bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Expression of Neuronal Genes Defines Subtypes of Disseminated Neuroblastoma with Favorable and Unfavorable Outcome
Authors: Fischer Matthias , Oberthuer André , Brors Benedikt , Kahlert Yvonne , Skowron Matthias , Voth Harald , Warnat Patrick , Ernestus Karen , Hero Barbara , Berthold Frank
Published: September 2006

Purpose: Identification of molecular characteristics of spontaneously regressing stage IVS and progressing stage IV neuroblastoma to improve discrimination of patients with metastatic disease following favorable and unfavorable clinical courses.

Experimental Design: Serial analysis of gene expression profiles were generated from five stage IVS and three stage IV neuroblastoma. Differential expression of candidate genes was evaluated by real-time quantitative reverse transcription-PCR in 76 pretreatment tumor samples (stage IVS n = 27 and stage IV n = 49). Gene expression-based outcome prediction was determined by Prediction Analysis for Microarrays using 38 tumors as a training set and 38 tumors as a test set.

Results: Comparison of serial analysis of gene expression profiles from stage IV and IVS neuroblastoma revealed ∼500 differentially expressed transcripts. Genes related to neuronal differentiation were observed more frequently in stage IVS tumors as determined by associating transcripts to Gene Ontology annotations. Forty-one candidate genes were evaluated by quantitative reverse transcription-PCR and 18 were confirmed to be differentially expressed (P ≤ 0.001). Classification of patients according to expression patterns of these 18 genes using Prediction Analysis for Microarrays discriminated two subgroups with significantly differing event-free survival (96 ± 6% versus 40 ± 8% at 3 years; P < 0.0001) and overall survival (100% versus 72 ± 7% at 3 years; P = 0.0003). This classifier was the only independent covariate marker in a multivariate analysis considering the variables stage, age, MYCN amplification, and gene signature.

Conclusions: Spontaneously regressing and progressing metastatic neuroblastoma differ by specific gene expression patterns, indicating distinct levels of neuronal differentiation and allowing for an improved risk estimation of children with disseminated disease.
A Molecular Diagnostic Test for Distinguishing Lung Adenocarcinoma from Malignant Mesothelioma Using Cells Collected from Pleural Effusions
Authors: Holloway Andrew J. , Diyagama Dileepa S. , Opeskin Ken , Creaney Jenette , Robinson Bruce W.S. , Lake Richard A. , Bowtell David D.L.
Published: September 2006

Purpose: Patients with malignant mesothelioma or adenocarcinoma of the lung often present with respiratory complications associated with a malignant pleural effusion. Distinguishing between these malignancies is frequently problematic, as many of the clinical, cytologic, and histologic features of the diseases overlap. Following cytologic analysis of pleural effusions, subsequent confirmatory tissue biopsies involve increased patient morbidity and expense. We have therefore designed a gene expression–based test to classify the primary tumor causing a malignant pleural effusion, using cells collected from the effusion itself.

Experimental Design: We have used microarray data for 190 lung adenocarcinomas and 33 malignant mesotheliomas to identify genes differentially expressed between the two diseases. Genes expressed in normal mesothelial cells were removed, allowing the development of a PCR-based test to measure the expression of genes that discriminate between mesothelioma and lung adenocarcinoma from cytology specimens.

Results: Applying an real-time PCR–based assay involving 17 genes to 13 independent samples from biopsy-proven malignant mesothelioma and lung adenocarcinomas resulted in the correct identification of all samples.

Conclusions: We have developed a test that is able to distinguish between lung adenocarcinoma and mesothelioma in cells collected from pleural effusions.
Vascular Endothelial Growth Factor Signaling Pathways: Therapeutic Perspective
Authors: Kowanetz Marcin , Ferrara Napoleone
Published: September 2006

The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis.
Statistical Aspects of Design and Analysis of Clinical Trials for the Prevention of Caries
Authors: Burnside G. , Pine C.M. , Williamson P.R.
Published: September 2006

This paper considers the methods used in design and analysis of recent clinical trials of topical fluoride interventions designed to prevent the development of dental caries in children, with particular consideration given to issues related to cluster-randomized trials. Studies which met the inclusion criteria were recent clinical trials of topical fluoride interventions published since 1990, conducted in children under 16 years of age, with caries as the outcome variable. Papers not published in English were translated. Information was extracted from the published trial reports on the units of randomization and analysis. The papers were also studied to assess if reporting allowed the assessment of potential consent bias in cluster-randomized trials and the reproduction of sample size calculations. Fifteen trials published since 1990 were included, of which five were cluster randomized. Only 1 of the 5 accounted for the clustering in the analysis. For the other four trials, it was possible to calculate that values from 0.002 (for DMFS) and 0.08 (for being caries free) for the intracluster correlation coefficient within schools could result in statistically non-significant findings. 3 of the 5 cluster-randomized trials did not report the consenting procedure in enough detail to judge whether consent bias could be present. Only 1 of the total 15 trials reported a sample size calculation. In summary, researchers should be aware of the importance of correctly analyzing cluster-randomized data and thorough reporting of clinical trials according to the CONSORT guidelines.
Are Mutans Streptococci Detected in Preschool Children a Reliable Predictive Factor for Dental Caries Risk? A Systematic Review
Authors: Thenisch N.L. , Bachmann L.M. , Imfeld T. , Leisebach Minder T. , Steurer J.
Published: September 2006

