Thesis (M.Med.Sc.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 73-81). Also available in print.

Galen’s theory of black bile is strongly influenced by his aim to bring together a wide range of material from the work of different physicians and philosophers that begins with Hippocrates. This has caused there to be a large amount of inconsistencies in his writing on black bile. There has been a tendency in modern scholarship either to try to resolve these inconsistencies or to ignore them completely. In many cases there has been an emphasis on the definition of black bile in the Hippocratic On the Nature of Man as the most important basis for understanding Galen’s characterisation of black bile. My analysis will challenge this assumption concerning the dominance of On the Nature of Man for Galen’s use of black bile in his explanation of health and disease in the body. I shall show that an investigation of the way that Galen characterises the physical properties and function of black bile reveals that it is better to understand his use of this humour in terms of his attempt to bring material from a wide range of authorities together to support the arguments that he presents in his treatises. Galen defines black bile as three distinct types of substance that differ in physical properties in order to account for the different ways that this humour is characterised and defined in the various medical sources that he draws upon. However, he is unable to produce a theory of black bile without inconsistencies relating to a number of issues that include such factors as his naming of the different forms of black bile and his concept of authenticity of texts in the Hippocratic Corpus. Galen’s strategy is to make his audience believe that there is a comprehensive and well-defined theory of black bile that originates in the work of Hippocrates and was followed by certain physicians and philosophers afterwards. But in reality this is just a façade and Galen defines and uses black bile in many different and inconsistent ways for his arguments and refutations that cannot always be reconciled with the content of his sources.

A infecção das vias biliares é uma doença freqüente com alta morbidade e mortalidade, que pode variar de 10 a 60% dependendo de sua gravidade. A causa mais comum desta infecção é a presença de cálculos na via biliar principal que propicia o surgimento de bacteriobilia. O profundo conhecimento das características microbiológicas da bile nos casos de coledocolitíase e infecção das vias biliares são fundamentais para o melhor diagnóstico desta infecção e escolha da antibioticoterapia a ser instituída. Assim, o objetivo deste estudo foi de caracterizar os principais aspectos microbiológicos da bile dos pacientes com e sem coledocolitíase e avaliar sua importância na escolha dos antimicrobianos para o tratamento da infecção das vias biliares. Foram analisados 33 pacientes que foram divididos em um grupo de 10 pacientes sem coledocolitíase (grupo controle) no momento da Colangiografia Endoscópica (CPER) e em outro grupo de 23 pacientes com coledocolitíase. A bile de todos os pacientes foi coletada no início do procedimento endoscópico, através de catater introduzido na via biliar. O exame de microscopia direta com coloração de Gram e as culturas da bile foram negativas nos 10 pacientes que não apresentaram coledocolitíase durante a CPER. Dos 23 pacientes com cálculos na via biliar principal, 19 (83%) apresentaram culturas positivas. Desses 19 pacientes com culturas de bile positivas, 18 (94,7%) apresentaram microorganismos detectáveis à microscopia direta com coloração de Gram. Apenas um paciente apresentou crescimento de germe anaeróbio (Bacteroides fragilis). O cultivo de 28 bactérias teve predominância de microorganismos Gram negativos (18 bactérias- 64,3%). Os germes isolados foram E. coli (9, 32,1%), Klebsiella pneumoniae (5, 17,9%), Enterococcus faecalis (5, 17,9%), Streptococcus alfa-haemoliticus (3, 10,7%), Streptococcus viridans (2, 7,1%), Enterobacter cloacae (2, 7,1%), Panteona aglomerans (1, 3,6%) e Pseudomonas aeruginosa (1, 3,6%). Todos os pacientes com microorganismos detectados pela microscopia direta com coloração de Gram tiveram crescimento bacteriano em suas culturas, por outro lado nenhum paciente com cultura negativa apresentou microoorganismos à microsopia direta ( p= 0,0005). Nesses casos, a microsopia direta apresentou uma especificidade de 100% e sensibilidade de 80%. A análise quantitativa das culturas da bile mostrou que das 19 culturas positivas, 12 (63,2%) tiveram pelo menos um germe com contagem superior a 105 ufc/ml. Todas as bactérias Gram positivas isoladas foram sensíveis à ampicilina, da mesma forma que todas as Gram negativas foram sensíveis aos aminoglicosídeos. Os achados deste estudo demonstram uma boa correlação entre a microscopia direta da bile com coloração de Gram e os achados bacteriológicos das culturas da bile coletada por colangiografia endoscópica retrógrada. O esquema terapêutico antimicrobiano tradicionalmente empregado em nosso hospital, que inclui a combinação de ampicilina e gentamicina, parece ser adequado, pois apresenta eficácia terapêutica contra os principais microorganismos responsáveis pela infecção das vias biliares. / Acute cholangitis is an important cause of emergency admission for acute abdomen. The bacterial infection of the biliary system is associated with obstruction caused by ductal stones. Ductal obstruction leads to a raised intrabiliary pressure with bacteriobilia, cholangiovenous reflux, and bacteremia, which may progress to septicemia. We have studied the bacteriology of bile and clinical manifestations of 23 patients with choledocholithiasis and 10 patients without evidence of choledocholithiasis by endoscopic retrograde cholangiography. Nineteen (82.6%) of 23 patients with choledocholithiasis had positive bile cultures, and none of the patients without choledocholithiasis had positive bile cultures. A single microorganism was detected in 11 (57.9%) patients, while a mixed growth, with pathogens ranging from two to three species, were seen in 8 (42,1%) patients. Patients with clinical manifestations of cholangitis such as fever, abdominal pain, and jaundice (Charcot’s triad) had significant higher counts of colonies per ml of bile (p <0.001). The predominant microorganisms isolated were Escherichia coli (32,1%), Klebsiella spp. (17,9%), Enterococcus faecalis (17,9%), Streptoccus alfa-hemoliticus (10,7%), Enterobacter cloacae (7,1%), Streptococcus viridans (7,1%), Pseudomonas aeruginosa (3,6%), and Bacteroides fragilis (3,6%). In vitro susceptibility testing of the aforementioned biliary pathogens revealed ampcillin and gentamicin to have higher spectrum of antimicrobial activity. In summary, patients with choledocholithiasis have a high recovery rate of bacteria from the bile. The severity of biliary infection is associated with higher concentrations of bacteria in the choledocal bile. The data suggest that antimicrobial therapy of biliary tract infections should combine good in-vitro activity against Enterobacteriaceae (mainly Escherichia coli and Klebsiella spp.) and Enterococcus. spp. Based on the in vitro susceptibility testing of the isolated biliary pathogens, the combination of ampicillin and gentamicin seems to be an appropriate therapeutic regimen for biliary tract inferctions.

