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Since the manufacture, import, and use of asbestos products have been completely abolished in Japan, the main cause of asbestos emissions into the atmosphere is the demolition and removal of buildings built with asbestos-containing materials. To detect and correct asbestos emissions from inappropriate demolition and removal operations at an early stage, a rapid method to measure atmospheric asbestos fibers is required. The current rapid measurement method is a combination of short-term atmospheric sampling and phase-contrast microscopy counting. However, visual counting takes a considerable amount of time and is not sufficiently fast. Using artificial intelligence (AI) to analyze microscope images to detect fibers may greatly reduce the time required for counting. Therefore, in this study, we investigated the use of AI image analysis for detecting fibers in phase-contrast microscope images. A series of simulated atmospheric samples prepared from standard samples of amosite and chrysotile were observed using a phase-contrast microscope. Images were captured, and training datasets were created from the counting results of expert analysts. We adopted 2 types of AI models-an instance segmentation model, namely the mask region-based convolutional neural network (Mask R-CNN), and a semantic segmentation model, namely the multi-level aggregation network (MA-Net)-that were trained to detect asbestos fibers. The accuracy of fiber detection achieved with the Mask R-CNN model was 57% for recall and 46% for precision, whereas the accuracy achieved with the MA-Net model was 95% for recall and 91% for precision. Therefore, satisfactory results were obtained with the MA-Net model. The time required for fiber detection was less than 1 s per image in both AI models, which was faster than the time required for counting by an expert analyst., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Study Design: Cross-sectional study., Purpose: This cross-sectional study aimed to investigate the risk factors for osteoporosis in men by assessing bone mineral density (BMD), skeletal muscle mass, body fat mass, grip strength, and advanced glycation end products (AGEs)., Overview of Literature: Fewer studies have reported the correlation between BMD and skeletal muscle mass in women. Moreover, a few studies have examined the relationship between osteoporosis and skeletal muscle mass., Methods: This study included 99 men (mean age, 74.9 years; range, 28-93 years) who visited Qiball Clinic for BMD and body composition examinations. The osteoporosis group consisted of 24 patients (mean age, 72.5 years; range, 44-92 years), and the control group consisted of 75 individuals (mean age, 74.9 years; range, 28-93 years). Whole-body skeletal muscle mass was measured using a bioelectrical impedance analyzer. BMD was measured by dual X-ray absorptiometry. Skin autofluorescence (SAF), a marker of dermal AGE accumulation, was measured using a spectroscope. Osteoporosis was defined as a bone density T score of -2.5 or less. Physical findings, skeletal muscle mass, BMD, grip strength, and SAF were compared between the osteoporosis and control groups., Results: The osteoporosis group had significantly lower trunk muscle mass (23.1 kg vs. 24.9 kg), lower leg muscle mass (14.4 kg vs. 13.0 kg), and skeletal mass index (7.1 kg/m2 vs. 6.7 kg/m2) than the control group (all p<0.05). Lower limb muscle mass was identified as a risk factor for osteoporosis in men (odds ratio, 0.64; p=0.03)., Conclusions: Conservative treatment of osteoporosis in men will require an effective approach that facilitates the maintenance or strengthening of skeletal muscle mass, including exercise therapy with a focus on lower extremities and nutritional supplementation.

