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Exercise and functional tasks among adults who are functionally limited.

This study compared the efficacy of 16 weeks of either resistance training, aerobic walking, or combined resistance training and aerobic walking on the performance of functional tasks among adults age 65 years and older with limited functional ability. One hundred thirty-one older adult individuals were randomized into four groups: resistance training, aerobic walking, combined resistance and aerobic walking groups, or a nonexercise control group. Each of the exercise groups documented 70% compliance with their respective exercise intervention, which included three weekly exercise sessions. At baseline, and 8 and 16 weeks following baseline, all participants completed six assessments of their functional ability. Analysis of covariance indicated that all three exercise intervention groups significantly improved measures of functional ability, with the resistance group demonstrating the most consistent gains over the six measures. These findings indicate that older adults who are functionally limited can improve their functional ability through a variety of types of exercise.

Activities of Daily Living↗

Functional analysis of zebrafish microfibril-associated glycoprotein-1 (Magp1) in vivo reveals roles for microfibrils in vascular development and function.

Mutations in fibrillin-1 (FBN1) result in Marfan syndrome, demonstrating a critical requirement for microfibrils in vessel structure and function. However, the identity and function of many microfibril-associated molecules essential for vascular development and function have yet to be characterized. In our morpholino-based screen for members of the secretome required for vascular development, we identified a key player in microfibril formation in zebrafish embryogenesis. Microfibril-associated glycoprotein-1 (MAGP1) is a conserved protein found in mammalian and zebrafish microfibrils. Expression of magp1 mRNA is detected in microfibril-producing cells. Analysis of a functional Magp1-mRFP fusion protein reveals localization along the midline and in the vasculature during embryogenesis. Underexpression and overexpression analyses demonstrate that specific Magp1 protein levels are critical for vascular development. Integrin function is compromised in magp1 morphant embryos, suggesting that reduced integrin-matrix interaction is the main mechanism for the vascular defects in magp1 morphants. We further show that Magp1 and fibrillin-1 interact in vivo. This study implicates MAGP1 as a key player in microfibril formation and integrity during development. The essential role for MAGP1 in vascular morphogenesis and function also supports a wide range of clinical applications, including therapeutic targets in vascular disease and cardiovascular tissue engineering.

Animals↗

Anatomic and functional leg-length inequality: a review and recommendation for clinical decision-making. Part II. The functional or unloaded leg-length asymmetry.

BACKGROUND: Part II of this review examines the functional "short leg" or unloaded leg length alignment asymmetry, including the relationship between an anatomic and functional leg-length inequality. Based on the reviewed evidence, an outline for clinical decision making regarding functional and anatomic leg-length inequality will be provided. METHODS: Online databases: Medline, CINAHL and Mantis. Plus library searches for the time frame of 1970-2005 were done using the term "leg-length inequality". RESULTS AND DISCUSSION: The evidence suggests that an unloaded leg-length asymmetry is a different phenomenon than an anatomic leg-length inequality, and may be due to suprapelvic muscle hypertonicity. Anatomic leg-length inequality and unloaded functional or leg-length alignment asymmetry may interact in a loaded (standing) posture, but not in an unloaded (prone/supine) posture. CONCLUSION: The unloaded, functional leg-length alignment asymmetry is a likely phenomenon, although more research regarding reliability of the measurement procedure and validity relative to spinal dysfunction is needed. Functional leg-length alignment asymmetry should be eliminated before any necessary treatment of anatomic LLI.

Journal Article↗

A pump-independent function of the Na,K-ATPase is required for epithelial junction function and tracheal tube-size control.

