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Systemic Diseases Caused by Oral Infection

Xiaojing Li,1* Kristin M. Kolltveit,1 Leif Tronstad,2 and Ingar OlsenDepartment of Oral Biology1 and Department of Endodontics,2  Faculty of Dentistry, University of Oslo, Oslo, Norway.

Summary: The theory of focal infection, which was promulgated during the 19th and early 20th centuries, stated that “foci” of sepsis were responsible for the initiation and progression of a variety of inflammatory diseases such as arthritis, peptic ulcers, and appendicitis (120). In the oral cavity, therapeutic edentulation was common as a result of the popularity of the focal infection theory.  However, A number of epidemiological studies have suggested that oral infection, especially marginal and apical periodontitis, may be a risk factor for systemic diseases.


  1. Aldrige, J. P., V. Lester, T. L. Watts, A. Collins, G. Viberti, and R. F. Wilson. Single-blind studies of the effects of improved periodontal health on metabolic control in type 1 diabetes mellitus. J. Clin. Periodontal 22:271-275.
  2. Aslkainen, S., and S. Alaluusa. 1993. Bacteriology of dental infections. Eur. Heart J. 14:43-50.
  3. Baltch, A. , H. L., Pressman, C. Schaffer, R. P. Smith, M. C. Hammer, M. Shayegani, and P. Michelsen. 1988. Bacteremia in patients undergoing prophylaxis as recommended by the American Heart Association, 1977. Arch. Intern Med. 148:1084-1088.
  4. Beck, J. , R. I. Garcia, G. Heiss, P. S. Vokonas, and S. Offenbacher. 1996. Periodontal disease and cardiovascular disease. J. Periodontol. 67:1123-1137.
  5. Beighton, D., and J. S. Life. Trypsin-like chymotrypsin-like and glycylprolyl dipeptidase activities in gingival crevicular fluid from human periodontal sites with gingivitis. Arch. Oral Biol. 34:843-846.
  6. Beighton, D., J. R. Radford, and M. N. Naylor. Protease activity in gingival crevicular fluid from discrete periodontal sites in humans with periodontitis or gingivitis. Arch. Oral Biol. 35:329-335.
  7. Bonten, M. J., C. A. Gaillard, F. H. van Tiel, H. G. Smeets, S. van der Geest, and E. E. Stobberingh. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest 105:878-884.
  8. Boon, N. A., and K. A. A. Fox. Disease of the cardiovascular system, p. 191-3122. In C. R. W. Edwards, I. A. D. Bouchier, C. Haslett, and E. R. Chilvers (ed.), Davidson’s principles and practice of medicine, 17th ed. Churchill Livingstone, New York, N.Y.
  9. Breslau, N., G. G. Brown, J. E. DelDotto, S. Kumar, S. Ezhuthachan, P. Andreski, and K. G. Hufnagle. Psychiatric sequelae of low birth weight at 6 years of age. J. Abnorm. Child Psychol. 24:385-400.
  10. Byrne, J., C. Ellsworth, E. Bowering, and M. Vincer. Language development in low birth weight infants: the first two years of life. J. Dev. Behav. Pediatr. 14:21-27.
  11. Carrol, G. C., and R. J. Sebor. Dental flossing and its relationship to transient bacteremia. J. Periodontol. 51:691-692.
  12. Chauncey, H. H., M. E. Muench, K. K. Kapur, and A. H. Wayler. The effect of the loss of teeth on diet and nutrition. Int. Dent. J. 34:98-104.
  13. Chen, M. K., and F. Lowenstein. Masticatory handicap, sociocconomic status, and chronic conditions among adults. J. Am. Dent. Assoc. 109:916-918.
  14. Childs, W. , 3d, and R. J. Gibbons. 1990. Selective modulation of bacterial attachment to oral epithelial cells by enzyme activities associated with poor oral hygiene. J. Periodontal Res. 25:172-178.
