25 research outputs found

    Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor

    Get PDF
    Blocking angiogenesis is an attractive strategy to inhibit tumor growth, invasion, and metastasis. We describe here the structure and the biological action of a new cyclic peptide derived from vascular endothelial growth factor (VEGF). This 17-amino acid molecule designated cyclopeptidic vascular endothelial growth inhibitor (cyclo-VEGI, CBO-P11) encompasses residues 79-93 of VEGF which are involved in the interaction with VEGF receptor-2. In aqueous solution, cyclo-VEGI presents a propensity to adopt a helix conformation that was largely unexpected because only \u3b2-sheet structures or random coil conformations have been observed for macrocyclic peptides. Cyclo-VEGI inhibits binding of iodinated VEGF165 to endothelial cells, endothelial cells proliferation, migration, and signaling induced by VEGF165. This peptide also exhibits anti-angiogenic activity in vivo on the differentiated chicken chorioallantoic membrane. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival without side effects. Taken together, these results suggest that cyclo-VEGI is an attractive candidate for the development of novel angiogenesis inhibitor molecules useful for the treatment of cancer and other angiogenesis-related diseases

    "Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

    Get PDF
    Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

    Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

    Get PDF

    Multidrug infusions in a Swiss palliative care unit: assessment of frequent combinations in terms of clinical effectiveness, compatibility, and stability.

    No full text
    The objectives of this study were to trace, monitor, and assess for clinical effectiveness, visual compatibility, and stability of commonly used combinations of drugs for patients hospitalized in a Swiss palliative care unit, over a 12-month period. In this longitudinal analysis, commonly used multidrug combinations were monitored with a duly created data collection sheet for healthcare professionals. Assessment of visual changes of the mixtures and the evaluation of major changes in the overall symptom control over time were recorded. The clinical changes were classified according to reasonable correlation to the modality of drug administration and not to clinical evolution of the underlying disease. Over a 12-month period, a total of 48 multidrug infusions were recorded and monitored. The infusions were composed of two, three, four, or five active principles. Infusions were given over a 24-h period, mainly intravenously, either through an implantable venous access port or a peripheral venous access. Main diluent was normal saline solution. Commonly used drug combinations included morphine and haloperidol, morphine, haloperidol and octreotide, morphine, haloperidol, octreotide, and chlorpromazine. No precipitations were observed during the study. Patients maintained a clinical stability and no salient changes in symptom control were attributed to inefficacy of the multidrug infusions. The use of multidrug infusions for parenteral administration appears to confirm an adequate visual compatibility and stability, while maintaining effectiveness in terms of overall symptom control

    Measurement of Cefaclor and Amoxicillin-Clavulanic Acid Levels in Middle-Ear Fluid in Patients with Acute Otitis Media

    No full text
    Concentrations of cefaclor (CFC) or amoxicillin-clavulanic acid (AMX/CA) in middle-ear fluid collected preserving the stability and clearing the cell contents has been compared to those obtained using the traditional method. Sixty-seven children with effusive otitis media were treated orally with CFC (20 mg/kg of body weight) or AMX/CA (20 mg/kg) (4:1 ratio). The concentrations in cell-free fluid (C−) appear higher than those in the total fluid (C+) (as assayed traditionally)

    Glucocorticoids Increase In Vitro and In Vivo Activities of Antibiotics against Chlamydophila pneumoniae

    No full text
    The in vitro and in vivo antichlamydial activities of dexamethasone and beclomethasone alone and in combination with an antibiotic were tested. In vitro, dexamethasone and beclomethasone decreased the number of inclusion-forming units versus the control number (P < 0.001). The combination of glucocorticoids with azithromycin, telithromycin, or levofloxacin was more active than antibiotics used alone (P < 0.001). The combination, tested in a murine Chlamydophila pneumoniae infection model, produced similar results
    corecore