British Journal
of Oral Surgery (1976), 13, 264-270
OSTEOMYELITIS OF THE JAWS AS A SEQUEL TO DENTAL LOCAL ANAESTHETIC INJECTIONS J. D. W. BARNARD,B.D.S.(Lond.),
F.D.S.R.C.S.(Eng.),
F.D.S.R.C.P.S.(Glasg.)l
Queen Victoria Hospital, East Grinstead Summary. Two cases of extensive osteomyelitis of the jaws are reported. In both cases there was a history of a recent local anaesthetic injection for a dental procedure.
INTRODUCTION OSTEOMYELITIS is an inflammatory condition of bone which can involve medullary bone and the adjacent cortex. With the introduction of antibiotics the incidence was markedly reduced, and the efficacy of treatment dramatically increased (Jaffe, 1972). However with the development of penicillin-resistant staphylococci the incidence of acute osteomyelitis increased, and while the mortality remained low, a smouldering persistent osteomyelitis became more frequent (Garrod et al., More recently the introduction of antibiotics effective against these 1973). organisms has improved the situation. The clinical picture and natural course of the disease depend upon an interplay between the causative agent or organism and the resistance of the patient. The most common aetiological factor is a pyogenic organism, with Staphylococcus aureus involved in go per cent of cases (Killey et al., 1971; Shafer, 1974). In the jaws the infection is usually of local origin and a haematogenous source is rare (Stones, 1951). A distinct clinical picture is seen in infants (McCash & Rowe, 1953). However, osteomyelitis may be produced by a non-pyogenic organism as in syphilis, tuberculosis and actinomycosis, and by physical and chemical agents e.g. phosphorus and X-irradiation. The patient’s resistance can be modified by a pre-existing systemic condition, e.g. diabetes or some blood dyscrasias, or by abnormal conditions in the affected bone, such as Paget’s disease, osteopetrosis or post-irradiation injury. In this age of increasing medication the effects on host resistance of drugs such as corticosteroids and immunosuppressive agents should also be remembered. Clinically pyogenic osteomyelitis may be acute or chronic. It usually affects the medullary bone, though there may be associated subperiosteal spread with reactive periostitis. Occasionally in a limited infection, the inflammatory process may be restricted to the subperiosteal site, sometimes producing an ‘onion-peel swelling of the cortex. However, in the established case both medulla and cortex are usually involved in the destructive process. Received 18.8.75. Accepted 20.8.75 1
Present address: Department
of Oral Surgery, Churchill Hospital, Oxford. 264
OSTEOMYELITIS OF JAWS AS SEQUEL TO LOCAL ANAESTHETIC
265,
FIG. I Case I. Full face showing swelling on left side.
CASE REPORTS Case I. A 32-year-old welder developed pain and swelling of the left cheek I week after the infiltration of local anaesthetic for routine conservative treatment of an upper molar. He was referred by his general medical practitioner to an E.N.T. surgeon who incised the swelling and prescribed a course of tetracycline. The situation did not fully resolve and one month later he was referred to the Oral Surgery Department. On examination he was generally well and afebrile. There was a fluctuant left facial swelling (Fig. I). Paraesthesia was present over the distribution of the left mental nerve and mandibular opening was restricted to 8 mm. Intraorally there was a sinus in the ITregion. Radiographs showed a moth-eaten appearance of the left ramus, condyle and coronoid process consistent with a diagnosis of osteomyelitis (Fig. 2). The patient was admitted, and under endotracheal anaesthesia the left ascending ramus was exposed via an intra-oral approach. Necrotic bone, which included the coronoid process and condyle was removed (Fig. 3). The lateral aspect of the ramus was then exposed via a submandibular approach and a partial lateral decortication performed. It was found that the medial cortex had been perforated in places. Drains were placed medial and lateral to the ramus before closure. Post-operatively drainage was maintained for 6 days. Culture of the diseased bone and this grew Staphylococcus aureus which was shown to be sensitive to clindamycin, antibiotic was prescribed for a total of 8 weeks. Histological examination revealed that the marrow spaces had been replaced with granulation tissue. There were abundant polymorphs and foci of fresh haemorrhage. There was some evidence of subperiosteal new bone. Long-term clinical and radiographic follow-up has revealed satisfactory repair with no recurrence of the infective process (Fig. 4). Mandibular function is good. Case 2. A fit g-year-old boy reported to his dental surgeon with toothache and slight left sided facial swelling, which had increased over the preceding 3 days. The
266
BRITISH
JOURNAL OF ORAL SURGERY
FIG. 2 Case I.
