11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours.

Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV - tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1-0.6). A subpopulation of tumours (n=69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be amplified at 11q13 (OR=6.5, 95% CI=1.8-23.9). As HPV+ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway.

Factors related to oral hygiene in persons with scleroderma.

OBJECTIVES: The purpose of this study was to assess potential risk factors for the development of poor oral hygiene and increased dental caries in individuals with scleroderma. METHODS: Twenty-two subjects with scleroderma participated in this study. All subjects were examined with the Patient Hygiene Performance (PHP) Index, which assesses the extent of plaque and debris over a tooth surface. In addition, oral aperature, xerostomia and dominant upper extremity strength, motion, skin thickness, and dexterity were measured. RESULTS: None of the subjects had good or excellent hygiene. Fifteen subjects had fair oral hygiene and seven subjects had poor oral hygiene as measured by the PHP Index. Significant differences were seen between these two groups for oral aperture, percentage of teeth with caries, skin thickness, dexterity and finger flexion. Dexterity and joint motion correlated significantly with the number of decayed surfaces and number of caries. Oral aperture correlated with the PHP Index and the number of dental caries. CONCLUSIONS: Subjects with poor oral hygiene required more time to complete manual dexterity task and had decreased hand strength and joint motion. Moreover, these same subjects had more contractures, scars, ulcers, and higher skin scores (more disease activity) than subjects in the fair hygiene group. In addition to frequent dental exam and routine cleaning, dental personnel may want to consider exercises to increase oral aperature and investigate toothbrush and dental floss selection used by persons with scleroderma.

Type 1 diabetes mellitus and oral health: assessment of coronal and root caries.

OBJECTIVES: The oral health of a large cohort of adult insulin-dependent diabetic patients (Type 1), diagnosed 24 years previously with juvenile onset, was comprehensively assessed. This paper describes the prevalence of coronal and root caries in this adult Type 1 diabetic population and evaluates demographic, dietary, behavioral, physiologic, salivary and medical variables associated with decayed and filled surfaces in the crown (DFS) or root (RDFS). METHODS: Type 1 diabetes mellitus subjects participating in this oral health evaluation had been monitored for 6-8 years as participants in the University of Pittsburgh, Department of Epidemiology, longitudinal study of medical complications associated with diabetes. Four hundred and six diabetic subjects received a comprehensive oral health examination during one of their regularly scheduled medical visits. Oral assessments included coronal and root caries, missing teeth, edentulism, periodontal status, soft tissue pathologies, salivary function and health behaviors. Sixteen diabetic subjects and one control subject were edentulous. Coronal and root caries data from the remaining 390 dentate diabetic subjects were compared with 202 dentate nondiabetic control subjects. RESULTS: The adult Type 1 diabetic subjects were not found to have significantly higher DFS rates as compared with our control subjects or published age-adjusted NHANES III findings. Both control and diabetic subjects had low decayed to filled tooth surface ratios. A linear regression model evaluated possible associations with coronal decayed and filled tooth surfaces (DFS) within the diabetic population. Significant factors included older age, women, fewer missing teeth, more frequent use of dental floss, more frequent visits to the dentist during the last 12 months, and diabetic nephropathy. The prevalence of RDFS was higher in the diabetic subjects as compared to recruited control subjects. Neither dietary behaviors nor glycemic control were found to contribute to coronal or root caries. CONCLUSIONS: Factors associated with presence of coronal and root caries and fillings are discussed. Possible causes and implications for the association between DFS and diabetic nephropathy are provided.

Insulin-dependent diabetes mellitus and oral soft tissue pathologies. I. Prevalence and characteristics of non-candidal lesions.

