- Email: [email protected]
Sir Ashley Miles
Journal
of Hospital
Infection
(1994)
27,
PIONEERS
161-166
IN INFECTION
Sir Ashley
CONTROL
Miles
R. E. 0. Williams Little
Platt,
Plush, Dorchester, Dorset DT2
Accepted for publication Keywords:
Miles,
12 May
cross-infection;
7RQ, UK
1994
inflammation.
Early days Ashley Miles’ introduction to pathology and bacteriology was in the Cambridge department presided over by the redoubtable Henry Dean, but it was not until after he qualified in medicine from St Bartholomew’s Hospital Medical College, had held house appointments and had obtained the MRCP, that he took any special interest in bacteriology. In 1929 he obtained a post in the Bacteriology Department at the newly established London School of Hygiene and Tropical Medicine, under Professor W. W. C. Topley. Topley set him to work under G. S. Wilson and together they studied the antigens of Brucella spp. using the classical ‘optimal proportions’ method devised by Dean and Webb. Miles continued to study BruceHa antigens for some years, after his return to the Pathology Department at Cambridge in 1931, in collaboration with N. W. Pirie. Miles and Misra In 1935 Miles was appointed Reader in Bacteriology in the newly created Postgraduate Medical School at Hammersmith and in the short time that he was there he initiated studies on the bactericidal power of normal human blood. With S. S. Misra he described and explored in a characteristically critical way, the method of counting viable bacteria, known ever since as ‘Miles and Misra’. University
College Hospital
When Miles took up the chair of Bacteriology at University College Hospital Medical School in 1938 he entered a department in which there was already work on the more epidemiological aspects of bacteriology to which he was 0195-6701/94/070161+06
0 1994 The Hospml
nSOS.OO/O
161
Infection
Society
162
R. E. 0. Williams
later to contribute so much. S. D. Elliott,’ working with Miles’ predecessor Okell, had used Griffith’s method for typing haemolytic streptococci and demonstrated the importance of streptococcal infection as a complication of ear, nose and throat surgery. Joyce Wright and colleagues3 had studied outbreaks of infection in the children’s wards of the hospital and had worked out guidelines for prevention. Soon after he arrived at UCH Miles and his colleagues investigated an outbreak of postoperative staphylococcal infection in the patients of one surgical team, and were able to trace the infection to one of the surgeons, who proved to be a profuse skin carrier of staphylococci.4 This finding was especially important because American authors had been laying great stress on the risks of airborne transfer in the causation of staphylococcal wound infection. In Miles’ studies it seemed clear that transfer was directly from the surgeon’s skin by contact through permeable surgical gowns or glove punctures. Medical students in the 1930s were expected to learn quite a lot of straight bacteriology and for the course at UCH Miles produced a minor textbook that provided so much detail that several of us continued to use it as a bench manual for some years. When he returned to teaching at the London Hospital Medical College in the 198Os, he found it very sad that relatively little real bacteriology was being taught to medical students. Miles’ lectures were also packed with information; they were hard going for most students but were the inspiration that started several of us on a career in microbiology. It was not only for the medical student that Miles devised teaching methods; both at UCH and later in Birmingham he organized classes in applied bacteriology for the nurses. The
Emergency
Medical
Service and wounds
streptococcal
infection
of war
At the outbreak of war in 1939 Miles was appointed to take charge of pathology in the Emergency Medical Service laboratories of the north west sector of London and was based in part of a poor-law workhouse at Shrodells Hospital in Watford, which he rapidly transformed into a very efficient laboratory. The introduction to the field of cross-infection in hospitals that he had gained at UCH soon proved valuable: the wounds of men evacuated from Dunkirk were soon shown to acquire streptococcal infection both prior to admission to hospital, and during their stay in hospital. In a long paper published in the British Medical Journal in the autumn of 1940, Miles and his colleagues documented the increase in the frequency with which haemolytic streptococci could be recovered from wounds during the patients’ stay in hospital and gave a clear example of one ward ‘outbreak’ of streptococcal infection among patients with war wounds. They discussed the possible channels of infection and laid out a number of principles on which prevention should be based. These were
Sir Ashley
163
Miles
