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Hidden Epidemic

Thomas E. Levy, MD, JD

Summary: Infected teeth, infected gums, infected tonsils, and even infected sinuses always cause enough discomfort to drive us to a physician or dentist, but none of these are life-threatening…right? Wrong! In fact, dead wrong! They often kill, and they typically do it in a silent fashion. The overwhelming evidence in Hidden Epidemic proves that these oral infections are responsible for most heart attacks and breast cancers, as well as a majority of other chronic degenerative diseases. The good news is that there are effective treatments for these infections that are inexpensive.

References

PART ONE: Undeniable Evidence

Chapter 1: The Prevalence of Undetected, Silent Oral Infections

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Chapter 2: The Pandemic Incidence of Chronic Degenerative Diseases

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  5. Centers for Disease Control, https://www.cdc.gov/heartdiesease/facts.htm (2017)
  6. Cardiovascular Disease: A costly burden for America, Projections through 2035, http://www.heart.org/idc/groups/heart-public/@wcm/@adv/documents/downloadable/ucm_491543.pdf, American Heart Association, 2017.
  7. American Diabetes Association, http://www.diabetes.org/diabetes-basics/statistics/ (2017)

Chapter 3: The Demonstrable Link Between Oral Infections and Chronic Diseases

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PART TWO: Underlying Empirical Science

Chapter 4: Increased Oxidative Stress: The Common Cause of All Diseases

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Chapter 5: Sources of Increased Oxidative Stress

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PART THREE: Types of Oral Infections

