Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Esse estudo avaliou as anastomoses colo-cÃlicas sem preparo intestinal comparando com anastomoses realizadas com preparo intestinal prÃvio. Foram utilizados 42 animais (Canis familiares) fÃmeas, pesando entre 8,4 a 16,9 Kg, clinicamente sadios, oriundos do Canil da Prefeitura Municipal de Teresina, PiauÃ. Foram distribuÃdos em 2 grupos de 21 animais: grupo I (controle) â animais submetidos ao preparo intestinal com soluÃÃo glicerinada a 12% via retal 24hs antes do procedimento e grupo II (estudo) â animais submetidos ao procedimento sem preparo intestinal prÃvio. Todos os animais de ambos os grupos foram submetidos à laparotomia com secÃÃo do cÃlon descendente e anastomose primÃria com fio de polipropileno e acompanhados no trans e pÃs-operatÃrio por um mÃdico veterinÃrio, sendo a dieta instituÃda quando ocorreu a primeira evacuaÃÃo. Esses animais foram submetidos à eutanÃsia no 21 dia de pÃs-operatÃrio apÃs anestesia venosa com cloridrato de cetamina e aplicaÃÃo de cloreto de potÃssio a 20% endovenosa; realizou-se nova laparotomia e avaliaÃÃo da anastomose colo-cÃlica. Avaliou-se a evoluÃÃo clÃnica, o grau de aderÃncias intestinais e a pressÃo de ruptura da anastomose. Utilizou-se o teste T para amostras nÃo pareadas para dados paramÃtricos e Mann-Whitney test para dados nÃo paramÃtricos. Ocorreu um (4,5%) Ãbito em cada grupo sendo o do grupo I (controle) no 7 dia pÃs-operatÃrio devido à deiscÃncia da anastomose colo-cÃlica e outro no 10 dia de pÃs-operatÃrio no grupo II(estudo) devido à infecÃÃo de sÃtio cirÃrgico incisional profunda com deiscÃncia total da parede abdominal. NÃo foi observado diferenÃa estatisticamente significante no grau de aderÃncias intestinais entre os grupos. Durante a realizaÃÃo do teste de pressÃo de ruptura ocorreu ruptura da anastomose de um animal em cada grupo e nÃo houve diferenÃa estatisticamente significante entre os grupos (p>0,05). A anastomose colo-cÃlica sem preparo intestinal apresentou a mesma seguranÃa e eficÃcia da anastomose realizada com preparo prÃvio. / Esse estudo avaliou as anastomoses colo-cÃlicas sem preparo intestinal comparando com anastomoses realizadas com preparo intestinal prÃvio. Foram utilizados 42 animais (Canis familiares) fÃmeas, pesando entre 8,4 a 16,9 Kg, clinicamente sadios, oriundos do Canil da Prefeitura Municipal de Teresina, PiauÃ. Foram distribuÃdos em 2 grupos de 21 animais: grupo I (controle) â animais submetidos ao preparo intestinal com soluÃÃo glicerinada a 12% via retal 24hs antes do procedimento e grupo II (estudo) â animais submetidos ao procedimento sem preparo intestinal prÃvio. Todos os animais de ambos os grupos foram submetidos à laparotomia com secÃÃo do cÃlon descendente e anastomose primÃria com fio de polipropileno e acompanhados no trans e pÃs-operatÃrio por um mÃdico veterinÃrio, sendo a dieta instituÃda quando ocorreu a primeira evacuaÃÃo. Esses animais foram submetidos à eutanÃsia no 21 dia de pÃs-operatÃrio apÃs anestesia venosa com cloridrato de cetamina e aplicaÃÃo de cloreto de potÃssio a 20% endovenosa; realizou-se nova laparotomia e avaliaÃÃo da anastomose colo-cÃlica. Avaliou-se a evoluÃÃo clÃnica, o grau de aderÃncias intestinais e a pressÃo de ruptura da anastomose. Utilizou-se o teste T para amostras nÃo pareadas para dados paramÃtricos e Mann-Whitney test para dados nÃo paramÃtricos. Ocorreu um (4,5%) Ãbito em cada grupo sendo o do grupo I (controle) no 7 dia pÃs-operatÃrio devido à deiscÃncia da anastomose colo-cÃlica e outro no 10 dia de pÃs-operatÃrio no grupo II(estudo) devido à infecÃÃo de sÃtio cirÃrgico incisional profunda com deiscÃncia total da parede abdominal. NÃo foi observado diferenÃa estatisticamente significante no grau de aderÃncias intestinais entre os grupos. Durante a realizaÃÃo do teste de pressÃo de ruptura ocorreu ruptura da anastomose de um animal em cada grupo e nÃo houve diferenÃa estatisticamente