The Management of Xerostomia
George M. Taybos, DDS, MSEd
Dorland’s Medical Dictionary defines xerostomia as a “dryness of the mouth from lack of the normal secretions.” Dry mouth as a clinical sign was first described in 1868 by Bartley.1 Bartley’s definition of this condition was based on objective clinical evidence of dry oral mucosa, obliteration of the salivary duct orifices, and/or glossitis. In 1889, Hutchinson gave the term xerostomia to this condition.2 Xerostomia is a subjective complaint. Not all patients who complain of a dry mouth have salivary gland dysfunction and decreased salivary secretions.3-6
The average person will produce between 0.5 to 1.5 liters of saliva every 24 hours.3 The three major salivary glands— parotid, submandibular, and sublingual— will contribute 90% of the entire saliva volume. The parotid saliva exits the gland through Stensen’s ducts located on the buccal mucosa in the proximity of the maxillary first and second molars. The submandibular and sublingual saliva exits their glands through Wharton’s ducts located in the anterior floor of the mouth. The minor salivary glands contribute the remaining 10% of the whole saliva volume.4 Whole saliva is not only a collection of secretions from the major and minor salivary glands, but also desquamated oral mucosal cells, food debris, oral microorganisms, gingival crevicular fluid, and blood cells.7 Saliva is 99% water and 1% proteins and salts. During the resting phase of saliva secretion, the submandibular glands are the major contributors to salivary secretion: 65% from the submandibular gland, 23% from the parotid gland, 8% from the minor salivary glands, and 4% from the sublingual gland. During stimulated saliva secretion, the parotid glands contribute 50% to the total salivary secretion.4-8 The parotid gland secretion is serous; the submandibular and sublingual glands have a mixed secretion consisting of both serous and mucous, while the minor salivary glands secretions are mucous.4,9
Saliva is a body fluid that has been used for thousands of years for both diagnosis of health problems as well as the monitoring/assessment of one’s overall health status. Ancient Chinese doctors treated blood and saliva as related bodily fluids; and they believed that changes in a person’s saliva would indicate the person’s health status. At that time, the thickness and smell of the patient’s saliva were important symptoms that could be related to specific disease states such as heartburn or spleen problems.10 The critical role that saliva plays in everyday activities as well as its medicinal properties are often taken for granted. However, when there is an interruption of normal salivary activity, the individual will experience deleterious effects to their oral and systemic health as well as their social interactions. Normal salivary secretions maintain oral homeostasis through their water and protein/salt constituents. To understand the importance of saliva in maintaining oral health, we must discuss the properties of saliva and their specific role in maintaining oral homeostasis.
Lubrication
The oldest function of saliva is to lubricate the tissues in the oral cavity and to coat the foods that are consumed.11 Three salivary components that are responsible for the lubrication of the hard and soft tissues of the oral cavity are mucins, proline-rich glycoproteins, and water.12 Mucins are derived from the mucous-secreting cells in the submandibular, sublingual, and minor salivary glands. The minor salivary glands contribute less than 10% of the resting saliva; however, these glands are responsible for 70% of the total mucin in the salivary secretion.13 The mucin covers the epithelial surfaces of the oral cavity. This results in both a lubricating surface as well as a selective permeability barrier that protects against desiccation and exogenous insults.9,14 Mucin coats the food and this allows the food to move through the esophagus into the stomach and through the intestines with minimal mechanical friction.15
Mucous Membrane Integrity
Mucosal integrity is maintained by the salivary components mucins, electrolytes, and water.12 The properties of mucin include low solubility, high viscosity, elasticity, and adhesiveness. These properties allow the mucins to adhere to the oral mucosal surfaces, where they form a barrier against desiccation and irritants in foods and liquids.9 Mucins maintain the oral mucosa in a hydrated condition and also protect the cells from changes in the osmotic pressure.16
Repair of Soft Tissues
Epidermal growth factor (EGF) is present in the secretions of the parotid and submandibular glands.17 In animal studies, EGF has been shown to increase the rate of wound contraction and to increase the rate of cutaneous healing.18,19
Lavage and Debridement
Lavage and debridement is accomplished by the flow of the water component of saliva in conjunction with the physical movement of the lips and tongue during swallowing and other movements. Lavage and debridement continuously remove bacteria from the teeth and mucosal surfaces as well as remove desquamated mucosal epithelial cells.
