A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Medicine (MMed). Johannesburg 2017 / BACKGROUND: The aim of the study was to assess whether African subjects with fragility fractures were being identified for assessment for osteoporosis on presentation to the orthopaedic department at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto. In addition, the recommendation for secondary prevention of disease for these subjects, was also assessed. METHOD: One hundred African subjects over the age of 50 years with fragility fractures were identified in the orthopaedic wards and clinics at CHBAH. These subjects were interviewed with two separate questionnaires addressing risk factors and education regarding osteoporosis, and whether further management was suggested. The first interview was conducted in June and July 2015. After 18 months, a follow up telephonic interview was conducted, in December 2016, with 37 of the original 100 subjects. RESULTS: Of the 100 subjects evaluated, 89 (89%) were asked at least one screening question. The most frequently asked question about risk factors for osteoporosis in the first interview, was regarding previous fractures and was asked of 61 (61%) of the 100 subjects. A further 37 (37%) of all subjects had been given advice regarding appropriate bone strengthening exercises to prevent osteoporosis. Only five subjects (5%) were asked to return for further assessment. The second interview showed that the most frequently asked question was regarding previous fractures in 24 (64.9%) of the 37 subjects and 18 (48.6%) of the 37 subjects had been advised to do bone strengthening exercises. Only two (5.4%) new subjects could confirm receiving a date to return for assessment. CONCLUSION: In this study, orthopaedic surgeons were proven to be inadequately assessing risk factors for osteoporosis and were infrequently referring patients for therapy. Orthopedic surgeons are often the only practitioners to see patients with fragility fractures and thus they have a crucial role in identifying and appropriately referring these patients for further investigations and medical management for osteoporosis. / MT2017

Thesis (MMed (Orth))--Stellenbosch University, 2014. / No abstract available

The patellofemoral joint (PFJ) is a common source of problems in Orthopaedics and is the source of poorly defined pain and poor function in both normal and replaced knees. Before problems of the PFJ can be fully comprehended a better understanding of the basic form and function of the PFJ is required. The aim of this thesis therefore is to investigate the shape and kinematics of the PFJ and their inter-relations in both normal and replaced knees. The first part of this thesis was concerned with the shape (or form) of the PFJ. Species from the human ancestry over the previous 400 million years were assembled and measurements taken from three dimensional, CT reconstructions, allowing the descriptions of evolutionary changes in the shape, and orientation of the patellofemoral joint in relation to the tibiofemoral compartments. The study chronicled the dramatic changes that occurred in relation to the adoption of the erect bipedal hominin stance which has resulted in varied anatomy at the PFJ, predisposing it to a wide range of pathologies. The articular surface geometry of normal human patellofemoral joints (bone and cartilage) were compared with those of total knee replacements, and patellofemoral joint replacements. Mapping of the trajectory of the apex of the trochlea groove revealed significant differences between native and replaced knees, with the trajectory being orientated laterally in normal knees and either centrally or medially in replaced knees. The second part of this work was concerned with the kinematics (or function) of the PFJ. With current technology it is impossible to measure coronal plane PFJ kinematics with any accuracy in both native and replaced knees. A novel method was developed combining Motion Analysis and UltraSound (MAUS). Validation experiments were undertaken that demonstrated acceptable error (1.8 mm). The MAUS technique was used to show statistically significant differences between the coronal plane kinematics of the patella in normal and replaced knees. In particular in some arthroplasty patients, the patella tracked in the opposite direction to that in normal subjects. The abnormal kinematics were a manifestation of non-anatomical joint replacements. This demonstrates that form and function are closely related. The interaction between form and function in the knee was further investigated using patients with anterior knee pain. Assessment was made of the relationship between patellar subluxation and multiple bony, cartilaginous and soft-tissue factors potentially predisposing to subluxation. The percentage of engagement of the patella in the trochlear groove in knee extension showed the strongest relationship with subluxation, with subjects less than 30% engaged tending to subluxate. This suggests that the most important factor in preventing subluxation is patellar engagement. A clinical study is now required to assess the effect of surgery aimed at improving engagement. The detailed insights into the variability of form and function in the PFJ obtained throughout this thesis will help address pathology in the native knee and guide decisions for new designs of knee replacements. A novel technology has been developed here for measuring patella kinematics which has great potential for future research. The MAUS technique will provide a clinical investigative tool and allow investigation into kinematic abnormalities in other joints.

No description available.