Chapter 6: Tooth and Gum Infections

  1. Kulacz R., Levy T. (2014) The Toxic Tooth: How a root canal could be making you sick. Henderson, NV: MedFox Publishing
  2. Siqueira Jr. J., Rocas I. (2009) Diversity of endodontic microbiota revisited. Journal of Dental Research, 88:969-981. PMID: 19828883
  3. Nobrega L., Delboni M., Martinho F. et al. (2013) Treponema diversity in root canals with endodontic failure. European Journal of Dentistry, 7:61-68. PMID: 23408792
  4. Antunes H., Rocas I., Alves F., Siqueira Jr. J. (2015) Total and specific bacterial levels in the apical root canal system of teeth with post-treatment apical periodontitis. Journal of Endodontics, 41:1037-1042. PMID: 25892512
  5. Vidana R., Sullivan A., Billstrom H. et al. (2011) Enterococcus faecalis infection in root canals—host-derived or exogenous source? Letters in Applied Micro-biology, 52:109-155. PMID: 21155997
  6. Martinho F., Chiesa W., Zaia A. et al. (2011) Comparison of endotoxin levels in previous studies on primary endodontic infections. Journal of Endodontics, 37:163-167. PMID: 21238796
  7. Gomes B., Endo M., Martinho F. (2012) Comparison of endotoxin levels found in primary and secondary endodontic infections. Journal of Endodontics, 38:1082-1086. PMID: 22794210
  8. Waltimo T., Sen B., Meurman J. et al. (2003) Yeasts in apical periodontitis. Critical Reviews in Oral Biology and Medicine, 14:128-137. PMID: 12764075
  9. Nair P., Pajarola G., Schroeder H. (1996) Types and incidence of human periapical lesions obtained with extracted teeth. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiiology, and Endodontics, 81:93-102. PMID: 8850492
  10. Siqueira Jr. J., Rocas I. (2007) Bacterial pathogenesis and mediators in apical periodontitis. Brazilian Dental Journal, 18:267-280. PMID: 18278296
  11. Siqueira Jr. J., Rocas I. (2013) Microbiology and treatment of acute apical abscesses. Clinical Microbiology Reviews, 26:255-273. PMID: 23554416
  12. Jakovlijevic A., Andric M., Knezevic A. et al. (2015) Human cytomegalovirus and Epstein-Barr virus genotypes in apical periodontitis lesions. Journal of Endodontics, 41:1847-1851. PMID: 26435368
  13. Hernandez Vigueras S., Donosos Zuniga M., Jane-Salas E. et al. (2016) Viruses in pulp and periapical inflammation: a review. Odontology, 104:184-191. PMID: 25796386
  14. Hommez G., De Meerleer G., De Neve W., De Moor R., (2012) Effect of radiation dose on the prevalence of apical periodontitis—a dosimetric analysis. Clinical Oral Investigations, 16:1543-1547. PMID: 22219024
  15. Nair P. (2004) Pathogenesis of apical periodontitis and the cause of endodontic failures. Critical Reviews in Oral Biology and Medicine, 15:348-381. PMID: 15574679
  16. Garcia C., Sempere F., Diago M., Bowen E. (2007) The post-endodontic periapical lesion: histologic and etiopathogenic aspects. Medicina Oral, Patologia Oral Y Cirugia Bucal, 12:E585-E590. PMID: 18059244
  17. Siqueira Jr. J., Rocas I., (2007) Bacterial pathogenesis and mediators in apical periodontitis. Brazilian Dental Journal, 18:267-280. PMID: 18278296
  18. Muliyar S., Shameem K., Thankachan R. et al. (2014) Microleakage in endodontics. Journal of International Oral Health, 6:99-104. PMID: 256t28496
  19. Petersen J., Glasl E., Nasseri P. et al. (2014) The association of chronic apical periodontitis and endodontic therapy with atherosclerosis. Clinical Oral Investigations, 18:1813-1823. PMID: 24338091
  20. Gomes M., Hugo F., Hilgert J. et al. (2016) Apical periodontitis and incident cardiovascular events in the Baltimore Longitudinal Study of Ageing. International Endodontic Journal, 49:334-342. PMID: 26011008
  21. Liljestrand J., Mantyla P., Paju S. et al. (2016) Association of endodontic lesions with coronary artery disease. Journal of Dental Research, Jul 27 [Epub ahead of print]. PMID: 27466397
  22. Cardoso F., Ferreira N., Martinho F. et al. (2015) Correlation between volume of apical periodontitis determined by cone-beam computed tomography analysis and endotoxin levels found in primary root canal infection. Journal of Endodontics, 41:1015-1019. PMID: 25935504
  23. Costa A., Yasuda C., Shibasaki’ W. et al. (2014) The association between periodontal disease and seizure severity in refractory epilepsy patients. Seizure, 23:227-230. PMID: 24456623
  24. An G., Morse D., Kunin M. et al. (2016) Association of radiographically diagnosed apical periodontitis and cardiovascular disease: a hospital records-based study. Journal of Endodontics, 42:916-920. PMID: 27091354
  25. Pessi T., Karhunen V, Karjalainen P. et al. (2013) Bacterial signatures in thrombus aspirates of patients with myocardial infarction. Circulation, 27:1219-1228. PMID: 23418311
  26. Caplan D. (2014) Chronic apical periodontitis is more common in subjects with coronary artery disease. The Journal of Evidence-Based Dental Practice, 14:149-150. PMID: 25234220
  27. Shaw L., Harjunmaa U., Doyle R. et al. (2016) Distinguishing the signals of gingivitis and periodontitis in supragingival plaque: a cross-sectional cohort study in Malawi. Applied and Environmental Microbiology, Aug 12 lEpub ahead of print]. PMID: 27520811
  28. Segura-Egea J., Castellanos-Cosano L., Machuca G. et al. (2012) Diabetes mellitus, periapical inflammation and endodontic treatment outcome. Medicina Oral, Patoloqia Oral y Cirugia Bucal, 17:e356-e361. PMID: 22143698
  29. Razi T., Mohammadi A., Ghojazadeh M. (2012) Comparison of accuracy of conventional periapical radiography and direct digital subtraction radiography with or without image enhancement in the diagnosis of density changes. Journal of Dental Research, Dental Clinics, Dental Prospects, 6:54-58. PMID: 22991637
