Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer.

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects.

Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect.

Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect.

A new model for determining the MTD during phase-I trials in pediatric oncology.

The primary goal of phase I studies in oncology is to determine the MTD (Maximum Tolerated Dose) for a drug. This MTD is determined with respect to an accepted risk (usually 33%) to see a limiting toxity for patients. In this paper we propose a new mathematical model to determine the MTD.

Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.

While immediate loading in the edentulous mandible is a well-documented procedure, there are limited scientific data on immediate loading in the partially edentulous mandible. Two-year success rates of immediate loading and conventional delayed loading of dental implants in partially dentate mandibles were compared. Patients were randomized into three groups: group A (n = 40), immediate provisionalization with nonocclusal loading; group B (n = 40), immediate provisionalization with occlusal loading; and group C (n = 37), delayed loading with single-stage surgery.

Non-traumatic rhabdomyolysis and diabetes.

The present clinical report describes the case of a spontaneously resolving rhabdomyolysis episode in a type 1 diabetic patient, who presented with multiple risk factors of this muscle complication, including uncontrolled brittle diabetes with sequences of hyper- and hypoglycaemic episodes in the same day, caloric restriction and intensive exercise. It should be borne in mind that rhabdomyolysis is not particularly rare in diabetes and can be severe. To raise clinicians' awareness of a possible rhabdomyolysis diagnosis, the various clinical conditions that are likely to lead to this complication in diabetic patients are also reviewed here.

Tumor growth modeling from clinical trials reveals synergistic anticancer effect of the capecitabine and docetaxel combination in metastatic breast cancer.

Purpose: Most of the cancer chemotherapy treatments employ drugs in combination. For combination treatments, it is relevant to assess interaction between two or more anticancer agents used in clinics. Based on clinical data and using modeling techniques, the work analyzes the pharmacodynamic interaction between capecitabine and docetaxel used in combination in metastatic breast cancer.

Physiopathology of somatolactotroph cells: from transduction mechanisms to cotargeting therapy.

In pituitary somatolactotroph cells, G protein-coupled receptors and receptor tyrosine kinases binding their specific ligands trigger an enzymatic cascade that converges to MAP kinase activation in the subcellular compartment. Different signaling pathways, such as AC/cAMP/PKA and PI3K/Akt pathways, interact with MAP kinase to regulate key physiological functions, such as hormonal secretion and cell proliferation. Abnormalities affecting these signaling pathways have been identified as preponderant factors of pituitary tumorigenesis.

Parvovirus 4 in French in-patients: a study of hemodialysis and lung transplant cohorts.

The epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French hemodialysis and lung transplant patients. Plasma samples (n=289) were tested for PARV4 by real-time PCR assay (ORF2), and amplification products selected at random were sequenced.

Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01).

Background: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population.

Patients And Methods: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks.

Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.

Background: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE.

Methodology/principal Findings: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls.

Surgical resection of liver non-small cell lung cancer metastasis: a dual weapon?

Liver resection for metastases from a colorectal cancer is well established and it is considered the treatment of choice. However, for patients with liver metastases from other carcinomas, the value of resection is incompletely defined and still debated. We report two cases of partial hepatectomies for liver metastases from non-small cell lung cancer leading to different outcomes.

VEGFR2 (KDR/Flk1) signaling mediates axon growth in response to semaphorin 3E in the developing brain.

Common factors are thought to control vascular and neuronal patterning. Here we report an in vivo requirement for the vascular endothelial growth factor receptor type 2 (VEGFR2) in axon tract formation in the mouse brain. We show that VEGFR2 is expressed by neurons of the subiculum and mediates axonal elongation in response to the semaphorin (Sema) family molecule, Sema3E.

Posture and muscular behaviour in emergency braking: an experimental approach.

In the field of numerical crash simulations in road safety research, there is a need to accurately define the initial conditions of a frontal impact for the car occupant. In particular, human models used to simulate such impacts barely take into account muscular contracting effects. This study aims to quantify drivers' behaviour in terms of posture and muscular activity just before a frontal impact.

Maternal outcome after conservative treatment of placenta accreta.

Objective: To estimate maternal outcome after conservative management of placenta accreta.

Methods: This retrospective multicenter study sought to include all women treated conservatively for placenta accreta in tertiary university hospital centers in France from 1993 to 2007. Conservative management was defined by the obstetrician's decision to leave the placenta in situ, partially or totally, with no attempt to remove it forcibly.

