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SPECIAL SUPPLEMENTARY ISSUE—FEB 2008
By Philip C. Fox, DDS, FDS, RCSEd
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Recognition and Management
By Philip C. Fox, DDS, FDS, RCSEd
Epidemiology and Etiology of Xerostomia
Xerostomia (dry mouth) is the subjective feeling of oral dry- Xerostomia is a common oral concern for many patients. It is ness. It is important to recognize that xerostomia is not a diag- estimated that up to 10 percent of the general population expe- nosis, but a symptom with multiple possible causes. Although riences persistent oral dryness.1,2 Xerostomia is more frequent
dry mouth is most frequently associated with altered salivary with increasing age, and over 25 percent of elders complain of gland function, there are other etiologies for this oral issue. It daily dryness.3 That percentage is even higher in institutional-
is important to perform a complete evaluation of the patient ized elders. However, it should be recognized that xerostomia is with dry mouth, determining, if possible, the cause of the not a result of aging per se, and should not be dismissed as xerostomia so that appropriate management can be instituted such. Salivary function in healthy, non-medicated elders does in a timely manner. The patient with xerostomia who has sali- not vary significantly from younger individuals. It is believed vary gland hypofunction is at risk for many oral complications that the increased frequency of dryness complaints with aging is and it is critical to institute appropriate preventive measures.
a result of systemic disease and medication use, both more com- Xerostomia may also be a consequence of systemic disease, and mon in elders and both associated with xerostomia.4
early recognition may aid in treatment. This monograph will As noted earlier, there are non-salivary causes of xerosto- review methods of evaluation for xerostomia and practical mia. These include conditions in which there are alterations of measures for management of the patient with dry mouth.
oral mucosal sensation or central cognitive changes, such as Philip C. Fox, DDS, FDS, RCSEd, received his BA and DDS degrees from Columbia
University and completed training in oral and maxillofacial surgery at Harlem Hospital
Center, New York, N.Y. and a fellowship in oral medicine at the National Institutes of
Health in Bethesda, Md. He was a member of the National Institute of Dental and
Craniofacial Research, National Institutes of Health, for 22 years, serving as chief of the
Clinical Investigations Section, Gene Therapy and Therapeutics Branch, and as clinical
director of the Intramural Research Program. At present, he is a visiting scientist at the
Department of Oral Medicine, Carolinas Medical Center, in Charlotte, N.C., and an
independent biomedical consultant focusing primarily in the area of clinical trial design
and analysis. He is a diplomate of the American Board of Oral Medicine.
This xerostomia supplement to Access magazine was funded by an educational grantsponsored by the Colgate Oral Pharmaceuticals Division of Colgate-Palmolive Company.
This supplement can also be accessed online at www.adha.org/CE_courses/ To obtain one hour of continuing education credit, complete the test atwww.adha.org/CE_courses/coursexxxxxx Supplement to Access—February 2008
following a cerebral vascular accident (stroke). Dryness has Table I. Systemic Conditions that May
been associated with depression, even in the absence of recog-nizable changes in salivary function. The most common causes Have Xerostomia as a Symptom
of xerostomia, however, are conditions or circumstances that Autoimmune connective tissue disorders result in alterations in salivary gland function, either quantita- • Sjögren's syndrome, primary and secondary tive or qualitative.1
Granulomatous diseases The most frequent cause of dry mouth complaints is the • sarcoidosis, tuberculosis use of prescription drugs. There are hundreds of pharmaceuti- cals that have xerostomia as a side effect.5,6 The salivary
glands are stimulated strongly by cholinergic agents. Therefore, anti-cholinergic medications, such as antihistamines, are most Diabetes (poorly controlled) likely to cause decreased salivary output and xerostomia.5
However, many other classes of medications, including seda- Human immunodeficiency virus infection tives, antipsychotics, antidepressants and diuretics are associat- ed with xerostomia. Interestingly, many herbal preparations • hypo- and hyper-thyroidism may induce complaints of oral dryness, and patients should Late stage liver disease always be questioned about non-prescription drug use.7
Affective disorder Examples of commonly used preparations include members of Eating disorders and malnutrition the Labiatae family (specifically all the salvias), capsicum, gar- anorexia, bulemia, dehydration lic, Ginkgo biloba, and St. John's Wort (Hypercicum perfora-tum). Herbal preparations with strong diuretic properties, suchas stinging nettle (Urtica dioica) and dandelion (Taraxacum for xerostomia to manifest. This emphasizes that dryness officinale) also may lead to complaints of dry mouth. Caffeine resulting from salivary dysfunction is usually indicative of sys- is well recognized as a cause of xerostomia.8 As many as 25
temic involvement. Table I provides a fuller listing of systemic million persons in the United States may experience xerosto- conditions with xerostomia as a possible symptom. mia as a result of medication use.
