Hyperuricemia in acute heart failure. More than a simple spectator?

BackgroundHyperuricemia is a prevalent condition in chronic heart failure (CHF), describing increased oxidative stress and inflammation. Although there is evidence that serum uric acid (UA) predicts mortality in CHF, its role as a prognostic biomarker in acute heart failure (AHF) has not yet been well assessed. The aim of this study was to determine if UA levels predict all-cause mortality. Additionally, as a secondary endpoint we sought the clinical predictors of UA serum level in this population.MethodsWe analyzed 560 consecutive patients with AHF admitted in a single university center. UA (mg/dl) was measured during early hospitalization. Patient survival status was followed up after discharge (median follow-up: 330 days). The independent association of UA level with all-cause mortality was analyzed using Cox regression analysis.ResultsDuring follow-up 165 (29.5%) deaths were identified. Patients with UA levels above the median value (≥ 7.7 mg/dl) exhibited higher mortality rates (21.1 vs. 37.9%; p < 0.001). In multivariable analysis, after adjusting for recognized prognostic factors and potential confounders, UA ≥ 7.7 mg/dl and per change in 1 mg/dl of UA was associated with an increased risk of mortality (HR 1.45, CI 95% = 1.03–2.44; p = 0.03 and HR 1.08, CI 95% = 1.01–1.15; p = 0.03, respectively).ConclusionUA serum levels is an independent predictor of all-cause mortality in an unselected patients admitted with AHF.     

Immunoneuroendocrine communication network and homeostasis regulation: the use of hormones and neurohormones as immunotherapy

The complex communication between the immune and neuroendocrine systems is bi-directional, and involves sharing different ligands and receptors in tissues and organs in vertebrate in general, and mammals in particular. It have been demonstrated that many hormones, neurohormones and neurotransmitters have profound effects on the immune system, and in turn, cytokines produced by cells of the immune system cause important changes in the neuroendocrine function. It has been shown in different animal models with induced and spontaneously occurring autoimmune diseases that alterations of the immunoendocrine interactions are involved in the breakdown of self tolerance, and by extend, the homeostasis. This review discusses the role of the neuroimmunoendocrine interactions in maintaining the homeostasis of mammals, and their role in the development of some autoimmune diseases. The finding that could exist a defective immunoneuroendocrine communication may lead to more specific therapy of several autoimmune human diseases.     

Efficacy and toxicity of intermediate-dose amphotericin B lipid complex as a primary or salvage treatment of fungal infections in patients with hematological malignancies

We treated 74 adults with a hematological malignancy and documented or suspected invasive fungal infection (IFI) with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Forty-five patients (61%) received upfront therapy and 29 patients (39%) received salvage therapy for their IFI. Forty-eight of 71 evaluable patients responded [complete responses in 40 (56%) and partial responses in 8 (11%)] and 15 (21%) died as a consequence of the IFI. Response rates in invasive aspergillosis were 33 out of 49 (67%) for probable/definite cases and 6 out of 11 (55%) for invasive candidiasis. In 40 patients with neutropenia-associated IFI, rapid neutropenic recovery ( < 10 days from study entry) was essential for response to therapy (90% vs. 32%, P < 0.01). Treatment was well tolerated, with 15% infusions followed by infusion-related adverse events, nephrotoxicity in 7% of patients and 11% of withdrawals due to toxicity. These data suggest that intermediate-doses of ABLC may be of similar efficacy than higher doses with less toxicity, making it a cost-effective alternative worthy of study in future trials.     

Latino populations: a unique opportunity for the study of race, genetics, and social environment in epidemiological research

Latinos are the largest minority population in the United States. Although usually classified as a single ethnic group by researchers, Latinos are heterogeneous from cultural, socioeconomic, and genetic perspectives. From a cultural and social perspective, Latinos represent a wide variety of national origins and ethnic and cultural groups, with a full spectrum of social class. From a genetic perspective, Latinos are descended from indigenous American, European, and African populations. We review the historical events that led to the formation of contemporary Latino populations and use results from recent genetic and clinical studies to illustrate the unique opportunity Latino groups offer for studying the interaction between racial, genetic, and environmental contributions to disease occurrence and drug response.     