repeated in a more prescriptive form in a War Memorandum published by the Medical Research Council in 1941 ,6 to which Miles had contributed substantially. Miles was always interested in a statistical approach to epidemiology, and indeed in his undergraduate lectures at UCH he had included a good introduction to statistical methods. With the neurosurgeon Wylie McKissock and Joyce Wright7 he tested the benefit of managing postoperative wounds with improved hygienic methods that relied principally on no-touch techniques and were based on the belief that the main cause of hospital infection was transfer of infective discharge from one patient’s wound to another by members of the medical and nursing staff. During a preliminary 4-month period 31.3% of 32 patients with head wounds resulting from air raids acquired haemolytic streptococci in their wounds; during a comparable period when improved techniques were used the rate was only 2.2% of 46 casualties. In his Kettle memorial lecture delivered in May 1941, Miles recalled that Kettle had deplored the dominance of the bacteriologist in the study of infective inflammation, because it had elbowed out studies of the host’s reaction and obscured the problem by accumulating so many irrelevant facts about the bacteria. Miles was hardly typical of the bacteriologists of the time, but he went on to show, from his own work on war wounds just described, how indispensable bacteriological methods are in the study of the pathogenesis of wound infection. Moreover (a word with which Miles himself liked to start a sentence) the details of the bacteria, far from being irrelevant, are needed if the distinction of the more from the less pathogenic varieties is to be achieved. Miles also summarized the then current views on the value of sulphonamides as a preventive agent (this was before penicillin became available for use) and speculated on the part played by host factors-a topic to which he was to return after the war. Infection
research
at the Birmingham
Accident
Hospital
In 1941 the Medical Research Council set up a small research unit in the Birmingham Accident Hospital to study wound infection, and Miles was invited to act as its part-time Director. The Accident Hospital had been established, largely as a result of pressure from industrialists, to cope with the considerable number of accidental wounds that were ocurring in workers in the engineering factories in Birmingham, and it seemed that these would provide a continuous source of wounds for the study of infection and its prevention, and could serve as a model for devising methods for the prevention of infection in war wounds. I was lucky enough to be appointed as the resident member of the unit, supported by one technician, G. J. Harper, and a cleaner. Miles visited the unit every 2 weeks and packed at least 48 hours’ worth of energy into the 30 or so hours he spent in Birmingham. It soon became clear that the streptococcal cross-infection
164
R. E. 0. Williams
Sir Ashley
Miles
seen in the war-wound studies was repeated in the industrial wounds so we set about trying to apply the rules laid down in the War Memo and had all postoperative wound dressings carried out with no-touch methods in a special ‘dressing’ room. Miles entered into all the planning with gusto, as he did later when the hospital was designing new outpatient facilities. All innovations had to be cleared with the Medical Director of the hospital, William Gissane, a process that was helped by the fact that Miles generally stayed the night with the Gissanes, but even so there was often need for a full dose of Milesian wile. The lessons from all these studies were summarized in an article Miles wrote for the British Medical Bulletin in 19449 and in our MRC Special Report.” While it had not been too difficult to control most of the streptococcal infections, application of the same control methods made less difference to the overall incidence of staphylococcal infections; with this organism, self-infection from carrier sites on the patient himself seemed of much greater relative importance. Work
on host defences
at the Department of Biological the Lister Institute
Standards
and
In 1947 Miles was appointed Director of the Department of Biological Standards at the National Institute for Medical Research and his interests
Sir Ashley
Miles
165
in infection turned from epidemiology to experimentation. He worked on the enhancement of infection that could be induced in experimental animals by prior treatment with adrenaline or other agents that inhibited the immediate vascular response, and he devised methods for estimating the contribution of various defensive mechanisms for protection against infection with a variety of pathogens. He stressed the importance of the killing of injected pathogens that occurred during the phase of plasma exudation, before the appearance of polymorphs, and showed that this killing was greatest with serum-sensitive organisms (work recalling his prewar studies of the bactericidal power of blood). This work was continued after Miles took up the post of Director of the Lister Institute in 1952. Miles was always something of a philosopher. Indeed I recall being taken to a meeting at the Wright Fleming Institute in 1941 during which Leonard Colebrook introduced Miles to Almroth Wright, saying that here was a young man who had read Wright’s Prolegomena to the Logic that searches after Truth. Miles’ introductory paper to the Fifth Symposium of the Society for General Microbiology in 195S1* discussed the