The effects of the employment of physical therapists and occupational therapists on the gait function of adult day service users after 1 year.

OBJECTIVE: The present study aimed to investigate the effects of the presence or absence of physical therapists (PTs) and occupational therapists (OTs) in an adult day service on the users' gait function, and to generalize the format of an effective service aimed at the preventing the exacerbation of the gait function and at promoting self-reliance in activities and participation. METHODS: The study population included 830 elderly day service users (mean age, 83.7±6.8 years; male, n=252; female, n=578) in Japan. Their normal gait speed was measured at the baseline and at 1 year. The sex, age, level of nursing care, and number of adult day service users were assessed at the baseline. The subjects were divided into 2 groups: (1) those who used services that employed PTs or OTs (the PTOT group) and (2) those who used services that did not employ PTs or OTs (the control group). We performed a univariate analysis to confirm the absence of differences between the groups in terms of all their baseline variables. Next, we performed a repeated measures analysis of variance using the presence or absence of PT or OT and time as factors. We subsequently performed a univariate analysis to examine the difference in the gait speed of the groups, as well as the differences in the gait speed between the groups at the baseline and at 1 year. RESULTS: Although the repeated measures analysis of variance did not show that time had a significant effect on the gait speed, it showed the significant effects of the presence or absence of PTs or OTs as well as the interaction between time and group. Intragroup comparisons showed a significant difference between the gait speed at baseline and that at 1 year in the PTOT group. However, there was also a significant difference in the baseline and 1-year gait speeds of the control group. The intergroup comparisons did not show a significant difference in the gait speed at baseline, but did show a significant difference in the gait speed at 1 year. CONCLUSION: The employment of PTs and OTs in adult day service controlled the exacerbation of the gait function. The gait speed in elderly individuals who require long-term care is associated with the activities of daily living and mortality rates; thus, the results of the present study indicate the need for the employment of rehabilitation specialists in adult day services.

The Thymidine Phosphorylase Imaging Agent 123I-IIMU Predicts the Efficacy of Capecitabine.

UNLABELLED: Recently, companion diagnostics with nuclear medicine techniques have been anticipated as more suitable means than biopsy for predicting treatment efficacy. The anticancer effect of capecitabine, an orally administered chemotherapeutic agent activated by thymidine phosphorylase (TP), is positively associated with tumor TP expression levels. This study aimed to assess whether TP imaging using a radiolabeled uracil derivative, (123)I-5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ((123)I-IIMU), could predict the efficacy of capecitabine treatment. METHODS: Sensitivity to doxifluridine, a metabolite of capecitabine and direct substrate for TP, was assessed by water-soluble tetrazolium salt assays in vitro for 3 human colon cancer cell lines with different TP expression profiles. The intracellular uptake and retention of (123)I-IIMU were evaluated. Mice inoculated with each cell line were treated with capecitabine for 2 wk, and tumor growth was compared. In vivo distribution studies and SPECT/CT imaging of (123)I-IIMU were performed in inoculated mice. RESULTS: In vitro experiments showed a positive relation between TP expression levels and doxifluridine sensitivity. In vitro studies revealed that intracellular uptake and retention of (123)I-IIMU were dependent on TP expression levels. In vivo experiments in inoculated mice showed that (123)I-IIMU accumulation in tumor tissue was in line with TP expression levels and susceptibility to capecitabine treatment. Moreover, SPECT/CT imaging of (123)I-IIMU in tumor-inoculated mice showed that (123)I-IIMU reflects TP expression levels in tumor tissues. CONCLUSION: (123)I-IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment.

A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism.

CONTEXT: Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. OBJECTIVE: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. METHODS: The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. RESULTS: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. CONCLUSIONS: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

Clinical usefulness of indoor life-space assessment in community-dwelling older adults certified as needing support or care.

PURPOSE: This study aimed to develop a questionnaire to evaluate indoor life-space mobility and assess its validity in community-dwelling older adults certified as needing support or care. METHODS: The participants included 37 community-dwelling older adults undergoing home-visit rehabilitation (mean age: 78.5±7.0 years). We developed a questionnaire to assess the degree of indoor life-space mobility (home-based life-space assessment (Hb-LSA)), evaluating the functional status (life-space assessment (LSA), time spent away from bed, functional independence measure (FIM), bedside mobility scale (BMS)), physical function (hand grip power (HGP), 30-second chair stand (CS-30), one-leg standing (OLS)) and cognitive status (mental status questionnaire (MSQ)). RESULTS: The average Hb-LSA score was 56.3±24.3 (minimum 4 to maximum 102.5). The test-retest reliability was high (intraclass correlation coefficients: (1, 1)=0.986, (1, 2)=0.993). The Hb-LSA scores were significantly associated with the LSA (r=0.897), time spent away from bed (r=0.497), FIM (r=0.786), BMS (r=0.720), HGP (r=0.388), CS-30 (r=0.541) and OLS (r=0.455). There were no significant associations between the Hb-LSA scores and the FIM cognitive subscores (r=0.180) or MSQ scores (r=-0.240). The Hb-LSA scores were significantly higher among the participants able to move independently indoors (75.8±18.8 points) than in those who required help to move (45.7±20.2 points). CONCLUSIONS: The Hb-LSA is a useful, reliable and valid tool for assessing the degree of indoor physical mobility in the life-space. The Hb-LSA score is related to the degree of independence of indoor mobility.