Orthopantomogram
showing moth-eaten appearance of condyle and ramus on the left side.
FIG. 3 Case I.
Excised cqndylar head showing osteolysis.
OSTEOMYELITIS
OF JAWS AS SEQUEL;TO
FIG.
Case
I.
Orthopantomogram
LOCAL
,
ANAESTHETIC
267
4
6 weeks after surgery.
Five days later the swelling had /DE were removed under local infiltration analgesia. The situation resolved and antibiotic increased and erythromycin was prescribed. therapy was stopped after 3 days. Ten days later a recurrence of the swelling was treated with tetracycline, but the picture became dramatically worse, and the boy was referred to the Oral Surgery Department. Examination showed an acutely ill child with a pyrexia of 37.92 and a pulse of 120. There was acute facial swelling on the left side. The left eye was closed and there was periorbital erythema. There was slight periorbital oedema on the right side. Intraorally the sulcus was tense in the /DE region. His medical history was unremarkable The E.S.R. was raised at 35 mm in the first except for a history of allergy to penicillin. hour. A course of a cephalosporin was commenced and under general anaesthesia the swelling was incised intra-orally. Copious pus was drained but no pathogens were cultured. Clinical resolution was rapid and the boy was discharged home. Five days later the swelling again closed the left eye. The antibiotic was changed to lincomycin and at this stage radiographs showed a loss of definition of the roof and lateral wall of the antrum, consistent with a diagnosis of osteomyelitis. Over the next 4 weeks the clinical picture gradually improved and X-rays demonstrated an increase in density of the antral margins. Antibiotic therapy was stopped. However, IO weeks later the swelling again recurred (Fig. s), and the X-ray appearance was consistent with a recurrence of the infective process in the left maxilla (Fig. 6). The boy was admitted and under endotracheal anaesthesia the left maxilla was exposed by an intra-oral approach. Removal of necrotic bone involved excision of the anterior, lateral and posterior antral walls, the root of the zygoma, the floor of the infraorbital canal and the tooth germs of 1456 with the associated alveolus. Drains were placed before closure. Culture of the diseased bone grew Staphylococcus aureus. Histological investigation showed vascular granulation tissue with evidence of osteoid formation. The antral lining was acutely inflamed in response to osteomyelitis in the subjacent bone. kost-operative progress was uneventful and long-term follow-up has shown no loss of facial symmetry. Radiographic density of the left maxilla has continued to increase.
BRITISH
268
JOURNAL OF ORAL SURGERY
FIG. 5 Case 2.
Profile showing facial swelling and periorbital flare.
FIG. 6 Case 2.
Occipitomental
radiograph showing loss of definition on the left side, particularly on the lateral antral wall. FIG. 7
Occipitomental radiograph 18 months after surgery. The left antrum is still Case 2. obscure but structures are becoming defined, including the lateral antral wall.