Research suggests that mutans streptococci play an important role in cariogenesis in children but the usefulness of bacterial testing in risk assessment is unknown. Our objective was to summarize the literature assessing the association of mutans streptococci and dental caries in preschool children, (Pre)Medline (1966–2003), Embase (1980–2003), the Cochrane Register of Controlled Trials (2003, issue 3), and reference lists of included studies were searched. All abstracts found by the electronic searches (n = 981) were independently scrutinized by 2 reviewers. Minimal requirements for inclusion were assessment of preschool children without caries at baseline, reporting of mutans streptococci present in saliva or plaque at baseline and assessment of caries presence after a minimum of 6 months of follow-up. Participants’ details, test methods, methodological characteristics and findings were extracted by one reviewer and cross-checked by another. Homogeneity was tested using χ2 tests. Results of plaque and saliva testing were pooled separately using a fixed effects model. Methodological quality of reports was low. Out of 9 studies included, data from 3 reports on plaque test assessment alone (n = 300) and from 4 reports on saliva test assessment alone (n = 451) were available for pooled analysis. The pooled risk ratio (95% CI) was 3.85 (2.48–5.96) in studies using plaque tests and 2.11 (1.47–3.02) in those using saliva testing. Presence of mutans streptococci, both in plaque or saliva of young caries-free children, appears to be associated with a considerable increase in caries risk. Lack of adjustment for potential confounders in the original studies, however, limits the extent to which interpretations for practice can be made.
Efficacy of Sealing Proximal Early Active Lesions: An 18-Month Clinical Study Evaluated by Conventional and Subtraction Radiography
Authors: Martignon S. , Ekstrand K.R. , Ellwood R.
Published: September 2006

This study assessed the efficacy of sealing proximal lesions on adult patients using a split-mouth design. Eighty-two 15- to 39-year-olds from the Dental Faculties in Copenhagen and Bogotá participated, each having 2 or more proximal lesions in the following radiographic stages: (1) lesion restricted to the outer half of enamel; (2) lesion from the inner half of enamel including the enamel dentine junction, and (3) lesion restricted to the outer third of dentine. Standardized geometrically aligned baseline and follow-up radiographs were obtained. One randomly selected lesion (test) in each patient was sealed with 1 of 2 resins. The patients were instructed to floss all the proximal lesions 3 times per week. The baseline to 18 months difference in caries lesion progression status was assessed using 3 methods: (1) radiographs were independently assessed visually; (2) radiographs were read in pairs, and (3) using subtraction radiography of digitized images. A total of 72 subjects finished the study (12.2% dropout). The compliance concerning flossing was poor (15%). For the repeated examinations kappa was 0.84 for the visual examination, 0.44 for the paired readings and 0.84 for the subtraction examination. Two test lesions and 1 control lesion were restored. For the independent radiograph assessment method 10 and 26% progressed in the test and control group, respectively (p > 0.05); with the paired radiograph method the corresponding data were 22% in the test and 47% in the control groups (p < 0.01). By subtraction radiography 44% of the test group and 84% of the control were judged to have progressed (p < 0.001). The sealing technique was superior to instructing patients to floss, and subtraction radiography appeared to be the most sensitive method for assessing lesion progression.
Xylitol Concentration in Saliva and Dental Plaque after Use of Various Xylitol-Containing Products
Authors: Lif Holgerson P. , Stecksén-Blicks C. , Sjöström I. , Öberg M. , Twetman S.
Published: September 2006

The study consisted of two sets of experiments, one in saliva and one in dental plaque. The xylitol concentration in saliva was determined enzymatically in 12 children (mean age 11.5 years) after a standardised use of various xylitol products: (A) chewing gums (1.3 g xylitol), (B) sucking tablets (0.8 g xylitol), (C) candy tablets (1.1 g xylitol), (D) toothpaste (0.1 g xylitol), (E) rinse (1.0 g xylitol), and (F) a non-xylitol paraffin. Unstimulated saliva was sampled 1, 3, 8, 16 and 30 min after use. The concentration in dental plaque was determined after mouthrinses with contrasting amounts of xylitol (LX = 2.0 g, HX = 6.0 g, and control) and supragingival plaque was collected and pooled after 5, 15 and 30 min. The mean xylitol concentration in saliva at baseline was ≈0.1 mg/ml. All xylitol-containing products resulted in significantly increased levels (p < 0.05) immediately after intake and remained elevated for 8–16 min in the different groups. The highest mean value in saliva was obtained immediately after use of chewing gums (33.7 ± 16.4 mg/ml) and the lowest was demonstrated after using toothpaste (8.2 ± 4.9 mg/ml). No significant differences were demonstrated between chewing gums (A), sucking tablets (B), candy (C) and rinses (E). In dental plaque, the mean values were 8.6 ± 5.4 and 5.1 ± 4.0 mg/ml 5 min after HX and LX rinses. Concerning the higher concentration, the values remained significantly elevated (p < 0.05) during the entire 30-min follow-up. In conclusion, commonly advocated xylitol-containing products gave elevated concentrations of xylitol in unstimulated whole saliva and dental plaque for at least 8 min after intake.
Microbiological Assessment of Occlusal Brown-Spot Lesions in Primary Molars
Authors: Arif N. , Beighton D. , Sheehy E.C.
Published: September 2006

