Xerostomia and hypofunction of the salivary glands in cancer therapy

Supportive Care in Cancer

Volumn 11, Issue 4, 2003, Pages 207-225

  Jensen, Siri Beier ^a,b   Pedersen, Anne Marie ^a,b   Reibel, Jesper ^a,b   Nauntofte, Birgitte ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Copenhagen Gerontol Oral H R C ^*  (Denmark)

Author keywords

Chemotherapy; Irradiation; Oral complications; Saliva

Indexed keywords

ACLARUBICIN; ALKYLATING AGENT; ANTHRACYCLINE DERIVATIVE; ANTIMETABOLITE; ANTIMITOTIC AGENT; ANTINEOPLASTIC AGENT; ASPARAGINASE; BLEOMYCIN; CHLORMETHINE; CISPLATIN; CYCLOPHOSPHAMIDE; CYTARABINE; CYTOSTATIC AGENT; DACARBAZINE; DAUNORUBICIN; DEXAMETHASONE; DOXORUBICIN; EPIRUBICIN; FLUOROURACIL; METHOTREXATE; MITOXANTRONE; PACLITAXEL; PEPLEOMYCIN; PREDNISONE; PROCARBAZINE; UNINDEXED DRUG; VINBLASTINE; VINBLASTINE SULFATE; VINCRISTINE; VINCRISTINE SULFATE;

BONE NECROSIS; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER THERAPY; DENTAL CARIES; DYSGEUSIA; DYSPHAGIA; EDEMA; FIBROSING ALVEOLITIS; HUMAN; IATROGENIC DISEASE; INFLAMMATORY DISEASE; MALIGNANT NEOPLASTIC DISEASE; MEDICAL LITERATURE; MOUTH MUCOSA; MUCOSA INFLAMMATION; ORAL BLEEDING; PAIN; PAROTITIS; PERIODONTAL DISEASE; PRIORITY JOURNAL; RADIATION INJURY; REVIEW; SALIVARY GLAND DISEASE; SALIVATION; SIDE EFFECT; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND; TOOTH MALFORMATION; TRISMUS; XEROSTOMIA;

EID: 0037937420     PISSN: 09414355     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00520-002-0407-7     Document Type: Review

References (184)

1. Aalto Y, Forsgren S, Franzen L, Henriksson R (1998) Is radiationinduced degranulation of mast cells in salivary glands induced by substance P? Oral Oncol 34:332-339
2. Abok K, Brunk U, Jung B, Ericsson J (1984) Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland. Virchows Arch [B] 45:443-460
3. Adams GL (1989) Treatment of head and neck cancer with combined modalities. Invest Radiol 24:562-567
4. Albertioni F, Rask C, Schroeder H, Peterson C (1997) Monitoring of methotrexate and 7-hydroxymethotrexate in saliva from children with acute lymphoblastic leukemia receiving highdose consolidation treatment: relation to oral mucositis. Anticancer Drugs 8:119-124
5. Almstahl A, Wikstrom M (1999) Oral microflora in subjects with reduced salivary secretion. J Dent Res 78:1410-1416
6. Almstahl A, Wikstrom M, Groenink J (2001) Lactoferrin, amylase and mucin MUC5B and their relation to the oral microflora in hyposalivation of different origins. Oral Microbiol Immunol 16:345-352
7. Almstahl A, Wikstrom M, Kroneld U (2001) Microflora in oral ecosystems in primary Sjögren's syndrome. J Rheumatol 28:1007-1013
8. Aoba T, Takahashi J, Yagi T, Doi Y, Okazaki M, Moriwaki Y (1981) Highvoltage electron microscopy of radiation damages in octacalcium phosphate. J Dent Res 60:954-959
9. Backstrom I, Funegard U, Andersson I, Franzen L, Johansson I (1995) Dietary intake in head and neck irradiated patients with permanent dry mouth symptoms. Eur J Cancer [B Oral Oncol] 31:253-257
10. 2. Arch Oral Biol 45:1-12
11. Bardow A, Nyvad B, Nauntofte B (2001) Relationships between medication intake, complaints of dry mouth, salivary flow rate and composition, and the rate of tooth demineralization in situ. Arch Oral Biol 46:413-423
12. Batsakis JG, Regezi JA, Luna MA, el Naggar A (1989) Histogenesis of salivary gland neoplasms: a postulate with prognostic implications. J Laryngol Otol 103:939-944
13. Baum BJ (1989) Salivary gland fluid secretion during aging. J Am Geriatr Soc 37:453-458
14. Baum BJ, Bodner L, Fox PC, Izutsu KT, Pizzo PA, Wright WE (1985) Therapy-induced dysfunction of salivary glands: implications for oral health. Spec Care Dentist 5:274-277
15. Ben Aryeh H, Gutman D, Szargel R, Laufer D (1975) Effects of irradiation on saliva in cancer patients. Int J Oral Surg 4:205-210
16. Bergmann OJ (1990) Humoral immunity of the oral cavity during remission-induction therapy in patients with acute myeloid leukaemia. Eur J Haematol 44:296-301