OSTEOMYELITIS
OF JAWS
AS SEQUEL,TO ~
LOCAL
ANAESTHETIC
269
DISCUSSION In both the cases reported acute osteomyelitis of the jaws developed following infiltration anaesthesia. In the first case there was no clinical evidence of a preexisting infection, and in the second case the original infection was clinically low grade. Although the cause and effect relationship is not proven, it seems reasonable to suppose that in the first case the infective process originated at the site of the local anaesthetic injection, perhaps as a sequel to haematoma formation in the pterygoid space. Pyogenic organisms may have been introduced by the injecting needle. Blake and Forman (1967) showed that a considerable number of organisms are likely to be implanted by intra-oral injections. However the incidence of needle track infection is extremely low (Howe & Whitehead, Ig72), and opinion has been varied as to the presence of a coagulase-positive staphylococcus as a commensal in the mouth [Stones, 1951; Lucas & Kramer, rg$g; White, 1963; Dubos, 1965; Blake & Forman, 1967; Katayama, 1974). Haematogenous spread from an unknown focus must also be considered. In the second case it seems likely that the local infection associated with /DE was disseminated by the injection. No general or local condition which might have increased the patient’s susceptibility to the infective process was apparent in either case. Once a positive diagnosis of osteomyelitis has been made, it should be assumed, until bacteriological results are to hand, that the causative organism is a peniAntibiotics have been found to be cillinase producing Staphylococcus aureus. most effective in the treatment of this organism include cephalosporins (Smith, 1971; Walker, rg73), cloxacillin (Harris, 1967; Blockley & Watson, rg7o), lincomycin and clindamycin (Geddes et al., 1964; McMillan et al., Ig67), fusidic acid and erythromycin (McAllister, 1974). Gentamicin, although very effective, should be kept in reserve for overwhelming Gram-negative infections. Rapid destruction of the bacteria is essential and therefore bacteriacidal antibiotics are to be preferred (Lancet, 1975). Penicillin is the drug of choice for penicillin sensitive infections, and Garrod et al. (1973) have suggested a combination of benzyl penicillin and an antibiotic active against penicillin-resistant staphylococci such as cloxacillin, a cephalosporin, fucidin, lincomycin or clindamycin. A penicillin and cloxacillin combination was recommended by Fickling (1967). Dosage should be adequate to permit penetration of necrotic bone, and therapy should be continued until the infective process is clinically arrested, and usually for at least 4 weeks (Smith, 1971). The indications for and timing of surgery have always been equivocal, and effective antibiotic therapy may iead to resolution with no surgical interference. However collections of pus should be drained at the earliest opportunity and extensive areas of necrotic bone will usually require surgical excision, particularly in the established case. Follow-up should be meticulous and sustained until radiographic consolidation is apparent. It is important to exclude a low-grade infection which may flare up after a long latent period. In the first case, once osteomyelitis had been diagnosed, radical excision of necrotic bone and prolonged treatment with a cephalosporin effected rapid resolution of clinical symptoms. Long-term follow-up has shown radiographic resolution. It could be argued that such radical surgery should have been deferred until the response to antibiotic therapy had been assessed, but it seemed unwise to leave the necrotic and infected bone in situ, once its wide extent became apparent at operation.
BRITISH
270
JOURNAL
OF ORAL
SURGERY
In the second case, particularly in view of the young age of the patient, it seems justified for the attempt to have been made to eradicate the infective process with antibiotics and drainage. However, the clinical picture became chronic, with recurrent acute episodes over a very long period. The smouldering infective process was only overcome by radical surgery and this achieved rapid and complete clinical resolution. The improvement in radiographic density has been gradual and progressive. ACKNOWLEDGEMENTS I would like to thank Mr Michael Awty, Mr Peter Banks and Professor David Poswillo for their helpful criticism during the preparation of this paper, and for permission to publish the case reports. My thanks are also due to the Photographic Department, Queen Victoria Epospital, East Grinstead for the illustrations. REFERENCES British DentalJournal, 123, 295. BLAKE, G. C. & FORMAN, G. H. (1967). BLOCKLEY,N. J. & WATSON, J. T. (1970). Journal of Bone and Joint Surgery, 52B, 77. Bacterial and Mycotic Infections, 4th Ed., p. 412. Pitman. ]DUBOS, R. J. (1965). Transactions of the 2nd Conference of the International Association FICKLING, B. W. (1967). of OraZ Surgeons, p. 250. Scandinavian University Books. British Medical Journal, iii, 680. HARRIS, N. H. (1967). GARROD, L. P., LAMBERT, H. I?. & O’GRADY, F. Antibiotic and Chemotherapy, 4th Ed., p. 340. Churchill Livingstone. British Medical Journal, 2, GEDDES, A. M., SLEET, R. A. & MCMURDOCH, J. McC. (1964). 670.