OBJECTIVE: A large epidemiologic study on oral health has found that several oral soft tissue lesions were more prevalent in subjects with insulin-dependent diabetes mellitus than in control subjects without diabetes. Our objective in part I of this article is to characterize those lesions not associated with Candida. STUDY DESIGN: This cross-sectional study determined the prevalence and characteristics of oral soft tissue diseases identified during a comprehensive oral evaluation of 405 adult subjects with diabetes and 268 control subjects without diabetes. RESULTS: Twenty specific oral soft tissue lesions were identified. Nearly twice as many subjects with diabetes as subjects without diabetes were found to have one or more oral soft tissue lesions (44.7% vs 25.0%; P <.0001). Subjects with diabetes also had significantly higher prevalence rates for 7 lesions, 3 of which were non-candidal: fissured tongue, irritation fibroma, and traumatic ulcers. (Four lesions generally associated with Candida infection-median rhomboid glossitis, denture stomatitis, generalized atrophy of the tongue papillae, and angular cheilitis-will be described in part II of this article.) There were no differences found between the subjects with diabetes and the control subjects for lichen planus, gingival hyperplasia, or salivary gland disease. CONCLUSIONS: Oral soft tissue lesions were seen more frequently in subjects with insulin-dependent diabetes than in the control subjects. Characterization of 3 non-candidal lesions suggests that they are associated with trauma, delayed healing, or both.

Insulin-dependent diabetes mellitus and oral soft tissue pathologies: II. Prevalence and characteristics of Candida and Candidal lesions.

OBJECTIVE: To assess the prevalence of Candida albicans and oral infection with Candida in patients with insulin-dependent diabetes mellitus (IDDM). STUDY DESIGN: This cross-sectional study compared the prevalence of candidiasis in 405 subjects with IDDM and 268 nondiabetic control subjects. Assessments included evidence of clinical manifestations of candidiasis and a quantitative measure of Candida pseudohyphae in a cytologic smear from the midline posterior dorsal tongue. RESULTS: More subjects with IDDM than control subjects without IDDM (15.1% vs 3.0%) were found to have clinical manifestations of candidiasis, including median rhomboid glossitis, denture stomatitis, and angular cheilitis. IDDM subjects were also more likely to have any Candida pseudohyphae in their cytologic smears (23.0% vs 5.7%; P <.0001), as well as pseudohyphae counts of >10/cm(2) (7.1% vs 0.8%; P <.0001). Diabetic subjects with median rhomboid glossitis were more likely to have a longer duration of IDDM and complications of nephropathy and retinopathy. Denture stomatitis was associated with smoking, retinopathy, higher Candida counts, poor glycemic control, and longer duration of IDDM. A multivariate regression analysis found 3 factors to be significantly associated with the presence of Candida pseudohyphae in the subjects with IDDM: current use of cigarettes (odds ratio, 2:4), use of dentures (odds ratio, 2:3), and elevated levels of glycosylated hemoglobin (odds ratio, 1:9). The use of antimicrobials, immunosuppressants, or drugs with xerostomic side effects was not related to the presence of Candida. CONCLUSIONS: Candida pseudohyphae and oral soft tissue manifestations of candidiasis were more prevalent in subjects with IDDM than in control subjects without diabetes. The presence of Candida pseudohyphae was significantly associated with cigarette smoking, use of dentures, and poor glycemic control.

Type 1 diabetes mellitus and oral health: assessment of periodontal disease.

BACKGROUND: The periodontal disease status of 320 dentate adults, diagnosed 23.7 years previously with Type 1 insulin dependent diabetes mellitus, was evaluated. These patients had been monitored at 2-year intervals as part of a large University of Pittsburgh longitudinal study assessing the medical complications associated with insulin dependent diabetes. METHODS: During one of their regularly scheduled medical examinations, a group of 320 adult dentate subjects (mean age of 32.1 years) received a periodontal examination as part of a comprehensive oral health assessment. The oral health assessment collected data regarding demographics, oral health behaviors, tooth loss, coronal and root caries, salivary functions, and soft tissue pathologies. For the periodontal assessments, 3 facial sites (mesial, midcervical, distal) of the teeth in the right maxillary/left mandibular or left maxillary/right mandibular quadrants were evaluated for calculus, bleeding on probing (BOP) and loss of gingival attachment (LOA). RESULTS: Attachment loss was significantly greater for older patients whereas BOP and calculus levels were relatively constant across age categories. Univariate analyses of factors possibly related to extensive periodontal disease (LOA > or =4 mm for at least 10% of sites examined) indicated an association with older age; lower income and education; past and current cigarette smoking; infrequent visits to the dentist; tooth brushing less than once per day; older age of onset; longer duration of diabetes; and the diabetic complication of neuropathy. A multivariate regression model of all possibly significant factors found current cigarette use (odds ratio [OR] = 9.73), insulin dependent diabetes onset after 8.4 years of age (OR = 3.36), and age greater than 32 years (OR = 3.00) explained the majority of the extensive periodontal disease in this group of diabetic patients. CONCLUSIONS: Management and prevention of extensive periodontal disease for Type 1 diabetic patients should include strong recommendations to discontinue cigarette smoking.