Oral Bacteria: Adherence and Aggregation
For the oral bacteria to survive and multiply, they must be able to adhere to oral tissues. The saliva performs numerous activities that will disrupt the oral bacteria’s ability to adhere to the intraoral hard and soft tissues. One activity of saliva, lavage and debridement, has already been discussed. A second activity of saliva is to cause the bacteria to aggregate to the extent that they cannot adhere to the oral hard and soft tissues and they are removed from the oral cavity by either swallowing or spitting.20 Amylase causes the aggregation of numerous oral microorganisms in the Streptococcus genus.21 A third action of saliva is the activity of secretory immunoglobulin A (IgA) in decreasing the bacteria’s ability to adhere to the oral tissues.22 Secretory IgA is by far the most abundant secretory immunoglobulin in saliva, and is part of the adaptive immunity present in saliva.23,24 Secretory immunoglobulin production occurs when one or more antigens is presented to B cells in the lymphoid tissue located adjacent to the salivary gland ducts.25-27 The total group of immunoglobulins present in saliva binds the majority of intraoral microbes.28
Antimicrobial Activity
An indirect antimicrobial activity of saliva is the salivary activity of debridement/ lavage and aggregation. Saliva also has a direct antibacterial activity. There is a complex of salivary proteins that act on oral bacteria by preventing them from producing cellular byproducts (acid), replicating, and/or directly killing the organism. Lysozyme is a cationic enzyme that binds to the cell surface of Streptococcus mutans and interacts with salivary anions to cause the cells to lyse.29,30 There is a cationic, histidine-rich peptide secreted by the parotid gland that has a growth-inhibitory as well as a bactericidal action on oral bacteria.31 Lactoferrin is the salivary gland equivalent of serum transferrin, the iron-binding protein. Lactoferrin possesses bacteriostatic and bactericidal properties by removing ferric iron, thus competing with organisms that require iron for metabolism.32 Salivary peroxidase enhances the activity of hydrogen peroxide produced by oral bacteria to catalyze salivary thiocyanate. This results in the production of oxidizing agents that act on the bacteria enzyme systems that affect the cells’ ability produce acid and to grow.33
The parotid gland secretes histidine-rich proteins known as histatins, which have strong antifungal activity.34,35 Individuals with decreased stimulated salivary function are more prone to develop Candida albicans infections.36-38 Saliva also has antiviral activity. Secretory IgA can directly neutralize viruses and mucins can inhibit human immunodeficiency virus (HIV) and herpes virus hominis (HVH-1) infections.39-41
Oral Acid-Base Maintenance
Saliva plays a major role in maintaining the neutral pH in the mouth, in the bacterial plaque, and in the esophagus during swallowing.42 The pH of whole saliva ranges from 6.7 to 7.4. The pH of fasting parotid saliva will be approximately 7.1, while the pH of fasting mandibular saliva will be approximately 6.77. The intraoral pH values for plaque will vary according to the location in the mouth. The plaque on the maxillary teeth has a lower pH than plaque on mandibular teeth; lingual surface plaque has a lower pH than plaque on labial/buccal surfaces. In the mandible, the posterior areas have a lower pH than the anterior areas. In the maxilla, the posterior areas have a higher pH than the anterior areas.43 The main buffering component in saliva is the bicarbonate system, but it is only effective at high flow rates. Urea is present in saliva. The amount is dependent on the amount of protein in the diet. Oral bacteria produce urases that convert the salivary urea to ammonia and carbon dioxide. The ammonia neutralizes acids with the end result being that the plaque pH is elevated to levels greater than those of unstimulated saliva.43-45
Protection of Teeth
