To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.
Treatment Outcome ; Time Factors ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Prognosis ; Neoplasm Metastasis ; Middle Aged ; Humans ; Female ; Disease-Free Survival ; *Classification ; Cell Nucleus/metabolism ; Carcinoma, Ductal, Breast/*classification/*diagnosis/pathology ; Breast Neoplasms/*classification/*diagnosis/pathology ; Aged ; Adult

Advanced heart failure (HF) is defined as the persistence of severe symptoms despite the use of optimized medical, surgical, and device therapies. These patients require timely advanced treatments, such as heart transplantation or long-term mechanical circulatory support (MCS). Inotropic agents are often used to reduce congestion and increase cardiac output, while renal replacement therapy may be beneficial if necessary. Cardiac resynchronization therapy has clear benefits in patients with HF with reduced ejection fraction, particularly with left bundle branch block (QRS duration > 130 ms). The role of implantable cardioverter-defibrillators in advanced HF patients requires further investigation considering the introduction of novel HF medications. In selected patients with significant secondary mitral regurgitation, transcatheter edge-to-edge repair can help delay heart transplantation or long-term MCS. In later stages, the appropriateness of heart transplantation should be evaluated, and the use of short- or long-term MCS may be considered. A multidisciplinary HF management program is crucial for patients with advanced HF. Recent treatment advances, including drugs, devices, and MCS, have broadened the options available to patients with advanced HF and this trend is expected to continue.

PURPOSE: Our aim was to evaluate the usefulness of fluid-attenuated inversion recovery (FLAIR) MR imaging for detection of acute subarachnoid hemorrhage (SAH) compared with unenhanced CT. MATERIALS AND METHODS: We compared FLAIR MR images with unenhanced CT scans in 28 patients with acute SAH. Findings of SAH on CT and MR images were graded as 0 (absence), 1 (suspicious), 2 (definite) in the cerebral sulci, sylvian fissure, basal cistern, and cisterns of the posterior fossa. We also compared FLAIR MR images of 28 patients with those of 35 normal subjects, and then the sensitivity, specificity, and diagnostic accuracy of FLAIR MR image for detection of acute SAH were calculated. RESULTS: FLAIR MR image was superior to CT in detecting SAH in the posterior fossa (1.41+/-.74 vs 0.78+/-.80; p<0.05) and cortical sulci(1.11+/-.80 vs 0.70+/-.83; p<0.05). There was no significant difference between FLAIR MR image and CT in detecting SAH in the basal cistern and sylvian fissure. The sensitivity, specificity, and diagnostic accuracy of FLAIR MR image for detection of SAH were 100% in all. CONCLUSION: FLAIR MR image is useful in detecting acute SAH, especially in patients with small amount of SAH or SAH in the posterior fossa.
Humans ; Magnetic Resonance Imaging* ; Sensitivity and Specificity ; Subarachnoid Hemorrhage* ; Tomography, X-Ray Computed

Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4’, 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dosedependent manner, with an estimated IC50 value of 54.4 μM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptormediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4’, 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dosedependent manner, with an estimated IC50 value of 54.4 μM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptormediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

The aim of the present study was to investigate the physiological role of nicotinamide phosphoribosyltransferase (NAMPT) associated with odontogenic differentiation during tooth development in mice. Mouse dental papilla cell-23 (MDPC-23) cells cultured in differentiation media were stimulated with the specific NAMPT inhibitor, FK866, and Visfatin (NAMPT) for up to 10 days. The cells were evaluated after 0, 4, 7, and 10 days. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mineralization assay was performed by staining MDPC-23 cells with Alizarin Red S solution. After cultivation, MDPC-23 cells were harvested for quantitative PCR or Western blotting. Analysis of variance was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. The expression of NAMPT increased during the differentiation of murine odontoblast-like MDPC-23 cells. Furthermore, the up-regulation of NAMPT promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers, such as dentin sialophosphoprotein, dentin matrix protein-1, and alkaline phosphatase in MDPC-23 cells. However, treatment of the cells with the NAMPT inhibitor, FK866, attenuated odontogenic differentiation, as evidenced by the suppression of odontoblastic biomarkers. These data indicate that NAMPT regulated odontoblastic differentiation through the regulation of odontoblastic biomarkers. The increase in NAMPT expression in odontoblasts was closely related to the formation of the extracellular matrix and dentin via the Runx signaling pathway. Therefore, these data suggest that NAMPT is a critical regulator of odontoblast differentiation during tooth development.