  15. Christgau, M., K. D. Palitzsch, G. Schmalz, U. Kreiner, and S. Frenzel. Healing response to non-surgical periodontal therapy in patients with diabetes mellitus: clinical, microbiological, and immunologic results. J. Clin. Periodontol. 25:112-124.
  16. Christianson, R. E., B. J. van den Berg, L. Milkovich, and F. W. Oechsli. Incidence of congenital anomalies among white and black live births with long-term follow-up. Am. J. Public Health 71:1333-1341.
  17. Cimasoni, G. Crevicular fluid updated. Monogr. Oral Sci. 12:1-152.
  18. Clinton, S. , J. C. Fleet, H. Loppnow, R. N. Salomon, B. D. Clark, J. G. Cannon, A. R. Shaw, C. A. Dinarello, and P. Libby. 1991. Interleukin-1 gene expression in rabbit vascular tissue in vivo. Am. J. Pathol. 138:1005-1014.
  19. Craven, D. , K. A. Steger, and T. W. Barber. 1991. Preventing nosocomial pneumonia: state of the art and perspectives for the 1990s. Am. J. Med. 91:44S-53S.
  20. Cull, R. , and R. G. Will. 1995. Diseases of the nervous system, P. 1021-1116. In C. R. W. Edwards, I. A. D. Bouchier, C. Haslett, and E. R. Chilvers (ed.), Davidson’s principles and practice of medicine, 17th ed. Churchill Livingstone, New York, N.Y.
  21. Cunha, B. A. Hospital-acquired pneumonias: clinical diagnosis and treatment. Hosp. Physician 22:12-17.
  22. Darveau, R. P., A. Tanner, and R. C. Page. The microbial challenge in periodontitis. Periodontol. 2000 14:12-32.
  23. Dasanayake, A. 1998. Poor periodontal health of the pregnant woman as a risk factor for low birth weight. Ann. Periodontol. 3:206-212.
  24. Debelian, G. , I. Olsen, and L. Tronstad. 1995. Bacteremia in conjunction with endodontic therapy. Endod. Dent. Traumatol. 11:142-149.
  25. Debelian G. , I. Olsen, and L. Tronstad. 1998. Anaerobic bacteremia and fungemia in patients undergoing endodontic therapy: an overview. Ann. Periodontol. 3:281-287.
  26. Deshpande, R. G., M. B. Khan, and C. A. Genco. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infect. Immun. 66:5337-5343.
  27. DeStefano, F., R. F. Anda, H. S. Kahn, D. F. Williamson, and C. M. Russell. 1993. Dental disease and risk of coronary heart disease and mortality. Br. Med. J. 306:688-691.
  28. Donley, T. G., and K. B. Donley. Systemic bacteremia following tooth brushing: a protocol for management of patients susceptible to infective endocarditis. Gen. Dent. 36:482-484.
  29. Donowritz, G. , and G. L. Mandell. 1990. Acute pneumonia, p. 540-555. In G. L. Mandell, R. G. Douglas, and J. E. Bennett (ed.), Principles and practice of infectious diseases. Churchill Livingstone, New York, N.Y.
  30. Drangsholt, M. T. Association of dental procedures and infective endocarditis: a meta-analysis, p. 43. Thesis. University of Washington, Seattle.
  31. Drangsholt, M. 1998. A new causal model of dental diseases associated with endocarditis. Ann. Periodontol. 3:184-196.
  32. Drinnan, A. J., and C. Gogan. 1990. Bacteremia and dental treatment. J. Am. Dent. Assoc. 120:378.
  33. Durack, D. T., P. B. Beeson, and R. G. Petersdorf. Experimental bacterial endocarditis. 3. Production and progress of the disease in rabbits. Br. J. Exp. Pathol. 54:142-151.
  34. Ebersole, J. , R. L., Machen, M. J. Steffen, and D. E. Wilmann. 1997. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin. Exp. Immunol. 107:347-352.