A tooth erupts into the oral cavity with its developmental cuticle. This cuticle is quickly worn away by normal tooth function. Tooth material can be lost by abrasion, attrition, erosion, and/or dental caries. Abrasion occurs as a result of the action of foreign materials against the teeth, while attrition results from repeated contact between opposing teeth. In both instances, saliva will form an acquired enamel pellicle which acts as a lubricant. Erosion occurs when the oral pH is less than the critical pH below which this fluid is unsaturated when compared to tooth mineral. This critical pH is 5.5 to 6.5 and it is inversely related to the salivary concentrations of calcium and phosphorus.44,46,48 Saliva protects the tooth material by producing the acquired enamel pellicle; diluting the acid; lavage and debridement; providing bicarbonate-phosphate buffer systems; and supersaturation with calcium and phosphate.44 Dental caries begins when acidogenic microorganisms in the dental plaque come in contact with sucrose or fermentable carbohydrates. Within 3 to 5 minutes of exposure to these food sources, the pH of dental plaque decreases. The pH in the dental plaque will decrease to as low as 4. At this pH level, minerals can be dissolved from the tooth surface, and this dissolution will continue until the plaque pH rises above the critical fluid pH of 5.1.47,48 The plaque pH may not return to a normal level for 3.5 hours or longer.43 In addition to its acid-buffering effect, saliva affects dental caries activity by remineralizing the enamel surface.46 Normal salivary secretion is responsible for sugar clearance, acid clearance, urea, and remineralization.44
Treating Xerostomia
It should be no surprise that an individual will experience intraoral problems when the saliva secretion is altered or decreased. The dental care provider must review and update the patient’s medical history. The medical history will reveal:5
Medication History: Xerostomia/dry mouth is a side effect of medications. Eighty percent of prescribed drugs cause xerostomia.49
Gender: Women are more susceptible to Sjögren’s syndrome, rheumatoid arthritis, scleroderma, hypothyroidism, depression, and eating disorders.5,36
Social History: Tobacco use, alcohol abuse, and recreational drugs all affect salivary function.
Medical History: Radiation therapy for head-and-neck cancer will adversely affect the salivary glands. The oral and pharyngeal effects of salivary hypofunction will include:36 dry mouth; dry lips; difficulty chewing; dental caries; mucositis; difficulty swallowing; altered taste; halitosis; gingivitis; candidiasis; traumatic lesions; poor denture retention; speech problems; and sleep problems.
A review of the medical history and the presence of any combination of the above listed oral problems should alert the dental care provider that this patient may have salivary gland dysfunction. The dental professional’s comprehensive care must include an assessment of the patient’s salivary gland function. Merely asking the patient if their mouth is dry does not constitute an assessment for xerostomia and salivary gland dysfunction. Fox et al50 has shown that the presence of mouth dryness at night or upon awakening does not correlate to decreased salivary gland activity. Navazesh4 has described “the gold standard” for the quantitative collection of both unstimulated and stimulated saliva. This technique, though exacting, may not be applicable to the salivary gland assessment in the general dentist’s office. She has shown that there is a strong association between “yes” responses to the following questions and salivary gland hypofunction:
- Does the amount of saliva in your mouth seem inadequate?
- Does your mouth feel dry when eating a meal?
- Do you have difficulty swallowing any food?
- Do you sip liquids to aid in swallowing dry food?
This would be a more suitable method for assessing salivary gland activity for most general dental care providers. But first the diagnosis of decreased salivary secretions, xerostomia, must be established. Once there is a diagnosis of xerostomia, can it be correlated to an identified medical disorder; the patient’s medications; and/or a history of radiation therapy to treat a head-and-neck malignancy? The second step is to identify the common xerostomia-associated oral problems, ie, dry mouth, altered taste, caries, candidiasis, and/or poorly retained removable prostheses. The management of xerostomia does not just focus on addressing the decreased amount of saliva in the oral cavity but also the other oral problems associated with the xerostomia. This patient must have an individual recall schedule based on the severity of their initial xerostomia-associated problems and their response to treatment/management. It may be necessary to evaluate these patients on a monthly basis until their xerostomia problems are under control.
Management of Dry Mouth
Chewing gum can increase the salivary flow rates to peak at 6 ml/minute in the very first minute of chewing. This flow rate decreases to plateau at 1 ml/minute and this rate can be maintained for more than 2 hours.59 Eating foods can cause the salivary flow rate to increase above 3 ml/minute, and if the oral cavity is exposed to 5% citric acid, the flow rate will exceed 7 ml/minute.60 There are two FDA-approved sialagogues, pilocarpine and cevimilene.36 Both medications are cholinergic agonists that act on the muscarinic receptors. Pilocarpine has an affinity for both of the exocrine muscarinic receptors, M1 and M3, as well as the muscarinic receptors located in cardiac tissue, M2 and M4.36 Cevimilene has an enhanced affinity for the exocrine muscarinic receptors, M1 and M3.36 Pilocarpine is approved for the treatment of salivary gland hypofunction in both Sjögren’s syndrome patients and head-and-neck radiation patients, while cevimilene is approved for salivary gland hypofunction in Sjögren’s syndrome patients.36 According to the medication’s prescribing information, the recommended dosing for pilocarpine for the head-and-neck radiation patient is 5 mg three times daily (8:00 am, 12:00 pm, and 4:00 pm). The patient must have uninterrupted therapy for 12 weeks to assess whether a beneficial response is achieved. The recommended pilocarpine dosing for the Sjögren’s syndrome patient is 5 mg four times daily. According to the medication’s prescribing information, the recommended dosing for cevimilene for the Sjögren’s syndrome patient is 30 mg three times daily. The first dose should be given between 6:00 am and 8:00 am; the second dose between 1:00 pm and 3:00 pm; and the third dose between 7:00 pm and 9:00 pm.
Oral moisturizers and topical saliva substitutes can be applied to the oral tissues either as a spray or gels placed directly on the tissues. A 5% aqueous solution of sodium carboxycellulose is one of the oldest surface moisturizers; the author has been using it since the early 1970s, when it was the only oral moisturizer available. The patient is instructed to use it as a rinse as frequently as needed to moisten the oral tissues. This preparation will moisten the tissues for approximately 30 minutes. The commercial products will moisten the tissues from 1 to 8 hours depending on the product.61
Artificial saliva and oral moisturizers are promoted for use when the mouth feels dry. Patients with salivary gland hypofunction always have an inadequate quantity of saliva and their assessment of the dryness of their mouth is purely subjective. A better approach to the use of the topical products would be to use them in a disciplined manner. These patients need maximum protection of the oral tissues at mealtimes. The author recommends that they use one of the products 5 to 10 minutes before each meal. The liquid/gel/spray should be placed in the mouth so that all of the soft tissues are coated. The mouth will have maximum lubrication at mealtime to prevent food from sticking to the tissues, and the tissues also will be protected from any irritants in the food and any beverages consumed. In addition to the use of moisturizing products before each meal, the patient should be instructed to increase their water intake, particularly at mealtime.8,44,62 Patients who experience xerostomia from medications have a normal stimulatory response at meal times. They will experience the dry mouth between meals. The patient should be instructed to use the oral moisturizers/artificial saliva regularly between meals.8
Management of Dental Caries
People with decreased salivary function have an increased risk of developing caries. This is because of a decrease in the antimicrobial activity of the saliva; a diminished debridement/lavage action; diminished aggregation action; compromised pH maintenance; and decreased remineralization. These patients must have frequent dental evaluations to reinforce and ensure optimal plaque control procedures. The daily use of topical fluoride agents and antimicrobial mouthrinses is extremely important. The fluoride may be delivered in the form of 0.4% stannous fluoride gel or 1.1% neutral or acidulated sodium fluoride gel directly to the teeth, or placed in customized fluoride carriers to be worn for 5 minutes daily.
Management of Oral Candidiasis
Salivary hypofunction can result in oral candidiasis as a result of a decrease or loss of the saliva actions of aggregation; debridement/lavage; and antimicrobial action. The oral presentation may be the classic pseudomembranous form, the erythematous form, or a burning sensation of the tongue or other areas of lining mucosa. Candidiasis may also be found associated with dentures and at the corners of the mouth, known as angular cheilitis.35 Oral candidiasis will respond to antifungal treatment. Topical antifungal agents are generally effective for the treatment of oral candidiasis caused by xerostomia.
Denture bases may harbor the candida organism and thus would be a source for reinfection. After ensuring that the dentures have an acceptable fit, the denture base also must be treated. Methods of disinfection include the immersion of the dentures into a solution of 1% sodium hypochlorite for 20 minutes or a 0.12% solution of chlorhexidine. If the fungal infection does not respond to the topical agents, then systemic antifungal therapy should be prescribed.
