Loosening and osteolysis are the most important processes limiting the longevity of total hip arthroplasty (THA). The macrophage, which represents 60--80% of the cell population of the proliferating pseudomembrane (PM) formed around a loose prosthesis, is the key cell responsible for many of the events associated with periprosthetic osteolysis. Phagocytosis of particulate debris by macrophages, incites a cascade of events that result in the release of substances capable of stimulating the bone resorption including IL-1, TNF-alpha, and PGE2. The exact mechanisms by which the inflammatory cells interact with osteoblast/osteoclast cells and the relative importance of the various chemical mediators on the ultimate bone lysis remain poorly understood. It was recently demonstrated that bisphosphonates inhibit bone resorption mediated by particle-induced foreign body macrophages. Moreover, it was demonstrated in vivo and in vitro that their actions implicate osteoclast and/or macrophage apoptosis. These results strongly suggest that the modulation of apoptosis at the prosthesis-bone interface may serve as a potent target for therapeutic control. The purpose of this study was to investigate the mechanism of PM cell death at the prosthesis-bone interface of failed THAs. (Abstract shortened by UMI.)

The purpose of this study was to evaluate the effect of non-invasive, low-intensity, pulsed ultrasound on bone growth into tantalum porous implants. Three transcortical cylindrical implants were inserted into both femora of 12 dogs. One leg underwent daily ultrasound stimulation for 40 consecutive minutes with the transducer positioned over the central, or "target" implant, while the contralateral leg served as the control. Six dogs were each treated for periods of two and three weeks. A quantitative analysis was performed to determine the volume fraction of bone ingrowth. At two weeks, there was 12.4 $ pm$ 5.4% bone ingrowth in the stimulated femora compared with 12.7 $ pm$ 6.5% in the controls (p = 0.74). At three weeks, bone growth into the stimulated and control implants was 21.1 $ pm$ 6.5% and 22.7 $ pm$ 7.3%, respectively (p = 0.53). Although a prior study showed that 20 minutes of ultrasound stimulation had a positive effect on bone ingrowth, the results of this study suggest that a treatment of 40 consecutive minutes does not enhance the amount of bone growth into porous metallic implants.

The objective measurement of the subglottic lumen has been a problem for many years. To date, no proposed system for this measurement has been adopted universally. The aim of this study was to evaluate, for the first time, B-mode ultrasound and a new video-bronchoscopic technique in the measurement of the subglottic lumen diameter. / This was a blind prospective animal study of 62 recently sacrificed rabbits. Different standardized diameters of the subglottis were measured on each intact animal using ultrasound followed by a video-bronchoscopic technique. These measurements were compared with the corresponding direct caliper results once the subglottis was surgically exposed. / Statistical analyses revealed clinically significant convergent values between both indirect (ultrasound and video-bronchoscopic) and direct (caliper) measurements. The study results clearly demonstrate that B-mode ultrasound and this new video-bronchoscopic technique are both precise measuring modalities for the subglottic lumen diameter.

Prostanoids are important mediators of inflammation and tissue homeostasis. Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids from arachidonic acid. Of the two isoforms of COX, COX-1 functions in tissue homeostasis whereas COX-2 is more abundant in inflammation. Selective COX-2 inhibition seems effective in reducing inflammation with fewer side effects compared with non-selective COX inhibitors. In this study, the expression of COX-2 in lung inflammation was investigated in two models, which include acute rejection and antigen-induced inflammation. The effect of selective COX-2 inhibition in these models was also determined. COX-2 was expressed in infiltrating cells in both models, in addition to constitutive expression in bronchial epithelium and bronchial smooth muscle cells. Selective COX-2 inhibition significantly reduced the extent of inflammation in both models. These results suggest that selective COX-2 inhibition may be effective in the treatment of acute rejection and asthma.

The visualization of two-dimensional and three-dimensional vascular structures is of significant interest in image-guided surgery. This assists clinicians in pre-operation planning, real-time operating room decision making, and post-operation monitoring. In order to achieve this goal, vascular networks must first be segmented from intensity data such as CT or MR angiography images. A framework for addressing this problem is the use of geometric flows where a curve (in two dimensions) or a surface (in three dimensions) is evolved under constraints from image forces so that it clings to features of interest in an intensity image. Recent variations on this theme take into account properties of enclosed regions and textures and allow for multiple curves or surfaces to be simultaneously represented. However, it is not clear how to apply these techniques to images of low contrast elongated structures, such as blood vessels. To address this problem we derive the gradient flow which maximizes the rate of increase of flux of an auxiliary vector field through a curve or surface. The calculation leads to a simple and elegant interpretation which is essentially parameter free. We illustrate its advantages with level-set based segmentations of 2D and 3D angiography images of blood vessels.

The differential diagnosis of a disease is often based on the information obtained from multiple diagnostic tests or multiple applications of the same test. The usual assumption in such situations is that the test results are statistically independent within each subject conditional on knowing the true disease status. This assumption greatly simplifies the statistical analysis of such data. In practice, however this assumption may be violated, as for example when there is a certain subject-related characteristic that may increase or decrease the probability of detection in two or more tests. The classical or frequentist solutions that account for the correlation between tests require a minimum of four different tests to obtain an identifiable solution. However, it is not always possible to have results from four different tests, particularly when tests are expensive, time consuming or invasive. Our objective in this thesis is to draw simultaneous inferences about the prevalence and test parameters while adjusting for the possibility of conditional dependence between tests, particularly in the situation when we have three or fewer tests, leading to a non-identifiable problem. We do so by way of a Bayesian approach, which utilizes available information about the prevalence and test parameters summarized in the form of prior distributions. The first of the two methods we propose models the dependence as a direct effect between each pair of tests. The second method uses a random effects model and simulates the dependence between tests via their sensitivity and specificity which are modeled as functions of a latent, subject-specific 'disease intensity'. Both models are based on dichotomous tests and the parameters are estimated using a Gibbs Sampler. It was found that ignoring the conditional dependence between tests could lead to misleading estimates of the sensitivities and specificities of the tests and of disease prevalence. Therefore, the methods presented here m