  35. Edwards, C. W., J. D. Baird, B. M. Frier, J. Shepherd, and A. D. Toft. 1995. Endocrine and metabolic disease, p. 669-774. In C. R. W. Edwards, I. A. D. Bouchier, C. Haslett, and E. R. Chilvers (ed.), Davidson’s principles and practice of medicine, 17th ed. Churchill Livingstone, New York, N.Y.
  36. Fiddian-Green, R. G., and S. Baker. Nosocomial pneumonia in the critically ill: product of aspiration or translocation? Crit. Care Med. 19:763-769.
  37. Fitzhardinge, P. M. Follow-up studies of the low birth weight infant. Clin. Perinatol. 3:503-516.
  38. Foster, D. W. Diabetes mellitus, p. 1979-2000. In K. J. Isselbacher, E. Braunwald, J. D. Wilson, J. D. Wilson, J. B. Wilson, J. B. Martin, A. S. Fauci, and D. L. Kasper (ed.), Harrison’s principles of internal medicine. McGraw-Hill, New York, N.Y.
  39. Genco, R. 1998. Periodontal disease and risk for myocardial infarction and cardiovascular disease. Cardiovasc. Rev. Rep. 19:34-37.
  40. Genco, R. , I. Glurich, V. Haraszthy, J. Zambon, and E. DeNardin. 1998. Overview of risk factors for periodontal disease and implications for diabetes and cardiovascular disease. Compendium 19:40-45.
  41. Reference deleted.
  42. Gibbons, R. J., D. I. Hay, W. C. Childs, 3d, and G. Davis. Role of cryptic receptors (cryptitopes) in bacterial adhesion to oral surfaces. Arch. Oral Biol. 35:107S-114S.
  43. Golub, L. , and I. Kleinberg. 1976. Gingival crevicular fluid: a news diagnostic aid in managing the periodontal patient. Oral Sci. Rev. 8:49-61.
  44. Grau, A. , F. Buggle, C. Ziegler, W. Schwarz, J. Meuser, A. J. Tasman, A. Buhler, C. Benesch, H. Becher, and W. Hacke. 1997. Association between acute cerebrovascular ischemia and chronic and recurrent infection. Stroke 28:1724-1729.
  45. Grossi, S. , and R. J. Genco. 1998. Periodontal disease and diabetes mellitus: a two-way relationship. Ann. Periodontol. 3:51-61.
  46. Grossi, S. , and F. B. Skrepcinski, T. DeCaro, D. C. Robertson, A. W. Ho, R. G. Dunford, and R> J. Genco. 1997. Treatment of periodontal disease in diabetics reduces glycated hemoglobin. J. Periodontol. 68:713-719.
  47. Grossi, S. , J. J. Zambbon, A. W. Ho, G. Koch, R. G. Dunford, E. E. Machtei, O. M. Norderyd, and R. J. Genco. 1994. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J. Periodontol. 65:260-267.
  48. Hack, M., B. Caron, A. Rivers, and A. A. Fanaroff. The very low birth weight infant: the broader spectrum of morbidity during infancy and early childhood. J. Dev. Behav. Pediatr. 4:243-249.
  49. Haffajee, A. , and S. S. Socransky. 1994. Microbial etiological agents of destructive periodontal diseases. Periodontol. 2000 5:78-111.
  50. Hammond, B. 1992. Major bacterial diseases, p. 165-190. In J. Slots and M. A. Taubman (ed.). Contemporary oral microbiology and immunology. Mosby, St. Louis, Mo.
  51. Reference deleted.
  52. Heimdahl, A., G. Hall, M. Hedberg. H. Sandberg, P. O. Soder, K. Turner, and C. E. Nord. Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures. J. Clin. Microbiol. 28:2205-2209.
  53. Hernichel-Gorbach, E., K. S. Kornman, S. C. Holt, F. Nichols, H. Meador, J. T. Kung, and C. A. Thomas. Host response in patients with generalized refactory periodontitis. J. Periodontol. 65:8-16.
