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Oral Systemic Connections & Bibliography

The Consequences of Oral Bacteria and Gum Disease Go Far Beyond the Mouth

Author: Dr. Ron McGlennen

OralDNA® Labs offers testing for the profile of oral bacteria that cause periodontal disease. These bacteria, especially at high levels, and in combination with an individual’s genetic inflammatory response, result in bad breath, painful, bleeding gums, loss of bone and eventually tooth loss. But the consequences of these same bacteria, present for years and decades, add significantly to the risk of wide range of life- threatening diseases beyond the mouth. Below are some of those diseases and the measurable risk of those diseases becoming serious if these oral pathogens are not treated.

Cardiovascular disease: There is consensus within the medical and dental professional organizations that periodontal bacteria contribute to the initiation, progression and prognosis of cardiovascular disease. From key meta-analysis studies, persons with untreated periodontal infections have up to a 20% increase in their risk of coronary vascular disease1. The multiple of risk for stroke (1.74-2.85 fold) and peripheral vascular disease (1.41-2.27 fold) is equal or greater1. More specifically, the risk of a first myocardial infarction is associated with periodontal disease (OR of 1.49) even after adjustment for a history of smoking, obesity, diabetes and selected socioeconomic factors2. But equally important is the concern for specific bacteria that are a basis for this risk including A.a., P.g., T.f., T.d., F.n. and P.i.3-7. Specifically, Fn carries a series of virulence factors that can contribute to inflammation of the arterial wall8. Toward the interest to prevent heart and vascular disease, testing your patients for which types and what levels of these dangerous bacteria are present will provide them better care.

Metabolic health and Diabetes: Elevated levels of periodontal bacteria can directly cause hyperglycemia9. Long term, the inflammation associated with increased pathogen burden can affect the health of the pancreas, and specifically, there is the risk of the loss of beta cells that produce insulin and respond to elevated blood glucose10. Correspondingly, persons with elevated blood glucose are at risk for progressive periodontal infection and inflammation11. So, by these opposing mechanisms, the relationship of periodontal disease and pre-diabetes and diabetes is viewed as a two- way street12. Early detection of periodontal infection and proactive management to reduce bacterial loads can improve blood sugar control and lessen the complications of diabetes as well as the consequence of periodontitis13.

Health During Pregnancy: The oral microbiota changes when women become pregnant, and levels of periodontal pathogens increase14. During pregnancy, periodontal inflammation worsens, mostly due to increased levels of A.a., P.g., F.n. and P.i.15. Among these oral pathogens, there is a marked risk of infection of the maternal blood and the placenta, which leads to an increase in pre-term labor, lower birth weight and even the chance of fetal loss due specifically to the bacteria P.g. and F.n. 16,17. Further, the long-term risk for systemic disease in mothers with periodontitis is evident in the progression of atherosclerosis and the increased risk of venous thrombosis due to F.n., P.g., T.f. and A.a.16,18. For these reasons, consider testing all women who are planning a pregnancy with the goal of reducing these bad bacteria.

Development of Cancer and Risk of Progression: Advanced periodontal disease is associated with a 2.5 fold increase in smoking related cancers19. Breast cancer is common, and persons with elevated levels of the bacteria A.a. and P.g. have a greater chance of recurrence or failed response to treatment. In another prospective study, persons with periodontal P.g. showed a 59% increased risk of pancreatic cancer. There are also reports of oral A.a. and T.d. linked to pancreatic tumors20. P.g., T.d. and T.f. are also linked to risk of esophageal cancers21,22. Reducing your patient’s risk of developing cancer by treating periodontal infection is another reason to visit your dentist and request a MyPerioPath® test. A role for the oral bacteria Fn in the progression of colorectal cancer is provocative. Several recent studies show that F.n. can be identified within the primary cancer cells from colonic tumors, and are carried to metastatic sites involving regional lymph nodes23,24. This is a newly observed phenomenon that will affect how cancer treatment protocols will be developed in the future.

Joint and Musculoskeletal Health: Rheumatoid arthritis is a chronic inflammatory condition. In a recent meta-analysis of 21 separate studies, there was a significantly increased risk of periodontitis in people with RA compared to healthy controls (relative risk: 1.13; 95% CI: 1.04, 1.23; p = 0.006; N = 153,277)25. The most prevalent pathogens found were P.g. and F.n. Importantly, the infection and the antibodies against these bacteria are typically found before the onset of symptoms26. The good news is that therapeutic reduction of bacterial load, as determined by molecular tests such as MyPerioPath®, may reduce symptoms and improve the prognosis of the arthritis27.