Purpose: We compared the clinical effects of Neurotropin, limaprost alfadex, and a combination of both drugs for lumbar spinal stenosis (LSS) with low back pain (LBP)., Methods: We conducted a multicenter, randomized, active-controlled, open-label trial from March 2021 to May 2022. Participants were patients diagnosed with LSS by MRI and were randomly assigned to three groups: Neurotropin/limaprost combination (NL group), Neurotropin (N group), and limaprost group (L group). Participants received the drugs administered orally for 12 weeks, and each examination and observation was performed before any drug administration and every 2 weeks thereafter. We recorded age, sex, height, weight, duration of symptoms, intermittent claudication distance, level of stenosis in MRI, and concomitant analgesics as examination items in the trial period. Items measured during the trial were visual analog scale (VAS) score (mm) for LBP, leg pain and numbness, walking activity (walking speed, stride length), standing balance (3 m Timed Up-and-Go (TUG) Test results, Five Times Sit-to-Stand Test (FTSST) results), LBP/Quality of Life (QOL)-related scores (Oswestry Disability Index (ODI), Euro QOL 5-Dimensions 5-Level (EQ-5D-5L), Roland-Morris Disability Questionnaire (RDQ)), psychological factors (Pain catastrophizing scale (PCS) and Pain Self-Efficacy Questionnaire (PSEQ) scores), and adverse events. Each item was evaluated using changes at each visit (weeks 2-12) from baseline value before drug administration (week 0), and changes were considered significant when p < 0.05., Results: We included results from 64 patients in the present study; 24 were assigned to the NL group (mean age 71.2 years), 20 to the N group (mean age 76.2 years), and 20 to the L group (mean age 74.4 years). There were no significant differences between the three groups in patient characteristics, concomitant analgesics, or baseline VAS score, gait balance, or QOL-related scores (p ≥ 0.05). The VAS and leg pain scores were significantly improved in Group L, and LBP was improved significantly in Group N. QOL and ODI scores improved significantly in the NL and L groups, EQ-5D score improved significantly in the L group, and RDQ score improved significantly in all groups (p < 0.05). Psychological factor and PCS scores improved significantly in the NL and L groups (p < 0.05). Walking speed and stride length were improved significantly in the NL and N groups (p < 0.05). TUG/FTSST scores were improved significantly in all groups (p < 0.05). Leg pain VAS score was improved significantly (p < 0.05) in the L group compared with the NL group after 6 and 12 weeks of administration, and LBP VAS was improved significantly in the N group after 6 weeks compared with the NL group (p < 0.05). Walking speed was significantly improved in the NL group after 2 weeks compared with the N group and improved significantly in the NL group after 6 weeks (p < 0.05) compared with the L group. RDQ was decreased significantly in the L group compared with the NL group after 8 weeks (p < 0.05)., Conclusions: Combined use of Neurotropin and limaprost showed an additional effect on walking speed compared with single drug administration. Neurotropin may contribute to the improvement of low back pain, walking speed/stride length, and standing balance., Trial Registration: Japan Registry of Clinical Trials (jRCTs031200282)., (© 2023. The Author(s).)

Purpose: We investigated changes in skeletal muscle mass and bone mineral density in degenerative lumbar scoliosis (DLS) patients during a 2-year follow-up following diagnosis., Method: This study included 418 Japanese women, identifying 50 patients for the DLS group (mean age 76.4 years) and 368 patients for the control group (mean age 73.4 years). Whole-body skeletal muscle mass was measured using a Bioelectrical Impedance Analyzer. Bone mineral density (BMD) was measured using DXA. Skin autofluorescence (SAF), a marker of advanced glycation end products in the skin, was measured using a spectroscope. Spinal alignment, skeletal muscle mass, BMD, grip strength, and SAF were examined and the amount of change 1 and 2 years from the initial examination for each item was compared between groups., Results: Height, body fat mass, grip strength, upper limb muscle mass, and trunk muscle mass in the DLS group were significantly lower, and lumbar spine BMD was significantly greater compared to controls at the first visit (p < 0.05). There was no significant difference in spinal alignment in the DLS group after 2 years compared with baseline. Trunk muscle mass also decreased significantly more in the DLS group (-2.7%) than in the control group (-1.1%) over the 2-year follow-up (p < 0.05)., Discussion: In this study, trunk muscle mass in the DLS group decreased about 2.4 times more in 2 years compared with the control group (p < 0.05). It may be possible to clarify the mechanism of kyphoscoliosis progression in the future with large-scale longitudinal studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other. Abbreviations : AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients.

