Family History of MI, Smoking, and Risk of Periodontal Disease.

Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI.

Amelogenin is a cell adhesion protein.

Amelogenin, the major protein component of tooth enamel, is shown to be a cell adhesion protein. Since it had been shown that an amelogenin-containing preparation, Emdogain, possessed cell-adhesive activity, we tested the hypothesis that amelogenin was responsible for cell-adhesive activity. Recombinant amelogenin was found to promote adhesion at less than 15 micro g/60-mm plate and requires divalent cations for activity. While we found that amelogenin does not bind to collagen or heparin under physiological conditions, it was demonstrated previously that amelogenin does bind to hydroxyapatite. The cell-adhesive activity of amelogenin may play a role in development and may provide a partial explanation for the therapeutic effects of Emdogain in periodontal regeneration.

Clinical validation of a new subtraction radiography technique for periodontal bone loss detection.

BACKGROUND: Diagnostic subtraction radiography (DSR) is a new digital radiographic image subtraction method designed to enhance detection of crestal or periapical bone density changes and to help evaluate caries progression in teeth. In this clinical study, the performance of the DSR method was evaluated for its ability to detect periodontal bone loss and was compared with that of conventional evaluation of radiographs and the standardized cephalostat-guided image acquisition and subtraction technique (LRA) which served as the "gold standard." METHODS: In each of 25 subjects with alveolar crestal bone loss created by periodontal surgery, one set of DSR radiographs and one set of LRA radiographs were obtained before and after the surgery. Subtraction images were then generated by both the proprietary DSR and the LRA techniques. Four viewers evaluated the paired film sets and both subtraction image sets using a 5 point confidence scale to determine the presence or absence of crestal bone loss. Receiver operating characteristics (ROC) statistical procedures were applied to analyze the diagnostic accuracy and statistical differences between the three imaging modalities. RESULTS: The DSR subtraction viewing generated an ROC area of 0.882. For 2 of the viewers this represented a statistically significant gain (P <0.05) over the conventional viewing of the radiographs which had an average ROC area of 0.730. In comparison, the LRA method achieved an area of 0.954. The differences between the LRA and the DSR subtraction methods were not statistically significant, but the statistical power for claiming equality was low ranging from 0.2 to 0.6. CONCLUSIONS: The use of the DSR technique in clinical radiographic image acquisition and subsequent subtraction analysis clearly enhanced the accuracy of alveolar crestal bone loss detection when compared to conventional film viewing. Because this methodology is less resource demanding than LRA and the film exposure techniques and computer-based image analysis skills may be acquired with only a few hours of training, the DSR has potential in clinical practice.

Healing in periodontal defects treated by decalcified freeze-dried bone allografts in combination with ePTFE membranes. Assessment by computerized densitometric analysis.

This study quantitatively assessed radiographic changes in alveolar bone density by computer-assisted densitometric image analysis (CADIA) in periodontal defects that were treated with decalcified freeze dried bone allograft (DFDBA) alone or in combination with interproximal expanded polytetrafluroethylene membranes (ePTFE). The radiographic changes where then analyzed for correlation with the clinically assessed changes. The radiographic changes were evaluated on standardized radiographs of treated sites treated prior to, 1 week after surgery, and 6 months post-operatively. 15 patients with one pair of bilateral interproximal periodontal defects of similar morphology and > or = 6 mm in pocket depth participated. Analysis of the changes 6 months after treatment showed that the increases in density in the defect areas that received the graft were significantly greater than the adjacent areas (p < 0.001). These adjacent areas, in contrast, demonstrated significantly larger loss in radiographic density than the defect area (p < 0.001). The placement of DFDBA into the defects produced in itself significant increases in radiographic density, as illustrated by the results of one week which remained at six months. Utilization of ePTFE addition to DFDBA did not lead to additional radiographic gains in the defect area. While at one week the analysis suggested increased resorption by the combined treatment over grafting alone, such differences did not persist at 6 months post-surgery. Analysis comparing CADIA derived values for change with those of the clinical assessment revealed some associations.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of integrin gene expression by substrate adherence.

Under substrate adherent conditions, integrin gene expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins. This report demonstrates a new mechanism that can differentially control the expression of several integrins. When MG-63 osteosarcoma cells are maintained in suspension, up-regulation of several integrin alpha-subunits takes place. Within as little as 4 h, the mRNA levels for both the alpha 2- and alpha 4-subunits are increased 4- and 6-fold, respectively. It was found that mRNA levels for the alpha 2-, alpha 4-, and alpha v-subunits were markedly increased in several differentiated cell lines under nonadherent conditions; however, cells that did not express a given integrin under substrate adherent conditions also did not express this integrin when maintained in suspension. The alpha 5-subunit did not upregulate during suspension growth. By immunocytochemistry, changes in integrin mRNA levels were confirmed at the protein level. Both cytochalasin B and a phorbol ester were found to induce the expression of the alpha 2-subunit, but not the alpha 4- and alpha 5-subunits, in a dose-dependent fashion. Many investigators have documented changes in gene expression that result from changes in "cell shape." These phenomena may result from up-regulation of integrin gene expression induced by the lack of substrate adherence.

Quantitative assay for morphogenesis indicates the role of extracellular matrix components and G proteins.