Dementia and Brain Health: Recent medical studies point to poor oral health, and high levels of the bacteria in our gums with the increased risk to develop Alzheimer’s and other types of dementia. Additionally, the direct effects of those oral bacteria to cause atherosclerosis in the vessels within the brain impart significant risk for stroke and vascular types of dementia.

Periodontal Bacteria Measured by the MyPerioPath® Test

Red Complex Pathogens
Actinobacillus actinomycetemcomitans
Porphyromonas gingivalis
Tanerella forsythia
Treponema denticola
 
Orange Complex Pathogens
Eubacterium nodatum
Prevotella intermedia
Peptostreptococcus micros
Fusobacterium nucleatum/periodontium
Campylobacter rectus
Green Complex Pathogens
Eikenella corrodens
Capnocytophaga species
 
 
 
Red Complex PathogensOrange Complex PathogensGreen Complex Pathogens
Actinobacillus actinomycetemcomitans Eubacterium nodatum Eikenella corrodens
Porphyromonas gingivalis Prevotella intermedia Capnocytophaga species
Tanerella forsythia Peptostreptococcus micros
Treponema denticola Fusobacterium nucleatum/periodontium
Campylobacter rectus

References

  1. Meurman JH, Sanz M, Janket SJ. Oral health, atherosclerosis, and cardiovascular disease. Crit Rev Oral Biol Med 2004;15:403-13.
  2. Ryden L, Buhlin K, Ekstrand E, et al. Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study. Circulation 2016;133:576-83.
  3. Pucar A, Milasin J, Lekovic V, et al. Correlation between atherosclerosis and periodontal putative pathogenic bacterial infections in coronary and internal mammary arteries. J Periodontol 2007;78:677-82.
  4. Radwan-Oczko M, Jaworski A, Dus I, Plonek T, Szulc M, Kustrzycki W. Porphyromonas gingivalis in periodontal pockets and heart valves. Virulence 2014;5:575-80.
  5. Range H, Labreuche J, Louedec L, et al. Periodontal bacteria in human carotid atherothrombosis as a potential trigger for neutrophil activation. Atherosclerosis 2014;236:448-55.
  6. Rath SK, Mukherjee M, Kaushik R, Sen S, Kumar M. Periodontal pathogens in atheromatous plaque. Indian J Pathol Microbiol 2014;57:259-64.
  7. Bale BF, Doneen AL, Vigerust DJ. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Postgrad Med J 2017;93:215-20.
  8. Liljestrand JM, Paju S, Pietiainen M, et al. Immunologic burden links periodontitis to acute coronary syndrome. Atherosclerosis 2018;268:177-84.
  9. Stanko P, Izakovicova Holla L. Bidirectional association between diabetes mellitus and inflammatory periodontal disease. A review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014;158:35-8.
  10. Janket SJ, Javaheri H, Ackerson LK, Ayilavarapu S, Meurman JH. Oral Infections, Metabolic Inflammation, Genetics, and Cardiometabolic Diseases. J Dent Res 2015.
  11. Kumar M, Mishra L, Mohanty R, Nayak R. "Diabetes and gum disease: the diabolic duo". Diabetes Metab Syndr 2014;8:255-8.
  12. Chee B, Park B, Bartold PM. Periodontitis and type II diabetes: a two-way relationship. Int J Evid Based Healthc 2013;11:317-29.
  13. Kaye EK, Chen N, Cabral HJ, Vokonas P, Garcia RI. Metabolic Syndrome and Periodontal Disease Progression in Men. J Dent Res 2016;95:822-8.
  14. Persson GR, Hitti J, Paul K, et al. Tannerella forsythia and Pseudomonas aeruginosa in subgingival bacterial samples from parous women. J Periodontol 2008;79:508-16.
  15. Carrillo-de-Albornoz A, Figuero E, Herrera D, Bascones-Martinez A. Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm. J Clin Periodontol 2010;37:230-40.
  16. Han YW, Houcken W, Loos BG, Schenkein HA, Tezal M. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer. Adv Dent Res 2014;26:47-55.
  17. Andonova I, Iliev V, Zivkovic N, Susic E, Bego I, Kotevska V. Can oral anaerobic bacteria cause adverse pregnancy outcomes? Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2015;36:137-43.
  18. Kurita-Ochiai T, Yamamoto M. Periodontal pathogens and atherosclerosis: implications of inflammation and oxidative modification of LDL. Biomed Res Int 2014;2014:595981.
  19. Zeng XT, Xia LY, Zhang YG, Li S, Leng WD, Kwong JS. Periodontal Disease and Incident Lung Cancer Risk: A Meta-Analysis of Cohort Studies. J Periodontol 2016:1-13.
  20. Jacob JA. Study Links Periodontal Disease Bacteria to Pancreatic Cancer Risk. JAMA 2016;315:2653-4.
  21. Nieminen MT, Listyarifah D, Hagstrom J, et al. Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation. Br J Cancer 2018;118:428-34.
  22. Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H. Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications. Ann Gastroenterol Surg 2017;1:99-104.
  23. Amitay EL, Werner S, Vital M, et al. Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study. Carcinogenesis 2017;38:781-8.
  24. Yamamura K, Baba Y, Nakagawa S, et al. Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis. Clin Cancer Res 2016;22:5574-81.
  25. Fuggle NR, Smith TO, Kaul A, Sofat N. Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis. Front Immunol 2016;7:80.
  26. Johansson L, Sherina N, Kharlamova N, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther 2016;18:201.
  27. Khare N, Vanza B, Sagar D, Saurav K, Chauhan R, Mishra S. Nonsurgical Periodontal Therapy decreases the Severity of Rheumatoid Arthritis: A Case-control Study. J Contemp Dent Pract 2016;17:484-8.