Aim: We aimed to develop a measurement method that can count fibers rapidly by scanning electron microscopy equipped with an artificial intelligence image recognition system (AI-SEM), detecting thin fibers which cannot be observed by a conventional phase contrast microscopy (PCM) method., Methods: We created a simulation sampling filter of airborne fibers using water-filtered chrysotile (white asbestos). A total of 108 images was taken of the samples at a 5 kV accelerating voltage with 10 000X magnification scanning electron microscopy (SEM). Each of three expert analysts counted 108 images and created a model answer for fibers. We trained the artificial intelligence (AI) using 25 of the 108 images. After the training, the AI counted fibers in 108 images again., Results: There was a 12.1% difference between the AI counting results and the model answer. At 10 000X magnification, AI-SEM can detect 87.9% of fibers with a diameter of 0.06-3 μm, which is similar to a skilled analyst. Fibers with a diameter of 0.2 μm or less cannot be confirmed by phase-contrast microscopy (PCM). When observing the same area in 300 images with 1500X magnification SEM-as listed in the Asbestos Monitoring Manual (Ministry of the Environment)-with 10 000X SEM, the expected analysis time required for the trained AI is 5 h, whereas the expected time required for observation by an analyst is 251 h., Conclusion: The AI-SEM can count thin fibers with higher accuracy and more quickly than conventional methods by PCM and SEM., (© 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Lower limb muscle mass and grip loss may be risk factors for vertebral compression fractures in women., Purpose: We examined the relationship between bone mineral density, bone strength, skeletal muscle mass, grip strength, and skin autofluorescence (SAF) in women with osteoporotic vertebral compression fractures (VCF)., Methods: A total of 1039 women (mean age 73.3 years) were included in our study. These included 222 cases of VCF (mean 77.8 years) and 817 controls (mean 72.0 years). Lumbar and femur BMD were measured for all participants using dual-energy X-ray absorptiometry (DXA). Bone strength surrogates, such as cross-sectional area (CSA) of the proximal femur, were evaluated using Advanced Hip Assessment software. SAF was measured with an autofluorescence reader. We used a bioelectrical impedance analyzer (BIA) to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m)) 2 . We measured bone density, geometric parameters related to bone strength, skeletal muscle mass, grip strength, and SAF in both groups. We also examined factors related to vertebral fracture using multiple logistic regression analysis., Results: Women with vertebral fractures had lower SMI (5.55 vs 5.76 kg/m 2 , p = 0.0006), smaller femoral cross-sectional area (97.20 vs 100.09, p = 0.014), lower grip strength (16.81 vs 19.16 kg, p < 0.0001), and increased skin autofluorescence (2.38 vs 2.25, p = 0.0002) compared to women without fractures. The prevalence of sarcopenia (SMI < 5.75) was 63.51% in VCF subjects and 52.02% in controls, revealing a high prevalence in VCF (p = 0.002). Skeletal muscle mass and grip strength were not significantly different between patients with acute and old VCF, suggesting that low skeletal muscle mass and muscle weakness may exist before fracture. From the multiple logistic regression analysis, lower femoral density (p = 0.0021), CSA (p = 0.0166), leg muscle mass (p = 0.0127), and left arm grip strength (p = 0.0255) were risk factors for vertebral compression fractures; all were negatively correlated with increased vertebral fractures., Conclusions: Lower limb muscle mass and grip loss may be closely related to the onset of vertebral compression fracture.

Purpose: We investigated the involvement of sarcopenia in middle-aged and elderly women with degenerative lumbar scoliosis (DLS)., Methods: A total of 971 women (mean age 70.4 years) were included in our study. These included 87 cases of DLS (mean 73.8 years) and 884 controls (69.8). Lumbar and femur BMD was measured for all participants using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m)) 2 . We determined bone density and skeletal muscle mass in both groups and determined the prevalence of sarcopenia. We examined the correlation between bone density and appendicular muscle mass in both groups. We also examined factors related to scoliosis using logistic regression analysis., Results: The DLS group showed significantly higher lumbar BMD, lower femur BMD, lower lean mass arm, and lower lean mass leg, and lower lean mass trunk (p < 0.05). Sarcopenia prevalence (SMI < 5.75) was 59.8% in DLS subjects and 42.8% in controls, revealing a high prevalence in DLS (p < 0.05). In both groups, lumbar and femur BMD were positively correlated with appendicular muscle mass. By logistic regression analysis, trunk muscle mass was detected as a risk factor for DLS independent of age (p < 0.05)., Conclusions: In middle-aged and elderly women, prevalence of sarcopenia was 59.8% in DLS cases and 42.8% in controls, which revealed a high prevalence in DLS. A decrease in trunk muscle was a significant risk factor for DLS that was independent of age. These slides can be retrieved under Electronic Supplementary Material.

