Validity, Responsiveness, and Predictive Ability of the Japanese Version of the Cumulated Ambulation Score in Patients with Hip Fracture.

OBJECTIVES: The aim of the current study was to investigate the validity, the responsiveness, and the predictive ability for discharge to own home of the Japanese version of the Cumulated Ambulation Score (CAS-JP). This was achieved by analyzing the CAS-JP after hip fracture surgery at multiple time points until patient discharge. METHODS: Patients who underwent hip fracture surgery were evaluated using CAS-JP, the Barthel Index, and walking ability on postoperative day (POD) 1, 7, and 14 and at discharge. Floor and ceiling effects, responsiveness, and correlations between CAS-JP and other functional outcomes were assessed at each time point. The predictive ability of CAS-JP for discharge to own home was also analyzed using the area under the curve (AUC) of the receiver operating characteristic. RESULTS: A total of 121 patients were included in this study. On POD7, POD14, and at discharge, strong correlations were observed between CAS-JP and the Barthel Index (r=0.81, 0.82, and 0.87, respectively), and between CAS-JP and walking status (r=0.82, 0.81, and 0.76, respectively). CAS-JP had a large effect size (1.64-2.25) and standardized response mean (1.49-1.81). The predictive ability of CAS-JP for discharge to own home, as indicated by the AUCs, were 0.73 (95% CI: 0.62-0.83) on POD7 and 0.74 (95% CI: 0.62-0.86) on POD14. CONCLUSIONS: CAS-JP has sufficient validity and responsiveness as a mobility assessment tool in postoperative hip fracture patients. Furthermore, this study showed that early postoperative mobility status evaluation using CAS-JP can sufficiently predict discharge to own home.

Translation, Inter-rater Reliability, Agreement, and Internal Consistency of the Japanese Version of the Cumulated Ambulation Score in Patients after Hip Fracture Surgery.

OBJECTIVES: The aim of this study was to translate the Cumulated Ambulation Score (CAS) from English into Japanese in cooperation with different types of healthcare providers and to investigate its inter-rater reliability and internal consistency. METHODS: Two physical therapists at each of three general hospitals in Japan measured the mobility of 50 consecutive post-operative hip fracture patients on two occasions between 2 and 6 days after surgery using the Japanese version of the CAS (CAS-JP). We analyzed the inter-rater reliability and agreement using both the linear weighted kappa and the interclass correlation coefficient; we also analyzed the internal consistency using Cronbach's alpha coefficient. RESULTS: The mean age of patients was 81 (SD: 11.6) years and 82% were women. Approximately half of the patients had severe cognitive impairment. Kappa was ≥ 0.93 for the three mobility activities and for the total CAS-JP score, the percentage agreement was ≥ 0.98, the ICC was ≥ 0.95, and Cronbach's alpha coefficient was 0.85. CONCLUSIONS: We found that the CAS-JP possessed good inter-rater reliability, agreement, and internal consistency. The CAS-JP is a reliable and easy-to-use evaluation tool suitable for daily clinical practice across different healthcare providers to monitor mobility in older hip fracture patients in Japan. We suggest that CAS-JP be evaluated in future studies for use in younger patients and in other patient groups with mobility problems.

Development of a screening program to assess motor function in the adult population: a cross-sectional observational study.

BACKGROUND: Motor dysfunction is a major reason why the elderly lose their independence in their daily lives. The concept of locomotive syndrome has been proposed to describe the risk of mobility dependence caused by various locomotive organ disorders. The preservation of locomotive organs is now socially important in the middle-aged and geriatric population. Therefore, it is important to establish a screening program to evaluate motor function and related quality of life in a wide range of ages. METHODS: We propose a new set of pre-existing scales (the Two-Step test, Stand-Up test, and 25-question Geriatric Locomotive Function Scale) as screening tools to identify the population at high risk for locomotive syndrome. We performed a preliminary survey on 777 subjects who had no apparent disorders related to motor function. We also examined the reliability of the Two-Step test and Stand-Up test. RESULTS: We found that each scale did not show ceiling or floor effects in various age groups. Because the correlations between the three scales were significant but weak, we assume that each scale covers different aspects of mobility. The test-retest reliability was found to be satisfactory for the Two-Step test and the Stand-Up test. CONCLUSION: Our results suggest that our "Short Test Battery for Locomotive syndrome" is a feasible and reliable tool for screening the adult population as a preventative strategy for locomotive syndrome in a super-aged society.