We investigated the incidence, predictors, and long-term clinical outcomes of new-onset diabetes mellitus (DM) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). A total of 6,048 patients treated with DES were retrospectively reviewed and divided into three groups: 1) known DM (n = 2,365; fasting glucose > 126 mg/dL, glycated hemoglobin > 6.5%, already receiving DM treatment, or previous history of DM at the time of PCI); 2) non-DM (n = 3,247; no history of DM, no laboratory findings suggestive of DM at PCI, and no occurrence of DM during follow-up); and 3) new-onset DM (n = 436; non-DM features at PCI and occurrence of DM during follow-up). Among 3,683 non-DM patients, 436 (11.8%) patients were diagnosed with new-onset DM at 3.4 ± 1.9 years after PCI. Independent predictors for new-onset DM were high-intensity statin therapy, high body mass index (BMI), and high level of fasting glucose and triglycerides. The 8-year cumulative rate of major adverse cardiac events (a composite of cardiovascular death, myocardial infarction, stent thrombosis, or any revascularization) in the new-onset DM group was 19.5%, which was similar to 20.5% in the non-DM group (P = 0.467), but lower than 25.0% in the known DM group (P = 0.003). In conclusion, the incidence of new-onset DM after PCI with DES was not low. High-intensity statin therapy, high BMI, and high level of fasting glucose and triglycerides were independent predictors for new-onset DM. Long-term clinical outcomes of patients with new-onset DM after PCI were similar to those of patients without DM.
Body Mass Index ; Coronary Artery Disease ; Diabetes Mellitus* ; Drug-Eluting Stents* ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence* ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Retrospective Studies ; Stents ; Thrombosis ; Triglycerides

A foreign body in heart is rare, but it is more frequently encountered than the past as iatrogenic causes are increasing. Clinicians should be aware that foreign body could be mistaken for normal structure of heart. In order for accurate diagnosis, multi-imaging modalities should be used for information of exact location, mobility and hemodynamic effects. A decision to intervene should be made based on potential harms harbored by foreign bodies. Endovascular retrieval should be considered as an option. However, when fatal complications occur or when foreign bodies are embedded deeply, a surgical removal should be attempted.
Cardiac Surgical Procedures/*methods ; Echocardiography ; Female ; Foreign Bodies/*radiography/*surgery ; Foreign-Body Migration/radiography ; Heart Injuries/diagnosis/etiology/*surgery ; Humans ; Iatrogenic Disease ; Middle Aged ; *Needles ; Treatment Outcome

A foreign body in heart is rare, but it is more frequently encountered than the past as iatrogenic causes are increasing. Clinicians should be aware that foreign body could be mistaken for normal structure of heart. In order for accurate diagnosis, multi-imaging modalities should be used for information of exact location, mobility and hemodynamic effects. A decision to intervene should be made based on potential harms harbored by foreign bodies. Endovascular retrieval should be considered as an option. However, when fatal complications occur or when foreign bodies are embedded deeply, a surgical removal should be attempted.
Cardiac Surgical Procedures/*methods ; Echocardiography ; Female ; Foreign Bodies/*radiography/*surgery ; Foreign-Body Migration/radiography ; Heart Injuries/diagnosis/etiology/*surgery ; Humans ; Iatrogenic Disease ; Middle Aged ; *Needles ; Treatment Outcome

As the survival rate of patients with complex congenital heart disease has improved and the number of adult patients with congenital heart disease has risen, arrhythmias and heart failure have become important issues in these patients. Cardiac implantable electronic devices, including pacemakers, are also on the rise. Transvenous implantation or epicardial pacemaker implantation is challenging in patients with complex congenital heart disease. Here we report a case in which a dual-chamber pacing, dual-chamber sensing, dual response and rate-adaptive (DDDR) pacemaker was implanted transvenously into a patient with congenital heart disease. A 34-year-old male with extracardiac conduit Fontan circulation complained of dizziness; an electrocardiogram revealed junctional bradycardia. We performed transvenous implantation of a DDDR pacemaker via trans-conduit puncture. In conclusion, transvenous implantation of a pacemaker is feasible in patients with extracardiac conduit Fontan circulation.
Adult ; Arrhythmias, Cardiac ; Bradycardia ; Dizziness ; Electrocardiography ; Fontan Procedure ; Heart Defects, Congenital ; Heart Failure ; Humans ; Male ; Pacemaker, Artificial ; Punctures ; Sick Sinus Syndrome ; Survival Rate