Introduction: Limb muscle mass measurement using dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the diagnosis of sarcopenia. Moreover, bioelectrical impedance analysis (BIA) is also recognized as a beneficial tool considering its high correlation with DXA. However, it remains to be elucidated whether DXA and BIA can accurately measure trunk lean mass. The aim of this study was to investigate the correlation between DXA and BIA measurements of trunk muscle mass and the cross-sectional area (CSA) of trunk muscles measured using magnetic resonance imaging (MRI) and to compare measures of trunk muscle mass obtained using DXA and BIA in patients with low back pain (LBP)., Methods: In total, 65 patients participated in the study. The correlation between DXA and BIA measurements and the CSA of trunk and paraspinal muscles at the L4-5 level were calculated. In addition, the correlation between DXA and BIA measurements of trunk muscle mass and the differences between these two measurements were determined., Results: The correlation coefficient between DXA and BIA trunk muscle mass measurement and trunk muscle CSA was 0.74 and 0.56 for men and 0.69 and 0.44 for women, respectively. DXA and BIA measurement values showed a significantly moderate correlation with the CSA of the erector spinae (ES) and psoas major (PM). The multifidus (MF) CSA did not correlate with measurements of DXA and BIA in both men and women. Although DXA and BIA measurements were significantly correlated, a significant difference between these two measurements was found. BIA overestimated the trunk muscle mass significantly compared with DXA., Conclusions: Trunk muscle mass measured with DXA and BIA was correlated with the CSA of most trunk muscles. Although the measurement of DXA and BIA showed a high correlation, BIA overestimated trunk muscle mass compared with DXA. Both DXA and BIA are beneficial for measuring trunk muscle mass., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2019 by The Japanese Society for Spine Surgery and Related Research.)

Study Design: A retrospective observational study was performed., Purpose: We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women., Overview of Literature: AGEs have been implicated in the pathogenesis of sarcopenia., Methods: We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2-C7 sagittal vertical axis (C2-C7SVA), C2-C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined., Results: Sarcopenia (SMI <5.75) was observed at a high prevalence in participants with DHS (77% compared to 22% of healthy controls). Height, weight, femoral bone mineral density, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. Serum and urinary pentosidine, and serum homocysteine were significantly higher in the DHS group compared to controls. Analysis of cervical alignment revealed a significant positive correlation of serum pentosidine with C2-C7SVA and C2S., Conclusions: Sarcopenia was involved in DHS, and high serum pentosidine levels are associated with severity of DHS in older women.

Study Design: Cross-sectional observational study., Purpose: To compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD). Overview of the Literature: If reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP., Methods: Measurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated., Results: BIA and DXA were highly correlated in both male and female patients (r =0.73-0.90, p <0.0001). However, BIA consistently overestimated ASMM by 1.5-2.5 kg on an average (p <0.0001) and underestimated WFM (-4.0 to -2.7 kg) on an average (p <0.0001). BIA-based ASMM correlated with BMD of the lumbar spine in both male and female patients (r =0.28-0.37, p ≤0.02) and that of the femoral neck (r =0.34-0.51, p ≤0.005). Regarding the calculated skeletal muscle index (SMI: ASMM/height [m2]) used as a criterion for sarcopenia, BIA-based SMI correlated with BMD of the lumbar spine in male patients (r =0.44, p =0.0004) and that of the femoral neck in female patients (r =0.33, p =0.009)., Conclusions: BIA may be a favorable alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Considering the overestimation of BIA-based ASMM and SMI, we recommend using the cutoff values for sarcopenia of 7.9 kg/m2 for males and 6.1 kg/m2 for females.