Somatosensory and spinal evoked potentials in patients with upper cervical neurinoma.

Scalp somatosensory evoked potentials (SEPs) and spinal evoked potentials (SpEP) were simultaneously recorded from the exposed surface of the upper cervical cord after median nerve stimulation in five patients undergoing surgery for upper cervical neurinomas. Two of the neurinomas were localized at C1 nerve root, two at C2, and one at C3. All patients showed good postsurgical recovery, suggesting that the tumors had not progressed to the stage where most of the nerve fibers were irreparably damaged. In patients with unaffected superficial and deep skin sensation, both SEP and SpEP were normal. In patients with more advanced tumor, the superficial sensation was abnormal but the deep skin sensation was intact. In these patients, the action potential propagation slowed down but continued partially through the tumor site on the relatively less affected side contralateral to the tumor; however, it stopped at the site of the tumor on the ipsilateral side. It is possible that full functional recovery becomes more difficult during the next stage of tumor development when the propagation of action potentials ceases bilaterally. The intraoperative monitoring of both SEP and SpEP thus appears useful for inferring details of functional integrity and prognosis of the spinal cord near a space-occupying tumor during the critical first two stages of neoplasm in which the spinal function is normal, or a sufficiently large fraction of ascending and descending nerve fibers are functionally suppressed, but are capable of recovery after a surgical intervention.

Diet and lifestyle associated with increased bone mineral density: cross-sectional study of Japanese elderly women at an osteoporosis outpatient clinic.

BACKGROUND: Several studies have already demonstrated that lifestyle characteristics, such as physical activity, smoking, and alcohol intake, are associated with bone mineral density (BMD). Coffee intake was shown to be negatively associated with BMD, whereas tea drinking was reported to be associated with increased BMD. A review of the literature, however, revealed that few studies have described the association between BMD and lifestyle, including characteristic Japanese foods such as fish, natto, and Japanese green tea. The aim of this study was to identify lifestyle factors associated with BMD. METHODS: A total of 632 women age > or =60 years were enrolled in this study. Subjects were interviewed about their lifestyle by means of a questionnaire regarding the consumption pattern of dietary items. BMD was measured at the lumbar spine by dual energy X-ray absorptiometry. RESULTS: The BMD was higher in subjects with the habits of alcohol drinking, green tea drinking, and physical activity and lower in those with the habits of smoking and cheese consumption. Multiple regression analysis showed that factors associated with BMD were smoking, alcohol consumption, green tea drinking, and physical activity after adjusting for age and body mass index (BMI). CONCLUSIONS: In this cross-sectional study at an osteoporosis outpatient clinic, patients with the habits of alcohol drinking, green tea drinking, and physical activity had significantly higher BMD, and those who smoked had significantly lower BMD than patients without each habit after adjusting for age, BMI, and other variables regarding lifestyle.

Clinical use of a newly developed calcium phosphate cement (XSB-671D).

BACKGROUND: Several kinds of thermally processed hydroxyapatite have been commonly used for bone defects due to bone diseases or fractures instead of autologous bone grafts. However, these materials do not change in form during surgery and are not absorbed over a long period. To overcome this disadvantage, calcium phosphate bone cements (CPCs) have been developed and are already in use in clinical cases. These materials have merit in that to be formed in situ they are injectable and absorbable, but there are still problems with their handling and their hardening properties. A newly developed CPC called XSB-671D hardens earlier and is more resistant to body fluids than other CPCs. The purpose of this article is to verify the effectiveness, safety and usefulness of this CPC (XSB-671D) as a bone defect filler. METHODS: We conducted clinical trials at five medical institutions based on a unified protocol in a total of 75 cases (30 males, 45 females). We observed the postoperative constitutional symptoms and local symptoms of the filling sites. The effectiveness of this material was evaluated by radiographs of the filled sites, and blood and urine were examined to evaluate any adverse effects. RESULTS: The ratio of the cases determined to be "effective" or "better" among the 74 cases we found qualified was 97.3%, and XSB-671D was confirmed to be a highly effective material with beneficial effects of biocompatibility and osteoconduction as a bone defect filler. Additionally, there were no adverse effects caused by XSB-671D except one local skin reaction, which disappeared 2 weeks later; its safety was also thus verified. CONCLUSIONS: We conclude that effective, safe treatment is possible using XSB-671D in cases requiring filling of a bone defect as well as those with serious osteoporosis.

