Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.

Clinical criteria for the diagnosis of salivary gland hypofunction.

There is considerable difficulty in the making of initial clinical decisions as to whether a given patient has salivary gland hypofunction, and hence requires additional salivary gland evaluation. This study identified a set of four clinical measures that, together, successfully predicted the presence or absence of salivary gland hypofunction. The four measures were: dryness of lips, dryness of buccal mucosa, absence of saliva produced by gland palpation, and total DMFT; they were derived from discriminant analysis of data collected from 71 individuals with normal and low salivary flow rates. These measures are proposed as criteria for clinical decision-making, as well as for classification of patients in studies of salivary gland dysfunction syndromes. This study also identified unstimulated whole salivary flow rates of 0.12-0.16 mL/min as the critical range separating individuals with salivary gland hypofunction from those with normal gland function.

The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women.

The association of xerostomia and salivary gland hypofunction with HIV infection has been established for men but not for women. We investigated the prevalence of these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV-negative women. Participants in this prospective cross-sectional study were recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva were collected under standardized conditions. The major salivary glands were also evaluated clinically. The prevalence of dry-mouth complaint, the absence of saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min) were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV-positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63). Significant (p = 0.03) univariate association was found between zero unstimulated whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated flow rates were not significantly different between seropositive and seronegative women. The prevalence of xerostomia and salivary gland hypofunction appears to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4 cell counts are significantly associated with xerostomia and salivary gland hypofunction in a population of HIV-positive women.

Comparison of whole saliva flow rates and mucin concentrations in healthy Caucasian young and aged adults.

Unstimulated and chewing-stimulated whole saliva samples were obtained from 42 healthy Caucasians; 21 were between 18 and 35 years of age, and 21 between 65 and 83 years of age. The unstimulated salivary flow rate was significantly lower in the aged group, but the stimulated flow rate was significantly higher in the aged than in the young group. Both groups showed significantly increased flow during salivary stimulation. MG1 and MG2 concentrations in unstimulated and stimulated saliva samples were significantly lower in the aged group. There were no significant correlations between salivary flow rates and MG1 and MG2 concentrations.

Age-related changes in mucins from human whole saliva.

The predominant mucins in human whole saliva, MG1 and MG2, serve to protect and to lubricate the oral cavity. In this study, both unstimulated and stimulated whole salivas were collected from two groups of subjects: young (18-35 years of age) and aged (65-83 years of age). The subjects were in apparent good health. Saliva samples from each subject were analyzed by SDS-PAGE. The gels were stained with Stains-all, and both MG1 and MG2 were quantitated by video-image densitometry. The protocol gave reproducible values for each mucin. The stimulated and unstimulated salivas from aged subjects showed significant reductions in concentrations of both MG1 and MG2, as quantitated in mucin dye-binding units. Possible associations of these reductions with the aging process are discussed.

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

Incidence of oral lesions in HIV-1-infected women: reduction with HAART.

Few studies assess the effectiveness of HAART on reducing the incidence and recurrence of oral lesions. We investigated such changes among 503 HIV+ women over six years in the Women's Interagency HIV Study. The incidence of erythematous candidiasis (EC), pseudomembranous candidiasis (PC), hairy leukoplakia (HL), and warts was computed over follow-up visits after HAART initiation compared with before HAART initiation. Analysis of our data demonstrates a strong decrease in candidiasis after HAART initiation. The incidence of EC fell to 2.99% from 5.48% (RR 0.545); PC fell to 2.85% from 6.70% (RR 0.425); and EC or PC fell to 3.43% from 7.35% (RR 0.466). No changes were seen in HL or warts. Higher HIV-RNA was associated with greater incidence of candidiasis and HL, but not warts. Analysis of these data indicates that recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independently of CD4 and HIV-RNA.

Prevalence of human herpesvirus-8 salivary shedding in HIV increases with CD4 count.

Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/microL was 63 times the odds of shedding at CD4 < 350 (95%CI, 1.3-3078), with an increase in effect size when the analysis was restricted to those with a CD4 nadir > 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.

Effects of pharmacologic reductions in salivary flow on taste thresholds in man.

