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T cell receptor excision circle assessment of thymopoiesis in aging mice.

Signal joint T cell receptor delta (TCRD) excision circles (TRECs) are episomal DNA circles generated by the DNA recombination process that is used by T lymphocytes to produce antigen-specific alpha/beta T cell receptors. Measurement of TRECs in thymocytes and peripheral blood T cells has been used to study thymus output in chickens and humans. We have developed a real-time quantitative-PCR assay for the specific detection and quantification of mouse TCRD episomal DNA circles excised from the TCRA locus during TCRA gene rearrangement (mTRECs). We found that the mouse TCRD TRECs detected with this assay were predominantly in naïve phenotype CD4(+) and CD8(+) T cells. In a series of aged mice (range 6-90-week-old) we determined the absolute number of thymocytes and the number of molecules of mTRECs/100,000 thymocytes. We found that the absolute number of thymocytes dramatically decreased with age (P<0.05) and that molecules of mTREC/100,000 thymocytes also declined with mouse age (P<0.05). Splenocytes were isolated from aging mice and the frequency of naïve phenotype CD4 and CD8 cells determined. There was a significant drop in both CD4 and CD8 naïve peripheral T cells in the aged mice over time. mTREC analysis in purified CD4(+) and CD8(+) splenocytes demonstrated a constant level of mTRECs in the CD4 compartment until age 90 weeks, while the mTRECs in the CD8 compartment fell with age (P<0.05). By combining the mouse TREC assay with T cell phenotypic analysis, we demonstrated that IL-7 administration to young mice induced both increased thymopoiesis and peripheral T cell proliferation. In contrast, IL-7 treatment of aged mice did not augment thymopoiesis, nor induce expansion of splenic T cells. Thus, thymus output continues throughout murine adult life, and the thymic atrophy of aging in mice is not reversed by administration of IL-7.

Aging↗

Application of the concise exposure index (OCRA) to tasks involving repetitive movements of the upper limbs in a variety of manufacturing industries: preliminary validations.

A summary of eight investigations is presented, which were carried out using standardized methods, for the purpose of quantifying exposure to tasks involving repetitive movements of the upper limbs, as well as quantifying the prevalence of work-related musculoskeletal disorders (WMSDs) of the upper limbs in groups of exposed workers. A total of 462 exposed workers were examined, and the study also took into account the data pertaining to a matched reference group comprising 749 workers not exposed to any specific occupational risk. Regarding the quantification of exposure to increased risk, use was made of a concise index (OCRA index), proposed by Occhipinti, in this issue. The data resulting from the eight investigations were used for the study of measurements and models of association among the exposure variables (mainly represented by the OCRA index), as well as the effect variables represented by the prevalence of the various WMSDs of the upper limbs taken both individually and jointly. Significant associations were reported between the OCRA index and an effect indicator represented by the prevalence of all the WSMDs of the upper limbs, calculated on the number of upper limbs at risk. When a logarithmic conversion of the relative exposure (OCRA) and injury indices was carried out, a simple linear regression model resulted that seems to provide a satisfactory predictive performance of the risk of WMSDs of the upper limbs, based on the exposure index. The study confirmed the efficacy of various other models designed to predict effects based on multiple linear regression functions, in which the independent variables are represented by both the OCRA exposure index and by parameters relative to the breakdown by gender and age of the groups of exposed workers.

Arm↗

[Osteolathyrism. Quantitative-morphological studies on the experimental rat skeletal disease].

In young growing rats, fed the lathyrogenic agent aminoacetonitrile for 3 weeks, characteristic skeletal changes developed resembling the chronic state of osteolathyrism. In both lathyritic and untreated control rats, the femoral head, the distal end of the femur, the proximal tibial end, the thalocalcanean joint and the first lumbar vertebra were investigated using undecalcified thin sections and ground sections. The following methods were employed: quantitative morphometrical analysis of bone structure and bone remodelling of the lumbar vertebra, histochemical demonstration of the composition of polysaccharides, detection of the course of collagenous fibres in cartilage and bone by the polarizing microscope, tetracycline-labelling and fluorescence microscopical determination of epiphyseal longitudinal growth and bone formation activity, photometrical quantification of microradiographies and computer-aided determination of the mineral content of bone.

