The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study.

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.

The use of soluble, salivary c-erbB-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study.

A surge of new technological developments, coupled with the limitations of existing disease-detection methodologies, is propelling the field of medical diagnostics forward at unprecedented rates. Advancements in proteomics and nanotechnology are paving the way for diagnostic tests that will be capable of rapid multi-analyte detection in both laboratory and non-laboratory settings. Technological advancements have also benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium that can be collected simply and non-invasively. Salivary biomarkers have been identified that may provide diagnostic information about a variety of cancers and other diseases. In particular, proof-of-principle has been demonstrated for salivary c-erbB-2, whose elevation has been shown to correlate strongly with breast malignancy in women. The purpose of this manuscript is to review the past literature and present the current research focused on the use of saliva as a diagnostic medium for the detection of malignancies that are remote from the oral cavity.

Comparison of alveolar bone loss, alveolar bone density and second metacarpal bone density, salivary and gingival crevicular fluid interleukin-6 concentrations in healthy premenopausal and postmenopausal women on estrogen therapy.

BACKGROUND: Osteoporosis is an age-related metabolic bone disease characterized by decreased mass and increased susceptibility to fracture. The literature suggests a relationship between oral bone loss and skeletal osteoporosis; however, most studies have produced conflicting results. The purpose of this study was to determine if a relationship exists among alveolar bone loss, alveolar bone density, second metacarpal density, salivary and gingival crevicular fluid interleukin 6 (IL-6), and IL-8 concentrations in premenopausal and postmenopausal healthy women receiving estrogen therapy. METHODS: Twenty-eight healthy women (aged 23-78) were evaluated for this study. A vertical bitewing and hand radiographs were taken, and the subjects were evaluated for the presence of active periodontitis. The bitewing and hand radiographs were digitized, and measurements were made from the cemento-enamel junction to the alveolar crest from both arches. Bone density was evaluated in the maxillary and mandibular alveolar process and at the mid-shaft of the second metacarpal. Percent cortical area and the moment of inertia measurements were also determined. Stimulated whole saliva was collected for a 5-min period using a cube of paraffin as a stimulant and was analyzed for total protein by a colorimetric reaction and IL-6 and IL-8 by ELISA. RESULTS: The results of the study showed that postmenopausal women on estrogen therapy had more alveolar bone loss, more missing teeth, and reduced alveolar and second metacarpal bone density than premenopausal women. In addition, postmenopausal women on estrogen therapy had higher salivary IL-6 concentrations than premenopausal women. Alveolar bone densities were also strongly correlated to second metacarpal densities. CONCLUSIONS: The results of the study suggest that changes in alveolar bone density and levels of bone resorptive cytokines in saliva may be secondary to changes in menopausal status. These changes may predispose loss of alveolar bone with resultant loss of teeth.

Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women.

BACKGROUND: Recent investigations have demonstrated that parotid salivary dysfunction is not a normal process of aging, but may be the consequence of systemic conditions and their treatment, including medications and menopause. The purpose of this study was to assess longitudinally the influence of age, menopausal status, hormone replacement therapy, and other medications on stimulated parotid flow rates (SPFRs) in healthy women. METHODS: Medical diagnoses, menopausal status, medication utilization, and 2% citric acid stimulated parotid salivas were collected from 396 women, aged 21 to 96 years, from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) over a 17-year span by three investigators. RESULTS: There was no overall longitudinal effect of time on SPFR. Age at first visit was a significant predictor of a decrease in SPFR when adjusted for time and xerostomic medications. However, the deleterious effect of taking one xerostomic medication was equivalent to approximately 14 years of aging. Menopausal status and hormone replacement therapy were not consistently associated with diminished SPFR. CONCLUSIONS: These results suggest that menopause and hormone replacement therapy are not associated with parotid salivary dysfunction. Aging may have a statistically significant yet small deleterious influence on SPFR; however, the adverse influence of xerostomic medications is much larger.

Cigar, pipe, and cigarette smoking as risk factors for periodontal disease and tooth loss.

