Correlates of health-related quality of life in type 2 diabetes.

Aims/hypothesis: We assessed the impact of medical comorbidities, depression, and treatment intensity on quality of life in a large primary care cohort of patients with type 2 diabetes.

Methods: We used the Health Utilities Index-III, an instrument that measures health-related quality of life based on community preferences in units of health utility (scaled from 0=death to 1.0=perfect health), in 909 primary care patients with type 2 diabetes.

Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy.

Aims: Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction.

Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers.

We conducted a randomized, crossover study in healthy adults to examine the effects of a nutritional supplement (Boost Plus) on posaconazole pharmacokinetics. In this study, coadministration of posaconazole with Boost Plus increased the maximum concentration of posaconazole in serum and area under the concentration-time curve from 0 to 72 h values 3.4- and 2.

Circulating adiponectin concentrations in patients with congestive heart failure.

Objectives: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF).

Methods: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n = 175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1beta, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor alpha and CD-40 ligand were determined.

Histology of the nasal septal swell body (septal turbinate).

Objective: To analyze the vascular and glandular elements of the nasal septal swell body (NSB) and quantitatively compare these to the inferior turbinate (IT) and non-swell body portion of septum.

Study Design: Fourteen healthy adults undergoing septoplasty and IT reduction were submitted to unilateral biopsies of the NSB, the adjacent inferior turbinate, and inferior septum. Photomicrography with morphometric analysis was used to determine the relative area proportions of each tissue type.

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.

Aerodynamic effects of inferior turbinate reduction: computational fluid dynamics simulation.

Objective: To investigate the aerodynamic consequences of conservative unilateral inferior turbinate reduction using computational fluid dynamics methods to accomplish detailed nasal airflow simulations.

Design: A high-resolution, finite-element mesh of the nasal airway was constructed from magnetic resonance imaging data of a healthy man. Steady-state, inspiratory airflow simulations were conducted at 15 L/min using the techniques of computational fluid dynamics.

Erythropoietin in heart failure.

The incidence of both congestive heart failure (CHF) and end-stage renal disease both are increasing. Anemia is common in both conditions and is associated with a marked increase in mortality and morbidity in both CHF and chronic kidney insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2.

Mediating effects of inflammatory biomarkers on insulin resistance associated with obesity.

Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C-reactive protein (CRP), E-selectin, and intercellular adhesion molecule-1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes.

Research Methods And Procedures: We stratified 510 initially non-diabetic women in the Nurses' Health Study cohort into four phenotypes above/below median BMI (27 kg/m2) and waist circumference (81 cm): low BMI-low waist (LBLW; N = 190), low BMI-high waist (LBHW; N = 74), high BMI-low waist (HBLW; N = 27), and high BMI-high waist (HBHW; N = 219).

Therapy insight: congestive heart failure, chronic kidney disease and anemia, the cardio-renal-anemia syndrome.

Congestive heart failure (CHF) and chronic kidney disease (CKD) often progress to end stage even with optimum medical therapy. One factor that is common to both conditions is anemia, which is present in about a third of CHF patients. CHF can cause or worsen both anemia and CKD, and CKD can cause or worsen both anemia and CHF.

Functional T-lymphocyte dichotomy in the peripheral blood of patients with unstable angina.

Objectives: Herein, we investigated the percentage of T-helper (Th1) and Th2 cells among the general T-cell population in the peripheral blood of patients with stable angina (SA) and unstable angina (UA).

Background: Recent evidence suggests that Th1 cells and the cytokines that they secrete (especially IFN-gamma) have a role in the activation of macrophages, promotion of clot formation and destabilization of atherosclerotic plaques. Thus, Th1 cytokines may contribute to the initiation and progression of UA.

Circulating matrix metalloproteinase-2 but not matrix metalloproteinase-3, matrix metalloproteinase-9, or tissue inhibitor of metalloproteinase-1 predicts outcome in patients with congestive heart failure.

Background: Extracellular matrix remodeling is thought to play an important role in the progression of heart failure (HF). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. Herein we evaluated the potential significance of circulating MMP and TIMP levels in patients with congestive HF (CHF) speculating it may assume prognostic value.

Partial inferior turbinectomy using the microdébrider.

Background: A microdébrider was selected to accomplish partial inferior turbinectomy, allowing for controlled and rapid removal of hypertrophic soft tissue while preserving the general turbinate form.

