Suitability of machine learning models for prediction of clinically defined Stage III/IV periodontitis from questionnaires and demographic data in Danish cohorts.

AIM: To evaluate if, and to what extent, machine learning models can capture clinically defined Stage III/IV periodontitis from self-report questionnaires and demographic data. MATERIALS AND METHODS: Self-reported measures of periodontitis, demographic data and clinically established Stage III/IV periodontitis status were extracted from two Danish population-based cohorts (The Copenhagen Aging and Midlife Biobank [CAMB] and The Danish Health Examination Survey [DANHES]) and used to develop cross-validated machine learning models for the prediction of clinically established Stage III/IV periodontitis. Models were trained using 10-fold cross-validations repeated three times on the CAMB dataset (n = 1476), and the resulting models were validated in the DANHES dataset (n = 3585). RESULTS: The prevalence of Stage III/IV periodontitis was 23.2% (n = 342) in the CAMB dataset and 9.3% (n = 335) in the DANHES dataset. For the prediction of clinically established Stage III/IV periodontitis in the CAMB cohort, models reached area under the receiver operating characteristics (AUROCs) of 0.67-0.69, sensitivities of 0.58-0.64 and specificities of 0.71-0.80. In the DANHES cohort, models derived from the CAMB cohort achieved AUROCs of 0.64-0.70, sensitivities of 0.44-0.63 and specificities of 0.75-0.84. CONCLUSIONS: Applying cross-validated machine learning algorithms to demographic data and self-reported measures of periodontitis resulted in models with modest capabilities for the prediction of Stage III/IV periodontitis in two Danish cohorts.

Lewis and AB0 blood group-phenotypes in periodontitis, cardiovascular disease, obesity and stroke.

The AB0 blood group has been linked to ischaemic heart disease, stroke, and periodontal disease, while the Lewis blood group has been linked to ischaemic heart disease and obesity, all of which have been associated with periodontitis. AB0 or Lewis blood group phenotype may therefore constitute common hereditary components predisposing to these disorders. In this study, we investigated if blood group phenotype associated with periodontitis in a subpopulation consisting of 702 participants from a Danish cross-sectional cohort and, secondarily, attempted to confirm their association with hypertension, ischaemic heart disease, stroke, and obesity. No significant association between blood group phenotype and periodontitis was detected, nor were previously reported associations between blood group phenotype and hypertension, ischaemic heart disease, stroke, and obesity confirmed. This may, at least partly, be attributed to differences in study type, outcome definitions, cohort sizes, and population attributable factors. However, our results suggested a strong association between self-reported stroke and the Lewis (a-b-) phenotype (P = 0.0002, OR: 22.28; CI 95: 4.72-131.63).

Impact of Oral Hygiene Discontinuation on Supragingival and Salivary Microbiomes.

The purpose of the present study was to characterize and compare supragingival and salivary microbiotas during a 10-d period of oral hygiene discontinuation. We tested the hypothesis that the composition of the salivary microbiota will reflect local microbial changes associated with accumulated biofilm formation and maturation. Pooled supragingival plaque (n = 145) and stimulated saliva (n = 145) samples were collected and plaque and gingival indices were recorded from 29 orally healthy individuals at baseline, during oral hygiene discontinuation (days 4, 7, and 10), and 14 d after resumption of oral hygiene. Supragingival and salivary microbiotas were processed by next-generation sequencing (Human Oral Microbe Identification using Next Generation Sequencing) and microbial community profiles were compared. Microbial composition of supragingival plaque samples collected after 4, 7, and 10 d of oral hygiene discontinuation, as well as 14 d after reuptake of oral hygiene, differed significantly from baseline samples, by a 3-fold increase in relative abundance Leptotrichia species and a 2-fold decrease in Streptococcus species (adjusted P < 0.01). In saliva samples, a significant increase in relative abundance of Leptotrichia species (adjusted P < 0.01) was evident at day 7 but completely reversed 14 d after resumption of oral hygiene. While the salivary microbiota was resistant to accumulated local biofilm formation, data from this study showed that compositional changes of supragingival microbiotas were not reversed 14 d after resumption of oral hygiene, despite the restoration of plaque to baseline levels. (ClinicalTrials.gov UCPH_OI_002, NCT02913235). Knowledge Transfer Statement: Data from this study showed compositional changes of supragingival microbiotas as a consequence of a 10-d period of oral hygiene discontinuation, that was not reversed 14 d after resumption of oral hygiene. Notably, oral hygiene discontinuation was associated with a significant increase in relative abundance of potential cariogenic Leptotrichia species and a decrease in Streptococcus species. Thus, findings from this study highlight the necessity of regular oral hygiene in the maintenance of oral homeostasis.

