Coronary calcium scoring using virtual non-contrast reconstructions on a dual-layer spectral CT system: Feasibility in the clinical practice.

PURPOSE: To evaluate the clinical applicability of a prototype virtual non-contrast (VNC) reconstruction algorithm based on coronary CT angiography (cCTA) to assess calcified coronary plaques by calcium scoring (CACS). METHODS: Eighty consecutive patients suspected of coronary artery disease were retrospectively included. All patients underwent a cardiac CT using a dual-layer spectral-detector CT system. The standardized acquisition protocol included unenhanced CACS and cCTA. Datasets were acquired using 120 keV. VNC-reconstructions were calculated from the cCTA images at 2.5 mm (VNC group 1), 2.5 of 0.9 mm (group 2), and 0.9 mm (group 3) slice thickness. We compared the Agatston score and Coronary Artery Calcium Data and Reporting System (CAC-DRS) of all VNC reconstructions with the true non-contrast (TNC)-dataset as the gold standard. RESULTS: In total, 73 patients were evaluated. Fifty patients (68.5 %) had a CACS > 0 based on TNC. We found a significant difference in the Agatston score comparing all VNC-reconstructions (1: 1.35, 2: 3.7, 3: 10.4) with the TNC dataset (3.8) (p < 0.001). Correlation analysis of the datasets showed an excellent correlation of the TNC results with the different VNC-reconstructions (r = 0.904-0.974, p < 0.001) with a slope of 1.89-2.53. Mean differences and limits of agreement by Bland-Altman analysis between TNC and group 1 were 83 and -196 to 362, respectively. By using the VNC-reconstructions, in group 1 23 patients (31.5 %), in group 2 10 (13.7 %), and in group 3 23 (31.5 %) were reclassified according to CAC-DRS compared to TNC. Classification according to CAC-DRS revealed a significant difference between TNC and group 1 (p = 0.024) and no significance compared to groups 2 and 3 (p = 0.670 and 0.273). CONCLUSION: The investigated VNC reconstruction algorithm of routine cCTA allows the detection and evaluation of coronary calcium burden without the requirement for an additional acquisition of an unenhanced CT scan for CACS and, therefore, a reduction of radiation exposure.

Dosimetric Comparison Between Helical Tomotherapy and Volumetric Modulated Arc Therapy in Patients With Malignant Pleural Mesothelioma.

AIMS: To carry out a dosimetric comparison and constraints feasibility proof of adjuvant radiotherapy through helical tomotherapy or volumetric modulated arc therapy (VMAT) for malignant pleural mesothelioma patients after pleurectomy/decortication. MATERIALS AND METHODS: Retrospective calculations were carried out on previously acquired simulations. A whole-pleura volume with 50.4 Gy in 28 fractions was prescribed, simulating a no residual tumour situation. Calculations were carried out using an anisotropic analytical algorithm with a 2.0 mm grid. Beam-on time, planning target volume (PTV) coverage, homogeneity index and organ at risk exposure were compared. RESULTS: Sixteen patient plans were calculated per device. Constraints were met overall by both modalities. For helical tomotherapy and VMAT plans, median beam-on times were 13.8 (11.6-16.1) min and 6.4 (6.1-7.0) min; P = 0.006. The median left-sided radiotherapy PTV D98 were 48.1 (48.0-48.8) Gy and 47.6 (46.5-48.3) Gy; P = 0.023. No significant difference for right-sided radiotherapy was found. PTV D2 for left-sided radiotherapy was higher with VMAT (P = 0.014). For right-sided radiotherapy, helical tomotherapy showed higher doses (P = 0.039). No homogeneity index differences for left-sided radiotherapy (P = 1.00) and right-sided radiotherapy (P = 0.598) were seen. Significant organ at risk exposure differences were found on left-sided radiotherapy whole-lung V20, as well as D50 (both P = 0.008). Higher contralateral lung and ipsilateral kidney exposures were found with VMAT plans for both treatment sides. CONCLUSION: Adjuvant radiotherapy after pleurectomy/decortication in malignant pleural mesothelioma patients, with a VMAT- or helical tomotherapy-based platform, is dosimetrically feasible. Lung sparing was mostly improved with helical tomotherapy. Technique selection must be carried out according to availability and clinical criteria.