meanings of the terms pathogenicity and virulence, as well as some of the methods for measuring virulence, and their philosophical and statistical limitations; he coined the phrase ‘The Fallacy of the Appropriate Substrate’ to refer to the danger of assuming that, because a pathogenic microbe had an enzyme that attacks some substrate present in the tissues, that enzyme is relevant to its virulence. At the Lister Institute and indeed for some years after 1971, when he retired and worked first at the MRC Clinical Research Centre and later at the London Hospital Medical College, Miles continued his studies of the ‘mechanisms’ of inflammation-a nice complement to his ‘dissent’ from Kettle’s assertion in that lecture of 1941. But by 1960 Miles had become an experimental pathologist as much as a bacteriologist. His contribution to the 1965 celebration of the centenary of Lister’s introduction of the Antiseptic Treatment of Wounds’* summarized the current notions, as he called them, of the origins of the vascular response and fluid exudation in acute infection. He spent much time searching for the relevant mediators of the inflammatory response without reaching any very conclusive results, an indication as he himself recognized of the need for new and more sophisticated techniques than he had time to master. But one part of all this work stands out as of practical importance, namely his studies, several with a young American surgeon J. Burke,13 which demonstrated the crucial importance of the first hours after the introduction of bacteria into the tissues in determining whether or not the bacteria could establish themselves. There is (l), a first phase of fluid exudation and rapid reduction in the number of bacteria brought about by the bactericidal effect of serum and tissue fluids, followed by (2), a subsequent phase of exudation mediated by one or more of the factors identified or yet to be identified, before (3), a third phase when there is vascular occlusion and when blood-borne agents can
166
R. E. 0. Williams
no longer reach the infected site. The lesson was learnt that if antibiotic prophylaxis was to be of value in preventing post-operative wound infection, the antibiotic must be in the circulation at the time when the infection might be introduced-that is during the operation. Ashley Miles was a classical bacteriologist: he enjoyed understanding bacteria as living organisms and devising ways of unravelling their interaction with human or animal hosts. He worked largely with simple methods and with his own hands, and he had a great facility for instilling his enthusiasm in others. His contributions to the study of infection were, first and foremost, the enthusiasm with which he conveyed ideas, whether to medical students or in the numerous symposia and meetings to which he contributed reviews and discussions; second, his strong advocacy for the use of quantitative methods and statistical analysis wherever possible; third, his belief that bacteriologists should be prepared to go out into the field and study the infections that matter where they matter; and last, his painstaking studies of the inflammatory process, which while not leading to a dramatic break-through laid a solid foundation on which new techniques could be built. References 1. Miles AA, Misra SS. The estimation of the bactericidal power of the blood. J Hyg (Camb) 1938; 38: 732-749. CC, Elliott SD. Cross-infection with haemolytic streptococci in otorhinological 2. Okell wards. Lancet 1936; 2: 836-842. J. Nosocomial infections in children’s wards. J Hyg (Camb) 1940; 40: 647-672. 3. Wright, EA, Miles AA. Control of staphylococcal infections in an operating-theatre. 4. Devenish Lancet 1939; 1: 1088-1094. 5. Miles AA, Schwabacher H, Cunliffe AC, Paterson Ross J, Spooner ETC, Pilcher RS, Wright J. Hospital infection of war wounds. BMJ 1940; 2: 855-859, 895-900. Research Council. The Prevention of Hospital Infection. (War Memorandum 6. Medical No. 6) London: HM Stationery Office 1940. 7. McKissock W, Wright J, Miles AA. The reduction of hospital infection of wounds. A controlled experiment. BMJ 1941; 2: 375-377. Miles AA. Some problems of wound infection. Lancet 1941; 2: 507-510. i: Miles AA. Observations on control of hospital infection. Br Med Bull 1944; 2: 276-280. REO, Miles AA. Infection and sepsis in industrial wounds of the hands. A 10. Williams bacteriological study of aetiology and prophylaxis. Spec Rep Ser MRC (Lond) 1949; No. 266. AA. The meaning of pathogenicity. Fifth Symposium of the Society for General 11. Miles MicrobioZogy. Cambridge: Cambridge University Press; l-l 6. 12, Miles AA. Current notions of acute inflammation. In: Illingworth C, Ed. “Wound Healing”, The Lister Centenary Meeting Symposium, London: J & A Churchill Ltd; 3-15. of defence reactions of the skin 13. Miles AA, Miles EM, Burke J. Th e value and duration to the primary lodgement of bacteria. Br J Exp Pathol 1957; 38: 79-96.
of Hospital
Infection
(1994)
27,
PIONEERS
161-166
IN INFECTION
Sir Ashley
CONTROL
Miles
R. E. 0. Williams Little
Platt,
Plush, Dorchester, Dorset DT2
Accepted for publication Keywords:
Miles,
12 May
cross-infection;
7RQ, UK
1994
inflammation.