  30. Kanagasingam S., Hussaini H., Soo I. et al. (2016) Accuracy of single and parallax film and digital periapical radiographs in diagnosing apical periodontitis—a cadaver study. International Endodontic Journal, Apr 11 [Epub ahead of print]. PMID: 27063356
  31. Estrela C., Leles C., Hollanda A. et al. (2008) Prevalence and risk factors of apical periodontitis in endodontically treated teeth in selected population of Brazilian adults. Brazilian Dental Journal, 19:34-39. PMID: 18438557
  32. Lofthag-Hansen S., Huumonen S., Grondahl K., Grondahl H. (2007) Limited cone-beam CT and intraoral radiography for the diagnosis of periapical pathology. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 103:114-119. PMID: 17178504
  33. Davies A., Mannocci F., Mitchell P. et al (2015) The detection of periapical pathoses in root filled teeth using single and parallax periapical radiographs versus cone beam computed tomography—a clinical study. International Endodontic Journal, 48:582-592. PMID: 25074727
  34. Leonardi Dutra K., Haas L., Porporatti A. et al. (2016) Diagnostic accuracy of, cone-beam computed tomography and conventional radiography on apical periodontitis: a systemic review and meta-analysis. Journal of Endodontics, 42:356-364. PMlD: 26902914
  35. Saidi A., Naaman A., Zogheib C. (2015) Accuracy of cone-beam computed tomography and periapical radiography in endodontically treated teeth evaluation: a five-year retrospective study. Journal of International Oral Health, 7:15-19. PMID: 25878472
  36. Estrela C. Bueno M., Azevedo B. et al. (2008a) A new periapical index based on cone beam computed tomography. Journal of Endodontics, 34:1325-1331. PMID: 18928840
  37. Venskkutonis T., Daugela P., Strazdas M., Juodzbalys G. (2014) Accuracy of digital radiography and cone beam computed tomography on periapical treated teeth. Journal of Oral & Maxillofacial Research, 5:e1. PMID: 25089173
  38. von Arx T., Janner S., Hanni S., Bornstein M. (2015) Agreement between 2D and 3D radiographic outcome assessment one year after periaical surgery. International Endodontic Journal, Sep 9 [Epub ahead of print]. PMlD: 26356580
  39. Davies A., Patel S., Foschi F. et al. (2016) The detection of periapical pathoses using digital periapical radiography and cone beam computed tomography in endodontically retreated teeth—part 2: a 1 year post-treatment follow-up. International Endodontic Journal, 49:623-635. PMID: 26174351
  40. de Paula-Silva F., Wu M., Leonardo M. et al. (2009) Accuracy of periapical radiography and cone-beam computed tomography scans in diagnosing apical periodontitis using histopathological findings as a gold standard. Journal of Endodontics, 35:1009-1012. PMID: 19567324
  41. Gumru B., Tarcin B., lriboz E. et al. (2015) Assessment of the periapical health of abutment teeth: a retrospective radiological study. Nigerian Journal of Clinical Practice, 18:472-476. PMID: 25966717
  42. Haheim L., Olsen I., Ronningen K. (2011) Association between tooth extraction due to infection and myocardial infarction. Community Dentistry and Oral Epidemiology, 39:393-397. PMID: 21557755
  43. Spivakovsky S. (2012) Myocardial infarction and tooth extraction associated. Evidence-Based Dentistry, 13:110. PMID: 23258177
  44. Brasil S., Santos R., Fernandes A. et al. (2016) Influence of estrogen deficiency on the development of apical periodontitis. International Endodontic Journal, Jan 28 [Epub ahead of print]. PMID: 26821330
  45. Garrido M., Dezerega A. Bordagary M. et al. (2015) C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. Journal of Endodontics, 41:464-469. PMID: 25748492
  46. Vidal F., Fontes T., Marques T., Goncalves L. (2015) Association between apical periodontitis lesions and plasmatic levels of C-reactive protein, interleukin 6 and fibrinogen in hypertensive patients. International Endodontic Journal, Oct 24 [Epub ahead of print]. PMID: 26499471
  47. Zhang J., Huang X., Lu B. et al. (2015) Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs? Clinical Oral Investigations. Nov 10 [Epub ahead of print]. PMID: 26556576
  48. Cintra L., Samuel R., Azuma M. et al. (2016) Multiple apical periodontitis influences serum levels of cytokines and nitric oxide. Journal of Endodontics, 42:747-751. PMID: 27059651
  49. Ma N., Qu L., Xu L. et al. (2016) [Expression of IL-34 in chronic periapical lesions and its clinical significance]. Article in Chinese. Shanghai Kou Qiang Yi Xue, 25:53-57. PMID: 27063309
  50. Kakehashi S., Stanley H., Fitzgerald R. (1965) The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surgery, Oral Medicine, and Oral Pathology, 20:340-349. PMID: 14342926
  51. Siqueira Jr. J. (2002) Endodontic infections: concepts, paradigms, and perspectives. Oral Surgery, Oral Pathology, Oral Radiology, and Endodontics, 94:281-293. PMID: 12324780
  52. Fabricius L., Dahlen G., Holm S., Moller A. (1982) Influence of combinations of oral bacteria on periapical tissues of monkeys. Scandinavian Journal of Dental Research, 90:200-206. PMID: 7051261
  53. Moller A., Fabricius L., Dahlen G. et al. (2004) Apical periodontitis development and bacterial response to endodontic treatment. Experimental root canal infections in monkeys with selected bacterial strains. European Journal of Oral Sciences, 112:207-215. PMID: 15154917
  54. Nair P., Pajarola G., Schroeder H. (1996) Types and incidence of human periapical lesions obtained with extracted teeth. Oral Surgery. Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 81:93-102. PMID: 8850492