Type 1 diabetes mellitus and oral health: assessment of tooth loss and edentulism.

OBJECTIVE: The oral health of an adult population previously diagnosed with juvenile onset insulin dependent-diabetes was comprehensively assessed. The goal of this exploratory cross-sectional evaluation was to described the characteristics related to partial tooth loss edentulism in subjects with Type 1 diabetes mellitus. METHODS: An adult population of 406 Type 1 diabetes mellitus subjects, who had been monitored for 6-8 years as part of a University of Pittsburgh longitudinal study of medical complications associated with diabetes, received an oral health examination for missing teeth, edentulism, coronal and root caries, periodontal status, and oral health behaviors. RESULTS: Of the 406 subjects evaluated, 204 had no missing teeth, 186 had partial tooth loss (1-27 missing teeth), and 16 were edentulous. Patients who had partial tooth loss or who were edentulous were generally older; had lower incomes and levels of education; and had higher rates of nephropathy, neuropathy, retinopathy, and peripheral vascular disease. A logistic regression model found partial tooth loss to be significantly associated with extensive periodontal disease in remaining teeth (OR = 7.35), a duration of diabetes longer than 24 years (OR = 5.32), not using dental floss (OR = 2.37), diabetic neuropathy (OR = 2.29), household income less than $20,000 (OR = 2.21), multiple coronal caries and fillings (OR = 1.98), and bleeding on probing (OR = 1.82). CONCLUSIONS: Although the majority of these adult Type 1 diabetes patients had serious medical complications associated with their diabetes, the possible impact of diabetes mellitus on oral health should be included in their overall management.

Reliability of self-reported heart murmur history: possible impact on antibiotic use in dentistry.

Administration of prophylactic antibiotics to a dental patient with a history of heart murmur, rheumatic fever or mitral valve prolapse should be based on a reliable diagnosis of heart valve disease. The authors conducted a study of 68 diabetic patients who reported having these conditions and found that at least 65 percent of these patients actually had no evidence of a pathological heart murmur during two previous physical examinations. They concluded that a self-reported history of heart valve disease should not be the sole criterion for antibiotic premedication.

Oral candidiasis: clinical manifestations, diagnosis, and treatment.

Oral candidiasis (candidosis) is an infection with multiple manifestations. To prevent prolongation of undiagnosed cases, it is essential that the dental clinicians have an understanding of the etiology, pathogenesis, and treatment of this disease. The learning objective of this article is the identification of the various clinical features of candidiasis. The underlying causes of oral candidiasis include antibiotic therapy, poor denture hygiene, xerostomia, immune deficiencies, diabetes, and some less common conditions. Candidal infection may be superimposed on other mucosal diseases and may disguise the underlying disease. The diagnosis is established using clinical appearance and patient history, and it may require diagnostic tests. A significant segment of the population carries intraoral Candida, without any symptoms of infection, complicating the use of diagnostic tests.

Loss of heterozygosity of the short arm of chromosomes 3 and 9 in oral cancer.

Loss of heterozygosity (LOH) on chromosomes 3p and 9p has been documented in a variety of malignancies, which suggests the presence of tumor suppressor gene loci on these chromosomes. We have studied 77 oral carcinomas for LOH using 16 microsatellite markers distributed over 5 human chromosomes. Fifty-five (71%) of these tumors showed LOH at one or more loci. A significant proportion of LOH at the informative tumors was observed at chromosomes 3p and 9p: 58% and 48%, respectively. A majority of the tumors showed losses at multiple loci on chromosomes 3p or 9p or on both. Our results suggest that tumor suppressor genes located on the short arms of chromosomes 3 and 9 may be involved in the pathogenesis of oral carcinoma. These regions of deletion observed in oral cancers overlap those reported in other neoplasms. However, we did not find any evidence of these changes in tumor margins with early pathological changes.

Microsatellite instability in oral cancer.

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.