HOWE, G. L. & WIIITEHEAD, F. I. H. (1972). Local Anaesthesia in Dentistry, p. 74. Bristol: Wright. Metabolic Degenerative and Inflammatory Diseases of Bones and Joints, JAFFE,H. J. (1972). p. 1016. Philadelphia: Lea and Febiger. Dentistry in Japan, p. 16. Japanese Association for Dental Science. KATAYAMA, A. (1974). An Outline of Oral Surgery, Part I, KILLEY, H. C., SEWARD, G. R. & KAY, L. W. (1971). p. 122. Bristol: Wright. LaYZCet(1975). Editorial, I, 153, LUCAS, R. B. & KRAMER, I. R. H. (1959). Bacteriology for Students of Dental Surgery, 2nd Ed., p. 130. London: Churchill. British Journal of Hospital Medicine, 12, 535. MCALLISTER, T. A. (1974). MCCASH, C. R. & ROWE, N. L. (1953). J ournal of Bone and Joint Surgery, 35B, 22. The Practitioner, 198, 390. MCMILLAN, N. L., MCRAE, R. K. & MCDOUGALL, A. (1967). British Dental Journal, 96, 259. MORRIS, E. 0. (1954). A Textbook of Oral Pathology, p. 453. SHAFER,W. G., HINE, M. K. & LEVY, B. M. (1974). Philadelphia: Saunders. Postgraduate Medical Journal, February supplement, p. 78. SMITH, I. M. (1971). STONES, H. H. (1951). Oral and DentaZ Diseases, p. 698. Edinburgh: E. and S. Livingstone. WALKER, S. H. (1973). Chnica~ Paediatrics, 12, 98. WHITE, R. G. (1963). Essentials of Bacteriology, p. 196. Pitman.
of Oral Surgery (1976), 13, 264-270
OSTEOMYELITIS OF THE JAWS AS A SEQUEL TO DENTAL LOCAL ANAESTHETIC INJECTIONS J. D. W. BARNARD,B.D.S.(Lond.),
F.D.S.R.C.S.(Eng.),
F.D.S.R.C.P.S.(Glasg.)l
Queen Victoria Hospital, East Grinstead Summary. Two cases of extensive osteomyelitis of the jaws are reported. In both cases there was a history of a recent local anaesthetic injection for a dental procedure.
INTRODUCTION OSTEOMYELITIS is an inflammatory condition of bone which can involve medullary bone and the adjacent cortex. With the introduction of antibiotics the incidence was markedly reduced, and the efficacy of treatment dramatically increased (Jaffe, 1972). However with the development of penicillin-resistant staphylococci the incidence of acute osteomyelitis increased, and while the mortality remained low, a smouldering persistent osteomyelitis became more frequent (Garrod et al., More recently the introduction of antibiotics effective against these 1973). organisms has improved the situation. The clinical picture and natural course of the disease depend upon an interplay between the causative agent or organism and the resistance of the patient. The most common aetiological factor is a pyogenic organism, with Staphylococcus aureus involved in go per cent of cases (Killey et al., 1971; Shafer, 1974). In the jaws the infection is usually of local origin and a haematogenous source is rare (Stones, 1951). A distinct clinical picture is seen in infants (McCash & Rowe, 1953). However, osteomyelitis may be produced by a non-pyogenic organism as in syphilis, tuberculosis and actinomycosis, and by physical and chemical agents e.g. phosphorus and X-irradiation. The patient’s resistance can be modified by a pre-existing systemic condition, e.g. diabetes or some blood dyscrasias, or by abnormal conditions in the affected bone, such as Paget’s disease, osteopetrosis or post-irradiation injury. In this age of increasing medication the effects on host resistance of drugs such as corticosteroids and immunosuppressive agents should also be remembered. Clinically pyogenic osteomyelitis may be acute or chronic. It usually affects the medullary bone, though there may be associated subperiosteal spread with reactive periostitis. Occasionally in a limited infection, the inflammatory process may be restricted to the subperiosteal site, sometimes producing an ‘onion-peel swelling of the cortex. However, in the established case both medulla and cortex are usually involved in the destructive process. Received 18.8.75. Accepted 20.8.75 1
Present address: Department
of Oral Surgery, Churchill Hospital, Oxford. 264
OSTEOMYELITIS OF JAWS AS SEQUEL TO LOCAL ANAESTHETIC
265,
FIG. I Case I. Full face showing swelling on left side.