Bibliography

Periodontal Disease Overview

  1. Vincent E. Friedewald, Kenneth S. Kornman, James D. Beck, Robert Genco, Allison Goldfine, Peter Libby, Steven Offenbacher, Paul M. Ridker, Thomas E. Van Dyke, and William C. Roberts.   The American Journal of Cardiology and The Journal of Periodontology Editors’ Consensus: Periodontitis and Atherosclerotic Cardiovascular Disease.  Journal of Periodontology 80 (2009): 1021-1032.
  2. Thomas Beikler and Thomas F. Flemmig. Oral biofilm-associated diseases: Trends and implications for quality of life, systemic health and expendituresPeriodontology 2000 55 (2010): 87-103. 
  3. Mario Aimetti, et al. One –Stage Full-Mouth Disinfection as a Therapeutic Approach for Generalized Aggressive Periodontitis. Journal of Periodontol 82 (2011): 845-853.
  4. Mariano Sanz and Arie Jan van Winkelhoff. Periodontal infections: Understanding  the Complexity-Consensus of  the Seventh European Workshop on Periodontology. Journal of Clinical Periodontology 38 (2011): 3-6.
  5. Frank Schwarz and Jΰrgen Becker. Perio-Implant Infection: Etiology, Diagnosis and Treatment. London: Quintessence Publishing Co, 2010.
  6. Liran Levin, Ronen Ofec, Yoav Grossmann, and Rachel Anner.  Periodontal disease as a risk for dental implant failure over time: A long-term historical cohort SourceJournal of Clinical Periodontology 38 (2011): 732-737.
  7. Georgios Charalampakis, Per Rabe, Asa Leonhardt, and Gunnar Dahlén.  A follow-up study of peri-implantitis cases after treatmentJournal of Clinical Periodontology 38 (2011): 864-871.
  8. Atsuo Amano.  Host-Parasite Interactions in Periodontitis:  Subgingival Infection and Host SensingPeriodontology 2000 52 (2010): 7-11.
  9. Hiroshima Yoshe, Tetsuo Kobyashim, Hideaki Tai, and Johnah C. Galicia.  The role of genetic polymorphisms in periodontitisPeriodontology 2000 43 (2007) 102-132.
  10. Steven Offenbacher, Silvana Barros and James D. Beck.  Rethinking Periodontal InflammationJournal of Periodontology Supplement (2008): 1577-1591.
  11. Sigmund S. Socransky and Anne D. Haffajee.  Dental biofilms: Difficult therapeutic targets. Periodontology 2000 28 (2008): 12-55.
  12. American Academy of Periodontology Statement on Risk AssessmentJournal of Periodontology 79 (2008): 202.
  13. Comprehensive Periodontal Therapy: A Statement by the American Academy of PeriodontologyJournal of Periodontology 82 (2011): 943-949.
  14. American Academy of Periodontology Statement on The Efficacy of Lasers in the Non-Surgical Treatment of Inflammatory Periodontal DiseaseJournal of Periodontology 82 (2011): 513-514.
  15. American Academy of Periodontology Statement Regarding Gingival Curettage; Journal of Periodontology 73 (2002): 1229-1230.
  16. American Academy of Periodontology Statement on Local delivery of Sustained or Controlled Release Antimicrobials as Adjunct Therapy in the Treatment of Periodontitis. Journal of Periodontology 77 (2006): 1458.
  17. American Academy of Periodontology Statement Regarding Periodontal Management of the Pregnant Patient. Journal of Periodontology 75 (2004): 495.
  18. Statement on Periostat® as an Adjunct to Scaling and Root Planing.  Online resource of the American Academy of Periodontology.  Published January 2000.
  19. For the dental patient: Women and periodontal disease. The Journal of the American Dental Association 133 (2002): 671.
  20. U.S. Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General. Rockville, MD: U.S. Dept. of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health: 2000.
  21. A.L. Russell. A system of classification and scoring for prevalence surveys of periodontal disease. J Dent Res 35 (1956): 350-359.
  22. Sigurd P. Ramfjord. The Periodontal Disease Index (PDI). Journal of Periodontology 38 (1967): 602-610.

