Many substances have been used during the last three decades to influence the course of experimental arteriosclerosis. Amongst these choline and other lipotropic agents have occupied a prominent place. No uniform results have, however, been obtained in these researches, so that it was considered worthwhile to re-investigate the problem, employing the rabbit as experimental animal and choline, which is not only a potent lipotropic substance but also, because of its many physiological functions, a potentially important therapeutic agent. [...]

During the last two years, investigation has been carried out by the author on the reaction of the subcutaneous connective tissue to locally injected cholesterol and various lipids. The general purpose of the work was to correlate the intensity of the cellular and metabolis response of the connective tissue with the severity of the atherosclerotic lesions subsequently induced by cholesterol feeding. [...]

<p>Since its first success in 1983, lung transplantation has become the treatment of choice for selected patients with end stage lung disease. However, long-term graft survival is relatively low compared to other solid organs, such as heart, liver and kidney. The primary factor limiting long-term survival of pulmonary allografts is obliterative bronchiolitis (OB), a form of chronic pulmonary graft rejection characterized by submucosal fibroproliferation of the small airways, which leads to luminal compromise and respiratory failure. Due to their unique anatomic location, lungs are exposed to environmental factors in the air which include potentially toxic agents. This suggests a possible importance of non-alloimmune mediated factors in the pathogenesis of pulmonary rejection in addition to alloimmunity. </p><p>Clinical reports reveal that gastroesophageal reflux disease (GERD) is commonly observed following lung transplantation, and it has been postulated that GERD after lung transplantation could accelerate the development of OB and subsequent lung allograft failure. Although clinical studies point to the importance of GERD in the survival of the transplant, the potential effects of GERD on pulmonary allografts still need to be identified. In this dissertation, the effects of GERD on pulmonary allografts, including ischemia-reperfusion (I-R) injury and the pH of the gastric fluid aspirate, are evaluated. Further, this dissertation explores the mechanisms by which GERD affects chronic lung allograft rejection, particularly the role played by mast cells in rejection.</p><p>I-R injury of the pulmonary graft has been associated with a higher risk of developing bronchiolitis obliterans syndrome (BOS) in clinical practice, and prolonged ischemic time has been correlated with poorer long-term survival after lung transplantation. To explore the relationship between GERD, I-R injury, and OB formation after lung transplantation, the effect of long and short ischemic times on WKY-to-F344 rat orthotopic left lung transplants receiving 8 weekly aspirations of gastric fluid was assessed. In this study, described in Chapter 2, long ischemic times led to significantly (p < 0.05) greater development of OB compared to short ischemic times. However, the development of OB was dependent on aspiration, as controls receiving aspiration with normal saline showed little development of OB, regardless of ischemic time (p < 0.05). The data suggest that prolonged ischemic time, while insufficient by itself to lead to OB, worked synergistically with chronic aspiration of gastric fluid to exacerbate the development of OB.</p><p>Also, it remains unknown whether pharmaceutical-induced increases in gastric pH might effectively prevent pulmonary injury associated with chronic aspiration. The hypothesis that neutralization of gastric fluid would affect the development of aspiration-associated OB was tested. The results, described in Chapter 3, revealed that the pH of the aspirated gastric fluid did not significantly affect pulmonary graft rejection. This finding suggests that clinical management of lung transplant patients with GERD should probably include more than just pharmaceutical blockage of gastric protons and/or antacid to neutralize the pH of gastric fluid. </p><p>Mast cells, the first responders of the innate defense system, might play a role in pulmonary allograft rejection due to their ability to orchestrate innate and adaptive immune responses. Correspondingly, increased mast cell numbers associated with increased rejection grade as well as the presence of OB were reported in a retrospective clinical study. Identifying how mast cells are involved with gastric fluid aspiration-associated pulmonary allograft rejection could uncover a potential method for treatment. With this in mind, cromolyn, a mast cell membrane stabilizer which prevents mast cell degranulation, was utilized to investigate the role of mast cells in the pathogenesis of pulmonary allograft failure. The results, described in Chapter 4, reveal that pulmonary allografts in rats treated with cromolyn and aspirated with gastric fluid developed significantly fewer OB lesions than those treated with gastric fluid alone (p<0.001). Further, the number of mast cells per small bronchiole significantly increased in the animals aspirated with gastric fluid regardless of the treatment of cromolyn. Therefore, cromolyn ameliorates the development of OB in pulmonary allografts, perhaps by qualitative (preventing mast cells degranulation), and not quantitative (numbers of mast cells) changes in the mast cells in the bronchioles. These findings suggest that mast cells play a substantial role in gastric fluid aspiration-mediated pulmonary allograft failure. &#8195;</p> / Dissertation

