 patients with transient neurological disorders were compared with changes in 20 patients without disorders. RESULTS: The rSO2 values significantly decreased after the beginning of RCP in both groups. There was no difference in the lowest rSO2 value during RCP and in the rate of decrease from pre-RCP to the lowest rSO2 between two groups. However, the difference more than 10% between left and right was significantly associated with neurological disorders. CONCLUSIONS: The rSO2 monitor could detect the decrease of cerebral perfusion during RCP. The wide asymmetry of rSO2 was associated with transient neurological disorders, although the lowest rSO2 value and the rate of decline did not relate.


Aortic Aneurysm/surgery , Aortic Dissection/surgery , Brain/metabolism , Nervous System Diseases/etiology , Oxygen Consumption , Perfusion/adverse effects , Perfusion/methods , Postoperative Complications , Aged , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative , Nervous System Diseases/epidemiology , Nervous System Diseases/prevention & control , Retrospective Studies
18.
J Am Soc Nephrol ; 20(7): 1504-12, 2009 Jul.
Article En | MEDLINE | ID: mdl-19406976

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.


Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Phosphorus, Dietary/pharmacology , Adult , Animals , Brachial Artery/drug effects , Brachial Artery/physiology , Cardiovascular Diseases/epidemiology , Cattle , Cells, Cultured , Cross-Over Studies , Disease Models, Animal , Double-Blind Method , Endothelium, Vascular/cytology , Humans , Hyperphosphatemia/blood , Hyperphosphatemia/complications , Male , Nitric Oxide Synthase Type III/metabolism , Phosphorus/blood , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Regional Blood Flow/drug effects , Risk Factors , Vasodilation/drug effects
19.
Masui ; 55(12): 1493-5, 2006 Dec.
Article Ja | MEDLINE | ID: mdl-17190324

A 61-year-old man showed clinical findings which suggest atypical malignant hyperthermia after pancreatoduodenectomy. He showed no abnormal findings in preoperative examinations. General anesthesia was induced with thiopental, fentanyl, and vecuronium, and epidural anesthesia was also used for the perioperative management. The surgery went on uneventfully and the patient returned to the ward. The laboratory data after the surgery showed extremely high creatine kinase and myoglobin. The patient's body temperature rose up and showed rigidity. We suspected atypical malignant hyperthermia and began its treatment. Four months later, we performed muscle biopsy and Ca-induced Ca release (CICR) test, which presented a typical rising pattern. This is the first case of malignant hyperthermia which occurred after the surgery and accompanied by a typical rise in CICR.


Calcium/metabolism , Malignant Hyperthermia/metabolism , Humans , Male , Malignant Hyperthermia/diagnosis , Middle Aged
20.
Nihon Jibiinkoka Gakkai Kaiho ; 108(12): 1158-64, 2005 Dec.
Article Ja | MEDLINE | ID: mdl-16440813

After treatments, several patients with sudden deafness (SD) continued to have symptoms, including hearing loss, tinnitus and dizziness. These unresolved symptoms and their effect on the quality of life (QOL) in SD patients have not been studied. We evaluated QOL using the Hearing handicap inventory (HHIA) and an original questionnaire in SD patients who had been treated more than 6 months prior to the study. Compared to results in bilateral sensorineural hearing were significantly lower in SD patients (p<0.01). In bil SNHL, this score peaked two to 10 years after onset of disease and decreased thereafter. The score peaked more than 10 years after onset of disease in patients with SD. While hearing and test scores were correlated in bil-SNHL, this was not observed in SD. About half of patients were embarrassed by hearing loss and tinnitus after treatment. Among patients who scored more than 44 points on HHIA, all reported hearing loss and tinnitus. When asked about subjective changes in hearing after treatment, 27% believed their hearing had improved, 60% believed there was no change, and 13% believed their hearing had deteriorated. Cases believing deterioration in hearing also had high scores on HHIA. Sequelae of SD may worsen QOL, driving embarrassed patients to visit other medical facilities in to improve their QOL. Even though hearing may not improve after initial treatment in ears affected by SD, informed consent about the clinical course and audiological follow-up should be done.


Hearing Loss, Sudden/psychology , Quality of Life , Adult , Aged , Aging , Female , Hearing , Hearing Loss, Sensorineural/psychology , Humans , Male , Middle Aged , Surveys and Questionnaires , Tinnitus/psychology
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