significante entre os grupos (p>0,05). A anastomose colo-cÃlica sem preparo intestinal apresentou a mesma seguranÃa e eficÃcia da anastomose realizada com preparo prÃvio. / The objective of this study was to evaluate the efficacy of colo-colonic anastomosis in dogs with and without preoperative bowel preparation. The experiment included 42 healthy female mongrel dogs (Canis familiaris) weighing 8.4-16.9 Kg, supplied by the municipal dog pound of Teresina, PiauÃ. The animals were distributed at random in two groups of 21 animals each: Group I (control) = submitted to bowel preparation with rectal administration of 12% glycerin solution one day before the procedure, and Group II (study) = without previous bowel preparation. All animals were submitted to laparotomy with sectioning of the descending colon and primary anastomosis using polypropylene thread under the peri and postoperative supervision of a veterinary physician. The animals were allowed access ad libitum to water and standard feed following the first evacuation. On the 21st postoperative day (POD 21), the dogs were euthanized with ketamine i.v. followed by 20% potassium chloride i.v., and a second laparotomy was performed through the same incision in order to evaluate the anstomosis. In addition, the abdominal cavity was evaluated for adhesions and the burst pressure of the anastomosis was tested. The unpaired samples were compared with Studentʼs t test for parametric data and with the Mann-Whitney test for non-parametric data. One animal in each group (4.5%) died. The death in Group I (control) occurred on POD 7 due to anastomotic dehiscence. The death in Group II (study) occurred on POD 10 due to deep incisional infection at the surgical site and complete dehiscence of the abdominal wall. The groups did not differ significantly with regard to adhesion grade or anastomotic burst pressure (one specimen burst in each group) (p>0.05). In conclusion, the level of safety and efficacy was the same for colo-colonic anastomosis with and without previous bowel preparation. / The objective of this study was to evaluate the efficacy of colo-colonic anastomosis in dogs with and without preoperative bowel preparation. The experiment included 42 healthy female mongrel dogs (Canis familiaris) weighing 8.4-16.9 Kg, supplied by the municipal dog pound of Teresina, PiauÃ. The animals were distributed at random in two groups of 21 animals each: Group I (control) = submitted to bowel preparation with rectal administration of 12% glycerin solution one day before the procedure, and Group II (study) = without previous bowel preparation. All animals were submitted to laparotomy with sectioning of the descending colon and primary anastomosis using polypropylene thread under the peri and postoperative supervision of a veterinary physician. The animals were allowed access ad libitum to water and standard feed following the first evacuation. On the 21st postoperative day (POD 21), the dogs were euthanized with ketamine i.v. followed by 20% potassium chloride i.v., and a second laparotomy was performed through the same incision in order to evaluate the anstomosis. In addition, the abdominal cavity was evaluated for adhesions and the burst pressure of the anastomosis was tested. The unpaired samples were compared with Studentʼs t test for parametric data and with the Mann-Whitney test for non-parametric data. One animal in each group (4.5%) died. The death in Group I (control) occurred on POD 7 due to anastomotic dehiscence. The death in Group II (study) occurred on POD 10 due to deep incisional infection at the surgical site and complete dehiscence of the abdominal wall. The groups did not differ significantly with regard to adhesion grade or anastomotic burst pressure (one specimen burst in each group) (p>0.05). In conclusion, the level of safety and efficacy was the same for colo-colonic anastomosis with and without previous bowel preparation.