Oral erythroplakia-What is it?

Oral erythroplakia is a rare type of lesion, and little is known about the origin of the lesion. It has traditionally been described as the red counterpart of oral leukoplakia, which implies that it is a red lesion that cannot be characterized clinically or pathologically as any other definable lesion. A definition by exclusion is less satisfactory than a positive description to define a lesion, and as erythroplakia probably is related to lichenoid lesions, a new approach to perceive the lesion is proposed based on the clinical features of a fiery red, sharply demarcated lesion situated at a slightly lower level than the surrounding mucosa. Such a definition would probably help clinicians distinguish erythroplakia from other red lesions of the oral mucosa. Although the course of such lesions varies, a significant proportion will develop malignancy, which is why they should be followed at short intervals.

Ligature-associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF-α or RAGE.

There is a bidirectional relationship between periodontal disease (PD) and type 2 diabetes mellitus (T2D). T2D may lead to ecological perturbations in the oral environment, which may facilitate an altered microbiota. However, previous studies have been inconclusive in determining the effect of T2D on oral bacterial profiles. Therefore, we aimed to evaluate the influence of T2D on the ligature-associated bacterial profile in a diabetic rat model with PD and investigated the impact of blocking inflammatory pathways with antibodies targeting either Tumor Necrosis Factor α (TNF-α) or the receptor of advanced glycation end-products (RAGE). A total of 62 Zucker obese rats (45 T2D) and 17 lean (non-T2D) were divided into 4 treatment groups; lean with PD, obese with PD, obese with PD and anti-TNF-α treatment, and obese with PD with anti-RAGE treatment. Periodontal disease was ligature induced. Ligature-associated bacterial profiles were analyzed using Human Oral Microbe Identification Microarray (HOMIM). Ligature-associated bacterial profiles differed between lean and obese rats. Furthermore, treatment with antibodies against TNF-α or RAGE had an impact on subgingival bacterial profiles. T2D phenotypes are associated with different ligature-associated bacterial profiles and influenced by treatment with antibodies against TNF-α or RAGE.

Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1.

BACKGROUND AND OBJECTIVES: Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red blood cells (RBCs). This may protect the bacterium from contact with circulating phagocytes without affecting its viability. MATERIAL AND METHODS: In this in vitro study, we investigated whether human peripheral blood neutrophils from 10 subjects with localized aggressive periodontitis (LAgP) and 10 healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation of ROS in subjects with LAgP in the absence of RBCs. CONCLUSIONS: Our data support that binding to RBCs protects P. gingivalis from ROS and concomitantly enhances neutrophil release of proinflammatory cytokines providing a selective advantage for P. gingivalis growth.