Management of Poor-Fitting Dentures
The proper retention of dentures depends on the saliva and its lubricating property in the denture base–mucosal interface. If there is salivary hypofunction, the denture will not be stable and may dislodge from the alveolar ridges, resulting in problems with eating and speaking. The movement of the denture base also will result in irritation to the supporting tissues.36 In evaluating the poor-fitting denture in the patient who has xerostomia, whether the denture has an acceptable fit must be determined first. If the denture fit is acceptable, then the problem is with the retention of the denture base on the supporting tissues. To resolve this problem, have the patient place an oral moisturizing gel on the supporting tissues and then place a fine layer of the gel onto the tissue-bearing side of the denture base. This will artificially create the saliva seal for retention. This must be done every time the denture is placed in the mouth.
Management of Dysgeusia
Dorland’s definition of dysgeusia is “the distortion or decrease in the sense of taste.” This distortion in taste may be caused by medications, xerostomia, or a zinc deficiency. Saliva stimulates gustatory receptors located on the taste buds and the saliva delivers tastants directly to the taste buds. When there is salivary hypofunction, the stimulation of the gustatory receptors and the delivery of tastants to the taste buds is greatly diminished.63 The use of oral moisturizers and artificial saliva immediately before meals will artificially create the presence of saliva in the oral cavity at meal time. The patient should also be encouraged to frequently sip water during their meals. When considering the patient who has received radiation therapy to the head-and-neck region, they may experience altered taste from the mucositis and xerostomia, and permanent taste loss if the tongue receives > 6,000 cGy. If the radiation dose is < 6,000 cGy, there will be some recovery of taste.64
Conclusion
The evaluation of the dental patient’s salivary function should be part of the comprehensive dental examination. Salivary hypofunction can be the result of medical disorders and medications. Not only must the oral dryness concerns of the patient be addressed, but also the oral problems that result from decreased salivary secretions, ie, caries, candidiasis, dysgeusia, and/or denture stability. Once the problem has been identified and a preventive and treatment schedule has been developed, we can restore and maintain optimal oral health for the patient with xerostomia. This also will affect the patient’s overall health and quality of life.
References
1. Bartley AG. Suppression of the saliva. Letter to the Editor. Medical Times Gazette. 1868;54:603.
2. Hutchinson J. A report on “xerostomia” or “dry mouth” with an additional case. Trans Clin Soc London. 1889;22: 25-27.
3. Atkinson JC, Wu AJ. Salivary gland dysfunction: causes, symptoms, treatment. J Am Dent Assoc. 1994;125:409-416.
4. Navazesh M, Kumar SKS. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008;139:35S-40S.
5. Navazesh M. How can oral health care providers determine if patients have a dry mouth? J Am Dent Assoc. 2003;134:613-618.
6. Sreebny LM, Valdini A. Xerostomia. Part I: Relationship to other oral symptoms and salivary gland hypofunction. Oral Surg. 1988; 66: 451-458.
7. Navazesh M. Methods for collecting saliva. Annals New York Academy of Sciences. 1993;694:72-77.
8. Navazesh M, Ship II. Xerostomia: diagnosis and treatment. Am J Otolaryngology. 1983; 4:283-292.
9. Tabak LA, Levine MJ, Mandell ID, Ellison SA. Role of salivary mucins in the protection of the oral cavity. J Oral Pathol. 1982; 11:1-17.
10. Hu Zhanzhi. The history of saliva based research. UCLA School of Dentistry Dental Research Institute, Saliva-Based Translational Research and Clinical Applications (Star CA). 2008: 1-4.
11. Young JA, Van Lennep EW. The Morphology of Salivary Glands. London: Academic Press, 1978.
12. Kaufman E, Lamster IB. The diagnostic applications of saliva: a review. Crit Rev Oral Biol Med. 2002;13(2):197-212.
13. Milne RW, Dawes C. The relative contributions of different salivary glands to the blood group activity of whole saliva in humans. Vox Sang. 1973; 25:298-307.
14. Adams D. The mucous barrier and absorption through the oral mucosa. J Dent Res. 1975;54:1319-1326.
15. Mandel ID. The role of saliva in maintaining oral homeostasis. J Am Dent Assoc. 1989; 119:298-304.
16. Gibbons RJ. Review and discussion of role of mucus in mucosal defense. In: Strober W, Hanson LA, Sell KW, eds. Recent Advances in Mucosal Immunity. New York: Raven Press. 1951;343-351.
17. Thesleff I, Kantomaa T, Mackie E, et al. The parotid gland is the main source of human salivary epidermal growth factors. Life Science. 1988;43:13-18.
