Validity of 2D lateral cephalometry in orthodontics: a systematic review

Lateral cephalometric radiography is commonly used as a standard tool in orthodontic assessment and treatment planning. The aim of this study was to evaluate the available scientific literature and existing evidence for the validation of using lateral cephalometric imaging for orthodontic treatment planning. The secondary objective was to determine the accuracy and reliability of this technique. We did not attempt to evaluate the value of this radiographic technique for other purposes. A literature search was performed using specific keywords on electronic databases: Ovid MEDLINE, Scopus and Web of Science. Two reviewers selected relevant articles, corresponding to predetermined inclusion criteria. The electronic search was followed by a hand search of the reference lists of relevant papers. Two reviewers assessed the level of evidence of relevant publications as high, moderate or low. Based on this, the evidence grade for diagnostic efficacy was rated as strong, moderately strong, limited or insufficient. The initial search revealed 784 articles listed in MEDLINE (Ovid), 1,034 in Scopus and 264 articles in the Web of Science. Only 17 articles met the inclusion criteria and were selected for qualitative synthesis. Results showed seven studies on the role of cephalometry in orthodontic treatment planning, eight concerning cephalometric measurements and landmark identification and two on cephalometric analysis. It is surprising that, notwithstanding the 968 articles published in peer-reviewed journals, scientific evidence on the usefulness of this radiographic technique in orthodontics is still lacking, with contradictory results. More rigorous research on a larger study population should be performed to achieve full evidence on this topic.     

An in vitro comparison of subjective image quality of panoramic views acquired via 2D or 3D imaging

Objectives

The objective of this study is to compare subjective image quality and diagnostic validity of cone-beam CT (CBCT) panoramic reformatting with digital panoramic radiographs.

Materials and methods

Four dry human skulls and two formalin-fixed human heads were scanned using nine different CBCTs, one multi-slice CT (MSCT) and one standard digital panoramic device. Panoramic views were generated from CBCTs in four slice thicknesses. Seven observers scored image quality and visibility of 14 anatomical structures. Four observers repeated the observation after 4 weeks.

Results

Digital panoramic radiographs showed significantly better visualization of anatomical structures except for the condyle. Statistical analysis of image quality showed that the 3D imaging modalities (CBCTs and MSCT) were 7.3 times more likely to receive poor scores than the 2D modality. Yet, image quality from NewTom VGi® and 3D Accuitomo 170® was almost equivalent to that of digital panoramic radiographs with respective odds ratio estimates of 1.2 and 1.6 at 95% Wald confidence limits. A substantial overall agreement amongst observers was found. Intra-observer agreement was moderate to substantial.

Conclusions

While 2D-panoramic images are significantly better for subjective diagnosis, 2/3 of the 3D-reformatted panoramic images are moderate or good for diagnostic purposes.

Clinical relevance

Panoramic reformattings from particular CBCTs are comparable to digital panoramic images concerning the overall image quality and visualization of anatomical structures. This clinically implies that a 3D-derived panoramic view can be generated for diagnosis with a recommended 20-mm slice thickness, if CBCT data is a priori available for other purposes.     

Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth

Black cohosh is an increasingly popular alternative to estrogen replacement therapy for the relief of menopausal symptoms, primarily hot flushes. However, an important consideration for long-term therapy is potential toxicity and carcinogenicity. Therefore, we undertook a study to assess the estrogenic activity of black cohosh to examine its safety for those with, or at high risk of developing, breast cancer. Several assays were utilized as listed: RNAse protection assays, which ascertain the regulation of the expression of E2-responsive genes; estrogen-responsive-element (ERE)-luciferase, which determines modulation of the ER function by transactivation of the ERE; the Ishikawa cell system, which has an E2-regulated endogenous alkaline phosphatase; and colony formation of ER-expressing breast cancer cells, which indicates possible progression of early stage breast cancer into a more aggressive state. Black cohosh extracts did not demonstrate estrogenic activity in any of these assay systems. This is an encouraging step in the assessment of the safety of black cohosh for treatment of menopausal hot flushes.     

Automated implant segmentation in cone-beam CT using edge detection and particle counting

Purpose

To develop a fully automated, accurate and robust segmentation technique for dental implants on cone-beam CT (CBCT) images.

Methods

A head-size cylindrical polymethyl methacrylate phantom was used, containing titanium rods of 5.15 mm diameter. The phantom was scanned on 17 CBCT devices, using a total of 39 exposure protocols. Images were manually thresholded to verify the applicability of adaptive thresholding and to determine a minimum threshold value \(({T}_{\mathrm{min}})\) . A three-step automatic segmentation technique was developed. Firstly, images were pre-thresholded using \({T}_{\mathrm{min}}\) . Next, edge enhancement was performed by filtering the image with a Sobel operator. The filtered image was thresholded using an iteratively determined fixed threshold \(({T}_{\mathrm{edge}})\) and converted to binary. Finally, a particle counting method was used to delineate the rods. The segmented area of the titanium rods was compared to the actual area, which was corrected for phantom tilting.

