24A61, 1953.Goetz! EJ: Enhancement of random migration and chemotactic response of human leukocytes by ascorbic CHAPTER 17 309ea pig to artificially induced inflammation, J Dent Res 1948.lickrrran I, Stoller M: The periodontal tissues of the albino Dent Res 27:758, I9AQt indeficiency,vitamin A dec ency,en esf_1TN: Irl, effect of,.,,,,an 1, Stone 1C, iaw a: The e ec o cortisonecetate upon the periodontium of white mice, I Periodontol cid, I Clin Invest 53:813, 1974.;Idmar. HM: Acute aleukemic leukemia, Am J Orthod ~89, 1940.man MH: Perleche: a consideration of its etiology and !'} iology, Bull Johns Hopkins Hosp 51:263, 1943.,ttsegen R: Dental and oral considerations in diabetes ellitus, NY J Med 62:389, 1962.vier WM, Grieg ME: Prevention of oral lesions in B1 rii1tarnincitic dogs, Science 98:216, 1943.g.yr,reenberg MS, Cohen SB, Boosz B, et al: Oral herpes infections in patients with leukemia, J Am Dent Assoc 114:483, 1987.9. Grossi SG, Zambon JJ, Ho AW, et al: Assessment of risk for}periperiodontal disease. 1. Risk indicators for attachment loss, odontalPeriodontol 65:260, 1994. usberti F, Grossman N, Loesche W: Puberty gingivitisin insulin-dependent diabetes, J Dent Res 61:201, 1982 (abstract).VI,' yden P, Buckley LA: Diabetes mellitus and periodontal #

318PART 5 Relationship between Periodontal Disease and Systemic HealthBCLDL

Periodontal pathogensPeriodontal infectionMO+ phenotypeRisk factors for atherosclerosis`" Vascular effectsHypercoagulability Atheroma formation ThromboembolismAtheroma formation Vessel wall thickening Thromboembolic eventsPeriodontal Medicine: Impact of Periodontal Infection on Systemic Health CHAPTER 18319Gram-negative bacteremia/LPSPeriodontitisEndothelial damagePlatelet adhesion/aggregationMonocyte infiltration/proliferationCytokine/growth factor productionThrombus formationChronic bacterial challengeProinflammatory cytokinesAcute phase reactants

320PART 5 Relationship between Periodontal Disease and Systemic Health From: We H: Diabetes Care I 6(5uppi 1):329, 1993.BOX 18-2Complications of Diabetes Mellitus

Periodontal Medicine: Impact of Periodontal Infection on Systemic Health CHAPTER 18321 'diabetic complications in these subjects.with reduced probing depths and bleeding onB.O.P.unchangedN=5N=4IB.O.P.

310PART 5 - Relationship between Periodontal Disease and Systemic Health

Influence of Systemic Disorders and Stress on the Periodontium CHAPTER 17311nse to non-surgical periodontal treatment in subjectsji"diabeteS mellitus, I Clin Periodontol 18:65, 1991.T, Sal edt E, Koppang HS: The effect of immunoSsivc agents on periodontal disease in man, Iontal Res 13:240, 1978.hopping NH, Fraser HE: Mouth lesions associated with dietary deficiencies in monkeys, Public Health Rep 54:416, 4319, 9,~6'111resky S, Fisher B, Glickman I: A histochemical study of e attached gingiva in pregnancy, I Dent Res I936. 6gel, R: Relationship of folic acid to phenytoin-induced -n -,Vgival overgrowth. In Hassell TM, Johnson M, Dudley K, F'editors: Phenytoin-induced teratology and gingival pathology,rew York, 1980, Raven Press. ogel R, Deasy M, Alfano M, et at: The effect of folic acid n girigival health of women taking oral contraceptives, Prey Dent 6:221, 1980.