  54. Herzberg, M. , and M. W. Meyer. 1996. Effects of oral flora on platelets: possible consequences in cardiovascular disease. J. Periodontol. 67:1138-1142.
  55. Herzberg, M. C., and M. W. Meyer. Dental plaque, platelets, and cardiovascular disease. Ann. Periodontol. 3:151-160.
  56. Hertzbergy, M. , G. D. Macfarlane, P. Liu, and P. R. Erickson. 1994. The platelet as an inflammatory cell in periodontal disease: interactions with Porphyromonas gingivalis, p. 247-255. In R. Genco, S. Hamada, T. Lehner, J. McGhee, and S. Mergenhagen (ed.), Molecular pathogenesis of periodontal disease. American Society for Microbiology, Washington, D.C.
  57. Hill, A. 1965. The environment and disease: association or causation? Proc. R. Soc. Med. 58:1217-1219.
  58. Hillier, S. L., J. Martius, M. Krohn, N. Kiviat, K. K. Holmes, and D. A. Eschenback. A xase-control study of chorioamnionic infection and histologic choriomniontits in prematurity. N. Engl. J. Med. 319:972-978.
  59. Hillier, S. L., R. P. Nugent, D. A. Eschenbach, M. A. Krohn, R. S. Gibbs, D. H. Martin, M. F. Cotch, R. Edelman, J. G. Pastorek, 2nd, and A. V. Rao. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N. Engl. J. Med. 333:1737-1742.
  60. Hugoson, A., H. Thorstensson, H. Falk, and J. Kuylenstierna. Periodontal conditions in insulin-dependent diabetics. J. Clin. Periodontol. 16:215-223.
  61. Joshi, N., T. O’Bryan, and P.C. Appelbaum. Pleuropulmonary infections caused by Eikenella corrodens. Rev. Infect. Dis. 13:1207-1212.
  62. Joshipura, K. , E. B. Rimm, C. W. Douglass, D. Trichopoulos, A. Ascherio, and W. C. Willett. 1996. Poor oral health and coronary heart disease. J. Dent. Res. 75:1631-1636.
  63. Kalkwarf, K. 1978. Effect of oral contraceptive therapy on gingival inflammation in humans. J. Periodontol. 49:560-563.
  64. Kilian, M. Systemic disease: manifestations of oral bacteria, p. 832-838. In J. R. McGhee, S. M. Michalek, and G. H. Cassell (ed.), Dental microbiology. Harpers & Row, Philadelphia, Pa.
  65. Kinane, D. 1998. Periodontal diseases’ contributions to cardiovascular disease: an overview of potential mechanisms. Ann. Periodontol. 3:142-150.
  66. Kleindienst, R., Q. Xu, J. Willeit, F. R. Waldenberger, S. Weimann, and G. Wick. Immunology of atherosclerosis: demonstration of heat stock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. Am. J. Pathol. 142:1927-1937.
  67. Knowler, W., D. J. Pettitt, M. F. Saad, and P. H. Bennett. 1990. Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab. Rev. 6:1-27.
  68. Komiyama, K., J. J. Tynan, B.F. Habbick, D. E. Duncan, and D. J. Liepert. Pseudomonas aeruginosa in the oral cavity and sputum of patients with cystic fibrosis. Oral Surg. Oral Med. Oral Pahtol. 59:590-594.
  69. Kornman, K. S., and W. J. Loesche. The subgingival microbial flora during pregnancy. Periodontal Res. 15:111-122.
  70. Kweider, M., G. D. Lowe, G. D. Murray, D. F. Kinane, and D. A. McGown. Dental disease, fibrinogen and white cell count: links with myocardial infarction? Scott. Med. J. 38:73-74.
  71. Lacassin, F., B. Hoen, C. Leport, C. Selton-Suty, G. Delahaye, V. Goulet, J. Etienne, and S. Briancon. 1995. Procedures associated with infective endocarditis in adults: a case-control study. Eur. Heart J. 16:1968-1974.