18. Hutson JM, Niall M, Evans D, Fowler R. Effect of salivary glands on wound contraction in mice. Nature. 1979;279: 793-795.
19. Niall M, Ryan GB, O’Brien BM. The effect of epidermal growth factor on wound healing in mice. J Surg Res. 1982;33: 164-169.
20. Liljemark WF, Boomquist CG, Germaine GR. Effect of bacterial aggregation on the adherence of oral streptococci to hydroxyapatite surfaces. Infect Immun. 1981;31: 935-941.
21. Scannapieco FA, Bergey EJ, Reddy MS, Levine MJ. Characterization of salivary alpha amylase binding to Streptococcus anguis. Infect Immun. 1989;57:2853-2863.
22. McNabb PC, Tomasi TB. Host defense mechanisms at mucosal surfaces. Annual Rev Microbiol. 1981;35: 447-496.
23. Teeuw W, Bosch JA, Veerman EC, Amerongen AV. Neuroendocrine regulation of salivary IgA synthesis and secretion: Implications for oral health. Biol Chem. 2004; 385:1137-1146.
24. Tenovuo J. Antimicrobial function of human saliva: How important is it for oral health? Acta Odontol Scand. 1998;56: 250-256.
25. Korsud FR, Brandtzaeg P. Quantitative immunohistochemistry of immunoglobulin and J-chain producing cells in human parotid and submandibular salivary glands. Immunology. 1993;39:129-140.
26. Mestecky J. Saliva as a manifestation of the common mucosal immune system. Ann New York Acad Sci. 1993;694:184-194.
27. Nair PN, Schroeder HE. Duct-associated lymphoid tissue of minor salivary glands and mucosal immunity. Immunology. 1986; 57: 171-180.
28. Van Nieuw Amerongen A, Bolscher JG, Veerman EC. Salivary proteins: protective and diagnostic value in cariology? Caries Res. 2004;38: 247-253.
29. Pollock JJ, Lotardo S, Gavai R, Grossbard BL. Lysozyme-protease-inorganic monovalent anion lysis of oral bacterial strains in buffers and stimulated whole saliva. J Dent Res. 1987;66:467-474.
30. Tortosa M, Cho MI, Wilkens TJ, et al. Bacteriolysis of Veillonella alcalescens by lysozyme and inorganic anions present in saliva. Infect Immun. 1984;32:1261-1273.
31. Mackay BJ, Denepitiya L, Iacono VJ, et al. Growth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutans. Infect Immun. 1984;44: 695-701.
32. Armold RR, Brewer M, Gauthier JJ. Bactericidal activity of human lactoferrin: sensitivity of a variety of organisms. Infect Immun. 1980;28:893-898.
33. Tenovuo J, Mansson-Rahemtulla B, Pruitt KM, Arnold R. Inhibition of dental plaque acid production by salivary lactoperoxidase system. Infect Immun. 1981;34:208-214.
34. Oppenheim FG, Xu T, McMillian FM, et al. Histatins, a novel family of histidine-rich proteins in human parotid secretion: isolation, characterization, primary structure, and fungiside effects on Candida albicans. J Biol Chem. 1988;263(16): 7472-7477.
35. Pollock JJ, Denepitiya L, Mackay BJ, Iacono VJ. Fungistatic and fungicidal parotid salivary histidine-rich polypeptides on Candida albicans. Infect Immun. 1984;44:702-707.
36. Turner MD, Ship JA. Dry mouth and its effects on the health of elderly people. J Am Dent Assoc. 2007;138:15S-20S.
37. Epstein JB, Freilich MM, Le ND. Risk factors for oropharyngeal candidiasis in patients who receive radiation therapy for malignant conditions of the head and neck. Oral Surg Oral Med Oral Pathol. 1993; 76:169-174.
38. Radfar L, Shea Y, Fischer SH, et al. Fungal load and candidiasis in Sjögren’s syndrome. Oral Surg Oral Med Oral Pathol. 2003;96:283-287.
39. Lu FX, Jacobsen RS. Oral mucosal immunity and HIV/SIV infections. J Dent Res. 2007;86:216-226.
40. Heineman HS, Greenberg MS. Cell protective effect of human saliva specific for herpes simplex virus. Arch Oral Biol. 1980; 25:257-261.