CASE REPORTS Case I. A 32-year-old welder developed pain and swelling of the left cheek I week after the infiltration of local anaesthetic for routine conservative treatment of an upper molar. He was referred by his general medical practitioner to an E.N.T. surgeon who incised the swelling and prescribed a course of tetracycline. The situation did not fully resolve and one month later he was referred to the Oral Surgery Department. On examination he was generally well and afebrile. There was a fluctuant left facial swelling (Fig. I). Paraesthesia was present over the distribution of the left mental nerve and mandibular opening was restricted to 8 mm. Intraorally there was a sinus in the ITregion. Radiographs showed a moth-eaten appearance of the left ramus, condyle and coronoid process consistent with a diagnosis of osteomyelitis (Fig. 2). The patient was admitted, and under endotracheal anaesthesia the left ascending ramus was exposed via an intra-oral approach. Necrotic bone, which included the coronoid process and condyle was removed (Fig. 3). The lateral aspect of the ramus was then exposed via a submandibular approach and a partial lateral decortication performed. It was found that the medial cortex had been perforated in places. Drains were placed medial and lateral to the ramus before closure. Post-operatively drainage was maintained for 6 days. Culture of the diseased bone and this grew Staphylococcus aureus which was shown to be sensitive to clindamycin, antibiotic was prescribed for a total of 8 weeks. Histological examination revealed that the marrow spaces had been replaced with granulation tissue. There were abundant polymorphs and foci of fresh haemorrhage. There was some evidence of subperiosteal new bone. Long-term clinical and radiographic follow-up has revealed satisfactory repair with no recurrence of the infective process (Fig. 4). Mandibular function is good. Case 2. A fit g-year-old boy reported to his dental surgeon with toothache and slight left sided facial swelling, which had increased over the preceding 3 days. The
266
BRITISH
JOURNAL OF ORAL SURGERY
FIG. 2 Case I.
Orthopantomogram
showing moth-eaten appearance of condyle and ramus on the left side.
FIG. 3 Case I.
Excised cqndylar head showing osteolysis.
OSTEOMYELITIS
OF JAWS AS SEQUEL;TO
FIG.
Case
I.
Orthopantomogram
LOCAL
,
ANAESTHETIC
267
4
6 weeks after surgery.
Five days later the swelling had /DE were removed under local infiltration analgesia. The situation resolved and antibiotic increased and erythromycin was prescribed. therapy was stopped after 3 days. Ten days later a recurrence of the swelling was treated with tetracycline, but the picture became dramatically worse, and the boy was referred to the Oral Surgery Department. Examination showed an acutely ill child with a pyrexia of 37.92 and a pulse of 120. There was acute facial swelling on the left side. The left eye was closed and there was periorbital erythema. There was slight periorbital oedema on the right side. Intraorally the sulcus was tense in the /DE region. His medical history was unremarkable The E.S.R. was raised at 35 mm in the first except for a history of allergy to penicillin. hour. A course of a cephalosporin was commenced and under general anaesthesia the swelling was incised intra-orally. Copious pus was drained but no pathogens were cultured. Clinical resolution was rapid and the boy was discharged home. Five days later the swelling again closed the left eye. The antibiotic was changed to lincomycin and at this stage radiographs showed a loss of definition of the roof and lateral wall of the antrum, consistent with a diagnosis of osteomyelitis. Over the next 4 weeks the clinical picture gradually improved and X-rays demonstrated an increase in density of the antral margins. Antibiotic therapy was stopped. However, IO weeks later the swelling again recurred (Fig. s), and the X-ray appearance was consistent with a recurrence of the infective process in the left maxilla (Fig. 6). The boy was admitted and under endotracheal anaesthesia the left maxilla was exposed by an intra-oral approach. Removal of necrotic bone involved excision of the anterior, lateral and posterior antral walls, the root of the zygoma, the floor of the infraorbital canal and the tooth germs of 1456 with the associated alveolus. Drains were placed before closure. Culture of the diseased bone grew Staphylococcus aureus. Histological investigation showed vascular granulation tissue with evidence of osteoid formation. The antral lining was acutely inflamed in response to osteomyelitis in the subjacent bone. kost-operative progress was uneventful and long-term follow-up has shown no loss of facial symmetry. Radiographic density of the left maxilla has continued to increase.