Pathogen Threshold Levels and Bacterial Risk

  1. McGlennen, Ronald MyPerioPath: December 2016 Test Updates and Enhancements
  2. Thomas F. Flemmig and Thomas E. Beikler. Control of oral biofilms.  Periodontology 2000 55 (2011): 9-15.
  3. Philip D. Marsh, Annette Moter, and Deirdre A. Devine. Dental plaque biofilms: communities, conflict and controlPeriodontology 2000 55 (2011): 16-35.
  4. Y. Abiko, T. Sato, G. Mayanagi, and N. Takahashi.  Profiling of subgingival plaque biofilm microflora from periodontally healthy subjects and from subjects with periodontitis using quantitative real-time PCR. Journal of Periodontal Research 45 (2010): 389-395.
  5. Ricardo P. Teles, Anne D. Haffajee, and Sigmund S. Socransky.  Microbiological goals of periodontal therapyPeriodontology 2000 42 (2006): 180­218.
  6. Sigmund S. Socransky, Anne D. Haffajee.  Microbial etiological agents of destructive periodontal diseasePeriodontology 2000 5 (1994): 78­111.
  7. Anne D. Haffajee, Ricardo P. Teles, and Sigmund S. Socransky.  The  effect of periodontal therapy on the composition of the subgingivalmicrobiota. Periodontology 2000 42 (2006): 219-258.
  8. Ljiljana Kesic, Jelena Milasin, Marija Igic, and Radmila Obradovic.  Microbial Etiology of Periodontal Disease: Mini Review. Medicine and Biology 15 (2008): 1-6.

MyPerioPath® Description/Clinical Utility of Periodontal Testing

  1. Mariano Sanz and Arie Jan van Winkelhoff.  Periodontal infections: Understanding  the Complexity-Consensus of  the Seventh European Workshop on Periodontology. Journal of Clinical Periodontology 38 Issue Supplement (2011): 3-6.
  2. Arie J. van Winkelhoff and Edwin G. Winkel. Microbiological diagnostics in periodontics: Biological significance and clinical validityPeriodontology 2000 39 (2005): 40­52.
  3. Sigmund S. Socransky, Anne D. Haffajee, M. Cugini, C. Smith, and R.L. Kent Jr.  Microbial complexes in subgingival plaqueJournal of Clinical Periodontology 25 (1998): 134­144.
  4. Ricardo P. Teles, Anne D. Haffajee, and Sigmund S. Socransky.  Microbiological goals of periodontal therapyPeriodontology 2000 42 (2006): 180­218 .
  5. Anne D. Haffajee and Sigmund S. Socransky.  Microbial etiological agents of destructive periodontal diseasePeriodontology 2000 5 (1994): 78­111 .
  6. Anne D. Haffajee, Ricardo P. Teles, and Sigmund S. Socransky.  The effect of periodontal therapy on the composition of the subgingivalmicrobiotaPeriodontology 2000 42 (2006): 219­258.
  7. Zhimini Feng, Aaron Winberg.  Role of bacteria in health and disease of periodontal tissuesPeriodontology 2000 40 (2006): 50­76.
  8. Sigmund S. Socransky and Anne D. Haffajee.  Dental biofilms: Difficult therapeutic targets. Periodontology 2000 28 (2008): 12-55.
  9. Susan Kinder Haake.  “Etiology of Periodontal Diseases” in Carranza’s Clinical Periodontology, 9th edition.  Los Angeles: Saunders (2002).  95­112.
  10. Rose LF, Steinberg BJ, Minsk L. The relationship between periodontal disease and systemic conditions. Compendium of Continuing Education in Dentistry 21 (2000): 870-7.