Pharmacokinetics and pharmacodynamics of a new ACT formulation: Artesunate/Amodiaquine (TRIMALACT) following oral administration in African malaria patients.

A new fixed-dose combination of artesunate (AS) plus amodiaquine (AQ) (TRIMALACT) was recently developed for the treatment of uncomplicated falciparum malaria. The originality of this combination lies in its galenic formulation which consists of a three-layer tablet with two layers containing each of the active ingredients, i.e.

Electromyographic tools to assess hemidiaphragm paralysis.

Non-invasive measurements of the phrenic nerve conduction time (CT) and diaphragmatic electromyographic response to voluntary inspiratory efforts may help to document an abnormal diaphragmatic function in the presence of hemidiaphragm elevation on chest radiographs. Twenty-one patients were addressed for the diagnosis of abnormal placement and motion of the right (13) or left (8) cupola on chest radiographs. CT was measured by recording the diaphragmatic M-wave evoked by electrical transcutaneous phrenic nerve stimulation.

Comparison of the biomechanical behavior of the liver during frontal and lateral deceleration.

Background: The trunk of a car occupant can be injured by a frontal or lateral impact. Lesions can be either intrusion injuries or due to the effects of deceleration alone. The aim of this study conducted with human cadavers was to explore the effects of deceleration on the liver during frontal or lateral deceleration.

Head-up tilt induced syncope and adenosine A2A receptor gene polymorphism.

Aims: High adenosine plasma levels and high expression of adenosine A(2A) receptors are observed in patients with unexplained syncope and a positive head-up tilt test (HUT). This study aimed to evaluate the single nucleotide polymorphism (SNP) (c.1364 T>C) which is the most commonly found polymorphism in the A(2A) receptor gene, in patients with unexplained syncope undergoing HUT.

An interface model for dosage adjustment connects hematotoxicity to pharmacokinetics.

When modeling is required to describe pharmacokinetics and pharmacodynamics simultaneously, it is difficult to link time-concentration profiles and drug effects. When patients are under chemotherapy, despite the huge amount of blood monitoring numerations, there is a lack of exposure variables to describe hematotoxicity linked with the circulating drug blood levels. We developed an interface model that transforms circulating pharmacokinetic concentrations to adequate exposures, destined to be inputs of the pharmacodynamic process.

Somatostatin receptor sst2 decreases cell viability and hormonal hypersecretion and reverses octreotide resistance of human pituitary adenomas.

In human somatotroph adenomas, growth hormone (GH) hypersecretion can be inhibited by somatostatin analogues such as octreotide. Unfortunately, serum GH levels reach normal values in only 60% of treated patients. The decreased sensitivity to octreotide is strongly related to a lower expression of somatostatin receptor sst2.

Current atrial fibrillation guidelines and therapy algorithms: are they adequate?

Management of patients with atrial fibrillation in clinical practice represents a major challenge. The 2001 ACC/AHA/ESC Atrial Fibrillation Guidelines have gained wide acceptance but recent advances have required their revision in 2006. Large strategy trials comparing rhythm control to rate control using drug therapy has shown no difference in terms of major endpoints including mortality.

Post-exercise heart rate recovery in healthy, obeses, and COPD subjects: relationships with blood lactic acid and PaO2 levels.

Because blood acidosis and arterial oxygenation (PaO(2)) play key roles in the chemoreflex control of cardiac activity, we hypothesized that heart rate (HR) decay rate after maximal exercise may be linked to post-exercise increase in blood lactate (LA) level and/or the resting PaO(2). Twenty healthy subjects and thirty five patients at risks of cardiovascular diseases (20 obeses; 15 patients with chronic obstructive pulmonary disease, COPD) performed a maximal cycling exercise. During the recovery period, HR was continuously measured for consecutive 10-s epochs allowing to compute linear or second order polynomial equations and to calculate every minute HR variations compared to peak HR value (DeltaHR).

Stature, economy and migration during the 19th century: comparative analysis of Haute-Vienne and Hautes-Alpes, France.

Data sources are achieved records of men workers' passbooks and registry for work permits in two rural parts of Southern France. We obtained three samples: masons from Rancon, a Limousin village, local sedentary alpine workers and Italian immigrants. The results obtained provide two types of information.

Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development.

The establishment of functional neural circuits requires the guidance of axons in response to the actions of secreted and cell-surface molecules such as the semaphorins. Semaphorin 3E and its receptor PlexinD1 are expressed in the brain, but their functions are unknown. Here, we show that Sema3E/PlexinD1 signaling plays an important role in initial development of descending axon tracts in the forebrain.