Purpose: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. The objective of the study was to investigate the prevalence of sarcopenia in degenerative lumbar scoliosis (DLS), and the relationship between biochemical markers including major AGEs, pentosidine, and DLS in older women., Methods: Our study participants were 20 elderly women with idiopathic DLS (mean age 76.4 years, range 56-88). Nineteen age- and sex-matched volunteers (mean age 74.0 years, range 62-86) served as controls. Spinal and femoral BMD of all participants was measured using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index [SMI; appendicular lean mass (kg)/(height (m)] 2 . SMI < 5.75 was considered diagnostic for sarcopenia. Coronal and sagittal spinal alignments were measured. The following biochemical markers were measured: serum and urinary pentosidine, serum homocysteine, 1,25(OA) 2 D, and 25(OH)D. The level of each variable was compared between DLS and controls. The relationship between biochemical markers including pentosidine and DLS was examined., Results: Sarcopenia was observed at a high prevalence in participants with DLS: 50% compared with 15.8% of healthy controls. Height, weight, femoral BMI, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DLS group. Serum pentosidine was significantly higher for the DLS group compared with controls. Correlations with serum pentosidine revealed a significant positive correlation between lumbar scoliosis, pelvic tilt, and pelvic incidence-lumbar lordosis mismatch, and a significantly negative correlation between thoracic kyphosis (P < 0.05)., Conclusions: We found that sarcopenia was involved in DLS, and high serum pentosidine levels are associated with severity of coronal and sagittal malalignment in older women, suggesting that high levels of AGEs are a potential biomarker for the progression of lumbar scoliosis and kyphotic deformity. Further studies are needed to clarify the pathogenesis of DLS.

Introduction: Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice., Methods: We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months., Results: The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup., Conclusions: In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women., Competing Interests: Conflicts of Interest: The authors declare that there are no conflicts of interest.

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na + group (<141 mEq/L) and a high Na + group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na + group and 62.5% in the low Na + group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na + group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

Background: Age-related sarcopenia may cause physical dysfunction. We investigated the involvement of sarcopenia in dropped head syndrome (DHS)., Methods: Our study subjects were ten elderly women with idiopathic DHS (mean age 75.1 years, range 55-89). Twenty age- and sex-matched volunteers (mean age 73.0, range 58-83) served as controls. We used a bioelectrical impedance analyzer (BIA) to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m)) 2 ). SMI <5.75 was considered diagnostic for sarcopenia. Cervical sagittal plane alignment: C2-7 sagittal vertical axis (SVA), C2-7 angle (C2-C7 A), and C2 slope (C2S) were also measured. We investigated sarcopenia prevalence in both groups, height, weight, BMI, lean mass arm, lean mass leg, lean mass trunk, appendicular lean mass, total lean mass, and SMI. In addition, we also examined the correlation between cervical spine alignment and SMI in DHS., Results: Sarcopenia was observed at a high rate in DHS subjects: 70% compared to 25% of healthy controls. Height, weight, BMI, lean mass arm, lean mass leg, axial lean mass, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. In particular, total lean mass, lean mass arm, and lean mass trunk were considerably lower in the DHS group. There was no correlation noted between cervical spine alignment and SMI., Conclusions: Sarcopenia prevalence was high in the DHS group-70 versus 25% in the control group, suggesting the involvement of sarcopenia in DHS. In particular, axial lean mass and lean mass arm were markedly reduced in the DHS group. DHS is due to significant weakness of the neck extensor group, and chin-on-chest deformity occurs. Until the present, evaluation of DHS has been done using only MRI; no studies have systematically examined skeletal muscle mass. In the present study, muscle mass decrease was noted not only in the neck muscles but also throughout the entire body. Involvement of trunk and upper limb muscles in particular suggests a disuse atrophy of the upper body and spinal muscles. BIA can easily and systemically evaluate skeletal muscle mass. We expect it to contribute to further elucidating the pathogenesis of DHS.