The heterodimeric Na,K-ATPase has been implicated in vertebrate and invertebrate epithelial cell junctions, morphogenesis and oncogenesis, but the mechanisms involved are unclear. We previously showed that the Drosophila Na,K-ATPase is required for septate junction (SJ) formation and that of the three beta-subunit loci, only Nrv2 isoforms support epithelial SJ barrier function and tracheal tube-size control. Here we show that Nrv1 is endogenously co-expressed with Nrv2 in the epidermis and tracheal system, but Nrv1 has a basolateral localization and appears to be excluded from the Nrv2-containing SJs. When the normally neuronal Nrv3 is expressed in epithelial cells, it does not associate with SJs. Thus, the beta-subunit is a key determinant of Na,K-ATPase subcellular localization as well as function. However, localization of the Na,K-ATPase to SJs is not sufficient for junctional activity because although several Nrv2/Nrv3 chimeric beta-subunits localize to SJs, only those containing the extracellular domain of Nrv2 have junctional activity. Junctional activity is also specific to different alpha-subunit isoforms, with only some isoforms from the major alpha-subunit locus being able to provide full barrier function and produce normal tracheal tubes. Importantly, mutations predicted to inactivate ATPalpha catalytic function do not compromise junctional activity, demonstrating that the Drosophila Na,K-ATPase has an ion-pump-independent role in junction formation and tracheal morphogenesis. These results define new functions for the intensively studied Na,K-ATPase. Strikingly, the rat alpha1 isoform has full junctional activity and can rescue Atpalpha-null mutants to viability, suggesting that the Na,K-ATPase has an evolutionarily conserved role in junction formation and function.

Alternative Splicing↗

A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function.

A functional model of adult human prostate epithelium is described. This model shows that stromal cells, but not an androgenic stimuli, are required for architectural organisation of prostate epithelium. Within an organised structure, androgenic stimulation is required for the establishment of secretory epithelial cell morphology and associated function. In the absence of stromal cells but in the presence of androgens architectural organisation and secretory function are lost. Epithelial parenchymal units (organoids) from human prostate tissue were isolated, cultured within a three-dimensional collagen matrix, and xenografted subcutaneously into athymic mouse hosts. The grafted gels were rapidly invaded by host fibroblasts. Epithelial organisation initially disappeared but was re-established concurrently with the stromal cell invasion. In intact male hosts, cuboidal and columnar cells that expressed human prostate-specific secretory markers were found. In castrated male and in female hosts epithelial structures were lined with flattened epithelium with no secretory function. This phenomenon could be reversibly replicated by treating intact male hosts with the anti-androgen Flutamide. Gels containing organoids grafted within 0.45 microns Millipore chambers were not invaded by stromal cells and rapidly lost all epithelial organisation and secretory function. When organoids cocultured with human foreskin fibroblasts were grafted within chambers, structural organisation of the epithelium was supported. These results indicate that both heterologous human fibroblasts and mouse stromal cells are capable of permissively supporting adult human prostate epithelial function.

Aged↗

Signal transduction events regulating integrin function and T cell migration: new functions and complexity.

Integrin receptors facilitate T cell function by mediating adhesive events critical for T cell trafficking and recognition of foreign antigen, including interactions with vascular endothelium, extracellular matrix components, and antigen-presenting cells. Consequently, the functional activity of integrin receptors is acutely regulated by various intracellular signals delivered by other cell surface receptors, resulting in rapid changes in T cell adhesion and migration. This review highlights recent insights into our understanding of the signaling events by which the CD3/T cell receptor complex and chemokine receptors regulate integrin function and T cell migration. These studies highlight novel functions for several signaling molecules, including the tyrosine kinases Itk and ZAP-70, and the adapter protein SLAP-130/Fyb. In addition, analysis of the regulation of integrin function and chemokine-mediated migration has highlighted the critical role that spatial localization of signaling molecules plays in signal transduction, and the importance of the actin cytoskeleton in T cell function.

Cell Adhesion↗

[Changes in glucose metabolism and endocrine function in the remnant pancreas after major pancreatectomy, with special reference to the function of the anti-insulin system in Sandmeyer's diabetes (author's transl)].

Changes in glucose tolerance and the function of the anti-insulin system after a major resection of the canine pancreas were divided into three types. Immediately after the removal of 90 per cent or more of the pancreas, diabetes developed, and the function of the anti-insulin system was depressed, showing a poor response of glucagon secretion to hypoglycemia after insulin load and degeneration or destruction of the islet cells and both A and B cells, and the dosage of insulin required to control blood sugar was close to that of a total pancreatectomy. 6 to 24 weeks after the removal of 70 to 90 per cent of the pancreas, so-called Sandmeyer's diabetes occurred, in which glucose tolerance and the function of the anti-insulin system were within the normal range during the early postoperative periods, but the function of the anti-insulin system was highly activated later, showing a high response of pancreatic glucagon secretion to hypoglycemia after insulin load, accompanied by degeneration of B cells, but not A cells. These results could well explain the fact that the insulin dosage needed to control blood sugar in Sandmeyer's diabetes was 3 to 4 times more than it was in total pancreatectomy. After the removal of 70 per cent or less of the pancreas, diabetes did not occur, and glucose tolerance and the function of the anti-insulin system were maintained well, without any significant change in the islets of the remnant pancreas. Insulin therapy relieved the disturbed function of the anti-insulin system in diabetes following pancreatectomy.

Animals↗

On the role of covarying functions in stimulus class formation and transfer of function.

This experiment investigated whether directly trained covarying functions are necessary for stimulus class formation and transfer of function in humans. Initial class training was designed to establish two respondent-based stimulus classes by pairing two visual stimuli with shock and two other visual stimuli with no shock. Next, two operant discrimination functions were trained to one stimulus of each putative class. The no-shock group received the same training and testing in all phases, except no stimuli were ever paired with shock. The data indicated that skin conductance response conditioning did not occur for the shock groups or for the no-shock group. Tests showed transfer of the established discriminative functions, however, only for the shock groups, indicating the formation of two stimulus classes only for those participants who received respondent class training. The results suggest that transfer of function does not depend on first covarying the stimulus class functions.

Adult↗

Comparison of subjective ratings of function with observed functional ability of frail older persons.

BACKGROUND: Important clinical decisions often hinge on patients' functional status. Previous studies have shown disagreement among sources of ratings of patients' functional status. This study compared patient self-ratings, family member ratings, and physician ratings of patient function to performance-based functional testing criteria. METHODS: Five activities of daily living of 73 older patients were studied at admission to a rehabilitation unit following discharge from an acute care community hospital. Data were collected from patients, family members, and physicians and were compared with performance-based function testing. RESULTS: Patient ratings were significantly more accurate than physician ratings for walking, transferring, and telephoning. Patients were significantly more accurate than family members for rating walking and telephoning, but patients were not significantly more accurate than family members or physicians for rating eating or dressing. CONCLUSIONS: We conclude that decisions about patients' functional level should be based on performance testing. If performance testing is unavailable, patients' own ratings are most accurate, followed by family ratings. Physicians' ratings are least accurate.

Activities of Daily Living↗

Functional training: muscle structure, function, and performance in older women.

Response to physical training at the cellular and whole muscle level has been established in older adults. However, the underlying molecular mechanism responsible for change has not been described nor have the relationships between change in muscle structure and functional performance been established. The purpose of this research study is to evaluate the changes of muscle ultrastructure, muscle strength, and whole body functional performance as a result of a functionally directed exercise program (stair climbing). Women (65-83 years old) selected either the control (no exercise; N = 6) or exercise (N = 7) group. The 1-year functionally based exercise program was both aerobic (75% heart rate reserve) and resistive (weighted stair climbing). Muscle ultrastructure, determined by quantitative morphometry of the vastus lateralis tissue, and maximal step-height achieved by each subject were related to isokinetic strength and muscle morphology. Changes in myofibrillar area accounted for 48% of the variance in muscle strength changes. Change in muscle contractile protein was the underlying basis for change in thigh strength which, in turn, was the basis for functional performance. These data provide evidence that, in older women, a mild functionally based training program results in improved muscle structure and performance of the lower body.