Chapter 7: Infected Tonsils

  1. Scadding G. (1990) Immunology of the tonsil: a review. Journal of the Royal Society of Medicine, 83:104-107. PMID: 2181132
  2. Issels J. (1999) Cancer, A Second Opinion, Garden City Park, NY: Avery Publishing Group
  3. Nair P. (2004) Pathogenesis of apical periodontitis and the causes of endodontic failures. Critical Reviews in Oral Biology and Medicine, 15:348-381. PMID: 15574679
  4. Hoddeson E., Gourin C. (2009) Adult tonsillectomy: current indications and outcomes. Otolaryngology—Head and Neck Surgery, 140:19-22. PMID: 19130955

Chapter 8: Infected Dental Implants

  1. Murray C., Thomson W., Leichter J. (2016) Dental implant use in New Zealand: a 10-year update. The New Zealand Dental Journal, 112:49-54. PMID: 27506001
  2. Adell R., Lekholm U., Rockler B., Branemark P. (1981) A 15-year study of osseointegrated implants in the treatment of the edentulous jaw. International Journal of Oral Surgery, 10:387-416. PMID: 6809663
  3. Bosshardt D., Chappuis V., Buser D. (2017) Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions. Periodontology 2000, 73:22-40. PMID: 28000277
  4. Valente N., Andreana S. (2016) Peri-implant disease: what we know and what we need to know. Journal of Periodontal & Implant Science, 46:136-151. ID: 27382503
  5. de Waal Y., Eijsbouts H., Winkel E., van Winkelhoff A. (2016) Microbial characteristics of peri-implantitis: a case-control study. Journal of Periodontology, Sep 26 [Epub ahead of print]. PMID: 27666672
  6. Perez-Chaparro P., Duarte P., Shibli J. et al. (2016) The current weight of evidence of the microbiologic profile associated with peri-implantitis: systematic review. Journal of Periodontology. 87:1295-1304. PMID: 27420109
  7. Ogata Y., Nakayama Y., Tatsumi J. et al. (2016) Prevalence and risk factors for peri-implant diseases in Japanese adult dental patients. Journal of Oral Science, Oct 7 [Epub ahead of print]. PMID: 27725369
  8. Lachmann S., Stehberger A., Axmann Q., Weber H. (2013) the peri-implant health in patients attending an annual recall program. A clinical and microbiological study in 74 patients from the Tubingen Implant Registry. Clinical Oral Implant Research, 24:1300-1309. PMID: 22905716
  9. Montececchi M., Angelini F., Checchi V. et al. (2016) Microbiological distribution of six periodontal pathogens between untreated Italian and Dutch periodontal patients. Oral Health & Preventive Dentistry, 14:329-337 PMID: 26870849
  10. Austin S., Bailey D., Chandu A. et al (2015) Analysis of commonly reported medical conditions amongst patients receiving dental implant therapy in private practice. Australian Dental Journal, 60:343-352. PMID: 25330368
  11. Lindhe J., Meyle J. (2008) Peri-implant disease: Consensus Report of the Sixth European Workshop on Periodontology. Journal to Clinical Periodontology, 35:282-285. PMID: 18724855
  12. Zitzmann N., Berglundh T. (2008) Definition and prevalence and prevalence of peri-implant diseases. Journal of Clinical Perioodontol
  13. Gurgel B., Montenegro S., Dantas P. et al. (2016) Frequency of perio-implant diseases and associated factors. Clinical Oral Implants Research, Aug 24 [Epub ahead of print]. PMID: 27557997
  14. Esposito M., Hirsch J., Lekholm U., Thomsen P. (2008) Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology. European Journal of Oral Sciences, 106:527-551. PMID: 9527353
  15. Esposito M., Hirsch J., Lekholm U., Thomsen P. (2008a) Biological factors contributing to failures of osseointegrated oral implants. (II), Etiopatho-genesis. European Journal of Oral Sciences, 106:721-764. PMID: 9672097
  16. Alvarez-Camino J., Valmaseda-Castellon E., Gay-Escoda C. (2013) Immediate implants placed in fresh sockets associated to periapical infectious processes. A systemic review. Medicina Oral, Patologia Oral y Cirugia Bucal, 18:e780-e785. PMID: 23722139
  17. Casap N., Zeltser C., Wexler A. et al. (2007) Immediate placement of dental implants into debrided infected dentoalveolar sockets. Journal of Oral and Maxillofacial Surgery, 65:384-392. PMID: 17307582
  18. Lazzara R. (1989) Immediate implant placement into extraction sites: surgical and restorative advantages. The International Journal of Periodontics & Restorative Dentistry, 9:332-343. PMID: 2640210
  19. Chen S., Wilson Jr. T., Hammerle C. (2004) Immediate or early placement of implants following tooth extraction: review of biologic basis, Clinical procedures, and outcomes. The International Journal of Oral & Maxillofacial Implants, 19 Suppl: 12-25. PMID: 15635942
  20. Romanos G., Froum S., Hery C. et al. (2010) Survival rate of immediately vs delayed loaded implants: analysis of the current literature. The Journal of Oral Implantology, 36:315-324. PMID: 20735268
  21. Konstantinidis I., Kotsakis G., Gerdes S., Walter M. (2015) Cross-sectional study on the prevalence and risk indicators of peri-implant diseases. European Journal of Oral Implantology, 8:75-88. PMID: 25738181