BRITISH
268
JOURNAL OF ORAL SURGERY
FIG. 5 Case 2.
Profile showing facial swelling and periorbital flare.
FIG. 6 Case 2.
Occipitomental
radiograph showing loss of definition on the left side, particularly on the lateral antral wall. FIG. 7
Occipitomental radiograph 18 months after surgery. The left antrum is still Case 2. obscure but structures are becoming defined, including the lateral antral wall.
OSTEOMYELITIS
OF JAWS
AS SEQUEL,TO ~
LOCAL
ANAESTHETIC
269
DISCUSSION In both the cases reported acute osteomyelitis of the jaws developed following infiltration anaesthesia. In the first case there was no clinical evidence of a preexisting infection, and in the second case the original infection was clinically low grade. Although the cause and effect relationship is not proven, it seems reasonable to suppose that in the first case the infective process originated at the site of the local anaesthetic injection, perhaps as a sequel to haematoma formation in the pterygoid space. Pyogenic organisms may have been introduced by the injecting needle. Blake and Forman (1967) showed that a considerable number of organisms are likely to be implanted by intra-oral injections. However the incidence of needle track infection is extremely low (Howe & Whitehead, Ig72), and opinion has been varied as to the presence of a coagulase-positive staphylococcus as a commensal in the mouth [Stones, 1951; Lucas & Kramer, rg$g; White, 1963; Dubos, 1965; Blake & Forman, 1967; Katayama, 1974). Haematogenous spread from an unknown focus must also be considered. In the second case it seems likely that the local infection associated with /DE was disseminated by the injection. No general or local condition which might have increased the patient’s susceptibility to the infective process was apparent in either case. Once a positive diagnosis of osteomyelitis has been made, it should be assumed, until bacteriological results are to hand, that the causative organism is a peniAntibiotics have been found to be cillinase producing Staphylococcus aureus. most effective in the treatment of this organism include cephalosporins (Smith, 1971; Walker, rg73), cloxacillin (Harris, 1967; Blockley & Watson, rg7o), lincomycin and clindamycin (Geddes et al., 1964; McMillan et al., Ig67), fusidic acid and erythromycin (McAllister, 1974). Gentamicin, although very effective, should be kept in reserve for overwhelming Gram-negative infections. Rapid destruction of the bacteria is essential and therefore bacteriacidal antibiotics are to be preferred (Lancet, 1975). Penicillin is the drug of choice for penicillin sensitive infections, and Garrod et al. (1973) have suggested a combination of benzyl penicillin and an antibiotic active against penicillin-resistant staphylococci such as cloxacillin, a cephalosporin, fucidin, lincomycin or clindamycin. A penicillin and cloxacillin combination was recommended by Fickling (1967). Dosage should be adequate to permit penetration of necrotic bone, and therapy should be continued until the infective process is clinically arrested, and usually for at least 4 weeks (Smith, 1971). The indications for and timing of surgery have always been equivocal, and effective antibiotic therapy may iead to resolution with no surgical interference. However collections of pus should be drained at the earliest opportunity and extensive areas of necrotic bone will usually require surgical excision, particularly in the established case. Follow-up should be meticulous and sustained until radiographic consolidation is apparent. It is important to exclude a low-grade infection which may flare up after a long latent period. In the first case, once osteomyelitis had been diagnosed, radical excision of necrotic bone and prolonged treatment with a cephalosporin effected rapid resolution of clinical symptoms. Long-term follow-up has shown radiographic resolution. It could be argued that such radical surgery should have been deferred until the response to antibiotic therapy had been assessed, but it seemed unwise to leave the necrotic and infected bone in situ, once its wide extent became apparent at operation.