  72. Levison, M. E. Pneumonia, including necrotizing pulmonary infections (lung abscess), p. 1184-1191. In K. J. Isselbacher, E. Braunwald, and J. D. Wilson (ed.), Harrison’s principles of internal medicine. McGraw-Hill, New York, N.Y.
  73. Limeback, H. The relationship between oral health and systemic infections mong elderly residents of chronic care facilities. Gerodontology 7:131-137.
  74. Little, J. W. Prosthetic implants: risk of infection from transient dental bacteremia. Compendium 12:160-164.
  75. Loe, H. Periodontal disease: the sixth complication of diabetes mellitus. Diabetes Care 16:329-334.
  76. Loe, H., and J. Silness. Periodontal disease in pregnancy: prevalence and severity. Acta Odontol. Scand. 21:532-551.
  77. Loesche, W. J. Ecology of the oral flora, p. 307-319. In R. J. Nisengard and M. G. Newman (ed.), Oral microbiology and immunology, 2nd ed. W. B. Saunders, Philadelphia, Pa.
  78. Loesche, W. 1994. Periodontal disease as a risk factor for heart disease. Compendium 15:976, 978-982, 985-986 passim.
  79. Loesche, W. 1997. Association of the oral flora with important medical diseases. Curr. Opin. Periodontol. 4:21-28.
  80. Loesche, W. J., and D. E. Lopatin. Interactions between periodontal disease, medical diseases and immunity in the older individual. Periodontol. 2000 16:80-105.
  81. Loesche, W. J., S. A. Syed, and J. Stoll. Trypsin-like activity in subgingival plaque. A diagnostic marker for spirochetes and periodontal disease? J. Periodontol. 58:266-273.
  82. Lofthus, J. , M. Y. Waki, D. L. Jolkovsky, J. Otomo-Corgel, M. G. Newman, T. Flemmig, and S. Nachnani. 1991. Bacteremia following subgingival irrigation and scaling and root planing. J. Periodontol. 62:602-607.
  83. Reference deleted.
  84. Lorenz, K. A., and P. J. Weiss. Capnocytophagal pneumonia in a healthy man. West. J. Med. 160:79-80.
  85. Marcus, A. , and D. P. Hajjar. 1993. Vascular transcellular signaling. J. Lipid Res. 34:2017-2031.
  86. Mattila, K. 1989. Viral and bacterial infections in patients with acute myocardial infarction. J. Intern. Med. 225:293-296.
  87. Mattila, K. J., M. S. Nieminen, V. V. Valtonen, V.P. Rasi, Y. A. Kesaniemi, S. L. Syrjala, P. S. Jungell, M. Isoluma, K. Hietaniemi, and M. J. Jokinen. Association between dental health and acute myocardial infarction. Br. Med. J. 298:779-781.
  88. Mattila, K. , M. S. Valle, M. S. Nieminen, V. V. Valtonen, and K. L. Hietaniemi. 1993. Dental infections and coronary atherosclerosis. Atherosclerosis 103:205-211.
  89. Mattila, K. , V. V. Valtonen, M. Nieminen, and J. K. Huttunen. 1995.
  90. McCall, M. , and D. D. Acheson. 1968. Respiratory disease infancy. J. Chronic Dis. 21:349-359.
  91. McCormick, M. C. The contribution of low birth weight to infant mortality and childhood morbidity. N. Engl. J. Med. 312:82-90.
  92. McGhee, J. 1982. Microbial pathogenic mechanisms, p. 374-387. In J. R. McGhee, Sm M. Michalek, and G. H. Cassell (ed.), Dental microbiology. Harper & Row, Philadelphia, pa.
  93. Mergran, D., and A. W. Chow. 1986. Bacterial aspiration and anaeribuc pleuropulmonary infections, p. 269-292. In M. A. Sande, L. D. Hudson, and R. K. Root (ed.), Respiratory infections. Churchill Livingstone, New York, N.Y.
