Re-redo cervical mediastinoscopy for a recurrent lung cancer

Indian Journal of Thoracic and Cardiovascular Surgery -     

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.     

Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia.

PURPOSE: The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. PATIENTS AND METHODS: Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). RESULTS: The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. CONCLUSION: The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.     

The assessment of placental blood vessels by three-dimensional power Doppler ultrasound

OBJECTIVE: This study was performed in order to compare the performance of classical two dimensional (2D) and three dimensional (3D) ultrasound, both with power Doppler technology, in the visualization of the placental vascular network during ongoing pregnancy. METHODS: 15 pregnant volunteers in the third trimester of pregnancy were examined by 2D and 3D power Doppler ultrasound. The aim of the study was to follow the branching of the main stem vessel as far as possible distally in the placenta. In addition, we assessed the visualization rate of terminal parts of uteroplacental circulation, radial and spiral arteries. RESULTS: There was no difference in the visualization of primary placental stem vessels by 2D and 3D power Doppler. However, 3D power Doppler performs better distally, with statistically significant differences at the level of secondary stem (p = 0.03), and even more prominent differences at the level of tertiary stem vessels (p = 0.0008). There was no difference in the visualization rate of radial and spiral arteries (p > 0.05). CONCLUSION: We found 3D superior to 2D ultrasound with power Doppler technology in the determination of the distal vascular branches of the fetal placental blood vessels.     

Evaluation of pulmonary blood flow in bilateral bidirectional Glenn shunts: value of 4‐D flow cardiac magnetic resonance in the evaluation of pulmonary artery confluence stenosis

Bilateral bidirectional Glenn shunts are associated with the risk of developing pulmonary artery bifurcation stenosis, resulting in variable pulmonary blood flow to either lung. This could negatively impact the subsequent stages of the single ventricle palliation pathway. This report highlights the value of 4D flow sequence from the cardiac magnetic resonance imaging in demonstrating the pulmonary blood flow characteristics following a bilateral bidirectional Glenn procedure. Mapping the blood flow pattern and its quantification to each lung provide objective insights into the possible predisposing factors for the development of pulmonary bifurcation stenosis.     

Enhancement of Confinement in Scaled RC Columns using Steel Fibers Extracted from Scrap Tyres

Steel fibers are widely extracted from scrap tyres, causing environmental concerns. This paper presents the use of steel fibers in variable proportions extracted from scrap tyres. The enhancement of the confinement was envisaged through the addition of steel fibers obtained from scrap tyres. The study included an experimental program for the development of constitutive material models for ordinary Portland cement (OPC) concrete and concrete with added steel fibers. A mix design was carried out for OPC, targeting a compressive strength of 3000 psi. Steel fibers were added to OPC in ratios of 1.0% to 3.0%, with an increment of 0.5%. Concrete columns, with cross-sectional dimensions of 6 × 6 inches and a length of 30 inches, were cast with both OPC and fiber-reinforced concrete. The column confinement was evaluated with a different spacing of ties (3- and 4-inch center-to-center). Compression tests on the concrete columns indicate that the addition of steel fibers to a concrete matrix results in an appreciable increase in strength and ductility. Overall, increasing the percentage of steel fibers increased the compression strength and the ductility of concrete. The maximum strain in the concrete containing 2.5% steel fibers increased by 285% as compared to the concrete containing 1% of steel fibers. An optimum percentage of 2.5% steel fibers added to the concrete resulted in a 39% increase in compressive strength, accompanied by a significant improvement in ductility. The optimum content of steel fibers, when used in confined columns, showed that confined compression strength increased with the addition of steel fibers. However, it is recommended that additional columns on the basis of the optimum steel fiber content shall be tested to evaluate their effectiveness in reducing the stirrup spacing.     

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

We previously identified two small-molecule CD4 mimetics—NBD-556 and NBD-557—and synthesized a series of NBD compounds that resulted in improved neutralization activity in a single-cycle HIV-1 infectivity assay. For the current investigation, we selected several of the most active compounds and assessed their antiviral activity on a panel of 53 reference HIV-1 Env pseudoviruses representing diverse clades of clinical isolates. The selected compounds inhibited tested clades with low-micromolar potencies. Mechanism studies indicated that they act as CD4 agonists, a potentially unfavorable therapeutic trait, in that they can bind to the gp120 envelope glycoprotein and initiate a similar physiological response as CD4. However, one of the compounds, NBD-09027, exhibited reduced agonist properties, in both functional and biophysical studies. To understand the binding mode of these inhibitors, we first generated HIV-1-resistant mutants, assessed their behavior with NBD compounds, and determined the X-ray structures of two inhibitors, NBD-09027 and NBD-10007, in complex with the HIV-1 gp120 core at ∼2-Å resolution. Both studies confirmed that the NBD compounds bind similarly to NBD-556 and NBD-557 by inserting their hydrophobic groups into the Phe43 cavity of gp120. The basic nitrogen of the piperidine ring is located in close proximity to D368 of gp120 but it does not form any H-bond or salt bridge, a likely explanation for their nonoptimal antagonist properties. The results reveal the structural and biological character of the NBD series of CD4 mimetics and identify ways to reduce their agonist properties and convert them to antagonists.     

Thrombin activatable fibrinolysis inhibitor and thrombin-antithrombin-III-complex levels in patients with gastric cancer

The relation between cancer and coagulation is the subject of investigation since a relation between tumor and thrombosis has been determined. Antithrombin III is an important thrombin inhibitor, and increased thrombin?Cantithrombin (TAT) complex levels activate coagulation. Activated thrombin activatable fibrinolysis inhibitor (TAFI) inhibits the conversion of plasminogen to plasmin. In addition, it directly inactivates plasmin. Defective fibrinolysis increases the risk of thrombosis. In this study, we evaluated homeostatic parameters, TAFI, and TAT levels in patients with gastric cancer applying to the medical oncology outpatient clinic. Fifty-two patients and 35 healthy controls were included. ELISA was used to measure TAFI and TAT complex levels. These were statistically higher in the patient group (p?<?0.05 and p?=?0.001, respectively). D-dimer levels were higher in stage IV (p?=?0.05). Correlations between lymph nodes and TAFI and TAT levels were examined. Weak but positive correlation between lymph nodes and TAFI was detected (R?=?0.452, p?=?0.027). TAFI and TAT levels were evaluated using relative operating characteristic analysis to differentiate the disease. TAT was more specific than TAFI according to this analysis (TAFI area under curve (AUC), 0.676; TAT AUC, 0.874). Thrombotic events and bleeding disorders need to be borne in mind in gastric cancer. This situation is due to the impairment of the balance between coagulation and fibrinolysis. Further studies are now needed to evaluate the effects of TAFI and TAT on survey and prognosis as well as the potential of these parameters as tumor markers for gastric cancer.