Phenotype of cardiomyopathy in cardiac-specific heat shock protein B8 K141N transgenic mouse.

A K141N missense mutation in heat shock protein (HSP) B8, which belongs to the small HSP family, causes distal hereditary motor neuropathy, which is characterized by the formation of inclusion bodies in cells. Although the HSPB8 gene causes hereditary motor neuropathy, obvious expression of HSPB8 is also observed in other tissues, such as the heart. The effects of a single mutation in HSPB8 upon the heart were analyzed using rat neonatal cardiomyocytes. Expression of HSPB8 K141N by adenoviral infection resulted in increased HSPB8-positive aggregates around nuclei, whereas no aggregates were observed in myocytes expressing wild-type HSPB8. HSPB8-positive aggresomes contained amyloid oligomer intermediates that were detected by a specific anti-oligomer antibody (A11). Expression of HSPB8 K141N induced slight cellular toxicity. Recombinant HSPB8 K141N protein showed reactivity against the anti-oligomer antibody, and reactivity of the mutant HSPB8 protein was much higher than that of wild-type HSPB8 protein. To extend our in vitro study, cardiac-specific HSPB8 K141N transgenic (TG) mice were generated. Echocardiography revealed that the HSPB8 K141N TG mice exhibited mild hypertrophy and apical fibrosis as well as slightly reduced cardiac function, although no phenotype was detected in wild-type HSPB8 TG mice. A single point mutation of HSPB8, such as K141N, can cause cardiac disease.

[Predictors of interruptions to living at home in elderly people enrolled in a home visit rehabilitation service].

AIM: The purpose of this study was to determine the predictors of interruption to living at home as a result of death, hospitalization, or admission to a long-term care facility in frail elderly people enrolled in a home visit rehabilitation service. METHODS: A total of 311 patients entered a home visit rehabilitation service within a study period of 1 September, 2005 to 31 March, 2010, 146 of whom met the criteria to be enrolled in this study and gave consent. Of these, 73 received a continuous home visit rehabilitation service (continuous group) of over 2 years and 73 experienced interruption to this service due to death, hospitalization, or admission to a long-term care facility (interruption group). The following physical, social, and medical factors were recorded and analyzed: age, sex, care level, disease diagnoses, gait disability, cognitive impairment, living with another person and cause of the interruption to the home-visit rehabilitation service. We compared each item between the interruption and continuous groups. Logistic regression analysis was used to identify the significant predictors of interruptions to living at home. RESULTS: Patients in the interruption group demonstrated significantly lower functioning in activities of daily living (ADL), gait ability and lower cognitive status, and higher rates of respiratory diseases and cancer compared with the continuous group. On logistic regression analysis, ADL score (odds ratio [OR]=0.97, p<0.01), and the presence of respiratory diseases (OR=4.35, p=0.04) and cancer (OR=13.46, p<0.01) were significantly associated with interruptions to living at home. CONCLUSIONS: Lower ADL functioning, respiratory diseases and cancer were significant predictors of interruption to living at home in frail elderly adults.

Combined effect of factors associated with burdens on primary caregiver.

BACKGROUND: It is argued that a multidimensional approach is necessary for burden assessment. Reducing caregiver burden is a social problem in the ageing Japan society. We examined the combined effect of factors affecting the care burden among community-dwelling handicapped people and their caregivers. METHODS: The participants were 49 handicapped people (aged 53-104 years) who received home-visit rehabilitation, and their 49 caregivers (age 42-85 years). Caregivers were provided questionnaires consisting of questions on social support, subjective well-being, self-efficacy with regard to care continuation, the Motor Fitness Scale and caregiver burden. Care recipients were assessed using the Bedside Mobility Scale and the Barthel Index. RESULTS: We prepared the hypothesis model using structural equation modeling with the bootstrap method within outcome measures. The hypothesis model did not fit the data well. The impact of the Motor Fitness Scale was shifted from the caregiver burden to care self-efficacy and well-being, having a cooperator for care and variable of spouse caregiver or others associated with caregiver well-being in the revised model. The fit of the revised model was acceptable (goodness of fit index, 0.903; comparative fit index, 0.998; root mean square error of approximation, 0.017). In the revised model, the care recipients' disabled state was associated with caregiver burden. In addition, higher burden and poor motor fitness of caregivers might lead to lower care self-efficacy in providing continuous care and lower caregiver well-being. CONCLUSION: These findings suggested that the program to reduce caregiver burden should focus on aspects of the care recipients' disabled state, the caregivers' well-being, fitness, and care self-efficacy.