The effects of short-term salivary flow reductions on human taste thresholds were measured. Recognition and detection thresholds were obtained from 65 subjects during periods of both normal and reduced salivary flow. Decreased salivary flow was achieved by oral administration of either Elavil, Benadryl or atropine. Thresholds were measured for NaCl, citric acid, quinine sulphate and sucrose with a traditional series of aqueous solutions as well as with a series of dry taste stimuli using a filter-paper base. Whole mouth resting flow and stimulated salivary flow were measured before and after taste testing. The pharmacologic agents produced depressions in salivary flow ranging between 30 and 75 per cent of normal levels. The large decreases in flow produced no measurable changes in taste thresholds with the exception that an increased sensitivity to aqueous and dry citric acid stimuli consistently was observed following atropine administration. Changes in salivary bicarbonate levels, produced by atropine, may have mediated the observed shifts in oral sensitivity to citric acid.

Bacterial agglutinin activity in the saliva of human identical and fraternal twins.

The major factor in human saliva responsible for the specific aggregation of oral streptococci is a high molecular-weight glycoprotein (agglutinin). To determine if the level of this glycoprotein in whole and parotid saliva was genetically determined, agglutinin activity for Streptococcus sanguis and Streptococcus mutans in saliva obtained from identical and fraternal twins was compared. Evidence for the heritability of agglutinin activity and also parotid flow rate and total protein was obtained. There was no evidence for a significant genetic contribution to salivary sodium concentration.

The influence of moderate reduction in dietary sodium on human salivary sodium concentration.

Twenty-four healthy subjects were placed for 12-13 weeks on diets that reduced average sodium intake from 145 to 74 m-equiv. Na+/day as determined by multiple 24-h urine collections before and during the diet. Whole-mouth resting and stimulated saliva was collected and analysed for flow rate and sodium concentration several times before and during the low-sodium period. Sodium restriction did not influence salivary flow rates but salivary sodium levels fell 25 per cent for resting and 17 per cent for stimulated saliva. Thus moderate reductions in sodium intake are accompanied by significantly lower salivary sodium levels.

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

Relationship between salivary flow rates and Candida albicans counts.

Seventy-one persons (48 women, 23 men; mean age, 51.76 years) were evaluated for salivary flow rates and Candida albicans counts. Each person was seen on three different occasions. Samples of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid saliva were collected under standardized conditions. An oral rinse was also obtained and evaluated for Candida albicans counts. Unstimulated and chewing-stimulated whole flow rates were negatively and significantly (p < 0.001) related to the Candida counts. Unstimulated whole saliva significantly (p < 0.05) differed in persons with Candida counts of 0 versus <500 versus < or = 500. Chewing-stimulated saliva was significantly (p < 0.05) different in persons with 0 counts compared with those with a > or = 500 count. Differences in stimulated parotid flow rates were not significant among different levels of Candida counts. The results of this study reveal that whole saliva is a better predictor than parotid saliva in identification of persons with high Candida albicans counts.

Relationship of medical status, medications, and salivary flow rates in adults of different ages.

Multiple systemic disorders and medications have been reported to cause xerostomia or salivary gland hypofunction. The purpose of this study was to evaluate the relationship among systemic disorders, medications, and salivary flow rates. Sixty-three ambulatory dental patients aged 23 to 82 years were randomly selected. The nature, duration, and number of systemic disorders and medications were documented. Repeated measurements of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid salivary flow rates were obtained. Data were analyzed with the Wilcoxon rank-sum test, nonparametric multivariate analysis of variance, and Fisher's exact test. For persons with systemic disorders who were taking medication, all salivary flow rates were significantly (p = 0.03 - 0.001) lower than the flow rates in healthy persons. Among persons with at least one systemic disorder who were taking medication, those who had been taking medication for longer than 2 years had significantly lower unstimulated whole saliva (p = 0.002), chewing-stimulated whole saliva (p = 0.0004), and candy-stimulated parotid saliva (p = 0.02) flow rates than those who had been taking medication for 1 to 2 years. The number of systemic disorders significantly (p = 0.02) and negatively affected the acid-stimulated parotid salivary rates. The prevalence of salivary hypofunction determined on the basis of unstimulated whole saliva and acid-stimulated parotid saliva was significantly higher (p = < 0.001, p = 0.007) in the those persons with systemic disorders and taking medications. The results suggest that salivary secretion is affected by the number of systemic disorders and duration of the potentially xerogenic medications.

Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study. Women's Interagency HIV Study.