Visualization of INT2 and HST1 amplification in oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) develops along a multistep genetic pathway including loss of tumor suppressor genes and alteration of oncogenes. We characterized seven OSCC cell lines by classical and molecular cytogenetic analysis and fresh tumor and adjacent oral mucosa corresponding to three of the cell lines by molecular cytogenetics. We observed homogeneously staining regions (hsrs) in four of the seven cell lines, at 11q13 in three and at 11q23 and in an unidentified marker chromosome in the fourth. Amplification of band 11q13 occurs in 30-60% of head and neck squamous cell carcinomas. To determine whether INT2 and HST1, both located in band 11q13, are amplified in the tissues and cell lines and to confirm the chromosomal location(s) of the amplification, we used dual-color fluorescence in situ hybridization (FISH) with DNA probes for these genes and the chromosome 11 centromere. We report chromosomal localization of INT2/HST1 amplification in OSCC. Coamplification of INT2 and HST1 was detected in the hsrs in cultured tumor cells from the four hsr-containing tumors and in directly harvested tumor cells, which were available from only two of these tumors. Amplification was not present in tumors lacking hsrs or adjacent oral mucosa corresponding to any of the seven tumors. The observation of amplification in fresh tumor cells suggests that the amplification was present in the patients, may play a key role in the development and/or progression of OSCC, and is not due to karyotypic evolution in vitro. The absence of amplification in the adjacent mucosa suggests that 11q13 amplification is a relatively late event in OSCC tumorigenesis.

A monoclonal antibody recognizing Golgi apparatus produced using affinity purified material from a patient with connective tissue disease.

Serum antibodies recognizing the Golgi apparatus have been reported in patients with connective tissue diseases, but little is known of their significance. Serum from a systemic lupus erythematosus patient with polymyositis was found to have high titers of anti-Golgi apparatus antibody. This serum recognized a 64 kD polypeptide in immunoblotting with HEp-2 cells. To verify that the 64 kD polypeptide was associated with the Golgi apparatus and to characterize which Golgi component was recognized, a monoclonal antibody was produced. IgG, isolated from this serum, was used in affinity chromatography to produce purified material which was used to generate a mouse monoclonal antibody. The monoclonal antibody had an indirect immunofluorescent pattern identical to that produced by the patient's serum, and similarly recognized a 64kD polypeptide in immunoblotting. A 59 kD polypeptide was also recognized by the monoclonal antibody, suggesting that the antigens recognized by the monoclonal and serum antibodies may be only partially identical. The antigen appears to be a glycoprotein and an integral component of the Golgi cisternae membranes.

Thermally induced 'nicotine' stomatitis. A case report.

A palatal lesion resembling "nicotine" stomatitis was found in a woman who did not smoke. However, the patient frequently drank extremely hot beverages. After she was instructed to reduce the temperature of the beverages, the lesion almost completely resolved. This suggests that heat was the primary cause of this lesion and also implicates heat as the major cause of nicotine stomatitis.

Odontodysplasia in a pediatric patient: literature review and case report.

A case of a three-year-old Caucasian male with odontodysplasia is presented. Although the etiology of this condition is unknown, this anomaly involves both the mesodermal and ectodermal dental components and results in deficient and abnormal formation of dentin and enamel. The orofacial characteristics and dental findings of the condition are presented in this case report.

Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats.

The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection.

Resolution of candidal lesions of the dorsal rat tongue by ketoconazole.

The purpose of this study was to determine whether the mucosal alterations of the dorsal rat tongue produced by Candida albicans infection were reversible upon treatment with the antifungal drug ketoconazole. Following experimentally-produced infection, 17 rats showed clinical evidence of persistent lesions over a period of 20 weeks. Eight of these animals were then treated with ketoconazole daily for 2 weeks (20 mg/kg/day). Appropriate non-infected controls and ketoconazole-only controls were also maintained. Five weeks after the ketoconazole treatment, all animals were killed and the dorsal tongues evaluated clinically and histologically. Control groups showed no abnormalities. Of the 8 animals in the treated-lesion group, all showed lesional resolution, while only 2 of the 9 animals in the untreated-lesion group showed resolution of their lesions (p = 0.002). These findings indicate that the epithelial changes produced by this candidal isolate for this period of time are reversible.

Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment.

An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique. The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal. A significant number of patients who did not carry C. albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy. The percentage of patients receiving head and neck radiation therapy who carried C. albicans prior to radiation therapy did not differ significantly from matched dental patient controls.