The most frequent cause of
Diagnosis of Xerostomia
dry mouth complaints is the use of
IT IS CRITICAL THAT ORAL health care practitioners recognize xerostomia and salivary gland dysfunction in their patients, assaliva plays an essential role in protection of oral hard and soft There are also medical therapies that result in xerosto- tissues and support of oral functions.16 One should follow a
mia. Radiotherapy to the head and neck region that includes systematic assessment approach to the patient with xerostomia: the salivary glands in the treatment fields can lead to signifi- listen for and elicit symptomatic complaints, examine for oral cant and persistent dry mouth. This is an expected complica- signs of salivary gland dysfunction and evaluate salivary gland tion at exposure levels above 5200 cGy.9,10 Systemically
administered radionuclides, such as 131I for treatment of thyroid The most frequently voiced complaint is a feeling of dry- cancer, are a recognized cause of dry mouth, particularly when ness of all the oral mucosal surfaces, including the throat.
re-treatment is required.11 Bone marrow transplantation also
Additionally, patients may report difficulty in chewing, swal- may have xerostomia as a side effect, due to the salivary gland lowing, or speaking. A need to drink fluids to help swallow involvement in graft-versus-host disease.12
while eating or an inability to swallow dry foods is also com- Another major cause of xerostomia is systemic disease.
mon. Many patients will carry fluids at all times for comfort There are a large number of conditions that can affect salivary and to aid in speaking and swallowing. Pain is often reported, gland function and lead to complaints of dryness, including and the oral mucosa may be sensitive to spicy or coarse foods, diabetes, thyroid disorders, cystic fibrosis and connective tissue which may limit the patient's diet and enjoyment of meals.
diseases.13 The most prominent of the connective tissue dis-
Patients may report that their lips and the oral mucosa ‘stick' eases is Sjögren's syndrome, an autoimmune condition that to their teeth. The salivary glands may swell intermittently or may affect up to 4 million people in the United States.
chronically. Removable denture wearers commonly report Xerostomia is one of the hallmark symptoms in Sjögren's syn- problems with retention and mucosal damage due to lack of drome, experienced by over 95 percent of patients.14 Patients
lubrication. When denture adhesives are used, they may not experience a number of dryness complaints in addition to fully develop their adhesive and retentive properties through xerostomia. These include eye, nose, throat, skin and vaginal failure to hydrate adequately. Patients should also be ques- dryness. Since complaints of oral dryness typically do not tioned concerning dryness in other areas. Eye, throat, nasal, appear until salivary function has been reduced by approxi- skin or vaginal dryness, in addition to xerostomia, may be mately 50 percent,15 more than a single gland must be affected
indicative of a systemic condition, such as Sjögren's syndrome.
Supplement to Access—February 2008
In addition to these physical effects on the oral cavity, a patient's quality of life is severely
impacted.18,19 Since adequate salivary func-
tion is important to support alimentation and
communication, salivary gland dysfunction
and xerostomia may adversely affect some of
our most critical activities of daily living.
Salivary gland function should be assessed in the patient with xerostomia. This may bedone easily in an office setting by determining Figure 2. The lips, tongue
the total unstimulated output of saliva, and all mucosal surfaces are
termed the whole saliva flow rate. Whole sali- dry in this patient with
va is the mixed fluid contents of the mouth.