Acetaminophen (APAP) is a commonly used nonsteroidal analgesic because it is considered safe. However, APAP is a major cause of acute poisoning because of its easy availability. APAP overdose causes hepatic failure. A previous study reported a case of death occurring 3-4 days after APAP overdose. Serum APAP level is an index for administration of N-acetyl-L-cysteine (NAC). We investigated cases of APAP overdose to determine the correlation between serum APAP level and estimated APAP dosage, NAC medication, hepatic failure, etc. In one case, we found that the use of estimated APAP dosage alone led to inappropriate NAC medication. Moreover, there were cases in which serum APAP level increased 4 hr after APAP overdose. Repeated cases of APAP overdose suggested that the presence of NAC medication caused a difference in liver function test values.

The adsorption characteristics of eight adsorbents, cholestyramine, colestimide, aluminum silicate, sucralfate, aluminum hydroxide, calcium polystyrene sulfonate, carbon sphere and medicinal carbon, on the drugs such as methotrexate, antidepressants, mizoribine and ciprofloxacin hydrochloride were investigated in vitro. Medicinal carbon showed an excellent adsorption of all the tested drugs while the carbon spheres showed a high but slow adsorption characteristic. Cholestyramine and colestimide showed a higher adsorption in methotrexate than the other adsorbents. Aluminum silicate and calcium polystyrene sulfonate showed higher adsorption in four antidepressants, clomipramine hydrochloride, imipramine hydrochloride, mianserin hydrochloride and trazodone hydrochloride. In mizoribine, there were no adsorbents that showed higher adsorption except for the medicinal carbon. In ciprofloxacin hydrochloride, aluminum preparations and calcium polystyrene sulfonate showed higher adsorption characteristics. It is suggested that several adsorbents are potentially useful treatments for drug overdoses, but that these adsorbents have the possibility of decreasing the effects of the co-administered medicines.

Vancomycin and certain fungicides may cause anaphylactoid reactions. We investigated the effects of vancomycin, miconazole and fluconazole on histamine release in rat peritoneal mast cells. Vancomycin and miconazole provoked histamine release in a dose-dependent manner. In contrast, fluconazole did not provoke histamine release at concentrations of 3 x 10(-6)-3 x 10(-3) M. Vancomycin is efficacious in the treatment of gram-positive bacterial infections; patients presenting themselves with mixed infections require concomitant therapy with a second antimicrobial agent. We investigated the effect of fosfomycin sodium, cilastatin sodium or fluconazole on vancomycin-induced histamine release. Fosfomycin sodium inhibited vancomycin-induced histamine release but neither cilastatin sodium nor fluconazole inhibited it in the mole ratios of daily doses used in humans. These results suggest that vancomycin and miconazole provoke histamine release in rat mast cells, but that fluconazole probably does not, while fosfomycin sodium may inhibit vancomycin-induced histamine release.

In vitro synthesis of the first component of complement C1s was examined by using hamster epiphyseal chondrocytes (HAC) and human chondrosarcoma cell line HCS-2/8. Hamster and human C1s produced by the cells were quantified by immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. It was possible to measure active and inactive C1s by sandwich ELISA, when we used anti-human C1s monoclonal antibodies, M241 recognizing only active C1s, and M365 and M81 recognizing both active and inactive C1s. Approximately 40% of C1s secreted from HCS-2/8 was found to be activated in the culture medium, whereas C1s from HAC was not. C1s production increased in accordance with chondrocyte differentiation induced by ascorbic acid. In contrast, transforming growth factor-beta1 and basic fibroblast growth factor, which inhibited differentiation, suppressed C1s production. These results confirmed our previous observation showing that C1s synthesis increased with differentiation into hypertrophic chondrocytes in vivo.

Expression of the first complement component (C1s) has been examined in chondrocytes of hamster epiphyseal cartilage during development and fracture healing. C1s is immunostained with anti-hamster C1s monoclonal antibody, PG11. The C1s staining increases in accordance with chondrocyte differentiation and reaches a maximal level in hypertrophic chondrocytes. This change is observed at both the tibia ossification center and at the callus in which the replacement of cartilage by bone marrow takes place. The concomitant increase of C1s and chondrocyte hypertrophy has been confirmed by RNA blot and by in situ hybridization. These results, in addition to previous findings on C1s collagenolytic and gelatinolytic activities, suggest C1s participation in cartilage remodeling.