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After analysis, it was found that severity of preeclampsia was correlated with a unique lipid profile. Pro-inflammatory hydroxyeicosatetraenoic acids and sphingolipids were elevated. Aspirin usage in patients who developed preeclampsia was found to attenuate accumulation of isoprostane oxidative stress markers and thromboxane production while preserving omega-3-fatty acid and increasing prostacyclin levels.

Doctor of Philosophy / This thesis describes experiments which were carried out at the Institute of Dental Research in Sydney and within the Department of Prosthetic Dentistry at the United Dental Hospital of Sydney between February 1991 and May 1996. The study is concerned with finding practical means of treating chronic atrophic candidosis, also referred to as Candida-associated denture stomatitis and to this purpose two methods of denture disinfection are investigated, namely, sodium hypoclorite denture soak and microwave irradiation. Although the aetiology of denture stomatitis is generally considered to be multifactorial, there is sufficient evidence that Candida species and in particular C. albicans play an important role in the aetiology of the condition. In Chapter 1, therefore, the literature review, which provides relevant background information for the experiments to be described in later chapters, is primarily concerned with Candida species. The characteristics and distribution of Candida species are described and factors affecting the distribution of or Candida are discussed. The literature relating to the cause of chronic atrophic candidosis is vast and consequently a detailed description is given of Candida-associated denture stomatitis in the section concerned with oral diseases caused by Candida and their treatment. Each of the subsequent chapters, contains a brief literature review of material relevant to the subject of the particular chapter. Chapter 2 describes laboratory work to assess the effect of sodium hypochlorite on the adhesion of Candida species to oral surfaces and the ability of Candida to coaggregate with oral streptococci. The results showed that sodium hypochlorite decreased the ability of Candida species to adhere to both inert surfaces and BECs. However, coaggregation of Candida with streptococci was increased. Thus, hypochlorite if used as a denture soak may initially reduce the ability of Candida species to adhere to the denture surface and may therefore assist the treatment of denture stomatitis. The effects of hypochlorite on the characteristics of Candida species that are associated with tissue invasion are described in Chapter 3. The production of acid proteinase, the formation of germ tubes and presence of major cell wall proteins at 43 and 27 kDa are demonstrated. The ability of the whole cells of certain species of Candida to aggregate human platelets was assessed. The results showed that sodium hypochlorite did not affect proteinase production by Candida species but the rate of germ tube formation and the production of Candida cell wall proteins were increased. Hypochlorite did not affect the ability of certain Candida species to aggregate human platelets. Mechanisms to defend the host against candidal invasion are discussed and include platelet aggregation where aggregated platelets release antimicrobial factors that are active against Candida. Chapter 4 describes an in vitro study to test the effects of sodium hypochlorite and microwave irradiation on the survival of Candida species and oral streptococci on denture surfaces. The results showed that 0.02% sodium hypochlorite denture soak for 8 h will eliminate Candida species and reduce the growth of streptococci. However, microwaving of dentures at medium setting for 6 min will eliminate both Candida and streptococci. This information servers as baseline data for clinical assessments described in Chapters 7 and 8. Denture hygiene is an important factor in the prevention and treatment of Candida-associated denture stomatitis. Hence, a clinical study to assess the microbiology of denture plaque is described in Chapter 5. The results showed that denture plaque was composed mainly of Gram-positive streptococci with varying proportions of Gram-positive rods, Gram-negative cocci and rods and is similar to dental plaque. Candida was not always isolated and when detected constituted a very small proportion (< 1%) of the total aerobic bacterial count. The results of an investigation to test the effect of soft denture liners in lower dentures on the colonization of denture surfaces by Candida species and aerobic bacteria are given in Chapter 6. There was no significant difference in Candida /bacterial colonization of dentures with soft denture liners and those without liners. Chapter 7 describes a clinical study to test the efficiency of sodium hypochlorite (0.02%) over-night denture soak as an effective denture disinfecting agent. Treatment of dentures with hypochlorite over a trial period resulted in reductions of Candida and aerobic bacteria and although the reductions were not significant the effect over the trial period could be assessed. A significant finding was that for the palate, treatment with hypochlorite over the trial period prevented an increase in candidal load. Thus, sodium hypochlorite may function as an effective disinfecting agent when used as 0.02% denture soak for a prolonged period. A pilot study to assess the effectiveness of microwaving dentures for ten min (350 W, 240 MHz) as a potential method of denture disinfection is described in Chapter 8. For practical reasons the dentures were microwaved only once only and therefore the effect over a trial period could not be assessed. However, one treatment resulted in significant reductions in the levels of Candida and aerobic bacteria. These findings have indicated that future research should be carried out to test the effect of daily consecutive microwave treatments on candidal and bacterial growth. The general discussion in Chapter 9 summarizes the data presented in the previous chapters and from the findings conclusions are made concerning the prevention and treatment of Candida-associated denture stomatitis. The limitations of this thesis are recognized and some important aspects of the study are recommended for future research.