Early days Ashley Miles’ introduction to pathology and bacteriology was in the Cambridge department presided over by the redoubtable Henry Dean, but it was not until after he qualified in medicine from St Bartholomew’s Hospital Medical College, had held house appointments and had obtained the MRCP, that he took any special interest in bacteriology. In 1929 he obtained a post in the Bacteriology Department at the newly established London School of Hygiene and Tropical Medicine, under Professor W. W. C. Topley. Topley set him to work under G. S. Wilson and together they studied the antigens of Brucella spp. using the classical ‘optimal proportions’ method devised by Dean and Webb. Miles continued to study BruceHa antigens for some years, after his return to the Pathology Department at Cambridge in 1931, in collaboration with N. W. Pirie. Miles and Misra In 1935 Miles was appointed Reader in Bacteriology in the newly created Postgraduate Medical School at Hammersmith and in the short time that he was there he initiated studies on the bactericidal power of normal human blood. With S. S. Misra he described and explored in a characteristically critical way, the method of counting viable bacteria, known ever since as ‘Miles and Misra’. University
College Hospital
When Miles took up the chair of Bacteriology at University College Hospital Medical School in 1938 he entered a department in which there was already work on the more epidemiological aspects of bacteriology to which he was 0195-6701/94/070161+06
0 1994 The Hospml
nSOS.OO/O
161
Infection
Society
162
R. E. 0. Williams
later to contribute so much. S. D. Elliott,’ working with Miles’ predecessor Okell, had used Griffith’s method for typing haemolytic streptococci and demonstrated the importance of streptococcal infection as a complication of ear, nose and throat surgery. Joyce Wright and colleagues3 had studied outbreaks of infection in the children’s wards of the hospital and had worked out guidelines for prevention. Soon after he arrived at UCH Miles and his colleagues investigated an outbreak of postoperative staphylococcal infection in the patients of one surgical team, and were able to trace the infection to one of the surgeons, who proved to be a profuse skin carrier of staphylococci.4 This finding was especially important because American authors had been laying great stress on the risks of airborne transfer in the causation of staphylococcal wound infection. In Miles’ studies it seemed clear that transfer was directly from the surgeon’s skin by contact through permeable surgical gowns or glove punctures. Medical students in the 1930s were expected to learn quite a lot of straight bacteriology and for the course at UCH Miles produced a minor textbook that provided so much detail that several of us continued to use it as a bench manual for some years. When he returned to teaching at the London Hospital Medical College in the 198Os, he found it very sad that relatively little real bacteriology was being taught to medical students. Miles’ lectures were also packed with information; they were hard going for most students but were the inspiration that started several of us on a career in microbiology. It was not only for the medical student that Miles devised teaching methods; both at UCH and later in Birmingham he organized classes in applied bacteriology for the nurses. The
Emergency
Medical
Service and wounds
streptococcal
infection
of war
At the outbreak of war in 1939 Miles was appointed to take charge of pathology in the Emergency Medical Service laboratories of the north west sector of London and was based in part of a poor-law workhouse at Shrodells Hospital in Watford, which he rapidly transformed into a very efficient laboratory. The introduction to the field of cross-infection in hospitals that he had gained at UCH soon proved valuable: the wounds of men evacuated from Dunkirk were soon shown to acquire streptococcal infection both prior to admission to hospital, and during their stay in hospital. In a long paper published in the British Medical Journal in the autumn of 1940, Miles and his colleagues documented the increase in the frequency with which haemolytic streptococci could be recovered from wounds during the patients’ stay in hospital and gave a clear example of one ward ‘outbreak’ of streptococcal infection among patients with war wounds. They discussed the possible channels of infection and laid out a number of principles on which prevention should be based. These were
Sir Ashley
163
Miles