Conventional cultural methods were used to compare the plaque flora and the level of infection of the dentine underlying 51 occlusal brown-spot lesions and 21 sound occlusal sites on the primary dentition. Freshly extracted primary molar teeth were used, and occlusal brown-spot lesions and sound occlusal sites were identified using laser fluorescence (LF) and clinical visual methods. A standardized plaque sample was taken from each site, and an LF score was recorded for one discrete site per tooth. The teeth were carefully opened at each predetermined site to determine the clinical status of the underlying dentine, and samples were collected using a sterile bur. The microbiota of the plaque and dentine samples were enumerated and identified. The mean LF scores for the sound sites and brown-spot lesions were 1.2 and 30.5 (p < 0.001), and all the sound sites exhibited hard sound dentine, but 6 out of 51 brown spots exhibited softened dentine. Overall there was no significant (p > 0.1) difference between the level of infection of the dentine of the sound and brown-spot sites, although some sites in the brown-spot lesions yielded high numbers of bacteria. However, the numbers of bacteria as log10(CFU per sample + 1) ± SE recovered from the plaque above the brown-spot lesions were significantly greater than above the sound sites, i.e. 2.89 ± 0.24 and 0.89 ± 0.33, respectively. These data indicate that brown-spot lesions may be more plaque retentive than sound sites and that they are either arrested or arresting lesions, which may require preventive intervention.
Statherin and Histatin 1 Reduce Parotid Saliva-Promoted Streptococcus mutans Strain MT8148 Adhesion to Hydroxyapatite Surfaces
Authors: Shimotoyodome A. , Kobayashi H. , Tokimitsu I. , Matsukubo T. , Takaesu Y.
Published: September 2006

Small salivary phosphoproteins – statherin (ST) and histatin 1 (HT1) – are found in the acquired enamel pellicle which modulates Streptococcus mutans adhesion onto dental enamel. However, their roles in S. mutans adhesion onto enamel surfaces are still undefined. The aim of this study was to investigate whether and how ST and HT1 affect (i) S. mutans adhesion and (ii) the adsorption of S. mutans adhesion-promoting salivary proteins onto hydroxyapatite (HA) in vitro. We fractionated human parotid saliva by adsorption to HA and further by gel filtration chromatography. Adhesion of [3H]-labeled S. mutans strain MT8148 onto sintered HA plates was promoted significantly (>10-fold) by high-molecular weight glycoprotein fraction (HMWGP), but not by purified ST or HT1. More interestingly, promotion of S. mutans adhesion onto HA by HMWGP was significantly reduced by adding purified ST or HT1 to HMWGP. [3H]-labeled S. mutans adhesion on HA was positively correlated to the [14C]-labeled HMWGP adsorption onto HA, which was also reduced by the addition of purified ST and HT1. Synthetic peptides corresponding to ST and HT1 reduced the parotid saliva-promoted S. mutans adhesion. However, removal of the negative charges in the N-terminal domains of ST and HT1 diminished their inhibitory effects on S. mutans adhesion promoted by parotid saliva. We conclude that ST and HT1 competitively inhibit the adsorption of salivary HMWGP, and thereby reduce S. mutans adhesion onto HA surfaces.
Effects of Human Milk on Adhesion of Streptococcus mutans to Saliva-Coated Hydroxyapatite in vitro
Authors: Wernersson J. , Danielsson Niemi L. , Einarson S. , Hernell O. , Johansson I.
Published: September 2006

Adhesion of bacteria to pellicle-coated tooth surfaces is the first step in biofilm formation on teeth. The aim of this study was to explore whether human milk prevents or promotes adhesion of cariogenic Streptococcus mutans to saliva-coated hydroxyapatite (HA) using an in vitromodel system. S. mutans binding to HA coated with human parotid saliva (s-HA) or human milk was studied, in addition to binding inhibition to s-HA by human milk. S. mutans did not bind to HA coated with milk. S. mutans binding to s-HA was inhibited by milk from 15 (71 %) of 21 women, whereas milk from the remaining 6 mothers enhanced binding of S. mutans to s-HA. Inhibition of S. mutans binding correlated with bacterial binding to s-HA (r = 0.76). Human milk does not mediate adhesion of S. mutans to HA in vitro, but affects adhesion in an individually varying fashion. Phenotypic variations in milk and saliva glycosylation may explain the inhibitory capacity and possibly affect susceptibility to colonization by S. mutans in childhood.
Effect of Weissella cibaria Isolates on the Formation of Streptococcus mutans Biofilm
Authors: Kang M.-S. , Chung J. , Kim S.-M. , Yang K.-H. , Oh J.-S.
Published: September 2006

The objective of this study was to isolate and identify lactic acid bacteria able to inhibit the in vitro formation of Streptococcus mutans biofilm as well as the in vivo formation of oral biofilm. Two strains, CMS1 and CMS3, exhibiting profound inhibitory effects on the formation of S. mutans biofilm and the proliferation of S. mutans, were isolated from children’s saliva and identified as Weissella cibaria by 16S rDNA sequencing. The water-soluble polymers produced from sucrose by the W. cibaria isolates also inhibited the formation of S. mutans biofilm. According to the results of thin-layer chromatographic analysis, the hydrolysates of water-soluble polymers produced by the isolates were identical to those of dextran, forming mostly α-(1–6) glucose linkages. In the clinical study, the subjects mouthrinsed with a solution containing W. cibaria CMS1 evidenced plaque index reduction of approximately 20.7% (p < 0.001). These results indicate that the W. cibaria isolates possess the ability to inhibit biofilm formation, both in vitro and in vivo.
Quantification of Dental Fluorosis Using Fluorescence Imaging
Authors: Pretty I.A. , Tavener J.A. , Browne D. , Brettle D.S. , Whelton H. , Ellwood R.P.
Published: September 2006