Vancomycin hydrochloride (VCM) has an antibacterial action against Gram positive bacteria, e.g., Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, there are patients with serious infections, being infected with not only MRSA, but also with Gram negative bacteria like Pseudomonas aeruginosa. Because VCM has the adverse reaction of nephrotoxicity, we are apprehensive about using VCM with other antibiotics, which might increase this problem. Therefore, the nephrotoxic effects and pharmacokinetics of VCM were examined in rabbits and compared with those in rabbits administered with VCM and other antibiotics. Responses indicating nephrotoxicity such as increases of serum creatinine concentration and BUN and morphological changes of the kidney were induced by the single injection of VCM at 300 mg/kg, i.v. In contrast, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM and imipenem (IPM)-cilastatin sodium (CS), flomoxef sodium (FMOX) or fosfomycin sodium (FOM). This was not true for groups injected with VCM and ceftazidime, cefpimizole sodium (CPIZ) or cefoperazone sodium. Clearance of VCM increased obviously in the groups injected with VCM and IPM-CS, FMOX or FOM, but decreased in those given VCM and CPIZ. Since the renal concentrations of VCM in the groups that were administered VCM with IPM-CS, FMOX or FOM were lower than that in the control group, IPM-CS, FMOX and FOM may decrease the nephrotoxicity of VCM by inhibiting its uptake into the kidney.

Hamster complement C1s cDNA was inserted into expression plasmid BCMGSNeo, and transfected to SEA7 cells, A31 mouse fibroblasts transformed by polyoma virus. The transfectant secreted a large amount of recombinant C1s that was activated in the serum free culture medium and hydrolyzed acetyl-Gly-L-Lys-naphthyl ester (AGLNE). C1s was purified to a homogeneity from the culture medium of the transfectant by DEAE-Sephadex, Dymatrex orange A and size-exclusion HPLC. Purified hamster C1s consumed human complement in hemolytic assay and hydrolyzed gelatin in enzymography. To investigate the enzymic action of C1s at molecular levels, several antibodies were prepared against hamster C1s. One peptide (amino-acid residues 379-391) and two peptides (amino-acid residues 478-496 and 560-583) corresponding to the heavy and the light chain, respectively, were synthesized. The amino-acid sequences of these regions is not conserved between hamster and human C1s. Antibodies against these peptides were raised in rabbits. The anti-peptide antibodies bound specifically to hamster serum and recombinant C1s but not to human C1s. They inhibited the esterase activity of recombinant C1s to varying degrees depending on each antibody's binding site.

A Twin Impinger was used to assess the influence of the number of puffs on the distribution patterns of two commercially available beclomethasone dipropionate (BDP) metered dose inhalers, and the effects of two kinds of spacer devices were also compared. No difference was observed in the distribution pattern up to the 10th puff between the two metered dose inhalers. Clinically, the amount of BDP inhaled into the lungs is said to depend on the number of puffs taken, but in this study, there was a significant difference in the distribution pattern between these 2 inhalers. In the stage assumed to represent the oropharynx site, the distribution ratio of BDP was greater after administration with an Aldecin than with a Becotide inhaler. In contrast, in the stage assumed to represent the lung, the distribution ratio of BDP was greater with the Becotide inhaler. This result suggests that the amount of BDP inhaled in the lungs may vary between these two preparations. The effects of spacer devices were also investigated in 4 puffs. These spacer devices caused the distribution ratio in the stage assumed to represent the oropharynx to decrease by at least 90%, irrespective of the type of metered dose inhaler. This result suggests that spacer devices are useful in reducing local side effects in the oropharynx. In the stage assumed to represent the lung, the distribution ratio achieved with the Becotide inhaler with Volumatic was greater than that with the Aldecin with InspirEase. This study suggests that the best therapeutic effects can be expected from a combination of Becotide inhaler and Volumatic.

