bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does clinic-measured gait speed differ from gait speed measured in the community in people with stroke?
Authors: Taylor Denise , Stretton Caroline M , Mudge Suzie , Garrett Nick 
Published: April 2006

Objective: To compare the extent to which gait speed measured in the clinic setting differs from that measured in the community. Design: Participants completed the 10-m walk test at a self-selected speed in a clinic setting. Following this they completed a 300-m community-based walking circuit that covered a variety of environmental conditions. Gait velocity was sampled at different points in the circuit. The same circuit and sampling points were used for all participants. Clinic gait velocity was compared to gait velocity measured on five occasions during the community-based circuit. Setting: Physiotherapy clinic and local shopping mall. Participants: Twenty-eight chronic stroke patients who regularly accessed the community divided into two groups based on their gait velocity in the clinic. Main outcome measures: Walking velocity. Results: Spearman rank correlation coefficient indicated that there was a strong correlation between the total time taken to walk the 300-m course and the clinic-based gait velocity (r=-0.88, P<0.0001). A linear mixed model with repeated measures analysis revealed significant interaction between community measures for group A versus group B (F4,26=4.49, P=0.0068) and significant differences across community conditions (F4,26=7.12, P=0.0005). Conclusion: The clinic-based 10-m walk test is able to predict walking velocity in a community setting in chronic stroke patients who score 0.8 m/s or faster. However, for those who score less than 0.8 m/s in the clinic test, gait velocity in the community may be overestimated.
Psychometric properties of the modified Emory Functional Ambulation Profile in stroke patients
Authors: Liaw Lih-Jiun , Hsieh Ching-Lin , Lo Sing-Kai , Lee Su , Huang Mao-Hsiung , Lin Jau-Hong 
Published: April 2006

Objective: To examine the test-retest reliability, convergent and predictive validity and responsiveness of the modified Emory Functional Ambulation Profile (mEFAP) in assessing gait function in stroke patients undergoing rehabilitation. Subjects: Forty subacute stroke inpatients were enrolled in the validity and responsiveness study. Twenty chronic patients participated in the reliability study. Setting: Rehabilitation department of a medical centre. Design: In the validity and responsiveness study, patients were tested using the mEFAP, 10-m walking speed test, Barthel Index and Rivermead Mobility Index at admission and at discharge. For the reliability study, the patients completed the mEFAP twice one week apart. Results: The patients' performances on the mEFAP were moderately to highly correlated with results of the 10-m walking speed test and Rivermead Mobility Index (absolute correlation coefficients ≥0.67), indicating good convergent validity. Patients' performance on the mEFAP at admission was moderately correlated with the Barthel Index and Rivermead Mobility Index scores at discharge (Spearman's rank correlation coefficients=-0.52 and-0.78, respectively), indicating good predictive validity. The standardized response mean of the mEFAP was 1.1 (P<0.0001), suggesting good responsiveness. The intraclass correlation coefficient ICC(3,1) for the mEFAP was 0.997, indicating excellent test-retest reliability. Conclusions: Our results provide strong evidence that the mEFAP has good reliability, validity and responsiveness for assessing stroke patients undergoing rehabilitation. The mEFAP is a useful scale for measuring walking function and recovery in stroke patients.
Using the Timed Up and Go Test to stratify elderly inpatients at risk of falls
Authors: Large Julienne , Gan Neesha , Basic David , Jennings Natalie 
Published: April 2006

Objective: To determine whether the Timed Up and Go Test is useful at stratifying acutely unwell elderly inpatients according to their risk for subsequent falls. Design: Prospective cohort study. Setting: Multidisciplinary acute care unit for the elderly at Liverpool Hospital, in Sydney, Australia. Participants: A total of 2388 consecutive admissions to the unit of mean age 82 years. Intervention: The Timed Up and Go, administered on admission to the unit, and two modifications (an ordinal scale and a dichotomous scale, both incorporating patients unable to complete the Timed Up and Go) were evaluated. Main outcome measures: Number of falls, and reasons for the inability to complete the Timed Up and Go. Results: During a median length of stay of nine days, 180 patients had at least one fall. The Timed Up and Go was unable to identify those patients who subsequently fell (P=0.78). When the Timed Up and Go was modified to include the majority of patients unable to complete the test, both the ordinal (range of values 1-8, odds ratio (OR) 1.12, 95% confidence interval (95% CI) 1.03-1.21, P=0.01) and dichotomous (OR 1.59, 95% CI 1.09-2.32, P=0.02) modifications significantly predicted falls in multivariate analyses. Patients unable to do the Timed Up and Go due to non-physical disability had the highest fall rate (11%), followed by those with physical disability (9%), while those able to do the Timed Up and Go had the lowest fall rate (6%) (P<0.001). Acutely unwell, immobile patients with dementia and delirium were not at excessive risk of falls. Conclusion: In the acute care setting, the value of the Timed Up and Go lies in the inability to complete the test, and the reasons for this inability, rather than the time recorded.
Distinguishing theories of dysfunction, treatment and care. Reflections on ‘Describing rehabilitation interventions’
Authors: Lettinga Ant T , van Twillert Sacha , Poels Bas JJ , Postema Klaas 
Published: April 2006