[Recommendations for unicondylar knee replacement in the course of time : A current inventory]. / Empfehlungen zur unikondylären Schlittenendoprothetik im Wandel der Zeit : Eine aktuelle Bestandsaufnahme.

BACKGROUND: A higher patient satisfaction stands in contrast to higher revision rates of unicondylar knee joint endoprosthetics (UKE) compared to total knee joint endoprosthetics (TKE). Furthermore, old "dogmas" regarding indications and contraindications persist, which is still reflected in the significantly different case numbers. AIM: The aim of this article is to provide an overview of the current literature regarding 1. indication and contraindication (BMI, age, sport, arthrosis of other compartments, ligament status) and 2. the "eternal rival" fixed or mobile bearing for UKE. RESULTS: The choice of the right patient remains essential, even if all the old "dogmas" of contraindications have been relativized or even outdated. Arthroses of the contralateral (in medial UKE correspondingly lateral) compartment and advanced arthroses of the lateral patella facet remain the only persistent contraindications. In contrast, a high BMI, age, chondrocalcinosis, medial patella facet and a defective (but particularly functionally stable) ACL are not contraindications; however, severe obesity is responsible for a significantly higher complication rate and probably a higher rate of loosening. Rather, the experience and thus the number of UKEs of the individual surgeon is decisive for the outcome, to which the discussion about mobile or fixed inlays must also be completely subordinated. CONCLUSION: The indications for UKE can, therefore, be extended with a clear conscience on the basis of literature, and the current 1:10 UKE:TKE ratio in Germany can be shifted significantly.

Improvements of diagnostic accuracy and visualization of vertebral metastasis using multi-level virtual non-calcium reconstructions from dual-layer spectral detector computed tomography.

OBJECTIVE: To evaluate feasibility and diagnostic performance of multi-level calcium suppression in spectral detector computed tomography (SDCT) for assessment of bone metastasis. MATERIALS AND METHODS: Retrospective IRB-approved study on 21 patients who underwent SDCT (120 kV, reference mAs 116) and MRI. Thoracic and lumbar vertebrae (n = 357) were included and categorized as normal (n = 133) or metastatic (n = 203) based on MRI (STIR, T1w, ±contrast). The multi-level virtual non-calcium (VNCa) algorithm computes dynamic soft tissue/calcium pairs allowing for computation of different suppression index levels to address inter-individual variance of prevalent calcium composition weights. We computed images with low, medium, and high calcium suppression indices and compared them with conventional images (VNCa_low/med/high and conventional images (CI)). For quantitative image analysis, regions of interest were placed in normal and metastatic bone. Two readers reviewed the datasets independently in multiple sessions. They determined the presence of vertebral metastases on a per vertebra basis using a binary scale. Statistic assessment was performed using ANOVA with Tukey HSD, Student's T test, and ROC analysis. RESULTS: Attenuation of both normal and metastatic bone was lower in VNCa images than that in conventional images (e.g., CI/VNCa_low, - 46.3 to 238.8 HU/343.3-60.2 HU; p ≤ 0.05). VNCa_low+med improved separation of normal and metastatic bone in ROC analysis (AUC, CI/VNCa_low/VNCa_med = 0.74/0.95/0.98; p ≤ 0.05). In subjective analysis, both sensitivity and specificity were clearly improved in VNCa_low as compared with CI (0.85/0.84 versus 0.78/0.82). Readers showed a good inter-rater reliability (kappa = 0.65). CONCLUSIONS: Multi-level VNCa reconstructed from SDCT improve quantitative separation of normal and metastatic bone and subjective determination of bone metastases when using low to intermediate calcium suppression indices. KEY POINTS: • Spectral detector CT allows for multi-level calcium suppression in CT images and low and medium calcium suppression indices improved separation of normal and metastatic bone. • Thus, multi-level calcium suppression allows to optimize image contrast in regard to dedicated pathologies. • Low-level virtual non-calcium images (index 25-50) improved diagnostic performance regarding detection of metastasis.