Blockade of RAGE in Zucker obese rats with experimental periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis and type 2 diabetes mellitus (T2D) are two interrelated chronic diseases. Periodontitis is more prevalent in patients with T2D than in healthy subjects, and studies indicate that periodontitis impacts the metabolic control of patients with T2D. Hyperglycemia in T2D leads to the formation of advanced glycation end-products (AGEs). Binding of AGEs to the receptor of AGE (RAGE) elicits an increased inflammatory response that may be a key modulator linking the two diseases. The present study aimed to elucidate the effect of blocking the RAGE on the interrelationship between periodontitis and T2D in a rat model of both diseases. MATERIAL AND METHODS: Zucker obese rats (HsdHlr:ZUCKER-Lepr fa/fa ) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti-RAGE IgG3 were injected into the rats three times a week. The diabetic state was evaluated by oral glucose tolerance tests (OGTTs), the homeostasis model assessment (HOMA), concentration of free fatty acids and repeated measurements of blood glucose. Markers of systemic inflammation, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor α, were evaluated in plasma. Kidney complications were evaluated by quantitative real-time PCR, the creatinine clearance rate, the albumin excretion rate and kidney hypertrophy. Periodontitis was evaluated by morphometric registration of alveolar bone loss and radiographic recording of bone support. RESULTS: The diabetic state was improved by antibody treatment for 4 wk, resulting in a lower area under the glucose concentration curve during OGTTs, lower insulin levels and a lower HOMA. Furthermore, the antibody treatment resulted in milder kidney complications, as evaluated by measuring the albumin excretion rate and the kidney weight. There was no impact of periodontal inflammation on the level of complications. Periodontal bone support was influenced by diabetes, but the altered diabetic status as a result of treatment with anti-RAGE Ig had no effect on periodontitis. CONCLUSION: In this study, treatment with anti-RAGE IgG3 resulted in improved glucose tolerance and attenuated renal complications. However, no effect was observed on the diabetes-associated periodontitis in Zucker obese rats. Furthermore, periodontitis had no effect on diabetic markers or renal complications. Therefore, activation of RAGE is important in the development of T2D.

In vitro complement activation, adherence to red blood cells and induction of mononuclear cell cytokine production by four strains of Aggregatibacter actinomycetemcomitans with different fimbriation and expression of leukotoxin.

BACKGROUND AND OBJECTIVE: The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro-atherogenic, and complement-mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs). MATERIAL AND METHODS: Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence-labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis. The levels of IgG to A. actinomycetemcomitans serotype b were quantified by ELISA, as was consumption of complement. RESULTS: The JP2 clone variants HK 1651 and, to a lesser extent, HK 2092, consumed complement efficiently, while HK 2108 (= strain Y4) consumed complement poorly. Nonetheless, the four tested strains adhered equally well to RBCs in the presence of autologous serum, without causing RBC lysis. The JP2 clone variant HK 2092, selectively lacking LtxA production, induced higher production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 by MNCs than did the other three strains, while the four strains induced similar production of IL-12p70. RBCs facilitated the HK 2092-induced production of TNF-α and IL-1ß, and IL-6 was enhanced by RBCs, and this facilitation could be counteracted by blockade of complement receptor 3 (CD11b/CD18). CONCLUSION: Our data suggest that the JP2 clone of A. actinomycetemcomitans, most closely resembled by the variant HK 1651, activates complement well, while strain Y4, represented by HK 2108, activates complement poorly. However, all strains of A. actinomycetemcomitans adhere to RBCs and, when capable of producing LtxA, prevent production of inflammatory cytokines by MNCs. This "immunologically silent" immune adherence may facilitate systemic spread and atherogenesis.

Bacterial composition in whole saliva from patients with severe hyposalivation--a case-control study.

OBJECTIVE: The purpose of this study was to compare the microbiota of stimulated whole saliva samples from patients with severe hyposalivation to samples from individuals with normal whole saliva flow rates. It was hypothesized that the two groups differ with regard to salivary bacterial profiles. METHODS: This cross-sectional study included 36 participants (24 females and 12 males, mean age 58.5 years) with severe hyposalivation and 36 gender-, age-, and geographically matched participants with normal salivary secretion from the Danish Health Examination Survey (DANHES). The microbiota of stimulated whole saliva samples was characterized by HOMINGS. RESULTS: The two groups had comparable caries experience measured by decayed, missed, filled surfaces/teeth and decayed, missed, filled root surfaces as well as active caries lesions. In addition, no single probe target was present with a significant difference in frequency or proportional presence between groups. Furthermore, data reduction by principal component analysis and correspondence analysis showed comparable bacterial community profiles between groups. CONCLUSIONS: The results indicate that the salivary bacterial profiles of patients with severe hyposalivation do not differ from those of individuals with normal salivary secretion, when there are virtually no untreated active caries lesions present in the oral cavity.

Oral leukoplakia-to treat or not to treat.