Aminoacetonitrile↗

Magnetic tracking: a novel method of assessing anterior cruciate ligament deficiency.

INTRODUCTION: The Lachman test is commonly performed as part of the routine assessment of patients with suspected anterior cruciate ligament (ACL) deficiency. A major drawback is its reliance on the clinician's subjective judgement of movement. The aim of this study was to quantify Lachman movement using a magnetic tracking device thereby providing a more accurate objective measure of movement. PATIENTS AND METHODS: Ten patients aged 21-51 years were assessed as having unilateral ACL deficiency with conventional clinical tests. These patients were then re-assessed using a Polhemus Fastrak magnetic tracking device. RESULTS: The mean anterior tibial displacement was 5.6 mm (SD = 2.5) for the normal knees and 10.2 mm (SD = 4.2) for the ACL-deficient knees. This gave an 82% increase in anterior tibial displacement for the ACL deficient knees. This was shown to be highly significant with P = 0.005. CONCLUSIONS: The magnetic tracking system offers an objective quantification of displacements during the Lachman test. It is convenient, non-invasive and comfortable for the patient and is, therefore, ideally suited for use as an investigative tool.

Adult↗

[The application of the concise exposure index to repetitive movement tasks of the upper limbs in various production settings: preliminary experience and validation].

A summary of eight investigations is presented, which were carried out using standardised methods, for the purpose of quantifying exposure to tasks involving repetitive movements of the upper limbs, as well as quantifying the prevalence of Work Related Musculo Skeletal Disorders of the upper limbs in groups of exposed workers. A total of 462 exposed workers were examined, and the study also took into account the data pertaining to a matched control group comprising 749 workers not exposed to any specific occupational risk. Regarding the quantification of exposure to increased risk, use was made of a Concise Index (OCRA), proposed by the Authors in a previous publication. The data resulting from the eight investigations were used for the study of measurements and models of association among the exposure variables (mainly represented by the OCRA index), as well as the effect variables represented by the prevalence of the various WMSDs of the upper limbs taken both individually and jointly. Significant associations were reported between the OCRA index and an effect indicator represented by the prevalence of all the WSMDs of the upper limbs, calculated on the number of upper limbs at risk. When a logarithmic conversion of the relative exposure (OCRA) and injury indices was carried out, a simple linear regression model resulted which seems to provide a satisfactory predictive performance of the risk of WMSDs of the upper limbs, based on the exposure index. The study confirmed the efficacy of various other models designed to predict effects based on multiple linear regression functions, in which the independent variables are represented by both the OCRA exposure index and by parameters relative to the breakdown by sex and age of the groups of exposed workers.

Adult↗

[FDG PET as an early nuclear medical diagnostic tool for aseptic wear-induced loosening of hip joint endoprostheses--a report of two cases].

To date, 2-[F-18]fluoro-2-deoxy-D-glucose PET (FDG PET) is used as a tool in oncology as well as myocardiological and cerebral functional diagnostics in the clinical routine. False positive results of tumor search imply new possibilities for use in diagnostics of inflammation. The two case reports presented here on aseptic loosening of endoprostheses caused by the rub of polyethylene with histological and immunohistological refurbishing call attention to the possible diagnostic valency of FDG PET as an early warning system regarding aseptic artificial limb loosening induced by the rub of polyethylene. By quantification of glucose metabolism with the "standard uptake value" (SUV) as well as specific storage samples from around the artificial limb, it is the aim of our study group in further examinations to develop an algorithm which permits to distinguish between septic and aseptic loosening.

Acetabulum↗

Reorganization of equilibrium and movement control strategies in patients with knee arthritis.

