Spontaneous vertebral fractures are a large and growing health care problem. Biomechanical factors, specifically, abnormal posture or gait‐related spinal motion may interact with age‐weakened bone to induce altered spinal biomechanics that in turn increase the likelihood of vertebral body fracture. This research takes steps towards the goal of reducing the number of vertebral fractures in two phases: 1) Validation of a noninvasive spinal motion measurement system in cadaver torsos and 2) Application of the measurement system in human subjects. The cadaver study compared vertebral motion at 4 levels (T7,T12,L3,L5) as measured by adhesive skin markers versus motion measured by bone pins implanted into the vertebrae. Cadaver torsos were tested in lateral‐bending, flexion and axialrotation. Mean differences in vertebral body angular motion between skin markers and bone pin markers were <0.5° around the anterior‐posterior and medial‐lateral axes and <0.9° around the superior‐inferior axis. This measurement method was able to accurately quantify vertebral body motion in cadaver torsos thus allowing for application to human subject testing. X‐rays and 3D motion capture were employed to quantify spinal posture and motion parameters during gait in 12 older and 12 younger normal, females. Vertebral motion around 3 axes was measured at 4 levels (T7,T10,T12,L2) using noninvasive retroreflective markers during treadmill gait at 3 speeds (0.5,0.7,0.9m/s). The average angular motion of all gait cycles at each speed was determined for each level. The triplanar ranges of motion and variability of motion were compared as a function of age. Older subjects had 31.7% larger frontal Cobb angles and up to 30.9% and 33.5% smaller ranges of spinal motion in the frontal and sagittal planes. Variability of motion in the sagittal plane was up to 42.9% less in older subjects. Decreased ranges of motion and variability of spinal motion observed in older subjects may imply that vertebral loading in these subjects may not be as uniformly distributed across the vertebrae as in younger subjects. Greater stresses may result from the abnormal motion, thus increasing fracture risk. Confirmation of this hypothesis requires a longitudinal study, but if verified, may lead to the development of inexpensive countermeasures to prevent fractures.

Osteoporosis is a significant healthcare issue due to the increasing elderly population. Bisphosphonates are used to treat osteoporosis by reducing the rate of resorption, increasing bone mineral density (BMD) and thereby reducing fracture risk. Long-term bisphosphonate treatment, however, has been associated with low-energy fractures. Bone microdamage may provide a partial explanation for one of the mechanisms responsible for these fractures since it has been shown to reduce bone toughness, fracture resistance, and bone strength. The goal of this study was to quantify the changes in bone microdamage parameters with the duration of bisphosphonate treatment. This study selected, stained, and histomorphometrically analyzed 40 iliac crest bone biopsies from controls and female patients with osteoporosis treated with bisphosphonates for varying durations (up to 12 years). All subjects were matched for age and low turnover. The results showed that microcrack density and microcrack surface density were significantly greater in patients who took bisphosphonates for at least 5 years compared to those who took bisphosphonates for less than 5 years or not at all. These results reveal novel, clinically relevant information linking microdamage accumulation to long-term bisphosphonate treatment without influences from age or turnover.

The Forsmark area, the main study area in this thesis, is located about 140 km north of Stockholm, central Sweden. It belongs to the Paleoproterozoic Svecokarelian orogen and contains several major ductile and brittle deformation zones including the Forsmark, Eckarfjärden and Singö zones. The bedrock between these zones, in general is less deformed and considered suitable for a nuclear waste repository. While several site investigations have already been carried out in the area, this thesis focuses primarily on (i) re-processing some of the existing reflection seismic lines to improve imaging of deeper structures, (ii) acquiring and processing high-resolution reflection and refraction data for better characterization of the near surface geology for the planning of a new access ramp, (iii) studying possible seismic anisotropy from active sources recorded onto sparse three-component receivers and multi-offset-azimuth vertical seismic profiling data (VSP). Reflection seismic surveys are an important component of these investigations. The re-processing helped in improving the deeper parts (1-5 km) of the seismic images and allowing three major deeper reflections to be better characterized, one of which is sub-horizontal while the other two are dipping moderately. These reflections were attributed to originate from either dolerite sills or brittle fault systems. First break traveltime tomography allowed delineating an undulating bedrock-surface topography, which is typical in the Forsmark area. Shallow reflections imaged in 3D, thanks to the acquisition design were compared with existing borehole data and explained by fractured or weak zones in the bedrock. The analysis of seismic anisotropy indicates the presence of shear-wave splitting due to transverse isotropy with a vertical symmetry axis in the uppermost hundreds of meters of crust. Open fractures and joints were interpreted to be responsible for the large delays observed between the transverse and radial components of the shear-wave arrivals, both on surface and VSP data.