Fluorescence imaging hardware and software have been recently employed to assess demineralization due to early dental caries. Dental fluorosis also presents as diffuse surface hypomineralization of enamel and in principle similar measurement methods might be applicable to both. The caries analysis system requires the user to select an area of sound enamel around the lesion so that the affected surface can be reconstructed and the lesion subtracted. Whereas early caries presents as discrete isolated lesions fluorosis is characterized by diffuse opacities covering most of the tooth. Consequently it is difficult to use commercial QLF software for the assessment of fluorosis, as there is typically no sound area of enamel to use for reconstruction. This study describes a fluorescent imaging device capable of recording digital images of the anterior teeth and also software that is able to objectively measure fluorosis area and severity. A convenience sample of 26 subjects with a range of fluorosis from TF scores 0–3 took part in the study. The upper left central incisor of these subjects was scored for fluorosis using the TF index, photographed using a conventional digital camera and imaged using the fluorescence imaging device. The TF index was then used to visually score the digital photographs and the fluorescence images. The data from the fluorescence method demonstrated a strong correlation with TF scores from fluorescence images (Kendall’s tau = 0.862). The fluorescence imaging method shows promise as an objective, potentially blinded system for the longitudinal assessment of enamel fluorosis in vivo.
Influence of Fluoride-Releasing Restorative Material on Root Dentine Secondary Caries in situ
Authors: Hara A.T. , Turssi C.P. , Ando M. , González-Cabezas C. , Zero D.T. , Rodrigues Jr. A.L. , Serra M.C. , Cury J.A.
Published: September 2006

The usefulness of fluoride-releasing restorations in secondary caries prevention may be questioned because of the presence of other common sources of fluoride and because of ageing of the restorations. This study tested the hypothesis that glass-ionomer cement restorations, either aged or unaged, do not prevent secondary root caries, when fluoride dentifrice is frequently used. Sixteen volunteers wore palatal appliances in two phases of 14 days, according to a 2 × 2 crossover design. In each phase the appliance was loaded with bovine root dentine slabs restored with either glass-ionomer or resin composite, either aged or unaged. Specimens were exposed to cariogenic challenge 4 times/day and to fluoridated dentifrice 3 times/day. The fluoride content in the biofilm (FB) formed on slabs and the mineral loss (ΔZ) around the restorations were analysed. No differences were found between restorative materials regarding the FB and the ΔZ, for either aged (p = 0.792 and p = 0.645, respectively) or unaged (p = 1.00 and p = 0.278, respectively) groups. Under the cariogenic and fluoride dentifrice exposure conditions of this study, the glass-ionomer restoration, either aged or unaged, did not provide additional protection against secondary root caries.
The Protective Effect of TiF4, SnF2 and NaF on Erosion of Enamel by Hydrochloric Acid in vitro Measured by White Light Interferometry
Authors: Hove L. , Holme B. , Øgaard B. , Willumsen T. , Tveit A.B.
Published: September 2006

The purpose of this in vitro study was to compare the protective effect of TiF4, SnF2 and NaF (all 0.5 M F) on the development of erosion-like lesions in human dental enamel. Four enamel specimens from each of 6 extracted molars were polished and embedded in epoxy resin. The enamel surfaces of 3 specimens from each tooth were treated with the different fluoride solutions for 2 min. Following fluoride treatments, the specimens were immersed in 0.01 M HCl (pH 2.0), for 2, 4 and 6 min in order to mimic a gastric reflux situation. One specimen from each tooth was used as a control and was only exposed to acid. The etching depths (in micrometres) after 6 min were: TiF4 0.8 (SD 0.8), SnF2 3.5 (SD 0.7), NaF 5.3 (SD 0.4), and 7.0 (SD 0.3) for the control specimens. Compared to the control, TiF4 protected the enamel surface from acid attack almost completely (88%), while SnF2 reduced the etch depth after 6 min by 50% and NaF by 25%.
Salivary Fluoride from Fluoride Dentifrices or Rinses after Use of a Calcium Pre-Rinse or Calcium Dentifrice
Authors: Vogel G.L. , Shim D. , Schumacher G.E. , Carey C.M. , Chow L.C. , Takagi S.
Published: September 2006

The low concentration of available calcium (Ca) in oral fluids limits the formation of Ca-mediated fluoride deposits that maintain oral fluoride (F) after a topical F treatment. The purpose of this study was to examine if a high concentration of Ca would increase salivary F when used before a F rinse or dentifrice. We found that a Ca pre-rinse (150 mmol/l Ca lactate) or Ca dentifrice (0.084 g Ca glycerolphosphate per gram dentifrice) used immediately before a 60 s 228-ppm F rinse (12 mmol/l NaF) produced a 4.6× or 3.6× increase (p < 0.05) respectively in the 1 h salivary F concentrations over the F rinse alone. Reducing the post-Ca F rinse to 10 s still produced a significant 2.2× increase in salivary F compared to the 60 s F rinse alone. Used with a conventional 1,100 ppm F (i.e. 1,100 µg F per gram) NaF dentifrice (Crest), the above Ca pre-rinse increased 1 h salivary F levels by 2.3× over the F dentifrice alone. However, a F rinse given before a Ca rinse produced no increase in 1 h salivary F concentrations. Although the persistence of these increases requires further study, these results suggest that a moderately high concentration of Ca given shortly before a F rinse or F dentifrice may increase the cariostatic effect of the F product.
DNA Flow Cytometry but Not Telomerase Activity as Predictor of Disease-Free Survival in pT1–2/N0/G2 Breast Cancer
Authors: Pinto António E. , André Saudade , Pereira Teresa , Silva Giovani , Soares Jorge
Published: September 2006