Results

Manual thresholding resulted in large variation in threshold values between CBCTs. After applying the edge-enhancing filter, a stable \({T}_{\mathrm{edge}}\) value of 7.5 % was found. Particle counting successfully detected the rods for all but one device. Deviations between the segmented and real area ranged between \(-\) 2.7 and + \(14.4\,\hbox {mm}^{2}\) with an average absolute error of \(2.8\,\hbox {mm}^{2}\) . Considering the diameter of the segmented area, submillimeter accuracy was seen for all but two data sets.

Conclusion

A segmentation technique was defined which can be applied to CBCT data for an accurate and fully automatic delineation of titanium rods. The technique was validated in vitro and will be further tested and refined on patient data.     

Antiestrogenic and DNA damaging effects induced by tamoxifen and toremifene metabolites

The antiestrogen, tamoxifen, has been extensively used in the treatment and prevention of breast cancer. Although tamoxifen showed benefits in the chemotherapy and chemoprevention of breast cancer, epidemiological studies in both tamoxifen-treated breast cancer patients and healthy women indicated that treatment caused an increased risk of developing endometrial cancer. These troubling side effects lead to concerns over long-term safety of the drug. Therefore, it is important to fully understand the relationship between the antiestrogenic and the genotoxic mechanisms of tamoxifen, other antiestrogens, and their metabolites. Previously, we have shown that o-quinone formation from tamoxifen and its analogues, droloxifene and 4-hydroxytoremifene, may not contribute to the cytotoxic effects of these antiestrogens; however, these o-quinones can form adducts with deoxynucleosides and this implies that the o-quinone pathway could contribute to the genotoxicity of the antiestrogens in vivo. To further investigate this potential genotoxic pathway, we were interested in the role of estrogen receptor (ER)(1) alpha and beta since work with catechol estrogens has shown that ERs seem to enhance DNA damage in breast cancer cell lines. As a result, we investigated the binding affinities of 4-hydroxy and 3,4-dihydroxy derivatives of tamoxifen and toremifene to ER alpha and beta. The antiestrogenic activities of the metabolites using the Ishikawa cells were also investigated as well as their activity in ERalpha and ERbeta breast cancer cells using the transient transfection reporter, estrogen response element-dependent luciferase assay. The data showed that the antiestrogenic activities of these compounds in the biological assays mimicked their activities in the ER binding assay. To determine if the compounds were toxic and if ERs played a role in this process, the cytotoxicity of these compounds in ERbeta41(2) (ERbeta), S30 (ERalpha), and MDA-MB-231 (ER(-)) cell lines was compared. The results showed that the cytotoxicity differences between the metabolites were modest. In addition, all of the metabolites showed similar toxicity patterns in both ER positive and negative cell lines, which means that the ER may not contribute to the cytotoxicity pathway. Finally, we compared the amount of DNA damage induced by these metabolites in these cell lines using the comet assay. The catechols 3,4-dihydroxytoremifene and 3,4-dihydroxytamoxifen induced a greater amount of cellular single strand DNA cleavage as compared with the phenols in all cell lines. The different amounts of DNA damage in ER positive and negative cell lines suggested that the ERs might play a role in this process. These data suggest that the formation of catechols represents a minor role in cytotoxic and antiestrogenic effects in cells as compared with their phenol analogues. However, catechols induced more DNA damage at nontoxic doses in breast cancer cells, which implies that o-quinones formed from catechols could contribute to genotoxicity in vivo, which is ER-dependent.     

Cell-based assay for the determination of estrogenic and anti-estrogenic activities

Methods are described for assessing the estrogenic or anti-estrogenic potential of test substances using cultured (human endometrial) Ishikawa cells. This cell line possesses an estrogen-inducible alkaline phosphatase, and estrogenic activity is indicated by assessing by the rate of p-nitrophenol generated from p-nitrophenylphosphate, subsequent to treatment with test compounds. Anti-estrogenic activity is indicated by a decrease in phosphatase activity when the cells are treated with test compounds in the presence of estrogen.     