No description available.

Large amounts of hydrocarbon reserves are trapped in fractured reservoirs where fluid flux is far more rapid along fractures than through the porous matrix, even though the volume of the pore space may be a hundred times greater than the volume of the fractures. These are considered extremely challenging in terms of accurate recovery prediction because of their complexity and heterogeneity. Conventional reservoir simulators are generally not suited to naturally fractured reservoirs’ production history simulation, especially when production processes are associated with large pressure and temperature changes that lead to large redistribution of effective stresses, causing natural fracture aperture alterations. In this case, all the effective processes, i.e. hydraulic, thermal and geomechanical, should be considered simultaneously to explain and evaluate the behavior of stress-sensitive reservoirs over the production period. This is called thermo-hydro-mechanical (THM) coupling. In this study, a fully coupled thermo-hydro-mechanical approach is developed to simulate the physical behavior of fractures in a plane strain thermo-poroelastic medium. A hybrid numerical method, which implements both the finite difference method (FDM) and the displacement discontinuity method (DDM), is established to study the pressure, temperature, deformation and stress variations of fractures and surrounding rocks during production processes. This method is straightforward and can be implemented in conventional reservoir simulators to update fracture conductivity as it uses the same grid block as the reservoir grids and requires only discretization of fractures. The hybrid model is then verified with couple of analytical solutions for the fracture aperture variation under different conditions. This model is implemented for some examples to present the behavior of fracture network as well as its surrounding rock under thermal injection and production. The results of this work clearly show the importance of rate, aspect ratio (i.e. geometry) and the coupling effects among fracture flow rate and aperture changes arising from coupled stress, pressure and temperature changes. The outcomes of this approach can be used to study the behavior of hydraulic injection for induced fracturing and promoting of shearing such as hydraulic fracturing of shale gas or shale oil reservoirs as well as massive waste disposal in the porous carbonate rocks. Furthermore, implementation of this technique should be able to lead to a better understanding of induced seismicity in injection projects of all kinds, whether it is for waste water disposal, or for the extraction of geothermal energy.

Väntetiden för patienter som ådragit sig höftfraktur till operation är ofta lång och kan uppgå till över ett dygn. I första delen av vårdkedjan är det ambulanssjuksköterskan som möter patienter som ådragit sig höftfraktur och omhändertagandet där smärtbehandling ingår genomförs med stöd av upprättade vårdriktlinjer. Ambulanssjuksköterskan har ett ansvar enligt svensk lag att den prehospitala akutsjukvården som genomförs ska vara evidensbaserad. Syftet med denna studie var att undersöka specialistutbildade ambulanssjuksköterskors uppfattningar om möjligheten att bedriva evidensbaserad vård vid prehospital smärtbehandling av patienter med höftfraktur. Detta är en kvalitativ studie med beskrivande design. Resultatet visade att den specialistutbildade ambulanssjuksköterskan uppfattade generellt att vårdriktlinjerna var tydliga och lätta att förhålla sig till. De uppfattade att smärtbehandling var väl fungerande och evidensbaserad. Vårdriktlinjerna var tydliga och lätta att förhålla sig till och informanterna uppfattade att smärtbehandlingen var väl fungerande och evidensbaserad. / The waiting time for patients that sustain hip fractures is often long and can be more than twenty-four hours. The Ambulance nurse provides the first care for those whom sustain a hip fracture.  These patients receive pain management care from the ambulance nurse as recommended by given guidelines.  The ambulance nurse has a responsibility by Swedish law to administer care in an evidence based care, prehospital in the emergency care. The intention of this study was to investigate the specialist educated ambulance nurses current opinions of the possibility to give evidence based care, during prehospital pain management to patients who have a hip fracture. This is a qualitative study with descriptive design. The outcome of this study shows that the specialist educated ambulance nurses believe that the guidelines are clear and easy to follow in general.  Their opinion was that the pain management was functional and evidence based. The guidelines were clear and easy to relate to and the informants experienced the pain management as evidence based.

Bone is refractory to most conventional biochemical Procedures. However because it is now possible to cut sections (e. g. lopm) of fresh, undemineralized adult bone, this tissue can be analyzed by suitably modified methods of quantitative cytochemistry. A new substrate for assaying hydroxyacyl dehydrogenase activity demonstrated that bone cells may use fatty acids as a major source of energy: detailed analysis of the activities of key enzymes indicated that the paradox of ‘aerobic glycolysis’ of bone could be explained by fatty acid oxidation satisfying the requirements of the Krebs' cycle and directing the conversion of pyruvate to lactate The influence of glucose 6-phosphate dehydrogenase (G6PD) activity in aerobic glycolysis has been considered. The inverse relationships between this activity and that of Na-K-ATPase led to the development of a new method for the latter, based on a new concept in cytochemistry ('hidden-capture' procedure). A major feature of fracture-healing is increased periosteal G6PD activity. The association with the vitamin K cycle has been investigated by feeding rats with dicoumarol which not only inhibited bone-formation but also G6PD activity. The stimulation of this activity in fracture-healing has been linked with ornithine decarboxylase (ODC) activity, for which a new method has been developed. Rats deficient in pyridoxal phosphate (cofactor for ODC) had decreased G6PD responses and also appeared to become osteoporotic. Studies on osteoporotic fractures in the human showed the presence of relatively large apatite crystals close to the fracture-site, and disorganized glycosaminoglycans (demonstrated by the new method of ‘induced birefringence’).

Delirium is probably the most common presenting symptom of disease in old age. Delirium, as defined in DSM-IV, is a neuropsychiatric syndrome characterized by disturbance in attention and consciousness, which develops over a short period of time and where the symptoms tend to fluctuate during the course of the day. The overall aim was to increase knowledge about the risk factors and outcome of delirium in old patients with femoral neck fracture and to develop and evaluate a multi-factorial intervention program for prevention and treatment of delirium in these patients. In a prospective study of 101 consecutive patients with a femoral neck fracture, 29.7% were delirious before surgery and another 18.8% developed delirium postoperatively. Of those who were delirious preoperatively all but one remained delirious postoperatively. The majority of those delirious before surgery were demented, treated with drugs with anticholinergic properties (mainly neuroleptics), had had previous episodes of delirium and had fallen indoors. Patients who developed postoperative delirium had perioperative falls in blood pressure and seemed to have more postoperative complications, such as infections. Patients with preoperative delirium had a poorer walking ability on discharge compared to patients with postoperative delirium only. In a five-year prospective follow up study 30 out of 78 (38.5%) non-demented patients with a femoral neck fracture developed dementia. Twenty out of 29 (69%) who were delirious postoperatively developed dementia compared to 10 out of 49 (20%) who were not delirious during hospitalization (p&lt;0.001). Twenty-one (72.4%) of those with postoperative delirium died within 5 years compared to 17/49 (34.7%) of those who remained lucid postoperatively (p=0.001). A non-randomized multi-factorial intervention study with the aim of preventing and treating delirium among patients with femoral neck fracture (n=49) showed that the incidence of delirium was significantly lower than reported in previously published studies. The incidence of other postoperative complications was also lower and a larger proportion of the patients regained independent walking ability and could return to their previous living conditions on discharge. A similar multi-factorial intervention program evaluated as a randomized controlled trial including 199 femoral neck fracture patients showed that fewer intervention patients than controls suffered postoperative delirium (56/102, 55% vs. 73/97, 75%, p=0.003). For intervention patients the postoperative delirium was also of shorter duration (5.0±7.1 days vs. 10.2±13.3 days, p=0.009). Eighteen percent in the intervention ward and 52% of controls were delirious after the seventh postoperative day (p&lt;0.001). Intervention patients suffered from significantly fewer in-hospital complications, such as decubital ulcers, urinary tract infections, nutritional complications, sleeping problems and falls, than controls. Total postoperative hospitalization was shorter in the intervention ward (28.0±17.9 days vs. 38.0±40.6 days, p=0.028). In conclusion, pre- and postoperative delirium is common and seems to be associated with various risk factors, which require different strategies for prevention and treatment. Delirium is also associated with the development of dementia and a higher mortality rate. Multifactorial intervention programs can successfully be implemented and result in the reduction of delirium, fewer complications and shorter hospitalization.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1994. / Includes bibliographical references (leaves 146-162). / Microfiche. / xiii, 162 leaves, bound ill. 29 cm

