Rapidly destructive osteoarthritis of the hip joint: a case series

<p>Abstract</p> <p>Background</p> <p>Rapidly destructive arthrosis of the hip is a rare and incompletely understood disorder with scarce literature about variations in natural history within a population.</p> <p>Methods</p> <p>A series of cases from North Wales with rapid progressive joint destruction and extensive subchondral bone loss in the femoral head and acetabulum are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities.</p> <p>Results</p> <p>Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average 14 months) in 18 patients documented rapid hip destruction, involvement being unilateral in 13 cases. All patients underwent total hip arthroplasty, and osteoarthritis was confirmed at pathologic examination.</p> <p>Conclusion</p> <p>The authors postulate that these cases represent an uncommon subset of osteoarthritis and regular review, both clinically and radiologically, are required to assess speed of progression and prevent rapid loss of bone stock without the surgeon being aware. These cases are unsuitable for being placed on long waiting list due to technical difficulties in delayed surgery and compromised outcome following surgery.</p

Articular cartilage mineralization in osteoarthritis of the hip

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the frequency of articular cartilage calcification in patients with end-stage hip OA. Further, its impact on the clinical situation and the OA severity are analyzed.</p> <p>Methods</p> <p>Eighty patients with OA of the hip who consecutively underwent total hip replacement were prospectively evaluated, and 10 controls were included. The patients' X-rays were analyzed for the presence of articular cartilage mineralization. A Harris Hip Score (HHS) was preoperatively calculated for every patient.</p> <p>Slab specimens from the femoral head of bone and cartilage and an additional square centimeter of articular cartilage from the main chondral defect were obtained from each patient for analysis of mineralization by digital contact radiography (DCR). Histological grading was also performed. In a subset of 20 patients, minerals were characterized with an electron microscope (FE-SEM).</p> <p>Results</p> <p>Calcifications were seen in all OA cartilage and slab specimens using DCR, while preoperative X-rays revealed calcification in only 17.5%. None of the control cartilage specimens showed mineralization. There was a highly significant inverse correlation between articular cartilage calcification and preoperative HHS. Histological OA grade correlated positively with the amount of matrix calcification. FE-SEM analysis revealed basic calcium phosphate (BCP) as the predominant mineral; CPPD crystals were found in only two patients.</p> <p>Conclusions</p> <p>Articular cartilage calcification is a common event in osteoarthritis of the hip. The amount of calcification correlates with clinical symptoms and histological OA grade.</p

Association and Interaction Analyses of GABBR1 and GABBR2 with Nicotine Dependence in European- and African-American Populations

Previous studies have demonstrated that the γ-aminobutyric acid type B (GABAB) receptor plays an essential role in modulating neurotransmitter release and regulating the activity of ion channels and adenyl cyclase. However, whether the naturally occurring polymorphisms in the two GABAB receptor subunit genes interact with each other to alter susceptibility to nicotine dependence (ND) remains largely unknown. In this study, we genotyped 5 and 33 single nucleotide polymorphisms (SNPs) for GABAB receptor subunit 1 and 2 genes (GABBR1, GABBR2), respectively, in a sample of 2037 individuals from 602 nuclear families of African- American (AA) or European-American (EA) origin. We conducted association analyses to determine (1) the association of each subunit gene with ND at both the individual SNP and haplotype levels and (2) the collective effect(s) of SNPs in both GABAB subunits on the development of ND. Several individual SNPs and haplotypes in GABBR2 were significantly associated with ND in both ethnic samples. Two haplotypes in AAs and one haplotype in EAs showed a protective effect against ND, whilst two other haplotypes in AAs and three haplotypes in EAs showed a risk effect for developing ND. Interestingly, these significant haplotypes were confined to two regions of GABBR2 in the AA and EA samples. Additionally, we found two minor haplotypes in GABBR1 to be positively associated with Heaviness of Smoking Index (HSI) in the EA sample. Finally, we demonstrated the presence of epistasis between GABBR1 and GABBR2 for developing ND. The variants of GABBR1 and GABBR2 are significantly associated with ND, and the involvement of GABBR1 is most likely through its interaction with GABBR2, whereas GABBR2 polymorphisms directly alter susceptibility to ND. Future studies are needed with more dense SNP coverage of GABBR1 and GABBR2 to verify the epistatic effects of the two subunit genes

Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Applications of Data Mining in Constraint-Based Intelligent Tutoring Systems

This report describes an investigation into the use of data mining processes, with respect to student interaction with Intelligent Tutoring Systems (ITSs). In particular, a framework for the analysis of constraint-based tutors is developed. The framework, which involves three phases (collection, transformation and analysis), is implemented to extract patterns in student interaction with an ITS called SQL-Tutor. This investigation identifies alternative techniques in each of the three phases, and discusses the advantages and disadvantages of each approach. The report also highlights a number of key knowledge areas in which the mining process can be used to find rules, relationships and patterns. A range of typical findings from an existing tutoring system are used to illustrate each of these knowledge areas. It is envisaged that the knowledge that is extracted using these techniques will be used to improve the tutoring systems

2.2 Example Insight Problems................................ 10

Insight problems are problems which are simple to state but relatively difficult to solve, and require some sort of ‘insight ’ (creative thinking) to solve them. This insight requires looking at the problem or some objects within the problem in an unconventional way, or some other form of restructuring the problem. This project looks at the impacts of providing feedback in two contrasting ways to people attempting to solve one insight problem, the nine-dots problem. Feedback is given in either a positive format – telling them what they should do, or a negative format – telling them what they should not do. The relative benefits of these two forms of feedback are evaluated, and it is concluded that a positive style is better because people who receive feedback phrased in a positiv