Objective: In the subgroup of patients with node-negative (N0) moderately differentiated (G2) breast cancer, the clinical decision of giving adjuvant therapy is critical. The aim of this study was to investigate the prognostic value of biomarkers (DNA flow cytometry and telomerase activity in correlation with routinely used estrogen receptors (ER) and HER oncoprotein) in pT1–2/N0/G2 breast cancer, for improving therapeutic management. Methods: The series involved 135 patients with pT1–2/N0/G2 breast cancer and median follow-up of 58.5 months. DNA ploidy and S-phase fraction (SPF) (≤5%; 5–10%; >10%) were assessed on frozen samples. Telomerase activity, ER and c-erbB-2 expression were analyzed by standardized immunohistochemistry techniques. A Cox regression analysis was performed for prognostic evaluation. Results: Aneuploidy significantly correlated with high SPF and lack of ER, while high SPF showed significant correlations with high telomerase activity, c-erbB-2 overexpression and absence of ER. Kaplan-Meier curves showed significant differences for ploidy and SPF in relation with disease-free survival (DFS) and overall survival (OS), and a statistical trend for ER. By Cox regression analysis, DNA aneuploidy (RR = 16.7; p = 0.007) and high SPF (RR = 23.1; p = 0.004) revealed significant correlations with worse DFS. Among patients with diploid (n = 76) and low/intermediate SPF (n = 85) tumors, only one had recurrence of the disease. No association between telomerase activity and clinical outcome was observed. Conclusion: In pT1–2/N0/G2 breast cancer patients, DNA ploidy and SPF are relevant prognostic biomarkers that should be considered as additional tools in the therapeutic planning.
Nuclear and Mitochondrial DNA Microsatellite Instability in Gastrointestinal Stromal Tumors
Authors: Kose K. , Hiyama T. , Tanaka S. , Yoshihara M. , Yasui W. , Chayama K.
Published: September 2006

Objective: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Nuclear (nMSI) and mitochondrial microsatellite instability (mtMSI) play important roles in tumorigenesis in various organs. The aim of this study was to evaluate the role of nMSI and mtMSI in GISTs. Methods: Samples from 74 mesenchymal tumors were collected. nMSI and mtMSI were examined by microsatellite assay at BAT26 and D310 mononucleotide repeats in mtDNA, respectively. We compared nMSI, mtMSI and clinicopathologic features, including patient age and sex, tumor location, tumor size, presence of tumor ulceration and presence of distant metastasis, for 51 GISTs for which these data were available. Results: nMSI and mtMSI were detected in 3 (5%) and 10 (16%) of the 62 GISTs, respectively. There was no significant relationship between nMSI, mtMSI and clinicopathologic features. Conclusion: These results suggest that mtMSI may play a role, but that nMSI may play little role in the development of GISTs.
Determinants for Prediction of Malignant Potential by Metalloproteinase:E-Cadherin Ratio in Prostate Core Needle Biopsy
Authors: Ohmori H. , Fujii K. , Sasahira T. , Ukai R. , Ikeda M. , Kobayashi K. , Maruyama A. , Kuniyasu H.
Published: September 2006

According to a good correlation between in situ hybridization-based metalloproteinase-2/9:E-cadherin ratio (MER) and the pathological stage of prostate cancer, we set the cutoff line of MER at 6.0 (MER>6) to distinguish between organ-confined (pT2) and advanced diseases (pT3a-b/N1). In this study, we looked at the factors affecting MER and leading to a misprediction of the pathological stage. We examined MER in 39 paired specimens of prostate core needle biopsy and prostatectomy from the same patient and compared these MERs. In 34 (87%) of 39 cases, the MER of biopsy was correlated with the final pathological stage (pT2 vs. pT3a-b/N1). MER ranges in pT3a-b/N1 cancer were significantly wider than those in pT2 cancer (p < 0.01). The number of MER>6 fields in Gleason score 8–9 cancer was larger than that in Gleason score 7 cancer (p < 0.0001). In 5 cases where there was a failure to distinguish pT2 from pT3a-b/N1, the misdiagnosis was significantly associated with a small number of biopsies (4 or 6 specimens; p = 0.0469), a small amount of tumor tissue in biopsy specimens (less than 5 mm; p = 0.0492), and a wide MER range (more than 5.0; high intratumoral heterogeneity; p = 0.0202). Considering these factors increases the usefulness of preoperative prediction of the final pathological stage by MER in prostate cancer.
Outcome of Patients in Relation to Duration of New-Onset Atrial Fibrillation following Acute Myocardial Infarction
Authors: Asanin Milika , Vasiljevic Zorana , Matic Mihailo , Vujisic-Tesic Bosiljka , Arandjelovic Aleksandra , Marinkovic Jelena , Ostojic Miodrag
Published: September 2006