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus.

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system.

Activation of ß-catenin signalling leads to temporomandibular joint defects.

Despite extensive research in knee and hip osteoarthritis (OA), the underlying mechanism of temporomandibular joint (TMJ) disorder remains largely unknown. The purpose of this study was to determine whether the constitutive activation of ß-catenin in the middle and deep layers of the articular cartilage can compromise the homeostasis of this tissue in the TMJ. Col2CreERT2 transgenic mice were bred with RosamT/mG reporter mice to determine Cre recombination efficiency. Col2CreERT2 mice were then crossed with ß-cateninflox(ex3)+ mice to generate ß-catenin conditional activation mice, ß-catenin(ex3)Col2ER. TMJ samples were harvested when the mice were 1-, 3- or 6-month-old and evaluated using histology, histomorphometry and immunohistochemistry. ß-catenin(ex3)Col2ER mice were further crossed with Mmp13flox/flox and Adamts5-/- mice to generate (ß-catenin(ex3)/Mmp13)Col2ER and ß-catenin(ex3)Col2ER)/Adamts5-/- double mutant mice to investigate the role of Mmp13 and Adamts5 in the development of TMJ disorder. High levels of Cre-recombination were seen in Col2CreERT2;RosamT/mGmice. Progressive TMJ defects developed in 1-, 3- and 6-month-old ß-catenin(ex3)Col2ER mice, as revealed by histology and histomorphometry. Results further demonstrated that the defects observed in ß-catenin(ex3)Col2ER mice were significantly decelerated after deletion of the Mmp13 or Adamts5 gene in (ß-catenin(ex3)/Mmp13)Col2ER or ß-catenin(ex3)Col2ER/Adamts5-/- double mutant mice. In summary, we found that ß-catenin is a critical gene in the induction of TMJ cartilage degeneration, and over-expressing ß-catenin in TMJ cartilage leads to defects assembling an OA-like phenotype. Deletion of Mmp13 and Adamts5 in ß-catenin(ex3)Col2ER mice ameliorates the development of TMJ defects. This study suggests that Mmp13 and Adamts5 could be potential therapeutic targets for the treatment of TMJ disorders.

Third-generation autofluorescence endoscopy for the detection of early neoplasia in Barrett's esophagus: a pilot study.

In Barrett's esophagus (BE), second-generation autofluorescence imaging (AFI-II) improves targeted detection of high-grade intra-epithelial neoplasia (HGIN) and early cancer (EC), yet suffers from high false-positive (FP) rates. The newest generation AFI (AFI-III) specifically targets fluorescence in malignant cells and may therefore improve detection of early neoplasia and reduce FP rate. The aim was to compare AFI-III with AFI-II for endoscopic detection of early neoplasia in BE. BE patients with endoscopically inconspicuous neoplasia underwent two diagnostic endoscopies (AFI-II/AFI-III) in a single session. End-points: number of patients and lesions with HGIN/EC detected with AFI-II and AFI-III after white-light endoscopy (WLE) and the value of reinspection of AFI-positive areas with WLE and narrow-band imaging. Forty-five patients were included (38 males, age 65 years). Nineteen patients showed HGIN/EC. AFI-II inspection after WLE increased detection of HGIN/EC from 9 to 15 patients (47 to 79%); AFI-III increased detection from 9 to 17 patients (47 to 89%). WLE plus random biopsies diagnosed 13/19 (68%) HGIN/EC patients. One hundred and four abnormal AFI areas were inspected; 23 (22%) showed HGIN/EC. AFI-II increased detection of HGIN/EC from 10 to 18 lesions (43 to 78%). AFI-III increased detection from 10 to 20 lesions (43-87%). FP rate was 86% for AFI-II and AFI-III. Reinspection with WLE or narrow-band imaging reduced FP rate to 21% and 22%, respectively, but misclassified HGIN/EC lesions as unsuspicious in 54% and 31%, respectively. This first feasibility study on third-generation AFI again showed improved targeted detection of HGIN/EC in BE. However, the results do not suggest AFI-III performs significantly better than conventional AFI-II.

