Sexual dimorphism in peri-articular tissue anatomy - More keys to understanding sex-differences in osteoarthritis?

Objective: Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes remains enigmatic. Albeit sex within humans cannot be reduced to female/male, this review focusses to the sexual dimorphism of peri-articular tissues, given lack of literature on non-binary subjects. Methods: Based on a Pubmed search and input from experts, we selected relevant articles based on the authors' judgement of relevance, interest, and quality; no "hard" bibliometric measures were used to evaluate the quality or importance of the work. Emphasis was on clinical studies, with most (imaging) data being available for the knee and thigh. Results: The literature on sexual dimorphism of peri-articular tissues is reviewed: 1) bone size/shape, 2) subchondral/subarticular bone, 3) synovial membrane and infra-patellar fad-pad (IPFP), 4) muscle/adipose tissue, and 5) peri-articular tissue response to treatment. Conclusions: Relevant sex-specific differences exist for 3D bone shape and IPFP size, even after normalization to body weight. Presence of effusion- and Hoffa-synovitis is associated with greater risk of incident knee osteoarthritis in overweight women, but not in men. When normalized to bone size, men exhibit greater muscle, and women greater adipose tissue measures relative to the opposite sex. Reduced thigh muscle specific strength is associated with incident knee osteoarthritis and knee replacement in women, but not in men. These observations may explain why women with muscle strength deficits have a poorer prognosis than men with similar deficits. A "one size/sex fits all" approach must be urgently abandoned in osteoarthritis research.

Sexual dimorphism in articular tissue anatomy - Key to understanding sex differences in osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) prevalence and incidence varies between women and men, but it is unknown whether this follows sex-specific differences in systemic factors (e.g. hormones) and/or differences in pre-morbid joint anatomy. We recognize that classifications of sex within humans cannot be reduced to female/male, but given the lack of literature on non-binary individuals, this review is limited to the sexual dimorphism of articular morphotypes. METHODS: Based on a Pubmed search using relevant terms, and input from experts, we selected articles based on the authors' judgment of their relevance, interest, originality, and scientific quality; no "hard" bibliometric measures were used to evaluate their quality or importance. Focus was on clinical rather than pre-clinical studies, with most (imaging) data being available for the knee joint. RESULTS: After introducing "sexual dimorphism", the specific literature on articular morphotypes is reviewed, structured by: radiographic joint space width (JSW), meniscus, ligaments, articular cartilage morphology, articular cartilage composition and deformation, and articular tissue response to treatment. CONCLUSIONS: Sex-specific differences were clearly observed for JSW, meniscus damage, ligament size, and cartilage morphometry (volume, thickness, and surface areas) but not for cartilage composition. Ligament and cartilage measures were smaller in women even after matching for confounders. Taken together, the findings indicate that female (knee) joints may be structurally more vulnerable and at greater risk of OA. The "one size/sex fits all" approach must be abandoned in OA research, and all observational and interventional studies should report their results for sex-specific strata, at least in pre-specified secondary or post-hoc analyses.

How the Ends of Bones Evolve and What They Do: The Anatomical and Biomechanical Perspective.

Skeletal ossification occurs either directly within mesenchymal tissues or indirectly through a template of hyaline cartilage. Between the epiphyses and diaphyses of long bones, hyaline cartilaginous growth plates remain and constitute the progenitor cell reservoir from which the tissue develops toward the diaphysis and determines longitudinal bone size. Growth plates exhibit a characteristic architecture with columnar cell organization and different zonal morphology. The cells increase their volume toward the diaphysis, and eventually the longitudinally arranged septa of extracellular matrix mineralize. Finally, the mineralized cartilage matrix is replaced by lamellar bone. The extracellular matrix is rich in glycosaminoglycans, proteoglycans, and collagen II; at the edges of the growth plates, collagen I, III, and collagen X, especially at the mineralization front, are also present.The geometry of the growth plates is regulated by the local mechanical environment. In general, all plates orient themselves perpendicular to the resulting compressive force vector; grooves, ridges, and lateral angulations are adaptations to withstand shear forces acting on the growth plates. The final shape of the fully grown bone is determined not only by the epiphyseal growth plates but also by their apophyseal counterpart. Both structures respond in a comparable fashion to the local mechanical environment.

