Emphysema

Chronic Obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality world-wide. The most common cause is chronic cigarette smoke inhalation which results in a chronic progressive debilitating lung disease with systemic involvement. COPD poses considerable challenges to health care resources, both in the chronic phase and as a result of acute exacerbations which can often require hospital admission. At the current time it is vital that scientific resources are channeled towards understanding the pathogenesis and natural history of the disease, to direct new treatment strategies for rigorous evaluation. This book encompasses some emerging concepts and new treatment modalities which hopefully will lead to better outcomes for this devastating disease

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Development of biomarkers for the risk stratification and targeted therapy of Barrett's oesophagus and oesophageal adenocarcinoma

Barrett's oesophagus is the most important risk factor for the development of oesophageal adenocarcinoma (OA), but progression is unpredictable. Dysplasia predicts which Barrett’s patients are at greatest risk for OA but achieving the diagnosis can be challenging. Immunohistochemistry with p53 is recommended as an adjunct to assist with dysplasia diagnosis. This thesis will examine if replication licensing factors and DNA ploidy status are as good if not better than p53 to assist in the diagnosis of dysplasia. Overexpression of HER2 in foregut cancer is an indication for HER2 targeted treatments. Its influence on prognosis is less understood. The relationships between clinicopathological variables, HER2 overexpression and prognosis will next be evaluated. Current ablative techniques for Barrett’s neoplasia are limited to superficial disease. Photodynamic therapy was a treatment for Barrett’s that could penetrate more deeply into diseased tissue but was limited by the side effects of off-target photosensitivity. Combining targeting vehicles such as antibodies to newer and more deeply penetrating photosensitiser drugs, may overcome the previous limitations of this technology. A photosensitive ADC against HER2 will be created and its efficacy in vitro and in vivo evaluated. However, even the most effective ADC against HER2 will not treat the majority of cancers, as we will show HER2 is only expressed in the minority of foregut tumours. The final experiments will look to characterise the mucin MUC1 in Barrett’s and associated neoplasia. Studies have previously shown it to be present in up to 100% of cancers while others say far fewer. We will show proof of principle data for the development of a MUC1 targeting photosensitive ADC in vitro and postulate how it may in future enable treatment of locoregional invasive tumours endoscopically

A multi-modality approach for enhancing the diagnosis of cholangiocarcinoma

Background: Cholangiocarcinoma (CC) is a malignancy of the bile ducts and mortality is high as patients present too late for curative surgery. In most cases of CC the aetiology is unknown, whilst diagnosis and staging are challenging. The hepatobiliary system excretes carcinogenic toxins and genetic mutations in biliary transporters lead to dysfunction and cholestasis, potentially contributing to cholangiocarcinogenesis. Polymorphisms in the NKG2D receptor have previously been associated with CC in primary sclerosing cholangitis (PSC). Such a role has not been investigated in sporadic CC. CC is difficult to diagnose, particularly in those with PSC. The transition from benign to malignant biliary disease is likely to be reflected in changes to the plasma proteome. However, current plasma biomarkers do not reliably distinguish benign from malignant biliary strictures. Elevation of neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated in the bile of patients with CC but has not been investigated as a plasma protein biomarker. Staging of CC is inaccurate, with only a minority of operated patients cured. Higher resolution MRI would improve diagnosis and staging. The work presented in this thesis represents a multimodality approach to enhance the diagnosis of CC: Genetic studies: Genetic variation in major biliary transporter proteins, and the NKG2D receptor, were investigated. Single nucleotide polymorphisms (SNPs) in candidate genes were selected using HapMap. DNA from 173 CC patients and 265 healthy controls was genotyped. SNPs in ABCB11, MDR3 and ATP8B1 were nominally associated with altered susceptibility to CC, suggesting a potential role in cholangiocarcinogenesis. The previous association of NKG2D variation with CC in PSC was not replicated in sporadic CC, suggesting a possible difference in pathogenesis. Protein studies: Plasma from subjects with CC, benign disease, and from healthy controls was studied. Two proteomic techniques, liquid chromatography-tandem mass spectrometry (LCMS/ MS) and surfaced enhanced laser desorption ionization time-of-flight MS (SELDITOF MS), were utilised. Differentially expressed proteins were identified where possible. LC-MS/MS fully identified six proteins that were differentially expressed in CC compared to gall stone disease patients. SELDI-TOF MS identified seven m/z peaks that showed significant utility in discriminating CC from PSC controls. An ELISA approach was used to study plasma NGAL levels in CC. Although differentially expressed between CC and healthy control groups, the utility of NGAL in discriminating CC from PSC was limited. Imaging studies: An endoscope-mounted MR coil and intraductal MR detector coil were developed. Quantitative resolution and signal-to-noise-ratio (SNR) testing, and qualitative tissue discrimination appraisal, were undertaken. Sub-0.7mm resolution and excellent SNRs have been demonstrated. High-resolution has been demonstrated in imaged tissue. Imaging with the new devices compares favourably with endoscopic ultrasound imaging