  22. Marcantonio C., Nicoli L., Marcantonio E., Zandim-Barcelos D. (2015) Prevalence and possible risk factors of peri-implantits: a concept review. The Journal of Contemporary Dental Practice, 16:750-757. PMID: 26522602
  23. Derks J., Schaller D., Hakansson J. et al. (2016a) Peri-implantitis—onset and pattern of progression. Journal of Clinical Periodontology, 43:363-388. PMID: 26900869
  24. Rokn A., Aslroosta H., Akbari S. et al. (2016) Prevalence of peri-implantitis in patients not participating in well-designed supportive periodontal treatment: a cross-sectional study. Clinical Oral Implants Research, Feb 26 [Epub ahead of print]. PMID: 26919480
  25. Misch C., Perel M., Wang H. et al. (2008) Implant success, survival, and failure: The International Congress of Oral Implantologists (ICOI) Pisa Consensus Conference. Implant Dentistry, 17:5-15. PMID: 18332753
  26. Benic G., Bernasconi M., Jung R., Hammerle C. (2016) Clinical and radiographic intra-subject comparison of implants placed with or without bone regeneration: 15-year results. Journal of Clinical periodontology, Dec 15 [Epub ahead of print]. PMID: 27978603
  27. Knofler W., Barth T., Graul R., Krampe D. (2016) Retrospective analysis of 10,000 implants from insertion up to 20 years—analysis of implantations using augmentative procedures. International Journal of Implant Dentistry, 2:25. PMID: 27915417
  28. Marconcin S., Barone A., Gelpi F. et al. (2013) Immediate implant placement infected areas: a case series. Journal of Periodontology, 84:196-202. PMID: 22509756
  29. Barone A., Marconcini S., Giammarinaro E. et al. (2016) Clinical outcomes of implants placed in extraction sockets and immediately restored: a 7-year single-cohort prospective study. Clinical Implant Dentistry and Related Research, 18:1103-1112. PMID: 26888632
  30. Chrcanovic B., Kisch J., Albrektsson T., Wennerberg A. (2016) Survival of dental implants placed in sites of previously failed implants. Clinical Oral Implants Research, Oct 14 [Epub ahead of print]. PMID: 27743398
  31. Crespi R., Cappare P., Crespi G. et al. (2016) Immediate implant placement in sockets with asymptomatic apical periodontitis. Clinical Implant Dentistry and Related Research, Apr 28 [Epub ahead of print]. PMID: 27126371
  32. Crespi R., Cappare P., Crespi G. et al. (2016a) Dental implants placed in periodontally infected sites in humans. Clinical Implant Dentistry and Related Research, May 16 [Epub ahead of print]. PMID: 27183325
  33. Han C., Mangano F., Mortellaro C., Park K. (2016) Immediate loading of tapered implants placed in postextraction sockets and healed sites. The Journal of Craniofacial Surgery, 27:1220-1227. PMID: 27391493
  34. Henningsen A., Smeets R., Wahidi A. et al. (2016) The feasibility of immediately loading dental implants in edentulous jaws. Journal of periodontal & Implant Science, 46:234-243. PMID: 27588213
  35. Srinivasan M., Meyer S., Mombelli A., Muller F. (2016) Dental implants in the elderly population: a systematic review and meta-analysis, Clinical Oral Implants Research, Jun 7 [Epub ahead of print]. PMID: 27273468
  36. Zhou W., Want F., Monje A. et al. (2016) Feasibility of dental implant implant replacement in failed sites: a systematic review. The International Journal of Oral & Maxillofacial Implants, 31:535-545. PMID: 27183062
  37. Pieralli S., Kohal R., Jung R. et al. (2017) Clinical outcomes of zirconia dental implants. Journal of Dental Research, 96:38-46. PMID: 27625355
  38. Derks J., Schaller D., Hakansson J. et al. (2016) Effectiveness of implant therapy analyzed in a Swedish population: prevalence of peri-implantitis. Journal of Dental Research, 95:43-49. PMID: 26701919
  39. Perka C., Haas N. (2011) Periprosthetic infection. [Article in German]. Der Chirurg, 82:218-226. PMID: 21340589
  40. Bakathir A., Moos K., Ayoub A., Bagg J. (2009) Factors to the spread of odontogenic infections: a prospective pilot study. Sultan Qaboos University Medical Journal, 9:296-304. PMID: 21509313
  41. Hauser-Gerspach I., Vadaszan J., Deronjic I. et al. (2012) Influence of gaseous ozone in peri-implantitis: Bactericidal efficacy and cellular response. An in vitro study using titanium and zirconia. Clinical Oral Investigations, 16:1049-1059. PMID: 21842144
  42. Esposito M., Grusovin M., Worthington H. (2013) Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications. The Cochrane Database of Systematic Reviews, 7:CD004152. PMID: 23904048
  43. Romanos G. (2015) Current concept in the use of lasers in periodontal and implant dentistry. Journal of Indian Society of Periodontology, 19:490-494. PMID: 26644712
  44. Alshehri F. (2016) The role of lasers in the treatment of peri-implant disease: a review. The Saudi Dental Journal, 28:103-108. PMID: 27656076
  45. Pommer B., Haas R., Mailath-Pokorny G. et al. (2016) Periimplantitis treatment: long-term comparison of laser decontamination and implantioplasty surgery. Implant Dentistry, 25:646-649. PMID: 27504533
  46. Salvi G., Cosgarea R., Sculean A. (2017) Prevalence and mechanisms of peri-implant diseases. Journal of Dental Research, 96:31-37. PMID: 27680028