BRITISH
270
JOURNAL
OF ORAL
SURGERY
In the second case, particularly in view of the young age of the patient, it seems justified for the attempt to have been made to eradicate the infective process with antibiotics and drainage. However, the clinical picture became chronic, with recurrent acute episodes over a very long period. The smouldering infective process was only overcome by radical surgery and this achieved rapid and complete clinical resolution. The improvement in radiographic density has been gradual and progressive. ACKNOWLEDGEMENTS I would like to thank Mr Michael Awty, Mr Peter Banks and Professor David Poswillo for their helpful criticism during the preparation of this paper, and for permission to publish the case reports. My thanks are also due to the Photographic Department, Queen Victoria Epospital, East Grinstead for the illustrations. REFERENCES British DentalJournal, 123, 295. BLAKE, G. C. & FORMAN, G. H. (1967). BLOCKLEY,N. J. & WATSON, J. T. (1970). Journal of Bone and Joint Surgery, 52B, 77. Bacterial and Mycotic Infections, 4th Ed., p. 412. Pitman. ]DUBOS, R. J. (1965). Transactions of the 2nd Conference of the International Association FICKLING, B. W. (1967). of OraZ Surgeons, p. 250. Scandinavian University Books. British Medical Journal, iii, 680. HARRIS, N. H. (1967). GARROD, L. P., LAMBERT, H. I?. & O’GRADY, F. Antibiotic and Chemotherapy, 4th Ed., p. 340. Churchill Livingstone. British Medical Journal, 2, GEDDES, A. M., SLEET, R. A. & MCMURDOCH, J. McC. (1964). 670.
HOWE, G. L. & WIIITEHEAD, F. I. H. (1972). Local Anaesthesia in Dentistry, p. 74. Bristol: Wright. Metabolic Degenerative and Inflammatory Diseases of Bones and Joints, JAFFE,H. J. (1972). p. 1016. Philadelphia: Lea and Febiger. Dentistry in Japan, p. 16. Japanese Association for Dental Science. KATAYAMA, A. (1974). An Outline of Oral Surgery, Part I, KILLEY, H. C., SEWARD, G. R. & KAY, L. W. (1971). p. 122. Bristol: Wright. LaYZCet(1975). Editorial, I, 153, LUCAS, R. B. & KRAMER, I. R. H. (1959). Bacteriology for Students of Dental Surgery, 2nd Ed., p. 130. London: Churchill. British Journal of Hospital Medicine, 12, 535. MCALLISTER, T. A. (1974). MCCASH, C. R. & ROWE, N. L. (1953). J ournal of Bone and Joint Surgery, 35B, 22. The Practitioner, 198, 390. MCMILLAN, N. L., MCRAE, R. K. & MCDOUGALL, A. (1967). British Dental Journal, 96, 259. MORRIS, E. 0. (1954). A Textbook of Oral Pathology, p. 453. SHAFER,W. G., HINE, M. K. & LEVY, B. M. (1974). Philadelphia: Saunders. Postgraduate Medical Journal, February supplement, p. 78. SMITH, I. M. (1971). STONES, H. H. (1951). Oral and DentaZ Diseases, p. 698. Edinburgh: E. and S. Livingstone. WALKER, S. H. (1973). Chnica~ Paediatrics, 12, 98. WHITE, R. G. (1963). Essentials of Bacteriology, p. 196. Pitman.
