Long-term stable expression of human growth hormone by rAAV promotes myocardial protection post-myocardial infarction.

Recombinant adeno-associated virus (rAAV)-based gene therapy represents a promising approach for the treatment of heart diseases. It has been shown that growth hormone (GH) exerts a favorable effect on cardiovascular function in clinical and animal studies. This study explores a chronic stage after myocardial infarction and the potential therapeutic effects of delivering a human GH gene by rAAV following coronary artery ligation in Sprague-Dawley rats.

NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure.

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity.

Gene and cell therapy for chronic ischaemic heart disease.

Viable treatment options are becoming available for the 'no-option' patient with chronic ischaemic heart disease. Instead of revascularising the highly diseased epicardial coronary arteries, scientists and clinicians have been looking at augmenting mother nature's way of providing biological bypass in an attempt to provide symptomatic relief in these patients. The novel use of gene and cell therapies for myocardial neovascularisation has exploded into a flurry of early clinical trials.

Brief review: coronary drug-eluting stents and anesthesia.

Purpose: Anesthesiologists managing patients with drug-eluting stents (DES) face the challenge of balancing the risks of bleeding vs perioperative stent thrombosis (ST). This article reviews DES and the influence of antiplatelet medications related to their use. A perioperative management algorithm is suggested.

Prospective assessment of computer-aided detection in interpretation of screening mammography.

Objective: The purpose of this study was to prospectively assess the usefulness of computer-aided detection (CAD) in the interpretation of screening mammography and to provide the true sensitivity and specificity of this technique in a clinical setting.

Subjects And Methods: Over a 26-month period, 5,016 screening mammograms were interpreted without, and subsequently with, the assistance of the iCAD MammoReader detection system. Data collected for actionable findings included dominant feature (calcification, mass, asymmetry, architectural distortion), detection method (radiologist only, CAD only, or both radiologist and CAD), BI-RADS assessment code, associated histopathology for those undergoing biopsy, and tumor stage for malignant lesions.

Changing pattern of the subcellular distribution of erythroblast macrophage protein (Emp) during macrophage differentiation.

Erythroblast macrophage protein (Emp) mediates the attachment of erythroid cells to macrophages and is required for normal differentiation of both cell lineages. In erythroid cells, Emp is believed to be involved in nuclear extrusion, however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp.

Discrepancy in the use of confirmatory tests in patients hospitalized with the diagnosis of chronic obstructive pulmonary disease or congestive heart failure.

Objective: To determine the prevalence of confirmatory use of spirometry in patients admitted to a tertiary-care facility with the diagnosis of chronic obstructive pulmonary disease (COPD), including those with respiratory failure, and compare that to the use of confirmatory 2-dimensional echocardiography (2-D echo) in patients admitted with the diagnosis of congestive heart failure (CHF), to determine preferential confirmatory testing practices.

Setting: Academic tertiary-care hospital.

Methods: A 6-month retrospective review of charts of patients with a primary or secondary discharge diagnosis of COPD, respiratory failure, and CHF, using the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes.

Comparison of the effects of a new conjugated oral estrogen, estradiol-3beta-glucoside, with oral micronized 17beta-estradiol in postmenopausal women.

The objective of this article is to evaluate the pharmacokinetics of serum estrone and estradiol levels in women who were taking either 17beta-estradiol-3beta-glucoside (E(2)-3beta-glucoside) or 17beta-estradiol (E(2)) daily and to examine the effects of E(2)-3beta-glucoside and E(2) on postmenopausal symptoms, gonadotropins, hepatic metabolism, and coagulation factors. Healthy postmenopausal women on estrogen who had undergone a hysterectomy were recruited. Subjects were randomly assigned to receive equivalent doses of either E(2)-3beta-glucoside or micronized E(2) for 28 days.

Anesthesia for cesarean section in a patient with placenta previa and methylenetetrahydrofolate reductase deficiency.

We describe the anesthetic management of a patient with placenta previa presenting for a cesarean section, who had methylenetetrahydrofolate reductase (MTHFR) deficiency. Methylenetetrahydrofolate reductase deficiency increases homocysteine levels in the body and, therefore, predisposes to thrombosis. After a cerebrovascular accident at 8 weeks of gestational age, the patient received anticoagulants throughout the course of her pregnancy.

Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial.

We studied the effect of rituximab in allowing a reduction in dose of intravenous immune globulin (IVIg) in six patients with IVIg-dependent, relapsing immune polyneuropathy. Rituximab (375 mg/m(2) intravenously each week for 4 weeks) was administered in a prospective, open-label design to two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), two with multifocal motor neuropathy (MMN), one with neuropathy and anti-myelin-associated glycoprotein (MAG) antibody neuropathy, and one with Sjögren syndrome (SS) ataxic neuropathy. The primary endpoint was a reduced cumulative IVIg dosage by at least 25% at 1 year after rituximab therapy compared to the previous year.

Transgenic expression of beta-APP in fast-twitch skeletal muscle leads to calcium dyshomeostasis and IBM-like pathology.