  94. Miller, L. , M. A. Manwell, D. Newbold, M. E. Reding, A. Rasheed, J. Blodgett, and K. S. Kornman. 1992. The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. J. Periodontol 63:843-848.
  95. Molvig, J. A model of the pathogenesis of insulin-dependent diabetes mellitus. Dan. Med. Bull. 39:509-541.
  96. Moore, W. E. C., and L. V. H. Moore. The bacteria of periodontal disease. Periodontol. 2000 5:66-77.
  97. Morris, J. F., and D. K. Sewell. Necrotizing pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: case report and review. Clin. Infect. Dis. 18:450-452.
  98. Nakamura, M., and J. Slots. Salivary enzymes: origin and relationship to periodontal disease. J. Periodontal Res. 18:559-569.
  99. Navazesh, M., and R. Mulligan. Systemic dissemination as a result of oral infection in individuals 50 years of age and older. Spec. Care Dentist. 15:11-19.
  100. Neill, D. J., and H. I. Phillips. The masticatory performance, dental state, and dietary intake of a group of elderly army pensioners. Br. Dent. J. 128:581-585.
  101. Niederman, M. S., and A. M. Fein. Pneumonia in the elderly. Clin. Geriatr. Med. 2:241-268.
  102. Offenbacher, S. Periodontal disease: pathogenesis. Ann. Periodontol. 1:821-878.
  103. Offenbacher, S., H. L. Jared, P. G. O’Reilly, S. R. Wells, G. E. Salvi, H. P. Lawrence, S. S. Socransky, and J. D. Beck. Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann. Periodontol. 3:233-250.
  104. Offenbacher, S., J. D. Beck, S. Lieff, and G. Slade. Role of periodontitis in systemic health: spontaneous preterm birth. J. Dent. Educ. 62:852-858.
  105. Offenbacher, S., J. G. Collins, B. Yalta, and G. Hardadon. Role of prostaglandins in high-risk periodontitis patients, p. 203-214. In R. Genco, S. Hamada, T. Lehner, J. McGhee, and S. Mergenhagen (ed.), Molecular pathogenesis of periodontal disease. American Society for Microbiology, Washington, D.C.
  106. Offenbacher, S., V. Katz, G. Ferik, J. Collins, D. Boyd, G. Maynor, R. McKaig, and J. Beck. Periodontal infection as a possible risk factor for preterm low birth weight. J. Periodontol . 67:1103-1113.
  107. Okabe, K., K. Nakagawa, and E. Yamamoto. Factors affecting the occurrence of bacteremia associated with tooth extraction. Int. J. Oral Maxillofac. Surg. 24:239-242.
  108. Okuda, K., and Y. Ebihara. Relationships between chronic oral infectious diseases and systemic diseases. Bull. Tokyo Dent. Coll. 39:165-174.
  109. Overholser, C. D., P. Moreillon, and M. P. Glauser. 1987. Experimental bacterial endocarditis after dental extractions in rats with periodontitis. J. Infect. Dis. 155:107-112.
  110. Page, R. C. The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm. Ann. Periodontol. 3:108-120.
  111. Papapanou, P. N. Periodontal diseases: epidemiology. Ann. Periodontol. 1:1-36.
  112. Pesonen, E., E. Kaprio, J. Rapola, T. Soveri, and H. Oksanen. Endothelial cell damage in piglet coronary artery after intravenous administration of E. coli endotoxin: a scanning and transmission electron-microscopic study. Atheroclerosis 40:65-73.
  113. Reference deleted.
  114. Rams, T. E., and J. Slots. Systemic manifestations of oral infections, p. 500-523. In J. Slots and M. A. Taubman (ed.), Contemporary oral microbiology and immunology. Mosby, st. Louis, Mo/.
  115. Ridker, P. , M. Cushman, M. J. Stampfer, R. P. Tracy, and C. H. Hennekens. 1997. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 336:973-979.
  116. Roberts, G. J., H. S. Holzel, M. R. Sury, N. A. Simmons, P. Gardner, and P. Longhurst. Dental bacteremia in children. Pediatr. Cardiol. 18:24-27.
  117. Romero, R., P. Baumann, R. Gomez, C. Salafia, L., Rittenhouse, D. Barberio, E> Behnke, D. B. Cotton, and M. D. Mitchell. The relationship between spontaneous rupture of membranes, labor, and microbial invasion of the amniotic cavity and amniotic fluid concentrations of prostaglandins and thromboxane B2 in term pregnancy. Am. J. Obstet. Gynecol. 168:1654-1664.
  118. Rothman, K. 1986. Causal inference in epidemiology, p. 7-21. In K. J. Rothman (ed), Modern epidemiology. Little Brown, Boston, Mass.
  119. Scannapieco, F. 1998. Position paper: periodontal disease as a potential risk factor for systemic diseases. J. Periodontol. 69:841-850.
  120. Reference deleted.
  121. Scannapieco, F. A., and J. M. Mylotte. Relationships between periodontal disease and bacterial pneumonia. J. Periodontol. 67:1114-1122.
  122. Scannapieco, F. A., G. D. Papandonatos, and R. G. Dunford. Associations between oral conditions and respiratory disease in a national sample survey population. Ann. Periodontol. 3:251-256.
  123. Seppala, B., and J. Ainamo. A site-by-site follow-up study on the effect controlled versus poorly controlled insulin-dependent diabetes mellitus. J. Clin Periodontol. 21:161-165.
  124. Shapira, L., W. A. Soskolne, M. N. Sela, S. Offenbacher, and V. Barak. The secretion of PGE2, IL-1 beta, IL-6, and TNF alpha by adherent mononuclear cells from early onset periodontitis patients. J. Periodontol. 65:139-146.
  125. Shapiro, S., M. C. McCormick, B. H. Starfield, J. P. Krischer, and D. Bross. Relevance of correlates of infant deaths for significant morbidity at 1 year of age. Am. J. Obstet. Gynecol. 136:363-373.
  126. Shinzato, T., and A. Saito. A mechanism of pathogenicity of “Streptococcus milleri group” in pulmonary infection: synergy with an anaerobe. J. Med. Microbiol. 40:118-123.
  127. Shlossman, M., W. C. Knowler, D. J. Pettitt, and R. J. Genco. Type 2 diabetes mellitus and periodontal disease. J. Am. Dent. Assoc. 121:532-536.
  128. Sinclair, D. , and T. W. Evans. 1994. Nosocomial pneumonia in the intensive care unit. Br. J. Hosp. Med. 51:177-180.
  129. Slots, J. Casual or causal relationship between periodontal infection and non-roal disease? J. Dent. Res. 77:1764-1765.
  130. Slots, J., and T. E. Rams. Microbiology of periodontal disease, p. 425-443. In J. Slots and M. A. Taubman (ed.), Contemporary oral microbiology and immunology. Mosby, St. Louis, Mo.
  131. Smith, G. T., C. J. Greenbaum, B. D. Johnson, and G. R. Persson. Short-term responses to periodontal therapy in insulin-dependent diabetic patients. J. Periodontol. 67:794-802.
  132. Sommerfelt, K., K. Troland, B. Ellertsen, and T. Markestad. 1996. Behavioral problems in low-birth weight preschoolers. Dev. Med. Child Neurol. 38:927-940.
  133. Syrjänen, J. Vascular diseases and oral infections. J. Clin. Periodontol. 17:497-500.
  134. Syrjänen, J., J. Peltola, V. Valtonen, M. Iivanaineu, M. Kaste, and J. K. Huttunen. Dental infections in association with cerebral infarction in young and middle-aged men. J. Intern. Med. 225:179-184.
  135. Thoden van Velzen, S. K., L. Abraham-Ipijn, and W. R. Moorer. Plaque and systemic disease: a reappraisal of the focal infection concept. J. Clin. Periodontol. 11:209-220.