Is domestic tap water a risk for infections in neutropenic patients?

BACKGROUND: Home care has become popular in the management of hemato-oncologic patients. Therefore, we conducted a prospective study to assess whether tap water from the domestic environment of neutropenic patients poses a risk for infections from the waterborne pathogens nontuberculous mycobacteria (NTM), Legionella spp., and Pseudomonas aeruginosa. MATERIALS AND METHODS: Tap water samples were taken in the homes of 65 hemato-oncologic patients who were discharged from the hospital whilst neutropenic and had a suspected period of neutropenia of a minimum of 10 days. Selective culture for Legionella, P. aeruginosa, and NTM was performed. Patients who required hospital readmission were monitored for infection with the aforementioned pathogens over the following 3 months. RESULTS: NTM were cultured in 62 (95.4%) households in concentrations from 1 to 1,000 CFU/500 ml. The facultative pathogenic species Mycobacterium chelonae (58.5% of taps) and M. mucogenicum (38.5% of taps) were most frequently detected. Legionella spp. was cultured from six households (9.2%), including five households with L. pneumophila in concentrations from 25 to 2,500 CFU/500 ml. P. aeruginosa was found in seven households (10.8%) in concentrations from 5 to 2,500 CFU/500 ml. While clinical infection with Legionella spp. was not detected in any patients, infection with M. chelonae and P. aeruginosa occurred in one and seven patients, respectively. However, transmission from household water could not be confirmed. CONCLUSION: Although the risk of infection from household water-borne pathogens appears low, preventive measures may be considered on an individual basis in patients with long-term immunosuppression as well as in patients with long-term central-vascular catheterization.

Putative signaling action of amelogenin utilizes the Wnt/beta-catenin pathway.

BACKGROUND AND OBJECTIVE: While it has long been known that amelogenin is essential for the proper development of enamel, its role has generally been seen as structural in nature. However, our new data implicate this protein in the regulation of cell signaling pathways in periodontal ligament cells and osteoblasts. In this article we report the successful purification of a recombinant mouse amelogenin protein and demonstrate that it has signaling activity in isolated mouse calvarial cells and human periodontal ligament cells. MATERIAL AND METHODS: To determine the regulatory function of canonical Wnt signaling by amelogenin, we used TOPGAL transgenic mice. These mice express a beta-galactosidase transgene under the control of a LEF/TCF and beta-catenin-inducible promoter. To investigate in greater detail the molecular mechanisms involved in the beta-catenin signaling pathway, isolated osteoblasts and periodontal ligament cells were exposed to full-length recombinant mouse amelogenin and were evaluated for phenotypic changes and beta-catenin signaling using a TOPFLASH construct and the LacZ reporter gene. RESULTS: In these in vitro models, we showed that amelogenin can activate beta-catenin signaling. CONCLUSION: Using the TOPGAL transgenic mouse we showed that amelogenin expression in vivo is localized mainly around the root, the periodontal ligament and the alveolar bone.

IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways.