Intracellular deposition of the beta-amyloid (Abeta) peptide is an increasingly recognized pathological hallmark associated with neurodegeneration and muscle wasting in Alzheimer's disease (AD) and inclusion body myositis (IBM), respectively. Previous reports have implicated dysregulation of beta-amyloid precursor protein (betaAPP) expression in IBM. Accumulation of full-length betaAPP, its various proteolytic derivatives including Abeta, and phospho-tau into vacuolated inclusions is an early pathogenic event.

IL-10-induced TNF-alpha mRNA destabilization is mediated via IL-10 suppression of p38 MAP kinase activation and inhibition of HuR expression.

Inflammation plays an essential role in vascular injury and repair. Mononuclear phagocytes are important contributors in these processes, in part, via adhesive interactions and secretion of proinflammatory cytokines. The antiinflammatory cytokine interleukin (IL)-10 suppresses such responses via deactivation of monocytes/macrophages and repression of inflammatory cytokine expression.

Roger s. Mitchell lecture. Chronic obstructive pulmonary disease phenotypes and their clinical relevance.

Phenotype is defined as the outward physical manifestation of patients with chronic obstructive pulmonary disease (COPD); anything that is part of their observable structure, function, or behavior. As such, for patients with COPD, the time has come to move from a disease expressed solely by the degree of airflow limitation, to a much broader and resourceful characterization of COPD. Recent advances in the detection of specific clinical phenotypes, such as persistent hypoxemia, hyperinflation with inhomogeneous emphysema, frequent exacerbators, and patients with peripheral muscle dysfunction, are resulting in specific forms of approaches to include therapy that are affecting outcomes.

Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem cells: safety of a high dose, "off-the-shelf", cellular cardiomyoplasty strategy.

Background: Efficacy of cellular cardiomyoplasty seems to occur in a dose-related manner. However, the safety of multiple transendomyocardial transplantation procedures to administer high cell dosages has not been previously reported. The aims of this study were to assess the short- and intermediate-term results of a repeated cell administration strategy and evaluate the safety of an "off-the-shelf" allogeneic mesenchymal stem cell (MSC) source.

Differential effects of mitochondrial heat shock protein 60 and related molecular chaperones to prevent intracellular beta-amyloid-induced inhibition of complex IV and limit apoptosis.

Defects in mitochondrial oxidative metabolism, in particular decreased activity of cytochrome c oxidase, have been reported in Alzheimer disease tissue and in cultured cells that overexpress amyloid precursor protein. Mitochondrial dysfunction contributes to neurodegeneration in Alzheimer disease partly through formation of reactive oxygen species and the release of sequestered molecules that initiate programmed cell death pathways. The heat shock proteins (HSP) are cytoprotective against a number of stressors, including accumulations of misfolded proteins and reactive oxygen species.

Cell cycle regulator E2F1 modulates angiogenesis via p53-dependent transcriptional control of VEGF.

The transcription factor E2F1 is known to regulate cell proliferation and has been thought to modulate tumorigenesis via this mechanism alone. Here we show that mice deficient in E2F1 exhibit enhanced angiogenesis. The proangiogenic phenotype in E2F1 deficiency is the result of overproduction of vascular endothelial growth factor (VEGF) and is prevented by VEGF blockade.

DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor.

Loss-of-function mutations in DJ-1 cause a subset of familial Parkinson disease (PD). However, the mechanism underlying the selective vulnerability in dopaminergic pathway due to the inactivation of DJ-1 is unclear. Previously, we have reported that DJ-1 is a neuroprotective transcriptional co-activator interacting with the transcriptional co-repressor pyrimidine tract-binding protein-associated splicing factor (PSF).

Absence of erythroblast macrophage protein (Emp) leads to failure of erythroblast nuclear extrusion.

In mammals, the functional unit for definitive erythropoiesis is the erythroblastic island, a multicellular structure composed of a central macrophage surrounded by developing erythroblasts. Erythroblast-macrophage interactions play a central role in the terminal maturation of erythroblasts, including enucleation. One possible mediator of this cell-cell interaction is the protein Emp (erythroblast macrophage protein).

CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils.

Background: Complement fragment C5a and neutrophils have been implicated in the pathogenesis of renal disease and C5a has also been shown to delay apoptosis of human neutrophils via a transcription-independent pathway. However, transcription-dependent pathways have not been well described. The present study examined whether activation of HL-60-derived neutrophils by C5a modulates the transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein (CREB) transcription factor mediates these effects through the phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated kinase (ERK) signalling pathways.

Long-term management of the tunneled venous catheter.

Despite their propensity for significant complications, tunneled central venous catheters have become a common means of vascular access in the United States for patients requiring maintenance hemodialysis for end-stage renal disease (ESRD). Reasons for their use include advanced patient age, peripheral vascular disease (arterial and venous), late referral for creation of vascular access, and more importantly, the lack of an interdisciplinary service line on vascular access among vascular surgeons, radiologists, and nephrologists. This review article summarizes complications commonly encountered in dialysis patients who use tunneled central venous catheters for vascular access-mainly thrombosis, stenosis, and infection.