Measurement of cerebral blood flow (CBF) using positron emission tomography (PET) with 15O-labelled water is commonly achieved using the one-compartment model of Kety. Unlike this model, a recently developed two-compartment CBF model accounts for nonextracted intravascular radioactivity and therefore provides with perfusion (CBF) as well as vascular, i.e., blood volume (CBV) related, information. The two parameters obtained from this two-compartment analysis, namely cerebral water clearance, KH2O1 , a measure of perfusion, and the apparent tracer distribution volume, Vo, provide more complete haemodynamic information than CBF alone. Still, accurate K1 values can only be obtained if appropriate corrections for tracer delay (Deltat) and dispersion (tau) have been applied. Building on this two-compartment model, we have derived new nonlinear and linear solutions where all parameters involved appear explicitly. Simulations were performed to evaluate the accuracy and precision with which K1, k2, Vo, Deltat and tau can be determined from multiparameter regression of the model equations on dynamic PET data. It was found that K1 and k2 can be estimated with less than 2% error using 5-parameter fitting. / We have applied our solutions to dynamic 15O-water bolus PET studies where a CBF change was produced either through neuronal activation triggered by visual stimulation (in normal subjects), or by external pharmacological control through vasodilatory insults induced by Diamox injection (in patients with cerebrovascular disease) and antioxidant LY231617 administration (in monkeys with unilateral middle cerebral artery occlusion). / We found that in addition to accurate pixel-by-pixel estimation of K 1 and k2, accurate changes in K1, Vo and the ratio Vo/K1 between baseline and activation states can also be obtained using our solutions of the two-compartment CBF model with implicit corrections for delay, dispersion and residual vascular radioactivity. These parameter changes provide potential indices of cerebrovascular reserve capacity, and of variations in cerebral vascular volume and mean vascular transit time. Our method may prove to be an elegant tool in the selection of candidates for revascularisation surgery.

This study was designed therefore, to investigate potential contributions of the cardiopulmonary bypass (CPB) procedure to the chronotropic limitation during exercise in surgically corrected CHD adolescents. Patients were divided into 3 groups: operated ventricular septal defect, where CPB is required (VSDop: n = 15); VSD closed spontaneously, no surgery or CPB required (VSDnop: n = 17); and operated patent ductus arteriosus, where surgery does not require CPB (PDA: n = 20). Fifteen healthy age-matched subjects served as the control group (C). All subjects were submitted to a graded maximal exercise cycle egometer test and completed 3 levels of submaximal exercise. Maximal oxygen consumption was similar in all groups. Cardiac index and stroke volume index at rest and during submaximal exercise were slightly lower in VSDop and PDA than VSDnop and C, however no statistical significance was found. The heart rate at rest was similar in all groups, however it was significantly lower in VSDop than all other groups. (Abstract shortened by UMI.)

It was hypothesized that skeletal muscle (SKM) satellite cells multiplied in vitro could be used to repair injured heart muscle. The purpose of this study was to test this hypothesis by auto-transplanting SKM satellite cells to a myocardial injury site. Fourteen dogs underwent explanation of the anterior tibialis muscle. Satellite cells were multiplied in vitro and their nuclei were labelled with tritiated thymidine 24 hours prior to implantation. The same dogs were then subjected to a myocardial injury by the application of a cryoprobe. The cells were suspended in serum free growth medium and implanted within the damaged muscle. / There was persistence of the implantation channels in the experimental sites when compared to the controls. Macroscopically, muscle tissue completely surrounded by scar could be seen. Masson trichrome staining showed homogeneous scar in the control site, but not in the test site where a patch of muscle fibres containing intercalated discs (characteristic of myocardial tissue) was observed. In 2 dogs, specimens were taken at 14 weeks post-implantation. Muscle tissue could not be found. Electrically stimulated skeletal muscle regenerates did not show histological evidence of cardiac transformation. / These results support the hypothesis that SKM satellite cells can form neo-myocardium within an appropriate environment. The specimens failed to demonstrate the presence of myocyte nuclei. (Abstract shortened by UMI.)

Pterygomaxillary separation during Le Fort I osteotomy has been associated with life-threatening complications. Fractures of the pterygoid plates may play a role in the occurrence of these problems and may impede desired movements of the maxilla. This study compares the incidence of complications and pterygoid plate fractures during Le Fort I osteotomy with and without the use of a curved osteotome. Patients were randomly assigned to one of two groups in which pterygomaxillary separation was achieved either with or without osteotome. Measurements of lateral maxillary wall thickness, clinical assessment of the presence and location of fractures, and a subjective evaluation of the ease of downfracture were recorded. Coronal and axial CT scans were obtained between the seventh and tenth postoperative day. / There was no significant difference in incidence of pterygoid plate fracture between the two groups. A strong clinical trend was detected for males to have a greater incidence of pterygoid plate fractures than females. The incidence of palatine bone fractures was low. Low level fractures of the pterygoid plates of the sphenoid bone are a commonplace occurrence during the Le Fort I osteotomy. Further studies assessing alternative methods of pterygomaxillary separation are recommended.