CHAPTER OUTLINE312

Periodontal Medicine: Impactof Periodontal Infection on Systemic Health CHAPTER 18313"x`1111 Qsses, Hunter also identified gingivitis and periodon-immunology. ti*as foci of infection. He advocated extraction of teethwith these conditions to eliminate the source of sepsis.EVIDENCE-BASED CLINICAL PRACTICE Hunter believed that teeth were liable to septic infectionPrimarily because of their structure and their relationshipare of the precepts of the focal infection theory areI'Alveolar bone. He stated that the degree of systemicbeing revived today in light of recent research demon-effect produced by oral sepsis depended on the virulenceany of the systemic conditions discussed in Chaptersof the oral infection and the individual's degree of resis-I'd 17 serve to modify the host's susceptibility tospecific He also believed that oral organisms had specifictiaiontitis. For example, patients with immune supacted on different0tissues and that these organisms acteddon may not be able to mount an effective hostby producing toxins, resulting in low-grade "subinfection,#'rise to subgingival microorganisms, resulting inwhich produced systemic effects over prolonged periods.(rapid and severe periodontal destruction. Althoughbetween Hunter believed that the connection betweenotential impact of many systemic disorders on thebe sepsis and resulting systemic conditions could be6dontilim is well documented, recent evidence suggeststooth by removal of the causative sepsis through tooth'periodontal infection may significantly enhance theextraction and observation of the improvement in syste-or certain systemic diseases or alter the naturalhealth. Because it explained a wide range of disordersse of systemic conditions .66 Conditions in whichfor which there was no known explanation at the time,nfluences of periodontal infection are documentedand theory became widely accepted in Britain and~de coronary heart disease (CHD) and CHD-relatedwholesale the United States, leading to wholesaleis such as angina and infarction, atherosclerosis,extraction of teeth.e, diabetes mellitus, preterm labor, low-birth-weightthefocal infection theory fell into disrepute in thevery, and respiratory conditions such as chronicof and 1950s when widespread extraction, often oftractive pulmonary disease",'9 (Box 18-1).the entire dentition, failed to reduce or eliminate thesystemic conditions to which the supposedly infectedCAL INFECTION THEORY REVISITED dentition had been linked. The theory, while offering a possible explanation for perplexing systemic disorders, arch in the area of periodontal medicine marks ahad been based on very little, if any, scientific evidence. rgence in the concept of focal infection. In 1900,Hunter and other advocates of the theory were unableilliam Hunter, a British physician, first developed thesystemic explain how focal oral sepsis produced these systemicPa that oral microorganisms were responsible for amaladies. They were also unable to elucidate possiblee range of systemic conditions that were not easilyinteractive mechanisms between oral and systemicgnized as being infectious in nature."," He claimedtooth Furthermore, the suggested intervention of tooth restoration of carious teeth instead of extraction re conditions often had no effect on the systemic conditions Sulted in the trapping of infectious agents under restora-for which patients sought relief. However, Hunter's ideas s- In addition to caries, pulpal necrosis, and periapicaldid encourage extensive research in microbiology andI.Furthermore, the importance of the host inWA I iible host is also imperative. In a host who is cognition of the importance of host susceptibility door to understanding the differences in the natural history, and progression of periodontitishost susceptibility, not all individuals are equally ~_a'ble to the destructive effects of periodontal patho-.Ading on the wound-healing capacity and suscepti-cal literature. For example, respiratory tract patho ay have minimal effect on many individuals, a susceptible host such as an elderly patient, these 'pathogens may cause life-threatening respiratory rillnesses.strating links between oral and systemic health. However,itiation and progression is clearly recognized.BOX 18pathogenic bacteria are necessary for periodontalSystems and Conditions Possibly Influenced~-Jfey are not sufficient alone to cause the disease.Infection Periodontal Infection-eptible to disease, pathogenic bacteria may haveSystem8a;~effect. Conversely, the susceptible host experi-Atherosclerosisnical signs of periodontitis in the presence ofCoronary heart disease (CHD)4 ic bacteria.AnginaMyocardialbrovascula infarction (MI)Cerer accident (stroke)f#"ughout the scientific literature. Because of differ-Endocrine SystemDiabetes mellitusjlri,js patients may not necessarily have similar dis-Reproductive Systemptession despite the presence of similar bacteria.Preterm low-birth-weight (LBW) infantsWise, the response to periodontal treatment may varyPreeclampsiathe host to further disease progression. TheRespiratory Syste of host susceptibility is clearly evident in theChronic obstructive pulmonary disease (COPD)m-Acute bacterial pneumonia