MyPerioID® Reference

  1. Ahmed Abd El-Meguid Mostafa Hamdy, Mohamed Abd El-Moniem Ebrahem. The Effect of Interleukin 1 Genotype 2 on the Individual’s Susceptibility to Peri-implantitis: Case Control Study.  Journal of Oral Implantology 37 (2011): 325-334.
  2. Yen-Chun, G. Liu, Ulf H. Lerner, and Yen-Tung A.Teng.  Cytokine responses against periodontal infection: Protective and destructive rolesPeriodontology 2000 52 (2010): 163-206.
  3. Dana Graves.  Cytokines that Promote Periodontal Tissue DestructionJournal of Periodontology 79 supplement (2008): 1585-1591.
  4. David Goteiner, Robert Ashmen, Neal Lehrman, Malvin N. Janal, and Barner Eskin.  Presence and Significance of Interleukin-1 Polymorphism in Patient Who Present With Acute Coronary Syndrome, Angina, and Chronic Periodontitis: An Epidemiologic Pilot Study.  Journal of Periodontology 79 (2008): 138-143.
  5. P. Axelsson. “Prediction of periodontitis risk and risk profiles” in Diagnosis and Risk Prediction of Periodontal Diseases, Vol. 3.  Chicago: Quintessence Publishing Co., 2002.  210­35.
  6. Corey LA, Nance WE, Hofstede P, Schenkein HA. Self­reported periodontal disease in a Virginia twin population. Journal of Periodontology 64 (1993): 1205­1208.
  7. M. DeSanctis and G. Zuchelli.  Interleukin­1 Gene Polymorphisms and Long-Term Stability Following Guided Tissue Regeneration. Journal of Periodontology 71 (2000): 606­13.
  8. L.J. Emrich, M. Shlossman, and R.J. Genco. Periodontal disease in non­insulin dependent diabetes mellitus. Journal of Periodontology 62 (1991):123­131.
  9. A. Feloutzis, N.P. Lang, M.S. Tonetti, W. Burgin, U. Bragger, D. Buser, G.W. Duff, and K.S. Kornman.  IL­1 gene polymorphism and smoking as risk factors for peri­implant bone loss in a well­maintained population. Clinical Oral Implants Research 14 (2003): 10­7.
  10. Kornman KS Crane A, Wang HY, et al. The Interleukin­1 genotype as a severity in adult periodontal disease. Journal of Clinical Periodontology 24 (1997): 72­77.
  11. Kornman KS. Mapping the Pathogenesis of Periodontitis: A New Look.  Journal of Clinical Periodontology 79 (2008): 1560­1568.
  12. McGuire MK, Nunn ME. Prognosis versus actual outcome. IV. The effectiveness of clinical parameters and IL­1 genotype in accurately predicting prognoses and tooth survival. Journal of Periodontology 70 (1999): 49­56.
  13. Michalowicz BS, Diehl SR, Gunsolley JC, et al. Evidence of a substantial genetic basis for risk of adult periodontitis. Journal of Periodontology 71 (2000): 1699­1707.
  14. Page RC, Korman KS. The pathogenesis of human periodontitis: an introduction. Periodontology 2000 14 (1997): 9­11.
  15. Papapanou PN. Periodontal diseases: epidemiology. Annals of Periodontology 1 (1996): 136.
  16. Tatakis DN, Kumar PS. Etiology and pathogenesis of periodontal diseases. Dental Clinics of North America 49 (2005): 491­516.
  17. Thomas WM, Braodbent JM, Welch D, Beck JD, Poulton R. Cigarette smoking and periodontal disease among 32­year­olds: a prospective study of a representative birth cohort.  Journal of Clinical Periodontology 34 (2007): 828­834.