BACKGROUND: Our purpose was to test the hypotheses that cigar and pipe smoking have significant associations with periodontal disease and cigar, pipe, and cigarette smoking is associated with tooth loss. We also investigated whether a history of smoking habits cessation may affect the risk of periodontal disease and tooth loss. METHODS: A group of 705 individuals (21 to 92 years-old) who were among volunteer participants in the ongoing Baltimore Longitudinal Study of Aging were examined clinically to assess their periodontal status and tooth loss. A structured interview was used to assess the participants' smoking behaviors with regard to cigarettes, cigar, and pipe smoking status. For a given tobacco product, current smokers were defined as individuals who at the time of examination continued to smoke daily. Former heavy smokers were defined as individuals who have smoked daily for 10 or more years and who had quit smoking. Non-smokers included individuals with a previous history of smoking for less than 10 years or no history of smoking. RESULTS: Cigarette and cigar/pipe smokers had a higher prevalence of moderate and severe periodontitis and higher prevalence and extent of attachment loss and gingival recession than non-smokers, suggesting poorer periodontal health in smokers. In addition, smokers had less gingival bleeding and higher number of missing teeth than non-smokers. Current cigarette smokers had the highest prevalence of moderate and severe periodontitis (25.7%) compared to former cigarette smokers (20.2%), and non-smokers (13.1%). The estimated prevalence of moderate and severe periodontitis in current or former cigar/pipe smokers was 17.6%. A similar pattern was seen for other periodontal measurements including the percentages of teeth with > or = 5 mm attachment loss and probing depth, > or = 3 mm gingival recession, and dental calculus. Current, former, and non- cigarette smokers had 5.1, 3.9, and 2.8 missing teeth, respectively. Cigar/pipe smokers had on average 4 missing teeth. Multiple regression analysis also showed that current tobacco smokers may have increased risks of having moderate and severe periodontitis than former smokers. However, smoking behaviors explained only small percentages (<5%) of the variances in the multivariate models. CONCLUSION: The results suggest that cigar and pipe smoking may have similar adverse effects on periodontal health and tooth loss as cigarette smoking. Smoking cessation efforts should be considered as a means of improving periodontal health and reducing tooth loss in heavy smokers of cigarettes, cigars, and pipes with periodontal disease.

Effect of estrogen deficiency on skeletal and alveolar bone density in sheep.

BACKGROUND: This study provides a longitudinal assessment of changes in alveolar and skeletal bone mineral density (BMD) in ovariectomized animals. METHODS: Following ovariectomy (OVX) (n = 6) or sham-operation (n = 6) intraoral radiographs were made at 4-month intervals and serum 17-beta-estradiol, osteocalcin, and interleukin (IL)-6, urinary deoxypyridinium, and salivary IL-6, deoxypyridinium, and osteocalcin concentrations were evaluated. Twelve months after surgery, animals were sacrificed and the mandible and radius/ulna removed. Bones were sectioned and radiographed. Mean BMD and cortical thicknesses were calculated from each region. RESULTS: OVX animals had a progressive decrease in serum 17-beta-estradiol, increased serum osteocalcin and IL-6, urinary deoxypyridinium and salivary IL-6, osteocalcin and deoxypyridinium (P < 0.001), suggesting that they were becoming osteoporotic. The BMD of the radius/ulna and mandibular alveolar bone was significantly reduced in OVX animals (P < 0.05 and P < 0.001, respectively). Reduced alveolar bone BMD became evident in OVX animals 6 months after surgery and became more severe during the subsequent 6 months. Alveolar crestal height was also significantly reduced in OVX animals (P < 0.001). These biochemical and density changes preceded a significant reduction in serum 17-beta-estradiol, which occurred between 4 and 8 months following surgery. CONCLUSIONS: Serial measurements of alveolar BMD predicts loss of skeletal BMD in OVX sheep. Changes in alveolar BMD precede estrogen deficiency, suggesting that early signs of reduced BMD may be detected in peri-menopausal women. The presence of biomarkers of bone metabolism within saliva and their correlation with reduced BMD suggests that saliva could be used as an adjunct screening method for assessment of skeletal bone density.

Alveolar bone loss one year following ovariectomy in sheep.