Ossification of the posterior atlantoaxial membrane and the transverse atlantal ligament.

STUDY DESIGN: Case report. OBJECTIVE: To report a case of ossification of the posterior atlantoaxial membrane (PAAM) and ossification of the transverse ligament of the atlas (TAL). SUMMARY OF BACKGROUND DATA: Ossification of the PAAM and TAL are both very rare clinical entities. This is the first case involving ossification of both the PAAM and TAL with the development of cervical myelopathy. METHODS: Patient's history, physical examination, radiographic evaluation, surgical treatment, and outcome are examined. Relevant literature is also reviewed. RESULTS: The patient's neurological symptoms significantly improved after posterior decompressive surgery. CONCLUSION: Ossification of various parts of the spinal ligament have been reported previously. Among them, ossification of both the PAAM and TAL has never been reported previously and is thus extremely rare. Surgical intervention improved the neurological impairment.

[Long-term care insurance system and osteoporosis].

The Long-term Care Insurance is the principal system that supports the Japanese elderly more than 24 million in number. The recipients of this system are increasing rapidly and get up to 3 million now. In Japan, hip fracture is one of the primary causes that make the elderly bedridden. In our study with the cases of hip fractures, 51.6% of the whole patients were self-reliant before fracture, but 25.6% one year after fracture. Keep it in mind that half of the self-reliant elderly will need support after fracture and encourage patients and their families to apply for certification of need for support.

A new artificial cyclase for polyprenoids: enantioselective total synthesis of (-)-chromazonarol, (+)-8-epi-puupehedione, and (-)-11'-deoxytaondiol methyl ether.

This paper describes a new artificial cyclase, optically pure 3-o-fluorobenzyloxy-2-hydroxy-2'-(p-methoxybemzyl)-1,1'-binaphthyl.SnCl4, which is effective for the enantioselective cyclization of 2-(polyprenyl)phenol derivatives to afford polycyclic terpenoids bearing a chroman skeleton such as (-)-chromazonarol, (+)-8-epi-puupehedione, a key synthetic intermediate of (+)-wiedendiol, and (-)-11'-deoxytaondiol methyl ether.

Neuroimaging features of epidermal nevus syndrome.

Epidermal nevus syndrome is a kind of neurocutaneous syndrome that is associated with epidermal nevus and a variety of congenital CNS disorders. Clinical presentations include seizures, paresis, mental retardation, and developmental delay. We report three cases with MR imaging and magnetoencephalography findings; one patient underwent ictal and interictal single photon emission CT. Both structural and functional imaging studies indicated that the frontal lobes had lesser involvement or were intact. One patient underwent hemispherectomy because of the medically intractable seizure. He remained seizure free with topiramate monotherapy.

Association between bone loss and promoter polymorphism in the IL-6 gene in elderly Japanese women with hip fracture.

Recently, a G/C polymorphism was found at position -573 of the interleukin-6 ( IL-6) gene promoter. We investigated how this genetic polymorphism relates to IL-6 production and osteoporosis in elderly Japanese women. Genomic DNA was extracted from an aliquot of monocytes in the bone marrow; the monocytes were simultaneously used to form osteoclast-like multinucleated cells (MNCs) and to produce IL-6. Of the 47 subjects with fractures, 96% had a C allele at position -573 of the IL-6 gene. Only 2 subjects possessed homozygotes of G at that position. We investigated IL-6 levels, MNC formation in bone marrow culture, and femoral neck bone mineral density (BMD) in the subjects with the GC and CC genotypes. There were no significant differences between these genotypes as regards IL-6 levels, MNC formation, and femoral neck BMD. However, in the CC genotype, there was a negative relationship between femoral neck BMD and IL-6 levels, and between femoral neck BMD and MNC formation, whereas in the GC genotype and combined (GC + CC) genotypes, femoral neck BMD tended to be related to IL-6 levels and MNC formation. Moreover, the stromal cells in the CC genotype showed higher IL-1alpha-stimulated IL-6 production than did the stromal cells in the GC genotype. Our findings suggest that important information might be obtained not only by continued comparison of different genotypes but also by comparative study within each particular genotype.

