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PubMed2004

Hamstring and quadriceps strength balance in normal and hamstring anterior cruciate ligament-reconstructed subjects.

OBJECTIVE: The purpose of this study was to evaluate and characterize the agonist-antagonist strength balance (hamstring/quadriceps [H/Q] ratio and dynamic control ratio [DCR]) about the knee specific to velocity, range of motion, and contraction type. We hypothesized that there would be systematic variation in the H/Q ratio and DCR based on knee joint angle, angular velocity, and contraction type. We also hypothesized that these ratios would be altered in the anterior cruciate ligament (ACL)-reconstructed group in favor of protecting the ACL graft (relative knee flexor strength when strain on the ACL is the greatest). DESIGN: Cross-sectional design. SETTING: A tertiary care sport medicine clinic. PATIENTS OR PARTICIPANTS: Sixteen subjects more than 1 year after hamstring tendon ACL reconstruction were compared with 30 active uninjured control subjects. INTERVENTIONS: Isokinetic strength testing was performed over 5 degrees to 95 degrees knee joint range of motion, 5 angular velocities (50, 100, 150, 200, 250 degrees/s), for concentric and eccentric contractions. MAIN OUTCOME MEASUREMENTS: Angle and velocity-matched H/Q ratio maps and DCR maps were produced for each group. Difference maps allowed quantification of the differences between the groups. RESULTS: Angle and velocity-matched H/Q ratio maps demonstrated systematic variation based on joint angle, velocity, and contraction type for both the control (H/Q, approximately 0-1.42; DCR, approximately 0-1.57) and the ACL-reconstructed group (H/Q, approximately 0-1.33; DCR, approximately 0-1.35). Difference maps demonstrate regional (angle and velocity-specific) alteration in the ratio between the ACL-reconstructed and control groups. CONCLUSIONS: Specific imbalances were demonstrated in the ACL-reconstructed group compared with control. In high knee flexion angles, the low H/Q ratio may represent a compromised ability of the hamstrings to stabilize the knee joint throughout the full range of motion. Near full knee extension shifts in favor of the knee flexors may represent an attempt to stabilize the knee at the angle of greatest ACL strain. These finding have implications for graft donor site selection and postoperative rehabilitation as well as provide insight into the neuromuscular control of the knee.

Adult↗
PubMed1999

Using sensitivity analysis for efficient quantification of a belief network.

Sensitivity analysis is a method to investigate the effects of varying a model's parameters on its predictions. It was recently suggested as a suitable means to facilitate quantifying the joint probability distribution of a Bayesian belief network. This article presents practical experience with performing sensitivity analyses on a belief network in the field of medical prognosis and treatment planning. Three network quantifications with different levels of informedness were constructed. Two poorly-informed quantifications were improved by replacing the most influential parameters with the corresponding parameter estimates from the well-informed network quantification; these influential parameters were found by performing one-way sensitivity analyses. Subsequently, the results of the replacements were investigated by comparing network predictions. It was found that it may be sufficient to gather a limited number of highly-informed network parameters to obtain a satisfying network quantification. It is therefore concluded that sensitivity analysis can be used to improve the efficiency of quantifying a belief network.

Algorithms↗
PubMed1990

A microcomputer-based video vector system for clinical gait analysis.

A microcomputer-based video vector system has been developed to display the resultant ground reaction force vector on a television image of the subject in real-time. For each television field the force platform signals are acquired and processed and the resultant force vector superimposed on the video image of the walking subject. The force platform results are stored on disc and the composite video signals recorded on video tape for further analysis. The system is easy to set up and use and the results can be readily interpreted. The external moments produced at the joint centers by the ground reaction forces can be observed visually and, if required, quantification of the external moments can be achieved following data collection. The spatial resolution of the system is 0.342% vertically and 0.156% horizontally. The force vector visualization technique has routine applications in orthotics and prosthetics. It is also a useful technique for the teaching of biomechanics.