Office Periodontal Protocols

  1. JØrgen Slots and Henrik Slots. Bacterial and viral pathogens in saliva: disease relationship and infectious riskPeriodontology 2000 55 (2011): 48-69.
  2. American Academy of Periodontology Statement on Risk AssessmentJournal of Periodontology 79 (2008): 202.
  3. Comprehensive Periodontal Therapy: A Statement by the American Academy of PeriodontologyJournal of Periodontology 82 (2011): 943-949.
  4. American Academy of Periodontology Statement on The Efficacy of Lasers in the Non-Surgical Treatment of Inflammatory Periodontal DiseaseJournal of Periodontology 82 (2011): 513-514.
  5. American Academy of Periodontology Statement Regarding Gingival Curettage; Journal of Periodontology 73 (2002): 1229-1230.
  6. American Academy of Periodontology Statement on Local delivery of Sustained or Controlled Release Antimicrobials as Adjunct Therapy in the Treatment of Periodontitis. Journal of Periodontology 77 (2006): 1458.
  7. American Academy of Periodontology Statement Regarding Periodontal Management of the Pregnant Patient. Journal of Periodontology 75 (2004): 495.
  8. Periostat® as an Adjunct to Scaling and Root Planing;http://www.perio.org/resources-products/periostat.htm
  9. Benjamin Ehmke, Annette Moter, Thomas Beikler, Edwin Milian, and Thomas F. Flemmig.  Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral ColonizationJournal of Periodontology 76 (2005): 749-759.
  10. J. Slots.  Selection of antimicrobial agents in periodontal therapyJournal of Periodontal Research 37 (2002): 389-398.
  11. Arie J. van Winkelhoff.  Commentary Antibiotics in periodontics: right or wrong? Journal of Periodontology 80 (2009): 1555-1558.
  12. D. Herrera et al.  Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilmJournal of Clinical Periodontology 35 Supplement 8 (2008) 45-66.
  13. Krista Louivukene, Ene-Renate Pahkla, Taive Koppel, Mare Saag, Paul Naaber.  The Microbiological Status of Patients with Periodontitis in Southern Estonia after Non-surgical Periodontal TherapyBaltic Dental and Maxillofacial Journal 7 (2005): 45-47.
  14. Kenneth S. Kornman.  Refractory periodontitis: critical questions in clinical management.  Journal of Clinical Periodontology 23 (1996): 293-298.
  15. J. Slots.  Systemic Antibiotics in PeriodonticsJournal of Periodontology 75 (2004): 1553­1565.
  16. Beikler, Prior, Ehmke, Flemming. Specific Antibiotics in the Treatment of Periodontitis - Proposed StrategyJournal of Periodontology 75 (2004): 169-175.
  17. J. Slots.  Selection of antimicrobial agents in periodontal therapyJournal of Periodontal Research 37 (2002): 389-398.
  18. J. Slots and M. Ting.  Systemic antibiotics in the treatment of periodontal disease. Periodontology 2000 28 (2002): 106­176.
  19. A.D. Haffajee, S.S. Socransky, and J.C. Gunsolley.  Systemic Anti­infective Periodontal Therapy. A Systematic Review; Annals of Periodontology 8 (2003): 115-181.
  20. J. Slots.  Selection of antimicrobial agents in periodontal therapyJournal of Periodontal Research 37 (2002): 389-398.
  21. Gomi, Yashima, Nagano, Kanazashi, Maeda, Arai.  Effects of Full-Mouth Scaling and Root Planing in Conjunction With Systemically Administered AzithromycinJournal of Periodontology 78 (2007): 422­429.
  22. Clay Walker and Katherine Karpinia.  Rationale for Use of antibiotics in Periodontics. Journal of Periodontology 73 (2002): 1188­1196.
  23. Benjamin Ehmke, Annette Moter, Thomas Beikler, Edwin Milian, and Thomas F. Flemmig.  Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral ColonizationJournal of Periodontology 76 (2005): 749-759
  24. D. Kaner, C. Christan, T. Dietrich, J.P. Bernimoulin, B.M. Kleber, A. Friedmann.  Timing Affects the Clinical Outcome of Adjunctive Systemic Antibiotic Therapy for Generalized Aggressive Periodontitis: Periodontology 78 (2000): 1201­1208.
  25. Petit, Steenbergen, Scholte, van der Velden, Graff.  Epidemiology and transmission of Porphymonasgingivalis and Actinobacillusactinomycetemcomitans among children and their family members. Journal of Clinical Periodontology 20 (1993): 641­650.
  26. J. Slots and M. Jorgensen.  Effective, safe, practical and affordable periodontal antimicrobial therapy: where are we going, and are we there yet? Periodontology 2000 28 (2002): 298-312.
  27. Quirynen, Teughels, DeSoete, and Steenberghe.  Topical antiseptics and antibiotics in the initial therapy of chronic adult periodontitis: microbiological aspects. Periodontology 2000 28 (2002): 72­90.
  28. Parameters of CareJournal of Periodontology 71 Supplement (2000): 847-883.