Various treatment modalities have been described for reducing or eliminating malignant development of oral leukoplakia, but no treatment has gained universal approval due to lack of randomized clinical studies. At present, it is uncertain whether we can do harm to the patients by treating or by not treating them. An essential aspect is the observation of cancer development even after surgical removal of the clinical lesions. Inadequate resection of the lesions or field cancerization may account for this phenomenon. Another challenge is whether surgical removal of the lesions in fact is associated with a cancer promotional effect resulting in increased risk of cancer. Moreover, unidentified existing cancer in non-suspicious oral leukoplakias may for diagnostic purposes imply that surgical removal is recommendable as well as serial section of all excised tissue. Intensive follow-up programmes for leukoplakias are important, independent of surgical intervention.

Influence of complement on neutrophil extracellular trap release induced by bacteria.

BACKGROUND AND OBJECTIVES: Neutrophil extracellular trap (NET) release has generally been studied in the absence of serum, or at low concentrations of untreated or heat-inactivated serum. The influence of serum complement on NET release therefore remains unclear. We examined the DNA release induced by Staphylococcus aureus and three oral bacteria: Actinomyces viscosus, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum subsp. vincettii. MATERIAL AND METHODS: Bacteria-stimulated NET release from the neutrophils of healthy donors was measured fluorometrically. Various complement containing and complement blocking conditions were used, including heat inactivation of the serum and antibody blockade of complement receptors 1 (CR1, CD35) and 3 (CR3, CD11b/CD18). RESULTS: While the presence of serum markedly enhanced NET release induced by S. aureus, A. actinomycetemcomitans, and to a lesser extent by A. viscosus, there was no enhancement of NET release induced by F. nucleatum. The serum-mediated enhancement of NET release by A. actinomycetemcomitans was neutralized by heat inactivation of serum complement, while this was not the case for S. aureus. Blockade of CR1, significantly reduced NET release induced by S. aureus, A. actinomycetemcomitans and A. viscosus, while blockade of CR3, had no effect. However, opsonization of S. aureus with antibodies may also have contributed to the enhancing effect of serum, independently of complement, in that purified IgG promoted NET release. CONCLUSIONS: In conclusion, complement opsonization promotes NET release induced by a variety of bacteria, including A. actinomycetemcomitans, and CR1 plays a dominant role in the process. Complement consumption or deficiency may compromise NETosis induced by some bacterial species, including A. actinomycetemcomitans. Within biofilms, the complement-inactivating abilities of some bacteria may protect other species against NETosis, while these are more vulnerable when adopting a planktonic lifestyle.

The complement system and its role in the pathogenesis of periodontitis: current concepts.

Periodontitis is a highly prevalent inflammatory disease in tooth supporting tissues, induced by bacteria growing in a biofilm on tooth surfaces. Components of the complement system are present in the periodontal tissue and the system is activated in periodontitis. Continuous complement activation and modulation by bacteria within the biofilm in periodontal pockets, however, may enhance local tissue destruction, providing the biofilm with both essential nutrients and space to grow. A more profound understanding of the mechanisms involved in complement-derived tissue degradation may facilitate the development of new treatment concepts for periodontitis. Further studies on the role of complement in periodontitis pathogenesis may also contribute to the understanding of why some individuals fail to resolve periodontitis. Here, we review evidence that links complement to the pathogenesis of periodontitis with an emphasis on interaction of complement with bacteria from periodontitis-associated biofilm.

Altered bacterial profiles in saliva from adults with caries lesions: a case-cohort study.

