Waranuch Pitiphat

Paan without tobacco: an independent risk factor for oral cancer.

Oral cancer is the second most common cancer in women and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of piper betel leaf that contains areca nut, lime, condiment, sweeteners, and sometimes tobacco, which is also used extensively. We did this study to clarify the independent association of paan and oral cancer. Between July 1996 and March 1998, we recruited biopsy‐proven, primary cases of oral squamous‐cell carcinoma, from 3 tertiary teaching centers in Karachi, Pakistan, and controls pair‐matched for age, gender, hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 cases and 149 controls. Approximately 68% of the cases were men, 49 years old on average, the youngest being 22 years old and the eldest 80. People with oral submucous fibrosis were 19.1 times more likely to develop oral cancer than those without it, after adjusting for other risk factors. People using paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as compared with non‐users, after adjustment for other co‐variates. This study identifies an independent effect of paan without tobacco in the causation of oral cancer. Its findings may be of significance in South Asian communities where paan is used, and among health‐care providers who treat persons from South Asia. Int. J. Cancer 86:128–131, 2000.

Alcohol Consumption Increases Periodontitis Risk

Alcohol consumption impairs neutrophil, macrophage, and T-cell functions, increasing the likelihood of infections. We examined the association between alcohol consumption and periodontitis, prospectively, among 39,461 male health professionals aged 40 to 75 years and free of periodontitis at the start of follow-up. Alcohol intake was assessed at baseline and updated every 4 years by a food-frequency questionnaire. Periodontal disease status was self-reported and validated against radiographs. Multivariate analysis was adjusted for age, smoking, diabetes, body-mass index, physical activity, time period, and caloric intake. During 406,160 person-years of follow-up, there were 2125 cases of periodontitis. Compared with non-drinkers, the relative risk (95% confidence interval) among men reporting usual alcohol intake of 0.1-4.9 g/day was 1.24 (1.09, 1.42); 5.0 to 14.9 g/day, 1.18 (1.04, 1.35); 15 to 29.9 g/day, 1.18 (1.01, 1.38); and > 30 g/day, 1.27 (1.08, 1.49). The results suggest that alcohol consumption is an independent modifiable risk factor for periodontitis.

Factors Associated with Delay in the Diagnosis of Oral Cancer

Early detection and treatment improve the prognosis for oral cancer. Delays from the onset of symptoms to clinical diagnosis are common. Our aim is to identify factors associated with this delay. Between 1995 and 1998, we interviewed 105 consecutive patients with histologically confirmed oral cancer in Greece. If 21 or more days elapsed from the time the patient noticed major symptoms to a definitive diagnosis, we called it a delay (52% of cases). We used logistic and linear regression to estimate odds ratios of delayed diagnosis and to identify correlates of length of delay, respectively. Former smokers had a 4.3 times greater risk of delayed diagnosis compared with current smokers (95% confidence interval: 1.1-17.1). The length of delay was greater among single patients, non-smokers, or those with stage IV tumors. Clinicians should be advised that delay in the diagnosis of oral cancer occurs frequently, even in individuals who do not smoke heavily.

Increased physical activity decreases periodontitis risk in men.

Background: Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. Methods: We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40–75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents – METs); the first report of professionally diagnosed periodontitis was considered a case. Results: Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95–0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76–1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (β = −0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. Conclusions: In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health.

Survival analyses of surgical miniscrews as orthodontic anchorage

INTRODUCTION The objectives of this study were to determine the survival rate of titanium surgical miniscrews and the clinical parameters that posed the highest risks for failure. METHODS Ninety-seven titanium surgical miniscrews (diameter, 1.2 mm; length, 8-12 mm) were placed in the maxilla of 49 patients, at either a high level (nonkeratinized area) or a medium level (mucogingival junction), with the 1-stage or the 2-stage surgical technique. Survival time, event of each screw (survival or failure), and 7 clinical parameters were gathered for survival analysis. Age and latency factors were analyzed with t tests. RESULTS The cumulative survival rates were 85% at 6 months and 57% at 1 year. The Kaplan-Meier log rank test indicated significant differences in 3 explanatory variables: surgical stage, level of placement, and tissue response. Cox proportional hazards regression indicated that the 2-stage surgical procedure had a higher risk than the 1 stage. Placement at the high level had a greater risk than placement at the medium level. Inflammatory hypertrophy tissue reaction showed a higher risk than normal or mild inflammation. The t test showed that age and latency period were not significant. CONCLUSIONS Titanium surgical miniscrews can be satisfactorily used as orthodontic anchorage. Controlling some aspects of the surgical protocol could reduce the failure rate.

Red bacterial complex is associated with the severity of chronic periodontitis in a Thai population.

