Incidence and characteristics of left ventricular false tendons and trabeculations in the normal and pathologic heart by second harmonic echocardiography.

We sought to review echocardiographic incidence of anomalous images (AI) as false tendons and trabeculations of the left ventricle (LV) in light of recent advancements in echocardiographic evaluation of heart anatomy. In 1580 patients the presence of false tendons, trabeculations, or thrombi was evaluated with transthoracic echocardiography and correlated to clinical characteristics and echocardiographic parameters. Incidence of AI was 46.7% (75% false tendons, 23% trabeculations, 2% thrombi), slightly higher in pathologic (48.9%) than in normal hearts (40.8%). AI were more frequent in male patients (52%) than in female patients (39.7%) and associated with LV dilatation, hypertrophy, and systolic dysfunction. False tendons and trabeculations were not related to age. Male sex was the most significant independent predictor of AI. In 2 patients, isolated LV noncompaction of myocardium was diagnosed and confirmed by magnetic resonance imaging. This study shows a high prevalence of AI for patients with and without pathologic hearts suggesting the need of updating LV echocardiographic anatomy. It also emphasizes the necessity for an awareness of these anatomic variants when evaluating patients for mural thrombi and cardiomyopathies.     

Patellar Resurfacing in Total Knee Arthroplasty: Systematic Review and Meta-Analysis

Background

Patellar resurfacing in total knee arthroplasty remains controversial. The aim of this study is to evaluate this technique through an analysis of comparative studies in the current literature.

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase.

This paper is the fifth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 3.     

C–C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C–C chemokines (RANTES, MIP-1α, and MIP-1β) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C–C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C–C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.     

NeoR-based transduced T lymphocytes detected by real-time quantitative polymerase chain reaction

To develop a trial with lymphocyte suicide gene therapy in patients with hematological malignancies, we transduced human T lymphocytes with a retroviral vector (LSN-tk) encoding the herpes simplex virus thymidine kinase (tk) and the neomycin resistance (NeoR) genes. Precise quantification of gene transfer is crucial for any gene therapy protocol, but methods using semiquantitative PCR are inaccurate and subject to variations. Real-time quantitative PCR could be a valid alternative. A TaqMan probe was designed to hybridize with the NeoR gene. The PCR product is 64 nucleotides long and readily quantified by TaqMan probe binding. The analysis was performed soon after transduction and repeated after the selection procedure. This method was more accurate, reproducible, and sensitive than the semiquantitative PCR assay. Accuracy was the same whether the analysis was performed at the highest rate or at the lowest rate of transduction. Additionally we used real-time PCR to monitor the kinetics of enrichment of the transduced cells over the selection time and showed how 7 days of selection are needed. This study precisely quantified the percentages of cells transduced by the retroviral vector and could have major implications in gene therapy studies.     

Regulatory Role of Nitric Oxide in Cutaneous Inflammation

Inflammation - Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound...     

Melatonin for refractory idiopathic thrombocytopenic purpura: a report of 3 cases

In addition to its well-known influence on circadian rhythms, melatonin has been described as being able to increase the number of platelets in circulating blood. This provided the rationale to evaluate melatonin for toxicity and efficacy in three patients with idiopathic thrombocytopenic purpura (ITP) refractory to initial treatment with corticosteroids or splenectomy (refractory ITP). Patients received melatonin for 1 month. The therapy was continued for 2 additional months in patients with stable or responding disease. After 3 months, the stable or responding patients continued the therapy for 3 months and more. All patients had a partial response after 1 month. Continuing with the treatment, none of the three patients had disease progression (average follow-up time of 31 months; range: 23-46 months). Toxicity was lacking, with the only side effect being drowsiness. Our experience suggests that melatonin may be safe and effective in patients with refractory ITP.     

Imatinib-mesylate blocks recombinant T-type calcium channels expressed in human embryonic kidney-293 cells by a protein tyrosine kinase-independent mechanism