Background: An editorial by Wade (Clinical Rehabilitation 2005; 19: 811-18. suggested a method for describing rehabilitation interventions. Objective: To review the editorial critically, and to suggest a more complete theory. Editorial: The editorial develops a model identifying factors that should be considered when analysing a complex rehabilitation problem, and provides a high-level description of the rehabilitation process. It explicitly does not address theories of behaviour change. New ideas: Three additional theoretical models are needed. The first considers the mechanisms that link the factors identified in Wade's model. For example how does self-esteem (in personal context) actually influence activity performance? This is a theory of dysfunction. The second needs to discuss how treatments alter their target. For example how does cognitive behavioural therapy alter pain perception and/or alter activity performance? This is a theory of treatment. It may be related to the theory of dysfunction. The third, which is less certain, needs to consider the process of giving support (maintaining the status quo). For example, how should one offer continuing opportunities for meaningful social role performance to someone with major cognitive losses? This is a theory of care. Conclusion: The two models that Wade integrated in his conceptual framework (the World Health Organization's International Classification of Functioning (WHO ICF) and the rehabilitation process) should primarily be considered as descriptive in character. Theories are still needed to understand how activity limitation arises and how treatments alter activity limitation, and possibly how a patient is supported to maintain a certain level of activity.
Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients
Authors: Wozniacka A , Lesiak A , Narbutt J , McCauliffe D P , Sysa-Jedrzejowska A 
Published: April 2006

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Published data have revealed that serum levels of proinflammatory cytokines are increased in SLE patients. The aim of our study was to evaluate whether monotherapy with chloroquine phosphate affects IL- 1β, IL-6, IL-18 and TNF-α serum levels in SLE patients. The study group consisted of 25 SLE patients with mild or moderate disease activity and 25 age- and sex-matched healthy control subjects. In SLE patients the cytokine levels were measured just before and three months after starting chloroquine treatment at a dose of 125 mg twice daily. Although the majority of SLE patients had a low systemic lupus activity measure (SLAM) index, the levels of IL-6, IL-18 and TNF-α were significantly higher than in the control group. After three-months of chloroquine therapy the mean level of IL-6, IL-18 and TNF-α decreased significantly. Minimal erythema doses (MEDs) were significantly increased in SLE patients after three months of chloroquine therapy. The results indicate that chloroquine treatment lowers some proinflammatory cytokines and may provide a photoprotective effect.
Osteoclastic Potential of Human CFU-GM: Biphasic Effect of GM-CSF
Authors: Hodge Jason M , Kirkland Mark A , Aitken Cathy J , Waugh Caryll M , Myers Damian E , Lopez Carolina M , Adams Brendan E , Nicholson Geoffrey C 
Published: April 2006