Calibration↗
PubMed2003

Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation (AHSCT) leads to a prolonged state of immunodeficiency characterized by low peripheral naive T-cell counts. To identify the mechanisms leading to this defect we quantitatively and qualitatively analyzed thymic function through quantification of T-cell receptor excision circle (TREC) frequencies (both the signal-joint TREC [sjTREC] and 6 different DbetaJbeta TRECs, by-products of T-cell receptor [TCR] alpha and beta gene rearrangement, respectively), in conjunction with immunophenotype and spectratype analyses in a cohort of patients sampled from 1 to 10 years following AHSCT. In this cohort, reduced thymic function was associated only with ongoing clinical chronic graft-versus-host disease (cGVHD). Nonetheless, the diversity of thymic production remained unchanged irrespective of the patient's cGVHD status. Interestingly, increased homeostatic proliferation was found in the naive T-cell compartment of cGVHD- patients who underwent transplantation. However, reduced expression of both the interleukin-7 receptor alpha (IL-7Ralpha) (CD127) chain and the antiapoptotic protein Bcl-2 was observed. Taken together, these data indicate that the inability to reconstitute the naive T-cell compartment for several years after AHSCT, in the absence of cGVHD, is a consequence of impaired naive T-cell survival rather than thymic dysfunction.

Adult↗
PubMed2025

Predicting and comparing transcription start sites in single cell populations.

The advent of 5' single-cell RNA sequencing (scRNA-seq) technologies offers unique opportunities to identify and analyze transcription start sites (TSSs) at a single-cell resolution. These technologies have the potential to uncover the complexities of transcription initiation and alternative TSS usage across different cell types and conditions. Despite the emergence of computational methods designed to analyze 5' RNA sequencing data, current methods often lack comparative evaluations in single-cell contexts and are predominantly tailored for paired-end data, neglecting the potential of single-end data. This study introduces scTSS, a computational pipeline developed to bridge this gap by accommodating both paired-end and single-end 5' scRNA-seq data. scTSS enables joint analysis of multiple single-cell samples, starting with TSS cluster prediction and quantification, followed by differential TSS usage analysis. It employs a Binomial generalized linear mixed model to accurately and efficiently detect differential TSS usage. We demonstrate the utility of scTSS through its application in analyzing transcriptional initiation from single-cell data of two distinct diseases. The results illustrate scTSS's ability to discern alternative TSS usage between different cell types or biological conditions and to identify cell subpopulations characterized by unique TSS-level expression profiles.

Transcription Initiation Site↗
PubMed1999

Late follow-up of femoral head avascular necrosis managed by intertrochanteric osteotomy & bone grafting.

A prospective study was carried out on fifty hips in forty-eight patients with Ficat stage III (Steinberg stage IV) avascular necrosis (head deformity evident on plain x-ray) involving the supero-ventral segment. Mean age was 33 +/- 8 years (mean and standard deviation). There were thirty-six male and twelve female patients. Followup was 3-14 years (mean 8 years). This study precluded patients who were more than 45 years old, had an underlying condition requiring continued chemotherapy or cortisone, who had extensive dorsal (posterior) head segment involvement or those who were poorly motivated. Avascular necrosis was associated with alcohol in 35% of hips, trauma in 26% and 39% were idiopathic. One pregnancy related case was included in the latter subgroup. Curettage of the avascular segment and impaction of the bone graft was performed via subcapital fenestration of the anterior femoral neck. Pain was the presenting symptom in all cases. The mean pre-operative Harris hip score was 36 points and the mean score at last assessment was 87 points. Seven hips (14%) failed, failure implied conversion to a hip replacement or a Harris hip score of less than 70 points. Failures were seen within the first 3 years after osteotomy. Kaplan Meyer Survivorship analysis demonstrated an overall survivorship probability of 86% at 14 years. One patient died 10 years post surgery, the head was retrieved for histological study. Statistical study (Mann-Whitney U test) was carried out to determine factors related to failure. Of significance were age of the patient at time of osteotomy, contralateral hip involvement and size of the lesion. X ray studies of the femoral head included measurement of the necrotic angle, evaluation of restoration and maintenance of head contour and graft incorporation or stabilisation. Subsequent CAT scan studies enabled accurate quantification and siting of the avascular segment. Secondary x ray degenerative changes of the joint tended to manifest with time but these changes had little bearing on the clinical outcome. Osteotomy does have a measure of unpredictability, but in the appropriate case a high incidence of satisfactory results would be anticipated.