OBJECTIVE: Abnormal maturation and ossification of the endplate chondrocytes play a central role in the pathogenesis of degenerative disorders of the cervical spine. It is widely held that insulin like growth factor-1 (IGF-1) stimulates chondrocyte proliferation and inhibits chondrocyte terminal differentiation both in vitro and in vivo. However, the mechanism underlying such regulation is not fully understood. The present study aimed to determine the role of IGF-1 on the mRNA expression of collagen type II, alpha 1 (Col2a1) and matrix metallopeptidase 13 (MMP-13) in rat endplate chondrocytes. The possible pathways that transduce IGF-1 effects such as phosphatidylinositol-3 (PI-3)-kinase (PI3K) and mitogen activated protein kinase (MAPK) were also investigated in these cells. METHODS: Cultured endplate chondrocytes harvested from rat cervical spines were treated with IGF-1 (100ng/ml), and the changes in Col2a1 and MMP-13 mRNA were monitored with real-time polymerase chain reaction (PCR). MMP-13 activity was also assayed. Activation of signaling proteins was evaluated by western blot analysis. Cells were also treated with pharmacological agents that block PI3K and MAPK signaling pathways. RESULTS: IGF-1 increased Col2a1 mRNA expression in rat endplate chondrocytes in a time- and dose-dependent manner. IGF-1 treatment resulted in a fourfold increase of Col2a1 mRNA with the effect maximizing at 24h. In contrast, IGF-1 treatment for 24h caused a roughly 50% reduction in MMP-13 mRNA. Similar effects were seen on the protein levels of type II collagen (col2) and MMP-13. Consistent with these results, IGF-1 also repressed MMP-13 activity. IGF-1 activated both the PI3K and the extracellular signal-regulated kinase (ERK) pathways as evidenced by phosphorylation of either Akt or ERK1/2 (respectively). The PI3K inhibitor Wartmannin significantly inhibited the IGF-1 effect on Col2a1 mRNA expression but did not affect IGF-1-induced repression of MMP-13 expression. In contrast, the ERK/MAPK inhibitor PD98059 significantly inhibited the effect of IGF-1 on MMP-13 mRNA repression and enhanced IGF-1-induced Col2a1 mRNA expression. CONCLUSIONS: In rat endplate chondrocytes the PI3K pathway mainly transduces IGF-1 effect on col2 expression while the ERK pathway mediates IGF-1 effect on MMP-13 expression.

Nebraska experience.

Nebraska agencies and public health organizations collaboratively addressed cyanobacterial issues for the first time after two dogs died within hours of drinking water from a small private lake south of Omaha on May 4, 2004. A necropsy on one of the dogs revealed that the cause of death was due to ingestion of Microcystin toxins. Within two weeks after the dog deaths, state and local officials jointly developed strategies for monitoring cyanobacterial blooms and issuing public health alerts and advisories. Weekly sampling of public lakes for microcystin toxins and cyanobacteria was initiated during the week of May 17, 2004. ELISA laboratory equipment and supplies were purchased to achieve a quick turnaround time for measuring weekly lake samples for total microcystins so that public health advisories and alerts could be issued prior to each weekend's recreational activities. A conservative approach was selected to protect human health, pets, and livestock, which included collecting worst-case samples from cyanobacterial blooms; freezing and thawing of samples to lyse algal cells and release toxins prior to laboratory analysis; and using action levels of 15 ppb and 2 ppb of total microcystins, respectively, for issuing health alerts and health advisories. During 2004, five dog deaths, numerous wildlife and livestock deaths, and more than 50 accounts of human skin rashes, lesions, or gastrointestinal illnesses were reported at Nebraska lakes. Health alerts were issued for 26 lakes and health advisories for 69 lakes. Four lakes were on health alert for 12 or more weeks. The primary cyanobacterial bloom-forming genera identified in Nebraska lakes were Anabaena, Aphanizomenon, and Microcystis. Preliminary assessments of lake water quality data indicated that lower lake levels from the recent drought and low nitrogen to phosphorus ratios may have contributed, in part, to the increased numbers of cyanobacterial complaints and problems that occurred in 2004.

A 26-year experience with surgical management of tetralogy of Fallot: risk analysis for mortality or late reintervention.