The mechanical properties of fresh versus fresh/frozen and preserved (Thiel and Formalin) long head of biceps tendons: A cadaveric investigation.

Human cadaveric specimens commonly serve as mechanical models and as biological tissue donors in basic biomechanical research. Although these models are used to explain both in vitro and in vivo behavior, the question still remains whether the specimens employed reflect the normal in vivo situation. The mechanical properties of fresh-frozen or preserved cadavers may differ, and whether they can be used to reliably investigate pathology could be debated. The purpose of this study was to therefore examine the mechanical properties of cadaveric long biceps tendons, comparing fresh (n=7) with fresh-frozen (n=8), formalin embalmed (n=15), and Thiel-preserved (n=6) specimens using a Universal Testing Machine. The modulus of elasticity and the ultimate tensile strength to failure was recorded. Tensile failure occurred at an average of 12N/mm2 in the fresh group, increasing to 40.1N/mm2 in the fresh-frozen group, 50.3N/mm2 in the formalin group, and 52N/mm2 in the Thiel group. The modulus of elasticity/stiffness of the tendon increased from fresh (25.6MPa), to fresh-frozen (55.3MPa), to Thiel (82.5MPa), with the stiffest being formalin (510.6MPa). Thiel-preserved and formalin-embalmed long head of biceps tendons and fresh-frozen tendons have a similar load to failure. Either the Thiel or formalin preserved tendon could therefore be considered as alternatives for load to failure studies. However, the Young's modulus of embalmed tendons were significantly stiffer than fresh or fresh frozen specimens, and these methods might be less suitable alternatives when viscoelastic properties are being investigated.

Development of the competency-based medical curriculum for the new Augsburg University Medical School.

Aim: With the resolution from April 28, 2014, the Bavarian state government in Germany decided to found a new medical school at Augsburg University, thereby requiring the development of a competency-based medical curriculum. Methods: Two interdisciplinary groups developed a spiral curriculum (following Harden) employing the model of Thumser-Dauth & Öchsner. The curriculum focuses on specifically defined competencies: medical expertise, independent scientific reasoning, argumentation and scholarship, as well as communication skills. Results: The spiral curriculum was developed as a hybrid curriculum. Its modular structure incorporates the mandatory subjects required by the German regulations for medical licensure (Approbationsordnung) into organ- and system-centered blocks which are integrated both horizontally and vertically. Basic preclinical sciences are covered in the blocks "Movement," "Balance" and "Contact." The clinical sciences are organized according to six pillars (conservative medicine, surgical medicine, men's-women's-children's medicine, the senses, the nervous system and the mind, and general medicine) which students revisit three times each over the course of the program. A longitudinal clinical course incorporates interdisciplinary education. A particular focus is on scientific education encompassing a longitudinal course in the sciences (including interdisciplinary classes with other university departments), block practicums, and two scientific projects. Conclusion: It is not only the degree of integration und intensity of the Augsburg University undergraduate medical degree program, but also its targeted advancement of academic, social and communication skills that have not yet been realized to such an extent elsewhere in Germany. On July 8, 2016, the German Council of Science and Humanities unanimously gave this concept a positive evaluation. Future research will examine and evaluate the Augsburg medical curriculum and the impact of the new medical school on the hospital and university in Augsburg.

Diffusion-tensor imaging of human articular cartilage specimens with early signs of cartilage damage.

PURPOSE: To assess the use of diffusion-tensor (DT) imaging of articular cartilage to detect and grade early cartilage damage in human specimens with early signs of cartilage damage. MATERIALS AND METHODS: This study was approved by the institutional review board. Forty-three cartilage-on-bone samples drilled from 21 human patellae were examined with 17.6-T magnetic resonance (MR) imaging and a diffusion-weighted spin-echo sequence (spatial resolution, 50 × 100 × 800 µm). Subsequently, samples underwent histologic analysis with safranin O staining. Cartilage damage on safranin O histologic slides was quantified with Osteoarthritis Research Society International (OARSI) grades; grades ranged from 0 (healthy) to 6 (bone remodeling). Maps of longitudinal diffusivity (λ(l)), transverse diffusivity (λ(t)), mean diffusivity (MD), and fractional anisotropy (FA) were calculated. Cartilage was segmented, and region of interest (ROI) analysis was performed and compared with histologic findings. Significant differences in MR parameters between the OARSI groups were assessed with the Tukey test. The value of DT imaging in the diagnosis and grading of cartilage damage was assessed with logistic regression analysis. RESULTS: Samples had OARSI grades of 0 (n = 14), 1 (n = 11), 2 (n = 12), 3 (n = 4), and 4 (n = 2). Samples with an OARSI grade greater than 0 had significantly increased λ(l), λ(t), and MD (7%-25% increase) in the superficial cartilage growing deeper into cartilage with increasing OARSI grade. Samples with an OARSI grade greater than 0 showed significantly decreased FA in the deep cartilage (-25% to -35% decrease), suggesting that changes in the collagen architecture may occur early in cartilage degradation. DTI showed excellent performance in the detection of cartilage damage (accuracy, 0.95; 41 of 43 samples) and good performance in the grading of cartilage damage (accuracy, 0.74; 32 of 43 samples). CONCLUSION: DT imaging of articular cartilage can enable physicians to detect and grade early cartilage damage.

Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy.

OBJECT: To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage. MATERIAL AND METHODS: DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture. RESULTS: From the articular surface to the bone-cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P < 0.01, r (2)=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness. CONCLUSIONS: Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.

Change of diffusion tensor imaging parameters in articular cartilage with progressive proteoglycan extraction.

OBJECTIVE: To investigate changes of diffusion tensor imaging (DTI) parameters (mean apparent diffusion coefficient [ADC], fractional anisotropy [FA], and first eigenvector) with increasing proteoglycan (PG) extraction of articular cartilage. MATERIAL AND METHODS: Twelve cylindrical cartilage-on-bone samples were drilled from 4 human patellae (3 per patella). Each sample was divided into 2 pieces. One piece underwent histologic examination to assess the PG content of the native sample by safranin-O staining and its collagen architecture by polarized light microscopy. The other underwent magnetic resonance imaging (MRI) at 17.6 T for DTI measurement. After MRI, 2 of the 3 samples from each patella were immersed in a dilute trypsin solution (0.1 mg/mL), whereas the third sample was kept as a negative control in physiological saline. After incubation (6, 48, 72, and 96 hours), the samples were reimaged, stained for PG content and for the collagen orientation. Maps of ADC, FA, and the orientation of the first eigenvector as well as histology were available for each sample before and after incubation. RESULTS: PG loss led to increased ADC and reduced safranin-O staining from the articular surface to the bone-cartilage interface. A significant correlation (r(2) = 0.86, P < 0.01) was observed between the change in bulk ADC and PG loss. Regional analysis from the articular surface to the tide mark demonstrated depth dependent significant correlations of ADC and PG loss. FA and first eigenvector as well as polarized light microscopy showed only small changes in the order of magnitude of measurement errors, not correlating with PG loss. CONCLUSION: Mean diffusivity evidence by the ADC is linearly correlated to progressive PG extraction in articular cartilage. FA and the first eigenvector seem to be specific to the collagen architecture of cartilage. DTI has the potential to become a valuable biomarker for the workup of cartilage degeneration in osteoarthritis, since evaluation of the PG content and collagen architectural properties of cartilage can be performed with a single, non­contrast-enhanced proton-based MRI measurement.

Spatial patterns of cartilage loss in the medial femoral condyle in osteoarthritic knees: data from the Osteoarthritis Initiative.

The objective of this study was to develop a technique for analyzing spatial patterns of cartilage loss in the medial femoral condyle (MF), and to study MF cartilage loss in participants of the Osteoarthritis Initiative. Using a 0.7 mm sagittal double echo at steady state (DESS) sequence, 160 osteoarthritic knees from 80 participants with varying degrees of medial joint space narrowing were imaged at baseline and 1-year follow-up. MF cartilage was segmented and cartilage loss determined. Rate of change varied significantly (P = 0.0067) along the anterior-posterior extension of the MF, with the greatest changes (-45 microm, -2.7%) observed 30-60 degrees posterior to the trochlear notch. The rate was greater in the central MF after excluding peripheral aspects of the MF from analysis. Sensitivity to change was greatest at 45-75 degrees (standardized response mean = -0.32) but was minimally affected by medial-lateral trimming. In conclusion, the greatest sensitivity to change was achieved when analyzing the posterior aspect of the central, weight-bearing MF.

Morphological adaptation of the tarso-metatarsal joints onto load transmission in the foot.

PURPOSE: Undefined middle foot pain among older individuals is an increasingly problem. Thereby the tarso-metatarsal joints (Lisfranc's joint, TMT joints) are particularly important for foot structure. The aim of this study was to obtain into force transmission in TMT joints by analysing degenerative morphological changes (DMC) of the articular cartilage and subchondral density patterns. MATERIALS AND METHODS: We used seven formalin-fixed foot preparations (average age 80.8) from the undergraduate dissection course. Applying the Collins schema, localisation of cartilaginous surface DMC was examined. For showing subchondral density patterns, the well-established method of CT-osteoabsorptiometry (CT-OAM) was used. RESULTS: The cartilaginous surface DMCs were frequently located at the medial edges. Maximum density areas were found at the medial and dorsal edges. There was a clear correlation of topical cartilage degeneration and subchondral density. CONCLUSION: In healthy feet, force transmission in the TMT joints appears to occur via the dorsal and medial edges. Considering the correlation of topical cartilaginous surface DMC and subchondral density patterns, clinical application of CT-OAM seems to be recommendable in the case of undefined middle foot pain.

Student learning preferences and the impact of a multimedia learning tool in the dissection course at the University of Munich.

How do students use multimedia tools to support their learning during a gross anatomy dissection course? We investigated this question in the anatomic dissection course for first year medical students at the University of Munich (n=850) by giving all participating students access to an anatomical multimedia CD-ROM. The use of this multimedia learning tool was voluntary and it was not essential for the end-of-course examination. After the examination, two questionnaires (return rate first questionnaire n(1)=347, approximately 41%; return rate second questionnaire n(2)=644, approximately 76%) were given to the surveyed students with the following content: evaluation of the multimedia learning tool, details about the usage of different kinds of available learning media, and finally an evaluation of the media used for teaching during the course. Furthermore we collected personal data from participants such as age, gender and the score achieved in the examination. Classical textbooks and anatomical atlases were used by 84% of students for preparation. The multimedia learning tool was used by 34% as an additional media for learning. The multimedia learning tool was not used alone. The data showed differences with regard to gender and performance of students, but not relating to age. Students rated the computer-specific features, e.g. three-dimensional (3D) models, virtual simulations, and an interactive quiz module, as major reasons for using the multimedia learning tool. Our results show that medical students use anatomic multimedia learning tools primarily as an additional medium for learning, and thus lead to the conclusion that the main learning media are still textbooks and anatomic atlases.

Mineralization density and apparent density in mandibular condyle bone.

OBJECTIVES: This study evaluated a method for determining the density and distribution of bone of mandibular condyles using proprietary computerized tomography (CT) software. STUDY DESIGN: Thirty-eight condylar specimens were investigated with a high-resolution multislice CT. The density was determined by using bone density analysis algorithms available within the proprietary software. Apparent density was estimated over the total cross-sectional area, the total trabecular bone area apart from the cortical fraction, and on individually selected points. Color-coded pictures were created to demonstrate density differences. RESULTS: The cortical bone presented significantly higher densities than the trabecular bone. The anterior cortical bone had significantly higher densities than the posterior. The central anterior cortical and the central trabecular areas showed significantly higher densities than the medial and lateral areas. CONCLUSION: This technique proved to be a valuable method for determination of the differences in density in the mandibular condyle. It shows potential in providing clinicians with an imaging modality for specific clinical use.

The trabecular architecture of the superior articular process of the lumbar spine (L2-S1).