repeated in a more prescriptive form in a War Memorandum published by the Medical Research Council in 1941 ,6 to which Miles had contributed substantially. Miles was always interested in a statistical approach to epidemiology, and indeed in his undergraduate lectures at UCH he had included a good introduction to statistical methods. With the neurosurgeon Wylie McKissock and Joyce Wright7 he tested the benefit of managing postoperative wounds with improved hygienic methods that relied principally on no-touch techniques and were based on the belief that the main cause of hospital infection was transfer of infective discharge from one patient’s wound to another by members of the medical and nursing staff. During a preliminary 4-month period 31.3% of 32 patients with head wounds resulting from air raids acquired haemolytic streptococci in their wounds; during a comparable period when improved techniques were used the rate was only 2.2% of 46 casualties. In his Kettle memorial lecture delivered in May 1941, Miles recalled that Kettle had deplored the dominance of the bacteriologist in the study of infective inflammation, because it had elbowed out studies of the host’s reaction and obscured the problem by accumulating so many irrelevant facts about the bacteria. Miles was hardly typical of the bacteriologists of the time, but he went on to show, from his own work on war wounds just described, how indispensable bacteriological methods are in the study of the pathogenesis of wound infection. Moreover (a word with which Miles himself liked to start a sentence) the details of the bacteria, far from being irrelevant, are needed if the distinction of the more from the less pathogenic varieties is to be achieved. Miles also summarized the then current views on the value of sulphonamides as a preventive agent (this was before penicillin became available for use) and speculated on the part played by host factors-a topic to which he was to return after the war. Infection
research
at the Birmingham
Accident
Hospital
In 1941 the Medical Research Council set up a small research unit in the Birmingham Accident Hospital to study wound infection, and Miles was invited to act as its part-time Director. The Accident Hospital had been established, largely as a result of pressure from industrialists, to cope with the considerable number of accidental wounds that were ocurring in workers in the engineering factories in Birmingham, and it seemed that these would provide a continuous source of wounds for the study of infection and its prevention, and could serve as a model for devising methods for the prevention of infection in war wounds. I was lucky enough to be appointed as the resident member of the unit, supported by one technician, G. J. Harper, and a cleaner. Miles visited the unit every 2 weeks and packed at least 48 hours’ worth of energy into the 30 or so hours he spent in Birmingham. It soon became clear that the streptococcal cross-infection
164
R. E. 0. Williams
Sir Ashley
Miles
seen in the war-wound studies was repeated in the industrial wounds so we set about trying to apply the rules laid down in the War Memo and had all postoperative wound dressings carried out with no-touch methods in a special ‘dressing’ room. Miles entered into all the planning with gusto, as he did later when the hospital was designing new outpatient facilities. All innovations had to be cleared with the Medical Director of the hospital, William Gissane, a process that was helped by the fact that Miles generally stayed the night with the Gissanes, but even so there was often need for a full dose of Milesian wile. The lessons from all these studies were summarized in an article Miles wrote for the British Medical Bulletin in 19449 and in our MRC Special Report.” While it had not been too difficult to control most of the streptococcal infections, application of the same control methods made less difference to the overall incidence of staphylococcal infections; with this organism, self-infection from carrier sites on the patient himself seemed of much greater relative importance. Work
on host defences
at the Department of Biological the Lister Institute
Standards
and
In 1947 Miles was appointed Director of the Department of Biological Standards at the National Institute for Medical Research and his interests
Sir Ashley
Miles
165
in infection turned from epidemiology to experimentation. He worked on the enhancement of infection that could be induced in experimental animals by prior treatment with adrenaline or other agents that inhibited the immediate vascular response, and he devised methods for estimating the contribution of various defensive mechanisms for protection against infection with a variety of pathogens. He stressed the importance of the killing of injected pathogens that occurred during the phase of plasma exudation, before the appearance of polymorphs, and showed that this killing was greatest with serum-sensitive organisms (work recalling his prewar studies of the bactericidal power of blood). This work was continued after Miles took up the post of Director of the Lister Institute in 1952. Miles was always something of a philosopher. Indeed I recall being taken to a meeting at the Wright Fleming Institute in 1941 during which Leonard Colebrook introduced Miles to Almroth Wright, saying that here was a young man who had read Wright’s Prolegomena to the Logic that searches after Truth. Miles’ introductory paper to the Fifth Symposium