Chapter 9: Cavitational Osteonecrosis

  1. Levy T., Huggins H. (1996) Routine dental extractions routinely produce capitations. Journal of Advancement in Medicine, 9:235-249.
  2. Yoneda T., Hagino H., Sugimoto T. et al. (2016) Antiresorptive agent-related osteonecrosis of the jaw: position paper 2017 of the Japanese Allied Committee on osteonecrosis of the jaw. Journal of Bone and Mineral Metabolism, Dec 29 [Epub ahead of print]. PMID: 28035494
  3. Vinitzky-Brener I., Ibanez-Mancera N., Aguilar-Rojas A., Alvarez-Jardon A. (2017) Knowledge of bisphosphonate-related osteonecrosis of the jaws among Mexican dentists. Medicina Oral, Patologia Oral y Cirugia Bucal, 22:e84-e87. PMID: 27918741
  4. Black G. (1915) A Work on Special Dental Pathology, Chicago: Medico-Dental Publishing Co.
  5. Bouquot J., Roberts A., Person P., Christian J. (1992) Neuralgia-inducing Cavitational osteonecrosis (NICO). Osteomyelitis in 224 jawbone samples from patients with facial neuralgia. Oral Medicine, Oral Surgery, and Oral Pathology, 73:307-319. PMID: 1545963
  6. Bouquot J., LaMarche M. (1999) lschemic osteonecrosis under fixed partial denture pontics: radiographic and microscopic features in 38 patients with chronic pain. The Journal of Prosthetic Dentistry, 9922427
  7. Gruppo R., Glueck C., McMahon R. et al. (1996) The pathophysiology of alveolar osteonecrosis of the jaw: anticardiolipin antibodies, thrombophilia, and hypofibrinolysis. The Journal of Laboratory and Clinical Medicine, 127:481-488. PMID: 8621985
  8. Lechner J., von Baehr V. (2013) RANTES and fibroblast growth factor 2 in jawbone capitations: triggers for systemic disease? International Journal of General Medicine, 6:277-290. PMID: 23637551
  9. Tozum T., Demiralp B. (2003) Platelet-rich plasma: a promising innovation in dentistry. Journal of the Canadian Dental Association, 69:664. PMID: 14611717
  10. Lacci K., Dardik A. (2010) Platelet-rich plasma: support for its use in wound healing. Yale Journal of Biology and Medicine, 83:1-9. PMID: 20351977
  11. Dhurat R., Sukesh M. (2014) Principles and methods of preparation of platelet-rich: a review and author’s perspective. Journal of Cutaneous and Aesthetic Surgery, 7:189-197. PMID: 25722595
  12. Jain N., Gulati M. (2016) Platelet-rich plasma: a healing virtuoso. Blood Research, 51:3-5. PMID: 27104183
  13. Brown D. (2009) Complete edentulism prior to the age of 65 years is associated with all-cause mortality. Journal of Public Health Dentistry, 69:260-266. PMID: 19453862
  14. Ando A., Tanno K., Ohsawa M. et al. (2014) Associations of number of teeth with risks for all-cause mortality and cause-specific mortality in middle-aged and elderly men in the northern part of Japan: the Iwate-KENCO study. Community Dentistry and Oral Epidemiology, 42:358-365. PMID: 24476489
  15. Hirotomi T., Yoshihara A., Ogawa H., Miyazaki H. (2015) Number of teeth and 5-year mortality in an elderly population. Community Dentistry and Oral Epidemiology, 43:226-231. PMID: 25600364
  16. Hu H., Lee Y., Lin S. et al. (2015) Association between tooth loss, body mass index, and all-cause mortality among elderly patients in Taiwan. Medicine, 94:e1543. PMID: 26426618
  17. Joshy G., Arora M., Korda R. et al. (2016) ls poor oral health a risk marker for incident cardiovascular disease hospitalization and all-cause mortality? Findings from 172,630 participations from the prospective 45 and Up Study. BMJ Open, 6:e012386. PMID: 27577588
  18. Vedin O., Hagstrom E., Budaj A. et al. (2016) Tooth loss in independently associated with poor outcomes in stable coronary heart disease. European Journal of Preventive Cardiology, 23:839-846. PMID: 26672609
  19. Kebede T., Hotfreter B., Kocher T. et al. (2017) Association of periodontal destruction and diabetes with mortality. Journal of Dental Research, 96:56-63. PMID: 27680027
  20. Polzer I., Schwahn C., Volzke H. et al. (2012) The association of tooth loss with all-cause and circulatory mortality. Is there a benefit of replaced teeth? A systematic review and meta-analysis. Clinical Oral Investigations, 16:33-351. PMID: 22086361
  21. Holmlund A., Holm G., Lind L. (2010) Number of teeth as a predictor of cardiovascular mortality in a cohort of 7,674 subjects followed for 12 years. Journal of Periodontology, 81:870-876. PMID: 20350152
  22. Watt R., Tsakos G., de Oliveira C., Hamer M. (2012) Tooth loss and cardiovascular disease mortality risk—results from the Scottish Health Survey. PLoS One, 7:e30797. PMID: 22363491
  23. Schwahn C., Polzer I., Haring R. et al. (2013) Missing, unreplaced teeth and risk of all-cause and cardiovascular mortality. International Journal of Cardiology, 167:1430-1437. PMID: 22560949
  24. Liljestrand J., Havulinna A., Paju S. et al. (2015) Missing teeth predict incident cardiovascular events, diabetes, and death. Journal of Dental Research, 94:1055-1062. PMID: 25991651