Tendon injury is painful and often debilitating, and is a one of the most prevalent soft tissue injuries encountered in the clinic. While common, the underlying molecular and genetic processes of tendon damage and repair remain poorly understood. The work described herein used genome-wide expression analyses to investigate tendon injury and healing from three perspectives. The first identified novel gene expression in tendon fibroblasts following their stimulation with nitric oxide (NO). Of particular relevance to tendon healing was the observation that stimulated fibroblasts express a number of extracellular matrix (ECM) genes in response to NO in a dose-dependent manner, and that NO significantly affects cellular adhesion, a critical process during tendon repair. These findings will be of use when optimising dosages of NO delivery in future work investigating NO as potential treatment for tendon injuries. The second study examined gene expression in an acute tendon injury model in the rat at 1, 7, and 21 days post injury, roughly representing the inflammation, proliferation, and remodelling phase of wound repair. Several novel genes and pathways were found to be differentially expressed at each stage of healing. Of particular interest were the presence of a significant number of genes related to glutamate signaling, a method of cellular communication that has not previously been shown to exist in tendon. Also upregulated were a number of genes which have previously only been associated with embryonic development. Finally, gene expression in a supraspinatus tendinopathy model in the rat was investigated. Several genetic pathways were identified in tendinopathic tendons which have not previously been associated with the disease, and, analogous to the acute injury model study, glutamate signaling gene overexpression was also prevalent. Further in vitro studies showed that the expression of these genes in tendon fibroblasts were stimulated by glutamate treatment, which in turn upregulated pro-apoptotic pathways causing cell death. This may prove to be an important causative factor in the tendon degeneration seen in tendinopathy, in which apoptosis has been identified as playing a significant role. The results of these studies contribute to a better understanding of the aetiology of several extremely common pathologies of this soft tissue, and may help to develop more targeted therapies for increasing the efficacy of tendon healing in future.

Congenital insensitivity to pain is a rare hereditary neuropathy. We present patients from a large family in Norrbotten, Sweden with a mutation in the nerve growth factor β gene (NGFß). Using a model of recessive inheritance, we identified an 8.3-Mb region on chromosome 1p11.2-p13.2 shared by the affected individuals in the family. Analysis of candidate genes in the disease-critical region revealed a mutation in the coding region of the NGFß gene specific for the disease haplotype. All three severely affected individuals were homozygous for the mutation. The disease haplotype was also observed in both unaffected and mildly affected family members, but in heterozygote form. We have identified 43 patients, 3 homozygous and 40 heterozygous. The homozygous patients have a severe congenital form with onset of symptoms at an early age, most often affecting the lower extremities with insidious progressive joint swellings or painless fractures. Fracture healing was normal, but the arthropathy was progressive, resulting in disabling Charcot joints with gross deformity and instability. These patients lacked deep pain perception in bones and joints and had no protective reflexes, leading to gross bone and joint complications. They also had abnormal temperature perception but normal ability to sweat. There was no mental retardation. Clinically, they fit best into the group HSAN type V. Sural nerve biopsies showed a moderate loss of thin myelinated fibers (Ad-fibers) and a severe reduction of unmyelinated fibers (C-fibers). 14 of the 40 heterozygous adult patients had mild or moderate problems with joint deformities, usually with only slight discomfort. Treatment was conservative with (if needed) different kinds of orthosis and in some cases joint replacement. Three patients had only neuropathy, and 16 patients had no symptoms. In congenital disorders like these, it is important to evaluate the age and also the slowly progressive nature, when considering treatment. There is an increased risk of growth disturbances in the very young. The orthopedic operations should therefore be planned from a long-term point of view, but patient education and orthosis are cornerstones in the treatment—to delay the development of neuropathic arthropathy. Arthrodesis, limb lengthening and spinal decompression with fusions are the only elective procedures that seem reasonable. This Norrbottnian disease is also interesting as a model system for the study of pain.

No description available.

No description available.

No description available.

Rotator cuff (RC) tears are the most common cause of shoulder disability, representing one of the highest days-away-from-work rates compared to other work-related injuries. Chronic, degenerative tears can cause pain, decreased range of motion, and weakness, with more than 50% of cases affecting individuals over 60 years of age. As Americans age, they remain active and contribute to the workforce longer than has been seen previously. Thus, the impact of RC pathology on activities of daily living and work activities is expected to grow. Previous work in the area of rotator cuff tear spans a number of scientific and clinical fields, but the results from each setting do not necessarily translate. Therefore, this necessitates coordinated, multi-faceted research into understanding how and why rotator cuff tendon tears initiate and progress. RC tears can be classified by their depth as either full or partial thickness tears, and previous clinical studies report a higher prevalence of partial thickness rotator cuff tears, though most research has focused on full thickness tears. Partial thickness rotator cuff tears are commonly asymptomatic, but may serve as an early timepoint that allows for improved, early clinical intervention. Therefore, the goal of this work was to develop a framework that collates information from clinical, cadaveric, simulation, and animal settings to quantify the changing mechanical environment surrounding partial rotator cuff tear and guide clinical assessment. In Chapter 2, using a seven degree of freedom glenohumeral testing system, we demonstrated 1) the effect of the rotator cuff muscle activation and 2) the role of negative intraarticular pressure during passive glenohumeral abduction. In Chapter 3, we utilize an adjustable material testing apparatus, biaxial tensile material testing of rotator cuff tendon specimens and material fitting to a hyperelastic, fiber-reinforced constitutive model to validate a specimen-specific finite element model of the rotator cuff. In Chapter 4, we formulate a procedure for evaluating partial rotator cuff tear patient motions that can be used as inputs to the validated finite element model. In Chapter 5, we develop an in-vivo small animal testing apparatus for evaluating the mechanical and biological response of tendon during cyclic loading. Ultimately this work serves as a foundation for a coordinated framework that takes partial rotator cuff tear patient information and provides the clinician with quantified rotator cuff tear progression risk. Futures studies that aim to achieve clinical utility will use this framework in conjunction with clinical insight to achieve clinical translation that reduce pain and loss of function due to rotator cuff tear. / 2023-01-26T00:00:00Z