Adult↗
PubMed2002

[Computed tomographic analysis of humeral retrotorsion and glenoid retroversion].

PURPOSE OF THE STUDY: Analysis of the anatomic relations of the humeral head and the glenoid cavity is particularly important for clinical study of shoulder arthroplasty and glenohumeral instability. Analysis of humeral retroversion and glenoid retroversion is quite difficult and data in the literature are scarse. We conducted a computed tomography (CT) analysis of stable shoulders to detail retroversion of the entire height of the glenoid cavity and to measure humeral retrotorsion using two comparative methods. We also compared glenoid retroversion and humeral retrotorsion observed in individual subjects. MATERIAL AND METHODS: This prospective study used a standardized CT analysis method. Both shoulders of 30 persons free of glenohumeral instability were studied. Two methods, described by Dähnert and Bernageau, were used to analyze humeral retrotorsion. The Benageau method was used to analyze glenoid retroversion. RESULTS: According to the Dähnert method, humeral retrotorsion was 10 degrees +/- 13 degrees; it was 24 degrees +/- 13 degrees with the Bernageau method; data dispersion was 60 degrees and 65 degrees respectively. According to the Dähnert method, retrotorsion was more pronounced on the dominant side compared with the non-dominant side. There was a significant correlation between retrotorsion values for the two sides. For 95% of the shoulders, glenoid retorversion decreased progressively from the superior part of the glenoid cavity (12.8 degrees +/- 6.4 degrees ) to the lower part (3.1 degrees +/- 4.4 degrees ). Glenoid retroversion was greater on the dominant side. For 21 of the 30 persons (70%), there was a significant correlation between retroversion for the two sides. Correlation coefficients between glenoid retroversion and humeral retrotorsion were negative. Greater humeral retrotorsion was thus related with less pronounced glenoid retroversion and vice versa. DISCUSSION: This study allowed quantification of glenoid retroversion and humeral retrotorsion. There is a spiral twist in the joint surface of the glenoid cavity with progressive decrease in glenoid retorversion from the upper to the lower part of the cavity for 95% of the shoulders. To our knowledge, this spiral twist in the glenoid cavity is not taken into consideration in any of the currently available implants. The correlation for both parameters between the right and left side is probably determined genetically. The influence of dominance could be explained by adaptation to more or less pronounced stress. The negative correlation between humeral retrotorsion and glenoid retroversion would improve glenohumeral stability. A comparative study with unstable shoulders would be required to verify this hypothesis. The validity of the Dähnert method for assessing humeral retorversion is, in our opinion, insufficiently established. The Bernageau method, which provides a direct measurement, appears to be preferable despite the difficulty in identifying anatomic landmarks.

Anthropometry↗
PubMed1995

Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

Animals↗
PubMed1999

Surface roughness quantification of CoCrMo implant alloys.