The efficacy of topical agents in the treatment of bacterial biofilms: an in vivo sheep study and an in vitro study.

Introduction: Recent evidence has demonstrated the presence of bacterial biofilms on the mucosa of patients with Chronic Rhinosinusitis (CRS), suggesting their role in the pathogenesis of the condition. This thesis contains two separate studies. The studies investigated novel topical therapies by using previously established in vitro and in vivo biofilm growth and detection methods. In the first study, several different proposed anti-biofilm agents were evaluated in a sheep biofilm model, each with varying degrees of immediate and short-term success against Staphylococcus aureus biofilms. A second study was conducted to determine the in vitro anti-bacterial and anti-biofilm properties of Chitosan/Dextran (CD) gel, a novel chitosan-based product with remarkable mucosal healing and haemostatic properties. Methods: Three alternative anti-biofilm treatments: Mupirocin, CAZS (Citric Acid Zwitterionic Acid) and Gallium Nitrate were evaluated in a prospective randomized controlled single-blinded trial using a previously established sheep biofilm model of CRS. The sheep mucosal samples were analyzed for presence of S. aureus biofilms using BacLight staining and CLSM, and the degree of biofilm involvement was determined using FISH (Fluorescence In-Situ Hybridization). The MIC/MBC values for CD gel and its constituents were determined by macro-dilution methods described by Jorgensen et al.[1]. Established in vitro biofilms grown from common CRS pathogens (ATCC strains and clinical isolates) were subjected to treatment by CD gel and its components (chitosan and dextran). A 96-well micro-titre crystal-violet staining method described by O’Toole and Kolter [2] was used to determine the anti-biofilm profile of CD gel against several bacterial strains with known biofilm-forming capacity. Results: Following 8 days of inoculation with S. aureus, all treatment groups in the sheep biofilm model showed a statistically significant reduction in biofilm surface coverage compared to no treatment. Importantly, sheep frontal sinuses treated with twice-daily mupirocin flushes for 5 days showed almost negligible biofilm growth after the follow-up period of 8 days (0.84% ± 1.25% surface area coverage per visual field). The overall data from the in vitro studies suggest that CD gel has marked anti-microbial activity against planktonic and biofilm-forming bacteria. It was inhibitory and bacteriocidal at sub-clinical concentrations (25mg/mL) for all bacteria tested except for E. coli. When tested against a nutrient-free environment as well as a positive growth control, bacteria were essentially unable to grow in its presence. Conclusion: Recalcitrant CRS is a difficult condition to manage and its pathogenesis has been closely linked to the presence of bacterial biofilms. Using a standardized biofilm sheep model of CRS, regular treatment with mupirocin flushes over a 5 day period showed an almost complete eradication of biofilms as assessed by mucosal surface coverage, with sustained effects over the 8 day period of follow-up. Equally as efficacious in the in vitro setting, CD gel demonstrated potent anti-bacterial and anti-biofilm activity against a number of pathogenic organisms suspected of being involved in acute and chronic rhinosinusitis. CD gel’s favourable haemostatic and mucosal healing profile posits it as an ideal post-ESS packing material. These two topical agents therefore hold promise as effective treatment options in the management of CRS.Thesis (M.S.) -- University of Adelaide, School of Medicine, 201

Advances in Ophthalmology

This book focuses on the different aspects of ophthalmology - the medical science of diagnosis and treatment of eye disorders. Ophthalmology is divided into various clinical subspecialties, such as cornea, cataract, glaucoma, uveitis, retina, neuro-ophthalmology, pediatric ophthalmology, oncology, pathology, and oculoplastics. This book incorporates new developments as well as future perspectives in ophthalmology and is a balanced product between covering a wide range of diseases and expedited publication. It is intended to be the appetizer for other books to follow. Ophthalmologists, researchers, specialists, trainees, and general practitioners with an interest in ophthalmology will find this book interesting and useful