Saliva Specimen Collection

  1. Thomas F. Flemmig and Thomas E. Beikler. Control of oral biofilms.  Periodontology 2000 55 (2011): 9-15.
  2. JØrgen Slots and Henrik Slots. Bacterial and viral pathogens in saliva: disease relationship and infectious riskPeriodontology 2000 55 (2011): 48-69.
  3. S. Paju, P. Pussinen, L. Suominen-Taipale, M. Hyvonen, M Knuuttila, E Kononen. Detection of Multiple Pathogenic Species in Saliva Is Associated with Periodontal Infection in Adults. Journal of Clinical Microbiology 47 (2009): 235-238
  4. S.C. Cortelli, M. Feres, A.A. Rodrigues, D.R. Aguino, J.A. Shibili, J.R. Cortelli.  Detection of Actinobacillusactinomycetemcomitans in Unstimulated Saliva of Patients With Chronic Periodontitis. Journal of Periodontology 76 (2005): 204-209.
  5. S. Paju, P. Pussinen, L. Suominen-Taipale, M. Hyvonen, M Knuuttila, E Kononen.  Population-Based Study of Salivary Carriage of Periodontal Pathogens in Adults. Journal of Clinical Microbiology 45 (2007): 2446-2451.
  6. K. Boutaga, P. Savelkoul, E. Winkel, A.J. van Winkelhoff.  Comparison of Subgingival Bacterial Sampling With Oral Lavage for Detection and Quantification of Periodontal Pathogens by Real-Time Polymerase Chain Reaction. Journal of Periodontology 78 (2007): 79-86.
  7. ADA Council of Scientific Affairs.  American Dental Association Council on Scientific Affairs Statement on Oral Fluid Diagnostics. 2008.
  8. Y.T. Teng, J. Sodek, and C.A.G. McCulloch.  Gingival Crevicular Fluid gelatinase and its relationship to periodontal disease in human subjects. Journal of Periodontal Research 27 (1992): 544-552.

OraRisk® HPV

  1. McGlennen, Ronald Oral HPV: An Overview of the Infection and its Role in the Development of Oral Cancer.
  2. Syrjanen, S., Bultzingslowen, A., Arduino, P., Campisis, G., Challacombe S., Ficarra, G., Flaitz C., Zhou H.M., Maeda H., Miller C., Jontell M.  Human papillomaviruses in oral carcinoma in oral potentially malignant disorders: a systematic reviewOral Diseases 17 Supplement (2011): 58-72.
  3. Anthoy N. Snow and Jennifer Laudadio. Human Papillomavirus Detection in Head and Neck Squamous Cell CarcinomasAdvances in Anatomic Pathology 17 (2010): 394-403.
  4. Maura L.Gillison, Gypsyamber D’Souza, William Westra, Elizabeth Sugar, Weihong Xiao,  Shahnaz Begum, and Raphael Viscidi.  Distinct Risk Factor Profiles for Human Papillomavirus Type 16-Positive and Human Papillomavirus Type 16-Negative Head and Neck CancersJournal of the National Cancer Institute 100 (2008): 407-420.
  5. G. D’Souza, A.R. Kreimer, R. Viscidi, M. Pawlita, C. Fakhry, W.M. Koch, W.H. Westra, M.L. Gillson.  Case-Control Study of Human Papillomavirus and Oropharyngeal CancerThe New England Journal of Medicine 356 (2007): 1944-56.
  6. Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review. Cancer Epidemiology, Biomarkers & Prevention 14 (2005): 467-475.  
  7. N. Termine, V. Panzarella, S. Falaschini, A. Russo, D. Matranga, L. Lo Muzio, G. Campisi.  HPV in oral Squamous cell carcinoma vs. head and neck Squamous cell carcinoma biopsies: a meta-analysis.   Annals of Oncology 19 (2008): 1681-1690.
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