|dc.description.abstract||1. The first studies of this thesis concerned human
phagocytic cells in vivo as they responded to physical
trauma in an experimental skin abrasion. This showed
the sequence of cellular responses during acute inflammation and provided quantitative data about the phagocytic cell concentrations at each stage.
2. In an identical skin abrasion several antibiotics,
administered systemically, were assayed. This provided
information about the approximate concentration of each
drug in acute inflammatory exudates.
3. A series of in vitro tests were performed to quantify
the rate at which phagocytic cells, or the various antibiotics, could inactivate Staphylococcus aureus type 42b.
The concentrations used were based on concentrations
measured in vivo (paragraphs 1 and 2 above).
These studies showed that phagocytosis by human
granulocytes is rapid (T-§- = 5.6 minutes), but subsequent
intracellular killing is much slower. In a cell-free
system different antibiotics had variable rates of bacterial inactivation but, in general, these rates were of
the same order as the rate of intracellular killing by
normal human granulocytes. All these experiments
utilised phagocytic cells and antibiotics separately.
4. The most important findings relate to the combined action of phagocytic cells and antibiotics (particularly
ampicillin). The first clinical studies showed that
during antibiotic therapy the rate of intracellular
killing usually decreased. This effect could not be
demonstrated by adding ampicillin in vitro to granulocytes during their phase of intracellular killing.
However, when ampicillin was administered orally
to 4 healthy subjects there was a decrease of intracellular killing at 1 and 2 hours. The exact cause
has not been established, but collaborative work indicates that this may be the result of inhibition by
ampicillin of leucocyte myeloperoxidase and interference
with other enzymes involved in the production or breakdown of intravacuolar hydrogen peroxide.
5. The importance of these findings is discussed in
the light of a growing awareness that antibiotic therapy
has considerable limitations and may have serious adverse
|dc.publisher||The University of Edinburgh||en
|dc.relation.ispartof||Annexe Thesis Digitisation Project 2016 Block 4||en
|dc.title||Antibiotics and human phagocytic cells||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en