The usefulness of MR imaging in the diagnosis of dysembryoplastic neuroepithelial tumor in children: a study of 14 cases

BACKGROUND AND PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are benign lesions affecting children and are associated with epilepsy. The goal of our study was to better characterize the clinical-radiologic-pathologic spectrum of DNTs (complex and simple forms only) in a series of 14 children. METHODS: Clinical, neuroradiologic, and pathologic features of all cases were retrospectively studied. RESULTS: Eleven cases of complex and three cases of simple DNTs were identified. Mean follow-up was 87 months, and no recurrence was recorded except for one case of simple DNT. We found that some neuroradiologic features may be helpful to support the diagnosis of DNT: presence of "septations," triangular pattern of distribution, and absence of contrast enhancement. CONCLUSION: The evidence of the specific glioneuronal element is found by pathologic examination, but the typical neuroradiologic aspect of DNT suggests this diagnosis preoperatively. Radiologic examination may be helpful for the diagnosis of DNT when pathologic findings are inconclusive.     

Dislocated wrap after previous reduction aortoplasty causes erosion of the ascending aorta

We report a patient with bicuspid aortic valve and dilatation of the ascending aorta who had previous aortic valve replacement and reduction aortoplasty with wrapping. After 4 years, reoperation because of coronary artery disease and paravalvular leakage revealed an erosion of the aortic wall due to dislocation of the wrap. This complication confirms the need for secure anchoring and good fitting of the Dacron wrap to avoid alterations of the underlying aortic wall.     

Current determinants of operative mortality in 1400 patients requiring aortic valve replacement

BACKGROUND: Determinants of operative mortality after aortic valve replacement vary with a changing patient population due to advances in operative management and increasing life expectancy. In order to predict current groups of high risk patients, a statistically valid large study population base recruited over a short period of time is required. METHODS: Between January 1996 and June 2001, 1408 aortic valves were replaced in 1400 patients (572 of them with simultaneous coronary artery bypass grafting). The data were analyzed by multivariate logistic regression to evaluate the operative risk. Mean age of the study population was 68 +/- 11 years (range 19 to 90 years old, 44% female). RESULTS: Overall operative mortality (within 30 days) was 3.8%. Independent predictive factors for operative mortality were previous bypass surgery, emergency operation, simultaneous mitral valve replacement, renal dysfunction, more than 80 years old, simultaneous bypass surgery in female patients with a body mass index greater than 29 kg/m(2), and height smaller than 1.57 m for patients more than 71 years old. Simultaneous coronary artery bypass grafting in general (p = 0.6), previous aortic valve replacement (p = 0.59), and implantation of stented bioprostheses (p = 0.39) or stentless bioprostheses (p = 0.7) were not identified as independent risk factors. CONCLUSIONS: Certain groups of patients with a high operative risk were identified: patients more than 80 years old, women with a body mass index greater 29 kg/m(2) undergoing simultaneous coronary artery bypass surgery, and "small" patients more than 71 years old.     

Emergency hospital admissions and three-year survival of adults with and without cardiovascular surgery for congenital cardiac disease

OBJECTIVE: This study determined the quantity and nature of emergencies leading to unscheduled hospital admissions of adults with congenital cardiac disease and their mid-term survival. RESULTS: During 1 year, 429 adults with congenital cardiac diseases were admitted 571 times, and 124 admissions (22%) of 95 patients (22%) were emergency admissions. Fifteen of the 95 patients were seen for the first time in 1 of the participating centers. The underlying anomalies were Fallot's tetralogy and pulmonary atresia (n = 26/7), univentricular heart after Fontan procedure (n = 25), atrial septal defect (n = 18), Eisenmenger syndrome (n = 12), complete transposition (n = 11), and others (n = 25). Indications for admission were cardiovascular complications (n = 103; 83%) (arrhythmia, cardiac failure, syncope, pacemaker problems, pericardial tamponade, and sudden death), infections (n = 8, 6%) (endocarditis, pacemaker infection, pneumonia, and cerebral abscess), acute chest pain (n = 7; 6%), and acute abdominal pain (n = 4; 3%). All patients required immediate emergency care, and 16 patients (17%) required urgent cardiovascular or abdominal surgery. Six patients died during the hospital stay. During a follow-up of 2.9 years (SD 0.8), 16 (18%) of the discharged patients died, and 2 additional patients underwent heart or heart-lung transplantation. CONCLUSION: Adults with congenital cardiac disease often experience serious emergency situations with a high in-hospital and mid-term post-hospital mortality. Care given by physicians with special expertise is important in this specific group of patients.     

Substrate dependent inhibition profiles of fourteen drugs on CYP3A4 activity measured by a high throughput LCMS/MS method with four probe drugs, midazolam, testosterone, nifedipine and terfenadine

The CYP3A4 enzyme is known for its atypical inhibition kinetics; ligand inhibition can differ depending upon the probe drug used. A high throughput-LCMS/MS CYP3A4 inhibition assay with four substrate drugs was developed to minimize the potential oversight of CYP3A4 inhibition. The assay uses a 96-well format, human liver microsomes, and four CYP3A4 substrate drugs, midazolam, testosterone, nifedipine and terfenadine. After incubation of the individual substrate with human liver microsomes, the reaction is stopped by solid phase extraction and the four probe metabolites produced are pooled and measured by LCMS/MS with multiple-ion-monitoring mode. Using this assay, the IC(50) values of fourteen compounds recognized as substrates/inhibitors of CYP3A4, were measured for the CYP3A4 catalyzed-metabolism of probe drugs. IC(50) values were also obtained for the common set of compounds by the microtiter plate fluorescent assays with cDNA-expressed CYP3A4. Comparison of the results from the two methods suggests that decision making should be cautiously executed to predict drug interaction potential caused by inhibition of CYP3A4 considering the gap between the two assays and various other factors.     

ADP receptor antagonists as antiplatelet therapeutics

With the cloning of the P2Y12 receptor, the molecular basis for ADP-induced platelet aggregation is seemingly complete. Two platelet-bound ADP receptors, P2Y1 and P2Y12, operate through unique pathways to induce and sustain platelet aggregation via the glycoprotein (GP)IIb-IIIa integrin. P2Y1 operates via a glycoprotein q (Gq) pathway, activates phospholipase C, induces platelet shape change and is responsible for intracellular calcium mobilisation. P2Y12 inhibits adenylyl cyclase through a glycoprotein i (Gi)-dependent pathway, and is the target of the clinically used thienopyridines, ticlopidine (Ticlid, F. Hoffman-La Roche) and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Synthelabo). In addition, the receptor is targeted by the ADP analogue AR-C66096, which is currently in Phase IIb clinical trials, as well as other non-nucleoside-based preclinical leads.     

OM197-MP-AC induces the maturation of human dendritic cells and promotes a primary T cell response

Dendritic cell (DC) maturation is critical for the induction of antigen-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. We investigated the effects on human DC of OM-197, a synthetic pseudodipeptide derived from amino acids, linked to three fatty acid chains and devoid of endotoxin properties. OM-197 upregulated the expression of HLA-DR, CD80, CD86, CD83, CD40 and CD54 at the surface of myeloid DC naturally present in blood as well as of DC generated in vitro from monocytes using IL-4 and GM-CSF. OM-197 also induced the release of IL-12 and TNF-alpha from DC. Finally, DC incubated with OM-197 after pulsing with hepatitis B surface antigen (HBs Ag) induced in vitro expansion of IFN-gamma-secreting HBs Ag-specific CD4(+) T lymphocytes from naive individuals. Taken together, these data identify OM-197 as a potential vaccine adjuvant for the induction of Th1-type responses.