Evidence that a metabolite of equine estrogens, 4-hydroxyequilenin, induces cellular transformation in vitro

Estrogen replacement therapy has been correlated with an increased risk of developing hormone-dependent cancers. 4-Hydroxyequilenin (4-OHEN) is a catechol metabolite of equilenin and equilin which are components of the estrogen replacement formulation marketed under the name of Premarin (Wyeth-Ayerst). Previously, we showed that 4-OHEN autoxidizes to potent cytotoxic quinoids which can consume reducing equivalents and molecular oxygen, and cause a variety of DNA lesions, including formation of bulky stable adducts, apurinic sites, and oxidation of the phosphate-sugar backbone and purine/pyrimidine bases [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. All of these deleterious effects could contribute to the cytotoxic/genotoxic effects of equine estrogens in vivo. In the study presented here, we studied the oxidative and carcinogenic potential of 4-OHEN and the catechol metabolite of the endogenous estrogen, 4-hydroxyestrone (4-OHE), in the JB6 clone 41 5a and C3H 10T(1/2) murine fibroblast cells. The relative ability of 4-OHEN and 4-OHE to induce oxidative stress was measured in these cells by oxidative cleavage of 2',7'-dichlorodiacylfluorosceindiacetate to dichlorofluoroscein. 4-OHEN (1 microM) displayed an increase in the level of reactive oxygen species comparable to that observed with 100 microM H(2)O(2). In contrast, 4-OHE demonstrated antioxidant capabilities in the 5-50 microM range. With both cell lines, we assessed single-strand DNA cleavage using the comet assay and the formation of oxidized DNA bases, such as 8-oxodeoxyguanosine, utilizing the Trevigen Fpg comet assay. 4-OHEN caused single-strand breaks and oxidized bases in a dose-dependent manner in both cell lines, whereas 4-OHE did not induce DNA damage. Since oxidative stress has been implicated in cellular transformation, we used the JB6 clone 41 5a anchorage independence assay to ascertain the relative ability of 4-OHEN and 4-OHE to act as tumor promoters. 4-OHEN caused a slight but significant increase in the extent of cellular transformation at the 100 nM dose; however, in the presence of NADH, which catalyzes redox cycling of 4-OHEN, the transformation ability of 4-OHEN was dramatically increased. 4-OHE did not induce transformation of the JB6 clone 41 5a in the 0.1-10 microM range. The initiation, promotion, and complete carcinogenic transformation potentials of both metabolites were measured in the C3H 10T(1/2) cells. 4-OHEN demonstrated activity in all stages of transformation at doses of 10 nM to 1 microM, whereas 4-OHE only demonstrated promotional capabilities at the 10 microM dose. These data suggest that oxidative stress could be partially responsible for the carcinogenic effects caused by 4-OHEN and that 4-OHEN is a more potent transforming agent than 4-OHE in vitro.     

The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. In this study, we have compared the chemistry of the major catechol metabolite of equilin (4-hydroxyequilin), which is found in several estrogen replacement formulations, to the equilenin catechol (4-hydroxyequilenin). Unlike endogenous catechol estrogens, both equilin and equilenin were primarily converted by rat liver microsomes to 4-hydroxylated rather than 2-hydroxylated o-quinone GSH conjugates. With equilin, a small amount of 2-hydroxyequilin GSH quinoids were detected (4-hydroxyequilin:2-hydroxyequilin ratio of 6:1); however, no peaks corresponding to 2-hydroxyequilenin were observed in incubations with equilenin. These data suggest that unsaturation in the B ring alters the regiochemistry of P450-catalyzed hydroxylation from primarily 2-hydroxylation for endogenous estrogens to 4-hydroxylation for equine estrogens. 4-Hydroxyequilenin-o-quinone reacts with GSH to give two mono-GSH conjugates and one di-adduct. The behavior of 4-hydroxyequilin was found to be more complex than 4-hydroxyequilenin as conjugates resulting from 4-hydroxyequilenin were detected in addition to the 4-hydroxyequilin-GSH adducts. The mechanism of decomposition of 4-hydroxyequilin likely involves isomerization to a quinone methide which readily aromatizes to 4-hydroxyequilenin followed by autoxidation to 4-hydroxyequilenin-o-quinone. Similar results were obtained with 2-hydroxyequilin, although, in contrast to 4-hydroxyequilenin, 2-hydroxyequilenin does not autoxidize and the reaction stops at the catechol. Since 4-hydroxyequilin is converted to 4-hydroxyequilenin and 4-hydroxyequilenin-o-quinone, similar effects were observed for this equine catechol, including consumption of NAD(P)H likely by the 4-hydroxyequilenin-o-quinone, depletion of molecular oxygen by 4-hydroxyequilenin or its semiquinone radical, and alkylation of deoxynucleosides and DNA by 4-hydroxyequilenin quinoids. Finally, preliminary studies conducted with the human breast tumor cell line MCF-7 demonstrated that the cytotoxic effects of the catechol estrogens from estrone, equilin, and 2-hydroxyequilenin were similar, whereas 4-hydroxyequilenin was a much more potent cytotoxin ( approximately 30-fold). These results suggest that the catechol metabolites of equine estrogens have the ability to cause alkylation/redox damage in vivo primarily through formation of 4-hydroxyequilenin quinoids.     

Comparison of ultimate force revealed by compression tests on extracted first premolars and FEA with a true scale 3D multi-component tooth model based on a CBCT dataset

Clinical Oral Investigations - The aim of this study was to develop a new method for creating a multi-component and true scale 3-dimensional (3D) model of a human tooth based on cone-beam computed...