There is little information concerning the incidence of alveolar bone loss in estrogen-deficient women. Ovariectomized sheep are valid models for study of the effects of estrogen deficiency on bone metabolism. The objective of this study was to compare alveolar bone loss in control (C) and ovariectomized sheep (OVX) at 3 and 12 months following surgery. OVX animals had decreased serum levels of 17-beta-estradiol and increased serum levels of osteocalcin, IL-6, and urinary levels of deoxypyridinoline which, taken together, suggest development of osteoporosis. The mean probing depths and percentage of sites with pocket depths 4 to 6 mm and > 6 mm were significantly greater in OVX than C at each time period and in OVX were significantly greater at 12 months that at 3 months. Gingival tissue interleukin-6 (IL-6) levels (but not the number of IL-6(+) cells) were elevated adjacent to deep periodontal pockets; however, there was no significant elevation of levels of the proinflammatory cytokines IL-1 beta and IL-8 within gingiva. Taken together, the data suggest a systemic contribution for progression of periodontal disease associated with estrogen deficiency. This may involve upregulation of systemic IL-6 synthesis and transfer to gingiva in serum, resulting in enhanced IL-6 accumulation within the gingival tissues or reduced bone density allowing for a greater amount of alveolar bone loss.

Sensitivity of various radiographic methods for detection of oral cancellous bone lesions.

OBJECTIVE: The purpose of this study was to determine the effectiveness in diagnosing cancellous bone defects of the following radiographic methods: conventional film, digitized film, enhanced digitized film, direct digital imaging, enhanced direct digital imaging, digital subtraction, and enhanced digital subtraction. STUDY DESIGN: Mechanical lesions of varying depths were generated beneath cadaver molar and premolar mandibular tooth roots. A portfolio of radiographic images of random types and lesion sizes was presented to 20 clinicians, and their diagnoses were evaluated. RESULTS: Positive identification of lesions was significantly improved by enhanced subtraction radiography over all other forms of radiography for the 4-mm lesions and was better than all forms except enhanced digital radiography and film for the 6-mm lesions. Subtraction radiography and enhanced subtraction radiography significantly reduced false positive diagnoses at all lesion sizes in comparison with the other radiographic methods except enhanced digital radiography at the 6-mm lesion size. CONCLUSIONS: For the methods evaluated, only subtraction radiography and enhanced subtraction radiography can significantly improve the clinician's diagnostic abilities for detection of oral cancellous bone lesions through increased rates for detection of existing defects and, even more importantly, through decreased rates of defect misdiagnosis.

Oral contraceptive usage and the expression of CA 15-3 and c-erbB-2 in the saliva of healthy women.

OBJECTIVE: This study was conducted to determine if oral contraceptive use affected the salivary levels of 2 cancer biomarkers, cancer antigen 15-3 (CA 15-3), and c-erbB-2 (erb) among women. STUDY DESIGN: A total of 40 women were recruited for this study, 20 controls and 20 using oral contraceptives. The average ages were 27.4 years (control) and 27.1 years (using estrogen supplements). Stimulated whole saliva specimens were collected from each woman. CA 15-3 levels were determined using enzyme immunoassay (EIA) while c-erbB-2 levels were determined by standard ELISA methods. RESULTS: Findings from this study indicate that there were no significant differences between the control and study groups. CONCLUSIONS: Therefore, saliva may be a useful tool for monitoring women with high estrogen levels due to either tumor load or any treatment regimen, i.e., the levels of the cancer biomarkers CA 15-3 and erb are not affected by increased levels of estrogen in the body.

Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men.

BACKGROUND: The protein c-erb B-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of the c-erb B-2 oncogene may be released from the cell surface and become detectable in patients with a carcinoma of the breast. Consequently, the purpose of this study is to assay soluble c-erb B-2 protein in the saliva of healthy men and women to determine the reliability of the assay. METHODS: To determine the diagnostic utility of this oncogene, we assayed the soluble form of the c-erb B-2 protein in the saliva with an enzyme-linked immunosorbent assay. The study population consisted of 10 healthy women and 9 healthy men who were serially sampled for saliva 3 times a day for a 5-day period. Saliva was collected from each subject at 9 AM, 4 PM, and 9 PM during the 5-day period. RESULTS: We found the presence of c-erb B-2 protein in the saliva of both groups of subjects. The salivary levels of c-erb B-2 were not significantly different when compared for gender differences. Likewise, the results suggest that sampling during various times of the day for salivary c-erb B-2 levels has no effect on marker concentration. Reliability analyses showed that supervised salivary collections were more reliable than unsupervised collections. CONCLUSIONS: The results of this pilot study suggest that the assay for salivary c-erb B-2 protein is reliable and might have potential use in the initial detection and follow-up screening for the recurrence of breast cancer in both men and women.