The aim of this study was to learn whether presence of caries in an adult population was associated with a salivary bacterial profile different from that of individuals without untreated caries. Stimulated saliva samples from 621 participants of the Danish Health Examination Survey were analyzed using the Human Oral Microbe Identification Microarray technology. Samples from 174 individuals with dental caries and 447 from a control cohort were compared using frequency and levels of identified bacterial taxa/clusters as endpoints. Differences at taxon/cluster level were analyzed using Mann-Whitney's test with Benjamini-Hochberg correction for multiple comparisons. Principal component analysis was used to visualize bacterial community profiles. A reduced bacterial diversity was observed in samples from subjects with dental caries. Five bacterial taxa (Veillonella parvula, Veillonella atypica, Megasphaera micronuciformis, Fusobacterium periodontium and Achromobacter xylosoxidans) and one bacterial cluster (Leptotrichia sp. clones C3MKM102 and GT018_ot417/462) were less frequently found in the caries group (adjusted p value <0.01) while two bacterial taxa (Solobacterium moorei and Streptococcus salivarius) and three bacterial clusters (Streptococcus parasanguinis I and II and sp. clone BE024_ot057/411/721, Streptococcus parasanguinis I and II and sinensis_ot411/721/767, Streptococcus salivarius and sp. clone FO042_ot067/755) were present at significantly higher levels (adjusted p value <0.01). The principal component analysis displayed a marked difference in the bacterial community profiles between groups. Presence of manifest caries was associated with a reduced diversity and an altered salivary bacterial community profile. Our data support recent theories that ecological stress-induced changes of commensal microbial communities are involved in the shift from oral health to tooth decay.

Maxillary sinus floor augmentation with Bio-Oss or Bio-Oss mixed with autogenous bone as graft in animals: a systematic review.

The objective of the present systematic review was to test the hypothesis of no differences between the use of Bio-Oss or Bio-Oss mixed with autogenous bone as graft for maxillary sinus floor augmentation (MSFA) applying the lateral window technique, as evaluated in animals. A MEDLINE (PubMed), Embase, and Cochrane Library search in combination with a hand-search of relevant journals was conducted by including animal studies published in English from 1 January 1990 to 1 June 2010. The search provided 879 titles and 14 studies fulfilled the inclusion criteria. The volumetric stability of the graft improved significantly with increased proportion of Bio-Oss. Bone regeneration, bone-to-implant contact (BIC), biomechanical implant test values, and biodegradation of Bio-Oss after MSFA with Bio-Oss or Bio-Oss mixed with autogenous bone have never been compared within the same study in animals. Thus, the hypothesis of no differences between the use of Bio-Oss and Bio-Oss mixed with autogenous bone as graft for MSFA could neither be confirmed nor rejected based on existing animal studies.

In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis.

Generalized aggressive periodontitis (GAgP) is an inflammatory condition resulting in destruction of tooth-supporting tissues. We examined the production of IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IL-12 and IL-10 in cultures of peripheral mononuclear cells (MNC) from 10 patients with GAgP and 10 controls stimulated with periodontal pathogens or a control antigen, tetanus toxoid (TT) in the presence of autologous serum. The pathogens used were Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, either as type strains or bacteria isolated from the participants' inherent oral flora. The P. gingivalis -induced production of IL-6 was approximately 2.5-fold higher in patients with GAgP than in healthy controls (P < 0.05), while the corresponding TNF-alpha production was non-significantly elevated. IL-1beta production induced by P. gingivalis, as all cytokine responses induced by Pr. intermedia, F. nucleatum and TT was similar in the two groups. A reduced IL-12p70 response to Pr. intermedia and F. nucleatum was observed in smokers compared to non-smoking patients (P < 0.02). To assess the role of serum factors in the elevated IL-6 response to P. gingivalis, MNC from two donors free of disease were stimulated with this bacterium in the presence of the various patient and control sera. An elevated IL-6 and TNF-alpha response was observed in the presence of patient sera (P < 0.01 and P < 0.04, respectively). The data suggest that an exaggerated production of IL-6 occurs in GAgP, and that pro-inflammatory serum factors play an essential role in the response.

Oral premalignant lesions: is a biopsy reliable?