The articulating surfaces of CoCrMo alloy wear specimens and retrieved femoral components of artificial total knee joints are subject to uneven wear. A repeatable and reliable measurement method is necessary to evaluate the surface damage. In this study, the surface roughness of CoCrMo alloy specimens subjected to in vitro third-body wear, and retrieved femoral components of knee joints were analyzed using a white light interference surface profilometer. Each third-body wear specimen was divided into a 19x19 grid of 1-mm(2) squares (361 squares) and each femoral condyle of retrieved specimens was divided into two 10x10 grids of 1-mm(2) squares (100 squares). The surface roughness average (Ra) and root mean square roughness (RMS) were measured for each of the squares. The average of all points measured was defined as the true surface roughness mean (TSRM). Measurements were then performed on 40-60 (in vitro specimens) or 30 (retrieved specimens) randomly selected points on each surface and a cumulative average was calculated. The cumulative average surface roughness value from only a few (5-15) measurement points generated large deviations (>40%) from the TSRM, but converged to the TSRM as the number of measurements increased. The number of randomly selected points necessary for the cumulative average roughness to be within 10% of the TSRM was defined as the representative measurement number (RMN). The RMN for the third-body wear specimens (surface area of 573 mm(2)) was 40 points, and the RMN for the retrieved femoral components (surface area of 100 mm(2)) was 20 points. To obtain the cumulative surface roughness average within a desired percentage of the TSRM, it is important to define or experimentally determine the critical minimum number of measurements, RMN. Several types of measurements may be necessary to understand wear and damage on metal components of artificial knee joints. The TSRM represents a consistent and reproducible measure of surface damage, and a starting point to develop appropriate measurement protocols to quantify damage on a specific surface.

Arthroplasty, Replacement, Knee↗
PubMed2006

Quantification of patella position by ultrasound scanning and its criterion validity.

Altered position of the patella has been associated with patellofemoral joint pain. The main techniques used for assessment of position are either expensive or invasive; there are limited reports of the use of ultrasound (US) scanning to assess patella position. The aim of this study was to establish the validity of a measure of patella position using US scanning compared with those found using magnetic resonance imaging (MRI). MRI and US scans were taken of 20 subjects and analyzed using previously described methods. The correlation between patella position assessed by US scan and lateral patella displacement on MRI showed a good statistically significant correlation (r = 0.64, p = 0.003). The correlation between the patella position assessed by US scan and the equivalent measure on MRI showed an excellent statistically significant correlation (r = 0.78, p = 0.0001). The method described has shown US scanning to be a reliable measure of patella position, with strong criterion validity compared with MRI measures.

Adolescent↗
PubMed2000

Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys.

The thymus is the primary organ responsible for the production of mature TCR alpha / beta T cells. Quantification of a DNA excision circle that is produced during TCR rearrangement, termed a signal joint TCR rearrangement excision circle (sjTREC) can be used as a measure of thymic function. Here sjTREC measurement has been applied to two monkey species used as animal models of human disease, rhesus macaques (Asian origin) and sooty mangabeys (African origin). Initial PCR analysis determined that the TCR deltaRec-PsiJalpha rearrangement leading to sjTREC formation occurs in both species. Primers to a DNA sequence conserved in macaques, mangabeys and humans were used in a quantitative competitive PCR assay to quantify sjTREC. We found that as in humans, sjTREC in these two monkey species decline with age. sjTREC are first generated in thymocytes during the early stages of TCR rearrangement. Lymph node CD4(+) and CD8(+) T cells contain more sjTREC than peripheral blood T cell populations, suggesting that recent thymic emigrants home to the lymphoid tissues. The sjTREC level is significantly higher within the peripheral blood CD4(+) and CD8(+) T cells of mangabeys compared to macaques. Removal of the thymus in four macaques led to a profound decrease in peripheral blood sjTREC level by 1 year post-thymectomy, indicating the lack of a significant extra-thymic source of peripheral naive T cells in macaques. Our results indicate that production, trafficking, and proliferation of recent thymic emigrants in these two monkey species represents a useful animal model system for understanding human immunological disorders.

Aging↗
PubMed2000

Evaluation of clinical tests used in classification procedures in pregnancy-related pelvic joint pain.