Salivary function and hypertension: a review of the literature and a case report.

Limited evidence suggests a relationship between the use of antihypertensive medications and reduced salivary function. This article provides a review of the literature concerning the relationship between hypertension, hypertensive therapy and salivary function. A case report is presented to illustrate changes in salivary function in response to different types of antihypertensive medications.

The effect of amalgam overhangs on alveolar bone height as a function of patient age and overhang width.

The purpose of this study was to compare the effects of amalgam restorations with and without overhangs on alveolar bone loss via digitized radiographs for subjects of varying ages and overhang widths. The first phase of this study compared the alveolar bone loss among teeth with clinically acceptable two-surface amalgam restorations with a control surface on the same tooth. The second phase was similar to the first phase with the exception that it compared defective amalgam restorations (those containing amalgam overhanging approximal margins) with the control surface on the same tooth. The collected data showed a significant loss of alveolar bone as a result of amalgam overhang presence (P < 0.02). However, overhang width and patient age did not affect the significance of the detrimental effects of the amalgam overhangs. Overall alveolar bone height was seen to decrease with patient age, independent of amalgam restorations. Digital radiography was seen to be an accurate method for evaluating alveolar bone height changes due to the local environment created by overhanging amalgam margins.

Relationship among stimulated whole, glandular salivary flow rates, and root caries prevalence in an elderly population: a preliminary study.

A comparison of salivary flow rates was made between two groups of healthy, unmedicated, elderly, Caucasian men and women ranging in age from 60 to 90 years. One group was a control group, while the other group had both active and restored root caries. The control group consisted of 69 individuals with a mean age of 73 years. The root caries group consisted of 39 individuals with a mean age of 71 years. The groups were evaluated for unstimulated (UPAR) and stimulated parotid gland flow rates (SPAR), unstimulated (USUB) and stimulated submandibular/sublingual gland flow rates (SSUB), and stimulated whole saliva flow rates (SWhole). Parotid flow rates were determined with the use of a Carlson-Crittenden cup, while submandibular/sublingual flow rates were determined by means of the NIDR collector. A 2% citrate solution was used for stimulation in glandular collections. Subjects chewed a 1-cm3 cube of paraffin to stimulate whole saliva. The results showed that the control group had higher UPAR, SPAR, USUB, SSUB, and SWhole than the root caries group.

Glycogen storage disease and von Willebrand's disease implications for dental treatment: dental management of a pediatric patient.

Glycogen storage diseases (GSD) are metabolic disorders which impair the body's ability to store glucose and utilize it later, requiring patients to take multiple daily dietary supplementation with a high carbohydrate content. Patients undergoing this treatment modality are placed at increased risk for gross dental caries and other oral abnormalities. Additionally, GSD may prolong the patient's bleeding time, which may necessitate consultation with the treating physician. In the following case, our patient required a multidisciplinary approach to address not only her dental needs, but also to coordinate the management of both her GSD and an additional complication, von Willebrand's disease. This was best achieved in a hospital setting.

Salivary sIgA concentrations and stimulated whole saliva flow rates among women undergoing chemotherapy for breast cancer: an exploratory study.

A study was conducted to evaluate the secretion of stimulated whole saliva (SWS) and secretory IgA (sIgA) among three groups of women. One group was a healthy control group, the second group consisted of women diagnosed with metastatic breast cancer before being placed on chemotherapy, while the third group consisted of women on chemotherapy taking CMF (cyclophosphamide, methotrexate, and fluorouracil) for at least one month. There were seven patients in each group. SWS was collected. Salivary sIgA concentrations were determined by enzyme-linked immunoabsorbant assay. The results of the study showed that the mean SWS flow rate for the chemotherapy group (x = 0.96 mL/min) was significantly lower (p > 0.03) than that of the control group (x = 2.33 mL/min) and lower than that of the group with cancer (x = 1.81 mL/min). Additionally, the results showed that the mean sIgA concentrations for the chemotherapy group (x = 10.9 ng/mg of protein) were slightly lower than those of the control group (x = 13.7 ng/mg of protein) and lower than those of the group with cancer (x = 12.6 ng/mg of protein). The results of this study suggest that women placed on CMF for treatment of carcinoma of the breast may have reduced stimulated salivary production.