Induction of protective antibodies against dengue virus by tetravalent DNA immunization of mice with domain III of the envelope protein

Dengue fever is a growing public health concern around the world and despite vaccine development efforts, there are currently no effective dengue vaccines. In the present study we report the induction of protective antibodies against dengue virus by DNA immunization with domain III (DIII) region of the envelope protein (E) in a mouse model. The DIII region of all four dengue virus serotypes were cloned separately into pcDNA 3 plasmid. Protein expression was tested in COS-7 cells. Each plasmid, or a tetravalent combination, were used to immunize BALB/c mice by intramuscular route. Presence of specific antibodies was evaluated by ELISA, and neutralizing antibodies were tested using a cytopathogenic effect (CPE) inhibition assay in BHK-21 cells, as well as in newborn mice challenged intracranially with dengue 2 virus. Mice immunized with individual DIII constructs or the tetravalent formulation developed antibodies against each corresponding dengue serotype. Antibody titers by ELISA were similar for all serotypes and no significant differences were observed when boosters were administered, although antibody responses were dose-dependent. CPE inhibition assays using Den-2 virus showed neutralization titers of 1:10 in mice immunized with individual DIII plasmid or those immunized with the tetravalent formulations. 43% of newborn mice challenged with Den-2 in combination with sera from mice immunized with Den-2 DIII plasmid were protected, whereas sera from mice immunized with the tetravalent formulation conferred 87% protection. Our results suggest that DIII can be used as a tetravalent DNA formulation to induce neutralizing and protective antibodies against dengue virus.     

Does Acid Suppressive Therapy Reduce the Risk of Laryngeal Cancer Recurrence?

OBJECTIVE/HYPOTHESIS: Gastroesophageal reflux disease (GERD) is implicated in laryngeal cancer pathogenesis and recurrence posttherapy. There are currently limited data on the effect of acid suppressive therapy in decreasing the recurrence of laryngeal cancer. Therefore, we conducted this study to identify potential effect of GERD and acid suppressive therapy on recurrences after larynx-preserving therapies. STUDY DESIGN: Case control study. METHODS: Cases and controls, derived from a single tertiary care center, were patients who had newly diagnosed localized laryngeal cancer (T3 or less and absence of nodes) and having undergone larynx-preserving surgery or radiotherapy/chemotherapy were followed between January 1, 2000 and December 31, 2003. Univariable associations were performed for demographics, smoking and alcohol patterns, stage of tumor, initial treatment, surgeon of record, presence of GERD, and the use of acid suppressive medications. Multivariable associations were performed for clinically significant variables. RESULTS: Of 258 patients with laryngeal cancer, 61 satisfied the selection criteria. Twenty-two of 61 (36%) developed recurrence and constituted cases, whereas 39/61 (64%) did not have recurrence and constituted controls. On univariable analysis, significant factors for decreased recurrences were GERD, hazard ratio 0.24 (95% confidence interval [CI] 0.08-0.71), and acid suppressive therapy, hazards 0.22 (95% CI 0.07-0.66). On multivariable analysis, laryngeal cancer recurrence was significantly less in those on acid suppressive therapy, hazard 0.31 (95% CI 0.13-0.75). CONCLUSIONS: Acid suppression postlaryngeal cancer therapies may have protective effect on laryngeal cancer recurrences. A prospective study is needed to better define this perceived beneficial effect.     

Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal autosomal recessive disorder seen in infants. It is characterized by lower motor neuron degeneration, progressive muscle paralysis and respiratory failure, for which no effective treatment exists. The phenotype of neuromuscular degeneration (nmd) mice closely resembles the human SMARD1. The identification of the mutated mouse gene in nmd mice, Ighmbp2, led to the discovery of mutations of the homologous gene in humans with SMARD1. We have studied the nmd mouse model with in vivo electrophysiological techniques and evaluated the efficacy of Mab2256, a monoclonal antibody with agonist effect on the tyrosine kinase receptor C, trkC, on disease progression in nmd mice. Treatment with Mab2256 resulted in a significant but transient improvement of muscle strength in nmd mice, as well as normalization of the neuromuscular depression during high-frequency nerve stimulation. These results suggest the potential of using monoclonal agonist antibodies for neurotrophin receptors in lower motor neuron diseases such as SMARD1.     

Reference values for peak expiratory flow rate in adults of African descent

Substantial racial differences in the values of peak expiratory flow (PEF) rate have been noted by several workers in the past. It has also been noted that applying prediction formulae derived from a Caucasian population overestimated the PEF values in Black Africans by 12%-15%. Yet reference values used up until the present, even among Black populations, are based on such formulae. This study provides new reference values for use in the Black population. They were obtained by using curvilinear formulae derived from the study of 1009 normal adult Nigerians (668 men and 341 women) between the ages of 15 years and 82 years, living and/or working in Port Harcourt, Nigeria and its hinterland.