Aim: The duration of new-onset atrial fibrillation (AF) following the acute myocardial infarction (AMI) was evaluated as well as its relation to in-hospital and 7-year mortality. Methods and Results: A total of 320 consecutive patients with AF following AMI were examined and patients with AF <7 h (n = 141) were compared to those with AF ≧7 h in duration (n = 179). Receiver Operating Characteristic analysis was performed to identify the most useful AF duration cut-off level for the prediction of poor outcome. Patients with longer AF duration were older and had more advanced heart failure than patients with short arrhythmia duration. Patients with longer AF duration had worse outcome, including higher in-hospital (22.3 vs. 12.8%) and 7-year (67.4 vs. 34.4%) mortality. After multivariate adjustment, longer AF duration remained an independent predictor of long-term mortality (relative risk = 2.04, 95% confidence interval = 1.39–2.99, p = 0.0002). Conclusion: New-onset AF ≧7 h in duration following the AMI independently predicts long-term mortality.
Atrial Fibrillation after Percutaneous Coronary Intervention: Predictive Importance of Clinical, Angiographic Features and P-Wave Dispersion
Authors: Gorenek Bulent , Parspur Afsin , Timuralp Bilgin , Birdane Alparslan , Ata Necmi , Cavusoglu Yuksel , Unalir Ahmet
Published: September 2006

Atrial fibrillation (AF) may occur during or after percutaneous coronary interventions (PCI). The purpose of the study was to determine the clinical, angiographic and electrophysiological predictors of AF after PCI. 225 patients undergoing PCI (mean age of 65 ± 11 years) who had sinus rhythm (SR) before balloon inflation were taken to study. Of these 22 developed AF in catheterization laboratory after balloon inflation or in 24 h following PCI (AF group), 203 did not (SR group). The patients in AF group were older (67 ± 9 vs. 63 ± 8 years, p < 0.05) and their ventricular ejection fraction was lower than SR group (56 ± 5 vs. 45 ± 7%, p < 0.05). The P-wave dispersion was significantly higher in AF group than SR group (53 ± 8 vs. 29 ± 10 ms, p < 0.001). For the patients with ST elevation myocardial infarction, the time from the onset of symptoms to balloon inflation was 3.7 ± 1.7 h in SR group. It was longer in AF group (4.1 ± 1.8 h, p < 0.05). TIMI perfusion grades 2 and 3 were achieved in 23 of 27 patients in SR group, and 5 of 8 patients in AF group. Multivessel disease was documented in 93 of the patients in SR group, and 12 in AF group. Clinical reperfusion was thought to be established in 20 in SR group, and 4 in AF group. In conclusion, our results show the importance of clinical factors, angiographic results and P-wave analysis in prediction of AF following PCI.
A Case of Pulmonary Alveolar Microlithiasis with Cardiac Constriction Secondary to Severe Adjacent Pleural Involvement
Authors: Kacmaz Fehmi , Alyan Omer , Celenk Mehmet , Ozdemir Ozcan , Turkvatan Aysel , Dogan Mehmet , Ilkay Erdogan
Published: September 2006

Pulmonary alveolar microlithiasis (PAM) is a rare disorder of uncertain etiology and pathogenesis that is characterized by tiny calcium phosphate depositions in lung alveoli. Ectopic organ involvement has been reported infrequently. We hereby present a patient with PAM complicated by severe pleural calcification that has caused a constrictive cardiac physiology, a heretofore unknown occurrence/association. Based on our observations in this particular case, we suggest that a non-invasive echocardiographic examination may be well worth in the investigation of PAM patients in whom symptom onset at an early age has occurred, particularly if severe pleural calcification adjacent to the heart is present.
Characteristics and Outcome of Acute Myocardial Infarction in Young Patients
Authors: Morillas Pedro , Bertomeu Vicente , Pabón Pedro , Ancillo Pablo , Bermejo José , Fernández Carmen , Arós Fernando
Published: September 2006

Background: The objective was to analyze the incidence, risk factors, management, and complications of acute myocardial infarction (AMI) in the young patient in Spain. Methods: Clinical characteristics, treatment, and outcome were analyzed in patients younger than 45 years admitted with an AMI diagnosis to the Coronary Units of 58 Spanish hospitals from 15th May to 15th December 2000. Results: Six thousand two hundred and ten consecutive patients were registered, 7% out of them were <45 years old. Outcome was better in the younger group, with a lower mortality rate at 28 days (3.7 vs. 11.9%; p < 0.001), demonstrating that age <45 years is an independent protective factor for mortality (relative risk: 0.41; 95% CI: 0.23–0.73; p < 0.001). This difference remained at 1-year follow-up. Conclusions: AMI in young patients presents distinct clinical characteristics, a different treatment, management and outcome with respect to the older group.
Are Elderly Patients with Suspected HF Misdiagnosed?
Authors: Olofsson Mona , Edebro Dan , Boman Kurt
Published: September 2006