Aged↗

Autonomic nervous system function in patients with functional abdominal pain. An experimental study.

Functional abdominal pain--that is, pain without demonstrable organic abnormalities--has often been associated with psychologic stress. The aim of the present study was to investigate whether sympathetic nervous system response to laboratory stress and basal parasympathetic neural activity were disturbed in 22 patients with functional abdominal pain (functional group) as compared with 14 healthy controls (healthy group) and 26 patients with organic abdominal pain (organic group) due to duodenal ulcer (DU), gallstones, or urinary tract calculi. Plasma adrenocorticotrophic hormone (ACTH) and serum cortisol measurements were included, to assess the pituitary-adrenocortical axis. Heart rate, systolic blood pressure, and plasma adrenaline increased significantly in all groups in response to a stress test (mental arithmetic). Plasma noradrenaline increased in the DU patients only, and plasma ACTH and serum cortisol did not increase at all in any of the groups. As a measure of parasympathetic neural activity, independent of sympathetic neural activity, the beat-to-beat variation of the heart rate was calculated. The functional patients had a significantly higher beat-to-beat variation expressed as the mean square successive differences of the R-R intervals (MSSD), indicating a higher basal parasympathetic neural activity (mean MSSD +/- SEM = 64 +/- 6 msec in the functional group, 46 +/- 6 msec in the healthy group, and 49 +/- 6 msec in the organic group; P = 0.03). A reduced sympathetic neural response as indicated by a lesser stress-induced increment in heart rate, was seen in both patient groups (functional, 13 +/- 2 beats/min; organic, 10 +/- 2 beats/min) as compared with the healthy group (19 +/- 2 beats/min; P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

Assessing the function of functional assessment: a consumer perspective.

The person who is most affected by the process of functional assessment is the consumer--the individual with a disability whose functional capacity is being assessed. Consumers want the functional assessment process to be conducted in a dignified manner and the results to be relevant to their needs. Many consumers, influenced by the independent living movement, focus primarily on their ability to live independently in their communities and on environmental barriers that prevent them from doing so. Yet, most functional status measures focus primarily on impairments and functional limitations, rather than on handicapping environmental factors. Consumers should be involved directly in the development and application of functional status measures so that these factors are considered appropriately. Such measures have important implications for defining programme eligibility, determining payment, assuring quality, and enhancing discharge planning.

Activities of Daily Living↗

[Change with aging in eustachian tubal function--eustachian tubal function of normal ears].

Eustachian tubal function was evaluated in two age groups: children aged 4 to 14 years and adults aged 23 to 74 years. The test group of children included 224 normal ears, the test group of adults 106 normal ears. Active opening function was determined by sonotubometric eustachian tubal function testing, which measures the duration of patency of the eustachian tube during swallowing. Passive opening function was determined by tubo-tympanoaerodynamic graphy (TTAG), which measures the naso-pharyngeus pressure when tubal opening is produced by the Valsalva maneuver. 1) The duration of patency of the Eustachian tube during swallowing in children was increased from the age of 8 and was nearly equal to the adult value at the age of 11. As the children got older, the naso-pharyngeus pressure when tubal opening is produced by the Valsalva maneuver increased and was nearly the same as the adult value at the age of 10. From the above, it seems that the pressure opening type Eustachian tubal function in children changes to the muscular opening type tubal function in adults at the age of 10 or 11. 2) The duration of patency of the Eustachian tube during swallowing was shorter in the group older than 60 years. The Valsalva maneuver was higher in the group above age of 50 than in younger adults. These characteristics of the Eustachian tubes of older age groups may be among the causes of adult type serous otitis media, which often occurs in older adults.

Adolescent↗

The generation of Th memory in neonates versus adults: prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates.