In vitro evaluation of Midwest Caries ID: a novel light-emitting diode for caries detection.

INTRODUCTION: Traditional detection techniques have limits in diagnosing occlusal caries. Thus, more accurate methods are needed. This study evaluates the ability of the Midwest Caries ID (Midwest) to detect caries. METHODS: Two hundred sixty-four extracted, nonrestored premolars and molars were cleaned and stored in 0.2% sodium azide. Teeth were divided into three groups of 88. One examination site on each occlusal surface was chosen. Each site was inspected by a calibrated examiner via visual, Midwest, and histologic exams. First, a visual exam was performed following the International Caries Detection and Assessment guidelines. Next, the same site was inspected using the Midwest device. Finally, the tooth was sectioned mesiodistally through the site. The half with greater caries progression was visualized under a stereomicroscope (64×). Histologic appearance was scored based on the Downer system. Data were analyzed using Kendall tau-b, partial correlation coefficients, and the receiver operating characteristics curve. RESULTS: Overall, the Midwest scoring assessment correlated with histologic assessments (tau = 0.32; p<0.0001), but the visual exam had a stronger correlation (tau = 0.53; p<0.0001) with the histologic exam. The sensitivity and specificity of the Midwest was also reported at 0.56 and 0.84, compared with 0.92 and 0.43, respectively, for the visual exam. CONCLUSIONS: Midwest Caries ID is a novel caries detection device that has limitations and should not be used as the sole means to detect occlusal caries.

Saliva as a diagnostic fluid.

In the last 10 years, the use of saliva as a diagnostic fluid has become somewhat of a translational research success story. Technologies are now available enabling saliva to be used to diagnose disease and predict disease progression. This review describes some important recent advances in salivary diagnostics and barriers to application and advancement. This review will also stimulate future research activity.

Digital x-ray imaging: a diagnostic aid for the clinician and a technological instrument for the researcher.

Digital x-ray imaging is a relatively new technology which may have potential for both the oral health care practitioner and the oral researcher. The ability to acquire low x-ray dose images is extremely important to patient care. Additionally, the ability to manipulate these images provides valuable clinical and research information which can enhance overall patient care.

Case record analysis: biopsied lesions in a high-risk white and African American Community.

OBJECTIVES: The purpose of this secondary data analysis was to characterize biopsied intraoral lesions documented from neighborhood health center records in a lower socioeconomic biracial community over an eight year period, (1982-1989.) METHODS: A thorough intraoral examination, which included radiographs, was completed by either a general dentist or an oral surgeon. Questionable lesions were referred to and biopsied in the Department of Pathology at Johns Hopkins Medical Center. Biopsied lesions were classified into three groups for analysis: benign, malignant/premalignant, and dental-related. RESULTS: Of 13,317 recorded dental visits, 10,819 (81.2%) visits were made by African Americans. There were 341 lesions biopsied, representing 69 different histologic diagnoses. Of identified lesions, 76.5% were in African Americans; 41.6% were in males, ranging in age from 41 to 94 years old (a mean age of 73 +/- 7 years). Approximately 50% of identified lesions in African American and Whites were benign. Among African Americans, 11.9% of the lesions were malignant premalignant, while 16.3% were among Whites. Within the malignant/premalignant category, squamous cell carcinoma was the most frequently identified malignant lesion. Hyperkeratosis was the most common premalignant lesion type. CONCLUSIONS: Neighborhood health centers can provide a valuable screening service identifying intraoral lesions in vulnerable communities. Future research should explore how socioeconomic factors affect differences in the prevalence of intraoral pathologies among White and African American subgroups as well as other subpopulations.