The 2-phenylaminopyrimidine derivative imatinib-mesylate, a powerful protein tyrosine kinase (PTK) inhibitor that targets abl, c-kit, and the platelet-derived growth factor receptors, is rapidly gaining a relevant role in the treatment of several types of neoplasms. Because first generation PTK inhibitors affect the activity of a large number of voltage-dependent ion channels, the present study explored the possibility that imatinib-mesylate could interfere with the activity of T-type channels, a class of voltage-dependent Ca2+ channels that take part in the chain of events elicited by PTK activation. The effect of the drug on T-type channel activity was examined using the whole-cell patch-clamp technique with Ba2+ (10 mM) as the permeant ion in human embryonic kidney-293 cells, stably expressing the rat Ca(V)3.3 channels. Imatinib-mesylate concentrations, ranging from 30 to 300 microM, reversibly decreased Ca(V)3.3 current amplitude with an IC(50) value of 56.9 microM. By contrast, when imatinib-mesylate (500 microM) was intracellularly dialyzed with the pipette solution, no reduction in Ba2+ current density was observed. The 2-phenylaminopyrimidine derivative modified neither the voltage dependence of activation nor the steady-state inactivation of Ca(V)3.3 channels. The decrease in extracellular Ba2+ concentration from 10 to 2 mM and the substitution of Ca2+ for Ba2+ increased the extent of 30 microM imatinib-mesylate-induced percentage of channel blockade from 25.9 +/- 2.4 to 36.3 +/- 0.9% in 2 mM Ba2+ and 44.2 +/- 2.3% in 2 mM Ca2+. In conclusion, imatinib-mesylate blocked the cloned Ca(V)3.3 channels by a PTK-independent mechanism. Specifically, the drug did not affect the activation or the inactivation of the channel but interfered with the ion permeation process.     

Interleukin 7-engineered stromal cells: a new approach for hastening naive T cell recruitment

In this study we determined whether human stromal cells could be engineered with a retroviral vector carrying the interleukin 7 (IL-7) gene and investigated the effects on T cells in vitro and in vivo in a murine model. Transduced mesenchymal cells strongly express CD90 (98.15%), CD105 (87.6%), and STRO-1 (86.7%). IL-7 production was 16.37 (+/-2 SD) pg/ml, which remained stable for 60 days. In vitro-immunoselected naive T cells maintained the CD45RA+ CD45RO- naive phenotype (4.2 times more than controls) after 7 days of culture with IL-7-engineered stromal cells. The apoptosis rate (4.7%) of the naive T cells cultured with transduced stromal cells overlapped with that of freshly isolated cells. Immunohistological analysis detected stromal cells in bone marrow, spleen, and thymus. Cotransplantation of IL-7-engineered stromal cells with CD34+ cells improved engraftment in terms of CD45+ cells and significantly increased the CD3+ cell count in peripheral blood, bone marrow, and spleen. These data demonstrate the following: (1) human stromal cells can be transduced, generating a normal layer; (2) transduced stromal cells in vitro maintain the naive T cell phenotype; and (3) IL-7-transduced stromal cells in vivo home to lymphoid organs and produce sufficient IL-7 in loco, supporting T cell development in a cotransplantation model. Because of their efficient cytokine production and homing, IL-7-engineered stromal cells might be an ideal vehicle to hasten immunological reconstitution in T cell-depleted hosts.     

Minimum data set for home care: a valid instrument to assess frail older people living in the community

BACKGROUND: Optimal care for frail elderly patients depends on comprehensive assessment. This is especially true in the complex setting of interdisciplinary home care programs. To facilitate comprehensive assessment, as well as to generate a useful, policy-relevant patient database, standardized, multidimensional, and validated instruments are very helpful. OBJECTIVES: The aim of the present study was to demonstrate that the Minimum Data Set assessment instrument for Home Care (MDS-HC) can be used to detect functional and cognitive impairment as defined by analogous research instruments. RESEARCH DESIGN: This was a cross-sectional correlation study. SUBJECTS: We studied 95 patients admitted to home care services of the Health Care Agency of Bergamo (Italy). MEASURES: The MDS-HC form was completed for all patients by well-trained nurses, independently of and with nurses blinded to the results from the research rating scales. The Barthel Activities of Daily Living (ADL) Index, the Instrumental Activities of Daily Living of Lawton (IADL), and the Mini Mental State Examination (MMSE) were considered the gold standard. RESULTS: Agreement between the MDS-HC scales and the research rating scales was assessed with Pearson's correlation coefficient. This coefficient was 0.74 for MDS-ADL versus Barthel Index, 0.81 for MDS-IADL versus Lawton Index, and 0.81 for Cognitive Performance Scale versus MMSE, indicating an excellent agreement. CONCLUSIONS: The MDS-HC scales, when performed by trained nurses using recommended protocols, provide a valid measure of function and cognitive status in frail home care patients. These findings point out the overall validity of the functional and clinical data contained in the MDS-HC assessment. Use of the MDS-HC gives the unique opportunity of setting up a database, a prerequisite for all epidemiological evidence-based medicine studies.