Background: Few studies are published on heart failure patients in primary health care, in elderly in advanced age. Objective: The purpose of this study was to examine the accuracy of the diagnosis of heart failure in all men and women with focus on age and gender. Methods: The patients were recruited from one selected primary health care in the city of Skellefteå, Sweden. The general practitioners included all patients who had symptoms and signs indicating heart failure. The patients were then referred for an echocardiographic examination and a final cardiology consultation. Results: The general practitioners identified 121 women and 49 men with suspected heart failure of whom 39% (51 women and 16 men) were above 80 years. Women were significantly older than men (mean age 78 and 75 years, respectively, p = 0.03). The main symptom was dyspnoea (80%). Confirmed heart failure was verified in 45% of the patients and was significantly more common in men than women (p = 0.02). Of all men and women above 80 years, 75% and 22%, respectively (p = 0.01) had a verified systolic heart failure, while there were no significant gender differences in patients younger than 80. In a multivariate regression analysis taking gender, age, smoking, atrial fibrillation, hypertension, angina, myocardial infarction and diabetes into account, myocardial infarction (OR = 4.3, CL = 1.8–10.6) hypertension (OR = 3.4, CI = 1.6–6.9) atrial fibrillation (OR = 2.8, CL = 1.0–7.9) remained significantly predictive of a confirmed diagnosis of heart failure. Conclusion: This study showed the difficulty of diagnosing heart failure accurately based only on clinical symptoms, especially in women above 80 years.
Aortic Pulse Pressure and Aortic Pulsatility in Patients with Coronary Slow Flow
Authors: Guray U. , Guray Y. , Yilmaz M.B. , Caldir V. , Cay S. , Sasmaz H. , Kormaz S.
Published: September 2006

Objective: Coronary slow flow (CSF) is an angiographic phenomenon characterized by delayed opacification of coronary arteries in the absence of obstructive coronary disease. Recently, increased aortic pulse pressure (PP) and aortic pulsatility were both linked to the presence of angiographic coronary artery disease. In this study aortic PP and aortic pulsatility, derived from the invasively measured ascending aortic pressure waveform, were analyzed in patients with CSF and otherwise normal epicardial coronary arteries and compared with those with completely normal coronary arteries. Methods: Fifty consecutive patients with CSF (35 men, mean age: 51.7 ± 10 years) and fifty age and gender-matched controls (34 men, 51.1 ± 9 years) were included in the study. For determination of coronary flow, the thrombosis in myocardial infarction (TIMI) frame count method was used. Blood pressure waveforms of the ascending aorta were measured during cardiac catheterization with a fluid-filled system. Aortic pulsatility was estimated as the ratio of aortic PP to mean pressure. Results: Study groups were well matched with respect to age, gender and atherosclerotic risk factors. Although systolic, diastolic and mean pressures of the ascending aorta were similar, aortic PP (60.5 ± 19 vs. 51.7 ± 14 mm Hg, p = 0.01) and aortic pulsatility (0.63 ± 0.1 vs. 0.54 ± 0.1, p = 0.006) were significantly higher in patients with CSF compared with the controls. Besides, in all subjects, corrected TIMI frame counts of all three coronary arteries correlated with both ascending aorta PP and aortic pulsatility values. No association was found between corrected TIMI frame counts of coronary arteries and aortic mean blood pressure or brachial blood pressure parameters. Conclusion: Our findings suggest that CSF is, as with obstructive coronary artery disease, associated with more diffuse vascular disease rather than being an isolated finding.
Discrete Delay Model for the Mammalian Circadian Clock
Authors: Sriram K. , Bernot Gilles , Képès François
Published: September 2006

A three-variable discrete delay model is proposed for the circadian rhythm of the mammals with BMAL1, PER-CRY complex and REV-ERBαprotein concentrations as the dynamical variables. The delay model is phenomenological in nature rather than the precise description of all the underlying complex processes. The goal of this paper is to study the effects of delay in the circadian rhythms of mammals that appears in both the positive and negative feedback loops of the model. The delay model exhibits 24-hour limit cycle oscillations, entrainment to light-dark (LD) cycles and phase response curves. The model is also found to exhibit quasiperiodic and chaotic oscillations under LD cycles when delay is varied. These are linked to non-24-hour sleep-wake syndrome and cancer incidence. The mutations in Bmal1–/– , PerBrdm1, Rev-Erbα–/–are explained in terms of delay, whereas the double mutations PerBrdm1/Cry2–/–and Cry1–/–/ Cry2–/–are explained in terms of the strength of delayed positive and negative regulations. The delay model in essence captures the core mechanism of the mammalian circadian rhythms with a smaller number of variables and parameters.
Self-Organization and Other Emergent Properties in a Simple Biological System of Microtubules
Authors: Tabony James
Published: September 2006

In biological systems, emergent properties may develop due to numerous individual molecular elements in a population being strongly coupled in a non-linear manner. Under suitable conditions, the formation in vitroof a population of microtubules, a major component of the cellular skeleton (cytoskeleton), behaves as a complex system and develops a number of emergent phenomena. These preparations, which initially contain just two molecular species, a nucleotide and a protein, self-organize by reaction and diffusion and the morphology that develops is determined at a critical moment early in the process by weak external factors, such as gravity and magnetic fields. The process also results in other emergent phenomena, namely replication of form, generation of positional information, and collective transport and organization of colloidal-sized particles. Microtubules are responsible both for cellular organization and the transport of subcellular particles from one part of the cell to another. Frequently, this behaviour is triggered by some weak internal or external factor. The in vitroobservations outlined thus illustrate how in a simple biological system, a complex behaviour may give rise to emergent phenomena that outwardly resemble major biological functions.
Chronic Development of Ischaemic Mitral Regurgitation during Post-Infarction Remodelling
Authors: Nixdorff Uwe , Klinghammer Lutz , Wüstefeld Gertrud , Mohr-Kahaly Susanne , von Bardeleben Ralph Stephan
Published: September 2006