of the Society for General Microbiology in 195S1* discussed the meanings of the terms pathogenicity and virulence, as well as some of the methods for measuring virulence, and their philosophical and statistical limitations; he coined the phrase ‘The Fallacy of the Appropriate Substrate’ to refer to the danger of assuming that, because a pathogenic microbe had an enzyme that attacks some substrate present in the tissues, that enzyme is relevant to its virulence. At the Lister Institute and indeed for some years after 1971, when he retired and worked first at the MRC Clinical Research Centre and later at the London Hospital Medical College, Miles continued his studies of the ‘mechanisms’ of inflammation-a nice complement to his ‘dissent’ from Kettle’s assertion in that lecture of 1941. But by 1960 Miles had become an experimental pathologist as much as a bacteriologist. His contribution to the 1965 celebration of the centenary of Lister’s introduction of the Antiseptic Treatment of Wounds’* summarized the current notions, as he called them, of the origins of the vascular response and fluid exudation in acute infection. He spent much time searching for the relevant mediators of the inflammatory response without reaching any very conclusive results, an indication as he himself recognized of the need for new and more sophisticated techniques than he had time to master. But one part of all this work stands out as of practical importance, namely his studies, several with a young American surgeon J. Burke,13 which demonstrated the crucial importance of the first hours after the introduction of bacteria into the tissues in determining whether or not the bacteria could establish themselves. There is (l), a first phase of fluid exudation and rapid reduction in the number of bacteria brought about by the bactericidal effect of serum and tissue fluids, followed by (2), a subsequent phase of exudation mediated by one or more of the factors identified or yet to be identified, before (3), a third phase when there is vascular occlusion and when blood-borne agents can
166
R. E. 0. Williams
no longer reach the infected site. The lesson was learnt that if antibiotic prophylaxis was to be of value in preventing post-operative wound infection, the antibiotic must be in the circulation at the time when the infection might be introduced-that is during the operation. Ashley Miles was a classical bacteriologist: he enjoyed understanding bacteria as living organisms and devising ways of unravelling their interaction with human or animal hosts. He worked largely with simple methods and with his own hands, and he had a great facility for instilling his enthusiasm in others. His contributions to the study of infection were, first and foremost, the enthusiasm with which he conveyed ideas, whether to medical students or in the numerous symposia and meetings to which he contributed reviews and discussions; second, his strong advocacy for the use of quantitative methods and statistical analysis wherever possible; third, his belief that bacteriologists should be prepared to go out into the field and study the infections that matter where they matter; and last, his painstaking studies of the inflammatory process, which while not leading to a dramatic break-through laid a solid foundation on which new techniques could be built. References 1. Miles AA, Misra SS. The estimation of the bactericidal power of the blood. J Hyg (Camb) 1938; 38: 732-749. CC, Elliott SD. Cross-infection with haemolytic streptococci in otorhinological 2. Okell wards. Lancet 1936; 2: 836-842. J. Nosocomial infections in children’s wards. J Hyg (Camb) 1940; 40: 647-672. 3. Wright, EA, Miles AA. Control of staphylococcal infections in an operating-theatre. 4. Devenish Lancet 1939; 1: 1088-1094. 5. Miles AA, Schwabacher H, Cunliffe AC, Paterson Ross J, Spooner ETC, Pilcher RS, Wright J. Hospital infection of war wounds. BMJ 1940; 2: 855-859, 895-900. Research Council. The Prevention of Hospital Infection. (War Memorandum 6. Medical No. 6) London: HM Stationery Office 1940. 7. McKissock W, Wright J, Miles AA. The reduction of hospital infection of wounds. A controlled experiment. BMJ 1941; 2: 375-377. Miles AA. Some problems of wound infection. Lancet 1941; 2: 507-510. i: Miles AA. Observations on control of hospital infection. Br Med Bull 1944; 2: 276-280. REO, Miles AA. Infection and sepsis in industrial wounds of the hands. A 10. Williams bacteriological study of aetiology and prophylaxis. Spec Rep Ser MRC (Lond) 1949; No. 266. AA. The meaning of pathogenicity. Fifth Symposium of the Society for General 11. Miles MicrobioZogy. Cambridge: Cambridge University Press; l-l 6. 12, Miles AA. Current notions of acute inflammation. In: Illingworth C, Ed. “Wound Healing”, The Lister Centenary Meeting Symposium, London: J & A Churchill Ltd; 3-15. of defence reactions of the skin 13. Miles AA, Miles EM, Burke J. Th e value and duration to the primary lodgement of bacteria. Br J Exp Pathol 1957; 38: 79-96.