Multimodality neuroimaging evaluation improves the detection of subtle cortical dysplasia in seizure patients.

The purpose of this study is to investigate if multimodality neuroimaging evaluation increases the detection of subtle focal cortical dysplasia as part of an epilepsy surgery evaluation. Three patients with normal magnetic resonance imaging and histopathological findings of focal cortical dysplasia were reviewed. Their magnetoencephalography recordings were performed on whole-head magnetoencephalography system. Magnetic resonance images were re-evaluated with special inspection in limited regions guided by magnetoencephalography spike localization. Two patients had ictal and interictal single photon emission computed tomography study after administration of Tc99m ECD. In two patients we found tiny focal abnormalities including slightly increased cortical thickness and blurred gray-white matter junction at the locations of interictal events after re-evaluation of the MR images indicating focal cortical dysplasia. The third patient showed focal atrophic change. All patients are seizure free after surgery. Both ictal and interictal single photon emission computed tomography showed hyperperfusion in the dysplastic cortex regions. Multimodality neuroimaging study can improve the detection of focal cortical dysplasia. Normal magnetic resonance images should be re-evaluated for subtle signs of focal cortical dysplasia especially when magnetoencephalography recording demonstrate focal epileptic discharges.

Localization of ictal and interictal bursting epileptogenic activity in focal cortical dysplasia: agreement of magnetoencephalography and electrocorticography.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In such cases, interictal frequent rhythmic bursting epileptiform activity (FBREA) on both scalp electroencephalography (EEG) and electrocorticography (ECoG) is generally accepted to be identical to the ictal epileptiform activity. We used magnetoencephalography (or Magnetic Source Imaging (MSI)) to determine the epileptogenic zone in a 6-year-old patient with histopathologically proven FCD and normal magnetic resonance imaging (MRI). MSI was used to localize the sources of both ictal activity and FRBEA, which was then compared with ECoG findings. The intracranial sources of both types of activity co-localized in the left inferior frontal and superior temporal gyri. The location and extent of the epileptogenic area determined by MSI was essentially identical to that determined directly through extra-operative ECoG. In the absence of structural abnormalities detectable on MRI, the noninvasive method of MSI provided valuable information regarding the location and extent of the primary epileptogenic area. This was critical for pre-surgical planning regarding placement of intracranial electrodes and for risk-benefit evaluation.

Chiral proton donor reagents: tin tetrachloride--coordinated optically active binaphthol derivatives.

The Lewis acid-assisted chiral Brønsted acids (chiral LBAs), which are prepared from tin tetrachloride and optically active binaphthol derivatives, are highly effective chiral proton donor reagents for enantioselective protonation and biomimetic polyene cyclization. These chiral LBAs can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding alpha-aryl or alpha-halo ketones and alpha-arylcarboxylic acids, respectively, with high enantiomeric excess (up to 98% ee). A catalytic version of enantioselective protonation was also achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active binaphthol in the presence of tin tetrachloride. The biomimetic cyclization of simple isoprenoids to polycyclic isoprenoids using chiral LBA is also described. This is the first example of a chiral Brønsted acid-induced enantioselective ene cyclization in synthetic chemistry. Geranyl phenyl ethers, o-geranylphenols, and homogeranylphenol derivatives were directly cyclized in the presence of (R)-binaphthol derivatives and tin tetrachloride (up to 90% ee). Compounds bearing a farnesyl group could also be cyclized under the same conditions to give the natural products (-)-ambrox((R)) and (-)-chromazonarol, and (-)-tetracyclic polyprenoids of sedimentary origin. These chiral LBAs recognize the prochiral face of a trisubstituted terminal olefin and site selectively generate carbocations on the substrates.

Detection and significance of focal, interictal, slow-wave activity visualized by magnetoencephalography for localization of a primary epileptogenic region.