The purpose of this study was to identify changes in equilibrium and movement control strategies in patients with arthritis of the knee. These strategies were expected to be different from those of healthy subjects because of the impairments caused by knee arthritis. The different phases of a side step were studied in patients with severe knee arthritis using a movement analysis system and force-plates. The duration of the postural phase and the intensity of the horizontal ground reaction forces during the postural phase were increased when the pathological limb was the supporting one. The monopodal phase was shortened on the pathological leg. These results show that knee arthritis patients develop new posturomotor strategies mainly aimed at shortening the monopodal phase when the affected leg is the supporting one. This movement analysis method enables quantification of differences that cannot be observed on clinical examination between knee arthritis patients and control subjects, and provides additional information to the usual clinical evaluation scales.

Aged↗

A method of quantification of stress shielding in the proximal femur using hierarchical computational modeling.

Stress shielding is a biomechanical phenomenon causing adaptive changes in bone strength and stiffness around metallic implants, which potentially lead to implant loosening. Accordingly, there is a need for standard, objective engineering measures of the "stress shielding" performances of an implant that can be employed in the process of computer-aided implant design. To provide and test such measures, we developed hierarchical computational models of adaptation of the trabecular microarchitecture at different sites in the proximal femur, in response to insertion of orthopaedic screws and in response to hypothetical reductions in hip joint and gluteal muscle forces. By identifying similar bone adaptation outcomes from the two scenarios, we were able to quantify the stress shielding caused by screws in terms of analogous hypothetical reductions in hip joint and gluteal muscle forces. Specifically, we developed planar lattice models of trabecular microstructures at five regions of interest (ROI) in the proximal femur. The homeostatic and abnormal loading conditions for the lattices were determined from a finite element model of the femur at the continuum scale and fed to an iterative algorithm simulating the adaptation of each lattice to these loads. When screws were inserted to the femur model, maximal simulated bone loss (17% decrease in apparent density, 10% decrease in thickness of trabeculae) was at the greater trochanter and this effect was equivalent to the effect of 50% reduction in gluteal force and normal hip joint force. We conclude that stress shielding performances can be quantified for different screw designs using model-predicted hypothetical musculoskeletal load fractions that would cause a similar pattern and extent of bone loss to that caused by the implants.

Arthroplasty, Replacement, Hip↗

Quantitative MR imaging evaluation of chondropathy in osteoarthritic knees.

PURPOSE: To determine the validity and the reliability of T1-weighted three-dimensional gradient-echo magnetic resonance (MR) imaging for quantification of articular cartilage abnormalities of osteoarthritic knees. MATERIALS AND METHODS: Forty-three patients (mean age, 63 years) with knee osteoarthritis (American College of Rheumatology criteria) of the medial tibiofemoral compartment underwent a prospective, cross-sectional study. Knees were examined with a T1-weighted three-dimensional gradient-echo sequence (1.4-mm contiguous sections), with use of a 0.2-T dedicated MR unit, before arthroscopic exploration. The tibiofemoral articular cartilage abnormalities were quantified blindly on both the MR and arthroscopic images with the French Society of Arthroscopy (SFA) score (0-100) and grading scheme (five grades). RESULTS: There was a statistically significant correlation between the SFA-arthroscopic score and the SFA-MR score (r = .83) and between the SFA-arthroscopic grade and the SFA-MR grade (weighted kappa = 0.84). The deepest cartilage lesions graded with arthroscopy and MR imaging showed correlation in the medial femoral condyle (weighted kappa = 0.83) and in the medial tibial plateau (weighted kappa = 0.84). The intraobserver reliability of the SFA-MR score was higher (r = .94) than the interobserver reliability (r = .80). CONCLUSION: Quantification of chondropathy with MR imaging is feasible and well correlated with anatomic cartilage breakdown.

Aged↗

[Backward fall in Alpine skiing. Case study of the effect of the back spoiler of the ski shoe on muscle activity and kinematics].