BACKGROUND: Over the past decade repair of tetralogy of Fallot (TOF) in infancy has gained favor. It is still uncertain what effect early complete repair will have on survival or late reoperation on the right ventricular outflow tract. METHODS: To assess these outcomes, we reviewed our experience (1971-1997) with 294 patients undergoing operation at one institution. Median follow-up was 10.6 years (range, 0.1 to 26 years), and was complete for 90.2% patients. RESULTS: Primary complete repair was done in 199 patients (68%), and a staged repair in 62 patients (21%). Thirty-three patients had only a palliative procedure. Sixty-eight patients (23.1%) had complex pathologic processes, including pulmonary atresia in 53. Hospital mortality for primary repair was 11.1% (22/199), for staged repair was 17.7% (11/62), and for palliative procedures was 15.5% (16/103 procedures). Since 1990 mortality has been 2.1%, 11.8%, and 0% respectively (p < 0.001), despite younger age at repair (0.6+/-0.1 versus 2.1+/-0.2 years; p < 0.001). Multivariate analysis identified longer period of hypothermic circulatory arrest, pulmonary artery patch angioplasty, earlier year of operation, and closure of the foramen ovale as risk factors for hospital death. For hospital survivors 20-year survival was 98%+/-3% for TOF with pulmonary stenosis and 88%+/-9% for TOF with pulmonary atresia (p=0.09). Reintervention on the right ventricular outflow tract was needed in 14.1% (37/261) patients. Freedom from reintervention on the right ventricular outflow tract at 20 years was 86%+/-4% for TOF with pulmonary stenosis and 43%+/-16% for TOF with pulmonary atresia (p=0.001). For the subgroup TOF with pulmonary stenosis, this was 85%+/-5% after primary repair and 91%+/-8% after staged repair (not significant). At 15-year follow-up, this was 78%+/-10% for patients not older than 1 year at operation compared with 88%+/-4% for older patients (not significant). CONCLUSIONS: Early mortality after primary repair of TOF has significantly improved and late survival is excellent. Primary repair in infancy does not increase risk for reintervention on the right ventricular outflow tract.

The influence of dentine permeability on cytotoxicity of four dentine bonding systems, in vitro.

Dentine adhesives are often placed directly on dentine from which the smear layer has been removed, the thickness of the dentine is minimal and the potential for diffusion of adhesive components into the pulp is greatest. The permeability of the dentine is one factor that should be critical to whether sufficient diffusion of adhesive components occurs to cause damage to pulpal cells. Dentine discs were prepared and divided into those with low-, medium-, and high-permeability. They were then treated with four different dentine adhesives, after which the pulpal side of the dentine was placed in contact with 1 mL of cell-culture medium. The medium was collected at 24 h intervals for 168 h, and was then placed on monolayers of human pulpal fibroblasts for 24 h. The response of the cells was assessed by succinic dehydrogenase activity (MTT method). The results showed that four dentine adhesive systems released sufficient components to cause suppression of cellular metabolism through dentine. High-permeability dentine generally allowed more diffusion of these components, but the effect of dentine permeability depended on the material. On the other hand, the time interval between the application of the bonding agent and collection of the eluant was consistently important for all materials. Materials were most cytotoxic at early intervals, and were generally less cytotoxic at later intervals, although there were exceptions and there was persistent (> 15%) suppression of cellular metabolism even at late (168 h) intervals. The results suggest that application of these materials to dentine, and particularly dentine with high permeability, poses a potential risk to the health of pulpal tissues.

Volume of the internal gap formed under composite restorations in vitro.

OBJECTIVES: The gap that develops at the interface of dentin composite restoration during the polymerization of the resin can be subsequently filled by fluid filtrating from the pulp via the dentinal tubules. This in vitro study was designed to determine the volume of such a gap, at the occlusal floor of class I restoration and as a result of different dentin treatments and restoration procedures. METHODS: Fifty-six human third molars had their pulp chambers first sealed and connected to a hydraulic apparatus permitting microlitre fluid shift recordings. The teeth then received class I cavities of uniform dimensions and were sampled into nine groups for three dentin treatments (bonding with a dentin bonding agent, lining with a resin modified light-cured glass ionomer, lining with a zinc phosphate cement) and three restoration procedures (Bulk placement of the composite material, Multilayer, Indirect inlay). Fluid displacements were recorded during the filling procedures and stopped 30 min after the completion of the restorations. RESULTS: Dentin bonding agent treated cavities consistently presented the smallest gap volumes, followed by the GI and the ZnPO4 lined specimen. Multilayer and Indirect restoration techniques reduced the formation of gaps. CONCLUSIONS: None of the materials or techniques tested assured a gap-free interface and more effort should be directed at increasing the adhesive and sealing properties of restorative materials to be placed on the dentin.