Figure 1. Dry mouth associated with Sjögren's
Sjögren's syndrome. Note also
Using the expectoration model, the patient syndrome. The tongue is dry and pale and has
the erosion and the presence
allows saliva to accumulate in the mouth and lost papillation of the surface.
of epithelial debris on the
then expectorates into a pre-weighed graduat- teeth, a sign of diminished
ed cylinder every 60 seconds, for 5 to 15 min- It is recognized that the severity of xerosto- salivary secretions.
utes.20 To insure an unstimulated sample,
mia is poorly correlated with salivary gland func- patients should refrain from eating, drinking, tion. Some individuals tolerate marked (or almost oral hygiene or smoking for 90 minutes prior complete) lack of salivation with few complaints, while for oth- to the collection. While inter-individual variability makes it ers, modest decreases in salivary output may trigger severe com- difficult to determine a "normal" value for salivary output, plaints of dry mouth and oral discomfort. The reasons for this there is agreement on the minimal values necessary to consider poor correlation are unclear and reflect a lack of knowledge salivary output normal. Unstimulated whole saliva flow rates of about the elements necessary for oral comfort. Although subjec- <0.1 mL/min are considered abnormally low and indicative of tive dryness does not correlate well with measurable salivary marked salivary hypofunction.21 It is important to recognize
gland dysfunction, some symptoms have been found to have that output higher than that amount does not guarantee that predictive value.17 When xerostomia is reported, patients
function is normal. For some individuals, this may be a should be questioned in greater detail about its nature, frequen- markedly reduced value. However, this value represents a gen- cy and duration. If questioning reveals difficulties with oral erally accepted lower limit of normal and is a useful guide for activities dependent on adequate salivation, such as chewing the clinician. Using a well-defined, standardized, and clearly and swallowing, it is likely that salivary function is diminished. documented procedure for collection will allow meaningfulcomparisons to published material and with repeat measures inan individual over time.
Clinical Assessment of Xerostomia
The composition of the collected saliva may be analyzed (sialochemistry). Over 60 components have been identified in On examination, the patient with xerostomia due to reduced saliva.22 There is increasing interest in salivary diagnostics for
salivary gland function usually has obvious signs of mucosal systemic and oral diseases.23 Saliva is used currently for deter-
dryness.1 The lips may be cracked, peeling and atrophic; the
mining blood alcohol levels, smoking and drugs of abuse as buccal mucosa pale and corrugated in appearance; and the well as for HIV testing and detection of exposure to other tongue smooth and reddened with loss of papillation (Figure microbes. Using newer genomic and proteomic techniques, 1). The oral mucosa may appear reddened, thinner and more researchers have begun to identify possible salivary biomarkers fragile. There is often a marked increase in erosion and dental for a number of oral and systemic conditions. This is a rapidly caries, particularly at the gingival margin, and even cusp tip expanding area of investigation.
involvement. The decay may be rapid and progressive even in Salivary function and gland integrity also can be exam- the presence of excellent oral hygiene (Figure 2). One should ined with technetium (Tc) pertechnetate scintiscanning.
consider whether the caries' history and current condition are Uptake of intravenously injected 99mTc tracer from the blood consistent with the patient's oral hygiene. Candidiasis, most into the glands and subsequent secretion into the oral cavity frequently of the erythematous form, is frequent and may con- can be monitored with a gamma camera. Salivary scintiscans tribute to mucosal sensitivity. The salivary glands should be correlate well with salivary function and can be used in clinical examined for enlargement, changes in texture, and pain and studies to monitor changes in function following also to determine if saliva can be expressed from the main excretory ducts. The saliva should be clear, watery and copi- Tumors and structural alterations in the salivary glands ous. A cloudy exudate may be a sign of bacterial infection, can be visualized with sialography, ultrasonography, MRI or CT although some patients with very low salivary output will have imaging.25 These techniques are useful to detect salivary stones
opaque secretions that are sterile.
(sialoliths), duct blockage, constriction or damage, tumors and Supplement to Access—February 2008
cysts. These are not functional measures, but are useful for For dry lips, a hydrating cream or ointment may help diagnosis of salivary dysfunctions.
relieve symptoms. Use of products with aloe vera or vitamin E Biopsy of the salivary glands can be done as well. The should be encouraged. Highly flavored toothpastes should be most common procedure is biopsy of the minor salivary glands avoided because they may irritate the dry mucosa and cause of the lower lip. Minor glands are abundant in this region and pain or sensitivity. A diet that contains moisture-rich foods can be removed with minimal morbidity.26 Characteristic
and not hot or spicy foods may be more comfortable for the changes are seen in these glands with Sjögren's syndrome. The patient. Alcohol and caffeine may produce further drying and labial minor salivary gland biopsy is considered the best sole should be avoided or used only in limited quantities. In addi- diagnostic criterion for the salivary component of Sjögren's tion to its other negative health consequences, smoking may be drying and irritating to the mucosa and should be avoided.
Laboratory studies may be helpful in the diagnosis of An increase in environmental humidity is exceedingly impor- Sjögren's syndrome. Patients often have characteristic autoim- tant. Patients, especially in the wintertime, often experience a mune alterations in the blood, including the presence of worsening of their symptoms. Use of room humidifiers, particu- autoantibodies directed against SS-A (Ro) and SS-B (La), larly at night, may improve discomfort markedly.
antinuclear antibodies and elevated immunoglobulins. Preventive measures are necessary to minimize oral hard- Using a systematic evaluation approach, the cause of dry and soft-tissue damage. Patients should be seen by the dental mouth complaints can be identified in about 80 percent of hygienist on a frequent recall schedule of at least three times patients. The remainder of patients are characterized as having per year, until symptoms are minimized and dental caries is idiopathic xerostomia, but still require palliative care for symp- controlled. They must be instructed in and practice vigilant home oral hygiene. Patients should brush with fluoride tooth-paste after each meal. At a minimum, rinsing the mouth imme-diately after eating to remove food debris is beneficial. Advice Dental Hygienists' Role and Management
on diet is critical. Hygienists must stress the importance ofextremely low sugar intake, the use of sugar-free substitutes and the avoidance of sticky, carbohydrate-rich foods to mini-mize the caries risk. Patients should also be aware of the THE DENTAL HYGIENIST HAS AN important role in recognition and increased risk of tooth wear. Patients must be careful not to management of the patient with xerostomia. With careful atten- consume acidic foods and beverages in excess (e.g. carbonated tion and regular management, most patients will achieve sodas) in an effort to relieve symptoms. Remineralizing mouth increased oral comfort and oral complications can be minimized. rinses are now available and their use should be encouraged.
Management may be viewed as a series of goals: to pro- vide symptomatic relief of dryness complaints; to instituteappropriate preventive measures; to treat any ongoing oralproblems; if salivary function is decreased, to stimulate remain- Hygienists must stress the importance of
ing function; and to address the underlying disease process.
extremely low sugar intake, the use of
Management of xerostomia is a team process, involving thedentist, the dental hygienist and the patient's physicians.
sugar-free substitutes and the avoidance
Effective communication is essential for optimal patient care.
of sticky, carbohydrate-rich foods to
Management starts with methods to relieve symptoms.
These approaches are useful for any patient with dry mouth minimize the caries risk.
complaints, regardless of the cause. Frequent sips of water willhelp to relieve dryness, ease swallowing, hydrate tissues andcleanse the mouth. As noted earlier, many patients with drymouth carry water with them at all times, and this should be Patients with dry mouth have an increased risk of fungal encouraged. Oral rinses and mouthwashes, gels, sprays and infections. Consumption of sugar-free yogurt containing active artificial salivas are frequently used and may reduce discomfort yeast cultures may help to control oral fungal populations. If a and improve function transiently. The dental hygienist should fungal infection is present, appropriate antifungal treatments advise the patient to use oral care products that have been should be started. Due to the salivary dysfunction, treatment specifically formulated for a dry mouth; that is, without alco- may be prolonged and re-treatment is frequently required. A hol, using only mild detergents and flavorings, having a neutral therapeutic agent should be selected that does not contain or alkaline pH, containing no sugar and with added lubricants.
sugar as a flavoring agent, as is common in many antifungal The use of chewing gums, lozenges, candies or mints may pro- lozenges. Nystatin rinses may be prepared by a pharmacist from vide symptomatic relief by stimulating salivation, but they must powder without the added flavoring ingredient(s).