A quantitative assay for morphogenesis is described that involves counting the organizing centers (swirling patterns) formed by many cultured fibroblasts. Organizing centers, which are found in vivo, represent one of the smallest units of morphogenesis. We show that macroscopically visible organizing centers form by the merger of smaller organizing centers. Parallel orientation of cells on plastic substrata requires cell-cell contact, but organizing centers can develop without cell-cell contact on collagen gels. On collagen gels, the orientation of collagen fibers determines the orientation of cells with respect to one another. Although organizing centers resemble fingerprints, we have shown that a stochastic process determines the spatial orientation of organizing centers. Treatment of transformed cell lines with agents that increase cAMP levels or alter the activity of guanine nucleotide binding proteins resulted in the generation of organizing centers. Cholesterol precursors involved in protein isoprenylation were found to be potent reverse-transformation agents that could alter the two-dimensional morphogenesis of cells. The simple assay described should permit the analysis of morphogenesis at the molecular and cellular levels.

IL-1 beta and prostaglandins regulate integrin mRNA expression.

The purpose of this study was to examine the effects of IL-1 beta on integrin expression in MG-63 human osteosarcoma cells. Human recombinant IL-1 beta (rIL-1 beta) produced significant increases in both alpha 2- and alpha 5-subunit mRNA levels, as well as a smaller increase in alpha v-subunit mRNA. In contrast, IL-1 beta decreased alpha 4-subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL-1 beta differentially regulates expression of integrins. When cultures were treated with both IL-1 beta and the cyclooxygenase inhibitor, indomethacin, the expression of alpha 2-, alpha 5-, and alpha v-subunit mRNA levels were dramatically increased relative to untreated controls; co-treatment with 0.5 mM prostaglandin E2 (PGE2) partially reversed this effect. Indomethacin alone did not affect integrin mRNA levels. Treatment with IL-1 beta or IL-1 beta + indomethacin also induced significant changes in MG-63 morphology (i.e., increased cell elongation) and increased the ability of cells to contract collagen gels. PGE2 reversed the above effects on cell morphology and gel contraction. These findings indicate that (a) IL-1 beta differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL-1 beta, may provide a negative feedback loop which counteracts the stimulatory effect of IL-1 beta on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins.

Relationship between the radiographic periodontal defect angle and healing after treatment.

This study radiographically evaluated the correlation between the changes in alveolar bone level occurring in bony defects after periodontal therapy and the corresponding pretreatment defect angles. The defect angle was defined by the bony defect surface and the root surface. The changes were determined from identically exposed and processed radiographs obtained just prior to surgery and 15 to 18 months later. The defect angle was clearly correlated to the radiographic changes in alveolar bone level. Most defects with an angle less than 45 degree showed a gain of bone while defects with the largest defect angles showed a loss. In addition, defects on root surfaces without furcations showed better healing than defects associated with furcations.

Clinical effects of electromagnetic stimulation as an adjunct to periodontal therapy.

The clinical effects of electromagnetic stimulation (EMS) on periodontal soft tissues and alveolar bone level were studied among 23 patients. The sides of the arch to receive EMS were randomly selected and exposed for a period of eight weeks following periodontal surgery. The contralateral control sides received surgery only. The electromagnetic signal was a multiple pulse signal with 21 asymmetrical quasirectangular pulses per burst and a burst frequency of 16.9 Hz. The peak magnetic field strength reached 0.46 Gauss. Changes from baseline in clinical attachment level, probing depth, and radiographic alveolar bone level were assessed at six, 12, and 18 months postsurgically. A greater gain of clinical attachment level following EMS was observed only for pockets with initial depth of 1 to 3 mm. There were no consistent differences between test (EMS) and control sides in the change of clinical attachment level or probing depth for pockets deeper than 4 mm. Radiographically, the test sides demonstrated statistically significant gain of alveolar bone level compared with the control sides at six months following surgery. Hereafter, the rates of change were similar in the stimulated and unstimulated sides, and the total gain of alveolar bone level remained greater in the test side throughout the observation period. Within the limitations of this study, it was concluded that electromagnetic stimulation does not promote gains in clinical attachment or alveolar bone level to the extent that it can be recommended as an adjunct to conventional periodontal therapy.

Repair of periodontal angular bony defects evaluated by one- and two-dimensional radiographic analysis.

The healing of eighteen angular periodontal bony defects was evaluated radiographically 1 year after treatment. The pretreatment and posttreatment radiographs were exposed and processed in such a way that identical images were obtained. There was no correlation between one- and two-dimensional expressions of healing in such defects, and relative area changes were consistently larger than relative linear changes of the same defects. The area gain of bone was strongly correlated to the following morphologic variables: length of bone surface, original defect area, and height of the defect.

Relief from pain localized to the lower back in early labour. A double blind trial of ketocaine, a new, highly effective, local, cutaneous analgesic (A 2358, Ane-Pad), and placebo.

Pain localized to the lower back in the first stage of labour in 47 primiparous women was treated by epicutaneous application of ketocaine or placebo compresses. Twenty-three patients were treated with ketocaine compresses (Ane-Ped), and 24 patients with compresses soaked with isotonic saline. The pain relieving effect was almost the same in both treatment groups. Pain localized to the lower back was reduced in about 50% of the patients after one hour's application of ketocaine or placebo compresses. Supplementary analgesics had to be administered in about 60% of the patients in each group. No maternal or foetal systemic side effects related to the treatment were registered. Local erythema on the application area was only reported in the ketocaine group. The frequency of feeling of warmth during the application of compresses of ketocaine were high compared to the placebo group, 78% and 29% respectively.