  136. Thom, D. , J. T. Grayston, D. S. Siscovick, S. P. Wang, N. S. Weiss, and J. R. Daling. 1992. Association of prior infection with Chlamydia pneumoniae and angiographicallly demonstrated coronary artery disease. JAMA 268:68-72.
  137. Thorstensson, H., and A. Hugoson. Periodontal disease experience in adult long-duration insulin-dependent diabetics. J. Clin. Periodontol. 20:352-358.
  138. Toews, G. B. Nosocomial pneumonia. Am. J. Med. Sci. 291:355-367.
  139. Tronstad, L. Recent development in endodontic research. Scan. J. Dent. Res. 100:52-59.
  140. Valtomen, V. 1991. Infection as a risk factor for infarction and atherosclerosis. Ann Med. 23:539-543.
  141. Van den Berg, B. J., and J. Yerushalmy. The relationship of the rate of intrauterine growth of infants of low birth weight to mortality, morbidity, and congenital anomalies. J. Pediatr. 69:531-545.
  142. Van der Bilt, A., L. W. Olthoff, F. Bosman, and S. P. Oosterhaven. The effect of missing postcanine teeth on chewing performance in man. Arch. Oral Biol. 38:423-429.
  143. Van der Meer, J. T., W. Van Wijk, J. Thompson, J.P. Vandenbroucke, H. A. Valkenburg, and M. F. Michel. 1992. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis. Lancet 339:135-139.
  144. Van Dyke, T. E., V. R. Dowell, Jr., S. Offenbacher, W. Snyder, and T. Hersh. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect. Immun. 53:671-677.
  145. Wayler, A. , K. K. Kapur, R. S. Feldman, and H. H. Chauncey. 1982. Effects of age and dentition status on measures of food acceptability. J. Gerontol. 37:294-299.
  146. Weinberg, A., S. Krisanaprakornkit, and B. A. Dale. Epithelial antimicrobial peptides: review and significance for oral applications. Crit. Rev. Oral Biol. Med. 9:399-414.
  147. Willet, W. C. Diet and coronary heart disease, p. 341-379. In W. C. Willet (ed.), Nutritional epidemiology. Oxford University Press, New York, N.Y.
  148. Williams, R., and C. Mahan. Periodontal disease and diabetes in young adults. JAMA 172:776-778.
  149. Xu, Q., G. Luef, S. Weimann, R. S. Gupta, H. Wolf, and G. Wick. Staining of endothelial cells and macrophages in atherosclerotic lesions with human heat-shock protein-reactive antisera. Arterioscler. Thromb. 13:1763-1769.
  150. Xu, Q., H. Dietrich, H. J. Steiner, A. M. Gown, B. School, G. Mikuz, S. H. Kaufmann, and G. Wick. Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65. Arterioscler. Thromb. 12:789-799.
  151. Xu, Q., J. Willeit, M. Marosi, R. Kleindienst, F. Oberhollenzer, S. Kleechl, T. Stulnig, G. Luef, and G. Wick. 1993. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet 341:255-259.
  152. Xu, Q., R. Kleindienst, W. Waitz, H. Dietrich, and G. Wick. Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65. J. Clin. Investig. 91:2693-2702.
  153. Young, R. A., and T. J. Elliott. 1989. Stress proteins, infection, and immune surveillance. Cell 59:5-8.
  154. Yuan A., K. T. Luh, and P. C. Yang. Actinobacillus actinomycetemcomitans pneumonia with possible septic embolization. Chest 105:64.
  155. Zambon, J. J., M. Nakamura, and J. Slots. Effect of periodontal therapy on salivary enzymatic activity. J. Periodontal Res. 20:652-659.
  156. Reference deleted.
  157. Zijlstra, E. E., G. R. Swart, F. J. Godfroy, and J. E. Degener. Pericarditis, pneumonia and brain abscess due to a combined actinomyces—Actinobacillus actinomycetemcomitans infection. J. Infect. 25:83-87.