Background/Aims: Mitral regurgitation (MR) following myocardial infarction (MI) may be a (sub)acute complication which independently predicts reduced survival. We sought to evaluate the chronic development of MR as potential consequence of left-ventricular (LV) remodelling, the latter being a long-term process. Methods and Results: Retrospectively, 103 post-MI patients were included according to a standardised Doppler echocardiogram <3 months following MI (20 ± 25 days post-MI) and a follow-up examination >6 months after the first examination (5.1 ± 3.1 years post-MI). Patients were clinically followed up for 7.6 ± 2.7 years. Group I patients were defined as those showing new development or deterioration in one of three grades of MR, and group II those without this criterion (MR grade acute 0.17 vs. 0.27, p = 0.7, and chronic 1.53 vs. 0.19, p < 0.0001). Patient characteristics were similar in respect of age, gender, size and location of infarction. However, group I patients had coronary artery disease with more vessels involved. With regard to echocardiographic parameters of significantly enlarged LV chamber size in group I vs. group II, the significant decrease in LV performance was more pronounced and occurred concomitant with a higher degree of symptomatic congestive heart failure and greater need for heart failure medications in group I. Mortality in group I patients was 39 versus 9% in group II patients (p = 0.0002), approximating an odds ratio of 6.4697 (95% confidence interval: 2.211–18.931). Conclusion: First of all, this retrospective study indicates that MR may be detected in patients after MI during a long-term follow-up most probably due to geometric distortions of LV remodelling resulting in a significantly higher mortality. Since this process is known to become irreversible at a certain point, serial echocardiography may help to detect MR in post-MI patients and thus pave the way for appropriate treatment.
Fibrosis of Collagen I and Remodeling of Connexin 43 in Atrial Myocardium of Patients with Atrial Fibrillation
Authors: Luo Ming Hua , Li Yu Shu , Yang Ke Ping
Published: September 2006

Background: Fibrosis in atrial myocardium is a common phenomenon for patients with atrial fibrillation (AF). Remodeling of connexins was found accompanying with AF. The aim of the study is to investigate whether it is by causing the remodeling of connexin 43 (Cx43) that the fibrosis of atrial muscle plays an important role during the initiation and maintenance of AF. Methods: Samples of right atrial appendage were taken from 24 patients with rheumatic valvular disease during surgery. Fibrosis and remodeling of Cx43 was examined by microscopy and ultramicroscopy technique and analyzed by image analyzer. The collagen volume fraction of type I (CVF-I) and the volume fraction of Cx43 (Cx43VF) were studied between AF and sinus rhythm (SR) groups. Results: (1) Microscopic examination demonstrated that CVF-I significantly increased and Cx43VF decreased in patients with AF compared to those with SR. (2) The CVF-I was negatively correlated with the Cx43VF. Conclusion: The results suggest that fibrosis and remodeling of Cx43 are involved in the pathophysiologic mechanism of human AF. Fibrosis of atrial muscle may play an important role in the process of AF by means of interfering with remodeling of connexins.
In vitro Evaluation of Metallic Coronary Artery Stents with Sub-Millimeter Multi-Slice Computed Tomography Using an ECG-Gated Cardiac Phantom: Relationship between In-Stent Visualization and Stent Type
Authors: Utsunomiya Daisuke , Awai Kazuo , Sakamoto Takashi , Hazeyama Hiroyuki , Nishiharu Taiji , Urata Joji , Yamashita Yasuyuki
Published: September 2006

The aim of this experimental study was to investigate visualization of various coronary artery stents with sub-millimeter multi-slice spiral computed tomography (MSCT) using a cardiac physical phantom. Four 3-mm stents of various designs were implanted in tubes with an inner diameter of 3 mm to simulate coronary artery. Stents were placed on a cardiac phantom and scanned at different heart rates. Retrospective ECG-gated adaptive segmental reconstruction technique was employed. Profile curves across longitudinal curved planar reconstruction images of the stents were generated. From the profile curve, the full width at half maximum was defined as the stent lumen index. The effect of heart rate and stent type on the stent lumen index was evaluated. Visual evaluation for each stent at various heart rates was also performed. The heart rate had no significant effect on in-stent visualization. However, in-stent visualization differed significantly for the various stent types for both profile curve analysis and visual evaluation (the Tukey-Kramer multiple comparisons test). Multiple regression analysis indicated that strut thickness, especially minimal strut thickness, was the significant influencing factor for the in-stent visualization. On the basis of four stent models examined it would appear that visualization of the coronary stent lumen varies depending on the stent type, but not on the heart rate. Stents with slim struts are preferable for in-stent evaluation with multi-slice spiral computed tomography.
Morphine State-Dependent Learning Sensitization and Interaction with Nitric Oxide
Authors: Zarrindast Mohammad-Reza , Askari Elham , Khalilzadeh Azita , Nouraei Negin
Published: September 2006

In the present study, the effects of nitric oxide (NO) precursor L-arginine and L-NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization of morphine were investigated. Pre-training administration of morphine (5 mg/kg) impaired memory retrieval compared to pre-training saline-treated animals. Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine (5 mg/kg).The retrieval impairment was also inhibited in mice which had received once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by 5 days of no drug treatment before training (in order to induce morphine sensitization). Administration of L-arginine (60 mg/kg/day – 3 days) or L-NAME (20 mg/kg/day – 3 days) before training did not alter morphine state dependency. During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20 min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L-NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased morphine state dependency. It is concluded that NO is involved in the morphine-induced sensitization.