Abstract
Human osteoclasts can be efficiently generated in vitro from cord blood mononuclear cells and derived CFU-GM colonies. However, CFU-M colonies are poorly osteoclastogenic. Short-term (2–48 h) treatment with GM-CSF stimulates osteoclast formation by proliferating precursors, whereas longer exposure favors dendritic cell formation.
Introduction: Osteoclasts (OC) differentiate from cells of the myelomonocytic lineage under the influence of macrophage-colony stimulating factor (M-CSF) and RANKL. However, cells of this lineage can also differentiate to macrophages and dendritic cells (DC) depending on the cytokine environment. The aims of this study were to develop an efficient human osteoclastogenesis model and to investigate the roles of granulocyte macrophage-colony stimulating factor (GM-CSF) and M-CSF in human OC differentiation.
Materials and Methods: A human osteoclastogenesis model, using as precursors colony forming unit-granulocyte macrophage (CFU-GM) colonies generated from umbilical cord mononuclear cells cultured in methylcellulose with GM-CSF, interleukin (IL)–3 and stem cell factor (SCF), has been developed. CFU-GM, colony forming unit-macrophage (CFU-M), or mixed colonies were cultured on dentine with soluble RANKL (sRANKL) and human M-CSF with and without GM-CSF. Major endpoints were OC number, dentine resorption, and CD1a+ DC clusters.
Results: Osteoclast generation from CFU-GM and mixed colonies treated with M-CSF and sRANKL for 7–14 days was highly efficient, but CFU-M colonies were poorly osteoclastogenic under these conditions. Pretreatment of precursors with M-CSF for 7 or 14 days maintained the precursor pool, but OCs were smaller and resorption was reduced. The effect of GM-CSF treatment was biphasic, depending on the timing and duration of exposure. Short-term treatment (2–48 h) at the beginning of the culture stimulated cell proliferation and enhanced OC formation up to 100%, independent of sRANKL. Longer-term GM-CSF treatment in the presence of sRANKL, however, inhibited OC generation with the formation of extensive CD1a+ DC clusters, accompanied by downregulation of c-Fos mRNA. Delaying the addition of GM-CSF resulted in progressively less inhibition of osteoclastogenesis.
Conclusions: Human CFU-GM, but not CFU-M, progenitors have high osteoclastogenic potential. GM-CSF plays an important role in osteoclastogenesis and has a biphasic effect: Short-term treatment potentiates OC differentiation by proliferating precursors, but persistent exposure favors DC formation.
The Signaling Adapter Protein DAP12 Regulates Multinucleation During Osteoclast Development
Authors: Humphrey Mary Beth , Ogasawara Kouetsu , Yao Wei , Spusta Steven C , Daws Michael R , Lane Nancy E , Lanier Lewis L , Nakamura Mary C 
Published: April 2006

Abstract
Deficiency of the signaling adapter protein DAP12 is associated with bony abnormalities in both mice and humans. We identify specific DAP12-associated receptors expressed by osteoclasts and examine function of DAP12 in murine osteoclasts in vivo and in vitro. These data show a new role for DAP12 signaling in regulating formation of multinucleated osteoclasts.
Introduction: Osteoclasts are bone-resorbing cells derived from hematopoietic precursors in the myeloid lineage. In other myeloid cell types, the signaling adapter protein DAP12 transmits activating signals on ligation of a DAP12-associated receptor (DAR). The aim of this study was to clarify the role of DAP12 signaling during osteoclast development.
Materials and Methods: Osteoclasts from DAP12−/− or control mice were analyzed in vitro for morphology, function, and for osteoclast markers. DARs were identified in osteoclast cultures through reverse transcriptase-polymerase chain reaction (RT-PCR). Bone density of DAP12−/− and control mice were analyzed by microcomputed tomography. DAP12−/− osteoclasts were retrovirally reconstituted with DAP12. RAW264.7 cells were transfected with FLAG-tagged DAP12 or TREM2 and stimulated by anti-FLAG antibody during in vitro osteoclastogenesis.
Results: C57BL/6 DAP12-deficient mice have higher bone mass than C57BL/6 wildtype controls. We verified the presence of DAP12 in pre-osteoclasts and osteoclasts derived from C57BL/6 or the pre-osteoclast line RAW 264.7 and identified the DARs expressed. DAP12−/− osteoclasts developed in vitro with macrophage colony-stimulating factor (M-CSF) and RANKL formed only intensely TRACP+ mononuclear cells and failed to generate multinuclear osteoclasts. These mononuclear cells are functional osteoclast-like cells because, by RT-PCR, they express other osteoclast markers and generate resorption pits on dentine slices, although quantitative assessment of bone resorption shows decreased resorption by DAP12−/− osteoclasts compared with C57BL/6 osteoclasts. Restoration of DAP12 expression by retroviral transduction of DAP12−/− osteoclast precursors rescued in vitro osteoclast multinucleation. Direct stimulation of DAP12 expressed in RAW264.7 during in vitro osteoclastogenesis led to a marked increase in the number of TRACP+ multinucleated osteoclast-like cells formed.
Conclusion: Our studies indicate that stimulation of the DAP12 adapter protein plays a significant role in formation of multinuclear osteoclasts and that DAP12 and DARs likely participate in the regulation of bony remodeling.
Pamidronate Prevents Bone Loss and Decreased Bone Strength in Adult Female and Male Rats Fed an Isocaloric Low-Protein Diet
Authors: Mekraldi Samia , Toromanoff Anne , Rizzoli René , Ammann Patrick 
Published: April 2006