When one looks at atherosclerotic plaques in an artery on the autopsy table, one is viewing a group of lesions that have been present for an unknown length of time and may have bad a multiplicity of causes. Perhaps this white fibrous plaque was initiated fifty years ago and has existed since then. Perhaps it lost lipid during a period of regression. That ulcerated atheroma may have slowly accumulated lipid following a surface thrombosis five years before death. A yellow plaque which could have developed following an intimal injury may have increased in size by short episodes of lipid accumulation associated with haemorrhage into its substance.

Living in an era of summits and far-reaching experimentation, are we to believe in the aphorism of Oberling that cancer is the failure of medicine? The death statistics of the more advanced countries like the U.K., the U. S. A. and Japan tell us that cancer to-day is the second greatest cause of death. The death of about 10% of all human beings is due to this dreadful and very ancient disease. This is in vivid contrast to the success of preventive and social medicine in these countries.

BACKGROUND: The pathological distinction between hyperplastic polyps and sessile serrated adenoma/polyps of the right colon is often difficult and may result in misdiagnosed polyps. OBJECTIVE: To review the proportion and accuracy of serrated polyp diagnosis within a one year retrospective review of colorectal polyp samples, focusing on hyperplastic polyps of the right colon, using criteria set forth by previous studies. MATERIALS & METHODS: 4096 Winnipeg patient cases from January 2009 to December 2009 were reviewed. The proportion of sessile serrated adenoma/polyps, traditional serrated adenoma and serrated adenoma were determined in the patient population. Additionally, pathological morphological variables were reassessed by two study pathologists to determine the frequency of sessile serrated adenoma/polyp initially diagnosed as hyperplastic polyps within the right colon. RESULTS: Approximately 5% of all polyps in the patient population where diagnosed as non-hyperplastic serrated polyps (SSA/P, TSA and SA) and 12.5% as hyperpalstic polyps. Of the non-hyperplastic serrated polyps, a majority were diagnosed as SA. Upon reassessment of right sided HP (n=121), 34% were re-classified as SSA/P. CONCLUSIONS: Winnipeg pathologists diagnose non-hyperplastic serrated polyps with a frequency similar to literature, but are not fully utilizing modern terminology, as majority of non-hyperplastic serrated polyps are reported as SA without further categorisation. Furthermore, a significant proportion of right sided hyperplastic polyps could be re-classified as sessile serrated adenomas on review. Given the difficulty in distinguishing sessile serrated adenomas from hyperplastic polyps, closer endoscopic surveillance should be considered for all individuals with all serrated polyps (including hyperplastic polyps) in the right colon or alternatively all such polyps should be routinely reviewed by two pathologists.

During the past two or three decades diseases of the cardiovascular system have become the most frequent cause of death. It is generally agreed that among these diseases atherosclerosis looms great and remains unconquered. The threat of this disease to our ageing population is well recognized and has given rise to intensive research in many medical centres of the world. [...]

It surprises us to read in the year 1953 that more than seventy years ago pathologists were already complaining of the numerous and unsuccessful efforts of their predecessors to unravel the riddle of atherosclerosis. In the intervening years, Anitschkow's great contribution to medicine - the production, at will, of atherosclerosis in experimenta1 animals, - has not been attended with the expected results, and to-day we are still only battling at the approaches of the problem.

Toward the end of the 19th century an unusual and new microscopic change was observed in the epithelium of the renal tubules in persons who had died in diabetic coma. The alteration consisted of marked swelling and almost complete cytoplasmic vacuolization of the involved epithelial cells. From the time of its early descriptions the lesion has been most widely known under the eponymic designation of the Armanni-Ebstein lesion, being named after its first describers. [...]

Restriction of the amount of sodium chloride in the diet of hypertensive patients has been a controversial topic since almost the beginning of the present century, and in recent years evidence suggesting that excessive ingestion of sodium chloride may of itself cause arterial hypertension in experimental animals and in man has been presented. In spite of much study of possible disturbances of electrolyte metabolism, relatively little work has been done on the electrolyte composition of tissues in hypertension, and it was therefore considered desirable to investigate the relationship of blood pressure to tissue electrolyte levels.