41. Fox PC, Wolff A, Yeh CK, et al. Saliva inhibits HIV-1 infectivity. J Am Dent Assoc. 1988;116:635-637.
42. Helm JF, Dodds WJ, Hogan WJ, et al. Acid neutralizing capacity of human saliva. Gastroenterology. 1982;83:69-74.
43. Kleinberg I, Jenkins GN. The pH of dental plaques in the different areas of the mouth before and after meals and their relationship to the pH and rate of flow of resting saliva. Arch Oral Biol. 1964;9:493-516.
44. Dawes C. Salivary flow patterns and the health of hard and soft oral tissues. J Am Dent Assoc. 2008;139:18S-24S.
45. Macpherson LM, Dawes C. Urea concentration in minor mucous gland secretions and the effect of salivary film velocity on urea metabolism by streptococcus vestibularis in an artificial plaque. J Periodont Res. 1991;26:395-401.
46. Dawes C. What is the critical pH and why does a tooth dissolve in acid? J Can Dent Assoc. 2003;69:722-724.
47. Stookey GK. The effect of saliva on dental caries. J Am Dent Assoc. 2008;139:11S-17S.
48. Ericsson Y. Enamel-apatite solubility: investigations into the calcium phosphate equilibrium between enamel and saliva and its relation to dental caries. Acta Odontol Scand. 1949;8:1-139.
49. Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth. Gerodontol. 1997;14:33-47.
50. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective measures of salivary gland performance. J Am Dent Assoc. 1987;115: 581-584.
51. Dawes C. Circadian rhythm in human salivary flow rate and composition. J Physiol. 1972;220:529-548.
52. Schneyer LH, Pigman W, Hanahan L, Gilmore RW. Rate of flow of human parotid, sublingual, and submaxillary secretions during sleep. J Dent Res. 1956;35:109-114.
53. Baum BJ. Evaluation of stimulated parotid saliva flow rate in different age groups. J Dent Res. 1981;60:1292-1296.
54. Ben-Aryeh H, Shalve A, Szargel R, et al. The salivary flow rate and composition of whole and parotid resting and stimulated saliva in young and old healthy subjects. Biochemical Medicine Metabolic Biology. 1986; 36:260-265.
55. Rhodus NL. Sjögren’s syndrome. Quintessence Int. 1999;30:689-699.
56. Greenspan JS, Greenspan D, Daniels T. The histopathology of Sjögren’s syndrome in labial salivary gland biopsies. Oral Surg. 1974;37:217-229.
57. Eisbruch A, Ten Haken RK, Kim HM, et al. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys. 1999;45:577-587.
58. Eisbruch A, Ship JA, Kim HM, et al. Partial irradiation of the parotid gland. Semin Radiat Oncol. 2001;11:234-239.
59. Dawes C, Kubienic K. The effects of prolonged gum chewing on salivary flow rate and composition. Arch Oral Biol. 2004; 49:665-669.
60. Watanabe S, Dawes C. The effects of different foods and concentrations of citric acid on the flow rate of whole saliva in man. Arch Oral Biol. 1988;33:1-5.
61. American Academy of Oral Medicine. Clinician’s Guide to Treatment of Common Oral Conditions. 6th Ed. Siegel MA, Sliverman S, Solliceto TP, eds. BC Decker; 2006:58.
62. Garg AK, Malo M. Manifestations and treatment of xerostomia and associated oral effects secondary to head and neck radiation therapy. J Am Dent Assoc. 1997;128: 1128-1133.
63. Spielman AI, Ship JA. Taste and smell. In: Clinical Oral Physiology. Miles TS, Nauntofte B, Svensson P, eds. Copenhagen, Denmark: Quintessence. 2004;53-70.
64. Oral Health in Cancer Therapy: A Guide for Healthcare Professionals. 2nd ed. Rankin KV, Jones DL, Redding SW, eds. Conference proceedings from the 2003 Oral Health in Cancer Therapy Conference developed by the Texas Dental Oncology Education Program. 2003:16.
About the Author
George M. Taybos, DDS, MSEd
Professor, Oral Medicine/Oral Oncology
Department of Otolaryngology and Communicative Sciences
University of Mississippi Medical Center
Jackson, Mississippi