Abstract
Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. Inhibition of increased bone resorption by the bisphosphonate pamidronate in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.
Introduction: Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. This negative bone balance is the consequence of increased bone resorption and decreased bone formation. Whether inhibition of bone resorption could prevent low-protein diet-induced bone loss and alteration of biomechanics is not known.
Materials and Methods: The effect of the bisphosphonate pamidronate was studied in 5.5-month-old female or 6-month-old male rats pair-fed a control (15% casein) or an isocaloric low-protein (2.5% casein) diet for 19 and 26 weeks, respectively. Pamidronate (0.6 mg/kg) was given subcutaneously 5 days/month for 4 months in female rats or for 5 months in male rats. BMD, microarchitecture, and bone strength were measured at the level of the proximal and midshaft tibia. Urinary deoxypyridinoline excretion, serum osteocalcin, and IGF-I were also measured.
Results: The increase in bone resorption in female rats (+100%) and in male rats (+33%) fed a low-protein diet was prevented by pamidronate treatment. The reduced osteocalcin levels observed in rats fed a low-protein diet were further decreased in both female (−34%) and male (−30%) rats treated with pamidronate. The bone turnover decrease induced by pamidronate prevented bone strength reduction, trabecular bone loss, microarchitecture, and BMD alterations induced by the isocaloric low-protein diet. Similar effects were observed at the level of the midshaft tibia. Significant decrease of plasma IGF-I was observed in rats fed a low-protein diet independently of the pamidronate treatment.
Conclusion: In conclusion, inhibition of increased bone resorption in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.
Spontaneous Fractures in the Mouse Mutant sfx Are Caused by Deletion of the Gulonolactone Oxidase Gene, Causing Vitamin C Deficiency
Authors: Mohan Subburaman , Kapoor Anil , Singgih Anny , Zhang Zhang , Taylor Tim , Yu Hongrun , Chadwick Robert B , Chung Yoon-Suk , Donahue Leah Rae , Rosen Clifford , Crawford Grace C , Wergedal Jon , Baylink David J 
Published: April 2006

Abstract
Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures.
Introduction: A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age.
Materials and Methods: Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay.
Results: Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by &gt;90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing ∼30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold.
Conclusion: The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.
RANKL is a Marker and Mediator of Local and Systemic Bone Loss in Two Rat Models of Inflammatory Arthritis
Authors: Stolina Marina , Adamu Stephen , Ominsky Mike , Dwyer Denise , Asuncion Frank , Geng Zhaopo , Middleton Scot , Brown Heather , Pretorius Jim , Schett Georg , Bolon Brad , Feige Ulrich , Zack Debra , Kostenuik Paul J 
Published: April 2006

Abstract
RANKL is an essential mediator of bone erosions, but the role of RANKL in systemic bone loss had not been studied in arthritis. RANKL protein was increased in rat joint extracts and serum at the earliest stages of arthritis. Osteoprotegerin (OPG) treatment reversed local and systemic bone loss, suggesting that RANKL is both a marker and mediator of bone loss in arthritis.
Introduction: RANKL is well established as an essential mediator of bone erosions in inflammatory arthritis, but the role of RANKL in systemic bone loss in arthritis had not been studied. We hypothesized that serum RANKL could serve as both a mediator and as a novel biomarker for local and systemic bone loss in arthritis. We challenged this hypothesis in two established rat models of inflammatory arthritis. We sought to determine whether serum RANKL was elevated early in disease progression and whether RANKL suppression could prevent both local and systemic bone loss in these models.
Materials and Methods: Detailed time-course studies were conducted in animals with collagen-induced (CIA) or adjuvant-induced (AIA) arthritis to evaluate the onset and progression of inflammation (paw swelling), bone erosions, osteoclast numbers, and RANKL protein levels in arthritic joints and in serum. Additional CIA and AIA rats (n = 8/group) received placebo (PBS) or recombinant OPG (3 mg/kg three times weekly) for 10 days beginning 4 days after disease onset (first macroscopic evidence of hind paw erythema and edema) to assess the role of RANKL in local and systemic bone loss.
Results: RANKL protein was significantly elevated in the joints and serum of CIA and AIA rats within 1–2 days of disease onset. Increased RANKL levels were associated with local (hind paw) and systemic (vertebral) osteopenia in both models. The RANKL inhibitor OPG prevented local and systemic osteopenia in both models of established disease.
Conclusions: RANKL protein is significantly increased both locally and systemically during the earliest stages of inflammatory arthritis in rats, suggesting that serum RANKL might have prognostic value for bone erosions and systemic osteopenia in this condition. RANKL inhibition through OPG prevented local and systemic bone loss in these arthritis models, suggesting that RANKL inhibition is a promising new approach for treating bone loss in arthritis.