Chapter 10: Infected Sinuses

  1. Dlugaszewska J., Leszczynska M., Lenkowski M. et al. (2016) The pathophysiological role of bacterial biofilms in chronic sinusitis. European Archives of Oto-Rhino-Laryngology, 273:1989-1994. PMID: 26024693
  2. Kennedy J., Borish L. (2013) Chronic sinusitis pathophysiology: the role of allergy. American Journal of Rhinology & Allergy, 27:367-371. PMID: 23601202
  3. Lam K., Schleimer R., Kern R. (2015) The etiology and pathogenesis of chronic rhinosinusitis: a review of current hypotheses. Current Allergy and Asthma Reports, 15:41. PMID: 26143392
  4. Min J, Tan B (2015) Risk factors for chronic rhinosinusitis. Current Opinion in Allergy and Clinical Immunology, 15:1-13. PMID: 25479315
  5. Taschieri S., Torretta S., Corbella S. et al. (2015) Pathophysiology of sinusitis of odontogenic origin. Journal of Investigative and Clinical Dentistry, Dec 14 [Epub ahead of print]. PMID: 266622929
  6. McCarty J., David R., Lensing S. et al. (2016) Root cause analysis: an examination of odontogenic origins of acute maxillary sinusitis in both immunocompetent & immunocompromised patients. Journal of Computer Assisted Tomography, Oct 29 [Epub ahead of print]. PMID: 27798445
  7. Kulacz R., Fishman G., Levine H. (2004) An unsuccessful sinus surgery caused by dental involvement within the floor of the maxillary sinus. Operative Techniques of Otolaryngology—Head and Neck Surgery, 15:2-3.
  8. Akhlaghi F., Esmaeelinejad M., Safai P. (2015) Etiologies and treatments of odontogenic maxillary sinusitis: a systematic review. Iranian Red Crescent Medical Journal, 17:e25536. PMID: 26756016
  9. Simuntis R., Kubilius R., Ryskiene S., Vaitkus S. (2015) Odontogenic maxillary sinusitis obscured by midfacial trauma. Stomatogija. 17:29-32. PMID: 26183855
  10. Longhini A., Ferguson B. (2011) Clinical aspects of odontogenic maxillary sinusitis: a case series. International Forum of Allergy & Rhinology, 1:409-415. PMID: 22287475
  11. Hoskison E., Daniel M., Rowson J., Jones N. (2012) Evidence of an increase in the incidence of odontogenic sinusitis over the last decade in the UK. The Journal of Laryngology and Otology, 126:43-46. PMID: 21933468
  12. Patel N., Ferguson B. (2012) Odontogenic sinusitis: an ancient but under-appreciated cause of maxillary sinusitis. Current Opinions in Otolaryngology & Head and Neck Surgery, 20:24-28. PMID: 22157162
  13. Shanbhag S., Karnik P., Sirke P., Shanbhag V. (2013) Association between periapical lesions and maxillary sinus mucosal thickening: a retrospective cone-beam computed tomographic study. Journal of Endodontics, 39:853-857. PMID: 23791251
  14. Fadda G., Berrone M., Crosetti E., Succo G. (2016) Monolateral sinonasal complications of dental disease or treatment: when does endoscopic endonasal surgery require an intraoral approach? Acta Otorhinolaryngologica Italica, 36:300-309. PMID: 27734983
  15. Bomeli S., Branstetter B., Ferguson B. (2009) Frequency of a dental source for acute maxillary sinusitis. Laryngoscope, 119:580-584. PMID: 19160401
  16. Matsumoto Y., Ikeda T., Yokoi H., Kohno N. (2015) Association between odontogenic infections and unilateral sinus opacification. Auris, Nasus, Larynx, 42:288-293. PMID: 25638394
  17. Pokorny A., Tataryn R. (2013) Clinical and radiologic findings in a case series of maxillary sinusitis of dental origin. International Forum of Allergy & Rhinology, 3:973-979. PMID: 24039196
  18. Rosenthal P., Lundy K., Massoglia D. et al. (2016) Incidental paranasal sinusitis on routine brain magnetic resonance scans: association with atherosclerosis. Forum of Allergy & Rhinology, 6:1253-1263. PMID: 27509266
  19. Onisor-Gligor F., Lung T., Pintea B. et al. (2012) Maxillary odontogenic sinusitis, complicated with cerebral abscess—case report. Chirurgia, 107:256-259. PMID: 22712359
  20. Coughlan C., Cerussi A., Kim J. et al. Near-infrared optical imaging for diagnosis of maxillary sinusitis. Otolaryngology—Head and Neck Surgery, 155:538-541. PMID: 27329417
  21. Wang K., Nichols B., Poetker D., Loehrl T. (2015) Odontogenic sinusitis: a case series studying diagnosis and management. International Forum of Allergy & Rhinology, 5:597-601. PMID: 25732329
  22. Troeltzsch M., Pache C., Troeltzsch M. et al. (2015) Etiology and clinical characteristics of symptomatic unilateral maxillary sinusitis: a review of 174 cases. Journal of Cranio-Maxillo-Facial Surgery, 43:1522-1599. PMID: 26319958
  23. Jeong K., Kim S., Oh J., You J. (2016) Implants displaced into the maxillary sinus: a systematic review. Implant Dentistry, 25:547-551. PMID: 26974033
  24. Kim S., Park J., Kim H. et al. (2016) Clinical features and treatment outcomes of dental implant-related paranasal sinusitis: a 2-year prospective observational study. Clinical Oral Implants Research, 27:e100-e104. PMID: 25675967

PART FOUR: Diagnosis and Treatment

Chapter 12: General Treatment Protocol for Chronic Degenerative Disease

  1. Huggins H., Levy T. (1999) Uninformed Consent. The hidden dangers in dental care. Charlottesville, VA: Hampton Roads Publishing
  2. Levy T. (2001) Optimal Nutrition for Optimal Health. New York, NY: Keats Publishing
  3. Levy T. (2006) Stop America’s #1 Killer. Proof that the origin of all coronary artery disease is a clearly reversible arterial scurvy. Henderson, NV: MedFox Publishing
  4. Levy T. (2008) GSH, Master Defender Against Disease, Toxins, and Aging. Henderson, NV: LivOn Books
  5. Levy T. (2011) Primal Panacea. Henderson, NV: MedFox Publishing
  6. Levy T. (2013) Death by Calcium. Proof of the toxic effects of diary and calcium supplements. Henderson, NV: MedFox Publishing
  7. Kulacz R., Levy T. (2014) The Toxic Tooth. How a root canal could be making you sick. Henderson, NV: MedFox Publishing
  8. Loria C., Klag M., Caulfield L., Whelton P. (2000) Vitamin C status and mortality in US adults. The American Journal of Clinical Nutrition, 72:139-145. PMID: 10871572
  9. Khaw K., Bingham S., Welch A. et al. (2001) Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet, 357:657-663. PMID: 11247548
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  12. Semba R., Houston D., Bandinelli S. et al. (2010) Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. European Journal of Clinical Nutrition, 64:203-209. PMID: 19953106
  13. Reffelmann T., lttermann T., Dorr M. et al. (2011) Low serum magnesium concentrations predict cardiovascular and all-cause mortality. Atherosclerosis, 219:280-284. PMID: 21703623

