390 research outputs found

    Incomplete oedipism and chronic suicidality in psychotic depression with paranoid delusions related to eyes

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    Self-enucleation or oedipism is a term used to describe self-inflicted enucleation. It is a rare form of self-mutilation, found mainly in acutely psychotic patients. We propose the term incomplete oedipism to describe patients who deliberately and severely mutilate their eyes without proper enucleation. We report the case of a 32-year-old male patient with a five-year history of psychotic depression accompanied by paranoid delusions centered around his belief that his neighbors criticized him and stared at him. A central feature of his clinical picture was an eye injury that the patient had caused by pouring molten lead into his right eye during a period of deep hopelessness and suicidality when the patient could not resolve his anhedonia and social isolation. Pharmacotherapy and psychotherapy dramatically improved his disorder

    Infection of Cultured Human Endothelial Cells by Legionella pneumophila

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    Legionella pneumophila is a gram-negative pathogen that causes a severe pneumonia known as Legionnaires' disease. Here, we demonstrate for the first time that L. pneumophila infects and grows within cultured human endothelial cells. Endothelial infection may contribute to lung damage observed during Legionnaires' disease and to systemic spread of this organism

    Chronic Granulomatous Disease; fundamental stages in our understanding of CGD

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    It has been 50 years since chronic granulomatous disease was first reported as a disease which fatally affected the ability of children to survive infections. Various milestone discoveries from the insufficient ability of patients' leucocytes to destroy microbial particles to the underlying genetic predispositions through which the disease is inherited have had important consequences. Longterm antibiotic prophylaxis has helped to fight infections associated with chronic granulomatous disease while the steady progress in bone marrow transplantation and the prospect of gene therapy are hailed as long awaited permanent treatment options. This review unearths the important findings by scientists that have led to our current understanding of the disease

    Ventricular Arrhythmia Burden in Patients With Heart Failure and Cardiac Resynchronization Devices: The Importance of Renal Function

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    Background: Chronic kidney disease (CKD) is a risk factor for arrhythmias in patients with heart failure (HF). However, the effects of CKD on ventricular arrhythmia (VA) burden in patients with cardiac resynchronization therapy and defibrillator (CRT‐D) devices in a primary prevention setting are unknown. Objective: To determine whether baseline CKD is associated with increased risk of VA in patients implanted with primary prevention CRT‐D devices. Methods and Results: In this retrospective study, 199 consecutive primary prevention CRT‐D recipients (2005–2010) were stratified by estimated glomerular filtration rate (eGFR) levels prior to device implantation with 106 (53.2%) ≥CKD III (eGFR III as the only predictor of sustained VA in this group (adjusted hazard ratio [HR] 2.92, CI = 1.39–6.1, P = 0.004). Conclusion: Baseline CKD is a strong independent risk factor for VA in primary prevention CRT‐D recipients. Further understanding of the underlying arrhythmogenic mechanisms relating to CKD may be of interest to allow appropriate correction and prevention. Device programming in this cohort may need to reflect this increased risk

    Molecular Mimicry by an F-Box Effector of Legionella pneumophila Hijacks a Conserved Polyubiquitination Machinery within Macrophages and Protozoa

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    The ability of Legionella pneumophila to proliferate within various protozoa in the aquatic environment and in macrophages indicates a remarkable evolution and microbial exploitation of evolutionarily conserved eukaryotic processes. Ankyrin B (AnkB) of L. pneumophila is a non-canonical F-box-containing protein, and is the only known Dot/Icm-translocated effector of L. pneumophila essential for intra-vacuolar proliferation within both macrophages and protozoan hosts. We show that the F-box domain of AnkB and the 9L10P conserved residues are essential for intracellular bacterial proliferation and for rapid acquisition of polyubiquitinated proteins by the Legionella-containing vacuole (LCV) within macrophages, Dictyostelium discoideum, and Acanthamoeba. Interestingly, translocation of AnkB and recruitment of polyubiquitinated proteins in macrophages and Acanthamoeba is rapidly triggered by extracellular bacteria within 5 min of bacterial attachment. Ectopically expressed AnkB within mammalian cells is localized to the periphery of the cell where it co-localizes with host SKP1 and recruits polyubiquitinated proteins, which results in restoration of intracellular growth to the ankB mutant similar to the parental strain. While an ectopically expressed AnkB-9L10P/AA variant is localized to the cell periphery, it does not recruit polyubiquitinated proteins and fails to trans-rescue the ankB mutant intracellular growth defect. Direct in vivo interaction of AnkB but not the AnkB-9L10P/AA variant with the host SKP1 is demonstrated. Importantly, RNAi-mediated silencing of expression of SKP1 renders the cells non-permissive for intracellular proliferation of L. pneumophila. The role of AnkB in exploitation of the polyubiquitination machinery is essential for intrapulmonary bacterial proliferation in the mouse model of Legionnaires' disease. Therefore, AnkB exhibits a novel molecular and functional mimicry of eukaryotic F-box proteins that exploits conserved polyubiquitination machinery for intracellular proliferation within evolutionarily distant hosts

    Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

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    OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

    A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

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    Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life
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