The first component of complement C1s has been shown to degrade type I and type II collagens (Yamaguchi et al. 1990), the latter of which is a major constituent of the cartilage matrix. In order to understand the physiological roles of C1s in cartilage resorption, the expression of C1s was examined by immunohistochemistry in the primary ossification center where the matrix is removed and replaced by bone marrow. Hypertrophic chondrocytes, endothelium and hematogenous elements in the capillary buds were intensely stained by a monoclonal antibody against C1s. Matrix metalloproteinase 9 (MMP-9, 92kDa gelatinase/type IV collagenase) was also immunolocalized in hypertrophic chondrocytes, mesenchymal cells in the primitive bone marrow and the cartilage matrix adjacent to the marrow. In addition, C1s was found to activate the zymogen of MMP-9. These observations suggest that C1s and MMP-9 coordinately participate in matrix degradation in cartilage.

Hamster-complement-C1s cDNA was inserted into an expression plasmid BCMGSNeo (BCMGSNeoHACS). BALB/c mouse fibroblast A31 cells, which do not produce C1s, were transfected with BCMGSNeoHACS and the transfectants were selected with G418. Normal C1s production by the transfectants was confirmed by Northern and immunoblot analysis and by an esterase assay. To examine the tumorigenicity of the transfectants, 1 x 10(6) cells were injected s.c. into 6-week-old BALB/c nu/nu mice. Three C1s cDNA transfectants (A3CS9, A3CS12, A3CS13) formed tumors whereas both A31 and A31 transfected with the vector alone (A3BCM1 and A3BCM3) did not. The tumors derived from the transfectants showed invasive growth, and many capillaries were observed in the tumors. A tumor derived from A3CS13 was examined immunohistochemically and found to be reactive with an anti-C1s monoclonal antibody. Tumor cells were cultured in vitro again and C1s secreted into the culture medium was examined by immunoblot analysis. C1s synthesized by the tumor cells derived from A3CS13 maintained its biological functions. Tumor cells derived from A3CS9 and A3CS12 cells, however, produced C1s having abnormal disulfide bonds.

Antibody independent activation of complement C1s was examined by immunoblot analysis using an antibody against a synthetic peptide of hamster C1s L chain. Approx. 50% of C1s secreted from hamster embryo malignant fibroblasts Nil2C2 was functionally active in its two-chain form in the serum free culture medium. In contrast, no active C1s was found in a culture medium of hamster embryo fibroblasts (HEF). Active C1s was detectable, however, in the culture medium after HEF became a cell line. The immune complex independent activation of C1s was also observed in rat cell lines but not in secondary rat embryo fibroblasts. C1s in a membrane fraction of Nil2C2 was a proenzyme form and was not activated by incubation of the membrane itself suggesting that C1s was activated after secretion. The activation of C1s was not inhibited by human C1 inhibitor (C1-INH), benzamidine or soy bean trypsin inhibitor (SBTI) but was inhibited by leupeptin, nitrophenyl guanidinobenzoate and DFP. Our results suggest that C1s is activated either by a serine proteinase(s) other than those reported to cleave C1s or by an activator which directly stimulates autoactivation of C1s.

The authors experienced three cases in which serum free theophylline concentrations (F) rose with unchanged or decreased serum total theophylline concentrations (T). To clarify the causes of changes in F or T within a short time, we studied the relationship between F and serum albumin concentration or T in patients, and the relationship between T and F using aminophylline alone or aminophylline and cefazoline (CEZ) in rabbits. In patients, the fraction of free theophylline (F/T) showed a reverse relation to the serum albumin concentration, and a positive relation to T. In rabbits, when aminophylline was injected with CEZ, F/T increased in proportion to the dose of CEZ and T decreased when aminophylline alone was injected. The data suggested that F/T increased accompanied with decreasing serum albumin concentration or increasing T, since the albumin binding-site of theophylline is limited. The present study also suggested that the protein-bound theophylline decreased in competition with CEZ, therefore F/T increased when aminophylline was injected with CEZ. It is likely that decreased T is a result of augmented movement of theophylline to the tissue due to decreased serum albumin concentration. To evaluate the clinical conditions of the patients taking theophylline, it is necessary to directly monitor F, or to measure serum albumin concentration if direct measurement of F is not possible.