For the investigation of the boot-induced anterior cruciate ligament injury and experimental case study with a prototype ski boot was performed. The back spoiler of this boot was designed to yield by only some degrees with a certain level of backward moment. A mechanical switch allowed to activate or to block this mechanism. Ten jumps over a prepared hill with activated and ten jumps with blocked spoiler mechanism were performed in randomised order. During the jump and landing the EMG of eight lower extremity muscles were recorded and synchronised to two S-VHS cameras suitable for 2D-analysis of the angle kinematics. The aim of these experiments was to quantify the muscular and kinematic effects caused by the new spoiler characteristics and also to establish a method for their judgement. For the quantification of the muscular effects an activity quotient was defined and for the analysis of the kinematics the time history of three body angles and their variation between the trials were found to be appropriate. The results of this case study showed an increase of the activity quotient for all observed muscles and a higher accuracy of motion with the activated spoiler mechanism. These findings an be taken as an indication for better muscular joint guiding in the knee and justify a randomised field study using the proposed methods.

Adult↗

Assessment of shoulder strength in professional baseball pitchers.

STUDY DESIGN: A bilateral comparison of strength and range of motion testing in professional baseball pitchers. OBJECTIVE: We studied 39 professional male baseball pitchers to determine if the shoulder used for throwing was weaker or had less passive range of motion, compared to the nondominant arm. BACKGROUND: Shoulder muscle weakness has been proposed as a possible risk factor for developing injury. Therefore, objective quantification of the strength of glenohumeral and scapular rotator muscle groups should be studied in a population of professional baseball pitchers. METHODS AND MEASURES: Passive internal and external range of motion was bilaterally measured at 90 degrees of abduction. Muscle strength of the following muscles was measured bilaterally with a hand-held dynamometer: external and internal glenohumeral rotators, supraspinatus, middle trapezius, lower trapezius, and serratus anterior. RESULTS: Passive external rotation of the glenohumeral joint at 90 degrees of abduction on the pitching side was significantly greater than on the nonpitching side. Passive internal rotation range of motion on the nonpitching side was significantly greater than on the pitching side. The pitching arm's internal rotators, when tested in abduction, were significantly stronger than the nonpitching arm. The nonpitching arm's external rotators in the plane of the scapula, and in abduction, were significantly greater than those of the pitching arm. The pitching arm's middle and lower trapezius muscles were significantly stronger than those of the nonpitching arm. CONCLUSION: The range of motion and strength characteristics measured in this study can assist clinicians in evaluating athletes who use overhead throwing motions.

Adolescent↗

Extractable latex allergens in airborne glove powder and in cut glove pieces.

BACKGROUND: Quantification of natural rubber latex (NRL) allergens of NRL glove extracts has been reported in several studies. Similarly, immunoassay studies reporting the level of NRL aeroallergens in air samples have been published. When studying the NRL allergens of gloves, however, little attention has been focused on identifying the relationship between extractable NRL allergens of medical gloves and NRL aeroallergens in indoor air. OBJECTIVE: In an experimental study we analysed NRL aeroallergens of medical gloves in joint relation to total airborne dust concentration and NRL allergen concentration in gloves. METHODS: NRL aeroallergen level was measured using a chamber setting with 18 lots of powdered medical gloves. In each setting 10 pairs of powdered NRL gloves were swinging in an unventilated chamber (9 m3). Air samples were collected using airflow through Millipore filters (pore size 0.8 microm). The filters were weighed before and after the experiment, and total airborne dust concentration in the chamber was calculated. The filter samples were then extracted and the NRL allergen level measured by IgE ELISA-inhibition assay. Furthermore, cut NRL gloves were extracted and analysed by the same method. Finally, levels of two major NRL allergens, Hev b1 and Hev b 6.02, were measured in three selected NRL glove brands. RESULTS: The NRL aeroallergen level in the chamber air ranged from < 0.9 to 2.9 allergen units (AU)/m3. The total airborne dust concentration in the chamber air remained low with all lots of gloves measured (range < 20 to 80 microg/m3). The NRL allergen level in cut glove extracts varied over 100-fold (< 10 to 1050 AU/mL). Statistically significant correlation between aeroallergen concentration and airborne dust (r = 0.8, P = 0.0015) concentration was found. Moreover, significant correlation between aeroallergen levels and allergen content of cut glove pieces was observed (r = 0.59, P < 0.05). Hev b 1 levels varied from 9 to 25 ng/mL and the levels of Hev b 6.02 from 1720 to 14460 ng/mL in the glove extracts. In the extracts from airborne dust samples, Hev b 6.02 content varied from 61 to 183 ng/m3, whereas Hev b 1 levels were very low (0.4 to 3 ng/m3). CONCLUSION: An elevated NRL aeroallergen level is rather related to a high level of airborne glove powder than to a high concentration of extractable NRL allergen in medical gloves.

Allergens↗

Measuring familial aggregation by using odds-ratio regression models.

Detection of familial aggregation of a disease is important for studying possible genetic and environmental factors contributing to disease etiology. Accurate quantification of familial aggregation can provide guidance for subsequent, more sophisticated genetic studies. This article presents a statistical model and method for detecting both inter- and intra-class aggregation of a binary trait with family data. The method used here is based on the logistic regression model which incorporates effects of individual covariates while measuring familial aggregation of risk as the odds ratios among classes of relatives. An estimation equation approach is presented where the joint distribution of binary traits among family members need not be fully specified. Data from a genetic epidemiologic study on liver cancer in Shanghai are analyzed for illustration, and reveal strong aggregation of risk even after adjusting for covariates. Effects of non-random sampling and ascertainment bias are also discussed.

Adolescent↗

BMP-7 loaded microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type-I gel.

In recent years, interest in chondrocyte cultures for transplantation has gained increasing attention. We investigated the use of PGLA microspheres as a new delivery system for BMP-7 and the effects on human chondrocytes cultivated in a 3D collagen gel culture. In an in vitro study, human chondrocytes obtained from osteoarthritic knee joints were released, transferred into a collagen type-I gel, and cultivated up to 14 days. In the treatment group PGLA microspheres loaded with human recombinant BMP-7 protein were added to the matrix. After the cultivation period, histological and immunohistochemical investigations were performed. In addition, the aggrecan core protein and type-II collagen mRNA concentrations were measured by real-time PCR. Histological staining for proteoglycan and collagen type-II protein and quantification via digital image processing revealed a significantly higher content in the samples cultivated with BMP-7 loaded microspheres in comparison to the control samples. Moreover, the collagen gel scaffold was partially remodeled by the chondrocytes and replaced by newly synthesized extracellular matrix. Cellular proliferation as well as apoptosis were low. In conclusion, we consider the PGLA microsphere system to be a functional device for the delivery of growth factors during the cultivation of articular chondrocytes leading to an increased content of type-II collagen and proteoglycan in the extracellular matrix.

Aged↗

Thermomechanical analysis of soft-tissue thermotherapy.

Soft-tissue thermotherapy based on sub-ablative heating of collagenous tissues finds wide-spread application in medicine such as tissue welding, thermokeratoplasty, skin resurfacing, elimination of discogenic pain in the spine and treatment of joint instability. In this paper, heat-induced thermomechanical response characteristics of collagenous tissues are quantified by means of in vitro experimentation with a representative model tissue (New Zealand white rabbit patellar tendon). Three distinct heat-induced thermomechanical response regimes (defined by the rate of deformation and the variation of material properties) are identified. Arrhenius damage integral representation of collagenous tissue thermal history is shown to be adequate in establishing the master response curves for quantification of thermomechanical response for modeling purposes. The trade-off between the improved kinematical stability and compromised mechanical stability of the heated collagenous tissue is shown to be the major challenge hindering the success of subablative thermotherapies.

Adaptation, Physiological↗

Ultrasonic indentation: a procedure for the noninvasive quantification of force-displacement properties of the lumbar spine.

