Peripheral arterial disease in HIV patients older than 50 years of age

Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.     

Criteria for assessing pain and nonarticular soft-tissue rheumatic disorders of the neck and upper limb

OBJECTIVE: To critically review the criteria used to diagnose nonarticular soft-tissue rheumatic disorders of the neck and upper limb. METHODS: An extensive search of the literature, including a search of Medline and EMBASE, authoritative recent reviews, and relevant textbooks, was completed. The diagnostic criteria used in epidemiologic studies were compared and the reliability and validity of these criteria were assessed. RESULTS: Altogether, the search identified 117 relevant research articles, among which 69 included a physical examination component, but few specified diagnostic criteria. Evidence supported respectable levels of between-observer repeatability regarding: symptom questionnaires (kappa, 0.52 to 0.79); measurement of shoulder range of motion with a goniometer (intraclass coefficients > 0.70); tests for carpal tunnel syndrome (Tinel's and Phalen's kappa, 0.53 to 0.80); and demonstration of neck tenderness (kappa = 0.43). The Katz hand diagram, and combinations of physical signs of carpal tunnel syndrome, show reasonable sensitivity and specificity for that diagnosis but only among patients referred to specialists with that putative diagnosis; no such validity has been shown among the general population. Only 1 diagnostic examination schedule has published data on both the reliability and the validity of its criteria and diagnoses. For the remaining soft-tissue upper-limb disorders, diagnostic criteria rely apparently on face and content validity and reliability data have not been published. CONCLUSION: Classification of specific disorders of the neck and upper limb requires a back to basics approach. At present, the diagnosis of most of these conditions relies heavily on the clinical opinions of investigators and there are insufficient data to indicate that these criteria are repeatable, sensitive, or specific. Recent European initiatives offer scope to follow a more disciplined approach, but more work is urgently required.     

Expansion Conditions for Early Hepatic Progenitor Cells from Embryonal and Neonatal Rat Livers

Long-term primary cultures were established fromfetal or neonatal livers by using cell suspensionsdepleted of red blood cells and by culturing the cellsin hormonally defined medium containing dimethyl sulfoxide. Two distinct populations of hepaticprogenitor cells were evident in the cultures, based onmorphology, proliferative ability, and liver-specificgene expression. Most colonies consisted of immature hepatic progenitors: small, blastlike cells,weakly expressing alpha-fetoprotein, albumin, and-glutamyltranspeptidase, and showing evidence ofproliferation as measured by bromodeoxyuridineincorporation. At the perimeter of these colonies of immaturecells and forming some colonies by themselves were moremature hepatic progenitor cells: larger cells, withincreased cytoplasmic to nuclear ratios, little proliferation, and strongly expressing albumin,alpha-fetoprotein, and -glutamyltranspeptidase.The latter two proteins were localized to the bilecanalicular membranes of these cells. Glycogen deposits were present in the mature cells from day 14embryos after eight days of culture. Thus, DMSOtreatment of hepatic parenchymal progenitors provides anovel system for studies of liver development.     

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.     

Characterization of paroxysmal and persistent atrial fibrillation in the human left atrium during initiation and sustained episodes

INTRODUCTION: Atrial fibrillation (AF) in the left atrium (LA) is poorly defined in terms of regional differences in the degree of organization, characteristics of paroxysmal and persistent variants, and electrophysiologic events that develop at the onset of episodes. METHODS AND RESULTS: The study population consisted of 21 patients (15 men and 6 women; mean age 58+/-9.4 years) with paroxysmal (10 patients) or persistent (11 patients) AF. Mapping of the LA during sustained episodes and the onset of AF was performed with a 64-electrode basket catheter. At the onset of AF, repetitive beats starting with atrial premature complexes and ending with generation of the earliest fibrillatory activity were defined as intermediary rhythm. Patients with paroxysmal AF had longer AF cycle lengths and more pronounced regional differences than patients with persistent AF. In total, AF cycle lengths in the LA in patients with persistent AF were 20% shorter than in patients with paroxysmal AF. Initiation of AF was preceded by an intermediary rhythm of 5.5+/-2.5 cycles (6.3+/-2.7 cycles in paroxysmal AF vs 4.2+/-1.0 cycles in persistent AF; P = 0.026). At the onset of AF, the earliest generators of fibrillatory activity were located more frequently in the posterior wall of the LA. CONCLUSION: AF in the LA displays substantial regional differences in terms of AF cycle lengths and degree of organization. Patients with persistent AF have shorter cycle lengths and a higher degree of disorganized activity than patients with paroxysmal AF. Intermediary rhythms play an important role in initiation of AF via activation of generator regions in the LA.     

