Polymerase Chain Reaction Screening for Fungemia and/or Invasive Fungal Infections in Patients with Hematologic Malignancies

INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS: PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI

Outcome and quality of life after aorto-bifemoral bypass surgery

<p>Abstract</p> <p>Background</p> <p>Aorto-bifemoral bypass (AFB) is commonly performed to treat aorto-iliac disease and a durable long-term outcome is achieved. Most studies documenting beneficial outcomes after AFB have been limited to mortality and morbidity rates, costs and length of hospital stay (LOS). Few studies have examined the dependency of patients and how their perception of their own health changes after surgery. The aim of the present study was to evaluate outcome after AFB and to study its determinants.</p> <p>Methods</p> <p>This retrospective study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. Out of 1597 intensive care patients admitted to the PACU, 75 were submitted to infrarenal AFB and admitted to these intensive care unit (ICU) beds over 2 years. Preoperative characteristics and outcome were evaluated by comparing occlusive disease with aneurysmatic disease patients. Six months after discharge, the patients were contacted to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in Activities of Daily Living (ADL) evaluated. Patient's characteristics and postoperative follow-up data were compared using Mann-Whitney U test, t test for independent groups, chi-square or Fisher's exact test. Patient preoperative characteristics were evaluated for associations with mortality using a multiple logistic regression analysis.</p> <p>Results</p> <p>The mortality rate was 12% at six months. Multivariate analysis identified congestive heart disease and APACHE II as independent determinants for mortality. Patients submitted to AFB for occlusive disease had worse SF-36 scores in role physical and general health perception. Patients submitted to AFB had worse SF-36 scores for all domains than a comparable urban population and had similar scores to other PACU patients. Sixty-six percent and 23% of patients were dependent in at least one activity in instrumental and personal ADL, respectively, but 64% reported having better general health.</p> <p>Conclusion</p> <p>This study shows that congestive heart disease and APACHE II were risk factors for mortality after AFB surgery. Survivors who have undergone AFB perceive an improved quality of life although they are more dependent in ADL tasks and have worse scores in almost all SF-36 than the population to which they belong.</p

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

This article analyzes the "Global Burden of Disease Study 2010" and examines the study's implications for neglected tropical diseases

Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization

Reactive oxygen species in phagocytic leukocytes

Phagocytic leukocytes consume oxygen and generate reactive oxygen species in response to appropriate stimuli. The phagocyte NADPH oxidase, a multiprotein complex, existing in the dissociated state in resting cells becomes assembled into the functional oxidase complex upon stimulation and then generates superoxide anions. Biochemical aspects of the NADPH oxidase are briefly discussed in this review; however, the major focus relates to the contributions of various modes of microscopy to our understanding of the NADPH oxidase and the cell biology of phagocytic leukocytes

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities

Fatores de atraso na alta hospitalar em hospitais de ensino

OBJETIVO Analisar os motivos de atraso na alta hospitalar de pacientes internados em enfermarias de clínica médica. MÉTODOS Foram analisados 395 prontuários de pacientes consecutivos das enfermarias de clínica médica de dois hospitais públicos de ensino: Hospital das Clínicas da Universidade Federal de Minas Gerais e Hospital Odilon Behrens. Foi utilizado o Appropriateness Evaluation Protocol para definir o momento a partir do qual as anotações do prontuário permitiam concluir que a permanência no hospital não mais era adequada. O intervalo entre esse momento e a data da alta hospitalar efetivada definiu o total de dias de atraso na alta hospitalar. Foi utilizado, sistematicamente, instrumento para categorizar os motivos de atraso da alta hospitalar, tendo sido realizada análise de frequências. RESULTADOS O atraso na alta hospitalar ocorreu em 60,0% das 207 internações do Hospital das Clínicas e em 58,0% das 188 internações do Hospital Odilon Behrens. O atraso por paciente foi em média de 4,5 dias no primeiro e 4,1 dias no segundo, o que corresponde à taxa de ocupação de 23,0% e 28,0% em cada hospital, respectivamente. Os principais motivos de atraso nos dois hospitais foram, respectivamente: espera para realização de exames complementares (30,6% e 34,7%) ou para liberação dos laudos dos exames (22,4% e 11,9%) e os relacionados à responsabilidade médica (36,2% e 26,1%), compreendendo a demora na discussão do caso clínico e na tomada de decisão clínica e dificuldades nas interconsultas, respectivamente (20,4% e 9,1%). CONCLUSÕES Foi constatado percentual elevado de atraso na alta hospitalar nos dois hospitais. O atraso foi devido principalmente a fatores relacionados a processos, que podem ser melhorados por intervenções da equipe assistencial e dos gestores. O impacto na média de permanência hospitalar e na taxa de ocupação foi expressivo e preocupante, num cenário de relativa escassez de leitos e longas esperas por internação