OBJECTIVE: To determine the prevalence of enlargement, tenderness, and absence of saliva on palpation as indicators of salivary gland disease in women who are human immunodeficiency virus (HIV)-positive. STUDY DESIGN: The study subjects are participants in the Women's Interagency HIV Study (WIHS), a multicenter study examining HIV-seropositive women and at-risk HIV-seronegative women. A total of 576 HIV-positive women and 152 HIV-negative women were examined at their baseline oral visit for clinical markers of salivary gland disease. Viral load levels, CD4 counts, and CD8 counts were obtained as part of the related core study. RESULTS: HIV-positive women had higher rates of salivary gland enlargement (4.3%), tenderness (6.9%), and absence of saliva on palpation (26.6%) compared with HIV-negative women, who had rates of 1.3%, 4.6%, and 13.2%, respectively. Absence of saliva was significantly different (P =. 001) between the 2 groups. When 2 of the 3 clinical findings were combined, comparisons between the HIV-positive women and HIV-negative women became significant at the P <.05 level for every combination, except for enlargement/tenderness for the submandibular/sublingual gland. For the HIV-positive women, the viral load was significantly related to enlargement (P =.019) and enlargement/absence of saliva on palpation (P =.037) for the parotids and enlargement (P =.046), absence of saliva (P =.043), and enlargement/absence of saliva (P =.022) for the submandibular/sublingual glands. Significant linear trends were found for increasing viral load and enlargement (P =.013) and enlargement/tenderness (P =.024) for the submandibular/sublingual glands. Significance was present for submandibular/sublingual absence of saliva and tenderness/absence of saliva for CD4 and CD8 medians. CONCLUSIONS: Serostatus is related to salivary gland disease as assessed by glandular enlargement, tenderness, and absence of saliva on palpation. Furthermore, our findings indicate that a multidimensional approach to gland assessment may provide a more complete and perhaps more adequate description of glandular involvement with HIV infection.

Xerostomia in the aged.

Xerostomia is a symptom associated with a variety of causes. Disorders in the production and transport as well as excessive depletion of saliva may lead to xerostomia. It is difficult to make any general statement about the functional significance of salivary gland changes associated with aging, as the clinical evidence is controversial and data from different studies do not encourage any uniform conclusion. Rational treatments of xerostomias may be performed casually (for example, withdrawal or exchange of drugs inhibiting salivary secretion), but will often only be practical as a symptomatic therapy. Special attention should be directed toward maintenance of adequate oral hygiene in order to prevent clinical complications such as increased dental caries, monilial infection, dysgeusia and tooth sensitivity, which are associated with xerostomia and are often observed in elderly xerostomic patients.

Tartar-control toothpaste as a possible contributory factor in the onset of superficial mucocele: a case report.

Superficial mucoceles are small, clear vesicles that occur on clinically non-inflamed mucosa and are often misdiagnosed as vesiculobullous disorders. Soft palate, retromolar pads, and posterior buccal mucosa are common sites of involvement. The lesions are more common in women than in men and need no treatment. This paper describes a 71-year-old female who demonstrated some of the pitfalls in diagnosis and a possible contributory role of a tartar-control toothpaste in the onset of the lesions.

Systemic dissemination as a result of oral infection in individuals 50 years of age and older.

The oral pathosis caused by systemic disorders in middle-aged and elderly adults has been the focus of many publications in recent years. The intraoral soft and hard tissue changes associated with systemic disorders, medications, chemotherapy, and radiation treatment have been well-investigated and -documented. Far less attention has been paid to the role of oral infection as the etiology of systemic disorders. A literature review (1980-1994) is provided here focusing on well-documented cases in which systemic disorders were caused by oral foci of infections. This paper attempts to raise the level of awareness of practitioners in considering possible systemic complications caused by oral infection. It also emphasizes the need for further longitudinal studies in this field involving healthy and medically compromised elderly individuals.

Toxic shock and Down syndromes in a dental patient: a case report and review of the literature.

A literature review of Toxic Shock Syndrome is presented, including epidemiology, etiology, signs, symptoms and management, and its relationship to infection susceptibility in the Down Syndrome patient. A case of a Down Syndrome patient with Toxic Shock Syndrome is described, and the role of odontogenic infection is discussed.

A pilot study comparing three salivary collection methods in an adult population with salivary gland hypofunction.

The purpose of this pilot study was to compare the reliability of three collection methods (draining, chewing of gum base, and the Saxon test) for whole saliva using a sample of middle-aged and older ambulatory adults (n = 18) with proven salivary gland hypofunction. The results demonstrated high reliability (r values ranging from 0.91 to 0.80, p < 0.001) for all three methods. MANOVA analysis revealed significant (p < 0.001) differences in flow rates among the draining, chewing-stimulated, and Saxon methods.