The synthesis of D-trihydroxyllysine-based oligopeptides as a hydrophilic scaffold and its application to the synthesis of bifunctional chelating agents for use as bone tracers.

An effective hydrophilic scaffold composed of D-trihydroxyllysine-based oligopeptides and its application in the synthesis of the various (111)In-DTPA conjugates with mono- to penta-bisphosphonate units for use as bone tracers are described. The D-trihydroxyllysine derivative with three orthogonal protecting groups was conjugated with functional devices at the gamma position and allowed oligomerization based on peptide chemistry. The radiopharmaceutical complexes of (111)In(III) with selected chelators, 4 and 8, were suitable for bone imaging. These results show that D-trihydroxyllysine 2 was an effective building block for the synthesis of multivalent ligands applicable to medical use.

[Factors burdening the caregiving relatives of community-dwelling disable Japanese people].

AIM: This study examined the factors associated with burdens on the primary caregivers of community-dwelling disabled people. METHODS: Participants were 78 disabled people (40 men, 38 women; mean age 77.8+/-11.5 years) who received home-based physical therapy and/or occupational therapy, and their 78 caregivers (20 men, 58 women; mean age 66.8+/-10.2 years). The caregiver burden was assessed using the short version of the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI_8). In addition, the primary caregivers completed questionnaires about burdens arising from supporting the activities of daily living (ADL) using a visual analogue scale, available social support, subjective well-being, and the Motor Fitness Scale. The performance of the disabled subjects was assessed using the Bedside Mobility Scale and the Barthel Index. The disabled subjects and the caregivers were divided into higher burden (J-ZBI_8 score, 10 points and over) and lower burden groups (J-ZBI_8 score, 9 points and under) to compare the group differences in the measurements. RESULTS: The disabled participants in the lower burden group (n=41) showed significantly higher Bedside Mobility Scale scores and Barthel Index scores than those in the higher burden group (n=37). The primary caregivers in the higher burden group showed significantly higher burden due to supporting the ADL, lower subjective well-being, and lower social support as compared to those in the lower-burden group. CONCLUSION: The burden levels of the primary caregivers relating to the mobility and ADL of their recipients were assessed. The caregivers with higher burden showed less social support and low subjective well-being.

[Functional status of very old people in urban area: the Itabashi Oldest-Old Study I].

It is predicted that the future increase in the oldest-old (85 years and older) population will have a marked influence on society. However, little is known about the features of various functions in the oldest-old. The purpose of this study was to clarify the functional status of the oldest-old. We surveyed all oldest-old residents in a small area of Itabashi ward in metropolitan Tokyo to clarify their living conditions. The oldest-old themselves and their family members were invited to participate, and 235 out of 311 residents (75.6%) agreed to do so. Forty-two percent of the participants were dependent and needed care from others. The ADL status measured by the Barthel Index showed that 30% of independent participants also had some deterioration of physical function. These results are indicative of increased frailty in the oldest-old. Comparison between independent and dependent (need care from others in daily living) showed that the functional status was lower in dependent group. However, the psychological well-being was the same in this two groups. These results indicate progressive functional deterioation and psychological adaptation to it, in the oldest-old. Further research to elucidate the process of psychological adaptation to frailty is necessary in order to promote the well-being among the oldest-old, in whom functional limitation is evident.

[Cognitive function among physically independent very old people in an urban community in Japan: the Itabashi Oldest-Old Study II].

This study was conducted to clarify the characteristics of cognitive function among physically independent very old people dwelling in an urban community in Japan. Five hundred and thirteen Old-Old (aged 75-84 years) and 168 Oldest-Old (aged 85-100 years) adults participated. We carried out the Mini-Mental State Examination (MMSE) for measuring cognitive functions in the elderly. Age-related differences in the total score and sub-scale scores of the MMSE were analyzed by sex using ANCOVA, controlling for education, vision and hearing problems. Mean MMSE scores for Old-Old and Oldest-Old males were 27.53 and 25.88, respectively, and those for Old-Old and Oldest-Old females were 27.77 and 24.98, respectively. Age-related differences in the MMSE total score between the Old-Old and Oldest-Old were observed in both sexes, suggesting that overall cognitive functions continue to decline over time in very old age. Age-related differences between the Old-Old and Oldest-Old in items measuring, registration, calculation and delayed recall were observed in both sexes, and in addition, time orientation, place orientation, delayed recognition, writing sentences, and copying figures were observed in females. These findings suggest that the faculties are those most sensitive to normal aging among very old individuals. There were no age group differences in five items: reverse spelling, naming objects, repeating a sentence, listening and obeying, and reading and obeying.

Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia.

Accumulating evidence indicates that the mitochondrial cell-death pathway, which involves the release of cytochrome c from mitochondria, participates in neuronal cell death after transient cerebral ischemia. However, the upstream events, that induce cytochrome c release after transient global ischemia are not fully understood. Bad is a pro-apoptotic member of the bcl-2 gene family that promotes apoptosis by binding to and inhibiting functions of anti-apoptotic proteins Bcl-2 and Bcl-xL. We investigated the effects of transient (15 min) global ischemia on the intracellular localization of Bad and the interaction of Bad with calcineurin, Akt or Bcl-xL in the vulnerable CA1 and resistant CA3/dentate gyrus of the hippocampus. Immunoblotting analysis revealed that the amount of Bad in mitochondria significantly increased after ischemia. Co-immunoprecipitation studies showed decreased interactions of Bad with Akt and calcineurin in the cytosol and increased binding with Bcl-xL in the mitochondrial fraction of hippocampal CA1, but not in the CA3/dentate gyrus region. Further, we examined the effect of recombinant Bad on the cytochrome c release from isolated mitochondria. Treatment with both recombinant Bad and calcium, but not with recombinant Bad alone, induced cytochrome c release. These results suggest that changes in localization and complex formation by Bad are, at least in part, involved in the vulnerability of cells after transient global ischemia.

The effects of monobromobimane on calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome C release in isolated brain mitochondria.

A possible involvement of inhibitory effects of monobromobimane (MBM), a thiol reagent, on the swelling and the release of cytochrome c in the isolated brain mitochondria was examined. MBM dose-dependently inhibited the calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome c release. Significant relationships between mitochondrial swelling and cytochrome c release were detected. Furthermore, effects of in vivo treatment with MBM on neuronal cell damage after transient (15 min) global ischemia in rats were examined. Infusion of MBM (1 or 3 microg/animal) to cerebral ventricles attenuated an increased number of TUNEL-positive cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion. These results suggest that MBM may have an ability to inhibit mitochondria-associated apoptotic pathways through attenuation of the mitochondrial swelling and the release of cytochrome c.

The effects of monobromobimane on neuronal cell death in the hippocampus after transient global cerebral ischemia in rats.

Calcium accumulation and free radical formation in the mitochondria are suggested to result in opening of the mitochondrial permeability transition pore that may be an initial step in neuronal cell death. The purpose of the present study was to determine whether monobromobimane (MBM) was a possible protective agent against neuronal cell death after transient global ischemia and the swelling of isolated hippocampal mitochondria. Infusion of MBM (1 or 3 microg) to cerebral ventricles 30 min before ischemia attenuated the expression of TUNEL-labeled cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion dose-dependently. Treatment with MBM inhibited an increase in caspase-3-like activity at 48 h of reperfusion in the hippocampus. MBM (30-300 microM) also inhibited an enhanced swelling rate induced by Ca2+ and phenylarsineoxide in the isolated hippocampal mitochondria. These results suggest that in vivo treatment with MBM may protect against neuronal cell death through inhibition of the mitochondrial swelling and caspase-3-dependent apoptotic pathway.

Effects of monochlorobimane on cerebral ischemia-induced damage to mitochondria.

A possible involvement of inhibitory effects of monochlorobimane (MCB) on the opening of mitochondrial permeability transition (MPT) pore in the cerebroprotection against the ischemic brain injury was examined. MCB (1 mM) inhibited the opening of MPT pore in vitro. Sustained cerebral ischemia was induced by injecting 900 microspheres (48 microm in diameter) into the right hemisphere of rats. At 12 to 72 h after microsphere embolism (ME), the mitochondrial activity was determined histochemically by staining cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) of the brain sections. The COX and SDH stainings in the hippocampus were observed intensively in the pyramidal neurons in the CA2-3 and dentate gyrus rather than those in the CA-1 region. The staining was decreased with time after the embolism. Pretreatment with 10 microg/animal MCB 30 min prior to the embolism significantly attenuated the ME-induced reduction in the staining of COX and SDH in the hippocampus, but not in the pariatal cortex. The results suggest that prevention of the opening of MPT pore by MCB may play an important role in the cerebroprotection against cerebral ischemic injury.