Cystic fibrosis case study

Case Study Cystic Fibrosis and Gene Therapy... 

The rationale for the need of recovery animals was frequently discussed. For drag substances which require chronic (live time) treatment (e.g. oral anti-diabetics, drags for treatment of hypertension, anti-Parkinson drugs, etc.) the question of recovery is less important than in the case of anti-infectives with, in most cases, short treatment periods where mild symptoms of intolerance, e.g. diarrhoea, are observed. However, inclusion of recovery animals is recommended in general because at the stage of development where first clinical studies are conducted, the whole set of indications is not finally known and line extensions can happen. One example is the use of quinolones and other anti-infectives for the treatment of cystic fibrosis. Another example is drugs used for chemotherapy of malignant diseases where recovery has to be studies anyway. 

Designed for students and instructors interested in clinical applications, the Clinical Companion is a rich compendium of medical case studies and clinical discussions. It contains numerous problems and references to the textbook. Such topics as glaucoma, cystic fibrosis, Tay-Sachs disease, and autoimmune diseases are covered from a biochemical perspective. 

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa. 

The levels of j8-D-2-acetamido-deoxyglucosidase activity in skin fibroblasts from cases of cystic fibrosis and controls have been compared. In a study of I-cell disease (mucolipidosis II) a model has been presented for the structure of the carbohydrate recognition site of fibroblast-derived )3-D-2-acetamido-2-deoxyhexosidase that may extend to the other affected hydrolases and that is responsible for specific uptake of the enzyme by fibroblasts. ... 

The levels of jS-D-galactosidase activity in skin fibroblasts from cases of cystic fibrosis and controls have been compared. Complementation studies have been conducted with enucleated fibroblasts from different variants of jS-D-galactosidase deficiency. ... 

The levels of a-D-mannosidase activity in skin fibroblasts from cases of cystic fibrosis and controls have been compared. The effects of pH, metal ions, and heat have been studied on a-D-mannosidase from normal and mannosidosis fibroblasts and in culture medium derived from these. The results showed that enzymes secreted from mannosidosis fibroblasts behaved identically to the enzymes present in culture medium from normal fibroblasts. The implication of this finding was discussed. Two acidic forms of a-D-mannosidase activity, A and B have been separated and characterized from fibroblasts from controls and patients with mannosidosis. In normal cells, A and B differ in adsorption on DEAE-cellulose, electrophoretic mobility, stability at 70 °C, and resistance to freezing at — 20 °C, In five of six mutant cell lines, A and B both exhibited altered K s for artificial substrates, and decreased thermal stability. Zn had no effect on A or B in mutant or normal cells. In contrast, Co + slightly inhibited B in normal cells but markedly enhanced the activity of B in mutant cells. It was concluded that the mutation in mannosidosis results... 

A meta-analysis of azithromycin for greater than 6 months in chronic lung disease was associated with a 2.7-fold increase in resistant pathogens (95% Cl 1.249-5.211) [105 ]. High rates of macrolide-resistant pathogens were also seen in controlled trials of Tanzanian children treated with Mass Distribution of Azithromycin for endemic Chlamydia trachomatis [lOh ] and in paediatric cystic fibrosis patients [107 ]. A French case-control study did not find an association between long-term Azithromycin use and M. abscessus in adult and paediatric cystic fibrosis patients [lOS ]. 

Burdge DR, Nakielna EM, Noble MA. Case-control and vector studies of nosocomial acquisition of Pseudomonas cepacia in adult patients with cystic fibrosis. Infect Control Hosp Epidemiol 1993 14 127-130. 

The studies referred to above use LDL in an in vitro assay, but the ultimate antioxidant test is whether these compounds work in animals or humans. There are very few examples of an in vivo antioxidant action of a carotenoid in humans. The best recent examples come from studies with children suffering from cystic fibrosis who are known to have relatively low levels of carotenoids in their serum. These patients are supplemented with large amounts of vitamin E, but still show significantly elevated levels of malondialdehyde in their serum. Two groups have supplemented patients with this disease with p-carotene, and in each case, they reported a decrease in the malondialdehyde levels [27, 20] as well as increased resistance of LDL to oxidant stress [27]. 

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