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A infecção das vias biliares é uma doença freqüente com alta morbidade e mortalidade, que pode variar de 10 a 60% dependendo de sua gravidade. A causa mais comum desta infecção é a presença de cálculos na via biliar principal que propicia o surgimento de bacteriobilia. O profundo conhecimento das características microbiológicas da bile nos casos de coledocolitíase e infecção das vias biliares são fundamentais para o melhor diagnóstico desta infecção e escolha da antibioticoterapia a ser instituída. Assim, o objetivo deste estudo foi de caracterizar os principais aspectos microbiológicos da bile dos pacientes com e sem coledocolitíase e avaliar sua importância na escolha dos antimicrobianos para o tratamento da infecção das vias biliares. Foram analisados 33 pacientes que foram divididos em um grupo de 10 pacientes sem coledocolitíase (grupo controle) no momento da Colangiografia Endoscópica (CPER) e em outro grupo de 23 pacientes com coledocolitíase. A bile de todos os pacientes foi coletada no início do procedimento endoscópico, através de catater introduzido na via biliar. O exame de microscopia direta com coloração de Gram e as culturas da bile foram negativas nos 10 pacientes que não apresentaram coledocolitíase durante a CPER. Dos 23 pacientes com cálculos na via biliar principal, 19 (83%) apresentaram culturas positivas. Desses 19 pacientes com culturas de bile positivas, 18 (94,7%) apresentaram microorganismos detectáveis à microscopia direta com coloração de Gram. Apenas um paciente apresentou crescimento de germe anaeróbio (Bacteroides fragilis). O cultivo de 28 bactérias teve predominância de microorganismos Gram negativos (18 bactérias- 64,3%). Os germes isolados foram E. coli (9, 32,1%), Klebsiella pneumoniae (5, 17,9%), Enterococcus faecalis (5, 17,9%), Streptococcus alfa-haemoliticus (3, 10,7%), Streptococcus viridans (2, 7,1%), Enterobacter cloacae (2, 7,1%), Panteona aglomerans (1, 3,6%) e Pseudomonas aeruginosa (1, 3,6%). Todos os pacientes com microorganismos detectados pela microscopia direta com coloração de Gram tiveram crescimento bacteriano em suas culturas, por outro lado nenhum paciente com cultura negativa apresentou microoorganismos à microsopia direta ( p= 0,0005). Nesses casos, a microsopia direta apresentou uma especificidade de 100% e sensibilidade de 80%. A análise quantitativa das culturas da bile mostrou que das 19 culturas positivas, 12 (63,2%) tiveram pelo menos um germe com contagem superior a 105 ufc/ml. Todas as bactérias Gram positivas isoladas foram sensíveis à ampicilina, da mesma forma que todas as Gram negativas foram sensíveis aos aminoglicosídeos. Os achados deste estudo demonstram uma boa correlação entre a microscopia direta da bile com coloração de Gram e os achados bacteriológicos das culturas da bile coletada por colangiografia endoscópica retrógrada. O esquema terapêutico antimicrobiano tradicionalmente empregado em nosso hospital, que inclui a combinação de ampicilina e gentamicina, parece ser adequado, pois apresenta eficácia terapêutica contra os principais microorganismos responsáveis pela infecção das vias biliares. / Acute cholangitis is an important cause of emergency admission for acute abdomen. The bacterial infection of the biliary system is associated with obstruction caused by ductal stones. Ductal obstruction leads to a raised intrabiliary pressure with bacteriobilia, cholangiovenous reflux, and bacteremia, which may progress to septicemia. We have studied the bacteriology of bile and clinical manifestations of 23 patients with choledocholithiasis and 10 patients without evidence of choledocholithiasis by endoscopic retrograde cholangiography. Nineteen (82.6%) of 23 patients with choledocholithiasis had positive bile cultures, and none of the patients without choledocholithiasis had positive bile cultures. A single microorganism was detected in 11 (57.9%) patients, while a mixed growth, with pathogens ranging from two to three species, were seen in 8 (42,1%) patients. Patients with clinical manifestations of cholangitis such as fever, abdominal pain, and jaundice (Charcot’s triad) had significant higher counts of colonies per ml of bile (p <0.001). The predominant microorganisms isolated were Escherichia coli (32,1%), Klebsiella spp. (17,9%), Enterococcus faecalis (17,9%), Streptoccus alfa-hemoliticus (10,7%), Enterobacter cloacae (7,1%), Streptococcus viridans (7,1%), Pseudomonas aeruginosa (3,6%), and Bacteroides fragilis (3,6%). In vitro susceptibility testing of the aforementioned biliary pathogens revealed ampcillin and gentamicin to have higher spectrum of antimicrobial activity. In summary, patients with choledocholithiasis have a high recovery rate of bacteria from the bile. The severity of biliary infection is associated with higher concentrations of bacteria in the choledocal bile. The data suggest that antimicrobial therapy of biliary tract infections should combine good in-vitro activity against Enterobacteriaceae (mainly Escherichia coli and Klebsiella spp.) and Enterococcus. spp. Based on the in vitro susceptibility testing of the isolated biliary pathogens, the combination of ampicillin and gentamicin seems to be an appropriate therapeutic regimen for biliary tract inferctions.