The role of the facet joint in low back pain has gained public attention lately. The objective of our study was to investigate whether there is any difference in the adaptation of the cancellous bone in the superior articular process depending on the specific stress condition in different levels of the spine. Therefore, the trabecular structure of the superior articular processes of L2 and S1 of 15 cadavers (aged 63-100 years) were studied using muCT (micro-computer tomography). Each sample was divided into five sections, each of which containing 20% of the slices. The following structure parameters were compared between L2 and S1 as well as within each process; bone-volume-fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure-model-index (SMI) and degree of anisotropy (DA). Statistically significant differences were observed between L2 and S1 for the BV/TV, SMI, Tb.Th and Tb.N in superior 2 sections. BV/TV, Tb.Th and Tb.N were higher in S1 than in L2. The SMI is lower, and even negative in S1 compared to L2, showing a more plate-like structure. Within the articular process all structure parameters show a similar distribution in L2 and S1. BV/TV, Tb.N and DA decreased from cranial to caudal while Tb.Th was highest in the most cranial and caudal sections, with the lowest value in the middle. The SMI, on the other hand, increased from cranial to caudal displaying more rod-like structures. These results can be explained by the different stress the processes of the different spinal levels are exposed to as well as the specific motion patterns of the facet joint. The processes of the os sacrum are exposed to a higher axial and ventral load due to their location and the lumbosacral flexion. In addition the upper sections of each process experience higher stress peaks than the lower ones. Therefore, this study shows the material distribution within the cancellous bone adapts to these specific stress conditions the facet joints are exposed to.

[Concept, implementation and evaluation of an interfaculty Master of Medical Education Programme]. / Konzeption, Implementierung und Evaluation eines interfakultären Master of Medical Education Programms.

The implementation of new medical licensing regulations (AAppO 2003) was the starting point for radical curricular changes in all German medical schools. In 2004, the postgraduate and interfaculty Master of Medical Education (MME) degree programme was established at the University of Heidelberg under the auspices of the Medical Faculty Association (Medizinischer Fakultätentag, MFT) and supported by the Association for the Promotion of Science and Humanities in Germany (Stifterverband für die Deutsche Wissenschaft). This new degree programme is intended to train multipliers and leaders in medical education, to build a German-speaking network and to strengthen educational research. The eight one-week MME modules are organised by seven locations in Germany (Munich, Tuebingen, Muenster/Essen, Berlin, Heidelberg, Cologne, Dresden) and an annually changing international faculty. The instructor teams are composed of national and international experts. Major focal points include: curriculum development, education theory, teaching and exam methods, evaluations, team building and group dynamics, project management, leadership, and faculty development, as well as educational research. The modules are connected with each other longitudinally: each participant conducts a project to improve teaching in his or her own faculty and writes a master's thesis about an educational research project. Overall, the participants earn 60 ECTS (European Credit Transfer System) in the course of two years while working. So far 100 participants (25 per year) from 33 of 34 medical faculties have started the program and 19 participants (50% of the participants from Cohort 1, 29% of the participants from Cohort 2) completed the program. The evaluation of the individual modules showed a very high level of participant satisfaction. In two modules, the evaluation results demonstrated a need for change. In 2006, an external evaluation conducted by international experts positively highlighted the MME Programme structure as a leading example emphasizing all aspects of modern medical education, including relevant managerial skills. The MME Programme as a contribution to the professionalization of medical education in the German-speaking area has become firmly established. The impact of the MME Programme on the career development of its participants and the institutional development of the medical faculties still remains to be evaluated.

[Integration of a seminar on the anatomical basis of otorhinolaryngology (ENT) into the clinical course improves the confidence and performance of students in the clinical discipline]. / Die Integration eines Seminars uber anatomische Grundlagen der HNO-Heilkunde in den klinischen Unterricht verbessert die Leistungen der Studierenden im klinischen Fach.