be sugar-free and non-acidic. Products containing xylitol as a Dental caries management is based on the severity of sali- sweetening agent should be encouraged, as xylitol has been vary dysfunction and the observed caries rate. All patients with shown to have anti-caries properties. xerostomia should use some supplemental fluoride, in addition Supplement to Access—February 2008
to a fluoride-containing toothpaste. Selection of the type, dose entanercept and thalidomide, which have shown benefit in and frequency of application should be made in consultation rheumatoid arthritis and lupus erythematosus, have shown no between the dentist, the dental hygienist and the patient.
significant efficacy in randomized controlled trials in Sjögren's Often a combination of office-applied and home-based fluoride treatments is optimal. At present, there is interest in modulation of B-cell acti- Stimulating salivary gland flow is effective for relief of vation. As there is well-documented B-cell hyperreactivity in dryness symptoms and provides the myriad benefits of natural Sjögren's syndrome, this approach may have an impact on the saliva. Chewing will stimulate salivary flow effectively, as will underlying disease. Rituximab is a humanized monoclonal anti- sour tastes. The combination of chewing and taste, as provided body that binds specifically to the CD20 antigen, which is pres- by gums or mints, can be very effective in relieving symptoms ent on B lymphocytes and is involved in cell activation. In an for patients who have remaining salivary function. As noted, open-label study, improvements in symptoms of dry mouth and however, patients must be told not to use products containing salivary gland function were demonstrated.37 Although these
sugar as a sweetener. Electrical stimulation of the salivary results are promising, a randomized controlled trial is necessary glands has been attempted, but application is a challenge and before recommendation of this treatment option for Sjögren's the results have been modest at best. Presently, newer devices syndrome. A recent open-label trial looked at an anti-CD22 are being investigated and show promise for the future.28
monoclonal antibody and reported very promising results in Systemic drugs, termed secretogogues, may be prescribed.
Sjögren's syndrome.38 Further studies are anticipated.
The Food and Drug Administration (FDA) has approved two
medications for the relief of dry mouth symptoms in Sjögren's
syndrome: pilocarpine (Salagen®) and cevimeline (Evoxac®).29-
31 These medications are parasympathomimetic, muscarinic
Management of xerostomia requires a
agonists, which induce a transient increase in salivary output team approach. The dentist and dental
and statistically significant improvement in complaints of oraldryness. Common side effects of both medications include hygienist should work together closely to
sweating, flushing, urinary incontinence and gastrointestinal minimize the patient's dryness complaints
discomfort. While rarely severe or serious, side effects are fre-quent, which may limit the usefulness of these agents in some and to preserve and protect the oral
individuals. Parasympathomimetics are contraindicated in tissues. Patient education is key.
patients with uncontrolled asthma, narrow-angle glaucoma,and acute iritis and should be used with caution in patientswith significant cardiovascular disease, Parkinson disease, asth-ma and chronic obstructive pulmonary disease. Pilocarpine is Management of xerostomia requires a team approach.
recommended at a dosage of 5 mg up to four times daily, while The dentist and dental hygienist should work together closely cevimeline is prescribed at 30 mg three times daily. These med- to minimize the patient's dryness complaints and to preserve ications are widely used and provide significant relief of dryness and protect the oral tissues. Patient education is key. The den- complaints in many patients. Pilocarpine has also been tal team needs to explain the oral sequelae of dry mouth and approved for treatment of xerostomia related to head and neck the problems and issues patients may encounter in their daily lives. The oral condition needs to be assessed and monitored A number of different approaches have been attempted closely, and issues such as oral hygiene care and diet should be to address the underlying disease process and therefore emphasized. Consultation with the patient's physician is indi- improve salivary gland dysfunction, particularly in Sjögren's cated if, for example, the xerostomia appears to be related to syndrome. Current studies are targeting specific biologic path- medication use. In this case, discussion of alternative medica- ways to modify the underlying autoimmunity.
tions or dosing regimens to minimize xerostomia is indicated. If Very low dose interferon-alpha, 150 or 450 IU once or systemic disease is suspected as the underlying cause of salivary three times a day orally, has been studied in primary Sjögren's dysfunction, patients should be referred to their physician or syndrome. Use of 150 IU interferon-alpha three times daily an appropriate specialist without delay. Ongoing review and resulted in increased stimulated whole salivary flow rates at 12 monitoring of the patient's oral and general health are impor- weeks compared to placebo.32 A subsequent phase 3 trial at
tant for optimal management.
this dose found increased unstimulated salivary function com-pared to placebo at 24 weeks. However, the co-primary end-points of stimulated whole saliva flow and oral dryness were Summary and Conclusions
not significantly improved relative to placebo,33 and further
clinical studies will be necessary.
Awareness and recognition of xerostomia are essential in order Another approach has been to modify the inflammatory to help patients minimize dryness symptoms, to institute pre- cytokine pathway, specifically targeting tumor necrosis factor ventive measures and to limit oral complications. The dental alpha (TNFα). Anti-TNFα agents, including infliximab, hygienist has the opportunity to ask every patient if they are Supplement to Access—February 2008
experiencing dry mouth. In particular, complaints of dryness Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomiaand objective measures of salivary gland performance. J Am while eating, or difficulty swallowing dry foods, or the necessity Dent Assoc 1987; 115(4): 581-4.
of using liquids to ease swallowing are important clues that Ikebe K, Matsuda K, Morii K, et al. Impact of dry mouth and salivary function may be impaired. As part of a routine oral hyposalivation on oral health-related quality of life of elderly examination, one should examine the oral cavity carefully for Japanese. Oral Surg Oral Med Oral Pathol Oral Radiol Endod signs of salivary gland dysfunction. Findings such as an increase 2007; 103(2): 216-22.
Perno Goldie M. Xerostomia and quality of life. Int J Dent Hyg in caries activity, mucosal alterations, infection or salivary 2007; 5(1): 60-1.
gland enlargement may indicate salivary dysfunction.
Navazesh M. Methods for collecting saliva. Ann NY Acad Sci Evaluation should be conducted proactively at each patient 1993; 694: 72-7.
visit. Early recognition will minimize damage and dysfunction Sreebny L. Saliva—salivary gland hypofunction (SGH). FDI and allow appropriate management to begin. Although the Working Group 10. J Dent Assoc S Afr 1992; 47(11): 498-501.
Pesce MA, Spitalnik SL. Saliva and the clinical pathology labora- salivary dysfunction may be irreversible, preventive measures tory. Ann NY Acad Sci 2007; 1098: 192-9.
and conservative treatments can avoid or limit mucosal break- Chiappin S, Antonelli G, Gatti R, De Palo EF. Saliva specimen: a down, infections and permanent damage to teeth. Adequate new laboratory tool for diagnostic and basic investigation. Clin symptomatic relief is possible with local palliative and systemic Chim Acta 2007; 383(1-2): 30-40.
measures in many patients. Appropriate management of symp- Baur DA, Heston TF, Helman JI. Nuclear medicine in oral andmaxillofacial diagnosis: a review for the practicing dental profes- toms and increasing saliva output may help patients feel more sional. J Contemp Dent Pract 2004; 5(1): 94-104.
comfortable and improve their quality of life. Thoeny HC. Imaging of salivary gland tumours. Cancer Imaging2007; 7: 52-62.
Fox PC. Simplified biopsy technique for labial minor salivaryglands. Plast Reconstr Surg 1985; 75(4): 592-3.
Daniels TE. Labial salivary gland biopsy in Sjögren's syndrome.
Assessment as a diagnostic criterion in 362 suspected cases.
Arthritis Rheum 1984; 27(2): 147-56.
Guggenheimer J, Moore PA. Xerostomia: etiology, recognition Strietzel FP, Martín-Granizo R, Fedele S, et al. Electrostimulating and treatment. J Am Dent Assoc 2003; 134(1): 61-9.
device in the management of xerostomia. Oral Dis 2007; 13(2): Atkinson JC, Grisius M, Massey W. Salivary hypofunction and xerostomia: diagnosis and treatment. Dent Clin North Am. 2005; Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the 49(2): 309-26.
treatment of dry mouth and dry eye symptoms in patients with Orellana MF, Lagravère MO, Boychuk DG, et al. Prevalence of Sjögren syndrome: A randomized placebo-controlled fixed-dose xerostomia in population-based samples: a systematic review. J multicenter trial. Arch Intern Med 1999; 159: 174–181. Public Health Dent 2006; 66(2): 152-8.
Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment Ship JA, Pillemer SR, Baum BJ. Xerostomia and the geriatric of xerostomia in patients with Sjogren syndrome: a randomized patient. J Am Geriatr Soc 2002; 50(3): 535-43.
trial. Arch Intern Med 2002; 162(11): 1293–1300.
Ciancio SG. Medications' impact on oral health. J Am Dent Petrone D, Condemi JJ, Fife R, et al. A double-blind, random- Assoc 2004; 135(10): 1440-8.
ized, placebo-controlled study of cevimeline in Sjogren's syn- Sreebny LM. Saliva in health and disease: an appraisal and drome patients with xerostomia and keratoconjunctivitis sicca.
update. Int Dent J 2000; 50(3): 140-61.
Arthritis Rheum 2002; 46(3): 748–54.
Abebe W. An overview of herbal supplement utilization with par- Ship JA, Fox PC, Michalek JE, et al. Treatment of primary ticular emphasis on possible interactions with dental drugs and Sjögren's syndrome with lowdose natural human interferon-alpha oral manifestations. J Dent Hyg 2003; 77(1): 37-46.
administered by the oral mucosal route: a phase II clinical trial.
Sreebny LM, Schwartz SS. A reference guide to drugs and dry IFN protocol study group. J Interferon Cytokine Res 1999; 19: mouth—2nd edition. Gerodontology. 1997; 14(1): 33-47.
Sciubba JJ, Goldenberg D. Oral complications of radiotherapy.
Cummins MJ, Papas A, Kammer GM, Fox PC. Treatment of pri- Lancet Oncol 2006; 7(2): 175-83.
mary Sjogren's syndrome with low-dose human interferon alfa Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerosto- administered by the oromucosal route: combined phase III mia in patients with head and neck cancer: a literature review.
results. Arthritis Rheum 2003; 49: 585–93.
Cancer. 2006; 107(11): 2525-34.
Mariette X, Ravaud P, Steinfeld S, et al. Inefficacy of infliximab in Mandel SJ, Mandel L. Radioactive iodine and the salivary primary Sjogren's syndrome: results of the randomized, con- glands. Thyroid 2003; 13(3): 265-71.
trolled trial of Remicade in Primary Sjogren's Syndrome Woo SB, Lee SJ, Schubert MM. Graft-vs.-host disease. Crit Rev (TRIPSS). Arthritis Rheum 2004; 50(4): 1270–6.
Oral Biol Med 1997; 8(2): 201-16.
Sankar V, Brennan MT, Kok MR, et al. Etanercept in Sjogren's von Bültzingslöwen I, Sollecito TP, Fox PC, et al. Salivary dys- syndrome: a twelve-week randomized, double-blind, placebo- function associated with systemic diseases: systematic review controlled pilot clinical trial. Arthritis Rheum 2004; 50(7): 2240–5.
and clinical management recommendations. Oral Surg Oral Med Pillemer SR, Leakan RA, Sankar V, et al. Prominent adverse Oral Pathol Oral Radiol Endod 2007;103 Suppl: S57.e1-15.
effects of thalidomide in primary Sjogren's syndrome. Arthritis Kassan SS, Moutsopoulos HM. Clinical manifestations and early Rheum 2004; 51(3): 505–6.
diagnosis of Sjögren syndrome. Arch Intern Med 2004; 164(12): Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjogren's syndrome: an open-label Dawes C. Physiological factors affecting salivary flow rate, oral phase II study. Arthritis Rheum 2005; 52(9): 2740–50.
sugar clearance, and the sensation of dry mouth in man. J Dent Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (human- Res 1987; 66 Spec No: 648-53.
ised anti-CD22 antibody) in primary Sjögren's syndrome: an Dodds MW, Johnson DA, Yeh CK. Health benefits of saliva: a open-label phase I/II study. Arthritis Res Ther 2006; 8(4): R129.
review. J Dent 2005; 33(3): 223-33.
Supplement to Access—February 2008
Recycling, Risk Management and Ressource Allocation Jakob Magid, Dept. Agriculture and Ecology Historical background Future inclusion of food production in cities? Waste recycling potentials and risks Risk related to recycling and to growing urban food Land and water associated with food production and waste disposal Jakob Magid, Dept. Agriculture and Ecology
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