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Surface modifications of bone-interfacing biomedical devices can increase their longevity by promoting bond formation and new bone growth, while reducing the toxic effects of corrosion and wear particles. Coatings which contain biocompatible polymers, bioceramics, drugs, and functional molecules are one route to achieve this. Here, a biomimetic approach is developed for the fabrication of poly(ethyl methacrylate) (PEMA) coatings. For the first time it is shown that PEMA can be solubilized in non-toxic solvents by naturally occurring bile acids. Their unique chemical structure and amphiphilicity allows for efficient solubilization of polymer macromolecules. Advancements in colloidal sciences enable a facile deposition method termed “dip coating” to be utilized. The feasibility of highly concentrated solutions of high molecular mass PEMA was a key factor for film deposition by dip coating. Singular layers or multilayered PEMA films could be deposited. Heat-treated PEMA films provided corrosion protection to stainless steels. This inexpensive and simple technique can be up scaled to larger manufacturing levels, leading to mass production and clinical development of novel coatings for biomedical applications. Additional challenges in the fabrication of composite coatings by dip coating were successfully addressed using bile acids. To produce high quality composite coatings by dip coating, a stable suspension is required. Particle aggregation leads to uneven coatings, poor adhesion, and weakened mechanical properties. It was shown that bile acids could act as dispersing agents to mediate this. PEMA coatings containing inorganic materials hydroxyapatite, silica, titania, and diamond were fabricated. The inorganic component of the films could be increased to 50 wt.%. Model drugs tetracycline and ibuprofen were used for the creation of drug-loaded PEMA coatings. Lastly, composite coatings containing functional molecules including heparin and nanocellulose were created. Overall, these coatings provide corrosion resistance to metallic orthopedic implants, while enhancing potential biocompatibility of the device. The biomimetic approach developed in this investigation was motivated by the role of bile acids and bile salts as solubilizers of cholesterol and other molecules within the digestive system of mammals. A solubilization mechanism has been proposed. This work paves the way for the fabrication of future composite coatings containing other high molecular mass polymers, inorganic nanomaterials, and functional materials or drugs. / Thesis / Master of Applied Science (MASc) / Biomedical devices have various properties they must possess to perform their function within the body without harming the patient. Coatings applied to these devices can mitigate the body’s response by reducing corrosion, preventing wear, and promoting bond formation. This increases the lifespan of the device and prevents invasive revision surgeries. Advances in materials engineering and colloidal sciences can help achieve these goals. Materials selection for novel coatings can be inspired by the composition of real bone - consisting of a polymer matrix with embedded inorganic nanomaterials. Additionally, manufacturing techniques that avoid high temperatures are desirable. Therefore, advances in colloidal sciences which enable coatings to be fabricated by a simple and inexpensive method known as dip coating is of paramount importance. This work used natural biosurfactants bile acids to aid in fabrication of coatings for biomedical devices using advanced polymer poly(ethyl methacrylate) and functional inorganic materials.

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