A sound knowledge of the scientific basis of medicine is a prerequisite for successful learning and understanding of clinical issues. Teachers of clinical medicine, however, often complain that their students' knowledge on the scientific basis of medicine is too low. In the clinical curricula of most medical schools in Germany, students rely on self-directed learning efforts to optimize their knowledge of basic issues for the study of clinical medicine. Using anatomy and otorhinolaryngology (ENT) as an example, we have compared the effects of a structured seminar for recall of anatomical knowledge and its elaboration under clinical perspective with self-directed learning efforts of the same contents. Effects on clinical performance and students confidence were compared in a randomized trial. We found that the clinical performance of students was significantly higher (6.9%) in the seminar group compared with the control group. Furthermore, the students' self-estimation of clinical competence was increased in the seminar group and they were more content with their clinical course in ENT. Based on the design of the study we believe that the improvement of clinical performance was a longterm effect due to deeper understanding of the clinical problems among participants of the seminar. Irrespective of their experimental study group, most students asked for more integration of seminars on the scientific basis of medicine into the clinical curriculum. With the significant increase in clinical performance shown in this study and the limited effort needed for implementation, these seminars could be an efficient way to improve the quality of teaching in clinical medicine.

Detailed pathological changes of human lumbar facet joints L1-L5 in elderly individuals.

Facet joints play an important role in intervertebral load transmission and are crucial for rotational kinematics. Clinically, the role of facet joints as a possible source of low back pain is seen as controversial and at present is not sufficiently investigated. In this study, human lumbar facet (zygapopyhysial) joints from donors with advanced age were analyzed macroscopically, for degenerative changes. The aim was to determine the extent and morphology of degenerative changes in these joints. Lumbar facet joints (L1-L5) of 32 donors were studied (mean age 80.1+/-11.2 years). Joint capsules were carefully removed and joint surfaces (5 zones) examined using magnifying glasses and probes. In the result, the majority of facet joints showed cartilage defects of varying extent. Defects were located mostly at the margins of the articular surface, the central zone being relatively well preserved. Defect localization was different between superior (most cartilage defects in superior zone) and inferior (most defects inferiorly) facets. Further, defects were more severe caudal (level of L5) and in older persons. Osteophytes were present in up to 30%, located mostly at the latero-dorsal enthesis of the joint capsule on the superior facet. In conclusion, most margins of the articular facets are subject to degenerative changes in the lumbar spine of elderly persons, the topographical pattern being different in superior and inferior facets. This observation can be explained by the segmental motion patterns during extension/flexion movements of the facets. Sometimes, due to the marginal extension, it is obvious that not all changes can be assessed by CT or MRI.

An immunohistochemical study of the tissue bridging adult spondylolytic defects--the presence and significance of fibrocartilaginous entheses.

UNLABELLED: Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. METHODS: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. RESULTS: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. CONCLUSIONS: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament-i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic gap.

An immunohistochemical study of the extracellular matrix of the tarsal plate in the upper eyelid in human beings.

The superior tarsus is a plate of tissue that stiffens the upper eyelid, gives it support and determines its form. The purpose of the present study was to relate the composition of its extracellular matrix to its function and to report regional differences that may influence the activity of its Meibomian glands. Fourteen methanol-fixed specimens were cryosectioned for immunohistochemistry and labelled with a panel of monoclonal antibodies against a wide range of collagens, glycosaminoglycans and proteoglycans. Labelling was detected with avidin-biotin-peroxidase. A further six specimens were formalin-fixed for routine histology. The tarsal plate immunolabelled strongly for types I, III and VI collagen and for aggrecan, versican, tenascin, cartilage oligomeric matrix protein (COMP) together with a variety of glycosaminoglycans (notably chondroitin 6 sulphate). A region of strong labelling for aggrecan, dermatan sulphate and chondroitin 6 sulphate immediately surrounded the Meibomian glands. The site of labelling corresponded to a layer of acellular and amorphous matrix seen histologically that we have termed the 'territorial matrix'. The results suggested that the tarsal plate is a specialized connective tissue that is neither purely fibrous nor cartilaginous, yet has an aggrecan content that probably contributes to its stiffness. Its unique character highlights the challenge in choosing an ideal mechanical substitute. As patients with rheumatoid arthritis often have problems relating to tear film deficiency, the ability of aggrecan or COMP to act as autoantigens may be significant. An immune reaction directed against these molecules could alter tarsal gland function by interfering with the interaction between the glands and their territorial matrix.