Includes list of papers arising from this thesis. "July 2004" Includes bibliographical references (leaves 253-297)

Microbial contamination of contact lenses is a significant risk factor leading to adverse responses. Adhesion of microorganisms to a contact lens is the first step in a series of events that leads to contact lens-related infections or inflammation. Recently, some of the non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have the ability to interfere with microbial biofilm formation. In this project, antibacterial properties of commonly used NSAIDs (salicylic acid, sodium diclofenac and ketorolac) were assessed and characterised using biological assays and molecular biological techniques. Salicylic acid, ketorolac and diclofenac reduced adhesion of a range of bacterial species isolated from corneal infection and inflammatory events to contact lenses in a dose-dependent manner. Salicylic acid also decreased the adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to human corneal epithelial cells in a dose-dependent manner. Results further demonstrated that NSAIDs had a significant impact on the production of virulence factors such as Type IV pili mediated (twitching) motility, flagella mediated swimming, elastase, protease IV and alkaline protease and affected the production of acylated homoserine lactones of P. aeruginosa. Salicylic acid and ketorolac affect the expression of P. aeruginosa outer membrane proteins. In the presence of the salicylic acid and ketorolac more than 85% of all detectable outer membrane proteins changed and most were down-regulated. Moreover, in the presence of salicylic acid at least five gene products, including Na+ - translocating NADH (Nrq1), choline dehydrogenase (CHDH), a hypothetical protein of unknown function, a gene product with no similarity to any known sequence in the database and a sequence similar to 23S rRNA of P. aeruginosa, were down-regulated. The results of this study clearly demonstrated that NSAIDs have a significant impact on virulence factors and the expression of acylated homoserine lactones by P. aeruginosa. This thesis has illustrated the potential of NSAIDs for preventing bacterial contamination of contact lenses by ocular pathogens and highlights the potential for NSAIDs as antibacterial agents. Therefore, this class of compound should be investigated further for their therapeutic efficacy in vivo.

Bibliography: leaves 107-109.

[Truncated abstract] Type 1 Diabetes is emerging as a significant public health problem faced by nearly every country in the world. It has major economic and social implications with considerable burden of illness. Approximately 140,000 Australians have been diagnosed with T1DM with an annual increase in incidence rate of 3% per year, comparable to the overall global increase. The management of T1DM requires insulin therapy which places considerable burden on the patient and their carers. Coping with daily insulin injections, dietary changes, modification of physical activity and vigilant monitoring of blood glucose levels, will impact on patient?s quality of life. The optimum goal for the treatment of type 1 diabetes is to safely achieve near-normal glycaemia and failure to maintain this goal accelerates the progression of the devastating long term complications of diabetes. Unfortunately attempts to achieve near normal glycaemia are limited by the risk of excessive lowering of blood glucose levels and hypoglycaemia remains a major barrier to strict glucose control of diabetes. In general this thesis focuses on two fundamental issues related to the epidemiology of severe hypoglycaemia. Namely, methodological consideration when analysing prospective observational data and application of the most robust methodology. A prospective open cohort study of the Princess Margaret Hospital diabetes clinic established in 1992, with 99% case ascertainment was used. This hospital is the only paediatric referral centre for type 1 diabetes and every child diagnosed in the state of Western Australia is treated at this centre. ... The results of this study showed that severe hypoglycaemia remains a major problem and recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycaemia. The study in chapter 7 investigates genetic risk factors related to severe hypoglycaemia. A significant relationship where the presence of the iv deletion (D) allele of the angiotensin-converting enzyme (ACE) increases risk of severe hypoglycaemia has been reported. This study concludes that the presence of D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia. In an attempt to optimize glycemic control, patients may suffer multiple episodes of severe hypoglycaemia which can adversely affect quality of life as well as educational and intellectual disadvantage. The study in chapter 8 investigates the factors related to recurrent severe hypoglycaemia. A rigorous and informative time-to-event approach is used to account for within child correlation, staggered enrolment and timevarying covariates. This allows important risk factors to change over time. Preschool children have an increased risk of experiencing recurrent severe hypoglycaemia. The findings of this thesis highlights the importance of selecting appropriate analytical methodology to identify risk factors associated with severe hypoglycaemia and also to dismiss factors that had previously been thought to be important. This will help in formulating management plans in order to limit the impact of severe hypoglycaemia.

