Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection

A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selective advantage. We performed high-throughput LV integration site analysis on human hematopoietic stem progenitor cells engrafted in immunodeficient mice and found the same CISs reported in patients with ALD. Strikingly, most CISs in our experimental model and in patients with ALD cluster in megabase-wide chromosomal regions of high LV integration density. Conversely, cancer-triggering integrations at CISs found in tumor cells from γ-retroviral vector-based clinical trials and oncogene-tagging screenings in mice always target a single gene and are contained in narrow genomic intervals. These findings imply that LV CISs are produced by an integration bias toward specific genomic regions rather than by oncogenic selection.     

Pulmonary histoplasmosis presenting with the reversed halo sign on high-resolution CT scan

We describe the case of a 23-year-old man with pulmonary histoplasmosis whose high-resolution CT scan demonstrated the reversed halo sign. We also extensively review the literature about this CT scan sign. The reversed halo sign has been described in a number of diseases, both infectious and noninfectious. However, to our knowledge, this is the first reported case of pulmonary histoplasmosis presenting with this radiologic finding.     

Social representations of people with diabetes regarding their perception of family support for the treatment

The objective of this qualitative study was to identify the social representations that people with diabetes have on their perception of family support for the treatment. The Theory of Social Representations was used as the theoretical and methodological framework. Participants were 41 people with diabetes assisted at a university in the state of S?o Paulo in 2007. The focal group strategy was used for data collection, and thematic content analysis was performed. Results revealed three categories: family support is present in the everyday life of people with diabetes; the family does not always support the person with diabetes in his or her needs; the person with diabetes assumes the responsibility to trigger family support. Participants see family support as a relevant factor for the treatment, but they also point out that excessive control from relatives limits their autonomy and originates ambiguous feelings. The multiprofessional team must take into consideration that knowing social representations helps improve the health care delivered to people with diabetes.     

Knowledge and attitudes of patients with diabetes mellitus in a primary health care system

The objective of this study was to characterize patients with type 2 diabetes mellitus, according to sociodemographic and clinical variables, and to analyze scores of knowledge and attitudes regarding the disease. Participants were 79 users who received care in a primary health care service, in 2008. The Diabetes Mellitus Knowledge (DKN-A) and Attitude (ATT-19) questionnaires were used for data collection. The population was formed by adults and elderly adults, who were between 30 and 80 years old. Most were literate (96.3%); married (63.3%); female (63.3%) and classified as class-2 obesity. As to the knowledge about the disease, subjects obtained scores lower than 8, indicating unsatisfactory results on self-care. Scores obtained regarding attitudes show difficulties to cope with the disease. Results evidence the need to adopt a Diabetes Education Program at the studied unit.     

Give or take? Intravenous immunoglobulin or plasma exchange for Guillain-Barré syndrome

A new randomised controlled trial suggested that plasma exchange hastened removal from the ventilator in mechanically ventilated children with Guillain-Barré syndrome compared with intravenous immunoglobulin. Two larger trials in adults showed the opposite result.     

Clinical and Imaging Manifestations of Hemorrhagic Pulmonary Leptospirosis: A State-of-the-Art Review

Leptospirosis, a spirochetal zoonosis, is frequently unrecognized due to its manifestation as an undifferentiated fever. It is an emerging infectious disease that has changed from an occupational disease of veterinarians, farmers, butchers, and other animal handlers to a cause of epidemics in poor and decayed urban communities in developing countries. Humans are infected when mucous membranes or abraded skin come into direct contact with the urine of infected animals, especially rats and dogs. Mortality from severe leptospirosis is high, even when optimal treatment is provided. The diagnosis of leptospirosis is based on clinical findings, history of direct or indirect exposure to infected animals in endemic areas, and positive serological tests. It should be considered in the differential diagnosis of patients with febrile illnesses associated with pneumonitis and respiratory failure, especially when hemoptysis is present. Severe pulmonary involvement in leptospirosis consists primarily of hemorrhagic pneumonitis. In advanced cases, adult respiratory distress syndrome and massive pulmonary hemorrhage may occur. Chest radiographs show bilateral alveolar infiltrates and/or resemble viral pneumonia, bronchopneumonia, tuberculosis, adult respiratory distress syndrome, and other causes of pulmonary hemorrhage such as Goodpasture syndrome. High-resolution computed tomography scans may show nodular infiltrates, areas of consolidation, ground-glass attenuation, and crazy-paving patterns. Bronchoalveolar lavage and autopsy studies have suggested that ground-glass opacities and air-space consolidations are secondary to pulmonary hemorrhage. Although not specific, the presence of these computed tomography findings in a febrile patient with an appropriate history should suggest a diagnosis of leptospirosis.