Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 50-57). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 50-57). Also available on the Internet.

Thesis (Ph. D.)--Illinois State University, 1973. / Title from title page screen, viewed Oct. 14, 2004. Dissertation Committee: William L. Daniel (chair), Herman E. Brockman, David F. Weber, Arlan Richardson, Howard Hetzel. Includes bibliographical references (leaves 53-66) and abstract. Also available in print.

Class of 2015 Abstract / Objectives: The primary objective of the study was to evaluate for change in vitamin D levels and regimens in cystic fibrosis (CF) patients following implementation of the 2012 Cystic Fibrosis Foundation (CFF) vitamin D guidelines. Secondary endpoints included clinician adherence to guideline recommendations for treatment and management of vitamin D deficiency. Methods: This retrospective chart review included CF patients with 25-hydroxy vitamin D (25(OH)D) levels from University of Arizona Medical Center (UAMC) between April 1, 2011-March 31, 2012 and July 1, 2012-June 30, 2013. Total 25(OH)D levels and vitamin D regimens were collected along with data on respiratory cultures, pulmonary function, and hospitalizations. Data were analyzed by Student’s T-tests and chi square analyses. Results: A total of 62 patients were included in the study. Mean 25(OH)D levels did not significantly differ between the study periods (28.9±10.5 ng/mL pre-guideline and 27.0±9.1 ng/mL post-guideline, p=0.158). Cholecalciferol use increased post-guideline (57.1%) versus pre-guideline (75.8%, p=0.027). Post-guideline cholecalciferol doses increased to 2836.5±2669.4 international units [IU] daily compared to 1518.0±912.0 IU daily pre-guideline (p<0.001). Clinician adherence to dose titration recommendations resulted in significant 25(OH)D level elevations (28.3±8.9 ng/mL versus 24.7±9.0, p=0.047). Conclusions: The prescribing pattern of clinicians significantly changed to reflect vitamin D regimens suggested by CFF guidelines. This finding suggests that had sufficient time been allowed following guideline implementation, a significant difference in 25(OH)D levels would have resulted. Additional research is needed concerning the effect of the guidelines on vitamin D status, clinical outcomes, and comorbidities.

Following reports by Shapira et al. that α₂Macro-globulin (α₂M) is abnormal in cystic fibrosis (CF), the author set out to examine the properties of α₂M isolated from the plasma of children with CF and from the plasma of age/sex matched controls. To do so, a technique capable of isolating pure, physiologically "active" α₂M from small plasma samples had to be developed. By a two-step chromatographic technique, involving Cibacron Blue Sepharose chromatography and immuno-adsorption, the author was able to isolate "active" CF and control α₂M of at least 98 percent purity from 5 ml of plasma, regardless of plasma haptoglobin type. Having accomplished this, comparative studies of CF and control α₂M were undertaken. Four parameters were investigated: (1) the molar protease binding of α₂M (2) the interaction of α₂M -bovine cationic trypsin (BCT) complexes with the low molecular weight substrate BAEE, (3) the stability of formed α₂M-BCT complexes, and (4) the subunit structure of α₂M. Contrary to the reports of Shapira and his colleagues, this author found no differences between the subunit structure of CF and control α₂M nor between the abilities of CF and control α₂M to interact with BCT. Based upon these findings, the author believes that no firm evidence exists to implicate an α₂M defect in the pathogenesis of cystic fibrosis. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

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A variety of phenotypes of P. aeruginosa can be isolated from the sputum of cystic fibrosis (CF) patients colonised by this organism. Previous studies have described an association between some of these phenotypes and suggested that their emergence was due to conversion or selection by temperate phage. As a result I carried out, (a) a comparative survey of phenotypes in 200 CF and 100 non-CF cultures of P. aeruginosa and a statistical analysis of their association, (b) a study of the rates of mutation for the predominant phenotypes and their genetic linkage, (c) a study of the incidence and properties of temperate phages in CF and non-CF cultures and their association with strain phenotype. A wide range of phenotypes were found in CF and the most frequent were mucoid colony type (50%), atypical serotype (86%), serum sensitivity (74%) and extreme sensitivity to antibiotics and antimicrobial agents, especially to carbenicillin (20%), Irgasan (25%), nalidixic acid (20%), EDTA (20%), cetrimide (10%) and trimethoprim (20%). In contrast, less than 1% of non-CF isolates exhibited these characteristics. Statistical analysis showed that with the exception of antibiotic hypersensitivity, the phenotypes of CF cultures were generally unrelated. Mutation rates determined for the predominant CF phenotypes showed that they were strain dependent and varied between each distinct phenotype. Although some evidence was found for linkage between some of the phenotypes, it was also strain related and the majority of traits varied independently of each other. The incidence of temperate phage was similar in CF and non-CF cultures. Furthermore, the lysogeny state did not influence strain phenotype. P. aeruginosa temperate phages isolated from both collections were similar in host range and serological properties, but were distinct from the typing phages. The selection and examination of the features of phage resistant variants by the use of virulent and temperate phages showed that some cultures exhibited characteristics similar to those isolated from CF. No evidence was found for the role of phage in promoting phenotype change in CF.

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