Immunization during the neonatal period often results in Th2-biased secondary responses. To understand the regulation of this phenomenon, we have examined all phases of Th development, from the generation of primary effectors to the duration of the primary effector stage to the production of memory effector function. First, we had previously reported that although primary responses in the neonatal lymph nodes are mature, mixed Th1/Th2-like, primary responses in the spleens of the same animals are exclusively Th2-like. To determine whether Th2-dominant secondary responses are due to the Th2-polarized primary function in the spleen, neonates were splenectomized before immunization. Even in the absence of primary neonatal splenic responses, the secondary responses of neonates were Th2 dominant. Thus, the overwhelmingly Th2 primary responses in the neonatal spleen are not required to generate Th2-dominant memory in the lymph nodes. Second, we have compared the kinetics of the primary response phase in neonates and adults. In adults, Ag-specific Th2 function disappeared rapidly from both the lymph nodes and spleen. In contrast, primary Th2 function persisted out to 5 wk in both neonatal organs. Third, the generation of Th memory responses was examined in animals initially immunized as neonates and in adults. These experiments demonstrated that neonates are selectively impaired in the development of Th1 memory effector function. Together, these results indicate that neonates are biased to Th2 function at all phases of an immune response.

Adjuvants, Immunologic↗

[Validation of the Italian versions of the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) in patients with ankylosing spondylitis].

OBJECTIVES: The Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) are the most commonly used instruments to measure functioning in ankylosing spondylitis (AS). The aim of this study was to translate, adapt and validate these instruments into the Italian language. METHODS: The BASFI and DFI questionnaires were translated into Italian by two independent bilingual physicians who were familiar with the medical aspects of AS and by one professional translator. Two rheumatologists familiar with instrument validation, and who were aware of the purpose of the study, examined semantic, idiomatic and conceptual issues and produced by consensus unified versions of each instrument. English back-translations from the Italian were done by a professional translator unaware of the original version. Both English versions were compared, and where needed, modifications to the Italian versions were made. RESULTS: A total of 95 patients were included: 77 males, age (mean+/-SD) 47.9+/-9.3years, and disease duration 12.4+/-6.6 years, and 18 females, age 45.9+/-8.7 years, and disease duration 11.3+/-8.2 years. Reliability, measured in 23 patients participating a physiotherapy program, showed an acceptable one-week test-retest intraclass correlation coefficient (ICC)--BASFI ICC: 0.91, 95% CI: 0,87-0.94 and DFI ICC: 0.86, 95% CI: 0.83-0.90. The internal consistency was 0.90 (Cronbach's alpha) for the BASFI and 0.87 for the DFI. For validity the functional indices were correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), modified Health Assesment Questionnaire (HAQ-S), SF-36 physical component summary (SF-36 PCS), stiffness, pain, physician's assessment of disease activity, Bath AS Radiology Index-total (BASRI-t), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The functional indices (BASFI and DFI) were correlated with each other (p<0.0001) and with activity variables. There was no significant relationship between functional indices and BASRI-t and acute phase reactants. The receiver operating characteristic (ROC) curve analysis indicated that the BASFI ranked superior compared to HAQ-S, (p = 0.019) and SF36 PCS (p = 0.002), but not respect to DFI (p = NS), in distinguishing between patients with high and low disease activity. CONCLUSIONS: The Italian versions of the BASFI and DFI showed adequate reliability and validity in patients with AS. Because of psychometric advantages, the BASFI may be preferred in clinical trial settings. However, sensitivity to changes due to drug therapy and/or rehabilitation remains to be determined.

Activities of Daily Living↗

Comparison of the Dougados Functional Index and the Bath Ankylosing Spondylitis Functional Index. A literature review.