17. Bergmann OJ (1991) Alterations in oral microflora and pathogenesis of acute oral infections during remissioninduction therapy in patients with acute myeloid leukaemia. Scand J Infect Dis 23:355-366
18. Berthong M (1986) Pathologic changes secondary to irradiation. World J Surg 10:155-170
19. Bertram U (1967) Xerostomia. Clinical aspects, pathology and pathogenesis. Acta Odontol Scand 25:Suppl 126
20. Bjordal K, Kaasa S, Mastekaasa A (1994) Quality of life in patients treated for head and neck cancer: a followup study 7 to 11 years after radiotherapy. Int J Radiat Oncol Biol Phys 28:847-856
21. Boyer AL, Geis P, Grant W, Carol M (1997) Modulated beam conformal therapy for head and neck tumors. Int J Radiat Oncol Biol Phys 39:227-236
22. Bressolle F, Jacquet JM, Galtier M, Jourdan J, Donadio D, Rossi JF (1992) Doxorubicin and doxorubicinol plasma concentrations and excretion in parotid saliva. Cancer Chemother Pharmacol 30:215-218
23. Brizel DM, Wasserman TH, Henke M, Strnad V, Rudat V, Monnier A, et al. (2000) Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 18:3339-3345
24. Brown LR, Dreizen S, Rider LJ, Johnston DA (1976) The effect of radiationinduced xerostomia on saliva and serum lysozyme and immunoglobulin levels. Oral Surg Oral Med Oral Pathol 41:83-92
25. Brown LR, O'Neill PA, Dreizen S, Handler SF, Riggan LJ, Perkins DH (1981) Relationship between saliva and serum agglutination titers and postirradiation caries activity in cancer patients. J Dent Res 60:10-18
26. Burlage FR, Coppes RP, Meertens H, Stokman MA, Vissink A (2001) Parotid and submandibular/sublingual salivary flow during high dose radiotherapy. Radiother Oncol 61:271-274
27. Chaillet MP, Cosset JM, Socie G, Pico JL, Grimaud E, Dubray B et al (1993) Prospective study of the clinical symptoms of therapeutic whole body irradiation. Health Phys 64:370-374
28. Chao KS (2002) Protection of salivary function by intensity-modulated radiation therapy in patients with head and neck cancer. Semin Radiat Oncol 12:20-25
29. Chaushu G, Itzkovitz-Chaushu S, Yefenof E, Slavin S, Or R, Garfunkel AA (1995) A longitudinal follow-up of salivary secretion in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:164-169
30. Cheng VS, Downs J, Herbert D, Aramany M (1981) The function of the parotid gland following radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys 7:253-258
31. Christensen ME, Hansen HS, Poulsen SS, Bretlau P, Nexo E (1996) Immunohistochemical and quantitative changes in salivary EGF, amylase and haptocorrin following radiotherapy for oral cancer. Acta Otolaryngol 116:137-143
32. Coppes RP, Roffel AF, Zeilstra LJ, Vissink A, Konings AW (2000) Early radiation effects on muscarinic receptor-induced secretory responsiveness of the parotid gland in the freely moving rat. Radiat Res 153:339-346
33. Cowman RA, Baron SS, Fitzgerald RJ, Stuchell RE, Mandel ID (1983) Comparative growth responses of oral streptococci on mixed saliva or the separate submandibular and parotid secretions from caries-active and caries-free individuals. J Dent Res 62:946-951
34. Dabadghao S, Srivastava A, Dennison D (1996) Bilateral submandibular salivary gland enlargement during chemotherapy for acute myeloid leukaemia beneficial effect of propranolol. Acta Haematol 96:112
35. Dawes C (1969) The effects of flow rate and duration of stimulation on the concentrations of protein and the main electrolytes in human parotid saliva. Arch Oral Biol 14:277-294
36. Dawes C (1983) A mathematical model of salivary clearance of sugar from the oral cavity. Caries Res 17:321-334
37. Dawes C, Watanabe S (1987) The effect of taste adaptation on salivary flow rate and salivary sugar clearance. J Dent Res 66:740-744
38. Dehpour AR, Ghafourifar P, Madani F, Mousavizadeh K, Abdollahi M (1995) Effects of vinca alkaloids on rat parotid and submandibular glands function in vivo. Gen Pharmacol 26:321-325
39. del Regato JA (1939) Dental lesions observed after roentgentherapy in cancer of the buccal cavity, pharynx and larynx. AJR Am J Roentgenol 42:404-410
40. Dens F, Boute P, Vinckier F, Declerck D (1995) Quantitative determination of immunologic components of salivary gland secretion in long-term, event-free pediatric oncology patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:701-704
41. Dens F, Boogaerts M, Boute P, et al (1996) Caries-related salivary microorganisms and salivary flow rate in bone marrow recipients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:38-43
42. D'Hondt E, Eisbruch A, Ship JA (1998) The influence of pre-radiation salivary flow rates and radiation dose on parotid salivary gland dysfunction in patients receiving radiotherapy for head and neck cancers. Spec Care Dentist 18:102-108
43. Distelhorst CW (2002) Recent insights into the mechanism of glucocorticosteroid-induced apoptosis. Cell Death Differ 9:6-19
44. Dreizen S, Brown LR, Handler S, Levy BM (1976) Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes. Cancer 38:273-278
45. Dreizen S, Brown LR, Daly TE, Drane JB (1977) Prevention of xerostomiarelated dental caries in irradiated cancer patients. J Dent Res 56:99-104
46. Dreizen S, Daly TE, Drane JB, Brown LR (1977) Oral complications of cancer radiotherapy. Postgrad Med 61:8592
47. Eisbruch A, Ship JA, Martel MK, et al (1996) Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results. Int J Radiat Oncol Biol Phys 36:469-480
48. Eisbruch A, Dawson LA, Kim HM, et al (1999) Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life. Acta Otorhinolaryngol Belg 53:271-275
49. Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA (1999) 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 45:577-587
50. Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA, Ship JA (2001) Xerostomia and its predictors following parotid-sparing irradiation of headand-neck cancer. Int J Radiat Oncol Biol Phys 50:695-704
51. El Mofty SK, Kahn AJ (1981) Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol Relat Stud Phys Chem Med 39:55-62
52. Eneroth CM, Henrikson CO, Jakobsson PA (1972) Effect of fractionated radiotherapy on salivary gland function, Cancer 30:1147-1153
53. Ericson S (1971) The importance of sialography for the determination of the parotid flow. The normal variation in salivary output in relation to the size of the gland at stimulation with citric acid. Acta Otolaryngol 72:437-444
54. Fajardo LF (1982) Salivary glands and pancreas. In: Pathology of radiation injury, Masson, New York, pp 77-87
55. Fox PC, Busch KA, Baum BJ (1987) Subjective reports of xerostomia and objective measures of salivary gland performance, J Am Dent Assoc 115:581-584
56. Frank RM, Herdly J, Philippe E (1965) Acquired dental defects and salivary gland lesions after irradiation for carcinoma. J Am Dent Assoc 70:868-883
57. Franzen L, Funegard U, Ericson T, Henriksson R (1992) Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort. Eur J Cancer 28:457-462
58. Funegard U, Franzen L, Ericson T, Henriksson R (1994) Parotid saliva composition during and after irradiation of head and neck cancer. Eur J Cancer [B Oral Oncol] 30:230-233
59. 2. Int J Radiat Biol Relat Stud Phys Chem Med 48:621-633
60. Harrison T, Bigler L, Tucci M, et al (1998) Salivary sIgA concentrations and stimulated whole saliva flow rates among women undergoing chemotherapy for breast cancer: an exploratory study. Spec Care Dentist 18:109-112
61. Hazuka MB, Martel MK, Marsh L, Lichter AS, Wolf GT (1993) Preservation of parotid function after external beam irradiation in head and neck cancer patients: a feasibility study using 3-dimensional treatment planning. Int J Radiat Oncol Biol Phys 27:731-737
62. Heintze U, Birkhed D, Bjorn H (1983) Secretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. Swed Dent J 7:227-238
63. Henriksson R, Frojd O, Gustafsson H, et al (1994) Increase in mast cells and hyaluronic acid correlates to radiationinduced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity. Br J Cancer 69:320-326
64. Henson BS, Eisbruch A, D'Hondt E, Ship JA (1999) Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment. Oral Oncol 35:234-241
65. Henson BS, Inglehart MR, Eisbruch A, Ship JA (2001) Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy. Oral Oncol 37:84-93
66. Humphries JE, Lee JT (1992) Acute bilateral parotitis during chemotherapy for acute lymphoblastic leukemia. Acta Haematol 88:55-56
67. Ishii E, Yamada S, Higuchi S, et al (1989) Oral mucositis and salivary methotrexate concentration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia. Med Pediatr Oncol 17:429-432
68. Izutsu KT, Truelove EL, Bleyer WA, Anderson WM, Schubert MM, Rice JC (1981) Whole saliva albumin as an indicator of stomatitis in cancer therapy patients. Cancer 48:1450-1454
69. Jansma J, Buskes JA, Vissink A, Mehta DM, Gravenmade EJ (1988) The effect of X-ray irradiation on the demineralization of bovine dental enamel. A constant composition study. Caries Res 22:199-203
70. Jarvinen VK, Rytomaa II, Heinonen OP (1991) Risk factors in dental erosion. J Dent Res 70:942-947
71. Jensen JL, Xu T, Lamkin MS, et al (1994) Physiological regulation of the secretion of histatins and statherins in human parotid saliva. J Dent Res 73:1811-1817
72. Jervoe P (1970) X-ray diffraction investigation on the effect of experimental and in situ radiation on mature human teeth. A preliminary report. Acta Odontol Scand 28:623-631
73. Johansson I, Saellstrom AK, Rajan BP, Parameswaran A (1992) Salivary flow and dental caries in Indian children suffering from chronic malnutrition. Caries Res 26:38-43
74. Johnson JT, Ferretti GA, Nethery WJ, et al. (1993) Oral pilocarpine for postirradiation xerostomia in patients with head and neck cancer. N Engl J Med 329:390-395
75. Joyston-Bechal S (1985) The effect of X-radiation on the susceptibility of enamel to an artificial caries-like attack in vitro. J Dent 13:41-44
76. Kalk WW, Vissink A, Spijkervet FK, Bootsma H, Kallenberg CG, Nieuw Amerongen AV (2001) Sialometry and sialochemistry: diagnostic tools for Sjögren's syndrome. Ann Rheum Dis 60:1110-1116
77. Kashima HK, Kirkham WR, Andrews JR (1965) Postradiation sialoadenitis. A study of the clinical features, histopathological changes and serum enzyme variations following irradiation of human salivary glands. AJR Am J Roentgenol [Radiother Ther Nucl Med] 94:271-291
78. Kinirons MJ, Fleming P, Boyd D (1995) Dental caries experience of children in remission from acute lymphoblastic leukaemia in relation to the duration of treatment and the period of time in remission. Int J Paediatr Dent 5:169-172
79. Kuten A, Ben Aryeh H, Berdicevsky I, et al. (1986) Oral side effects of head and neck irradiation: correlation between clinical manifestations and laboratory data. Int J Radiat Oncol Biol Phys 12:401-405
80. Laine P, Meurman JH, Tenovuo J, et al (1992) Salivary flow and composition in lymphoma patients before, during and after treatment with cytostatic drugs. Eur J Cancer [B Oral Oncol] 28:125-128
81. Lartigau E, Saunders MI, Dische S, Warburton MF, Des RC (1991) A comparison of the late radiation changes after three schedules of radiotherapy. Radiother Oncol 20:139-148
82. Lenander-Lumikari M, Loimaranta V (2000) Saliva and dental caries. Adv Dent Res 14:40-47
83. Leslie MD, Dische S (1994) The early changes in salivary gland function during and after radiotherapy given for head and neck cancer. Radiother Oncol 30:26-32
84. Leung WK, Dassanayake RS, Yau JY, Jin LJ, Yam WC, Samaranayake LP (2000) Oral colonization, phenotypic, and genotypic profiles of Candida species in irradiated, dentate, xerostomic nasopharyngeal carcinoma survivors. J Clin Microbiol 38:2219-2226
85. LeVeque FG, Montgomery M, Potter D, et al (1993) A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiationinduced xerostomia in head and neck cancer patients. J Clin Oncol 11:1124-1131
86. Liem IH, Olmos RA, Balm AJ, et al (1996) Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours. Eur J Nucl Med 23:1485-1490
87. Litman T, Druley TE, Stein WD, Bates SE (2001) From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell Mol Life Sci 58:931-959
88. Liu RP, Fleming TJ, Toth BB, Keene HJ (1990) Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. Oral Surg Oral Med Oral Pathol 70:724-729
89. Lockhart PB, Sonis ST (1981) Alterations in the oral mucosa caused by chemotherapeutic agents. A histologic study. J Dermatol Surg Oncol 7:1019-1025
90. Main BE, Calman KC, Ferguson MM, et al (1984) The effect of cytotoxic therapy on saliva and oral flora. Oral Surg Oral Med Oral Pathol 58:545-548
91. Makkonen TA, Nordman E (1987) Estimation of long-term salivary gland damage induced by radiotherapy. Acta Oncol 26:307-312
92. Makkonen TA, Tenovuo J, Vilja P, Heimdahl A (1986) Changes in the protein composition of whole saliva during radiotherapy in patients with oral or pharyngeal cancer. Oral Surg Oral Med Oral Pathol 62:270-275
93. Mandel ID (1980) Sialochemistry in diseases and clinical situations affecting salivary glands. Crit Rev Clin Lab Sci 12:321-366
94. Mansson-Rahemtulla B, Techanitiswad T, Rahemtulla F, McMillan TO, Bradley EL, Wahlin YB (1992) Analyses of salivary components in leukemia patients receiving chemotherapy. Oral Surg Oral Med Oral Pathol 73:35-46
95. Marks JE, Davis CC, Gottsman VL, Purdy JE, Lee F (1981) The effects of radiation of parotid salivary function. Int J Radiat Oncol Biol Phys 7:1013-1019
96. Matin SB, Wan SH, Karam JH (1974) Pharmacokinetics of tolbutamide: prediction by concentration in saliva. Clin Pharmacol Ther 16:1052-1058
97. McBride RK, Siegel IA (1988) Effect of methotrexate on protein and amylase secretion by rat parotid and submandibular salivary glands. Arch Oral Biol 33:245-249
98. McBride RK, Harper C, Siegel IA (1987) Methotrexate-induced changes in rat parotid and submandibular gland function. J Dent Res 66:1445-1448
99. McCarthy GM, Awde JD, Ghandi H, Vincent M, Kocha WI (1998) Risk factors associated with mucositis in cancer patients receiving 5-fluorouracil. Oral Oncol 34:484-490
100. Meurman JH, Laine P, Keinanen S, Pyrhonen S, Teerenhovi L, Lindqvist C (1997) Five-year follow-up of saliva in patients treated for lymphomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83:447-452
101. Meurman JH, Laine P, Lindqvist C, Teerenhovi L, Pyrhonen S (1997) Five-year follow-up study of saliva, mutans streptococci, lactobacilli and yeast counts in lymphoma patients. Oral Oncol 33:439-443
102. Milano G, Thyss A, Santini J, et al (1989) Salivary passage of 5-fluorouracil during continuous infusion. Cancer Chemother Pharmacol 24:197-199
103. Mira JG, Wescott WB, Starcke EN, Shannon IL (1981) Some factors influencing salivary function when treating with radiotherapy. Int J Radiat Oncol Biol Phys 7:535-541
104. Mira JG, Fullerton GD, Wescott WB (1982) Correlation between initial salivary flow rate and radiation dose in the production of xerostomia. Acta Radiol Oncol 21:151-154
105. Moreno EC, Varughese K, Hay DI (1979) Effect of human salivary proteins on the precipitation kinetics of calcium phosphate. Calcif Tissue Int 28:7-16
106. Mossman K, Shatzman A, Chencharick J (1982) Long-term effects of radiotherapy on taste and salivary function in man. Int J Radiat Oncol Biol Phys 8:991-997
107. Mossman KL (1983) Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy. Radiat Res 95:392-398
108. Mossman KL, Shatzman AR, Chencharick JD (1981) Effects of radiotherapy on human parotid saliva. Radiat Res 88:403-412
109. Nagler RM (1998) Short- and longterm functional vs morphometrical salivary effects of irradiation in a rodent model. Anticancer Res 18:315-320
110. Nagler RM, Laufer D (1998) Protection against irradiation-induced damage to salivary glands by adrenergic agonist administration. Int J Radiat Oncol Biol Phys 40:477-481
111. Nagler RM, Baum BJ, Miller G, Fox PC (1998) Long-term salivary effects of single-dose head and neck irradiation in the rat. Arch Oral Biol 43:297-303
112. Nasman M, Bjork O, Soderhall S, Ringden O, Dahllof G (1994) Disturbances in the oral cavity in pediatric long-term survivors after different forms of antineoplastic therapy. Pediatr Dent 16:217-223
113. Nauntofte B (1992) Regulation of electrolyte and fluid secretion in salivary acinar cells. Am J Physiol 263:G823-G837
114. Nauntofte B, Jensen JL (1999) Salivary secretion. In: Yamada T, Alpers DH, Laine L, Owyang C, Powell DW (eds) Textbook of gastroenterology. Lippincott-Williams & Wilkins, Philadelphia, pp 263-278
115. Navazesh M, Christensen CM (1982) A comparison of whole mouth resting and stimulated salivary measurement procedures. J Dent Res 61:1158-1162
116. Navazesh M, Wood GJ, Brightman VJ (1995) Relationship between salivary flow rates and Candida albicans counts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80:284-288
117. Niedermeier W, Matthaeus C, Meyer C, Staar S, Muller RP, Schulze HJ (1998) Radiation-induced hyposalivation and its treatment with oral pilocarpine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:541-549
118. Nunn JH, Welbury RR, Gordon PH, Kemahan J, Craft AW (1991) Dental caries and dental anomalies in children treated by chemotherapy for malignant disease: a study in the north of England. Int J Paediatr Dent 1:131-135
119. O'Connell AC (2000) Natural history and prevention of radiation injury. Adv Dent Res 14:57-61
120. O'Connell AC, Redman RS, Evans RL, Ambudkar IS (1999) Radiationinduced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling. Radiat Res 151:150-158
121. Öhrn KE, Wahlin YB, Sjoden PO (2001) Oral status during radiotherapy and chemotherapy: a descriptive study of patient experiences and the occurrence of oral complications. Support Care Cancer 9:247-257
122. Öhrn KE, Sjoden PO, Wahlin YB, Elf M (2001) Oral health and quality of life among patients with head and neck cancer or haematological malignancies. Support Care Cancer 9:528-538
123. Oliff A, Bleyer WA, Poplack DG (1979) Methotrexate-induced oral mucositis and salivary methotrexate concentrations. Cancer Chemother Pharmacol 2:225-226
124. Oppenheim FG, Xu T, McMillan FM, et al (1988) Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J Biol Chem 263:7472-7477
125. Overholser CD, Peterson DE, Williams LT, Schimpff SC (1982) Periodontal infection in patients with acute nonlymphocyte leukemia. Prevalence of acute exacerbations. Arch Intern Med 142:551-554
126. Pajari U, Poikonen K, Larmas M, Lanning M (1989) Salivary immunoglobulins, lysozyme, pH, and microbial counts in children receiving antineoplastic therapy, Scand J Dent Res 97:171-177
127. Pajari U, Ollila P, Lanning M (1995) Incidence of dental caries in children with acute lymphoblastic leukemia is related to the therapy used. ASDC J Dent Child 62:349-352
128. Patterson AJ, Ritschel WA, Zellner D, Kim SH (1981) Methotrexate serum and saliva concentrations in patients. Int J Clin Pharmacol Ther Toxicol 19:381-385
129. Pedersen AM, Nauntofte B (2001) Primary Sjögren's syndrome: oral aspects on pathogenesis, diagnostic criteria, clinical features and approaches for therapy. Expert Opin Pharmacother 2:1415-1436
130. Pedersen AM, Reibel J, Nordgarden H, Bergem HO, Jensen JL, Nauntofte B (1999) Primary Sjögren's syndrome: salivary gland function and clinical oral findings. Oral Dis 5:128-138
131. Pedersen AM, Bardow A, Jensen SB, Nauntofte B (2002) Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis 8:117-129
132. Peterson DE, Minah GE, Overholser CD, et al (1987) Microbiology of acute periodontal infection in myelosuppressed cancer patients. J Clin Oncol 5:1461-1468
133. Purdell-Lewis DJ, Stalman MS, Leeuw JA, Humphrey GB, Kalsbeek H (1988) Long term results of chemotherapy on the developing dentition: caries risk and developmental aspects. Community Dent Oral Epidemiol 16:68-71
134. Pyykonen H, Malmstrom M, Oikarinen VJ, Salmo M, Vehkalahti M (1986) Late effects of radiation treatment of tongue and floor-of-mouth cancer on the dentition, saliva secretion, mucous membranes and the lower jaw. Int J Oral Maxillofac Surg 15:401409
135. Redding SW, Zellars RC, Kirkpatrick WR, et al (1999) Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer. J Clin Microbiol 37:3896-3900
136. Reynolds MA, Minah GE, Peterson DE, et al (1989) Periodontal disease and oral microbial successions during myelosuppressive cancer chemotherapy. J Clin Periodontol 16:185-189
137. Rhodus NL, Bereuter J (2000) Clinical evaluation of a commercially available oral moisturizer in relieving signs and symptoms of xerostomia in postirradiation head and neck cancer patients and patients with Sjögren's syndrome. J Otolaryngol 29:28-34
138. Roesink JM, Terhaard CH, Battermann JJ (1998) Quantitative dose-volume response analysis of salivary gland function. Radiother Oncol 48:S105
139. Roesink JM, Konings AW, Terhaard CH, Battermann JJ, Kampinga HH, Coppes RP (1999) Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms. Int J Radiat Oncol Biol Phys 45:483-489
140. Roesink JM, Terhaard CH, Moerland MA, van Iersel F, Battermann JJ (2000) CT-based parotid gland location: implications for preservation of parotid function. Radiother Oncol 55:131-133
141. Roesink JM, Moerland MA, Battermann JJ, Hordijk GJ, Terhaard CH (2001) Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region. Int J Radiat Oncol Biol Phys 51:938-946
142. Romaniuk K, Gavin JB, Adkins KF (1983) The effect of methotrexate on salivary glands in the rat (abstract no 261). J Dent Res 62 [special issue]:678
143. Rössler R, Mitropoulos S, Klimek J (1995) Quantification of mineral loss after in vitro demineralization of irradiated enamel by longitudinal microradiography. Caries Res 29:307
144. Sagulin GB, Roomans GM (1989) Effects of thyroxine and dexamethasone on rat submandibular glands. J Dent Res 68:1247-1251
145. Schmidt-Nielsen B (1946) The solubility of tooth substance in relation to the composition of saliva (Thesis). Acta Odontol Scand 7 [Suppl. 2]:1-88
146. Schum CA, Izutsu KT, Molbo DM, Truelove EL, Gallucci B (1979) Changes in salivary buffer capacity in patients undergoing cancer chemotherapy. J Oral Med 34:76-80
147. Schwartz-Arad D, Michaeli Y, Zajicek G (1991) Compensatory hyperplasia of the rat submandibular gland following unilateral extirpation. J Dent Res 70:1328-1331
148. Shannon IL, Starcke EN, Wescott WB (1977) Effect of radiotherapy on whole saliva flow. J Dent Res 56:693
149. Shannon IL, Trodahl JN, Starcke EN (1978) Radiosensitivity of the human parotid gland. Proc Soc Exp Biol Med 157:50-53
150. Shannon IL, Wescott WB, Starcke EN, Mira J (1978) Laboratory study of cobalt-60-irradiated human dental enamel. J Oral Med 33:23-27
151. Ship JA, Fischer DJ (1997) The relationship between dehydration and parotid salivary gland function in young and older healthy adults. J Gerontol [A Biol Sci Med Sci] 52:M310-M319
152. Ship JA, Eisbruch A, D'Hondt E, Jones RE (1997) Parotid sparing study in head and neck cancer patients receiving bilateral radiation therapy: one-year results. J Dent Res 76:807-813
153. Sholley MM, Sodicoff M, Pratt NE (1974) Early radiation injury in the rat parotid gland. Reaction of acinar cells and vascular endothelium. Lab Invest 31:340-354
154. Shulin W (1989) Human enamel structure studied by high resolution electron microscopy. Electron Microsc Rev 2:1-16
155. Sonis AL, Waber DP, Sallan S, Tarbell NJ (1995) The oral health of longterm survivors of acute lymphoblastic leukaemia: a comparison of three treatment modalities. Eur J Cancer [B Oral Oncol] 31:250-252
156. Sonis ST (1998) Mucositis as a biological process: a new hypothesis for the development of chemotherapyinduced stomatotoxicity. Oral Oncol 34:39-43
157. Sonis ST, Sonis AL, Lieberman A (1978) Oral complications in patients receiving treatment for malignancies other than of the head and neck. J Am Dent Assoc 97:468-472
158. Spak CJ, Johnson G, Ekstrand J (1994) Caries incidence, salivary flow rate and efficacy of fluoride gel treatment in irradiated patients. Caries Res 28:388-393
159. Spiechowicz E, Rusiniak-Kubik K, Skopinska-Rozewska E, et al (1994) Immunological status of patients with denture stomatitis and yeast infection after treatment of maxillofacial tumors. Arch Immunol Ther Exp (Warsz) 42:263-267
160. Sreebny LM (2000) Saliva in health and disease: an appraisal and update. Int Dent J 50:140-161
161. Sreebny LM, Schwartz SS (1997) A reference guide to drugs and dry mouth, 2nd edn. Gerodontology 14:33-47
162. Stephens LC, Ang KK, Schultheiss TE, King GK, Brock WA, Peters LJ (1986) Target cell and mode of radiation injury in rhesus salivary glands. Radiother Oncol 7:165-174
163. Stephens LC, King GK, Peters LJ, Ang KK, Schultheiss TE, Jardine JH (1986) Acute and late radiation injury in rhesus monkey parotid glands. Evidence of interphase cell death. Am J Pathol 124:469-478
164. Stephens LC, King GK, Peters LJ, Ang KK, Schultheiss TE, Jardine JH (1986) Unique radiosensitivity of serous cells in rhesus monkey submandibular glands. Am J Pathol 124:479-487
165. Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ (1991) Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 67:1539-1543
166. Tabak LA (1995) In defense of the oral cavity: structure, biosynthesis, and function of salivary mucins. Annu Rev Physiol 57:547-564
167. Taylor SE, Miller EG (1999) Preemptive pharmacologic intervention in radiation-induced salivary dysfunction. Proc Soc Exp Biol Med 221:14-26
168. Thaysen JH, Thorn NA, Schwartz IL (1954) Excretion of sodium, potassium, chloride and carbon dioxide. Am J Physiol 178:155-159
169. Tomita Y, Osaki T (1990) Gustatory impairment and salivary gland pathophysiology in relation to oral cancer treatment. Int J Oral Maxillofac Surg 19:299-304
170. Tsuji H (1985) Quantitative doseresponse analysis of salivary function following radiotherapy using sequential RI-sialography. Int J Radiat Oncol Biol Phys 11:1603-1612
171. Umazume M, Ueta E, Osaki T (1995) Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy. J Clin Microbiol 33:432-439
172. Valdez IH, Atkinson JC, Ship JA, Fox PC (1993) Major salivary gland function in patients with radiationinduced xerostomia: flow rates and sialochemistry. Int J Radiat Oncol Biol Phys 25:41-47
173. Verhey LJ (1999) Comparison of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy systems. Semin Radiat Oncol 9:78-98
174. Vissink A, 's-Gravenmade EJ, Ligeon EE, Konings WT (1990) A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands. Radiat Res 124:259-265
175. Vissink A, Konings AW, Ligeon EE, 's-Gravenmade EJ (1990) Irradiationinduced changes in secretion and composition of rat saliva. J Biol Buccale 18:3-8
176. Vissink A, Kalicharan D, Gravenmade EJ, et al (1991) Acute irradiation effects on morphology and function of rat submandibular glands. J Oral Pathol Med 20:449-456
177. Wahlin YB (1991) Salivary secretion rate, yeast cells, and oral candidiasis in patients with acute leukemia. Oral Surg Oral Med Oral Pathol 71:689-695
178. Walker R (1975) Direct effect of radiation on the solubility of human teeth in vitro. J Dent Res 54:901
179. Watanabe J, Hayashi Y, Iwamoto K, Ozeki S (1985) Salivary excretion of 5-fluorouracil. I. Fluctuation of the saliva/plasma concentration ratio and salivary clearance in beagle dogs following bolus intravenous administration. Chem Pharm Bull (Tokyo) 33:1187-1194
180. Wescott WB, Mira JG, Starcke EN, Shannon IL, Thornby JI (1978) Alterations in whole saliva flow rate induced by fractionated radiotherapy. AJR Am J Roentgenol 130:145-149
181. Wolff A, Moreira JE, Marmary Y, Fox PC (1989) Lack of acute effects of methotrexate on rat parotid salivary gland function. Arch Oral Biol 34:109-115
182. Wu Q, Manning M, Schmidt-Ullrich R, Mohan R (2000) The potential for sparing of parotids and escalation of biologically effective dose with intensity-modulated radiation treatments of head and neck cancers: a treatment design study. Int J Radiat Oncol Biol Phys 46:195-205
183. Young JA, van Lennep EW (1978) Microscopic anatomy. The morphology of salivary glands. Academic Press, New York
184. Young W, Khan F, Brandt R, Savage N, Raze AA, Huang Q (2001) Syndromes with salivary dysfunction predispose to tooth wear: case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjögren's syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:38-48