Although Hormone Therapy (HT) is the most effective treatment for alleviating menopausal vasomotor symptoms and reducing bone loss, many women are reluctant to take this treatment due to side effects and concerns about safety. Epidemiological studies suggest that a significant proportion of women use Complementary and Alternative Medicine (CAM) therapies to alleviate vasomotor symptoms and improve quality of life. Anecdotal and clinical evidence indicate a number of CAM therapies, such as herbal medicine, may be effective in alleviating symptoms and modulating bone metabolism. Hence, in the context of concerns over the safety of HT and the extensive history of the clinical use of herbal medicine, this thesis investigated issues pertinent to CAM use and the menopausal transition. The aims of this thesis were to: • Examine the nature and extent of CAM use by women transitioning through menopause • Evaluate the effectiveness of a herbal formula containing Chinese herbs and Cimicifuga racemosa for alleviating vasomotor symptoms, improving quality of life and modulating bone turnover markers. From July 2003 until July 2004 the Women’s Health during Midlife Survey recruited 1,296 women aged 45-65 who were symptomatic when transitioning through menopause or asymptomatic but taking menopause specific treatments. A validated 19-item survey instrument assessed the use of CAM modalities and menopause specific products. The instrument was completed voluntarily and anonymously by women recruited from three strata; menopause clinics, clinics of general practice and government agencies. Approximately 54% of respondents had visited a CAM practitioner and/or used a CAM product during the previous 12 months. The most popular practitioners were the naturopath (7.2%) and acupuncturist (4.8%), while soy (25.4%) and evening primrose oil (EPO, 18.4%) were the most popular products. Massage and chiropractic were considered the most effective therapies, while phytoestrogen tablets and EPO were the most efficacious products. Although 26.4% of respondents indicated their doctor asked about CAM use, 71% of CAM users said they informed their physician about using CAM. Of the 60% of women using pharmaceutical medicines, 62.5% reported using a CAM product during the preceding 12 months. The survey results confirm the continued popularity of CAM use amongst women transitioning through menopause. A number of treatments were perceived to be effective in relieving symptoms. However, communication between medical practitioners and patients about CAM use is inadequate, and given the high use of pharmaceutical medicines this oversight may unnecessarily expose women to drugherb interactions. A randomised, double-blind, placebo controlled clinical trial was conducted to evaluate the effectiveness of a herbal formula derived from two traditional Chinese herbal formulae with the addition of Cimicifuga in alleviating vasomotor symptoms. The trial recruited 93 healthy women who reported at least six vasomotor symptoms per day. After a four week baseline period, women were randomly allocated to receive either herbal treatment or identical looking placebo tablets for 16 weeks. During the trial women recorded the number and severity of their flushes on a Daily Flush Diary, and at each monthly consultation two quality of life scales were completed. Forty nine eligible trial women were entered into a pilot study to assess the effect of the formula on bone turnover markers; bone specific alkaline phosphatase and deoxypyridinoline (corrected for creatinine). The herbal formula was found to be no more effective than placebo in reducing the frequency of flushing and the composite hot flush score or in improving quality of life. The pilot study found the formula had no effect on bone turnover markers after 16 weeks of treatment. Therefore, this formula cannot be recommended as a treatment for vasomotor symptoms and is unlikely to have any long term effect on bone. The use of CAM during the menopausal transition is very popular. Although this thesis found the current herbal formula to be an ineffective treatment, the scientific evaluation of potential CAM therapies is imperative so that health care professionals and consumers can make informed decisions concerning treatment options for the alleviation of symptoms. / Doctor of Philosophy (PhD)

Bibliography: leaves 196-251 / ii, 251 leaves : ill ; 31 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, 1987

"April 2004" / Bibliography: leaves 121-142. / xviii, 142, [19] leaves : ill. (some col.), plates (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Attempts to build a complete understanding of the cellular mechanisms associated with gastrointestinal mucositis through investigations of the effects throughout the gastrointestinal tract of chemotherapeutic agents Methotrexate and Irinotecan, the possible ameliorating potential of the cytokine Interleukin-11 in reducing the side effects of chemotherapy, the expression of pro- and anti-apoptopic proteins and transcription factors along the gastrointestinal tract in normal human patients and the time-course of development of oral mucositis in human patients. Suggests that the entire gastrointestinal tract follows a similar pattern of development of mucositis. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2004