Patched, the receptor of Hedgehog, is a lipoprotein receptor

The Hedgehog (Hh) family of secreted signaling proteins has a broad variety of functions during metazoan development and implications in human disease. Despite Hh being modified by two lipophilic adducts, Hh migrates far from its site of synthesis and programs cellular outcomes depending on its local concentrations. Recently, lipoproteins were suggested to act as carriers to mediate Hh transport in Drosophila. Here, we examine the role of lipophorins (Lp), the Drosophila lipoproteins, in Hh signaling in the wing imaginal disk, a tissue that does not express Lp but obtains it through the hemolymph. We use the up-regulation of the Lp receptor 2 (LpR2), the main Lp receptor expressed in the imaginal disk cells, to increase Lp endocytosis and locally reduce the amount of available free extracellular Lp in the wing disk epithelium. Under this condition, secreted Hh is not stabilized in the extracellular matrix. We obtain similar results after a generalized knock-down of hemolymph Lp levels. These data suggest that Hh must be packaged with Lp in the producing cells for proper spreading. Interestingly, we also show that Patched (Ptc), the Hh receptor, is a lipoprotein receptor; Ptc actively internalizes Lp into the endocytic compartment in a Hh-independent manner and physically interacts with Lp. Ptc, as a lipoprotein receptor, can affect intracellular lipid homeostasis in imaginal disk cells. However, by using different Ptc mutants, we show that Lp internalization does not play a major role in Hh signal transduction but does in Hh gradient formation.     

Macrophagic Myofasciitis in Childhood: The Role of Scanning Electron Microscopy/Energy-Dispersive Spectroscopy for Diagnosis

Macrophagic myofasciitis (MMF) is an inflammatory myopathy related to aluminum-containing vaccines. Described in 1998, most cases were reported in adults, with only 22 cases being reported in children. Three children aged between 13 months and 3½ years were investigated in our institution for neuromuscular symptoms. They underwent thorough clinical, familial, and laboratory investigations, electroneuromyography, muscle biopsy with transmission electron microscopy, scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS), and, in one case, brain magnetic resonance imaging. They had received regular immunizations. Two patients were hypotonic and one presented with myotonia. Muscle biopsy of all patients presented macrophagic infiltrates with intracytoplasmic aluminum content as revealed by SEM/EDS analysis. Their diverse clinical picture does not support a direct relationship between local morphologic findings and systemic symptoms. The atypical clinical presentation of these children may not result from the superposition of MMF upon a background systemic neuromyopathy, suggesting instead that they are two coincident and independent conditions. Although the finding of macrophage infiltrates in muscle tissue is not new, the identification of aluminum content is recent. The use of tissue sections for aluminum detection and mapping by SEM/EDS is conclusive for, diagnosis; it has not been reported previously in a pathology journal, to the authors' knowledge.     

Gesture imitation in autism: II. Symbolic gestures and pantomimed object use

We report an experimental study of imitation of two types of meaningful gestures: (a) social-communicative gestures, and (b) pantomimed actions with objects (including counterfunctional object use) by children and adolescents with autism. Controls were (a) children with nonautistic developmental delays, matched for chronological age and receptive language age, and (b) typically developing children matched for receptive language. Children in both comparison groups imitated actions more accurately than did children with autism, who nonetheless demonstrated understanding of the meaning of the gestures. However, the autistic group tended to have difficulty naming gestures and also was less able than controls to produce actions on verbal request. Children with lower levels of language ability, including those with autism, had difficulty imitating unconventional use of objects, instead using the object for their conventional functions. The discussion addresses the implications of these results and our own previous related findings for representational and executive accounts of praxic deficits in autistic spectrum disorders.     

SENSE OF COMMUNITY AND SATISFACTION WITH LIFE AMONG IMMIGRANTS AND THE NATIVE POPULATION

The aim of this study was to analyze the influence of the sense of community (SOC) on satisfaction with life (SWL) in native and immigrant populations in Spain. The main hypothesis was that SOC would moderate the negative effects associated with the immigrant adaptation process. It was further hypothesized that there would be no differences in SWL between immigrants with a high SOC and the native population. The study included 1,646 participants living in Malaga (Spain), comprising 946 natives and 700 immigrants. Data were collected using random route sampling and survey methodology. The results showed that people with higher SOC had significantly greater SWL. It was also found that SWL was greater in natives than in immigrants when the level of SOC was low or medium. However, when SOC was high there were no significant differences between the groups in SWL. The data support the hypothesis that SOC acts as a moderating variable that buffers the effect of the adaptation process experienced by immigrants.