In vitro cytotoxicity and dentin permeability of HEMA.

An in vitro diffusion chamber was used to measure the diffusion of 2-hydroxyethyl methacrylate (HEMA) through etched human dentin disks. Concentrations of HEMA, which diffused through dentin, were measured by ultraviolet spectroscopy, and the effect of initial HEMA concentration, dentin thickness, and back pressure on diffusion were assessed. The cytotoxicity of HEMA was determined using BALB/c 3T3 mouse fibroblasts in direct contact with HEMA for 12 or 24 h. HEMA diffused rapidly through dentin under all conditions, but increased thickness, back pressure, or decreased initial concentration all reduced diffusion. The permeability coefficient of HEMA was approximately 0.0003 cm/min, and diffusion through 0.5 mm of dentin reduced the HEMA concentration by a factor of approximately 6,000 (with 10 cm of H2O back pressure). It was concluded that the risk of acute cytotoxicity to HEMA through dentin was probably low, but that decreased dentin thickness, lack of polymerization, or extended exposure times might increase the risk significantly.

Esthetic restorations for posterior teeth: practical and clinical considerations.

The current abundance of posterior esthetic restorative materials and techniques may be confusing. This paper describes a simple and logical global concept that assists clinicians in choosing the appropriate therapeutic modality according to well-defined clinical criteria. Practical considerations about cavity preparation, base-lining, filling, luting, and finishing procedures are reviewed.

Stratification of composite restorations: systematic and durable replication of natural aesthetics.

A thorough knowledge of the internal structure of natural dentition provides invaluable information for increasing the aesthetic potential in dental restorations. To achieve the optimal aesthetic results, this knowledge must be integrated in a systematic therapeutic procedure. The learning objective of this article is to guide the practitioner in clinical case analysis, evaluation, and the application of a personalized technique of stratification for each individual case in direct composite restorations. The article evaluates treatment demarcations, differences in composite stratification between anterior and posterior teeth, color selection, and the "sandwich technique." The treatment protocol section discusses the element of reference, which can be either an adjacent natural tooth or provisional restorations, permitting the diagnostic study of a more extensive case. The structure of the element of reference is analyzed as to the enamel, dentin, and incisal edge, and replicated. Since light penetration is different in the anterior and posterior dentition, the color stratification must differ accordingly. The "worn" tooth must be distinguished from the "unworn" tooth. In color selection, the luminosity and saturation of the teeth are evaluated first; tint is selected from the element of reference.

Limited sampling models for reliable estimation of etoposide area under the curve.

Limited sampling models are able to estimate the area under the concentration-time curve (AUC) from plasma concentrations measured at only a few time points. The purpose of this study was to establish a model estimating etoposide AUC independently of specific chemotherapy protocols, underlying malignancies, concomitant diseases and age. Pharmacokinetic parameters were measured in 30 patients treated with polychemotherapy including etoposide (80-150 mg/m2). Etoposide analysis was performed by thin layer chromatography and consecutive quantitative sample detection by 252Cf-plasma desorption mass spectrometry. Data from the first 15 patients formed the training set. Based on the training data, five different models were generated, with the multiple regression coefficient r ranging from 0.91 to 0.96. The following model was selected as "most accurate": AUC = 343 (min)C4h(micrograms/ml) + 650(min)C8h(micrograms/ml) + 1252 (min micrograms/mol), where C4h is the plasma concentration of etoposide at 4 h after the end of infusion and C8h at 8 h. This model was validated on the test set, comprising the data of the remaining 15 patients. The mean predictive error (MPE) was -0.2% and the root mean square predictive error (RMSE) was 4.7%. When used for a large number of patients, this practicable and simple model is an instrument for use in prospective studies, to measure a correlation between drug dosage and efficacy or toxicity of the drug.