OBJECT: Magnetoencephalography (MEG) is a novel noninvasive diagnostic tool used to determine preoperatively the location of the epileptogenic zone in patients with epilepsy. The presence of focal slowing of activity recorded by electroencephalography (EEG) is an additional indicator of an underlying pathological condition in cases of intractable mesial temporal lobe epilepsy (MTLE). In the present study the authors examined the significance of focal, slow-wave and interictal spike activity detected using MEG in 29 patients who suffered from MTLE that was not associated with structural brain lesions. METHODS: All patients underwent resective surgery after MEG and EEG monitoring. Equivalent single-dipole modeling was applied to focal low-frequency magnetic activity (LFMA) and interictal paroxysmal activity. Lateralized LFMA was defined as trains of rhythmic activity over the temporal area, with frequencies lower than 7 Hz, which were easily distinguished from background activity. Lateralized LFMA was found in 17 patients (58.6%); it always occurred on the side ipsilateral to the side of resection and displayed a maximum amplitude over the temporal area. Dipolar sources of magnetic flux computed during slow-wave trains were found in the majority of cases in the posterior superior temporal region and, occasionally, in mesial temporal structures that were subsequently resected. With respect to lateralization there was never disagreement between LFMA and MEG interictal spike sources. Thus, in patients with MTLE that is not associated with a mass lesion LFMA is topographically related to the epileptogenic area and, therefore, has value for reliable determination of the side and, possibly, the location of this area. CONCLUSIONS: Although focal slowing of EEG background activity is generally considered to be a nonspecific sign of functional disturbance, interictal LFMA in patients with MTLE should be conceptualized as a distinct electrographic phenomenon that is directly related to the epileptogenic abnormality. Analyzing the interictal MEG distribution of LFMA and sharp activity improves the diagnostic utility of MEG in patients with suspected TLE who are undergoing surgical evaluation.

Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts.

1. We examined the effects of endogenous prostaglandin E(2) (PGE(2)) on the production of interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF) by interleukin-1beta (IL-1beta)-stimulated human synovial fibroblasts. 2. NS-398 (1 microM), a cyclo-oxygenase-2 (COX-2) inhibitor, inhibited IL-6 and VEGF production (35+/-4% and 26+/-2%, respectively) but enhanced M-CSF production (38+/-4%) by IL-1beta (1 ng ml(-1)) in synovial fibroblasts isolated from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Exogenous PGE(2) completely abolished the effects of NS-398 on the production of each mediator by OA fibroblasts stimulated with IL-1beta. 3. 8-Bromo cyclic AMP and dibutyryl cyclic AMP, cyclic AMP analogues, mimicked the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA fibroblasts. 4. The EP(2) selective receptor agonist ONO-AE1-259 (2 nM) and the EP(4) selective receptor agonist ONO-AE1-329 (2 or 20 nM), but not the EP(1) selective receptor agonist ONO-DI-004 (1 microM) and the EP(3) selective receptor agonist ONO-AE-248 (1 microM), replaced the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA and RA fibroblasts stimulated with IL-1beta in the presence of NS-398. 5. Both OA and RA fibroblasts expressed mRNA encoding EP(2) and EP(4) but not EP(1) receptors. In addition, up-regulation of EP(2) and EP(4) receptor mRNAs was observed at 3 h after IL-1beta treatment. 6. These results suggest that endogenous PGE(2) regulates the production of IL-6, M-CSF, and VEGF by IL-1beta-stimulated human synovial fibroblasts through the activation of EP(2) and EP(4) receptors with increase in cyclic AMP.

Enantio- and diastereoselective stepwise cyclization of polyprenoids induced by chiral and achiral LBAs. A new entry to (-)-ambrox, (+)-podocarpa-8,11,13-triene diterpenoids, and (-)-tetracyclic polyprenoid of sedimentary origin.

An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Brønsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2'-hydroxy-1,1'-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF(3)CO(2)H.SnCl(4) as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn.SnCl(4). Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn.SnCl(4) and subsequent diastereoselective cyclization induced by BF(3).Et(2)O/EtNO(2) or CF(3)CO(2)H .SnCl(4).