Chapter 13: Ozone and Oral Focal infections

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  2. Bocci V. (2011) Ozone. A New Medical Drug. Second Edition. New York, NY:Springer.
  3. Bocci V., Luzzi E., Corradeschi F. et al. (1993) Studies on the biological effects of ozone: 4. Cytokine production and glutathione levels in human erythrocytes. Journal of Biological Regulators and Homeostatic Agents, 7:133-138. PMID: 8023701
  4. Larini A., Bianchi L., Bocci V. (2003) The ozone tolerance: 1) enhancement of antioxidant enzymes is ozone does-dependent in Jurkat cells. Free Radical Research, 37:1163-1168. PMID: 14703728
  5. Verdin E. (2016) NAD+ in aging, metabolism, and neurodegeneration. Science, 350:1208-1213. PMID: 26785480
  6. Yamato M., Kawano K., Yamanaka Y. et al. (2016) TEMPOL increases NAD(+) and improves redox imbalance in obese mice. Redox Biology, 8:316-322. PMID: 26942863
  7. Rilling S., Viebahn R. (1987) The Use of Ozone in Medicine, Second Revised Edition, First English Edition. Heidelberg:Haug.
  8. Bocci V., Larini A., Micheli V. (2005) Restoration of normozia by ozone therapy may control neoplastic growth: a review and a working hypothesis. Journal of Alternative and Complementary Medicine, 11:257-265. PMID: 15865491
  9. Kucuksezer U., Zekiroglu E., Kasapoglu P. et al. (2014) A stimulatory role of ozone exposure on human natural killer cells. Immunological Investigations, 43:1-12. PMID: 24063543
  10. Valacchi G., Bocci V. (2000) Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells. Mediators of Inflammation, 9:271-276. PMID: 11213910
  11. Bocci V. (1999) Biological and clinical effects of ozone. Has ozone therapy a future in medicine? British Journal of Biomedical Science, 56:270-279. PMID: 10795372
  12. Nogales C., Ferrari P., Kantorovich E., Lage-Marques J. (2008) Ozone therapy in medicine and dentistry. The Journal of Contemporary Dental Practice, 9:75-84. PMID: 18473030
  13. Saini R. (2011) Ozone therapy in dentistry: a strategic review. Journal of Natural Science, Biology and Medicine, 2:151-153. PMID: 22346227
  14. Bocci V., Zanardi I., Borrelli E., Travagli V. (2012) Reliable and effective oxygen-ozone therapy at a crossroads with ozonated saline infusion and ozone rectal insufflation. The Journal of Pharmacy and Pharmacology, 64:482-489. PMID: 22420654

PART FIVE: More Help

Appendix C: A Guide to the Optimal Administration of Vitamin C

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  7. Klenner F (1971) Observations of the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology, Journal of Applied Nutrition 23:61-88.
  8. Cathcart R (1981) Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy, Medical Hypotheses 7:1359-1376. PMID: 73211921
  9. Cathcart R (1985) Vitamin C: the nontoxic, nonrate-limited, antioxidant free radical scavenger, Medical Hypotheses 18:61-77. PMID: 4069036
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  14. Pokorski M, Ramadan A, Marczak M (2004) Ascorbyl palmitate augments hypoxic respiratory response in the cat, Journal of Biomedical Science 11:465-471. PMID: 15153781
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  17. Gosenca M, Bester-Rogac M, Gasperlin M (2013) Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate, European Journal of Pharmaceutical Sciences May 3. [Epub ahead of print]. PMID: 23643736
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  20. Levy T (2011) Primal Panacea. Henderson, NV: MedFox Publishing
  21. Padayatty S, Sun A, Chen Q, et al. (2010) Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects, PLoS One 5:e11414. PMID: 20628650
  22. Rawat A, Vaidya B, Khatri K, et al. (2007) Targeted intracellular delivery of therapeutics: an overview, Die Pharmazie 62:643-658. PMID: 17944316
  23. Yamada Y, Harashima H (2008) Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases, Advanced Drug Delivery Reviews 60:1439-1462. PMID: 18655816
  24. Goldenberg H, Schweinzer E (1994) Transport of vitamin C in animal and human cells, Journal of Bioenergetics and Biomembranes 26:359-367. PMID: 744110
  25. Liang W, Johnson D, Jarvis S (2001) Vitamin C transport systems of mammalian cells, Molecular Membrane Biology 18:87-95. PMID: 11396616
  26. Welch R, Wang Y, Crossman A Jr. (1995) Accumulaiton of vitamin C (assorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms, The Journal of Biological Chemistry 270:12584-12592. PMID: 7759506
  27. Ling S, Magosso E, Khan N, et al. (2006) Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes, Drug Development and Industrial Pharmacy 32:335-35. PMID: 16556538
  28. Lubin B, Shohet S, Nathan D (1972) Changes in fatty acid metabolism after erythrocyte peroxidation: stimulation of a membrane repair process, The Journal of Clinical Investigation 51:338-344. PMID: 5009118
  29. Mastellone I, Polichetti E, Gres S, et al. (2000) Dietary soybean phosphatidylcholines lower lipidemia: mechanisms at the levels of intestine, endothelial cell, and hepato-biliary axis, The Journal of Nutritional Biochemistry 11:461-466. PMID: 11091102
  30. Buang Y, Wang Y, Cha J, et al. (2005) Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid, Nutrition 21:867-873. PMID: 15975496
  31. Demirbilek S, Karaman A, Baykarabulut A, et al. (2006) Polyenylphophatidylcholine pretreatment ameliorates ischemic acute renal injury in rats, International Journal of Urology 13:747-753. PMID: 16834655
  32. Levy T (2002) Curing the Incurable. Vitamin C, Infectious Diseases, and Toxins. Henderson, NV: MedFox Publishing
  33. Klenner F (1971) Observations of the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology, Journal of Applied Nutrition 23:61-88.