Investigation of activated remodelling in the healing of experimental stress fractures and the influence of anti-inflammatory treatments Lisa Jane Kidd Abstract Targeted and focal remodelling are important processes in bone homeostasis and pathology. However, the factors that initiate and direct remodelling to repair microcracks, or respond to excess loading are still poorly understood. The rat ulna-loading (RUL) model has been widely used to examine modelling and remodelling responses to axial cyclic loading. However the model has not yet been fully characterised. Stress fractures are common amongst athletes, dancers and military recruits, but there is almost no information available on the mechanism of healing of these fractures. Although cyclooxygenase-2 (COX-2) is a key mediator of bone resorption and bone formation, very little information is available on the effect of non-steroidal antiinflammatories (NSAIDs) on stress fracture healing. Remodelling may play a role in the pathogenesis of stress fractures, and there is growing interest in the potential use of bisphosphonates to prevent them. Nonetheless, the effect of bisphosphonates on stress fracture healing is not known. PMX53 is a C5a receptor antagonist developed as a novel anti-inflammatory agent. It is effective against inflammatory arthritis, but has not been tested in any fracture models. The aims of this study were to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by RUL, and to use this model to determine the effects of selective and non-selective NSAIDs, a bisphosphonate and PMX53 on stress fracture healing. To characterise the RUL model, fatigue fractures were created by loading ulnae until displacement was observed to increase by between 4% and 50%. Ulnae were bulk-stained in basic fuchsin and processed for undecalcified histology. For all remaining experiments, loading was stopped when the displacement had increased by 10%. For detailed histology and histomorphometry, ulnae were decalcified, paraffin embedded and stained with toluidine blue, saffranin-O or for tartrate resistant acid phosphatase (TRAP). Ulnae were examined at 1, 2, 4, 6, 8, and 10 weeks after loading. The effects of DFU (a selective COX-2 inhibitor, 2 mg/kg po), ibuprofen (a non-selective NSAID, 30 mg/kg po) and PMX53 (10 mg/kg po) were examined at 2, 4 and 6 weeks after loading. Effects of risedronate (a bisphosphonate) were examined at a high (1.0 mg/kg po) and low dose (0.1 mg/kg po) at 2, 6 and 10 weeks after loading. RUL did not create isolated intracortical microcracks, but curvilinear fatigue fractures that occurred at a standard position in the medial cortex of the distal ulna diaphysis. These stress fractures induced rapid periosteal woven bone formation and direct intracortical remodelling along the fracture line that originated at the periosteum and progressed towards the medullary cavity. Basic multicellular units (BMUs) could be followed through serial sections extending along the fracture line towards the centre of the bone. Quantitative, real-time PCR was performed at 4 hours, 24 hours, 4 days, 7 days and 14 days after fatigue fracture. Following each period, bones were dissected and mRNA was extracted using standard protocols. Gene expression was compared between loaded and unloaded ulnae and to an unloaded control group. Four hours after loading, there was a marked, 220-fold increase (P<0.0001) in expression of Interleukin-6 (IL-6). There were also prominent peak increases in mRNA expression for Osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) (all P<0.0001). At 24 hours there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days there was a significant increase in mRNA expression for Bcl-2, COX-1, bone morphogenic protein (BMP)-2, insulin-like growth factor (IGF)-1, osteopontin (OPN), and stromal cell derived factor SDF-1. At 7 days there was a significant increase in mRNA expression of Receptor activator of nuclear factor kappa β ligand (RANKL) and OPN. The dramatic, early up-regulation of IL-6 and IL-11 suggests they play a central role in initiating signalling events for stress fracture healing. Treatment with PMX53 did not affect any measures of woven bone formation or stress fracture remodelling. There were no treatment effects of Ibuprofen or DFU on the area of woven bone. DFU treatment resulted in a significant reduction in the area of porosity (resorption) and BMU area along the fracture line at 2 weeks after fracture. Ibuprofen treatment resulted in a significant reduction in length and area of BMUs and new bone formation along the fracture line at 6 weeks (p < 0.05). This is the first report to demonstrate a negative effect on stress fracture healing of both a selective COX-2 inhibitor and a non-selective NSAID. These data confirm the importance of cyclooxygenase in bone resorption and formation during remodelling. Bisphosphonates are potent inhibitors of osteoclastic bone resorption Two, 6 and 10 weeks after loading, measures of resorption and new bone formation were significantly reduced along the fracture line by high dose risedronate treatment, but not by the low dose. Only the porosity along the fracture line 2 weeks after loading was significantly reduced by the low dose risedronate. The low dose more closely resembles the clinical dose used to treat patients. Woven bone formation and consolidation were not affected by the low or high doses of risedronate. In conclusion, fatigue fractures in the rat ulna are highly reproducible, induce exuberant periosteal woven bone formation, and heal by direct remodelling along the fracture line. Remodelling is associated with gene expression for molecules typically associated with bone resorption and formation, angiogenesis and cell signalling. Remodelling of the stress fracture line was adversely affected by treatment with selective and non-selective COX inhibitors, by high dose treatment with risedronate, but not by PMX53, a C5a antagonist.