CommentsProvides relatively weak, retrospective anecdotal evidence.May suggest further study is needed.Compares groups of subjects at a single point in time.Stronger than case report.Fairly easy to conduct.Relatively inexpensive to conduct. Follows groups of subjects over time. Stronger than cross-sectional study.Studies with control group are much stronger than studies without controlsType of StudyStrength of EvidenceCase report+/Cross-sectional study+Longitudinal study++intervention trial+++More difficult and expensive to conduct.Examines effects of some interventions.Studies with control group (i.e., placebo) much stronger than studies without controls.Strongest form of evidence is randomized controlled intervention trial. Difficult and expensive to conduct.

Periodontal Medicine: ltnpact of Periodontal Infection on Systemic Health CHAPTER 18315no. evidence. Only the occasional case report and k-~.1 tl to the 11 cdotes were availablesubstantiate e L theory.I planatory mechanisms were proposed, none dated with scientific research. Unfortunately, ry predated current concepts of evidence-basedleading to unnecessary extraction of ,practice,teeth. Currently, in reexamining the potential oral infections and systemic co Lions betweenJimportant determinecrLant to ewhat evidence (1) st is It I"fey( ) is still needed to substantiate the associa- andvalidates the possible mechanisms of asso-jjon is chapter reviews current knowledge relating4i F , ,o al infection to overall systemic health.ERIODONTAL DISEASE AND MORTALITY.e ultimate medical outcome measure is mortality. BGINGIVAL ENVIRONMENT AS RESERVOIR fiBACTERIA1,; f in with diubgingivai micro u a n patients wperiodontitis des a significant and persistent grain-negativek~w.*ial challenge to the host (see Chapters 9 and 13). A their products, andFI suchasI lipopolychan e (LPS), have ready access to the periodontal sues and to the circulation via the sulcular epithelium, i is frequently ulcerated and discontinuous. Even 0ireatment, complete eradication of these organisms "difficult, and their reemergence is often rapid. The al surface area of pocket epithelium in contact with bgingival bacteria and their products in a patient with neralized moderate periodontitis has been estimated .;approximately the size of the palm of an adultaneven larger areas of exposure in cases of morey4hced periodontal destruction.78 Bacteremias are*-G? !ynon after mechanical periodontal therapy and alsofrequently during normal daily function and oral 0giene procedures .26,33,65 Just as the periodontal tissues bunt an immunoinflammatory response to bacteria and eir products, systemic challenge with these agents also duces a major vascular response. This host response ay offer explanatory mechanisms for the interactions tween periodontal infection and a variety of systemic "tilers.

3161 PART 5 Relationship between Periodontal Disease and Systemic Health pathogenic mechanisms.

Periodontal Medicine: Impact of Periodontal Infection on Systemic Health - CHAPTER 18317Coronary heart diseaseSystemic or periodontal(CHID) risk factorsinfectionChronicAcuteThromboembolismFibrinogenWhite blood cell count 't' von Willebrand factorOcclusion ofcoronaryarteriesBlood viscosityMyocardial ischemiaIschemic heartdiseaseAnginaMyocardial infarctionure 18-1 Acute and chronic pathways to ischemic heart Isease. CHID-related events such as angina or myocardial'%'firction may be precipitated by either pathway or both.;pathways.figure 18-2 Factors affecting blood viscosity in health.ewise been associated with the risk of ischemic heart disease.82