BACKGROUND The distribution of periodontal pathogens differs in various geographic locations and racial/ethnic groups. This study investigated the microbiological features of chronic periodontitis (CP) patients in Thailand. METHODS Subgingival plaque samples from 20 non-periodontitis subjects, 20 patients with mild CP, and 20 patients with moderate to severe CP were examined using polymerase chain reaction (PCR) to identify Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans. RESULTS In the moderate to severe CP patients, there was high prevalence of P. gingivalis (95%), T. forsythia (95%), T. denticola (80%), as well as the red complex (coexistence of all three species at the same lesion) (75%). A. actinomycetemcomitans was detected in only 35% of the patients in this study group. P. gingivalis was detected in as high as 45% of the non-periodontitis controls. CP and disease severity were significantly related to the presence of T. forsythia together with T. denticola and the red complex. The red complex was not found in any non-periodontitis site. CONCLUSION Red complex bacteria were predominant periodontal pathogens of the moderate to severe form of CP in this Thai population. The presence of T. forsythia together with T. denticola, and the red complex species at the same site were significantly associated with the disease severity.

Induction of toll-like receptor expression by Porphyromonas gingivalis.

BACKGROUND Toll-like receptors (TLRs) play pivotal roles in host immune responses and have been suggested to be involved in the development of many infectious diseases. In this study, the mRNA expression levels of TLR2, TLR4, and TLR9 and their relationship with periodontopathic bacteria in periodontal tissue are examined. Furthermore, the mechanism of TLR induction by Porphyromonas gingivalis is investigated in human gingival fibroblasts (HGFs). METHODS Gingival tissue and subgingival plaque samples were collected from 19 patients with chronic periodontitis (CP) and 16 control individuals without periodontitis. Gene expression levels in the tissues and in HGFs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The numbers of periodontopathic bacteria were determined by quantitative real-time PCR. RESULTS The expression levels of TLR2 and TLR9 were significantly higher in the tissues of patients with CP compared to the tissues of control individuals. The mRNA levels of TLR2 and TLR9, but not TLR4, were positively correlated with the number of P. gingivalis in subgingival plaque. P. gingivalis sonicated extract, P. gingivalis lipopolysaccharide, P. gingivalis DNA, and tumor necrosis factor-α(TNF-α) could significantly upregulate the mRNA expression of TLR2 in HGFs. Furthermore, P. gingivalis-mediated TLR2 expression was suppressed by TNF-α antibody. CONCLUSIONS This study suggests that P. gingivalis infection induces TLR2 and TLR9 upregulation in patients with CP. P. gingivalis-induced TLR2 expression in HGFs is partially dependent on TNF-α and may lead to sensitization of HGFs to bacterial components encountered in the periodontal microenvironment.

Modulation of Wnt5a Expression by Periodontopathic Bacteria

Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.

Periodontitis and Gestational Diabetes Mellitus in Non-Smoking Females

BACKGROUND Chronic inflammation has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Periodontal disease is associated with increased levels of inflammatory mediators and may be a risk factor for GDM. The authors aimed to examine the association between periodontitis and GDM among non-smoking pregnant females. METHODS This case-control study included 50 females who were diagnosed with GDM and 50 age- and hospital-matched females without diabetes in Khon Kaen, Thailand. Full-mouth periodontal examinations were performed during pregnancy by two calibrated dentists who were unaware of the case-control status. Periodontitis was defined as ≥1 site with probing depth (PD) ≥5 mm and clinical attachment level (CAL) ≥2 mm at the same site. Serum samples were collected to measure C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Analyses were performed using conditional logistic regression. RESULTS Fifty percent of the case females had periodontitis compared to 26% of the controls. Females with GDM had significantly higher mean PD and CAL, more sites with bleeding on probing, and increased levels of CRP compared to the controls. Periodontitis was significantly associated with GDM (odds ratio = 3.00, 95% confidence interval = 1.19 to 7.56). The association remained significant with additional adjustment for family history of diabetes, prepregnancy body mass index, and weight gain during pregnancy. CONCLUSIONS The results suggest that periodontitis is associated with GDM. Therefore, clinicians should assess periodontal conditions of pregnant females.

Trefoil Factors in Saliva and Gingival Tissues of Patients With Chronic Periodontitis

BACKGROUND Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis. The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme-linked immunosorbent assay and immunohistochemical methods were used to evaluate the expression of TFFs (TFF1, TFF2, and TFF3) in saliva and gingival tissues, respectively. Periodontopathic bacteria were quantified by real-time polymerase chain reaction. RESULTS Reduced salivary TFF1 and TFF3 concentrations were observed in patients with CP (P = 0.003 and P <0.001, respectively). Decreased TFF3 expression in gingival tissues of patients with CP was demonstrated (P = 0.041). Levels of salivary TFF3 concentrations were negatively correlated with periodontal pathology and number of Porphyromonas gingivalis and Tannerella forsythia (formerly known as Bacteroides forsythus). CONCLUSIONS Altered expression of TFFs in saliva and gingival tissues was detected in patients with CP. The results suggest that TFF3 may be involved in the pathogenesis of periodontal disease.