The preliminary core set for endpoints in ankylosing spondylitis (AS) clinical trials includes physical function. The objective of this review was to compare properties and performance of the 2 most widely used measures of functional capacity in AS: the Dougados Functional Index (DFI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). A MEDLINE search was performed covering the years 1988 through April 1998. AS studies were identified and selected if they included the DFI and/or the BASFI. Additional studies were identified by scrutinizing the references cited in the retrieved articles and by correspondence with the authors of the 2 questionnaires. The instruments were examined with respect to development, truth, discrimination, and feasibility. We identified 27 articles dealing with the instruments. Both are valid and reliable measures of functional capacity in AS. While the DFI was sensitive to change in one disease controlling (DC-ART) and in 4 symptom modifying antirheumatic drug (SMARD) clinical trials, the BASFI is not sufficiently tested in these settings. The only direct comparison of both indices in a physical therapy setting confirmed 4 other studies that suggested a better discriminative capacity of the BASFI in physical therapy clinical trials. Two likely reasons for the lack of responsiveness of the DFI in these settings are the distribution of baseline scores showing a tendency towards normal values and the less sensitive scoring system. Discriminative capacity of the BASFI was found to be superior in patients with mild functional disability. It remains to be seen whether the BASFI performs as well as or better than the DFI in SMARD and DC-ART clinical trials.

Activities of Daily Living↗

New functional polar maps for estimating regional cardiac function using ECG-gated technetium-99m-tetrofosmin SPECT.

OBJECTIVE: The purpose of this work was to develop functional parameters to analyze regional cardiac function using ECG-gated 99mTc-tetrofosmin SPECT. Our goal was to develop a methodology that used slice thickness correction, the generation of a time-activity curve and a polar map. METHODS: Fourteen normal patients without evidence of coronary artery disease were studied. One hour after intravenous injection of 740-1110 MBq (20-30 mCi) 99mTc-tetrofosmin, ECG-gated SPECT data were acquired by dividing a cardiac cycle into 12 frames. The SPECT data were reconstructed from 11 of 12 frames into 3 views. The reconstruction of these images was repeated after performing slice thickness correction. Excluding the effect of different apex-to-base lengths at any frame during a cardiac cycle, 10 short-axis images with the same slice thickness were obtained. Each short-axis image was divided by 40 radii into 40 segments. The time-activity curve was generated from the total counts included in each segment plus both neighboring segments. Subsequently the curve fitting was performed using the second Fourier function. RESULTS: From fitted curves and their differentials, we calculated end-systolic count, end-diastolic count, percent count increase, uptake, peak contraction rate, peak distention rate and contraction time. CONCLUSION: The functional polar maps visually demonstrated regional myocardial function. This method is expected to be helpful for assessing regional cardiac function using 99mTc-tetrofosmin.

Adult↗

Method for quantitatively evaluating the lateralization of linguistic function using functional MR imaging.

BACKGROUND AND PURPOSE: Various methods for evaluating the lateralization of linguistic function using functional MR imaging have been proposed. However, the optimal method remains controversial. The purpose of this study was not only to establish a method for quantitatively evaluating the lateralization of linguistic function but also to evaluate its optimality. METHODS: Internal speech tasks were measured by functional MR imaging in 17 healthy adult volunteers by use of z scores. The laterality index (LI) was calculated first by a previously reported method and second by our newly designed method, in which we investigated the correlation between the z scores and the number of activated pixels in the regions of interest; that is, we made scatter diagrams (z scores versus number of activated pixels). To obtain detailed information, we searched a regression function that fit the scatter diagrams well. RESULTS: We found the number of activated pixels was proportional to (1/z score)(4) and the correlation coefficient was very high. Each hemisphere showed an original proportional constant. Our newly designed LI was calculated from these two constants and was found to be a fixed value. In contrast, the reported LI varied with the z score. We found our LI differed in robustness and reproducibility from the reported LI. CONCLUSION: Our LI method proved more optimal than the reported LI. The lateralization of linguistic function can be evaluated quantitatively using our new LI method.

Adult↗