Pain in the pelvic joints and lower back, a major problem for pregnant women, has proved resistant to precise measurement and quantification. To develop a classification system, the clinical tests used must be able to separate pelvic from low back pain; they must also have a high inter-examiner reliability, sensitivity and specificity, and preferably be easy to perform. The aim of this study was to describe a standardised way of performing tests for examining the pelvis, and to evaluate inter-examiner reliability, and establish the sensitivity and specificity of 15 clinical tests. It was designed as a longitudinal, prospective, epidemiological cohort study. First, 34 pregnant women were examined by blinded examiners to establish inter-examiner reliability. Second, a cohort of 2269 consecutive pregnant women, each responded to a questionnaire and underwent a thorough and highly standardised physical examination (15 tests with 48 possible responses) of the pelvic joints and surrounding areas. The 535 women who reported daily pain from the pelvic joints and had objective findings from the joints were divided, according to symptoms, into four classification groups and one miscellaneous group. The results of the study showed inter-examiner agreement of the tests was high, calculated in percentage terms, at between 88 and 100%. Using the Kappa coefficient, most tests kept the high agreement: six tests had an inter-examiner agreement of between 0.81 and 1.00, three between 0.61 and 0.80, and two between 0.60 and 0.41. Five tests showed superior sensitivity. The specificity of the tests was between 0.98 and 1.00, except the value for pelvic topography, which was 0.79. These results show that it is possible to standardise examination and interpretation of clinical tests of the pelvic joints, resulting in a high degree of sensitivity, specificity and inter-examiner reliability.

Arthralgia↗
PubMed1998

Somatostatin immunoreactivity in bone and joint tissues.

Using immunoelectron microscopy we have investigated the presence of somatostatin in normal bone and joint tissues. We observed somatostatin labeling in the myelinated nerve fibers of the periosteum, the bone marrow cells and in the mature bone matrix but only slightly in the synovial cells. Quantification of somatostatin in bone tissue by radioimmunoassay showed highest levels in bone marrow followed by periosteum and cortical bone. These findings suggest a role for somatostatin in bone and joint physiology.

Animals↗
PubMed2006

Quantification of intrinsic and reflexive properties during multijoint arm posture.

This study estimates intrinsic and reflexive properties of single- and two-joint muscles acting around the human shoulder, elbow and wrist joint during posture maintenance. External force disturbances were applied to the hand while subjects (n = 5) were instructed to minimize their hand displacement amplitude in a horizontal plane. To examine how the nervous system modifies intrinsic and reflexive muscle properties, we varied external damping, disturbance power and arm configuration. A new identification method is introduced to quantify a large set of model parameters describing intrinsic, activation and reflexive properties, the latter representing afferent feedback gains from muscle spindles and Golgi tendon organs. Consistent estimates were found for the gains of the different types of reflex pathways. The results showed that intrinsic visco-elasticity of shoulder muscles was minimal, whereas reflexive feedback was largest compared to the elbow and wrist joint. Intrinsic and reflexive properties of the two-joint shoulder-elbow muscles were larger than the two-joint elbow-wrist muscles. Contrasting to previous single-joint studies, the reflex gains did not vary with the experimental conditions. It is concluded that during redundant multijoint posture maintenance, the mechanical properties are efficiently controlled on the joint level and not on the endpoint level.

Adult↗
PubMed1998

Quantification of the bone-related mRNAs at the bone/prosthetic interface.

Aseptic loosening is one of the major reasons for failure of joint prostheses. The periprosthetic tissue has previously been described microscopically; however, little work has been devoted towards quantitating genes expressed by cells at the materials/tissue interface. This study aims to characterize the phenotypic expression of osteoblasts and test the feasibility of quantifying the level of gene expression in periprosthetic tissue sections by combining in situ hybridization and image analysis techniques. There are many factors to consider when quantifying mRNA, in that comparing labeling between different cDNA probes, these should have comparable length and base comparison. The probes should be labeled with the same specific activity, that is the amount of probe to label added is the same, both between different probes and between batches of the same probe. Chromagen color reactions are variable in that the color development is not always linear and more likely follows a sigmoidal curve. Samples should only be compared when it is known that the reaction has been in the linear range. The image analysis of such staining introduces further factors which should be considered and controlled. Color analysis is a very complex problem with respect to reproducibly analyzing histological sections. The brightness component of the image should be independent of the colors within the image, in conventional RGB (red, green and blue) signalling mode this is not possible, while when using HSI (hue saturation and intensity) mode this becomes possible, and factors like staining intensity and brightness of the image become much more accountable and controllable. With these factors identified, we consider that the quantitative image analysis approach does allow comparison of patterns of bone-related mRNAs and demonstrates differences in expression in these osteogenic factors depending on distance from the prosthesis, tissue type, patient and device.

Journal Article↗
PubMed2005

Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration.

OBJECTIVE: To determine whether the focal susceptibility to cartilage degeneration in joints is related to a differential response to cytokine stimulation. METHODS: Compare aggrecan and collagen catabolism in in-vitro models of cartilage degradation induced by retinoic acid (RA), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF) and IL-1 plus oncostatin M (OSM). Glycosaminoglycan (GAG) and hydroxyproline (HyPro) quantification and Western immunoblot analyses of aggrecan and collagen degradation products were undertaken in explant cultures of normal cartilage from regions of equine joints with a known high and low susceptibility to degeneration in disease. RNA isolation and semi quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis were performed to determine the expression of aggrecanases, matrix metalloproteinases (MMPs) and their inhibitors. RESULTS: Although the rate of basal cartilage aggrecan turnover was dependent on joint region there was no difference in the response of different cartilages to cytokines. Individual animals did show a significant difference in the response of certain cartilages to cytokines, with both decreased and increased aggrecan loss in cartilage with a low susceptibility to degeneration. Aggrecan release in both short- and long-term cultures from all cartilages was associated with increased cleavage by aggrecanases rather than MMPs. There was a poor correlation between expression of aggrecanases, MMPs or their inhibitors and cytokine induced aggrecan catabolism. IL-1 alone was able to stimulate collagen breakdown in equine articular cartilage and surprisingly, significantly more collagen loss was induced in cartilage from regions less susceptible to degeneration. CONCLUSIONS: Collectively, these studies suggest that a regional difference in response to catabolic cytokines is unlikely to be a factor in the initiation of focal cartilage degeneration in osteoarthritis (OA).

Aggrecans↗
PubMed2005

Quantification of soft tissue artefact in motion analysis by combining 3D fluoroscopy and stereophotogrammetry: a study on two subjects.

BACKGROUND: Soft tissue artefact is the most invalidating source of error in human motion analysis using optoelectronic stereophotogrammetry. It is caused by the erroneous assumption that markers attached to the skin surface are rigidly connected to the underlying bones. The quantification of this artefact in three dimensions and the knowledge of how it propagates to relevant joint angles is necessary for the interpretation of gait analysis data. METHODS: Two subjects, treated by total knee replacement, underwent data acquisition simultaneously with fluoroscopy and stereophotogrammetry during stair climbing, step up/down, sit-to-stand/stand-to-sit, and extension against gravity. The reference 3D kinematics of the femur and tibia was reconstructed from fluoroscopy-based tracking of the relevant prosthesis components. Soft tissue artefact was quantified as the motion of a grid of retro-reflecting makers attached to the thigh and shank with respect to the underlying bones, tracked by optoelectronic stereophotogrammetry. The propagation of soft tissue artefact to knee rotations was also calculated. FINDINGS: The standard deviation of skin marker trajectory in the corresponding prosthesis-embedded anatomical frame was found up to 31 mm for the thigh and up to 21 mm for the shank. The ab/adduction and internal/external rotation angles were the most affected by soft tissue artefact propagation, with root mean square errors up to 192% and 117% of the corresponding range, respectively. INTERPRETATIONS: In both the analysed subjects the proximal thigh showed the largest soft tissue artefact. This is subject- and task-specific. However, larger artefact does not necessarily produce larger propagated error on knee rotations. Propagated errors were extremely critical on ab/adduction and internal/external rotation. These large errors can nullify the usefulness of these variables in the clinical interpretation of gait analysis.

Aged↗