BACKGROUND: Alterations in the normal force-displacement (FD) properties of spinal tissues have been associated with specific forms of pathology, such as degenerative disk disease. Unfortunately, few current procedures exist that assess spinal FD properties in an accurate, reliable, and noninvasive manner. Consequently, the clinical relevance of the relation between spinal disorders and spinal FD properties is not fully understood. OBJECTIVE: To investigate the accuracy and reliability of spinal FD measures obtained through use of a procedure in which real-time ultrasonic imaging (ultrasonic indentation) is used during load-controlled external indentation. SETTING: McCaig Centre for Joint Injuries and Arthritis Research, University of Calgary. METHODS: The bench-top accuracy and reliability of ultrasonic indentation were assessed by cyclic indentation of a spring-mounted platform. These data were compared with criterion data derived from a materials testing machine. A porcine preparation was then used to assess the accuracy of ultrasonic indentation-generated estimates of vertebral displacement in comparison with a criterion of optically tracked displacement. In addition, previously unreported parameters relating to indentation accuracy (frame deflection and off-axis loading) were characterized. RESULTS: Reliability of ultrasonic indentation ranged between 0.99 and 1.00 (intraclass correlation coefficient). Error values in force, displacement, and stiffness ranged from 0.81% to 13.62% over varying experimental conditions. CONCLUSIONS: Ultrasonic indentation is a unique procedure that is capable of assessing, noninvasively, FD properties of spinal tissues, including vertebral displacement in the indentation plane. The results of this study suggest that ultrasonic indentation is a potentially useful technique for quantifying spinal FD properties in vivo.

Animals↗

Advantages of an increased dose of MRI contrast agent for enhancing inflammatory synovium.

MRI intravenous contrast enhancement of inflammatory synovium has been studied at two different doses to determine to what extent enhancement is dose dependent. 19 patients with clinically active rheumatoid arthritis involving a knee were scanned twice, one week apart, using 0.1 mmol/kg of gadoteridol (ProHance) on the first occasion and 0.3 mmol/kg on the second. Static pre-and post-contrast images together with dynamic images immediately following injection were obtained on a 1.0T scanner. On subjective assessment, 84% of patients showed improved enhancement. 47% showed more enhancing tissue, a clearer delineation of enhancing tissue or both. Objectively, enhancement was increased significantly at the higher dose, as judged by the percentage increase in mean signal intensity within regions of interest plotted over the suprapatellar pouch (1723% v. 1005% enhancement P < 0.05). In practical terms the better visualization of enhancing tissue achieved with higher doses is likely to reduce margins of error in attempts at quantification from MRI scans, particularly of synovial volume, but emphasizes also the need for care and consistency to be exercised in calculating the exact dose of contrast medium to be administered.

Adult↗

Radiographic and computed tomographic determination of femoral varus and torsion in the dog.

Diagnosis and quantification of femoral varus and femoral torsion using radiographs is technically challenging due to the difficulty in determining proper positioning. The purpose of this study is to describe a computed tomographic technique for determination of femoral varus and femoral torsion and to compare this technique, and standard radiography, to anatomic preparation, for the measurement of femoral varus and femoral torsion in normal dogs. Nine canine cadavers, visually and radiographically free of orthopedic disease of the hip and stifle joints, were utilized for analysis. Femoral varus was determined using a craniocaudal radiograph, a craniocaudal radiograph obtained after confirming accurate positioning using horizontal beam fluoroscopy, and computed tomography (CT). Femoral torsion (expressed as angle of version) was determined using an axial radiographic projection obtained from distal to proximal and CT. Each femur was dissected free of soft tissues, and direct determination of femoral varus and femoral torsion was performed using digital photographic images. All radiologic and photographic images were digitally measured to quantify the magnitude of femoral varus and femoral torsion. For femoral varus, no difference (P = 0.149) between the three different imaging techniques and the anatomic preparation was identified. For femoral torsion, no difference (P = 0.059) between the two imaging techniques and the anatomic preparation was identified. Well positioned radiographs and the described computed tomographic method are both as accurate as anatomic preparation for the measurement of both femoral varus and femoral torsion in normal dogs.

Animals↗