PURPOSE: The purpose of the present retrospective study was to learn whether a biopsy of oral premalignant lesions, leukoplakia and erythroplakia, shows histopathological findings representative of the whole surgically removed lesion. Moreover, to see whether histopathological characteristics of the whole lesion are significant for future malignant development after surgery. MATERIALS AND METHODS: A total of 101 lesions in 96 patients were included, 42 lesions (41%) being homogenous and 50 (50%) non-homogenous leukoplakias, whereas nine (9%) were erythroplakias. The lesions were biopsied and subsequently surgically removed on the average of 10.4 months after biopsy. Surgical specimens were examined in two or more step sections distributed throughout the specimen. The histological findings of the biopsies were compared with those of the whole lesions. After surgical intervention the patients were followed (mean 6.8 years, range: 1.5-18.6), and new biopsies taken in case of recurrences. Smokers (73%) were encouraged to quit smoking and candidal infections were treated. The possible influence of different variables on the risk of malignant development was estimated by means of logistic regression analysis. RESULTS: Histological examination of the whole lesions showed that seven lesions (7%) harboured a carcinoma and 70 lesions (69%) showed a degree of epithelial dysplasia or carcinoma in situ. Eleven lesions (12%) developed carcinoma after a mean follow-up period of 7.5 years. A comparison of the degree of dysplasia in the biopsies with that of the whole lesion demonstrated variation with concurrent diagnosis in 49% of the lesions and in 79% after inclusion of lesions with one degree up or down the scale of epithelial dysplasia. CONCLUSION: The estimated odds ratio showed that none of the associated variables including presence of any degree of epithelial dysplasia in the whole lesion, site, demarcation and smoking had influence on the risk of malignant development.

Is pre-term labour associated with periodontitis in a Danish maternity ward?

OBJECTIVES: To reveal differences in periodontal status and presence of subgingival bacteria in a Scandinavian population of women with pre-term birth compared with women who delivered at term. MATERIALS AND METHODS: Twenty-one women with pre-term labour (before week 35) and 33 women with term labour (between weeks 38 and 41) were included in this case-control study. Periodontal measurements included plaque index (PlI), probing pocket depth (PPD) and bleeding on probing (BOP). Inter-proximal distances from the cemento-enamel junction (CEJ) to the marginal bone crest (MBC) were measured on bitewing radiographs. In 31 patients (16 cases and 15 controls) the subgingival plaque was analysed using "checkerboard" DNA-DNA hybridization. RESULTS: Differences between the two examined groups were found related to "Twin births" (p=0.0064) and "Smokers" (p=0.03). None of the periodontal measurements showed any association. Significant differences were found concerning presence of Tannerella forsythensis, Treponema denticola, Peptostreptococcus micros, Streptococcus intermedius, Streptococcus oralis, Streptococcus sanguis and Capnocytophaga ochracea but when defining sites with >10(5) bacteria as heavily colonized, no statistical difference was found between the two groups. CONCLUSION: A relation between pre-term birth and periodontitis was not revealed in the present study.

Long-term treatment outcome of oral premalignant lesions.

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm(2), and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5-18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm(2) and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1-20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9-11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm(2). No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.

The effect of spironolactone on experimental periodontitis in rats.

BACKGROUND: Elevated levels of tumour necrosis factor (TNF) have been found in patients with adult periodontitis. Animal studies have shown that TNF plays an important role in the pathogenesis of periodontitis. New findings suggest that the aldosterone-inhibitor spironolactone possesses an anti-TNF effect. The purpose of the study was to determine the anti-TNF effect of spironolactone in an endotoxic shock rat model and to disclose the effect of oral administration of spironolactone on the development of experimental periodontitis in rats. METHODS: The study was divided in two parts. Part 1: oral administration of spironolactone (100 mg/kg) followed by intravenous lipopolysaccharide (1 mg/kg) infusion 45 min later. Blood samples were taken before and 90 min after lipopolysaccharide infusion to determine the TNF levels in spironolactone treated and non-treated rats. Part 2: oral administration of spironolactone [100 mg/(kg day)] starting 2 days prior to induction of experimental periodontitis established by peridental ligatures. Morphometrical and radiographical registrations of alveolar bone destruction were carried out to determine the effect of spironolactone on the progression of experimental periodontitis. RESULTS: In part 1 the endotoxic shock model showed a significant reduction in TNF levels in the spironolactone-treated group compared to the non-treated group, suggesting that spironolactone acts as a TNF inhibitor. In part 2 spironolactone-treated rats did not demonstrate significantly less alveolar bone destruction compared to non-treated rats. CONCLUSIONS: The insignificant effect of spironolactone treatment could be explained by the fast metabolism of spironolactone and that spironolactone does not completely inhibit TNF production in rats. Moreover, many other cytokines and mediators involved in alveolar bone destruction may account for the lacking response to spironolactone.