Objective: To assess the clinical outcome, healing, and any adverse consequences from the microdébrider partial turbinectomy procedure.

Setting: A public hospital in north-central Israel.

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

Background: It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame.

Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner.

Objectives: Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization.

Anaemia as a contributor to morbidity and mortality in congestive heart failure.

Anaemia is present in approximately 40% of cases of congestive heart failure (CHF) and is associated with a higher mortality, a lower left ventricular ejection fraction, a lower cardiac functional status, a higher rate of hospitalization, signs of malnutrition, a lower exercise capacity, a progressive fall in renal function, an increased need for high dose diuretics, hyponatraemia, an increased plasma volume, a reduced red cell volume and a lower quality of life. In both uncontrolled and controlled studies, correction of the anaemia with subcutaneous erythropoietin and, in some cases, with the addition of intravenous iron, has been shown to improve these parameters. A vicious circle is present between CHF, chronic kidney insufficiency (CKI) and anaemia, each capable of causing or being caused by the other, the so-called cardio renal syndrome.

An unusual cause of refractive chronic bilateral leg ulceration.

Background: Ulceration of the lower extremities is a common disorder that can be very painful. It occurs most frequently in the elderly population as a result of venous hypertension. We report an unusual case of a 32-year-old man with an 11-year history of extensive, painful, bilateral leg ulcers resistant to conventional treatment necessitating above-knee amputation of the left leg.

Linking solubility and permeability assays for maximum throughput and reproducibility.

Solubility and permeability are intimately linked in drug absorption processes. They have, however, been traditionally assayed separately. To support this linkage, a combined solubility/permeability assay was developed for determining absorption properties of chemical entities.

Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers.

Background: Considerable morbidity and mortality are still associated with congestive heart failure (CHF) syndromes, despite improvement in therapy. Activation of neurohormonal, inflammatory, and oxidative mechanisms has been shown to contribute to the significant morbidity and mortality. Erythropoietin (EPO) is a cytokine known to regulate erythroid proliferation, attenuate apoptosis and oxidative stress, and promote angiogenesis.

Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes.

Objective: Diabetes eliminates the protective effect of female sex on the risk of coronary heart disease (CHD). We assessed sex differences in the treatment of CHD risk factors among patients with diabetes.

Research Design And Methods: A cross-sectional analysis included 3,849 patients with diabetes treated in five academic internal medicine practices from 2000 to 2003.

Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations.

Background And Objective: Posaconazole is a potent, extended-spectrum triazole antifungal agent currently in clinical development for the treatment of invasive fungal infections. This study was conducted to compare the bioavailability and resulting serum concentrations of posaconazole 800 mg following administration of three different dose regimens to fasting adults.

Study Design: This was a randomised, open-label, three-way crossover study.

The role of anemia in the progression of congestive heart failure. Is there a place for erythropoietin and intravenous iron?

Anemia is found in about one-third of all cases of congestive heart failure (CHF). The most likely common cause is chronic kidney insufficiency (CKI), which is present in about half of all CHF cases. The CKI is likely to be due to the renal vasoconstriction that often accompanies CHF and can cause long-standing renal ischemia.

Effects of treatment with epoetin beta on outcomes in patients with anaemia and chronic heart failure.

Unlabelled: Anaemia is frequently found in patients with chronic heart failure (CHF) and has been associated with an increase in mortality and morbidity, impaired cardiac and renal function and a reduced quality of life (QoL) compared with non-anaemic CHF patients. Correction of anaemia with recombinant human erythropoietin (epoetin) has been associated with an improvement in CHF in both controlled and uncontrolled studies. The present study describes our findings in a series of 78 consecutive patients with symptomatic CHF and anaemia (haemoglobin (Hb) level <12.

A high-throughput turbidometric assay for screening inhibitors of protein disulfide isomerase activity.

Protein disulfide isomerase (PDI) plays a key role in protein folding by catalyzing rearrangements of disulfide bonds in substrate proteins following their synthesis in eukaryotic cells. Besides its major role in the processing and maturation of secretory proteins in the endoplasmic reticulum, this enzyme and its homologs have been implicated in multiple important cellular processes; however, they have not served as targets for the development of therapeutic agents. The authors developed a high-throughput screening assay for PDI and its homologous enzymes in 384-well microplates.

The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome.

Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure.